PLAINSBORO, N.J., Sept. 21, 2007 (PRIME NEWSWIRE) — Integra LifeSciences Holdings Corporation (Nasdaq:IART) announced the release of the OCS2 Ojemann Cortical Stimulator at this week’s annual meeting of the Congress of Neurological Surgeons in San Diego, CA. The OCS2 Ojemann Cortical Stimulator has an FDA clearance in the United States and a CE Mark Certification in the European Union.

Originally developed in collaboration with Dr. George Ojemann at the University of Washington, the new device contains updated electronics and an improved design for usability. The Ojemann Cortical Stimulator is the industry standard for cortical stimulation procedures that identify and map eloquent tissue during brain surgery. It is a compact, battery-powered unit, which supplies up to 20 milliamps constant current, and has easy to use controls for treatment in awake and anesthetized patients.

The neurosurgeon’s primary goal, for patients with brain cancer and epilepsy, is to completely remove abnormal tissue while sparing normal areas. During surgery, the neurosurgeon places the OCS probe onto the brain’s cortex in all areas surrounding tissue considered for resection. Responses to direct cortical stimulation reveal the functional areas, either by evoking an observed motor response in an anesthetized patient, or for an awake patient, triggering sensations or causing an interruption in the patient’s speech. These responses help the neurosurgeon determine the boundaries between abnormal and normal areas, and facilitate removal of the cancer or epileptic region.

“We are excited to bring this updated technology to the U.S. and international markets. The Ojemann Cortical Stimulator allows surgeons to accurately identify eloquent tissue and reduce language and motor defects while performing resections,” said Jason D. Ellnor, director of marketing for Integra’s stereotactic products.

There are approximately 200,000 patients diagnosed with brain cancer each year in the United States. Epilepsy is estimated to affect an additional 3 million people in the United States, making it one of the most common neurological diseases.

The Integra NeuroSciences direct sales organization will sell the OCS2 Ojemann Cortical Stimulator in the US and internationally. Integra NeuroSciences is a leading provider of implants, devices, instruments and systems used in neurosurgery, neuromonitoring, neuro-trauma, and related critical care. The Integra NeuroSciences’ direct selling effort in the United States and Europe involves more than 200 professionals. In all other markets, Integra NeuroSciences products are sold through a network of distributors.

Integra LifeSciences Holdings Corporation, a world leader in regenerative medicine, is dedicated to improving the quality of life for patients through the development, manufacturing, and marketing of cost-effective surgical implants and medical instruments. Integra’s products, used primarily in neurosurgery, extremity reconstruction, orthopedics and general surgery, are used to treat millions of patients every year. The company’s headquarters are in Plainsboro, New Jersey, and it has research and manufacturing facilities throughout the world. For more information visit www.Integra-LS.com.

This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements concerning the future use of OCS2 Ojemann Cortical Stimulator. Such forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from predicted or expected results. Among other things, the willingness of physicians to use this product may affect the prospects for its use in clinical procedures. In addition, the economic, competitive, governmental, technological and other factors, identified under the Risk Factors included in Item lA of Integra’s Annual Report on Form 10-K for the year ended December 31, 2006, and information contained in subsequent filings with the Securities and Exchange Commission, could affect actual results.

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 CONTACT: Integra LifeSciences Holdings Corporation          John B. Henneman, III, Executive Vice President, Chief            Administrative Officer, Acting Chief Financial Officer           (609) 936-2481           [email protected]          Gianna Sabella, Public Relations Manager           (609) 936-2389           [email protected] 

By Getahun, Darios Ananth, Cande V; Oyelese, Yinka; Peltier, Morgan R; Et al

Abstract Objective. To examine whether acute and chronic respiratory diseases are associated with an increased risk of spontaneous premature rupture of the membranes (PROM).

Methods. We used the 1993-2004 National Hospital Discharge Survey data of singleton deliveries in the USA (N = 41 250 539). The International Classification of Diseases Ninth Revision was utilized to identify acute (acute upper respiratory diseases, viral/ bacterial pneumonia, and acute bronchitis/bronchiolitis) and chronic (chronic bronchitis and asthma) respiratory conditions and spontaneous PROM. All analyses were adjusted for potential confounders.

Results. The incidence of PROM was 5%, and rates of acute and chronic respiratory conditions were 2.1 and 9.5 per 1000 pregnancies, respectively. Chronic bronchitis was associated with a reduced risk of PROM (RR 0.39, 95% CI 0.31, 0.48). Asthma was significantly associated with PROM at preterm (RR 1.15, 95% CI 1.14, 1.17) and term (RR 1.27, 95% CI 1.23, 1.30). Stratification by race showed that acute upper respiratory disease was associated with preterm PROM in whites (RR 1.90, 95% CI 1.71, 2.11) and blacks (RR 6.76, 95% CI 5.67, 8.07). Viral/bacterial pneumonia was associated with preterm PROM in blacks and term PROM in both races. Asthma was associated with term PROM in blacks but not whites.

Conclusions. Acute respiratory diseases and asthma during pregnancy are associated with spontaneous PROM, with substantially stronger association among blacks than whites. We speculate that timely diagnosis and treatment, coupled with closely mentoring of pregnant women may help reduce the rate of PROM and associated complications.

Keywords: Respiratory disease, asthma, bronchitis, spontaneous premature rupture of membranes

Introduction

In the USA, premature rupture of the membranes (PROM) complicates about 10% of pregnancies and most cases occur spontaneously without apparent cause [1,2]. Of all singleton preterm births at <37 weeks, approximately 10% are attributable to PROM [3]. PROM is associated with an increased risk for obstetrical complications such as oligohydramnios and placental abruption [4-6]. Infants delivered preterm following PROM are also at increased risk for bronchopulmonary hypoplasia [7], neonatal sepsis, and neonatal death [5,8,9].

Despite the speculative etiology, epidemiologic studies have documented risk factors associated with PROM, including young maternal age [10], black race [11], multiparity [12], maternal smoking and cocaine use [13,14], previous PROM or preterm birth [11], multiple gestation [12], cervical incompetence [11], and obstetrical procedures such as cervical cerclages [5,15]. A significant proportion of PROM cases have an underlying inflammatory etiology following sexually transmitted diseases [16] and upper genital tract infections [17,18].

Despite the widespread use of antimicrobial therapy and advances in respiratory therapy, respiratory conditions during pregnancy remain important risk factors for maternal and fetal morbidity and mortality [19]. The incidence of communityacquired pneumonia during pregnancy is approximately 1.5 to 2.7 per 1000 pregnancies [20], with rates similar to that in the general population [21]. However, if contracted during pregnancy, pneumonia portends a virulent course [22], and is associated with an increased risk of delivering preterm [19,23], delivering small-for-gestational age [21], and neonatal mortality [19].

Asthma is a ubiquitous yet a serious medical condition, complicating pregnancy [24] with an estimated prevalence of 3.7% to 8.4% among pregnant women in the USA [25]. Uncontrolled asthma may lead to reduced oxygenation and/or an asthma-related inflammatory response at the maternal-fetal interface, which may be associated with increased risk of adverse pregnancy outcome. Asthma during pregnancy is associated with an increased risk of preeclampsia and preterm birth [24].

We hypothesized that acute and chronic respiratory diseases are associated with increased risk of spontaneous PROM through bacteremia and increased levels of proinflammatory cytokines. Therefore, we examined the association between acute and chronic respiratory conditions and spontaneous PROM to test our hypothesis using a large population-based cohort of singleton pregnancies in the USA.

Methods

We used the National Hospital Discharge Survey (NHDS) data [26] assembled by the National Center for Health Statistics (NCHS). This survey comprises discharges from non-institutional hospitals in the USA between 1993 and 2004, exclusive of federal, military, and Veterans Administration hospitals, located in the 50 States and the District of Columbia. Short stay (average length of hospitalization <30 days) general, as well as pediatric general hospitals participated in the annual survey. Discharge diagnosis and medical procedures, as well as demographic characteristics such as age, gender, race, marital status, adequacy of prenatal care, smoking, cocaine use, geographic location, and type of insurance coverage were extracted. In the NHDS dataset, self-reported maternal race was grouped as white, black, American Indian/Eskimo, Asian/Pacific Islander, and Others’ irrespective of the Hispanic origin. Thus, white race includes both white nonHispanics and white Hispanics. Similarly, the black race group includes both black non-Hispanics and black Hispanics. We excluded American Indian/ Eskimo and Asian/ Pacific Islander from the analysis due to small counts.

The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were utilized to identify pregnancies complicated with the following respiratory tract conditions: acute respiratory conditions including acute upper respiratory diseases (ICD-9-CM 465.8 and 465.9), acute bronchitis (ICD-9-CM 466.0-466.19), and viral/ bacterial pneumonia (ICD-9-CM 480.0-487.0), as well as chronic respiratory conditions including chronic bronchitis (ICD-9-CM 491.0-492.8 and 495.9-506.0) and asthma (ICD-9-CM 493.0-493.9). Women who had both conditions in a pregnancy were excluded from all analyses due to the very small count (<0.01% in the cohort). Data on singleton births (ICD-9-CM V270, V271, V301, V302, V3000, and V3001) and spontaneous premature rupture of membranes (ICD-9-CM 658.10-658.23) were also extracted. Spontaneous PROM was denned as the rupture of membranes at any given time during pregnancy prior to the onset of labor.

Statistical analysis

The distributions of socio-demographic and behavioral characteristics of women with acute and chronic respiratory tract conditions were compared using Chi-square tests. Multivariable logistic regression analysis was performed to examine the association between acute and chronic respiratory conditions and spontaneous premature rupture of membranes after controlling for potential confounders. These included maternal age (categorized as 14-24, 25-34, and 35-49 years), maternal race (white, black, and others), marital status (married or unmarried), adequacy of prenatal care (adequate or inadequate), maternal smoking (yes or no), cocaine use (yes or no), insurance type (Medicare, Medicaid, indemnity, uninsured, and others), geographic location (Northeast, Midwest, South, and West) and birth year (1993-94, 1995-96, 1997-98, 1999- 2000, 2001-02, and 2003-04).

We repeated the analysis after stratifying the data on whether PROM occurred at preterm (<37 weeks) or at term, as well as maternal race categories. Relative risks (RR) and 95% confidence intervals (CI) were used to describe the associations. Under the rare disease assumption, the odds ratio can be considered a valid estimate of the relative risk. All statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC, USA).

The study was approved by the Institutional Review Board of UMDNJ- Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Results

After incorporating the sampling weight, there was a total of 41 250 539 singleton pregnancies between 1993 and 2004 in the USA. The overall rates of PROM and acute and chronic respiratory conditions were 50, 2.1 and 9.5 per 1000 singleton pregnancies, respectively. Of all singleton births, 16.3% preterm and 4% at term were attributable to PROM. Hospitalized pregnant women with acute and chronic respiratory conditions were more likely to be young, unmarried, smoke cigarettes, use cocaine, be enrolled in the Medicaid program, and to be residents of Northeast and Midwest geographic regions (Table I). While white women were more likely to have acute respiratory conditions, black women were more likely to have chronic respiratory conditions.

Table II shows the associations between acute (acute upper respiratory diseases, viral and bacterial pneumonia, and acute bronchitis) and chronic (chronic bronchitis and asthma) respiratory conditions and spontaneous PROM based on the overall cohort. Of the acute respiratory conditions, acute upper respiratory disease and viral and bacterial pneumonia were associated with PROM, but not acute bronchitis. Of the chronic respiratory conditions, asthma was associated with PROM, but chronic bronchitis was not.

Table I. Distribution of maternal characteristics among women with acute and chronic respiratory conditions: USA, 1993-2004. Figure 1 shows the associations between acute and chronic respiratory conditions at preterm and term gestations using the overall cohort. A strong association was observed between acute upper respiratory disease and PROM at preterm (RR 1.67, 95% CI 1.56, 1.78), but not at term gestations. Viral and bacterial pneumonia was strongly associated with PROM at term (RR 2.28, 95% CI 2.16, 2.42), but not at preterm gestations. Acute bronchitis was not associated with PROM at preterm and term gestations. Among the chronic respiratory conditions, asthma was strongly associated with PROM both at term (RR 1.27, 95% CI 1.23, 1.30) and preterm (RR 1.15, 95%> CI 1.14, 1.17) gestations, but chronic bronchitis was associated with reduced risk at term gestation.

The association between acute and chronic respiratory conditions and spontaneous PROM for white and black women at preterm and term gestations is shown in Table III. Although acute upper respiratory disease was associated with preterm PROM in both races, the strength of association was substantially higher for blacks than for whites. Viral and bacterial pneumonia was significantly associated with preterm PROM among blacks only. In both races, viral and bacterial pneumonia was associated with term PROM. Acute upper respiratory disease was significantly associated with term PROM among blacks, but not among whites. Among whites, acute bronchitis was associated with term PROM. Of the chronic conditions, maternal asthma was associated with term PROM among black women only.

Discussion

In this population-based study, we found that acute respiratory tract conditions and asthma during pregnancy increased the risk of spontaneous PROM. More importantly, acute upper respiratory tract diseases were associated with preterm PROM, whereas viral and bacterial pneumonia was associated with term PROM. In addition, these associations demonstrated strong race-disparity. Relative risks for spontaneous preterm PROM among those with acute respiratory tract conditions, and at term gestation among asthmatic women were substantially higher for black than for white women.

It has been hypothesized that ascending bacterial infections at the maternal-fetal interface are a significant component in the primary pathophysiologic mechanism leading to PROM [5,17,18]. Recent evidence suggests that inflammatory processes at sites remote from the genital tract may lead to increased levels of proinflammatory cytokines at the maternal-fetal interface [23] . This is perhaps best studied for periodontitis and adverse pregnancy outcomes including preterm birth, preterm PROM, etc. Increased levels of inflammatory markers such as interleukin (IL)- 6 and IL-8 in amniotic fluid are correlated with colony-forming units of periodontal pathogens in subgingival plaque of pregnant women [27,28] . Increased levels of fetal cord IgM have also been documented in response to microorganisms known to be associated with periodontitis [27], suggesting that these organisms can stimulate an immune response at the maternal-fetal interface. It is possible that similar inflammatory changes can occur at the maternal-fetal interface in response to acute and chronic inflammatory respiratory conditions. Thus, it is conceivable that both respiratory tract infections and periodontal inflammatory processes predispose to PROM through a common process: increased intrauterine concentrations of various proinflammatory cytokines, prostaglandins, and matrix metalloproteinease [5,27,28]. Another mechanism may be by infective inflammatory respiratory conditions causing systemic dissemination of the microorganisms that may consequently lead to intrauterine inflammation.

Table II. Associations between maternal acute and chronic respiratory conditions and spontaneous premature rupture of membranes: USA, 1993-2004.

Figure 1. Relative risk for spontaneous premature rupture of membranes at preterm (left panel) and term (right panel) gestations and respiratory disease among singleton pregnancies: USA, 1993- 2004. Relative risks were adjusted for maternal age, race, marital status, prenatal care, insurance, geographic location, birth year, smoking, and cocaine use. [dagger]The small number of cases precluded subgroup analysis.

Table III. Associations between maternal acute and chronic respiratory conditions and spontaneous premature rupture of membranes by maternal race at preterm and term gestation: USA, 1993- 2004.

Our findings of an increased risk of PROM among women with asthma during pregnancy corroborate previous findings [29], but are at variance with others studies. Sorensen et al. [30] reported the absence of association between maternal asthma and risk of preterm PROM (OR 1.63, 95%> CI 0.50, 5.33), contradicting our findings. Nonetheless, closer examination of our data shows that the association between asthma and PROM is present only for black women when spontaneous PROM occurs at term gestations. Despite advances in knowledge regarding potential risk factors and pathophysiologic mechanisms for asthma and advances in therapy, the prevalence, severity, and mortality from asthma have increased over the past decade with a disproportionately higher rate among blacks [31], The increased risk for spontaneous PROM among asthmatic black women could be consistent with disparity in access to health care that may have resulted in a higher asthma hospitalization rate among blacks relative to whites [32,33]. This suggests that black women are perhaps disproportionately affected by relatively severe forms of asthma in their pregnancy, and consequently PROM.

The reduced risk of PROM among women with acute and chronic bronchitis may be driven by the widespread use of antibiotics. Antibiotics are generally thought to be ineffective in preventing preterm births. But studies on monkeys suggest they can be effective if given prior to the start of uterine contractions [34]. Similarly, frequent use of antibiotics to treat respiratory tract infections may have an unintended benefit of removing undiagnosed subclinical infections at the maternal-fetal interface that could cause PROM. Further studies are needed to ascertain the mechanisms by which upper respiratory tract disease, pneumonia, and asthma exert their effect on the risk of PROM and also the potential protective effect of acute and chronic bronchitis. Policies that are designed to increase the awareness of patients and care takers for early recognition and management, and implementing preventive methods such as active immunization or prophylactic therapy are of importance.

It is important to recognize the limitations of large administrative databases. Foremost among them is the possibility of data on the prevalence of respiratory diseases being underreported in the NHDS data. Women hospitalized for any respiratory conditions during pregnancy (remote from the delivery-related hospitalization) or those who received outpatient treatment may not have been captured in the study. Thus, our reported associations are modestly conservative.

Data on maternal race were missing for up to 20%> of records between 1995 and 2001, and in up to 30% of records thereafter [26]. The NCHS reported that counties with non-reporting hospitals have higher proportions of whites compared to counties with reporting hospitals, suggesting differential reporting of race in the NHDS data [35]. We excluded discharge records with missing data on race in our race-stratified analysis and this exclusion may have resulted in an overestimation of rates of acute and chronic respiratory diseases among whites. In order to assess whether missing data on maternal race had biased the findings of our analysis on race- disparities in the association between acute and chronic respiratory conditions and PROM, we conducted a sensitivity analysis after assigning all missing values to white race. The result of the sensitivity analysis did not differ substantially from the results found after excluding the missing values on race from the analysis. Since our study was based on the data of women who required hospitalizations, the reported prevalences of respiratory tract conditions are likely underestimated, limiting generalizability to pregnant women seen as outpatients. However, these results do underscore the need for careful monitoring and timely treatment of respiratory conditions in order to prevent PROM. The discharge survey is based on random samples of hospitals and may not be representative of all non-federal short-term hospitals. Since the dataset lacks temporality between onset of respiratory conditions and PROM, it is unlikely to establish a cause-and-effect relationship. Because information about medications during pregnancy is not well documented in the NHDS data it is difficult to determine if the increased risk of PROM in an asthmatic woman is a result of the disease or anti-asthmatic drugs. Furthermore, the risk of PROM due to these drugs at prophylactic doses remains unknown. However, previous studies have reported the risk associated with asthma medications used during pregnancy to be minimal compared to the risks associated with largely uncontrolled asthma [36-38]. Only a small fraction of an administered dose of inhaled corticosteroid reaches the lung, and therefore this is considered safe during pregnancy [39]. Asthmatic pregnant women generally have poor asthma knowledge and skills [40]. Patient education on self-management and timely diagnosis and treatment, coupled with closely mentoring this pregnant population may help to reduce the rate of PROM and associated complications.

On the other hand, the strengths of the study include its large sample size, a population-based cohort, and control for potential confounding factors. Previous studies have reported that the precision of coding of diagnoses and procedures in the dataset exceeds that of other datasets from the NCHS. Coding errors for procedures and diagnosis were estimated to be about 0.9% [41,42]. Pregnancies complicated by acute respiratory tract conditions and asthma requiring hospitalization are associated with PROM, especially among blacks. We speculate that patient education, timely diagnosis and treatment, and closely mentoring this pregnant population may help reduce the rate of PROM.

Acknowledgements

DG, CVA, and JCS are partly supported through a grant (HD038902) from the National Institutes of Health awarded to CVA.

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DARIOS GETAHUN1, CANDE V. ANATH1, YINKA OYELESE2, MORGAN R. PELTIER2, JOHN C. SMULIAN2, & ANTHONY M. VLNTZILEOS2

1 Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences,

UMDNJ-Robert Wood Johnson Medical School, NJ, USA and 2 Division of Maternal-Fetal Medicine, Department of

Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, NJ, USA

(Received 9 January 2007; revised 30 May 2007; accepted 15 June 2007)

Correspondence: Darios Getahun, MD, MPH, Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901-1977, USA. Tel: +1 732 235 5178. Fax: +1 732 235 6627. E-mail: [email protected]

Copyright Taylor & Francis Ltd. Sep 2007

(c) 2007 Journal of Maternal – Fetal & Neonatal Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

The Alzheimer’s Association, families affected by Alzheimer’s, celebrity advocates, businesses, Governor Patrick, and mayors across the commonwealth, including Boston’s Mayor Menino, are stepping up to focus public attention on the rapidly growing health crisis of Alzheimer’s disease. Friday, September 21st is World Alzheimer’s Day, an internationally recognized day that unites opinion leaders, people with dementia, their care-givers and family, medial professionals, researchers, and the media from around the world. The Alzheimer’s Association’s Massachusetts Chapter supports the day’s simple message — now is the time to act.

“More than five million people in the U.S. have Alzheimer’s, and that number is about to increase catastrophically,” said James Wessler, President/CEO of the Alzheimer’s Association in Massachusetts.

On Friday, organizers and advocates will be at Quincy Market, City Hall Plaza, and the Boston Common from Noon to 2:00 p.m. dressed in purple tee-shirts and distributing information about Alzheimer’s disease and the Alzheimer’s Association. The tee-shirts will be emblazoned with the campaign slogan “VOICE,” which encourages people to speak up on behalf of individuals with Alzheimer’s who are not able to speak for themselves.

Events will also take place at the Basketball Hall of Fame in Springfield from Noon — 1:00 p.m. Carl Beane, who serves as the public-address announcer for Boston Red Sox games at Fenway Park, will be at center court to give a free talk. Beane will speak about family memories, baseball memories, and how Alzheimer’s can destroy them. Helen Caulton-Harris, director of health and human services for the Springfield Department of Health will also take part in the program, conveying the World Alzheimer’s Day message. Employees at local participating businesses are being asked to wear purple.

Recently, Massachusetts-based celebrities including singer/actress Joanna “Jo Jo” Levesque, author/talk show host Keith Ablow, KISS 108’s Matt Siegel, WCVB’s Mary Richardson, Boston Bruin Marc Savard, Fox 25’s Kim Carrigan, Magic 106.7’s Nancy Quill, and many others lent their image to the cause by becoming Alzheimer’s Champions, urging people to take action against this disease.

Governor Deval Patrick has joined the following mayors throughout Massachusetts by signing proclamations in support of World Alzheimer’s Day:

 

 

Boston – Thomas M. Menino

Easthampton – Michael Tautznik

Fall River – Edward M. Lambert, Jr.

Greenfield – Christine Forgey

Lawrence – Michael J. Sullivan

Lowell – William F. Martin Jr.

Lynn – Mayor Edward J. Clancy, Jr.

New Bedford – Scott W. Lang

Pittsfield – James M. Ruberto

Springfield – Charles V. Ryan

Westfield – Charles Medeiros

Worcester – Konstantina B. Lukes

Researchers predict that by 2050 the global prevalence of the disease will quadruple, affecting more than 100 million individuals. If you don’t know someone with this mind-robbing disease, you soon will, said Wessler of the Alzheimer’s Association.

“Alzheimer’s has been tagged an old persons’ disease, and we’ve all heard the jokes about ‘old-timers’ disease, but the fact is that it’s a fatal disease, not normal aging. It is a devastating disease for those who have it and those who love them,” said Wessler.

It’s not too late for anyone who wants to get involved, Wessler said. It’s as simple as wearing purple on this Friday, and telling people why. Or get involved in one of the “Memory Walks” now happening across the commonwealth over the next two weekends. According to Wessler, national funding for Alzheimer’s research is losing ground in the important battle to find a treatments and an eventual cure. Information is available at www.alz.org/MA.

About The Alzheimer’s Association, Massachusetts Chapter

Headquartered in Watertown, Massachusetts, the Massachusetts Chapter of the Alzheimer’s Association opened its doors in 1980 as one of the founding Chapters of the national association. Throughout the state of Massachusetts, we strive to offer a high level of programs and services to individuals with Alzheimer’s and their caregivers. To meet the increasing demands for service and support, the Massachusetts Chapter has expanded programs, and has added four regional offices around the state: Lowell, Sandwich, Springfield and Worcester. In 2007, the Chapter assumed responsibility for providing services to families and professionals living and working in New Hampshire. For more information visit alz.org/ma or call (617) 868.6718.

Spiration, Inc., a developer of novel medical technology designed to benefit patients with acute and chronic conditions of the lung, today reported further results of a pilot study of its IBV Valve System for patients with severe emphysema. Data were presented at the European Respiratory Society’s Annual Congress in Stockholm by Daniel Sterman, M.D., director of Interventional Pulmonology at the University of Pennsylvania Medical Center in Philadelphia.

“Encouraging results continue to indicate that Spiration’s treatment holds promise for improved quality of life for patients with severe emphysema, many of whom do not respond well to current medical treatments or are not eligible for major surgery such as lung volume reduction or lung transplantation,” said Dr. Sterman. “There are currently few treatment options for these patients. I am excited that Spiration’s therapy may offer hope.”

For the treatment of emphysema, the IBV Valve System is designed to redirect airflow from diseased portions of the lung to healthier areas. During the minimally invasive procedure, a catheter is passed through a bronchoscope (a flexible tube passed into the bronchial tubes through the mouth or nose) to deploy the small umbrella-shaped valves into the airways of the upper lobes of the lungs. Although the valves are intended to be permanent, they are designed to be removed via a minimally invasive procedure if necessary.

Retrospective Subset Analysis Provides Insight into Treatment’s Mechanism of Action

In another session during the conference, Steven Springmeyer, M.D., FCCP, vice president and medical director for Spiration, presented a retrospective subset analysis of data from U.S. patients enrolled the IBV Valve System pilot study that concluded that most responses to bronchial valve treatment for emphysema are due to redirection of inspired airflow.

“This analysis broadens our understanding of this innovative treatment for emphysema, providing insight into the mechanism of action of the IBV Valve System and demonstrating that overall lung volume reduction is not necessary to achieve a clinically meaningful improvement in quality of life,” said Dr. Springmeyer. “Spiration is pleased with these results and with the progress we have made with the IBV Valve System to date. We are looking forward to enrolling the first patients in the U.S. pivotal trial of the IBV Valve in the near future.”

Design of Randomized, Blinded European Study Presented

Earlier at the conference, on Sunday, September 15, Vincent Ninane, M.D., of the St. Pierre Hospital in Brussels, Belgium presented details about the design of Spiration’s current European clinical study of the IBV Valve System.

“The use of valves to block airflow to areas of severe emphysema has been shown to be safe, with reports of improved quality of life. However, these studies have been case series without blinding,” said Dr. Ninane. “Since health status improvements can be influenced by placebo effects, effectiveness evaluations require a rigorous clinical study design. The European study of Spiration’s therapy is the first and currently the only announced study of a bronchial valve to meet these rigorous requirements.”

The objective of the European clinical study of the IBV Valve System is to augment the clinical data used to obtain the CE Mark with data from a randomized, blinded study. Study endpoints are lung volume changes as measured by CT scan quantification and changes in disease specific health status as measured by the St. George’s Respiratory Questionnaire in patients who have been randomized and are blinded to either treatment or control groups.

The first patients were enrolled in the European study in April 2007. Investigators are actively recruiting patients. The study is open to men and women age 40 to 74 who have been diagnosed with predominantly upper lobe emphysema and shortness of breath with exertion. Eligible patients are able to participate in pulmonary function and standardized exercise tests, have not smoked for four months and are willing to not smoke during the study. Additional criteria must be met for participation in the study. For more information, including trial site locations, please visit www.spiration.com.

About Emphysema

Emphysema, a component of Chronic Obstructive Pulmonary Disease (COPD), is a common, debilitating lung disease with no cure in which the tiny air sacs that make up the lungs (alveoli) are enlarged or destroyed. This impairs the exchange of oxygen and carbon dioxide with the blood, reduces the lungs’ ability to exhale air, and is accompanied by coughing and breathing difficulties, initially with exertion and eventually also while at rest. The most common cause of emphysema is an inflammatory reaction to inhaled smoke. Currently available treatments for emphysema are generally palliative and include medications, home oxygen therapy, pulmonary rehabilitation, lung volume reduction surgery and lung transplantation.

About the IBV Valve System

Spiration’s IBV Valve System is a minimally invasive device under investigation in the U.S. for the treatment of severe emphysema. The system has received CE Mark approval for the treatment of diseased and damaged lung in Europe and is an investigational device in Canada.

About Spiration, Inc.

Spiration, Inc. is committed to improving quality of life for patients with acute and chronic conditions of the lung through the development of novel therapies. Founded in 1999 in Redmond, Wash., the privately held company is backed by prominent investors including Three Arch Partners, New Enterprise Associates, Versant Ventures, New Leaf Ventures, InterWest Partners, Investor Growth Capital, GE Capital, Boston Scientific Corporation and Olympus Medical Systems Corporation. For more information, visit the company’s website at www.spiration.com.

CAUTION — Investigational Device. Limited by Federal (or United States) Law to Investigational Use.

BOCA RATON, Fla., Sept. 19 /PRNewswire-FirstCall/ — Eclipsys Corporation(R), , The Outcomes Company(R), today announced that Bronx-Lebanon Hospital Center Health Care System, Bronx, NY, will implement Sunrise Clinical Manager as the information solution to support its continuous improvement culture.

(Logo: http://www.newscom.com/cgi-bin/prnh/20050209/FLW006LOGO )

Bronx-Lebanon, the largest voluntary not-for-profit health system serving the South and Central Bronx, will implement Eclipsys’ Sunrise Clinical Manager integrated platform, including the modules Sunrise Acute Care(TM), Sunrise Emergency Care(TM), Sunrise Ambulatory Care(TM), Sunrise Critical Care(TM), Sunrise Pharmacy(TM), Knowledge-Based Medication Administration(TM), and Knowledge-Based Charting(TM).

To help ensure that patient information flows seamlessly from registration and scheduling to the point of care, Bronx-Lebanon will also implement Eclipsys Sunrise Patient Registration(TM) and Sunrise Enterprise Scheduling(TM), both of which are integrated with Sunrise Clinical Manager.

“When the Eclipsys program is fully implemented in the next two years, we will have the important advantage of a fully integrated electronic medical record system for the inpatient, ER and outpatient areas; thereby enabling us to keep pace with the latest technological advances in the field,” stated Steven Anderman, chief operating officer, Bronx-Lebanon Hospital Center Health Care System.

Integrated Platform to Better Connect Care Providers

Eclipsys integrated clinical solutions will connect caregivers so no matter where a patient presents – across the enterprise or in the community – each clinical team member has access to the up-to-date health records. It will leverage the evidence-based order sets in Eclipsys Knowledge-Based CPOE(TM) solution to help improve efficiency and drive adherence to standard practices. Eclipsys’ user-friendly interface will enable Bronx-Lebanon physicians to build their own order sets, thereby engaging them in the implementation process, and helping to drive high rates of solution adoption.

“Bronx-Lebanon has a long history of using clinical information solutions to improve the quality of care delivery. As the organization looked for a modern platform, the selection of Sunrise Clinical Manager reflects on the quality of our XA architecture and our proven ability to help our clients achieve outcome improvements,” said Jay Deady, Eclipsys executive vice president, Client Solutions. “Eclipsys and Bronx-Lebanon both share an organizational commitment to continuous improvement. Our Outcomes Methodology incorporates this philosophy into our implementation process, and we look forward to working with Bronx-Lebanon to help refine its clinical workflows so that rapid clinician adoption and outcome improvements are achieved and then consistently improved.”

Taking Order Reconciliation to the Next Level

By connecting its care teams with a shared database and electronic medical record (EMR), Sunrise Clinic Manager will help clinicians deliver medications safely to patients anywhere in the healthcare system, or in the community. As patients move from one setting to another, clinicians will have access to previous medication orders, the opportunity to review them alongside new orders and plans for care, and a chance to reconcile any differences in a proactive manner. From the physician placing the orders, to the pharmacist dispensing the medication, to the nurses administering medications incorporating the “five rights,” Eclipsys provides an end-to-end solution that connects the care team and helps prevent errors.

Using Content to Help Transform Care Delivery

With Sunrise Clinical Manager’s care transforming content, clinicians will receive actionable knowledge at the point of decision making to help improve care delivery. Eclipsys’ executable clinical content will help maintain high standards of care by providing clinicians easy access to the latest clinical evidence and increasingly complex regulatory requirements.

The Eclipsys solutions will be remotely hosted by the ISO 9001:2000- certified Eclipsys Technology Solutions Center in Mountain Lakes, NJ.

About Bronx-Lebanon Hospital Center

Bronx-Lebanon Hospital Center Health Care System is continuing to fulfill its essential leadership role as “Doctor to the Community.” It is the largest teaching and voluntary not-for-profit health care system serving the South and Central Bronx, with 964 beds at two major hospital divisions, two special long-term care facilities, and an extensive BronxCare network of more than 70 outpatient practices that provided 926,000 visits in 2006. Bronx-Lebanon is fully accredited by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), with 14 residency programs that are certified by the Accreditation Council for Graduate Medical Education (ACGME); strong indicators of its medical excellence.

About Eclipsys

Eclipsys is a leading provider of advanced integrated clinical, revenue cycle and access management software, clinical content and professional services that help healthcare organizations improve clinical, financial, operational and client satisfaction outcomes. For more information, see http://www.eclipsys.com/ or email [email protected].

Statements in this news release concerning the benefits provided by Eclipsys software, content, and implementation and remote hosting services are forward-looking statements and actual results may differ from those projected due to a variety of risks and uncertainties. Implementation and customization of Eclipsys software is complex and time-consuming. Results depend upon a variety of factors and can vary by client. Each client’s circumstances are unique and may include unforeseen issues that make it more difficult than anticipated to implement or derive benefit from software, content or services. The success and timeliness of the company’s services will depend at least in part upon client involvement, which can be difficult to control. Eclipsys is required to meet specified performance standards, and the contract can be terminated or its scope reduced under certain circumstances. More information about company risks is available in recent Form 10-Q and 10-K filings made by Eclipsys from time to time with the Securities and Exchange Commission. Special attention is directed to the portions of those documents entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” Eclipsys Corporation and The Outcomes Company are registered trademarks of Eclipsys Corporation. Sunrise Clinical Manager, Sunrise Acute Care, Sunrise Emergency Care, Sunrise Ambulatory Care, Sunrise Critical Care, Sunrise Pharmacy, Knowledge-Based Medication Administration and Knowledge-Based Charting are trademarks of Eclipsys Corporation. Other product and company names in this news release are trademarks and/or registered trademarks of their respective companies.

   Eclipsys   Jason Cigarran   Director of Media Relations   (media)   (561) 322-4355   [email protected]    Robert J. Colletti   Chief Financial Officer (investors)   (561) 322-4655   [email protected]    Bronx-Lebanon   Errol C. Schneer   Vice President Planning, Marketing & Public Relations   (718) 901-8595  

Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/20050209/FLW006LOGOAP Archive: http://photoarchive.ap.org/PRN Photo Desk, [email protected]

Eclipsys Corporation

CONTACT: Media, Jason Cigarran, Director of Media Relations,+1-561-322-4355, [email protected]; or Investors, Robert J.Colletti, Chief Financial Officer, +1-561-322-4655,[email protected], both of Eclipsys; or Errol C. Schneer, VicePresident Planning, Marketing & Public Relations, of Bronx-Lebanon,+1-718-901-8595

Web site: http://www.eclipsys.com/

By DANIEL ELKAN

THE SYMPTOMS sound like something from The X Files sufferers complain of a crawling sensation all over the body, egg-like lumps under the skin and, even more bizarrely, cuts which produce tiny red and blue fibres.

Many doctors, however, are highly sceptical dismissing the symptoms as imaginary and patients as delusional.

But a growing number of experts believe the symptoms are genuine, and the U.S. government’s Centre for Disease Control and Prevention (CDC) is investigating the condition Morgellons disease as reported today in the New Scientist.

This belated recognition comes as a great relief to the many thousands of sufferers, such as Beverley Warren, who have struggled for years with this debilitating condition.

‘It feels like tiny insects crawling or biting under my skin,’ says Beverley, 63, from Manchester.

As a result she hardly sleeps at night, constantly woken by the intense itching on her arms.

‘I scratch and scratch, but it doesn’t help. I’ve suffered hundreds of nights like this. Sometimes I just lie awake, crying.’ Beverley’s arms are covered with dozens of sores. Some have tiny, white, egg-like lumps on them, just under the skin surface.

More bizarrely, when Beverley scratches her arms, small black specks, which look like tiny grains of pepper, appear from under the surface of the skin.

The problem appeared 11 years ago. Doctors and dermatologists have been unable to give her a diagnosis, and two skin biopsies have provided no answer.

At the suggestion of a dermatologist, Beverley applies creams to try to soothe the itching and then bandages her arms for two days to protect the area. Unfortunately, this hasn’t helped.

‘The only thing that provides relief is when I put ice on my arms,’ she says.

Then in April, Beverley discov- ered that she was not the only person with the problem. After typing ‘itching on the arms’ into an internet search engine, she came across a website for Morgellons disease.

‘My husband looked at the screen and said: “My God, those are all the symptoms you’ve described.” ‘ Incredibly, more than 10,000 people worldwide had registered on the website claiming they suffered, too. But in addition to Beverley’s symptoms, many complained of something even stranger: tiny fibres, of various colours, growing out of their skin.

One of them is Rita, who lives in Somerset. She says: ‘The fibres are 1mm or 2mm long and are either pinky red, blue, brown, black or transparent. They look like little hairs and most grow out of the lesions on my arms, legs and torso.’ Four years ago, Rita, 47, started being affected by what many sufferers describe as brain fog.

‘My thinking became cloudy and forgetful,’ she explains. ‘I jumble up my words and sometimes, if someone is talking to me, I can’t understand what they are saying so I have to ask them to repeat themselves.’ The condition forced Rita to give up her career as a legal secretary.

‘The doctors are very dismissive.

One doctor sent the fibres off to a lab, but all she said was that nothing abnormal had been detected.’ AMONG Morgellons sufferers, this is a common experience.

The disease was named in 2002 by an American mother, Mary Leitao, whose two-year-old son one day pointed to his lip and said ‘bugs’.

Mary was alarmed to find fibres growing there, but soon became frustrated that no doctor would investigate her son’s condition.

She began researching it for herself, and came across a 17th- century article which described a condition, ‘The Morgellons’, where unusual hairs would grow out of the skin.

In the U.S., where the majority of cases are found, the number of people claiming to have the same symptoms and the absence of a medical explanation led to last month’s launch of the government’s CDC investigation, involving a team of specialists in epidemiology, environmental health, dermatology, chronic diseases, infectious diseases, pathology and mental health.

However, most experts believe the condition is a psychological disorder called delusional parasitosis. Sufferers convince themselves the crawling sensations and fibres are evidence of an infection by a parasite.

‘The brain tells them something is crawling on or under their skin,’ says

Professor Lynn Kimsey, an expert on insects and disease at the University of California.

‘The human brain is wired to make connections between events, but we don’t always draw the right conclusions.

Only in a small proportion of cases do real parasites such as mites cause this type of thing.’ Instead, Prof Kimsey says, the skin sensations are likely to be the result of changes in brain and nerve chemistry, commonly triggered by drug or alcohol abuse or hormonal changes such as the menopause.

The patients constantly scratch their skin a process called neurotic excoriation creating sores that never get the chance to heal.

As Professor Noah Scheinfeld, a dermatologist at Columbia University in the U.S., explains: ‘The skin becomes a sink for nervous energy and the slightest sensation can lead people to itch.’ Even the fibres have a simple explanation: ‘They inevitably turn out to be lint from clothes, household fibres or hair,’ Kimsey says.

‘Sores and scabs attract and trap these fibres.’ The sceptics say Morgellons is best treated with dermatological creams for the sores and possibly anti-psychotic drugs in severe cases.

But a handful of experts have found evidence that seems to contradict conventional explanations.

Randy Wymore, assistant professor of pharmacology at Oklahoma State University, stumbled across the Morgellons website and, surprised by the number of people claiming to be affected, offered to test some of the fibres at his lab.

‘I thought it would be easy to determine their origin,’ he says. But contrary to his expectations, the fibres did not match any common environmental ones. So Wymore invited some Morgellons patients in to be examined by a colleague, Rhonda Casey.

She found that even under unbroken skin there were masses of fibres.

After extensive tests, scientists including a police forensics team drew a blank as to their origin, despite comparing them to more than 90,000 organic compounds. MEANWHILE, at the State University of New York, Vitaly Citovsky, professor of biochemistry and cell biology, found that the lesions of Morgellons patients test positively for the presence of agrobacterium, a bacterium used in the commercial production of genetically modified food but not normally found in skin sores.

Psychiatrist Robert Bransfield has studied a database of 3,000 Morgellons patients and argues that the psychological profile of Morgellons patients does not fit with a diagnosis of delusional parasitosis.

‘Before the onset of their illness, their mental status appears to be quite representative of the general population,’ says Bransfield.

‘Later on they may become paranoid and delusional; but they don’t start out that way.’ Immunopsychology experts such as Bransfield are discovering that the body’s own immune reaction to invasion by a parasite can significantly affect levels of brain chemicals, such as serotonin.

In other illnesses, such as hepatitis C, this can result in altered psychological states and mental symptoms.

Morgellons could work this way, too, Bransfield suggests.

Some test results have led researchers to speculate that Morgellons may be caused by an unusual fungal parasite. For Beverley, the new investigation cannot come soon enough.

‘I’m not delusional,’ she says. ‘I just want to find out what is happening to my body.’

(c) 2007 Daily Mail; London (UK). Provided by ProQuest Information and Learning. All rights Reserved.

VIRGINIA BEACH, Va., Sept. 17 /PRNewswire-FirstCall/ — AMERIGROUP Corporation today announced that Mary McCluskey, MD, has been named Chief Medical Officer to oversee healthcare services for the Company’s 1.5 million members.

“We are excited to welcome Dr. McCluskey to AMERIGROUP,” said James G. Carlson, AMERIGROUP President and Chief Executive Officer. “Throughout her career, she has distinguished herself as an attending clinician, physician executive and leader of a major healthcare organization. She has the experience and the commitment to help AMERIGROUP expand its mission of bringing quality healthcare to the financially vulnerable, seniors and people with disabilities.”

“I’m honored to join such an experienced team and to assist AMERIGROUP and the 1.5 million members it serves,” McCluskey said. “This is an exciting time for the Company, and I look forward to contributing to its efforts of bringing quality care and service coordination to those who need it most.”

For the past eight years, Dr. McCluskey has served in a variety of senior medical positions with Aetna Inc., most recently as Chief Medical Officer, Northeast Region. In this role, she was the senior clinical and medical quality leader for a division that provided health insurance for 2.4 million people through employer-sponsored and Medicare programs. Under her guidance, the company’s Northeast region earned an excellent accreditation rating from the National Committee for Quality Assurance. Her previous positions at Aetna included National Medical Director/Head of Clinical Cost Management and Senior Regional Medical Director, Southeast Region.

Prior to Aetna, McCluskey was Vice President of Medical Affairs for Medpartners Medical Management in Tampa. She previously served as Internist/Medical Director of Bridgeton Health Center in St. Louis. McCluskey began her career as an Urgent Care Physician in St. Louis. A graduate of St. Louis University and the St. Louis University School of Medicine, she completed her residency in Internal Medicine at Jewish Hospital/Washington University in St. Louis.

AMERIGROUP offers disease management programs for 11 different conditions, ranging from asthma and diabetes to AIDS and schizophrenia, eight of which are accredited by the National Committee for Quality Assurance. The Company’s health plan in the District of Columbia has also obtained accreditation and a rating of commendable from the NCQA. All AMERIGROUP health plans in the District and nine states offer members a range of initiatives that are designed to connect the 1.5 million members with quality, preventive healthcare programs that target the specific needs of low-income Americans.

About AMERIGROUP Corporation

AMERIGROUP Corporation, headquartered in Virginia Beach, Virginia, improves healthcare access and quality for the financially vulnerable, seniors and people with disabilities by developing innovative managed health services for the public sector. Through its subsidiaries, AMERIGROUP Corporation serves more than 1.5 million people in the District of Columbia, Florida, Georgia, Maryland, New Jersey, New York, Ohio, Tennessee, Texas and Virginia. For more information, visit http://www.amerigroupcorp.com/ .

   CONTACTS:   Investors:  Julie Loftus Trudell      News Media:  Kent Jenkins, Jr.               AMERIGROUP Corporation                 AMERIGROUP Corporation               Senior Vice President,                 Senior Vice President,               Investor Relations                     Communications               (757) 321-3597                         (757) 518-3671  

AMERIGROUP Corporation

CONTACT: Investors: Julie Loftus Trudell, Senior Vice President,Investor Relations, +1-757-321-3597, or News Media: Kent Jenkins, Jr., SeniorVice President, Communications, +1-757-518-3671, both of AMERIGROUPCorporation

Web site: http://www.amerigroupcorp.com/

Evercare®, one of the nation’s largest health care coordination programs, today announced it has received approval from the Centers for Medicare and Medicaid Services (CMS) to offer the first Medicare Advantage Special Needs Plan for people with Alzheimer’s disease and chronic dementia. The Company also announced it will expand its portfolio of Chronic Illness Special Needs Plans, designed for people with a high burden of illness due to complex health conditions such as heart disease, diabetes and chronic obstructive pulmonary disease (COPD).

Evercare continues its legacy of providing innovative approaches to health care coordination by offering the first Medicare Advantage Special Needs Plan designed exclusively for Medicare beneficiaries with Alzheimer’s disease and chronic dementia. The Evercare® Health Plan for People with Alzheimer’s Disease and Related Dementia provides full Medicare coverage as well as extra benefits and services tailored to meet the unique needs of people living with Alzheimer’s — a debilitating condition that affects five million Americans. With the plan benefits and services delivered through Evercare’s proven care model, members and their family caregivers will receive the support they need to cope with the stress and issues of living with Alzheimer’s. The plan will be available in Maricopa County, AZ.

In 2008, Evercare will more than quadruple the availability of its Chronic Illness Special Needs Plans from seven to 34 states. These plans are designed for Medicare beneficiaries with complex and multiple chronic health conditions — individuals who are among the heaviest users of medical care in the nation. People with five or more chronic conditions make up just 20 percent of Americans age 65 and older, yet they account for 68 percent of all Medicare spending. By providing personalized attention focused on prevention, integration of treatments and ongoing health care coordination, as well as more benefits and services than those covered by Medicare alone, Evercare Chronic Illness Specials Needs Plans help members and their families manage their conditions, avoid complications and unnecessary costs.

At the heart of all Evercare health plans is the unique and innovative Evercare Care Model. It provides the personal attention and coordinated care necessary to support people with complex and often multiple health conditions who often take several medications daily and receive care from an array of health care professionals. Nurse Practitioners and Professional Care Managers serve as trusted partners to Evercare members by helping to orchestrate communication and services so that physicians, health care providers, families and members are all working in concert to keep the member healthy and living as independently as possible.

“Caring for people with Alzheimer’s disease and other chronic illnesses places extraordinary demands on those living with the disease, their families, health care providers, and the nation’s health care system. With the introduction of our Special Needs Plan for people with Alzheimer’s and the expansion of our plans for individuals living with chronic illness, Evercare will bring its proven Care Model to those who need it most,” said John Mach, M.D., a geriatrician and CEO of Evercare.

Enrollment for the new Evercare Chronic Illness Special Needs Plans and the Evercare® Health Plan for People with Alzheimer’s Disease and Related Dementia begins November 15, 2007 for coverage beginning January 1, 2008.

Evercare’s Explosive Growth, Proven Success

Evercare was created 20 years ago, guided by the vision of two innovative Nurse Practitioners who observed that the neediest Medicare beneficiaries could benefit from more care delivered in a personalized, compassionate and highly focused way. Evercare’s deep understanding of the Medicare population’s complex needs and its ability to address those needs have fueled tremendous growth for the Company. Since the beginning of the decade, Evercare has greatly expanded its spectrum of offerings to meet the evolving health and lifestyle needs of people with more complex conditions wherever they live and has nearly tripled its member base since 2003

Data shows that the pioneering Evercare Care Model delivers greater access to medical and non-medical services, better health outcomes, and lower costs to Medicare and Medicaid. According to a report by Robert Kane, University of Minnesota, and as reported in the Journal of American Geriatrics Society (2003), the Evercare approach and continuity of care has been shown to help prevent some problems before they become serious — reducing hospitalizations for nursing home residents by 45 percent and trips to the emergency room by 50 percent.

In addition, 97 percent of family members/other responsible parties are satisfied with Evercare’s plan for nursing home residents, while 91 percent of members and responsible parties in Evercare Medicaid plans are satisfied and 95 percent intended to continue with Evercare.

Today, Evercare applies the innovative Evercare Care Model to those in institutional, community and hospice settings, and who are eligible for support through both Medicare and Medicaid. In addition, Evercare offers services for caregivers and for individuals in advanced stages of illness through Evercare™ Solutions for Caregivers and Evercare™ Hospice & Palliative Care, respectively.

The Birth of Special Needs Plans — Medicare Reform

Special Needs Plans are a special type of health plan designed to ensure that the people who need the most care — those with complex health care needs and chronic conditions — receive it in a personalized, coordinated way. By emphasizing preventive care and early intervention, SNPs reduce unnecessary hospitalizations, emergency room visits, and the over-prescribing of medications.

Congress looked to Evercare as a primary model for the creation of Special Needs Plans under the Medicare Modernization Act of 2003 (MMA), and today, Evercare is the leading provider of SNPs in the continental U.S. Special Needs Plans help make health care more effective and cost-efficient. While people with five or more chronic conditions made up just 20 percent of all Medicare beneficiaries in 2004, they accounted for over two-thirds of the program’s costs according to Partnership for Solutions in a 2004 report. Evercare will again be working with Congress to ensure that Special Needs Plan authority is reauthorized so that these kinds of innovative plans can continue to be made available beyond 2008.

“Special Needs Plans are a vital part of the health care system in that they allow high-risk Americans, or people with the most complex, most burdensome conditions, to receive the level of care and support they need,” said Richard Bringewatt, President of the National Health Policy Group and Chair of the Special Needs Plan Alliance, a national leadership organization of leading Specialty Healthcare Programs and the only national organization specifically dedicated to representing the needs and interests of Special Needs Plans. “The SNP Alliance is committed to stabilizing Special Needs Plan legislation for the long-term so that innovative organizations like Evercare, which has a legacy of serving the special needs of this population, can continue to do so.”

About Evercare

Evercare is one of the nation’s largest care health coordination programs for people who have long-term or advanced illness, are older or have disabilities. Founded in 1987, Evercare today serves more than 150,000 people nationwide through Medicare, Medicaid and private-pay health plans, programs and services — from health plans for people in community and skilled nursing settings, to caregiver support and hospice care. Evercare offerings are designed to enhance health and independence, and in the complex world of health care, make getting care easier. Evercare is part of Ovations, a division of UnitedHealth Group (NYSE:UNH) dedicated to the health care needs of Americans over age 50. For more information about Evercare, call 1-888-834-3721 (TTY 1-888-685-8480) or visit EvercareHealthPlans.com.

By Chang, Tzu-Yuan Chou, Kang-Ju; Tseng, Chin-Feng; Chung, Hsiao-Min; Et al

Key words: Albumin – C-reactive protein – Folic acid – Hemodialysis – Homocysteine – Vitamin B ABSTRACT

Objective: Folic acid and vitamin B coplex administration in uremic patients has been reported to lower plasma total homocysteine (tHcy) levels, but whether or not this has a beneficial effect on the inflammatory state is not clear.

Methods: We conducted a randomized open labeled study to determine the effects of folic acid (5 mg daily) and vitamin B complex administration on plasma tHcy levels as well as inflammatory (serum high-sensitivity C reactive protein, hs-CRP) and nutritional (serum markers in patients on maintenance hemodialysis. Treatment was given for 3 consecutive months to 61 patients on maintenance hemodialysis. Another 60 patients, all age-, sex-, hemodialysis duration- matched served as control group.

Main outcome measures: Plasma tHcy, serum hs-CRP, albumin, creatinine (Cr), post-dialysis body] weight (BW), and normalized protein catabolism rate (nPCR).

Results: After 3 months, levels of plasma tHcy and serum hs-CRP, Cr, and nPCR were significantly decreased while levels of serum albumin, vitamin B,;, folate, and BW were significantly increased. The dialytic dose (KTW) and dietary intake remained unchanged. However, correlations between the magnitude of reduction of tHcy & hs-CRP, tHcy & Cr, and Cr & nPCR were statistically significant,

Conclusions: Folic acid and vitamin B complex co-administration effectively lowers tHcy and hs-CRP levels and increases albumin levels in stable hemodialysis subjects, underscoring their potential benefit to attenuate the state of inflammation and possibly improve the nutritional status in patients on hemodialysis.

Introduction

Hyperhomocysteinemia is a known risk factor for cardiovascular events and mortality in the general population1,2. In uremic patients, plasma total homocysteine levels (tHcy) are remarkably elevated3. In the past, numerous prospective studies4,5 have considered hyperhomocysteinemia as a risk factor for cardiovascular disease (CVD) as well as worsening survival in uremic patients. Recent prospective studies regarding the ability of tHcy to predict cardiovascular event or death in end-stage renal disease (ESRD) have shown that a low, rather dian a high tHcy is an indicator of poor outcome in hemodialysis patients6-8. These different results might be explained by the latest atudies of Ducloux et aV and Suliman et al.10 which showed a graded increase in relative risk with high tHcy levels after adjustment for confounders including nutritional and inflammatory markers. At present, there is concern over whether lowering plasma homocysteine is beneficial for dialysis patients11.

Folic acid is known to lower tHcy concentration in the general population and uremic patients1-3. However, several large prospective atudies revealed that folic acid and vitamin B supplement do not lower the risk of CVD12-14 in the high risk population for CVD. Until now there are only a few studies addressing this dilemma in uremic patients. Wrone et al.1 found no significant difference in the incidence of cardiovascular events and the mortality rate in patients on hemodialysis given varying doses of folic acid. On the contrary, Righetti et al.15 reported that homocysteine-lowering vitamin B (including folic acid) treatment decreases cardiovascular events in hemodialysis patients.

Since the presence of malnutrition and inflammation may confound the association between tHcy and clinical outcome in ESRD patients6, study designs to evaluate the homocysteine-lowering effect of the combination therapy with folic acid and vitamin B should consider the influence of underlying nutritional and inflammatory status. To date, no study has investigated how combined folic acid and vitamin B complex administration for the treatment of hyperhomocysteinemia may affect levels of serum inflammatory markers and nutritional status in uremic patients. Our study aims to examine the changes in the levels of tHcy, the inflammatory and the nutritional markers on stable hemodialysis patients who were given folic acid and vitamin B complex.

Patients and methods

Study design

Because of the inconclusive evidence regarding the role of hyperhomocysteinemia in uremia, most of the patients in our hemodialysis center had not been prescribed folic acid and vitamin B supplements in the 2 years prior to this study. This study included stable hemodialysis patients who were not taking folic acid and vitamin B complex in the past 6 months prior to the investigation. The same patients were on hemodialysis three times per week for more than 6 months using low-flux polysulfone membranes with surface areas ranging from 1.1 to 1.9 m^sup 2^. The criteria for exclusion were chronic infections such as tuberculosis and osteomyelitis, malignancy, liver disease (cirrhosis diagnosed by sonography and acute hepatitis diagnosed by elevated liver enzyme and symptoms/ signs) and drug intake (statins, fibrate, nonsteroidal anti- inflammatory drugs, steroids16, phenytoin, methotrexate, theophylline, estrogen”). The trial was designed as a randomized, controlled open-label study. A total of 136 patients were eligible and agreed to participate. Group matching with gender, age (within 5 years), and duration of hemodialysis (within 1 year) was conducted for every pair group and they were then randomly assigned to either active treatment or control group. A total of 72 patients were randomized to a treatment group who were given folic acid (5 mg daily) and vitamin B complex (B1: 5 mg, B2: 3 mg, nicotinamide: 20mg, B6: 0.5 mg, B12: 1 [mu]g, calcium pantothenate: 3 mg three times daily) for 3 consecutive mondis. A total of 64 patients were assigned to the control group who continued taking their usual prescription which did not include folic acid and vitamin B supplement. This study was approved by the medical ethics committee of our institution and all participants gave their informed written consent.

Since recording of food intake is the only method available to estimate dietary energy intake in dialysis patients in clinical practice, these patients were encouraged not to change their usual dietary habits, as supervised by a skilled dietitian18. Body weight (post-dialysis weight), body mass index (BMI), mean blood pressure, plasma tHcy, serum hs-CRP, IL-6, albumin, creatinine (Cr), total cholesterol, hematocrit, vitamin B12, folate, ALT level, clearance of urea per dialysis (KT/V) and normalized protein catabolism rate (nPCR) were recorded at baseline and after 3 months.

Pre- and postdialysis levels of serum urea were recorded for evaluation of single-pool KT/V (Daugirda method)19. nPCR was calculated from monthly kinetic modeling sessions by applying the two-blood urea nitrogen (2-BUN) method20 to predialysis BUN level, and an estimate of equilibrated postdialysis BUN level obtained using the Daugirdas-Schniditz equation. Body mass index (BMI in kg/ m^sup 2^) was calculated from patient height obtained at study entry and postdialysis weight measurements obtained at monthly kinetic modeling sessions.

Some of the participating subjects had a history of diabetic mellitus and CVD. Diabetic mellitus (DM) was defined as a past DM history or two measurements of fasting blood sugar above 126mg/dL. CVD was defined by history with cerebrovascular disease, peripheral artery disease, and coronary heart disease.

Blood measurements

A total of 6 ml of pre-dialysis fasting blood sample was drawn from each patient, 2 ml of which were added to ethylenediaminetetraacetic acid (EDTA), centrifuged within 15 min of collection, and the plasma stored at -7O0C until analysis. The remaining 4 ml of blood was centrifuged and the serum stored at – 70[degrees]C. Routine monthly blood testing was continued for all the patients studied.

Levels of fasting plasma tHcy (Immulite, DPC Cirrus Inc. Los Angeles, CA, USA), serum hs-CRP (Immulite, DPC Cirrus Inc., Los Angeles, CA, USA) and the proinflammatory cytokine, IL-6 (Immulite, Euro/ DPC Ltd, UK) were measured by enzyme-amplified chemiluminescence. The normal range for tHcy was 5-13.5 [mu]mol/L. Serum hs-CRP and IL-6 levels were monitored as indices of the degree of inflammation, with normal limits below 0.6 mg/dL and 9.7 pg/ml, respectively.

Serum folate and vitamin B12 levels were determined using a radioassay kit (MP Vitamin B12/folate Simul TRAC-SNB, MP Biomedicals Inc., NY, USA). The normal limit for serum folic acid was above 1.5 ng/ml, and the normal range for vitamin B12 was 160-970 pg/ml.

Levels of serum total cholesterol, albumin, Cr, urea and ALT, which are included in the routine monthly blood tests, were studied as a homogenous assay in a liquid phase on a Hitachi 7600 (Hitachi Ltd, Tokyo, Japan). Hematocrit was measured by automated hematology analyzer K-4500 (Sysmex Corporation, Japan).

Statistical analysis

Continuous variables are expressed as mean +- SD and categorical values are expressed in frequency and percentage. The normality test was performed initially. If the data were normally distributed, the chi-square or Fisher exact test and Student t-test were used to compare the difference between control and experimental groups. Paired f-test was applied to compare the values obtained at baseline and after 3 months. Pearson correlation coefficients were applied to evaluate the correlations between the baseline levels of plasma tHcy, serum albumin, hs-CRP, and nPCR. It was also used to evaluate the correlations between the magnitude of increase/reduction levels of plasma tHcy, serum hs-CRP, albumin, Cr and nPCR after 3 months’ treatment. The Mann-Whitney U-test or Wilcoxon test was used if the normality test failed. The p-value

In the experimental group, 61 of the 72 subjects completed the study. The remaining 11 subjects failed for various reasons, including hospitalization due to acute illness (four), poor ‘compliance (three), nausea and abdominal discomfort due to medications (two), transfer to another hemodialysis center (one), and death (one). In the control group, 60 of the 64 subjects completed the study. The remaining four subjects failed because of hospitalization due to acute illness (three) and withdrawal of consent for blood extraction at the end of the study (one). Patient compliance with folic acid and vitamin B complex intake in the experimental group was verified by two mediods: daily record- keeping of actual pill intake and monitoring of vitamin B12, folate and tHcy levels. Dietary intake was also monitored.

Table 1 shows the baseline demographic, clinical characteristics and biochemistry profile (values are expressed as mean +- standard deviation) of all the subjects. There was no remarkable difference between the two groups except albumin level (p = 0.045). The baseline median (range) of serum hs-CRP were 0.60 (0.21-1.11) and 0.51 (0.37-0.63) mg/dL in the experimental and control group, respectively, and tHcy were 31.9 (22.33-40.16) and 33.3 (29.60- 38.89) [mu]mol/L. The causes of ESRD in the experimental group are: diabetic nephropathy (16), chronic interstitial nephropathy (13), chronic glomerular nephropathy (9), lupus nephritis (2), polycystic kidney disease (2), gouty nephropathy (1), trauma-related nephrectomy (1), and unknown (1 7). In the control group, the causes of uremia were: diabetic nephropathy (16), chronic interstitial nephropathy (14), chronic glomerular nephropathy (10), lupus nephritis (3), polycystic kidney disease (1), and unknown (16).

Table 2 compares the clinical features and the biochemistry findings before and after treatment. In the experimental group, levels of plasma tHcy (mean +- standard deviation 34.01 +- 14.89 vs. 22.01 +- 10.55 [mu]mol/L, p

Table 1. Clinical characteristics and biochemistry data, at inclusion, for hemodialysis subjects with or without folic acid and vitamin B therapy

In the baseline data (Table 3) only Cr and albumin showed a positive significant correlation [r = 0.282, p = 0.0276). However, we observed positive correlated trends between nPCR & albumin (p = 0.0521), tHcy & hs-CRP (p = 0.065), and tHcy & Cr (p = 0.0695), but a negative correlated trend between hs-CRP & albumin (p = 0.0553). In comparing the correlation (Table 4) between the magnitude of increase [(final level – initial level)/initial level] of serum albumin , and the magnitude of reduction [(initial level – final level)/ initial level] of serum hs-CRP, Cr, plasma tHcy or nPCR in the experimental group, only the magnitude of reduction of tHcy and hs-CRP, the magnitude of reduction of serum Cr and nPCR and the magnitude of reduction of Cr and tHcy were significantly correlated (r = 0.527, p

Figure 1. Pearson correlation of reduction rates of tHcy (X axis) and hs-CRP (Y axis) after 3 months of treatment in experimental subjects (r = 0.527, p

Discussion

This study showed that folic acid and vitamin B complex administration for 3 months significantly decreased plasma tHcy and serum hs-CRP levels and increased serum albumin levels in stable hemodialysis patients. The present study suggests that folic acid and vitamin B treatment on hemodialysis patients without previous intake may (1) lower the tHcy level, (2) decrease the inflammation marker hs-CRP, and (3) increase the nutritional marker albumin.

Table 2. Comparison of clinical characteristics and biochemistry data in hemodialysis subjects before and after 3 months of treatment

Table 3. Pearson correlation coefficient data between the baseline of tHcy, hs-CRP, albumin, Cr, and nPCR in the experimental group

Chronic inflammation, with increased levels of various acute phase reactants such as hs-CRP, has recently been shown to be a common feature which increases cardiovascular risk and predicts a worse outcome in patients with ESRD3,21,22. The relationship between hyperhomocysteinemia and inflammation has long been the goal of research23-25. Several studies have proved that Hcy itself may serve as an inflammatory marker26-28. Thus, the reduction in tHcy levels achieved after vitamin supplementation may lead to patients presenting very similar reductions in CRP concentrations. In our study, both the control and experimental groups had baseline high- normal levels of hs-CRP, indicating that all of our study subjects have modest inflammation before treatment. After 3 months of treatment, hs-CRP levels significantly decreased in the experimental group. Our study also found significant correlations between the magnitude of reduction of hs-CRP and tHcy levels after treatment. Since the liver is considered the most likely major organ for Hey metabolism in renal patients29 and that CRP is produced predominantly by hepatocytes, therefore, it would not be unexpected that Hcy-lowering treatment would lower CRP levels as well. Our data strongly suggested that folic acid and vitamin B treatment induced a decrease in serum hs-CRP as a consequence of the decrease in the plasma tHcy26-28. Thus, combination therapy with folic and vitamin B complex in stable hemodialysis patients not only lessens plasma tHcy but also attenuates modest inflammation.

Table 4. Pearson correlation coefficient data between the rates of increase of serum albumin and the rates of reduction of hs-CRP, tHcy, Cr, nPCR levels in the experimental group

Elevation of serum IL-6 levels may be an important predictor of outcome in patients on dialysis30. Kimmel et al.31 have reported that higher levels of circulating pro-inflammatory cytokines, such as IL-6, are associated with increased mortality. The cytokine IL-6 is a 2OkDa polypeptide secreted by fibroblasts, adipocytes, monocytes and endothelial cells31. Dialysis-related uremia or an oxidative state may increase IL-6 levels, since IL-6 levels are positively correlated with time on hemodialysis, an observation which is not apparent with CRP32. Serum IL-6 levels were not changed signifkantiy in our subjects after 3 months of treatment. However, it should be noted that most of our patients had relatively low levels of baseline IL-6, which underscores the fact that our subjects did not have obvious inflammation. On the other hand, IL-6 analysis was done with enzyme-amplified chemiluminescence assay which is much less sensitive for values in the lower range as our data showed.

Stenvinkel et al.33 have proposed the existence of a syndrome consisting of malnutrition, inflammation and atherosclerosis (the MIA syndrome) in some patients with chronic renal failure. The MIA syndrome involves a chain of events triggered by inflammatory agents stimulating the hepatic secretion of proinflammatory cytokines and CRP. It is generally accepted that inflammation exerts an effect on albumin level34. Inflammation acting through nuclear factor kappa B (NF-kappaB) causes decreased albumin gene expression, with resultant decreased rate of albumin synthesis27,35, consequently leading to a reduced serum albumin concentration. Our study found significant decrease in the levels of hs-CRP after 3 months of treatment. During the same period, albumin levels were increased significantly. These findings may indicate that attenuation of the degree of inflammation as a result of folic acid and vitamin B complex supplementation may lead to the improvement of the nutritional status36.

Both CRP and albumin are produced in the liver. Hepatic synthesis of albumin is lower in dialysis patients with elevated CRP levels37. Aldiough different stimuli may govern their production, any change in liver function will have considerable effects on bodi CRP and albumin production. Our study showed no significant changes in serum ALT levels during the study period. Likewise, the dialysis dosage, KT/V, during the study period also showed no obvious change. Thus, these two variables could not have played a significant role in the modulation of the inflammatory and nutritional status in our study subjects. Our result is similar to a study by Vernaglione et al.38 which showed that atorvastatin, a lipid-lowering agent, decreases serum CRP levels in hemodialysis patients after 6 months of treatment, with a corresponding increase in serum albumin levels.

nPCR, also called the protein equivalent of nitrogen appearance (PNA), is the parameter used in most hemodialysis units to assess dietary protein intake only in patients who are in a steady state. We use nPCR in our analysis as a surrogate for nutritional intake. Clearly, there is a mismatch between nPCR and dietary nitrogen ingestion, since it frequently overestimates nitrogen intake, especially in the inflammatory situation39. Although nPCR is often viewed as a variable that can be manipulated independently, it varies directly with the Kt/V, a measure of dialysis adequacy. Our study showed that folic acid and vitamin B treatment obviously decreased nPCR which may indicate decreasing protein catabolism. The dialysis dosage and the dietary habits during the study period were unchanged in our study groups. Apparendy, Kt/V and dietary intake did not seem to play an important role in modulating protein catabolism in our patient groups. However, the inflammatory status was explicitly decreased as serum hs-CRP showed. Therefore, lessening the degree of inflammation may lower the nPCR. Strikingly similar results were observed for the serum Cr concentration. In dialysis patients, serum Cr concentration may serve as a surrogate marker of somatic protein in tiiat it is a reflection of muscle mass34. Indeed, Cr concentration is a function of production, including that contributed by diet, distribution, and removal. Clearly, dialysis intensity would be expected to affect predialysis serum Cr levels. However, our data presented here showed consistent dialytic dosage during the study period. After 3 mondis of treatment, our study group showed a marked decrease in serum Cr and a slight but significant increase in body weight. In the absence of obvious blood pressure changes during the study period, the observed minimal increments in the body weights of our subjects may be due to increased intracellular water. Meanwhile, the observed decline in levels of creatinine (Cr) is probably partly due to loss of muscle mass in the treated group. In addition, creatine synthesis and homocysteine formation are metabolically connected. Hey is derived from methionine in a multiple step metabolic cycle39. Methionine can intracellularly be converted to S-adenosyl methionine, which acts as a universal metbyl donor in numerous transmethylation reactions in vivo. On the other hand, creatine is synthesized in humans by two successive metabolic steps. First, guanidinoacetate is synthesized mainly in the kidney, then guanidinoacetate is metiiylated in the liver to creatine by guanidinoacetate-metiiyltransferase (GAMT] widi S-adenosylmediionine as metiiyl donor40. Exogenous folic acid and vitamin B supplementation can, thus, be expected to decrease endogenous Hey synthesis with parallel decrease in creatine synthesis which may then contribute to a lower serum Cr level.

In conclusion, we found tiiat treatment of hyperhomocysteinemia with folic acid and vitamin B complex significantly lowers plasma tHcy and serum hs-CRP levels, with corresponding increases in serum albumin levels. Such treatment with folic acid and vitamin B is effective and beneficial for stable maintenance in hemodialysis patients, but whether the amelioration of inflammation and improvement of the nutritional status may provide a degree of cardiovascular protection deserves further elucidation.

Acknowledgments

The research for this article was supported by Kaohsiung Veterans General Hospital grant VGHKS94-018.

We are deeply grateful to Ms. Yang YC and Mr. Chiu CC for their excellent technical and administrative help.

* This work was presented in part at the XLIII ERA-EDTA (European Renal Association – European Dialysis and Transplantation Association) annual congress, Glasgow, United Kingdom, July 15-18, 2006

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18. Kloppenburg WD, Stegeman CA, Hooyschuur M, et al. Assessing dialysis adequacy and dietary intake in the individual hemodialysis patient. Kidney Int 1999;55:1961-9

19. Burr T. Two sample hemodialysis urea kinetic modeling. Validation of the method. Nephron 1995;69:49-53

20. Daugridas JT, Schneditz D. Overestimation of hemodialysis dose depends on dialysis efficiency by regional blood flow, but not by conventional 2-pool urea kinetic analysis. ASAIO J 1995;41:M7 19- 24

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23. Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 2002;22:6-13

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CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-3915_3, Accepted for publication: 05 June 2007

Published Online: 29 June 2007 doi:10.1185/030079907X218077

Tzu-Yuan Chang(a), Kang-Ju Chou(a), Chin-Feng Tseng(b), Hsiao- Min Chung(a), Hua-Chang Fang(a), Yao-Min Hung(a), Ming-Jei Wu(a), Huey-Ming Tzeng(c), Chang-Chung Lind and Kuo-Cheng Lu(b)

a Division of Nephrology, Department of Medicine & Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan

b Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, Hsin-Tien City, Taipei, Taiwan

c Division of Nursing Business and Health Systems, the University of Michigan, School of Nursing, Ann Arbor, Ml, USA

Address for correspondence: Kuo-Cheng Lu, MD, Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, 23rd F, No 65, Min-Chiuan Road, Hsin-Tien City, Taipei, Taiwan. Tel: + 886-2-29155739; Fax: + 886-2-29107920; [email protected]

Copyright Librapharm Aug 2007

(c) 2007 Current Medical Research and Opinion. Provided by ProQuest Information and Learning. All rights Reserved.

By Wagenitz, Andreas Mueller, Edgar A; Frentzel, Adrian; Cambon, Nathalie

Key words: Analgesia – Diclofenac – Non-inferiority analysis – NSAID – Osteoarthritis – Sustained-release ABSTRACT

Objective: To compare the analgesic efficacy and tolerability of a sustained-release pellet formulation of diclofenac (Olfen-100 SR Depocaps, SR-CAP, Mepha Ltd, Aesch, Switzerland) with the standard reference formulation (Voltaren retard 100, SR-TAB, Novartis Pharma AG, Basel, Switzerland), both containing 100 mg diclofenac sodium, in patients with osteoarthritis (OA) of the knee and/or hip. In addition, diclofenac’s current place in the symptomatic therapy ol OA is briefly reviewed.

Methods: In this 2-week double-blind, active-controlled, non- inferiority trial, 210 OA patients were randomised to receive either SR-CAP once daily or SR-TAB once daily (n = 105 for both groups). The primary efficacy endpoint was the change in visual analogue scale (VAS) pain score (0-100 mm) at rest at Day 14 compared with baseline. Secondary variables included the change in VAS pain score on movement and global assessments of efficacy and tolerability using verbal rating scales (VRS).

Results: Between baseline and Day 14, mean +- SD VAS pain score at rest decreased by 44.4 +- 18.5 mm in the SR-CAP group (n = 89) compared with 41.2 +- 19.8 mm in the SR-TAB group (n= 82) based on the per protocol population. Comparable changes were observed in the intention-to-treat population. The lower bound of the 1-sided 97.5% confidence interval was -2.7 mm and greater than the prespecified non-inferiority limit of -10 mm. There was a trend towards a better tolerability with SR-CAP compared with SR-TAB based on mean +- SD VRS scores (SR-CAP, 0.6 +- 0.68; SR-TAB, 0.9 +- 1.0 for assessment by patients; p = 0.063).

Conclusion: SR-CAP is as effective as and possibly better tolerated than SR-TAB in patients suffering from painful OA.

Introduction

Osteoarthritis (OA) is the most prevalent disease of the locomotory apparatus with an associated risk of mobility disability, especially in the elderly. OA can occur in any synovial joint but is most common in the hands, knees and hips1. There is no cure and current therapeutic strategies are primarily aimed at reducing pain and improving joint function. Non-steroidal anti-inflammatory drugs (NSAIDs] are among the most widely prescribed medications in the world and are frequently taken by patients with OA. NSAIDs primarily act on the cyclo-oxygenase (Cox) enzyme that converts arachidonic acid into prostaglandins. Amongst other functions, prostaglandins mediate inflammation and pain. Two principal forms of the Cox enzyme have been described; Cox I and Cox II2. Cox I is normally present in platelets, vascular endothelial cells, the stomach and the kidney whereas Cox II is usually produced in response to inflammatory stimuli2. However, Cox II can also be found in brain and kidney in the absence of inflammation3. Research results indicated that the gastrointestinal (GI) adverse events associated with the use of NSAIDs are caused by Cox I inhibition and the desired anti- inflammatory action is mediated via the inhibition of Cox II3. This led to the development of selective Cox II inhibitors (coxibs). However, they have been associated with an increased risk for cardiovascular complications and a class effect has been suggested4. Since the withdrawals of rofecoxib and valdecoxib, the benefit/risk ratio of the remaining coxibs is still under debate3,5.

Current guidelines recommend the use of a simple analgesic, paracetamol (acetaminophen), or a NSAID given either systemically or topically as first-line or second-line therapies in patients with symptomatic OA6-8. Less than 10 NSAIDs are used on a regular basis with diclofenac being the most frequently administered NSAID worldwide9. Diclofenac is regarded as one of the better tolerated NSAIDs10 and has been available for many years in various formulations for the treatment of acute and chronic rheumatic disorders. Daily dosages ranging between 75 mg and 150 mg proved to be both efficacious and well tolerated in the symptomatic treatment of OA, with a maximum effect usually reached within 2 weeks11-14. Due to its short half-life of 1-2 h, sustained release formulations of diclofenac have been developed to allow for less frequent treatment schedules and possibly improving compliance.

Olfen-100 SR Depocaps, Mepha Ltd, Aesch, Switzerland (SR-CAP) is a sustained-release pellet formulation containing 100 mg diclofenac sodium. A preceding unpublished multiple dose relative bioavailability study in 24 healthy male and female volunteers showed that SR-CAP delivers bioequivalent diclofenac exposure (in terms of area under the curve [AUC]) to the reference drug, Voltaren retard 100, Novartis Pharma AG, Basel, Switzerland (SR-TAB). The latter is a sustained release tablet (dragee) also containing 100 mg diclofenac sodium. The bioavailability study followed an open, randomized, crossover design and each preparation was administered once daily for 4 days. Blood samples for determination of diclofenac in plasma were collected over 24 h following morning drug intake (fasting conditions) on Day 4. The rate of diclofenac absorption was lower with SR-CAP compared to SR-TAB as reflected by an approximately 30% lower mean maximum plasma concentration (C^sub max^).

Against this background the present study was performed. We compared the efficacy and tolerability of SR-CAP (test) with that of SR-TAB (reference) in patients with painful osteoarthritis of the knee and/or hip. The main objective of the study was to demonstrate clinical non-inferiority of the analgesic effect of SR-CAP when compared with SR-TAB, thereby supporting the assumption that a lowered C^sub max^ has no impact on the efficacy of the drug.

Moreover, a reappraisal of diclofenac’s place in the symptomatic therapy of OA is provided in the light of new warnings concerning coxibs in patients with increased risk of cardiovascular thrombotic events.

Patients and methods

The study was carried out at 10 centres (general practice) in Germany as a randomised, active-controlled, double-blind clinical trial with two parallel treatments in adult male and female patients. The first patient was enrolled in June 2005 after approval of the study protocol had been obtained from independent ethics committees, and the study was completed in December 2005. All patients had given their informed consent before enrolment. The study was performed in accordance with the Declaration of Helsinki with all its amendments taking into account the principles of Good Clinical Practice (GCP). Each patient was assigned in chronological order to one of two treatment groups using a computer generated block randomisation list (allocation ratio 1:1).

Outpatients, aged 18-75 years, were eligible for enrolment if they had a confirmed diagnosis of primary OA of the knee and/or hip, based upon clinical and diagnostic radiographic (Kellgren & Lawrence Index grade II or III15) criteria. A diagnosis according to the American College of Rheumatology (ACR) was required and the patient had to be in functional class I, II or III16. Patients had to suffer from OA symptoms for at least 3 months and, in the judgement of the investigator, would need analgesic treatment for at least the duration of the study. Moreover, patients were required to present a pain intensity at rest of >/= 50 mm on a horizontal 100 mm visual analogue scale (VAS; 0 mm = no pain, 100 mm = unbearable pain).

Pregnant women and women of child-bearing potential not using effective means of contraception were excluded, as well as patients with blood coagulation/haematological disorders and patients who had known allergies to diclofenac or to ingredients of the study medication. In addition, patients with acute OA requiring additional treatment and/or arthroplastic surgery during the course of the study did not qualify for enrolment. Likewise, patients were not eligible for inclusion if they had received intra-articular corticosteroid or hyaluronic acid injections within 3 months prior to the study, underwent treatment with systemic corticosteroids or anticoagulants within 4 weeks before the trial, had a history or presence of gastroduodenal ulcer or GI bleeding, or presented with severe cardiac, hepatic, or renal disorders as well as any other concomitant severe or chronic disease. Patients with inducible porphyria or presenting with osteonecrosis/aseptic necrosis were also excluded. The use of NSAIDs (including coxibs) or any other analgesic treatment (except paracetamol for rescue) was not allowed within 3-7 days before study start, depending on the half-life of the drug. Physiotherapy was not permitted during the wash-out and treatment period. During the study, patients were instructed not to take any other NSAIDs (except study medication), anticoagulants, analgesics, corticosteroids (> 5 mg/day of prednisone), other antiarthritic drugs, immunosuppressives and drugs interacting with diclofenac. Low dose aspirin was permitted.

Eligible patients were randomly allocated to receive either oral SR-CAP or SR-TAB, containing 100 mg of diclofenac sodium each. The study medication was ingested by the patients once daily in the morning for 14 days. Both SR-CAP and SR-TAB were to be taken with 150 mL of water in close relation to a meal. The percentage of unused study medication assessed at the end of treatment served as a measure of compliance (at least 80% of the scheduled study medication was to be taken to be compliant). Patients received their study drug at baseline (Visit 1). They had to return to the study site for efficacy and safety assessments at Day 7 (Visit 2) and Day 14 (Visit 3); a deviation of +- 2 days was permitted. Study medication (Olfen-100 SR Depocaps and Voltaren retard 100) was supplied by Mepha Ltd., Aesch, Switzerland. An independent statistician produced the randomisation list for this clinical trial and the study medication was packaged according to this randomisation list by an independent contract research organisation (CRO). Nobody else had access to the randomisation list until the database was closed. For blinding purposes, both medications were filled in identical-looking capsules and backfilled with lactose. Thus, test and reference preparations were visually indistinguishable.

Demographic characteristics, medical and drug history as well as classification of OA disease were assessed before study enrolment at the baseline examination. Patients also underwent a complete physical examination. For patients requiring a wash-out period, an additional screening visit took place within 3-7 days before baseline; at that time paracetamol rescue medication was dispensed. Vital signs were determined at all study visits. Routine haematological (erythrocyte sedimentation rate, haemoglobin, haematocrit, red blood cells, white blood cells and differential platelets) and biochemical (sodium, potassium, calcium, alanine aminotransferase [ALAT], aspartate aminotransferase [ASAT], gamma glutamyl transpeptidase [gamma-GT], alkaline phosphatase, cholesterol, glucose, uric acid, creatinine, total protein, albumin) laboratory measurements were performed before (screening or baseline) and after the study (at Visit 3). The thromboplastin time was additionally determined at baseline. All female patients of childbearing potential had a urine pregnancy test before and after the study.

Patients assessed their pain intensity at the target joint (hip or knee) both at rest and on movement at all three study visits (considering the last 24 h) using the 100 mm VAS. The primary efficacy endpoint was the change in VAS pain score at rest at Visit 3 (Day 14) compared with baseline. Secondary efficacy endpoints included the change in VAS pain score at rest at Visit 2 (Day 7) compared with baseline, the change in VAS pain score on movement at Visits 2 and 3 compared with baseline and a global efficacy assessment by patients and investigators using a 5-point verbal rating scale (VRS) (much better, better, unchanged, worse, much worse) at Visit 3.

Safety and tolerability was evaluated on the basis of adverse events and changes in laboratory parameters. In addition, patients and investigators assessed the tolerability of the study medication using a 5-point VRS (very good, good, moderate, poor, very poor) at the end of the study.

Statistical analysis

Efficacy analyses were performed for the intention-to-treat (ITT) and per protocol (PP) populations. The ITT population included all randomised patients who received at least one dose of study medication and for whom at least one efficacy assessment was performed. The PP population included all patients of the ITT population without major protocol violations, the definition of which had been prospectively defined in die statistical analysis plan before database lock. Safety was analyzed for the safety population, defined as all patients who received at least one dose of study medication.

The primary efficacy analysis (change in VAS pain score for the target knee or hip at rest between Visits 1 and 3) was based on the PP population. The robustness of these results was tested by comparison with ITT analysis results. The primary analysis (non- inferiority analysis) was an analysis of covariance (ANCOVA) including treatment and study centre as terms and the baseline VAS score (at rest) as covariate. A 1-sided 97.5% confidence interval (CI) was calculated for the between-group difference in VAS score changes (test minus reference) using least square means. Clinical non-inferiority of SR-CAP compared with SR-TAB was accepted if the lower bound of this CI was greater than -10 mm. For secondary efficacy variables on VAS, 1-sided 97.5% CIs were calculated for the differences between treatments. For statistical analysis of VRS results, ratings were allocated to figures between 0 and 4 (0 = best, 4 = worst). VRS scores were analysed according to the analysis of variance (ANOVA) procedure with treatment and study centre as factors. Safety parameters were evaluated descriptively.

The clinically relevant non-inferiority margin (delta) for the primary efficacy variable was defined as 10 mm on the VAS pain scale (0-100 mm). Such a non-inferiority margin has been previously applied for these types of studies17-19. Standard deviations (SD) for VAS assessments between 18 mm and 27 mm have been reported17,20,21. A sample size of 100 patients per group was determined to conclude non-inferiority of SR-CAP to SR-TAB based on the following assumptions: delta = 10 mm, SD = 23 mm, level of significance alpha = 2.5% (1-sided t-test), power (1-beta) = 80%, dropout/non-valid patient rate = 15%.

Table 1. Demographic and clinical characteristics of patients at baseline (ITT population)

Results

In total, 210 patients (105 per treatment group) were randomised to treatment groups. Twenty-five patients (10 SR-CAP, 15 SR-TAB) discontinued the study prematurely. Of these, 20 discontinued for adverse events (8 SR-CAP, 12 SR-TAB); a further 2 patients (1 per group) were withdrawn because of serious adverse events. Other reasons were unsatisfactory therapeutic response (n = 1) and protocol violation (n = 1), both in the SR-TAB group. One SR-CAP patient withdrew consent; this subject never took study medication and was, therefore, excluded from the ITT population. Hence, the ITT population comprised a total of 209 patients (104 SR-CAP, 105 SR- TAB).

For the definition of the PP population, the 25 patients discontinuing the study prematurely were excluded. A further 14 patients were excluded because of pain intensity at rest of < 50 mm on VAS at time of randomisation (n = 3), no return of study medication rendering judgement of compliance impossible (n = 3), intake of study medication > 16 days (n = 3), documented non- compliance (n = 2), missing pain assessment at Visit 3 (n = 1) or intake of disallowed concomitant medication (n = 2). Therefore, the PP population consisted of 171 patients (89 SR-CAP, 82 SR-TAB). The ITT population and the population analysed for safety were identical in this clinical trial.

Demographic and clinical characteristics were well balanced between treatment groups and typical for the population investigated. This applies to both the ITT population (Table 1) and the PP population (data not shown). The majority of patients (88.5%) had multiple joints affected by OA, whereas OA localized to specific joints (hip or knee) was reported in 17.7% of patients. Moreover, medical and surgical history was comparable between treatment groups, and there was no difference in baseline VAS scores.

Analgesic efficacy

Both SR-CAP and SR-TAB markedly reduced pain at rest without notable differences between groups at any time during the treatment period (Figure 1). The mean VAS pain scores at rest assessed during the study and the mean changes from baseline are summarised in Table 2, for both the ITT and PP population. Between baseline and Day 14, mean VAS pain score at rest decreased by 44.4mm in the SR-CAP group compared with 41.2 mm in the SR-TAB group based on the PP data set. The lower bound of the 97.5% CI for the between-group difference was -2.7mm and thus greater than the prespecified non-inferiority limit of -10 mm. The results for the ITT population were supportive for claiming non-inferiority of SR-CAP to SR-TAB. For the ITT population, mean VAS pain score at rest decreased between baseline and Day 14 by 43.7mm in the SR-CAP group compared with 36.6mm in the SR-TAB group with a lower bound of the 97.5% CI for the between- group difference of 1.5 mm (indicating possible superiority of SR- CAP in this particular analysis).

Table 2 and Figure 1 also show the reduction in VAS pain scores at rest between baseline and Day 7 (Visit 2). For both, the ITT and PP population, the lower limits of the 97.5% CI for the between- group differences were again greater than -10 mm.

The mean VAS pain scores on movement and the mean changes from baseline are summarised in Table 3 (ITT and PP populations). Both diclofenac formulations, SR-CAP and SR-TAB, markedly reduced pain on movement without notable differences between groups at any time during the treatment period. All analyses yielded lower limits of the 97.5% CI for between-group differences greater than -10mm.

In the investigator’s overall assessment of efficacy at the end of the study, a comparable proportion of patients in both treatment groups were recorded with ‘much better’ or ‘better’ with regard to their current OA status (SR-CAP, 91.0%; SR-TAB, 89.0%). The patient’s assessment of efficacy revealed almost identical results (SR-CAP, 92.1%; SR-TAB, 86.6%). In each group there was one patient who judged his/her OA status as ‘worse’. These assessments are reflected by mean +- SD VRS scores which showed no statistically significant difference (based on ANOVA) between treatment groups for both the investigator’s rating (SR-CAP, 0.6 +- 0.6; SR-TAB, 0.7 +- 0.7) and patient’s rating (SR-CAP, 0.7 +- 0.6; SR-TAB, 0.8 +- 0.7).

Table 2. Pain visual analogue scale (VAS) score* at rest in patients treated with SR-CAP and SR-TAB (PP and (PP and ITT population) Figure 1. Visual analogue scale (VAS) pain scores at rest (mean +- standard deviation) at baseline and during treatment with SR-CAP (n = 89) and SR-TAB (n = 82); per protocol population

Table 3. Pain visual analogue scale (VAS) score* on movement in patients treated with SR-CAP and SR-TAB (PP and ITT population)

Tolerability

Overall, both treatments were well tolerated, with a numerically lower proportion of patients reporting at least one adverse event in the SR-CAP group (30.8%) than in the SR-TAB group (39.0%). Most of the adverse events were considered drug-related and of mild to moderate severity; all patients recovered without sequelae. The most frequently reported adverse events were related to the GI tract (primarily diarrhoea, abdominal pain and nausea), occurring in 25.0% and 32.4% of patients in the SR-CAP and SR-TAB group, respectively (Table 4). Non-GI adverse events occurred in a similar frequency in both groups. One patient in each group experienced a serious adverse event. Both subjects had signs of bleeding in the GI tract (bloody stool and black stool) which resolved upon discontinuation of the study medication. Overall, 20 patients discontinued the study for adverse events (8, SR-CAP, 12, SR-TAB). Except for one case of hypertension, these adverse events were all related to the GI tract (primarily diarrhoea and abdominal pain).

The overall tolerability was assessed as ‘very good’ or ‘good’ by 85.4% of the patients in the SR-CAP group compared with 78.1% in die SR-TAB group (Table 4). The investigator’s assessment of tolerability yielded similar results, whereas tolerability was reported to be ‘poor’ in 1 (1.1%) SR-CAP patient compared with 8 (9.8%) patients in the SR-TAB group. The mean VRS scores for tolerability were lower for the SR-CAP group. Although this difference did not achieve significance, a statistical trend was apparent (p = 0.063 and p = 0.090 for assessment by patients and investigators, respectively).

No clinically relevant changes in vital signs were noted during the study. Likewise, haematological and biochemical variables revealed no statistical or clinically meaningful differences between treatment groups during the course of the study. Two patients in the SR-TAB group had increased liver transaminases which were reported as adverse events.

Discussion

This randomised, active-controlled, double-blind clinical trial was designed to compare the analgesic efficacy and tolerability of two sustained-release 100 mg formulations of diclofenac, SR-CAP (test) and SR-TAB (reference). The results demonstrate non- inferiority of the analgesic effect of SR-CAP when compared with SR- TAB in OA patients. Moreover, SR-CAP shows a trend towards better tolerability than SR-TAB.

Table 4. Number (%) of patients with adverse events during treatment with SR-CAP and SR-TAB, irrespective of cause (safety population)*, and global tolerability assessments by investigators and patients (PP population)

In a preceding multiple dose relative bioavailability study in healthy volunteers, it was shown that SR-CAP is bioequivalent to SR- TAB (in terms of AUC) but diclofenac C^sub max^ was approximately 30% lower. A post-hoc analysis of that study investigated the time above minimum effective diclofenac plasma concentrations of 50-100 ng/mL previously suggested22,23. There was no statistical difference between SR-CAP and SR-TAB widi respect to tiiat parameter indicating the potential for equal analgesic efficacy of both formulations (unpublished data). The present study confirms the assumption that the lowered C^sub max^ of diclofenac has no impact on the efficacy of SR-CAP by demonstrating non-inferiority to the reference drug in a population for whom diclofenac use is very common. In fact, there was a rapid reduction in VAS pain scores at rest (primary efficacy variable) in both per protocol treatment groups, indicating a rapid analgesic effect of both diclofenac preparations. Analyses of secondary efficacy parameters (VAS pain scores on movement and VRS scores) consistendy supported non-inferiority of SR-CAP to SR-TAB. Moreover, the robustness of study results was demonstrated by results from ITT analyses, which were in good agreement with those assessed in the PP population. The reductions in VAS pain scores observed in the present study are in line witii previous investigations on the efficacy of diclofenac in OA patients using the same daily diclofenac dose and a similar trial design20,24. In the study performed by Goei The and colleagues24, the reduction in VAS pain scores on movement at 2-3 weeks was less pronounced compared to our study, which can be explained by the lower mean baseline VAS score on movement of 59.7mm compared to approximately 70mm in this trial.

The use of NSAIDs is traditionally associated with several adverse events, particularly those involving the GI tract. This was also seen in our study, in which most adverse events were GI- related. Overall, both diclofenac formulations were well tolerated with only two serious adverse events reported. It is noteworthy that there were numerically fewer adverse events with SR-CAP than with SR- TAB. Furthermore, the global tolerability assessments showed that patients and physicians had similar perceptions of the tolerability of both formulations, but better VRS scores were obtained with SR- CAP. This was supported by statistical analysis results showing a trend towards a better tolerability with SR-CAP compared to SR-TAB based on VRS scores. The latter observation may be related to the fewer GI adverse events seen in the SR-CAP treatment group. The lower diclofenac C^sub max^ could be the underlying reason for the better GI tolerability with SR-CAP. Although local irritation by orally administered diclofenac allows back diffusion of acid into the gastric mucosa and induces tissue damage, parenteral administration also can cause gastric damage25. Hence, lower maximum diclofenac plasma concentrations might be beneficial to patients in terms of GI tolerability.

Our study has a potential limitation in the fact that placebo control is lacking. However, since numerous previous studies have shown that NSAIDs (including diclofenac) are more effective than placebo in the symptomatic short-term treatment of OA patients, the inclusion of a placebo arm was not considered necessary or ethical26,27.

Place of diclofenac in therapy

For decades, NSAIDs have been frequently taken by patients with symptomatic OA. Many studies and meta-analyses thereof demonstrated the efficacy of oral NSAIDs in the management of pain associated with that disorder26,27. NSAIDs effectively relieve pain by about half and increase mobility in about 60% of subjects with OA as demonstrated by a meta-analysis of two Cochrane reviews28. However, the use of NSAIDs can cause GI toxicity which is dose dependent as evidenced by several systematic reviews8. The identification of Cox II and the subsequent introduction of the selective Cox II inhibitors (coxibs) were thought to be a major breakthrough with the expectation of an analgesic efficacy similar to NSAIDs but a reduction in GI side-effects. In fact, two systematic reviews concluded a significant reduction of GI toxicity with coxibs whilst there was no evidence that coxibs are more effective than traditional NSAIDs29,30. There is, however, a major concern over potential cardiovascular complications (e.g., myocardial infarction or stroke) with the use of coxibs. In 2005, the scientific committee of the European Medicinal Products for Human Use (EMEA) decided to impose restrictions on the use of coxibs. They should no longer be used in patients who have established ischemic heart disease and/or cerebrovascular disease, or in patients with peripheral artery disease. Furthermore, healthcare professionals should exercise caution when prescribing such drugs to patients with risk factors for heart disease. Meanwhile, rofecoxib and valdecoxib have been withdrawn from the market; for the remaining coxibs the benefit/ risk ratio is still under debate3,5.

In view of the safety concerns with coxibs, traditional NSAIDs experienced a renewed interest and strategies were explored for their use in patients at risk for NSAID-related GI complications. A number of strategies have been used to minimise the GI risk due to NSAIDs. Several systematic reviews provided evidence to support the co-administration of NSAIDs with gastroprotective agents such as misoprostol, H^sub 2^ blockers or proton pump inhibitors (PPIs)8. Cost-effective analyses indicated that the addition of a PPI to a conventional NSAID is the most cost-effective option in patients at risk for GI toxicity or cardiovascular event, and hence it was proposed that this strategy is preferable to the use of a coxib31. Recently, a moderate increase in the risk of serious vascular events was suggested also for certain traditional NSAIDs32. Another analysis of a large data set (74 838 users of NSAIDs) found no additional cardiovascular risk from NSAID use33. So far, no placebo- controlled randomised trial has studied the risk of cardiovascular events for NSAIDs.

There is insufficient information to rank the pain-relieving efficacy of different NSAIDs in the treatment of OA34, but it was suggested that diclofenac (100-150 mg) and naproxen (500-750 mg) are more effective than low doses of ibuprofen, and more effective than paracetamol28. In terms of safety, diclofenac is regarded as one of the better tolerated NSAIDs as far as GI toxicity is concerned10. In one meta-analysis, high-dose diclofenac has been associated with a moderately increased risk of thrombotic cardiovascular events32 but this could not be confirmed by others, and, in contrast to coxibs, has never been substantiated by placebo-controlled randomised trials33.

Current treatment guidelines recommend the use of paracetamol or a NSAID as first-line or second-line therapies in patients with symptomatic OA6-8. Two surveys in which patients with OA were asked to rate medications based on their previous experiences provided similar results. The majority of patients preferred NSAIDs to paracetamol because of their better efficacy35-37. Out of the NSAIDs, diclofenac is currently the most widely prescribed NSAID in the world9. Despite the recent debate concerning its potential cardiovascular toxicity, diclofenac has still to be considered as one of the most important drugs in the treatment of painful OA. It should be prescribed at the lowest effective dose for the minimum requisite period of time. Long-term use, if needed, requires regular safety monitoring, especially for blood pressure. Like other NSAIDs, diclofenac should be combined with a gastroprotective agent in patients at high-risk for GI adverse events. Available data support its use, alone or in combination witii a gastroprotective agent, rather than of a coxib; an assessment which is shared by others3,37,38. Conclusion

The results of this study demonstrate the clinical noninferiority of SR-CAP compared with SR-TAB in reducing pain in patients suffering from painful OA of the knee and/or hip. Moreover, SR-CAP shows a trend towards better tolerability than SR-TAB in this patient population. Diclofenac is still one of the most important drugs allowing osteoarthritic patients to live with an acceptable quality of life.

Acknowledgements

Declaration of Interest: Mepha Ltd, Aesch, Switzerland provided the study medication and funded the study. Drs. A. Frentzel and N. Cambon are employees of Mepha Ltd.

We would like to acknowledge the collaboration and commitment of the local investigators and their staff (all located in Germany): Dr. Andreas Wagenitz, Berlin; Dr. Gert Voss, Berlin; Dr. Thomas Burghardt, Munchen; Dr. Volkmar Herkt, Dresden; Dr. Johannes Hettwer, Bad Hersfeld; Dr. Axel Hoist, Hamburg; Dr. Axel Kaden, Hamburg; Dr. Georg Kovacs, Frankfurt; Dr. Jurgen Roch, Dresden; Dr. Dieter Veith, Emmendingen.

* Clinical trial registration number: 2005-000799-42

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CrossRef links are available in the online published version of this paper: http ://www. cmrojournal.com

Paper CMRO-3997_2, Accepted for publication: 20 June 2007

Published Online: 12 July 2007

doi: 1 0. 1 1 85/030079907X223251

Andreas Wagenitz(a), Edgar A. Mueller(b), Adrian Frentzel(c) and Nathalie Cambon(c)

a Clinical practice for orthopaedics, Berlin, Germany

b Institute for Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany

c Medical Department, Mepha Ltd, Aesch, Switzerland

Address for correspondence: Dr. Andreas Wagenitz, Praxis fur Orthopadie, Leonorenstr. 96-98, 12247 Berlin, Germany. Tel.: +49 307 744 342; fax: +49 307 732 7127; e-mail: dr.andreas@wagenitz- berlin.de

Copyright Librapharm Aug 2007

(c) 2007 Current Medical Research and Opinion. Provided by ProQuest Information and Learning. All rights Reserved.

By Rhoades, Torre Lohr, Joann; Jennings, Mark

ALTHOUGH THERE ARE SEVERAL benign appendiceal tumors, there is no clinical significance of benign tumors except when they cause obstruction of the appendiceal lumen and lead to acute appendicitis.1 We report a patient presenting with symptoms of acute appendicitis perhaps caused by an appendiceal neuroma. Case Report

A 43-year-old woman presented with a four-day history of right lower quadrant abdominal pain, generalized malaise, and anorexia. Her last menstrual period was one week before presentation.

Physical exam showed localized peritoneal irritation in the right lower quadrant. She was afebrile and other positive findings were absent. Laboratory studies were normal and a presumptive diagnosis of a viral illness was made. Abdominal ultrasound and computerized tomographic scan were normal. Laparoscopy was performed for persistent symptoms, and thorough inspection of suspected etiologies disclosed no abnormalities. Although there was no apparent evidence of pathology of the appendix, it was removed. The appendix measured 3.5 cm in length and 0.4 cm in diameter. When the appendix was sectioned, it was noted to have a very narrow lumen grossly. There were no inflammatory changes found on the microscopic report. The microscopic description showed fibrous obliteration of the appendiceal lumen. There were spindle cells noted to be within a myxoid background. Nerve fibers and ganglion cells were also noted. These findings were consistent with a diagnosis of appendiceal neuroma. The patient’s pain slowly decreased and she was discharged to home three days after the exploratory laporoscopy with removal of the appendix.

Discussion

Based on the literature review of appendiceal neuroma, it seems that this finding is a rare histologie finding. There are three microscopic histologie patterns for neuroma. A central obliterative appendiceal neuroma has a fibromyxoid core with patchy chronic inflammation and lymphoid aggregates. This type of neuroma occurs most commonly. The lesion consists of loosely arranged aggregates of spindle cells in a background network of eosinophilic cell processes. The proliferation of the lumen consists of fibrous tissue that rests on the submucosa. There is an extensive capillary network throughout each appendiceal neuroma. The second type is described as an intramucosal pattern. These findings are similar to the neural proliferation of central obliterative appendiceal neuroma. The third type of neuroma is the nodular appendiceal neuroma.

The significance of a histologie diagnosis of appendiceal neuroma is thought to be an incidental finding in acute appendicitis. Appendiceal neuroma is potentially a precursor to carcinoid. Carcinoid tumors are characterized with neuron-specified enolase and by neurosecretory granules that are found on electron microscopy. These cells have been designated subepithelial neurosecretory cells (SNC) and have been suggested to be preprogenitors of appendiceal carcinoid tumors.2- 3 Both SNC and carcinoid show an affinity for argentaffin stains. The nest and rosettes formed by SNC are found in half of appendiceal carcinoids. There is variation in electron density of the core of the granules believed to be due to the different states of maturation and proliferation. These findings all suggest that SNC is a progenitor cell of carcinoid tumors. Patients and normal evaluation may, on occasion, have benign appendiceal processes such as fibromas and neuromas. This patient’s pathology may have been a coincidental finding, not related to her symptoms. However, after her appendectomy, her symptoms resolved. This could represent an early presentation for appendiceal neuromas because the lumen of the appendix was narrowed and could have been contributing to her pain.

REFERENCES

1. Chan W, Fu KH. Value of routine histopathological examination of appendices in Hong Kong. J Clin Path 1987;40:429-33.

2. DeLellis RA, Dayal Y, Wolfe HJ. Carcinoid tumors: Changing concepts and new perspectives. Am J Surg Path 1984;8:295-300.

3. Rode J, Dhillon AP, Papadaki L, Griffiths D. Neurosecretory cells of the lamina propia of the appendix and their possible relationship of carcinoids. Histopathology 1982;6:69-79.

TORRE RHOADES, M.D., JOANN LOHR, M.D., MARK JENNINGS, M.D.

From the Department of Surgery, Good Samaritan Hospital, Cincinnati, Ohio

Presented during Poster Grand Rounds at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Lake Buena Vista, FL, February 18-21, 2006.

Address correspondence and reprint requests to Torre Rhoades, M.D., c/o Joy Rusche, Hatten Research Institute-11J, Good Samaritan Hospital, 375 Dixmyth Avenue, Cincinnati, OH 45220. E-mail: [email protected].

Copyright Southeastern Surgical Congress Aug 2007

(c) 2007 American Surgeon, The. Provided by ProQuest Information and Learning. All rights Reserved.

By Bengmark, Stig

ABSTRACT. Background: High levels of glycated and lipoxidated proteins and peptides in the body are repeatedly associated with chronic diseases. These molecules are strongly associated with activation of a specific receptor called RAGE and a long-lasting exaggerated level of inflammation in the body. Methods: PubMed reports over 5000 papers plus > 13,500 articles about the related HbA^sub 1c^, most of them published in the past 5 years. Most of the available abstracts have been read and approximately 800 full papers have been studied. Results: RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation end products, known since 1992, functions as a master switch, induces sustained activation of nuclear factor kappaB (NFkappaB), suppresses a series of endogenous autoregulatory functions, and converts long-lasting proinflammatory signals into sustained cellular dysfunction and disease. Its activation is associated with high levels of dysfunctioning proteins in body fluids and tissues, and is strongly associated with a series of diseases from allergy and Alzheimers to rheumatoid arthritis and urogenital disorders. Heat treatment, irradiation, and ionization of foods increase the content of dysfunctioning molecules. Conclusions: More than half of the studies are performed in diabetes and chronic renal diseases; there are few studies in other diseases. Most of our knowledge is based on animal studies and in vitro studies. These effects are worth further exploration both experimentally and clinically. An avoidance of foods rich in deranged proteins and peptides, and the consumption of antioxidants, especially polyphenols, seem to counteract such a development. (Journal of Parenteral and Enteral Nutrition 31:430-440, 2007) It has been almost 100 years since Malliard1 described the nonenzymatic pathway for glycation of proteins and suggested that such chemically modified proteins could play a role in the pathogenesis of chronic diseases (ChDs), particularly diabetes (DM). However, it is only during the last 2 decades, and especially the last 5 years, that this concept has received wider attention among scientists. Still, most practicing physicians and nutrition experts are still unaware of the concept and its eventual implications on health. Contributory to the recent increase in interest is the observation that glycated hemoglobin, HbA^sub 1c^,2,3 is deeply involved in DM and in various age-associated diseases and, probably more important, the identification of several receptors in the body, which are involved in these processes, of which RAGEs are the most well known and studied.4,5 More than 5000 papers about the biology of advanced glycation products, plus over 13,500 articles about HbA^sub 1c^) are presently available on PubMed.

RAGE: A Master Switch

Metabolic syndrome, with all its clinical manifestations, is strongly associated with the development of ChDs. A discrete, often long-lasting, increased inflammation plays an important role in the development of and maintenance of this syndrome,6 and in the pathogenesis of ChDs. Common to ChDs are, in addition to the increased inflammatory state, a significant elevated oxidant stress (OS) and OS-induced gene expression.6-9 RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation end products (AGEs), functions as a master switch, converting long-lasting proinflammatory signals into sustained cellular dysfunction and disease (Table I).10- 11 This receptor and various other receptors for AGEs and lipoxidation end products (ALEs) play important roles in both oxidative stress and inflammation. RAGE induces a sustained activation of proinflammatory transcription factor NFkappaB and suppresses a series of endogenous autoregulatory functions.12 Experimental studies suggest that increased deposition of AGEs/ALEs in tissues is strongly associated with down-regulation of leptin expression in adipocytes and metabolic syndrome.13 Reducing the inflammatory environment through reduction of tissue accumulation of AGE and ALE ligands has also been shown to reduce sustained exaggerated inflammation and cellular dysfunction, and to improve outcome of disease.10,14

Tissue Accumulation of AGEs and ALEs

As described by Vlassara,14 industrial processes aimed to make food safer, flavorful, and colorful, such as heating, irradiation, and ionization, do this but in combination with gross overnutrition, and also contribute significantly to production of, exposure to, and accumulation of AGEs/ALEs in the body. Vlassara and her group16,16 have demonstrated in human studies significant correlation between ingested AGEs, circulating AGEs, and induction of markers of inflammation. In animal studies, dietary restriction of AGEs has shown “protective” effects against impaired immune function in induced ChDs and in complications to ChDs: DM-induced vasculopathy,17 nephropathy,18 and impaired wound healing.19 Furthermore, it was concluded that the animals remained nearly free of pathology despite the remaining presence of the underlying disease.14 Dietary AGE restriction in animals seemed to be as effective in extending lifespan as caloric restriction (CR).20 Similar observations have been made in human studies, in DM, vascular disease, and kidney disease: patients who were supplied a low-AGE diet responded with a considerable reduction in inflammatory markers and vascular dysfunction.15,21

TABLE I

Cytokines and cellular events associated with AGE or RAGE activation

AGEs constitute a complex and heterogenous group of compounds formed by nonenzymatic reactions of reducing sugars with amino acids, nucleic acids, peptides, and proteins. The first compounds produced, generally called Amadori products, will slowly undergo complex changes, cyclization, dehydration, oxidation, condensation, cross-linking, and polymerization, to finally form more irreversible chemical products, referred to as AGEs/ALEs. These processes are also called Maillard reactions and the products, Maillard products. Some highly reactive carbonyls such as glyoxal and methylglyoxal have been found to rapidly modify reactive side chains of proteins. The epsilon-amino group of lysine and the guanido group of arginine are identified as the most preferential targets for the highly reactive dicarbonyls, which makes lysine- and arginine-rich tissues and foods special targets for such processes. High intracellular and extracellular concentrations of reactive carbohydrates such as glucose, and especially the highly reactive fructose, are important triggers for increased glycation and formation of glyoxal, methylglyoxal, and 3-deoxyglucosan, which glycate proteins, which accumulate both intra- and extracellularly. Significantly elevated visceral AGE formation, serum AGE levels, caspase-3 activation, and cytoplasmic DNA fragmentation are observed in organs such as heart, liver, and kidneys in animals with dyslipidemia due to high-fat diet (32-42% fat),22 findings well in line with >50-year-old observations that a high-fat diet contributes to manifestations of diseases: thrombus formation, renal infarcts, and myocardial infarctions.23

Glyoxal and methylglyoxal formation constitutes an intermediate stage in the Maillard reaction, whereas pentoside, an often-studied glyco-oxidation product and fluorescent cross-link, is formed in the late stage of the reaction, where it becomes more stable and irreversible. Many AGE/ALE compounds have been identified in tissues, and new previously unknown substances are identified at a rate of 2-3 per year. Most studies thus far have focused only on a handful of these substances, apart from HbAlc, mainly pentoside, N^sup epsilon^-(carboxymethyDlysine (CML) and N^sup epsilon^- carboxyethyl) lysine (CEL). Recent and increasing evidence suggests that lipids are as important contributors as carbohydrates to chemical modification of proteins, accumulation in tissues of Maillard products, and pathogenesis of diseases.24 As diary products and meat are the dominating sources of fats and are usually exposed to higher temperature, it is these foods that are the largest contributor of ALEs to the body. Some Maillard products are formed from both carbohydrate and lipid sources; one such example is CML.25 Products derived only from carbohydrate sources, AGEs, are pentoside, crosslines, vesperlysines, and 3DG-imidozolones. MaIondialdehyde (MDA), acrolein adducts of lysine, histidine, and cysteine are specific AGEs.24

AGEs/ALEs and Disease

The levels of AGEs/ALEs in individuals with incipient or manifest ChDs are, when compared with healthy individuals, dramatically and significantly increased. There is, however, great variation in pattern of AGEs/ALEs in the tissues and in the circulation between various patients and groups of patients with ChDs. Both AGEs and ALEs will, when accumulated in tissues, significantly increase the level of inflammation in the body,26,27 reduce antioxidant defense,28 weaken the immune system,29 impair DNA repair mechanisms,30 and increase accumulation of toxins within the tissues26 and increase the rate of infection.26,27 The differences are great; glycated proteins are suggested to produce almost 50 times more free radicals than nonglycated proteins,31 and the plasma concentrations of free CML are reported to be increased about 8- fold with CEL reported at 22-fold in hemodialysis patients.32 Accumulation of modified insoluble, indigestible, and dysfunctional proteins (AGEs/ALEs) occurs predominantly in long-lived tissues such as collagen, neural myelins, and lenses. It leads to decreased elasticity of collagen-rich tissues, which seems to explain the agedependent (and ChD-dependent) increase in stiffness of lenses, joints, skeletal muscles, vascular walls, and an increase in systolic and decrease in diastolic pressure.33 AGEs/ALEs exert strong effects also on shortlived cells such as endothelial cells and pericytes, stimulate growth, interact with cell-surface receptor RAGE, and activate the NFkB pathway, induce vascular endothelium growth factor (VEGF), inhibit prostacycline production, and stimulate plasminogen activator inhibitor-1 (PAI-I) synthesis by endothelial and other cells. Table 1 summarizes documented cellular events and changes associated with AGE and RAGE activation.

Hormones Potentiate AGE/ALE-Induced Inflammation

The process of inflammation is, in addition to being dependent on the status of oxidation/antioxidation, also enhanced by hormones, especially growth and sex hormones, and low levels of vitamins, particularly vitamin D. 17ss-Estradiol, for example, has been shown to significantly up-regulate RAGE mRNA in human microvascular endothelial cells34 and VEGF-dependent angiogenesis.35 This could explain a common observation, exacerbation of diabetic vasculopathy and retinopathy during pregnancy. This assumption is further supported by the finding that RAGE mRNA activation on endothelial cells induced by 7beta-estradiol is abolished when an antiestrogen such as 4-OH tamoxifen is supplemented.36 These observations might also explain why commercial bovine milk, rich in not only AGEs/ALEs but also in estrogens (eg, 17ss-estradiol) have been associated with ChDs such as allergy,36 coronary heart disease,37,38 DM,39-41 Parkinson disease (PD).42 and various cancers such as breast,43’44 prostatic,45,46 testicular,46 and to some extent ovarian47,48 malignancies. It might not be a coincidence that ChDs and rate of complications to ChDs are significantly higher, especially during the winter, at higher altitudes (northern Europe, northern North America), where also secondary hyperparathyroidism, due to poor supply of vitamin D, is more often found.49,50 Parathyroid hormone is known to induce IL-6 and is claimed to significantly increase IL- 6 both in hyperthyroid patients (16-fold) and in overweight patients.49

The Role of AGE/ALE Tissue Deposition in Common ChDs

The deposition of dysfunctioning proteins in tissues will, when pronounced, result in accumulation of histologic changes referred to as amyloid, a common feature in various ChDs. These deposits of AGEs/ ALEs produce a significant fluorescence, and the degree of ALE/AGE in tissues and body fluids can easy and reliably be measured in organs such as the skin, blood, and lenses through estimation of their fluorescence.61 There is with aging a continuous but slow increase in content of AGEs/ALEs also in healthy individuals, but the increase is significantly more pronounced in individuals who are developing or have acquired ChDs. Pronounced increase in levels of AGEs/ALEs in tissues is reported to be strongly associated to metabolic syndrome4,52 and to down-regulation of leptin expression in adipocytes.63

Clinical Relevance of AGEs/ALEs in Specific Groups of Diseases

Accumulation of AGEs/ALEs in tissues and changes suggested to be induced by AGEs/ALEs have been reported in the following ChDs.

Allergy and autoimmune diseases. Thermal processing, curing, and roasting of foods introduce major changes in allergenicity of foods and will often introduce neoantigens and increase allergenicity. Further studies are needed, however, as reduced allergenicity has sometimes been reported.64,65 Heated foods like milk, roasted peanuts and soy are reported to induce significant increases in AGE levels and affect the IgE-binding capacity.56,57 Significantly elevated urinary levels of the AGE pentosine are observed in allergic children with clinical signs of exacerbation of atopic dermatitis.68

Alzheimers disease (AD) and other neurodegenerative diseases. Similarities between AD and type 2 diabetes (T2DM) exist to the extent that AD has been called “the diabetes of the brain.” The incidence of AD is also reported to be 2- to 5-fold increased in T2DM.59 A common feature of both diseases is accumulation of amyloid deposits, a process that progresses during the course of disease. Increased levels of AGEs/ALEs have repeatedly been demonstrated with immunohistochemical methods in senile plaques, tau proteins, amyloid beta proteins, and in neurofibrillary tangles. [degrees]’61 A 3- fold increase in content of AGE is also reported in the brains of AD patients compared with age-matched controls.62 Increased levels of AGEs and signs of oxidative damage are also observed in olfactory bulbs, known to be early targets of AD.62 A strong association between severity of disease, RAGE-expression in microglia, and increases in RAGE protein has been reported.63 Signs of amyloidosis, Pertubation of neuronal properties and functions, amplification of glial inflammatory response, increased oxidative stress, increased vascular dysfunction, increased Ass in the blood-brain barrier, and induction of autoantibodies were also reported.63 Involvement of AGEs/ALEs in the pathogenesis of other neurodegenerative diseases is also reported: PD,64,65 amyotrophic lateral sclerosis (ALS),66-68 Huntington disease, stroke,70 familial amyloidotic polyneuropathy,71 and Creutzfeldt-Jakob disease.72 Early accumulation of AGEs is also observed in Down syndrome and early antiglycation treatment suggested to reduce cognitive impairments.73 It was recently suggested that bovine spongiform encephalopathy (BSE), a disease with its significant similarities to AD, might also be associated with increased glycation and lipoxidation.74 AGEs, amyloid fibrils, and prions seem all to have the same target, RAGE, and all activate the NFkB pathway. Involvement in BSE of glycation products and activation of prion proteins are also suggested by other authors.75,76

Atherosclerosis and cardiovascular diseases. Oxidative stress (lipid peroxidation) and protein glycation have repeatedly been associated with extensive arteriosclerosis. A recent study reports significant increases in both chemical AGEs (carboxymethyl lysine) and fluorescent AGEs (spectrofluorimetry) in 42 patients with atherosclerosis when compared with 21 healthy controls (p

Cancers. The influence of AGEs/ALEs on the pathogenesis of malignant tumors and their ability to grow is not extensively studied. However, it is reported that the sRAGE receptor, highly expressed in healthy lung tissues and especially at the site of alveolar epithelium, is significantly down-regulated in lung carcinomas,8 and the RAGE expression is reported to be elevated in human pancreatic cells with high metastatic ability and decreased in tumor cells with low metastatic ability.84 High RAGE expression is also reported in colonic and prostatic86 cancers. Little information is available about other types of cancers, including breast cancer, but it has recently been suggested that inhibition of AGE-RAGE interaction might have a potential as a molecular target for both cancer prevention and therapy.84,86

Cataract and other eye disorders. AGEs/ALEs accumulate with age in all ocular tissues, including lacrimal glands, and trigger pathogenic events, especially in diabetic patients, in all parts of the eye.87

DM. More than 2000 publications listed in PubMed (ie, almost half of all DM papers listed) deal with AGEs/AGEs and their role in DM. Several excellent reviews have recently been published.88-90 Overconsumption of fat and carbohydrates, not only of glucose but also other carbohydrates such as lactose and fructose, contribute especially in diabetic patients to a significant accumulation of AGEs/ALEs in the tissues. Consumption of high-fructose corn syrup in the United States exceeds that of sucrose and is suggested to be the major contributor not only to obesity and hepatic steatosis but especially to T2DM and to severe complications of both types 1 and 2 DM.91 The feeding of dairy cows have in recent years, similar to human foods, undergone significant changes from mainly foragebased feeds to significant amounts of starch-rich and fast-absorbed carbohydrates: corn, maize grains, barley, molasses, and dextrose, feeds that induce insulin resistance in cows and, if the cows are allowed to live long enough, will lead to manifest DM. Insulin resistance is also observed in calves when intensively fed milk and lactose.92 Endocrine disorders. Many if not most of the signs and symptoms of aging, as well as age-associated diseases, are identical to manifestations seen in hormone deficiencies and in premature aging, which is strongly associated with multiple hormone deficiencies. Most consequences of aging such as excessive free radical formation, imbalanced apoptosis system, tissue accumulation of waste products, failure of repair systems, deficient immune system, poor gene polymorphisms, and premature telomere shortening are also associated, if not caused, by hormone deficiencies.93 Up- regulation of putative pathologic pathways, accumulation of AGEs, activation of the renin-angiotensin system, oxidative stress, and increased expression of growth factors and cytokines are all associated with aging. However, little information either in health or disease, is available about content of AGEs/ALEs in endocrine organs: the pituitary gland, thyroids, parathyroids, adrenals, ovaries, and testes. Increased serum AGE levels and activation of RAGE are reported in women with polycystic ovary syndrome.94

Activation of the renin-angiotensin system, known to have a pivotal role in ChDs such as DM and chronic renal disease, contributes to enhanced pathogenic mechanisms: increased oxidative stress, increased general inflammation, increased serum levels of free fatty acids, increased glycotoxicity and lipotoxicity, and advanced glycation and lipoxidation.95-97

Gastrointestinal disorders. It is likely that digestive tract disorders such as liver cirrhosis and liver steatosis, as well as inflammatory bowel disorders, are associated with elevated AGEs/ ALEs. A recent study reports a 14- to 16-fold increase of glyoxal- derived adducts in portal and hepatic venous plasma of cirrhotic patients compared with healthy controls.98 Plasma AGE levels were also measured in 51 patients with liver cirrhosis, 5 patients after liver transplantation, and 19 healthy controls.99 Patients with liver cirrhosis demonstrated significantly increased AGE levels, almost to the same extent as seen in patients with end-stage renal disease. A dramatic improvement was observed in patients after liver transplantation, although the AGE levels did not return to those seen in healthy controls, and the preoperative decrease in renal function did persist. One hundred ten patients with chronic liver disease (CLD) were recently studied and compared with 124 healthy controls. Serum levels of AGE (CML) were significantly affected by the stage of liver cirrhosis and closely associated with liver function capacity, and AGE (CML) level was reported to positively correlate with levels of hyaluronic acid (HA; r = 0.639; ?

Pulmonary disorders. Lack of homeostasis in oxidant/antioxidant balance is obvious in a variety of airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and idiopathic pulmonary fibrosis. Interaction of AGEs/ ALEs and RAGE plays a large role, if not a dominating one, in the pathogenesis of these pulmonary diseases, and depletion of antioxidants, particularly GSH, in lung epithelial lining is suggested to play a key role in these disorders.103-105

Rheumatoid arthritis and other skeletomuscular disorders. A very strong expression of RAGE, and some of the highest levels of AGEs in the body are found in tissues with slow turnover, such as tendons, bone, cartilage, skin, and amyloid plaques. Changes, frequently associated with change in color from white to yellow-brown, include increased fluorescence, increased expression of proinflammatory cytokines, matrix metalloproteinases (MMP), especially MMP-I and – 9. These manifestations are likely responsible for the observed increased tissue stiffness and brittleness in structures such as intervertebral discs, bones tendons, cartilages, synovial membranes, and skeletal muscles and will most likely constitute a major pathogenic factor in diseases such as osteoarthritis,106,107 rupture of intervertebral discs,108 Achilles tendons109 and eventually menisci, and are involved also in rheumatoid diseases110-112 such as rheumatoid arthritis (RA) and fibromyalgia. A significant increase in glycation of myosin occurs with age,113 which most likely contributes to age-associated muscular disorders. Observations in subjects with osteoporosis of significantly elevated levels of pentosidine and CML in serum11 and significantly increased pentosidine in cortical bone115 are of considerable interest. It has also been observed that the remodeling of senescent bone is impaired by AGEs both through stimulation of bone-resorbing cytokines and enhancement of bone resorption by osteoclasts.116 The role of bovine milk in prevention of osteoporosis could be found to discredit what has been claimed for decades, should future studies verify that osteoporosis is more due to interactions of RAGE and AGEs/ALEs than to lack of minerals.

Skin and oral cavity. Skin has a high density of AGE receptors. AGEs/ALEs are known to accumulate in dermal elastin and in collagene also, and are known to interact with dermal fibroblasts, inhibiting their proliferation capacity. A 10-times reduction in proliferation rate is described as normal in humans between the second and seventh decade,117 which might well explain the reduced healing capacity of age-related wounds and especially chronic wounds such as those in the extremities of people with DM. It has also been observed that accumulation of AGEs/ALEs in the skin reflects the AGE/ALE deposition in the rest of the body to such a degree that skin autofluorescence has been suggested as a measure of cumulative metabolic stress and AGEs in the body.118 Skin autofluorescence is suggested to be so exact that it is able to predict progression of retinopathy and nephropathy in DM, as well as mortality in hemodialysis patients.118 RAGE and AGE/ALE-induced apoptosis and enhanced loss of fibroblasts and osteoblasts are also regarded as major pathogenic factors in periodontal pathology, especially in chronic periodontitis.119 A 50% increase in RAGE mRNA is observed in gingiva of diabetic patients compared with controls (p

Urogenital disorders. Nephropathy is common in the modern world and its incidence is fast increasing, much in parallel to the increase in DM. Diabetic nephropathy alone affects today 15%-25% of patients with type 1 DM and as many as 30%-40% of patients with T2DM. Furthermore, it is the single most important cause of end- stage renal failure in the western world.121 The kidney appears as both culprit and target of AGEs/ALEs, and it is well documented that RAGE is significantly activated and levels of AGEs/ALEs are markedly elevated in patients with renal failure. More than 500 papers on PubMed deal with RAGE and AGEs/ALEs in renal diseases. A decrease in renal function and reduced renal clearance are observed much in parallel to increases in circulating AGEs. AGEs are also involved in the structural changes observed in progressing nephropathies such as glomerulosclerosis, interstitial fibrosis, and tubular atrophy122; more detailed information has been published in recent excellent reviews.122-127 Patients with mild chronic uremic renal failure are reported to have plasma glycation free adduct concentrations increased up to 5-fold; patients with end-stage renal disease, as much as 18-fold when receiving peritoneal dialysis and up to 40- fold when receiving hemodialysis.128 Kidney transplantation is reported to improve but does not fully correct the increased levels of AGE/ALE in patients who have been previously dialyzed.129

Dietary Measures to Reduce AGEs/ALEs

The greatest of contributors by far of AGEs/ALEs by food (Table II) seem to be dairy products130 (Figure 1), bread, and meat, not only because they are rich in these substances but also as these foods constitute the bulk of modern food, especially in the western world. Also, plants contribute to accumulation of AGEs/ALEs in the body, especially fruits, which contain larger amounts of fructose, which is highly reactive with proteins. However, consumption of carbohydrates seem mainly, or only, to be of considerable risk when consumed as industrially concentrated products, refined sugar, and high-fructose corn syrup.91

TABLE II

Short list of foods rich in AGEs/ALEs131

Consuming a vegan diet, known to be low in AGEs/ALEs, seems to result in statistically lower systolic and diastolic blood pressure, lower serum total cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood glucose, fewer weight problems, and less incidence of ChDs, especially DM and its complications. However, there are also problems with a vegetarian (lactovegetarian and vegan) lifestyle which need to be corrected, among them risk of shortage in vitamin B12 and poor taurine status,132 and for lactovegetarians, higher serum levels of homocysteine. The serum levels of AGEs/ALEs are reported as higher in longtime healthy lactovegetarians than in healthy omnivorous people.133 One explanation could be, as suggested by the authors, a higher intake of fructose, especially because this carbohydrate is significantly more reactive with proteins than sucrose. Another explanation could be a higher consumption of various milk products, especially cheese and milk powder, known to be rich in AGEs/ALEs, meant to substitute meat and fish in the diet. FIGURE 1. Relative furosine content in various milk-based products. A, Milk powder kept for 2 years in room temperature. B, Milk powder kept for 1 year at room temperature. C, DIF with whey plus casein. D, DIF with hydrolyzed whey. E, Milk powder kept for 1 year at 4[degrees]C. F, Fresh milk powder. G, Raw (whole) bovine milk. Reprinted from Baptista JAB, Carvalho RCB. Indirect determination of Amadori compounds in milk-based products by HPLC/ELSD/UV as an index of protein deterioration. Food Res Int. 2004;37:739-747, with permission from Elsevier.

DIF, dietetic infant formulas; UHT, ultraheat treatment.

Several measures have been demonstrated to significantly decrease serum and tissue concentrations of AGEs/ALEs, among which are the following.

Calorie restriction. Evidence from animal studies suggests that restriction in food intake is an effective means to extending median lifespan and preventing ChDs.15 Few studies are, unfortunately, available in primates and almost no studies in humans. Significant benefits of long-term (2-11 years) CL compared with normal western diet were recently reported in a study in healthy humans: blood pressure 102 +- 10/61 +- 7 vs 131 +- 11/83 +- 6 mm Hg, c-reactive protein (CRP) 0.3 +- 0.3 vs 1.9 +- 2.8 mg/L, tumor necrosis factor (TNF)-a 0.8 +- 0.5 vs 1.5 +- 1.0 pg/mL, transforming growth factor (TGF)-ss 29.4 +- 6.9 ng/mL vs 35.4 +-7.1 ng/mL respectively.134 Patients with RA receiving a low-energy diet for 54 days demonstrated a significant reduction in both urinary pentosidine level and RA disease activity.135 However, studies on the effects of CL on AGEs/ALEs are thus far lacking in other groups of ChDs.

Vitamins and antioxidants. Glutathione (7-glutamylcysteinyl glycine [GSH]) is regarded as an important factor for optimal cellular function and defense against oxidative stress. Dietary supply of GSH has been shown to reduce glycation and prevents diabetic complications such as diabetic nephropathy and neuropathy.136 Rich supply of vitamins A, C, E, and particularly B6, B12, and folic acid (Figure 2) is often emphasized in the literature.137 Vitamin D should most likely also be supplemented, especially at higher latitudes. Several thousands of plant-derived chemopreventive agents, polyphenols, and many others, most often yet unexplored, have the potential to reduce the speed of aging and prevent degenerative malfunctions of organs, among them, isothiocyanates in cruciferous vegetables, anthocyanins and hydroxycinnamic acids in cherries, epigallocatechin-3-gallate (EGCG) in green tea, chlorogenic acid and caffeic acid in coffee beans and also tobacco leaves, capsaicin in hot chili peppers, chalcones in apples, eugenol in cloves, gallic acid in rhubarb, hisperitin in citrus fruits, naringenin in citrus fruits, kaempferol in white cabbage, myricetin in berries, rutin and quercetin in apples and onions, resveratrol and other procyanidin dimers in red wine and virgin peanuts, various curcumenoids, the main yellow pigments in turmeric curry foods,138 and daidzein and genistein from the soybean. These compounds have all slightly different functions and seem to complement each other well. Several, most likely the majority, of these substances have a great capacity to inhibit the second phase of the glycation process, eg, the conversion of the Amadori products to AGEs. A significant number of animal studies support health benefits of these antioxidants and AGE/ALE scavengers.139,140 Again, human studies are largely lacking.

FIGURE 2. Involvement of homocysteine, folic acid, and vitamins B6 and B12 influences metabolism and possible mechanisms whereby elevated homocysteine contributes to increased risks of chronic diseases. Reprinted from Mattson MP. Will caloric restriction and folate protect against AD and PD? Neurology. 2003;60:690-695, with permission from Lippincott Williams & Wilkins.137

Taurine, carnitine, carnosine, histidine. Taurine, a sulfonic acid compound, is normally found in high concentrations intracellularly in most animal tissues, and especially in blood cells, retina, and nervous tissues. The highest concentrations are found in neutrophils, where it is suggested to reduce inflammation.141 The richest sources of taurine are seafood, fish, and poultry. Moderate amounts are also found in meat, whereas plants, with the only known exception of some algae, and consequently also vegan diets, are devoid of this amino acid.142 Taurine has strong hypoglycemic effects, observed already in the 1930s.143 It reduces production of AGEs/ALEs and prevents high- fructose-diet-induced collagen abnormalities in animals.144,145 In vitro and animal studies suggest that similar effects are obtained also from supplementing amino acids such as histidine or peptides such as carnitine and carnosine. Again, no human studies have been undertaken.

Pre- and pro-biotics. Plant-derived antioxidants and AGE/ALE scavengers need to be released from the plant fibers during passage through the digestive tract. This process is mainly dependent on microbial enzymes, provided by the flora in the lower gastrointestinal tract. This flora is reported to be severely impaired in about 75% of omnivorous Americans and one-third of vegetarian Americans.146 Lactic acid bacteria (LAB) are also in their own capacity strong oxidation scavengers and effective inhibitors of inflammation. LAB might also have the capacity, before the food is absorbed to eliminate AGE/ALE protein and peptides, as was earlier demonstrated for gluten147 and carcinogens.148 Support for such an assumption derives from an in vitro study, where fructose lysine, the main modified molecule in heated milk,126 is eliminated (deaminated) when incubated with live flora.149

Future Directions

In the past, most studies on lifestyle-associated disease have focused mainly on coronary heart disease, T2DM, and chronic renal disease. Increasing evidence suggests that an “unhealthy” lifestyle is negatively associated with most, if not all, ChDs. Common to the ChDs is a permanent, often silent, exaggerated inflammation, strongly associated with metabolic syndrome and increased deposits in tissues of AGEs/ALEs. ChD patients, including those with obscure etiology and those with inherent genetic disorders (Down syndrome,73,150 cystic fibrosis,151,152 schizophrenia,153,154 and mental depression155-157) might well benefit from reduced AGE/ALE intake. However, more studies are needed. Studies performed in the United States have reported that the incidence of a number of chronic diseases would be greatly reduced if people would follow a “healthy lifestyle.” These estimates suggest that the incidence of coronary artery disease could be reduced by 83%, diabetes mellitus in women could be reduced by 91%, and colon cancer in men by 71%.160 It is likely that controlled intake and cellular production of AGEs/ ALEs constitute important contributions to such a healthy lifestyle.

Exaggerated inflammation is also observed in patients who have complications to acute diseases: sepsis, trauma, and advanced surgical and medical treatments such as transplantations. Complications and sequelae to these events are significantly more common in elderly people and in those with ChDs. Clearly, lifestyle of the individual and inflammation before the trauma will significantly influence outcome.161 Presence of metabolic syndrome has been shown to have a strong negative influence on outcome in acute morbidities and in ICU patients. Future attempts to minimize accumulation of such substances in the body might provide significant benefits in both acute and chronic morbidities. It is important to stress that research in this field is in its infancy, and many more studies are needed, particularly in humans. I wish such studies will be given the highest priority.

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146. Finegold SM, Sutter VL, Mathisen GE. Normal indigenous intestinal flora. In: Hentges DJ, ed. Human Intestinal Microflora in Health and Disease. London: Academic Press; 1983:3-31.

147. di Cagno R, de Angelis M, Alfonsi G, et al. Pasta made from durum wheat semolina fermented with selected lactobacilli as a tool for a potential decrease of the gluten intolerance. J Agrie Food Chem. 2005;53:4393-4402.

148. Tavan E, Cayuela C, Antoine JM, Cassand P. Antimutagenic activities of various lactic acid bacteria against food mutagens: heterocyclic amines. J Dairy Res. 2002;69:335-341.

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151. Hudson VM. New insights into the pathogenesis of cystic fibrosis: pivotal role of glutathione system dysfunction and implications for therapy. Treat Respir Med. 2004;3:353-363.

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157. Muller N, Schwarz MJ, Dehning S, et al. The cyclooxygenase- 2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, r

By Patel, Vijaykumar G Rao, Arundathi; Williams, Reginald; Srinivasan, Radha; Et al

Acute epiploic appendagitis (EA) is a rare and often misdiagnosed cause of acute abdominal pain. Though a benign and often self- limiting condition, EA’s ability to mimic other disease processes makes it an important consideration in patients presenting with acute abdominal symptoms. Careful evaluation of abdominal CT scan findings is crucial in the accurate diagnosis of epiploic appendagitis, thus avoiding unnecessary surgical intervention. We report a case of a 29-year-old male presenting with a two day history of generalized abdominal pain. Physical exam revealed a diffusely tender abdomen with hypoactive bowel sounds. The patient had a leukocytosis of 18,000 and abdominal CT scan revealed right lower quadrant inflammatory changes suggestive of acute appendicitis. Laparoscopic exploration revealed an inflamed gangrenous structure adjacent to the ileocecal junction. Pathologic evaluation revealed tissue consistent with epiploic appendagitis. Retrospective review of the CT scan revealed a normal appearing appendiceal structure superolateral to the area of inflammation. The patient recovered uneventfully with resolving leukocytosis. We present a case of cecal epiploic appendagitis mimicking acute appendicitis and review the current literature on radiographic findings, diagnosis, and treatment of this often misdiagnosed condition. General surgeons should be aware of this self-limiting condition and consider this in the differential diagnosis. PRIMARY EPIPLOIC APPENDAGITIS (PEA) usually presents as an acute clinical condition that often mimics a surgical emergency. PEA is an uncommon condition and is due to appendix epiploica torsion or spontaneous venous thrombosis of its’ draining vein.1 Patients present with nonspecific symptoms that can mimic appendicitis, diverticulitis, ovarian torsion, gallbladder disease, ectopie pregnancy, colon cancer, mesenteric adenitis, duodenal ulcer, and, on rare occasions, pulmonary embolus.2,3 Failure to diagnose PEA results in an unnecessary surgical intervention and incurred hospital costs. Therefore, it is imperative to appropriately diagnose this self- limiting condition to avoid surgery and prevent furthermore unwarranted hospitalization.

Case Report

A 29-year-old male presented to the emergency department with a two-day history of generalized abdominal pain and constipation. The patient was tachycardie and tachypneic with a temperature of 102[degrees] F. Physical exam revealed a 400 pound obese male in moderate distress with a diffusely tender abdomen and hypoactive bowel sounds. A leukocytosis of 18,000 and a urinalysis was negative for bacteria, blood, and nitrites. CT scan revealed a normal seeming cecum. However, right lower quadrant inflammation and a small amount of free fluid in the pelvis was reported by the attending radiologist, as suggestive of acute appendicitis (Fig. 1). Laparoscopic exploration revealed an inflamed gangrenous structure adjacent to the ileocecal junction, which seemed to be the appendix.

Pathologic evaluation revealed tissue consistent with epiploic appendagitis. Retrospective review of the CT scan revealed a normal seeming appendiceal structure superolateral to the area of inflammation (Fig. 1). Postoperatively, the patient remained afebrile with resolving leukocytosis and was discharged home after two days.

Discussion

First described by Versalius in 1543, epiploic appendages are adipose tags attached in two parallel rows adjacent to the anterior and posterior taenia coli along the entire length of the colon.2′ 4 These appendages develop in the 2nd trimester of fetal life and grow throughout adulthood and can reach lengths from 0.5 cm to 15 cm and 1 to 2 cm thick.2- 5 They are located primarily along the sigmoid colon (57%), and ileocecum (26%), followed by the ascending colon (9%), transverse colon (6%), and descending colon (2%).5 Epiploic appendices have a delicate blood supply consisting of a small end artery and a tortuous vein, which pass through narrow pedicles. The extreme mobility of these appendices predisposes to torsion, kinking, stretching, and surrounding inflammatory processes, resulting in venous thrombosis.6

FIG. 1. Abdominal CT scan images showing inflammatory changes medial to the cecum (c). Hypodense area in the ileocecal region is consistent with fatty epiploic appendagitis (ea).

Ly nn et al. first coined the phrase epiploic appendagitis in 1956, describing the inflammatory result of these torsed appendages.7 Primary epiploic appendagitis is a result of spontaneous torsion or lymphoid hyperplasia with subsequent inflammation. Secondary epiploic appendagitis is much more common and most often occurs secondarily in the inflammatory setting of appendicitis, diverticulitis, and cholecystitis.8

Epiploic appendagitis occurs in all ages with slightly higher predilection towards middle-aged males with a peak incidence at age 40 years.4,6 Appendagitis may be more common in obese people or those who have recently lost weight.9 Many patients will present with a recent history of strenuous stretching or exercising as the precipitating event.2

Patients usually present with a sudden onset of localized abdominal pain and tenderness lasting several days to almost a week in duration (100%).6 Pain can be quite severe, and stretching of the abdominal wall may furthermore elicit pain (100%).6 Rebound tenderness was also noted in 91 per cent of patients in one study.1 Fever and leukocytosis are common, along with gastrointestinal symptoms, in as many as 25 per cent of patients, as was seen in our case report. Some studies suggest absence of gastrointestinal symptoms and fever in true PEA.5 With this variable presentation; it is easy to see why accurate diagnosis of PEA based on clinical evaluation alone is often difficult.

In 1986, abdominal CT scan findings of PEA were first described. PEA has a pathognomonic appearance on abdominal CT scan, consisting of a one to four centimeter pedunculated, ovoid paracolic mass with hyper attenuation of the rim and surrounding fat stranding.10 Other documented findings include thickening of the bowel with or without compression of the bowel wall and a high central attenuation dot/ linear sign.3 The ultrasonographic appearance of PEA consists of a solid hyper echoic noncompressible ovoid mass with no color Doppler flow.11 Abdominal MRI findings in PEA are also pathognomonic. Tl- weighted images reveal high-signal paracolic lesions with a thin rim and a central low-signal dot. Lesions are best seen on postgadolinium Tl-weighted fat suppressed images.

Despite these imaging techniques, erroneous diagnoses are still common, as was seen in our case. Epiploic appendages surrounding the colon are clustered most prominently in the cecal and recto-sigmoid region, hence the mistaken diagnosis of diverticulitis and appendicitis are most common.4 Misdiagnosis usually leads to operative intervention and can present as a dilemma if a laparoscopie diagnosis is made. Vazquez-Frias et al. published recommendations in favor of excising infarcted appendages during laparoscopy.12

Radiological or clinical misdiagnosis can contribute substantially to unnecessary surgery, medical treatment, and hospital resources utilization.1 Patients with true PEA require analgesics alone. Spontaneous symptom resolution occurs within one to two weeks in most cases.6 Close follow-up is imperative because potential complications such as bowel obstruction, intussusception, and possible abscess formation can arise.2

Conclusion

Awareness of PEA is of crucial importance because clinical signs and symptoms are often nonspecific. Well-established abdominal CT scan and ultrasound findings in diagnosing this unusual entity have been well described. Therefore, with careful radiological evaluation, the diagnosis of PEA can be made with confidence, thus preventing unnecessary surgical intervention, antibiotic therapy, and prolonged hospitalization. General surgeons and radiologists should be aware of this rare, self -limiting condition and consider this in the differential diagnosis, particularly in obese male patients. With increasing utilization of CT scans in the diagnosis of appendicitis, this rare self-limiting entity may be recognized more frequently with increased awareness.

REFERENCES

1. Rao PM, Rhea JT, Wittenberg J, Warshaw AL. Misdiagnosis of primary epiploic appendagitis. Am J Surg 1998;176:81-5.

2. Legome EL, Sims C, Rao PM. Epiploic appendagitis: Adding to the differential of acute abdominal pain. J Emerg Med 1999;17:823- 6.

3. Keng SN, Tan GST, Chen KKW, et al. CT features of primary epiploic appendagitis. Eur J Radiol 2006;59:284- 8.

4. Sangha S, Soto JA, Becker JM, Farraye FA. Primary epiploic appendagitis: An underappreciated diagnosis. A case series and review of the literature. Dig Dis Sci 2004;49:347-50.

5. Killer N, Berelowitz D, Hadas-Halpern I. Primary epiploic appendagitis: Clinical and radiological manifestations. Isr Med Assoc J 2000;2:896-8.

6. Vriesman ACB, Otterloo AJCM, Puylaert JBCM. Epiploic appendagitis and omental infarction. Eur J Surg 2001;167:723-7.

7. Lynn TE, Dockerty MB, Waugh JM. A clinico-pathologic study of the epiploic appendages. Surg Gynecol Obstet 1956;103:423-4.

8. Boardman J, Kaplan KJ, Hollcraft C, Bui-Mansfield LT. Torsion of the epiploic appendage. Am J Roentgenol 2003;180:748. 9. Hanson JM, Kam AW. Paracolic echogenic mass in a man with lower abdominal pain. Is epiploic appendagitis more common than previously thought? Emerg Med J 2006;23:17.

10. Danielson K, Chemin MM, Amberg JR, et al. Epiploic appendicitis: CT characteristics. J Comput Assist Tomogr 1986; 10: 142-3.

11. Boulanger BR, Barnes S, Bernard AC. Epiploic appendagitis: An emerging diagnosis for general surgeons. Am Surg 2002; 68:1022-5.

12. Vazquez-Frias JA, Castaneda P, Valencia S, Cueto J. Laparoscopie diagnosis and treatment of acute epiploic appendagitis with torsion and necrosis causing an acute abdomen. JSLS 2000;4:247- 50.

VIJAYKUMAR G. PATEL, M.B., B.S., F.R.C.S., F.R.C.S.(ED)., F.A.C.S.,* ARUNDATHI RAO, M.D.,* REGINALD WILLIAMS, M.D.,* RADHA SRINIVASAN, M.D.,t JAMES K. FORTSON, M.D., F.A.C.S.,* WILLIAM L. WEAVER, M.D., F.A.C.S.*

From the *Department of Surgery, Morehouse School of Medicine and tSouth Fulton Medical Center,

Atlanta, Georgia

Presented during Poster Grand Rounds at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Savannah, GA, February 10-13, 2007.

Address correspondence and reprint requests to Vijaykumar G. Patel, M.B., B.S., F.R.C.S., F.R.C.S.(Ed), F.A.C.S., Associate Professor of Surgery, Department of Surgery, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30311. E-mail: [email protected].

Copyright Southeastern Surgical Congress Aug 2007

(c) 2007 American Surgeon, The. Provided by ProQuest Information and Learning. All rights Reserved.

By Sherry Jacobson, The Dallas Morning News

Dermatologists in North Texas were alerted Friday to be on the lookout for a rare skin infection caused by a parasite that may have migrated north from the Mexican border.

The disease, leishmaniasis, typically causes a half-dollar-sized boil that takes six to 12 months to heal. It is not considered life-threatening.

Doctors at UT Southwestern Medical Center said they have identified nine cases of the skin disease in North Texans in recent months. The Centers for Disease Control and Prevention confirmed that all nine people, both adults and children, were infected by the parasite, Leishmania mexicana.

Typically found in Mexico or along the Texas border, it is carried by wood-burrowing rats and spread by tiny sand flies that bite both the rats and humans.

“None of the North Texas cases had traveled south or to parts of the world where the disease is endemic, which suggests they got it here,” said Dr. Kent Aftergut, a Dallas dermatologist who identified the first apparent local infection in March.

Weldon Hatch, a 58-year-old Waxahachie man, said he sought Dr. Aftergut’s care after two small red spots appeared on his shoulder in February. Later, the lesions grew to the size of a quarter, became itchy and painful.

“All the creams and salves didn’t do anything,” he said. “So my doctor gave up, and I went to an expert.”

Dr. Aftergut diagnosed the skin ailment and later shared Mr. Hatch’s case with other Dallas-area dermatologists, who realized they had treated similar cases.

The other leishmaniasis cases were confirmed in Hillsboro in Hill County, Tom Bean in Grayson County, Anna and Nevada in Collin County, Savoy in Fannin County, North Richland Hills in Tarrant County, and in Glenn Heights, which straddles Dallas and Ellis counties.

Dr. Barbara Herwaldt of the CDC’s division of parasitic diseases said Texans should not be especially fearful of being infected, especially because doctors are being alerted to watch for it.

“It shouldn’t be a cause for alarm because physicians in Texas will be looking for certain skin lesions that don’t go away,” she said. “When you know to look for something, you know to diagnose it.”

Several treatments are available, doctors said, though the lesions can heal by themselves over time.

Although the parasite’s presence in North Texas appears to be new, doctors can’t say for sure.

“It’s entirely possible that there were cases like this that were never reported before because we weren’t looking for them,” said Dr. Erin Welch, an assistant professor of dermatology at UT Southwestern. “What we know is that these are all isolated cases. The people weren’t travelers, and they had no connection to each other.”

Dr. R. Doug Hardy, infectious disease specialist at UT Southwestern, said he couldn’t help but believe that something changed to allow the parasite to move north.

“We’ve had intermittent cases along the Mexican border,” he said. “But to have all these cases so close together, outside the border, in kids and adults without travel, is very unusual.”

A few were guessing that environmental changes, including higher temperatures, could have allowed infected rats and sand flies to move into North Texas.

Dr. Hardy noted that experiments have been conducted to try to isolate the parasite from local sand flies. So far, nothing has been confirmed. “It’s also possible that we have a different insect or rodent in North Texas that can carry the parasite,” he said.

Leishmaniasis (pronounced Leash — man — EYE — a — sis) typically has been diagnosed among people who had traveled to the Middle East and South America. In recent years, U.S. soldiers have returned from Iraq and Afghanistan with leishmaniasis, often referred to as a “Baghdad boil.”

“The good news is that it’s not something that typically goes beyond the skin,” Dr. Herwaldt said. “This is something we know how to handle, and it’s not spread by casual contact.”

ABOUT THE SKIN DISEASE

What is leishmaniasis?

It’s an infectious skin disease spread by sand flies.

What should I do if I develop a boil?

Go to your doctor and be tested for the parasite that causes the disease.

How serious is the disease?

It’s a mild disease, though the boil could be painful and large. It often is misdiagnosed and can take as long as a year to heal.

How do you avoid being infected?

You should use insect repellent and wear protective clothing when outdoors between dusk and dawn, when the flies usually feed.

SOURCE: UT Southwestern Medical Center

CHICAGO and PITTSBURGH, Sept. 14 /PRNewswire-FirstCall/ — Allscripts , the leading provider of clinical software, connectivity and information solutions that physicians use to improve healthcare, announced today that West Penn Allegheny Health System (WPAHS) has selected Allscripts as its Electronic Health Record (EHR) provider for its primary care network.

(Logo: http://www.newscom.com/cgi-bin/prnh/20061005/ALLSCRIPTSLOGO-b)

Comprised of some of the oldest and best-known names in health care in western Pennsylvania, WPAHS includes two tertiary and four community hospitals with a total of more than 2,000 beds. Allegheny General Hospital serves as the Pittsburgh clinical campus for the Drexel University College of Medicine in Philadelphia, and The Western Pennsylvania Hospital serves as the clinical campus for Temple University School of Medicine in Philadelphia. The health system, which admits more than 80,000 patients into its hospitals each year, also owns a primary care network of 36 physician practices employing 165 physicians who will receive the Electronic Health Record.

“We selected Allscripts first as our e-prescribing vendor, but it soon became clear to us that the full electronic health record would have a profound impact on improving the quality of care and reducing expenses for our physicians in the primary care network,” said Nick Valadja, Vice President of Information Systems for West Penn Allegheny Health System. “Allscripts will provide an electronic dialogue among all the members of a patient’s care team no matter their location, and help to deliver truly integrated patient care.”

The Electronic Health Record brings WPAHS physicians instant access to patient information when and where they need it — at the hospital, in their offices or while on-call at home. Allscripts automates everyday clinical tasks such as prescribing and refilling medications, ordering and reviewing tests, and documenting patient care, while making the process more efficient and safer than ever before. An easy-to-use and customizable solution, the Electronic Health Record features robust clinical tools that support safe medical practices, including health maintenance alerts, clinical decision support, and automated drug safety checking.

“Our experience with West Penn demonstrates how electronic prescribing, the first application they started with, can serve as an on-ramp to the electronic healthcare highway and lead to the adoption of a comprehensive Electronic Health Record,” said Glen Tullman, Chief Executive Officer of Allscripts. “West Penn’s commitment to connect 36 separate physician practices, two tertiary and four community hospitals and their two clinical campus locations demonstrates their vision of moving toward an interconnected healthcare system, something we believe is not only compelling but necessary to advance our national healthcare system. We applaud their leadership.”

In addition to providing the core Electronic Health Record to its primary care physicians, WPAHS will provide view-only access to key parts of the Electronic Health Record for all employed caregivers in the system’s hospitals. That functionality ensures that hospital caregivers will have access to the medication history, problems, allergies and other critical information about patients admitted to the hospital from the primary care group.

The health system will integrate Allscripts with IDX/GE’s Centricity Business, the practice management system used by its employed physicians. Linking the clinical and financial information systems will help WPAHS’s physician practices become more productive while improving service to patients.

About West Penn Allegheny Health System

West Penn Allegheny Health System includes Allegheny General Hospital and The Western Pennsylvania Hospital, both in Pittsburgh; Alle-Kiski Medical Center in Natrona Heights; Canonsburg General Hospital in Canonsburg; The Western Pennsylvania Hospital — Forbes Regional Campus in Monroeville; and AGH-Suburban Campus in Bellevue. Offering a comprehensive range of medical and surgical services, the hospitals serve Pittsburgh and the surrounding five- state area, house more than 2,000 beds and employ more than 13,000 people. Together, the WPAHS hospitals admit more than 80,000 patients each year, log in excess of 173,000 emergency visits and deliver nearly 6,000 newborns. Combined, the hospitals are among the leaders in percentages of total surgeries, cardiac surgeries, neurosurgeries and cardiac catheterization procedures performed throughout the region.

West Penn Allegheny Health System hospitals have won — and continue to win — both national and international recognition for their programs in numerous specialty areas. Supporting both a charitable and an academic mission, WPAHS has a strong commitment to medical research and education and is also dedicated to training future generations of health-care professionals. For more information, visit http://www.wpahs.org/.

About Allscripts

Allscripts is the leading provider of clinical software, connectivity and information solutions that physicians use to improve healthcare. The Company’s business units provide unique solutions that inform, connect and transform healthcare. Allscripts award-winning software applications include Electronic Health Records, practice management, e-prescribing, document imaging, emergency department, and care management solutions, all offered through the Company’s Clinical Solutions units. Additionally, Allscripts provides clinical product education and connectivity solutions for physicians and patients through its Physicians Interactive(TM) unit, and medication fulfillment services through its Medication Services unit. To learn more, visit Allscripts on the Web at http://www.allscripts.com/.

This announcement may contain forward-looking statements about Allscripts Healthcare Solutions that involve risks and uncertainties. These statements are developed by combining currently available information with Allscripts beliefs and assumptions. Forward-looking statements do not guarantee future performance. Because Allscripts cannot predict all of the risks and uncertainties that may affect it, or control the ones it does predict, Allscripts’ actual results may be materially different from the results expressed in its forward-looking statements. For a more complete discussion of the risks, uncertainties and assumptions that may affect Allscripts, see the Company’s 2006 Annual Report on Form 10-K, available through the Web site maintained by the Securities and Exchange Commission at http://www.sec.gov/.

Photo: http://www.newscom.com/cgi-bin/prnh/20061005/ALLSCRIPTSLOGO-bAP Archive: http://photoarchive.ap.org/PRN Photo Desk, [email protected]

Allscripts

CONTACT: Dan Michelson, Chief Marketing Officer, +1-312-506-1217,[email protected], or Todd Stein, Senior Manager-Public Relations,+1-312-506-1216, [email protected], both of Allscripts; or ThomasChakurda, Vice President, Communications and Marketing of West Penn AlleghenyHealth System, +1-412-359-6896, [email protected]

Web site: http://www.allscripts.com/http://www.wpahs.org/

Provider of radiation therapy products and services North American Scientific has signed an agreement to sell its Nomos Radiation Oncology business to Best Medical International in a transaction valued at $3.6 million.

Under the terms of the deal, Best Medical will purchase Nomos Corporation assets, including stock of Nomos subsidiaries, Nomos GmbH and Nomos China USA. The purchase price is $500,000 cash at closing, plus assumption of certain obligations and liabilities, including $3.1 million of liabilities for warranty and maintenance agreements and Nomos facility lease in Cranberry. CIBC World Markets acted as the company’s financial advisor.

John Rush, president and chief executive of North American Scientific, said: “Our agreement with Best Medical represents the achievement of a major milestone in our strategy to build shareholder value through the focus on our core brachytherapy business.”

Krishnan Suthanthiran, president of Best Medical, added: “We are very excited about this acquisition. We wish to thank the Nomos and NASI team for concluding this agreement that is beneficial for all involved. The acquisition of Nomos Radiation Oncology business fits our strategy of expanding our product line in diagnostic and therapeutic radiology. We remain committed to the radiation oncology customers and look forward to integrating Nomos into the Best Medical family of companies.”

The deal is expected to close by September 17, 2007.

By Kumar, Coleen P

PURPOSE. This paper aims to illustrate the process of theory- based nursing practice by presenting a case study of a clinical nurse specialist’s assessment and care of a woman with type 2 diabetes. DESIGN. Orem’s self-car e deficit theory and standardized nursing language, NANDA, NIC (Nursing Interventions Classification), and NOC (Nursing Outcomes Classification), guided assessment and the identification of outcomes and interventions related to the client’s management of diabetes.

FINDINGS. Theory-based nursing care and standardized nursing language enhanced the client’s ability to self-manage the chronic illness: diabetes.

CONCLUSION. Nursing theory and standardized nursing language enhance communication among nurses and support a client’s ability to self-manage a chronic illness.

Search terms: Nursing diagnoses, nursing classifications and nursing outcomes, Orem’s self-care deficit theory, standardized nursing language, theory-based nursing practice

Introduction

As the average lifespan is extended, more individuals are coping with chronic illnesses such as diabetes, which has reached epidemic proportions with more than 20 million people in the United States having this diagnosis (Gordois, Scuffham, Shearer, Oglesby, & Tobian, 2003). The American Diabetes Association (ADA) estimates that a million people will be diagnosed of diabetes every year (2004). Long-term complications of diabetes are costly to both the individual and the healthcare system. Over the past decade, diabetes research has focused on pharmacological approaches and lifestyle interventions to the illness (Odegard, Setter, & Iltz, 2006). Recent evidence in the forum of diabetes care revealed a need for healthcare professionals to assess and empower individuals in the self-management of this illness.

For the purposes of this case study, health assessment by nurses was defined by Fuller and Schaller-Ayers (2000) as a process of systematically collecting and analyzing data to make judgments about health and life processes of individuals, families, and communities. In addition, the assessment included the integration of theory, diagnosis, intervention, and outcomes into practice and the use of theory to make decisions related to complex practice problems (Sandstrom, 2006). The plan of care was organized by the use of standardized nursing language, nursing diagnoses (NANDA International, 2007), nursing interventions (McCloskey & Bulechek, 2003), and nursing outcomes (Johnson & Maas, 2004). This provided a framework that is adaptable to specific health situations. A case study of a client with type 2 diabetes was used to illustrate the use of Orem’s self-care deficit theory and the integration of standardized nursing language in the care of this individual. The use of this theoretical base and nursing languages elucidated the effects of the illness on the individual and the individual’s various needs and responses (Sandstrom). The nurse caring for the client, Stella C, is a clinical nurse specialist (CNS).

Case Study and Application of Orem’s Theory

Stella C. is an obese 49-year-old single Italian American woman who has had type 2 diabetes for 10 years. Recently, she experienced signs of diabetes complications such as pain and numbness in both her lower extremities. Stella was seen by her primary care physician and was referred to a vascular surgeon for the painful neuropathy in her lower extremities. The surgeon ruled out peripheral vascular disease and referred Stella to the CNS diabetes educator employed in the vascular surgeon’s office for diabetes selfmanagement skills and education.

Because conceptual frameworks and models guide the plan and implementation of care in a purposeful way (Hamric, Spross, & Hanson, 2004), Orem’s self-care deficit theory provided a theoretical framework to guide assistance of a client with diabetes to meet self-management requirements (Orem, 2001). Ideally, the interpersonal relationship between a nurse and a client contributes to the alleviation of the client’s stress and that of the family, enabling the client and the family to act responsibly in matters of health (Orem). This assessment and plan of care utilized Orem’s four client-related concepts (self-care, self-care agency, therapeutic self-care demand, and self-care deficit) and two concepts that relate to nurses and their roles (nursing agency and nursing system). In addition, the linking concepts called basic conditioning factors, which include age, gender, developmental state, health state, sociocultural orientation, healthcare system elements, family system elements, patterns of living, environmental factors, and resource availability (Orem). Using Orem’s nursing theory, concepts can be integrated with middle range theories pertaining to health promotion and family systems to guide health assessment, selection of appropriate health outcomes, and carrying out nursing interventions. The use of the standardized nursing languages of NANDA, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC) thus ensures compatibility of care documentation across healthcare systems.

Comprehensive functional health pattern assessment (Fuller & Schaller-Ayers, 2000), including health promotion patterns, and family systems assessment, was essential to empower Stella in the self-management of her chronic illness. Each family member’s strengths, limitations, and unresolved personal issues were evaluated (Rutledge, Donaldson, & Pravicoff, 1999). In coping with a chronic illness such as diabetes, the degree of illness, illness progression, and the expected outcomes depend on and affect the responses of the family (Lubkin & Larsen, 2006). A thorough assessment of Stella’s family assisted the CNS to collaborate with her and her family in the selection of the most accurate nursing diagnoses, and the most appropriate outcomes and interventions.

Self-Care

Orem’s concept of self-care, or the practice of activities that adults initiate to maintain health, life, and well-being, is usually initiated voluntarily (2001). Family-centered care is based on the assumptions that professionals alone cannot and do not know what is best for clients, that the family has significant influence on the therapeutic regimens of individual clients (Rutledge et al., 1999), and that placement in the family constellation affects the individuals’ ability for self-care (Orem). Self-care is Stella’s continuous contribution to her own continued existence, health, and well-being, and is a human regulatory function that involves actions performed deliberately to regulate health, functioning, and development (Orem).

Stella is a college graduate who is employed as a financial controller in a small firm located close to her home. She enjoys theater, eating out, and being with her family. Stella lives in an apartment with her 80-year-old widowed mother, Mary, who has chronic rheumatoid arthritis, mild hypertension, and type 2 diabetes controlled with oral medication. Mary’s arthritis has limited her mobility. Stella’s father passed away 4 years ago. She has one sibling, a married brother, Mario, who has no chronic illnesses and maintains his weight within the normal range for his height.

Since Stella’s father died, she has assumed the role of head of the household. Mary is dependent on Stella for all of her activities. Although her brother is married and lives elsewhere, he tries to help with the care of their mother, but Mary puts him off, preferring to rely on Stella for all her needs. Stella maintains the house, shopping, and cleaning on the weekends. With the excess weight, however, heavy cleaning is difficult for her. Stella said to the nurse: “I am so tired all the time. I want to hire a cleaning lady once a week but my mother thinks we don’t need anyone. She was always so good to us when we were growing up. The least I can do is take care of her and make sure she is happy now.”

In order to maintain glycemie control of her type 2 diabetes, Stella should include activities such as self-monitoring of blood glucose (SMBG) and the integration of a prescribed diet, exercise, and medication regimen into daily living. To assist her to perform selfcare action for a specific purpose, the nurse must first have knowledge of the action and how it is related to continued life, well-being, and health. For example, with the ADA’s National Standards for Diabetes Self-Management Education, treatment is aimed at lowering blood glucose to near-normal levels. The risks of development or progression of diabetic retinopathy, nephropathy, and neuropathy are all greatly decreased by meeting this treatment goal (2007). It is possible that these complications may even be prevented by early normalization of metabolic status (Diabetes Control and Complications Trial Research Group, 1993). The prescribed regimen for type 2 diabetes includes emphasis on medical nutrition therapy, exercise, weight loss when indicated, SMBG, use of oral glucose-lowering agents, along with attention to family history and cardiovascular risk factors (ADA, 2007).

Self-Care Agency

Self-care agency, as defined by Orem (2001), refers to the power of individuals to engage in self-care and their capability for self- care. The person who uses this power or self-care ability is the self-care agent. Self-care agency is acquired and affected by the environment. In the long term, family members may affect the client’s adherence to behavioral changes and treatment regimens and overall outcomes (Rutledge et al., 1999). There is a power component to self-care agency, which addresses the importance of knowledge, attitudes, and skills that enable the individual to engage in self- care (Orem). If Stella feels that she is powerless to control the course of her disease, has environmental factors that are negatively influencing her self-management, and has a low self-esteem, this will negatively impact on self-care agency. Upon assessment, it was determined that Stella has an impaired self-care agency as indicated by being “exhausted” from working all day and caring for her elderly mother. She assumed the head of the household role and spends much of her time worrying over her mother’s health care, leaving little available time for thinking and caring for her own needs. She takes her medication as prescribed but has no time to think about diet management. When questioned about SMBG, she replied: “I have a monitor somewhere, but I don’t really have time to use it. I try to avoid eating foods I shouldn’t.” Management of obesity is essential in prevention of complications of type 2 diabetes (Davis, Emerenini, & Wylie-Rosett, 2006). She stated that she feels too tired to engage in an exercise program.

Therapeutic Self-Care Demands

Therapeutic self-care demands refers to those actions that Stella should perform over time to maintain life, health, and well-being. This has been further delineated to include universal therapeutic self-care demands (e.g., water and food), developmental self-care demands (e.g., death of a loved one), and health deviation therapeutic self-care demands, which applies to clients with chronic illnesses such as diabetes mellitus. The demand for therapeutic self- care in regard to health deficit refers to those health changes that bring about needs for action to prevent further problems or to control or overcome the effects of the existing deviations from health (Orem, 2001).

Stella is experiencing a common complication of long-term diabetes: peripheral neuropathy (Martinez & Reimer, 2005). Stella was not aware of the correlation between her maintenance of the prescribed regimen and control of her diabetes. Examination of Stella’s feet and legs revealed palpable pedal and posterior-tibial pulses. Both legs and feet were pale, and the soles flat. Peripheral neuropathy is associated with a characteristic posture of the foot, the classic claw foot, resulting in high pressure points under the metatarsal heads and decreased ability to feel pain (Martinez & Reimer). Stella may unknowingly injure her feet during normal daily activities due to this lack of sensation. The skin on Stella’s feet was intact but plantar calluses were noted bilaterally. This places Stella at higher risk for developing a diabetic foot ulcer. Despite being a protective mechanism, callus formation concentrates the stresses and can result in inflammation, hemorrhage, and breakdown of the underlying soft tissue and eventual ulcer formation. Treatment of diabetic neuropathy involves control of the diabetes (Martinez & Reimer). Individuals affected by neuropathy are often asymptomatic at first (Gordois, Scuffham, Shearer, Oglesby, & Tobian, 2003), but this condition places the individual at high risk for more serious complications. Diminished sensation in the lower extremities makes foot ulcerations a common occurrence. The ordinary act of walking may in fact be a risky endeavor for an individual with diabetic neuropathy. Unfortunately, ulceration is not the only risk. Approximately 50% of all nontraumatic lower extremity amputations in the United States occur in people with diabetes (ADA, 2004; Martinez & Reimer).

Self-Care Deficit

The concept of self-care deficit refers to the relationship between the self-care agency and the self-care demand. Stella has a partial self-care deficit. She has some capabilities for meeting her self-care demand but, as is evident in her poor glycemie control and peripheral neuropathy, she needs assistance in meeting her health deviation self-care demands. In order for nursing to be legitimate, self-care deficit must exist (Polit & Hungler, 2003).

Nursing Agency

Nursing agency, in this case study the CNS, was developed and exercised for the benefit and well-being of Stella and can be further described as activated or inactivated. An activated nursing agency yields nursing diagnoses and a plan for self-care of people with self-care deficits. Nursing agency is the expression of the purpose of nursing, which is to compensate for or to overcome known or emerging health-associated limitations of clients for self-care (Orem, 2001). The CNS diabetes educator is an expert in diabetes management and applies a broad range of nursing interventions to assist Stella engage in self-care through knowledge and empowerment of her selfcare agency. Diabetes self-management is key to successful outcomes for this client. The CNS, as activated nursing agency, served as both educator and facilitator with a primary responsibility to Stella and her family.

Nursing System

When a nursing agency is activated, a nursing system is produced (Orem, 2001). A nursing system is all of the actions and interactions of nurses and clients in nursing practice situations that meet components of the client’s therapeutic self-care demands and protects and regulates the development of the client’s self- care agency (Orem). There are three types of nursing systems: wholly compensatory, partly compensatory, and supportive educative.

Stella required a supportive educative nursing system. The CNS performed actions to support and educate Stella and her family. The CNS provided information about diabetes self-management and supported Stella psychologically, thus enhancing her self-care agency.

Analysis of Assessment Data Using Standardized Nursing Languages

The first step of analysis was to identify Stella’s strengths. The CNS and Stella identified the strengths of having a close relationship with her family, particularly her brother, and having a strong sense of spirituality. Stella is a Roman Catholic and stated, “I get great solace from prayer and going to church.” In the Italian American culture, there is an emphasis on extended and close family ties and support as well as strong religious practices (Leininger & McFarland, 2005). When a family member’s illness becomes chronic, families who are able to “reframe the situation” and find positive meaning tend to cope better (Rutledge et al., 1999).

Standardized nursing language names what nurses do (NANDA International, 2007). Nursing diagnosis necessitates investigation and the accumulation of data about a client’s self-care agency and therapeutic self-care demand and the relationship between them. Collaboration by Stella and the CNS on her responses to her health problems and life processes resulted in the identification of several nursing diagnoses. This process is based on knowledge of nursing diagnoses and of the role the client can fill in the management of self-care (Orem, 2001).

Stella thought that she was not as healthy as she should be and she expressed concern about her health: “My father died from complications of diabetes. My mother has diabetes. I really need to do something.” Her insufficient knowledge related to the management of diabetes was important to address, as it would have a profound effect on the other identified human responses. During the assessment, it became clear that Stella’s knowledge about her illness was more limited than at first impression. Diabetes is a self-managed illness. Nursing diagnosis: Deficient knowledge related to management of diabetes mellitus.

Stella was interested in getting her diabetes under control and losing weight. “I’m not looking to be skinny, I want to feel better, have more energy,” she said. Stella was 5 feet 6 inches and weighed 250 pounds. Stella’s interest in weight loss was a necessary condition of engagement in weight-loss behavior. Stella is Italian American and this may present a problem when adjusting her diet, as she likes to eat pasta and bread and family gatherings are centered around meals. Foods high in carbohydrate content and calories may contribute to her lack of glycemie control. Two thirds of adults in the United States are overweight and 30.5% are obese; thus, Stella is surrounded by a culture of noncompliance related to weight control (National Institutes of Health, 2003). Nursing diagnosis: Imbalanced nutrition: More than body requirements.

With the CNS, Stella determined that she had a sedentary lifestyle. She lives in an apartment building with an elevator, and rarely uses the stairs. She was not aware that her existing poor glycemie control, lack of physical activity, and obesity could be contributing to her feelings of fatigue (Porth, 2006). The CNS noted that an overly aggressive approach to exercise could exaggerate her existing clinical condition (peripheral neuropathy). Stella’s lower extremity pain could also be a barrier to action in which Stella may not increase activity in order to avoid an increase in pain. Nursing diagnosis: Pain: Chronic.

Her cultural background and beliefs influenced management of her illness. She believes that most things are not in her control but are “in God’s hands.” Stella has a potentially dysfunctional self- concept. She has feelings of powerlessness: “This is the hand I was dealt. There really isn’t much I can do to change things.” This may interfere with Stella’s self-efficacy to incorporate SMBG into her daily routine. She will have to learn the necessary relationship between the types of food she chooses to eat and her blood sugar levels. In addition, her weight-loss success will be influenced by her diet. She has assumed her deceased father’s role as head of the household and is the primary caregiver for her elderly, chronically ill mother. The family caregiving experience is shaped by race and ethnicity as these two factors influence one’s life experiences in terms of socioeconomic status, education, marital status, living arrangements, and general lifestyle (Lubkin & Larsen, 2006). Stella is not coping well with the changes in her home and physical health. Her mother has become increasingly more dependent on her and Stella’s physical health has deteriorated and she has developed symptoms related to complications of type 2 diabetes. Adapting successfully to chronic illness includes the conviction that a meaningful quality of life is worth the struggle. Nursing diagnosis: Powerlessness. Stella feels that things at home have not been the same since her father died. “My mother was such a dynamo. Now she waits for me to come home and bring the world to her. She doesn’t want to do anything with anyone else,” she said. When the demands of providing for a family member are perceived as exceeding available resources, caregivers experience stress. Stress often leads to feelings of burden, depression, and a sense of powerlessness (Lubkin & Larsen). Nursing diagnosis: Caregiver role strain.

Projected Health Outcomes

Outcomes describe client states that follow and are influenced by an intervention (Johnson & Maas, 2004). In structuring a nursing system, it is necessary to identify the health outcomes sought or changes required (Orem, 2001). Utilizing Orem’s theory as a guide, Stella and the CNS planned for projected health outcomes. The CNS collaborated with Stella and formulated self-care requisites (health outcomes) necessary to Stella’s well-being and health (Orem). Self- care requisites are the expressed purposes of self-care and are attained through action (Orem). A priority-projected outcome that was agreed on was “knowledge: diabetes management.” It was decided that Stella was at level 2, limited understanding about diabetes, and its control but needed to be at level 4, substantial knowledge of diabetes and its management (Johnson & Maas).

Another agreed on projected health outcome was pain control. Stella did not realize that her extremity pain was related to poor glycemie control (Apfel, 1999). “Imbalanced nutrition: more than body requirements” was linked to the health outcome “nutritional status: nutrient intake.” Guided by her primary care physician, Stella would follow a prescribed diet specifically tailored for her. This would increase the probability that Stella would be compliant with the dietary changes. A contract was made that stipulated that she would be weighed in 1 month. A short-term goal of a 5-pound weight loss was agreed on.

To address Stella’s feelings of “powerlessness,” the outcome of “health beliefs: perceived control” was evaluated as level 2, weak personal conviction that one can influence a health outcome, with the goal of achieving a level 4, strong conviction that a health outcome can be self-influenced (Johnson & Maas, 2004). Outcomes expectations affect individuals’ adherence to diabetes regimens (Chlebowy & Garvin, 2006). Stella stated that she loves her mother and felt that it was her choice to care for her in her last years, but agreed that it would also be better to have more time for herself. Stella and the CNS agreed to address the NOC outcomes of caregiver well-being, and caregiver physical health. Her levels were identified as 2, substantially compromised, at initiation of the plan of care with a goal of moving to level 4, mildly compromised, within 1 month (Johnson & Maas). Stella needed respite care for her mother and guidance in using the community resources available to her family in coping with the demands of caring for her elderly mother.

Nursing Interventions

In selecting nursing interventions for Stella, six factors were considered: desired client outcomes, characteristics of the nursing diagnosis, research base for the intervention, feasibility for doing the intervention, acceptability to the individual, and the capability of the nurse (McCloskey & Bulechek, 2003). Designing effective and efficient regulatory nursing involves selecting valid ways of assisting a client (Orem, 2001). The NIC intervention for the diagnosis “deficient knowledge: disease process” was “teaching: disease process”; “teaching: prescribed diet”; “teaching: prescribed medication”; and “teaching: procedure/treatment” (McCloskey & Bulechek). The rationale for these interventions was related to weight loss being the single most important therapeutic objective for overweight individuals with type 2 diabetes. Moderate weight loss – 10 to 20% of body weight – has been shown to lead to improved glycemie control (ADA, 1999).

The nursing diagnosis of chronic pain and NOC outcome of pain control was addressed with the nursing interventions of pain management, physicianprescribed antiinflammatory drugs, and relaxation therapy (McCloskey & Bulechek, 2003). Stella enjoyed relaxation therapy and found a self-help group through her church. The CNS recommended incorporating learned relaxation techniques into her daily routine. In addition, Stella would begin keeping a diary. This diary would not only document her finger stick results and food intake but also include expression of her feelings. Improved glycemic control will decrease her neuropathic pain.

The nursing interventions related to Stella’s weight and nutritional management were identified as nutrition management and weight reduction assistance. Careful meal planning and engaging in mild to moderate exercise three to four times per week can reduce blood glucose significantly (Dow, 2005). The nursing interventions related to Stella’s feelings of powerlessness are self-esteem enhancement and emotional support. A client’s response to loss of control depends on the meaning of the loss, individual patterns of coping, personal characteristics, and responses of others (Carpenito, 2004). The nursing interventions for Stella’s risk for caregiver role strain are caregiver support, family involvement promotion, and respite care (McCloskey & Bulechek, 2003). Pursuing personal goals during caregiving assists caregivers to be able to focus on their own interests and loves (Carpenito). Arrangements were made to have Stella’s brother, Mario, visit on a regular basis to allow her time for herself. The CNS facilitated communication between Stella and her family by arranging a meeting among family members with the CNS acting as facilitator and educator.

Evaluation of Health Outcomes

Several factors were considered when establishing health outcomes related to Stella’s nursing diagnoses. Successful management of her illness as a result of her increased knowledge was indicated by the following self-care actions:

1. Stella performed SMBG daily and her diary indicated an average blood sugar of 140.

2. Her food diary indicates food choices that support good glycemic control.

3. At the 1-month follow-up visit with the CNS, Stella had lost a total of 7.6 pounds, exceeding her short-term goal.

4. Stella reports that the pain in her legs is improving, a result of better glycemic control.

5. She is coping more effectively with her caregiver role by sharing some of the burden with her brother who visits weekly. Mary has agreed with Stella to hire a cleaning service once per month. Stella is planning to attend a trip to Atlantic City and to continue attending the monthly prayer group.

Clinical nurse specialists are appropriate healthcare providers for coordinating care across a variety of settings based on their skills in education and counseling. Increasingly, healthcare providers are forming partnerships with clients in which both provider and client collect information and discuss choices. This collaborative approach is a hallmark of the CNS diabetes educator. As the number of clients with diabetes increases, the need for experts in the field increases.

The goal of management of the chronic illness diabetes is self- care. Orem’s self-care deficit theory directs the CNS diabetes educator in the guidance of a client through the process of self- management (self-care) of diabetes. The use of standardized nursing language, NANDA, NIC, and NOC, facilitates and enhances communication among nurses and assists in standardizing knowledge for nursing practice.

References

American Diabetes Association. (2004). Preventive foot care in people with diabetes position statement. Diabetes Care, 27(1), S63- 64.

American Diabetes Association. (2007). National standards for diabetes self-management education. Diabetes Care, 30, S96-103S.

Apfel, S. (1999). Diabetes polyneuropathy. Medscape diabetes & endocrinology clinical management. Retrieved February 21, 2007, from http://www.neurology.medscape.com/Medscape/endocrinology/ ClinicalMgmt/CM.v01/pnt-CM.v01

Carpenito, L. (2004). Nursing care plans and documentation nursing diagnoses and collaborative problems (4th ed.). Philadelphia: Lippincott.

Chlebowy, D., & Garvin, B. (2006). Social support, self- efficacy, and outcome expectations. Diabetes Care, 32(5), 777-786.

Davis, N., Emerenini, A., & Wylie-Rosett, J. (2006). Obesity management: Physician practice patterns and patient preference. Diabetes Educator, 32(4), 557-561.

Diabetes Control and Complications Trial Research Group. (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine, 329(14), 977-986.

Dow, N. (2005). Tight insulin control: Making it work. RN, 68(7), 46-52.

Franz, M., & Bantle, J. (Eds.) (2003). American Diabetes Association guide to medical nutrition therapy for diabetes(clinical education series). Canada: Author. Fuller, J., & Schaller-Ayer, J. (2000). Health assessment: A nursing approach (3rd ed.). Philadelphia: Lippincott.

Gordois, A., Scuffham, P., Shearer, A., Oglesby, A., & Tobian, J. (2003). The health care costs of diabetic peripheral neuropathy in the U.S. Diabetes Care, 26(8), 2305-2310.

Hamric, A., Spross, J., & Hanson, C. (2004). Advanced nursing practice: An integrative approach (2nd ed.). Philadelphia: W.B. Saunders.

Johnson, M., & Maas, M. (Eds.) (2004). Nursing interventions classification (NOC), Iowa outcomes project (2nd ed.). St. Louis, MO: Mosby.

Leininger, M., & McFarland, M. (2005). Culture care diversity & universality: A worldwide theory of nursing (2nd ed.). New York: Jones & Bartlett.

Lubkin, I. M., & Larsen, P. (2006). Chronic illness: Impact and interventions (6th ed.). Boston: Jones & Bartlett.

Martinez, N., & Reimer, T. (2005). Diabetes nurse educators’ prioritized elder foot care behaviors. Diabetes Educator, 31(6), 858- 868.

McCloskey, J., & Bulechek, G. (Eds.) (2003). Nursing interventions classification (NIC), Iowa intervention project (4th ed.). St. Louis, MO: Mosby.

NANDA International. (2007). NANDA-I Nursing diagnosis definitions and classifications (2007-2008). Philadelphia: Author.

National Institutes of Health. (2003). Statistic related to overweight and obesity. Retrieved July 1, 2004, from http:// www.niddk.nih.gov/health/nutrit/pubs/statobes.htm

Odegarde, P., Setter, S., & Iltz, J. (2006). Update in the pharmacologic treatment of diabetes mellitus: Focus on pramlintide and exenatide. Diabetes Educator, 32(5), 693-712.

Orem, D. (2001). Nursing concepts of practice (6th ed.). St. Louis, MO: Mosby.

Polit, D., & Hungler, B. (2003). Nursing research principles and methods (7th ed.). Philadelphia: Lippincott.

Porth, C (2006). Pattophysiology concepts of altered health states (6th ed.). Philadelphia: Lippincott.

Rutledge, D, Donaldson, N., & Pravicoff, D (1999). Patient education in disease and symptom management: Diabetes mellitus. Online Journal of Clinical Innovations, 3(2), 1-35.

Sandstrom, S. (2006). Use of case studies to teach diabetes and other chronic illnesses to nursing students. Journal of Nursing Education, 45(6), 229-232.

Coleen P. Kumar, RN, MSN, CNS

Coleen P. Kumar, RN, MSN, CNS, is Assistant Professor of Nursing, Kingsborough Community College, Brooklyn, New York.

Author contact: [email protected]

Copyright Nursecom, Inc. Jul-Aug 2007

(c) 2007 Nursing Diagnosis. Provided by ProQuest Information and Learning. All rights Reserved.

Medical Staffing Network Holdings, Inc. (NYSE: MRN), the third largest healthcare staffing company and the largest provider of per diem nurse staffing services in the nation as measured by revenues, announced today that it has completed the asset acquisition of AMR ProNurse for $11.0 million in cash. AMR ProNurse provides nurses, allied healthcare and other medical professionals to healthcare facilities in the greater Chicago area and is a market leader in healthcare Vendor Management Services (VMS) with their OneSource VMS program. AMR’s annualized revenue run rate exceeds $15.0 million.

Robert J. Adamson, MSN’s chairman and chief executive officer, said, “We are pleased to have completed the acquisition of AMR, whose market-leading vendor management service expertise in the Chicago marketplace is an asset that we hope to leverage throughout our national client base. I am excited that the management team behind AMR’s success will remain in place to spearhead this growth initiative for MSN. Increasingly, clients are expressing an interest in this process for managing their contingent labor force with solutions that are effective in controlling costs while providing an environment conducive to optimal patient care. We believe that the addition of AMR’s VMS portfolio in addition to our current book of VMS business will establish Medical Staffing Network as one of the largest providers of healthcare staffing Vendor Management Solutions.”

Fully integrating within an organization, AMR ProNurse’s OneSource VMS streamlines and standardizes every facet of staffing from order processing, reporting, invoicing, quality initiatives and payment processes, resulting in vast efficiencies and the best possible cost savings, quality, and fill ratio performance. The OneSource VMS program has received national recognition from The Advisory Board Company (Washington, D.C.) as well as the American College of Healthcare Executives Congress.

In commenting on the acquisition, Mark Gallagher, chief executive officer of AMR ProNurse, added, “We are very excited to announce this transaction. We believe our innovative approach to helping our clients manage their supplemental staffing needs and processes through our OneSource solution will flourish within MSN’s national framework. I am thrilled that the team that built our leadership position in the Chicago healthcare market will remain in place to serve our current clients and will have opportunities for growth within MSN. I am excited to be joining the MSN executive management team.”

About Medical Staffing Network Holdings, Inc.

Medical Staffing Network Holdings, Inc. is the largest provider of per diem nurse staffing services in the United States as measured by revenues. The Company also is a leading provider of travel nurse staffing services and of allied health professionals, such as radiology and diagnostic imaging specialists, clinical laboratory specialists, rehabilitation specialists, pharmacists and respiratory therapists and other similar healthcare vocations.

About AMR ProNurse

AMR ProNurse is the leader in the Chicago healthcare staffing market through the development of its OneSource vendor management service for hospital and clinics. The company’s clients include some of the most prestigious healthcare organizations in the country. Headquartered in downtown Chicago and relying upon a state-of-the-art technology platform, the company supports clients and healthcare professionals with the innovative solutions needed in today’s demanding healthcare market.

Some of the statements in this press release are “forward-looking statements,” as that term is defined in the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding our acquisition of AMR ProNurse. Forward-looking statements do not relate strictly to historical or current matters. Rather, forward-looking statements are predictive in nature and may depend upon or refer to future events, activities or conditions. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward-looking statements. These factors include: our ability to successfully integrate the business, operations and employees of AMR ProNurse into MSN; our ability to maintain the operations of AMR ProNurse’s VMS program; our ability to achieve continued revenue growth previously achieved by AMR ProNurse; and our ability to continue to grow AMR ProNurse’s VMS program. Additional information concerning these and other important factors can be found within the registrant’s filings with the Securities and Exchange Commission. Forward-looking statements in this press release should be evaluated in light of these important factors. Although the registrant believes that these statements are based upon reasonable assumptions, the registrant cannot provide any assurances regarding future results. The registrant undertakes no obligation to revise or update any forward-looking statements, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

TROY, Mich., Sept. 13 /PRNewswire-FirstCall/ — Medical device maker Somanetics Corporation today announced that The Society of Thoracic Surgeons (STS) has added cerebral oximetry as a metric to be collected as part of the STS Adult Cardiac Surgery Database effective January 1, 2008.

Somanetics’ INVOS System is a cerebral oximeter that helps medical professionals protect patients during cardiac surgery by reflecting whether the brain has adequate oxygenation throughout the operation.

“The STS’ decision to incorporate cerebral oximetry into its database supports our company’s evidence-based philosophy with regards to demonstrating the role of technology to potentially improve patient outcomes,” states Bruce J. Barrett, president and CEO of Somanetics. “We are excited that cerebral oximetry will be a part of this quality initiative.”

To date, there are more than 500 published clinical papers, abstracts and conference presentations evaluating the benefits of cerebral oximetry via the INVOS System. These include studies showing a correlation with reduction of stroke, major organ morbidity and mortality, post-op cognitive difficulties, adverse cardiac events, respiratory failure and ventilator time. Data has shown that reducing these surgical complications correlates with decreased patient length of stay in the post-op intensive care unit – one of the most costly care areas – as well as the overall length of hospital stay.

“The clinical popularity of cerebral oximetry seems to merit inclusion in the STS database,” explains Nicholas J. Gawrit, president of heartbase inc., a clinical registry reporting firm whose software is certified by STS for use by Adult Cardiac Surgery Database participants. “The addition of this metric to the database is an opportunity to validate the outcome benefit of patient management guided by cerebral oximetry in thousands of patients.”

According to the STS, the STS Adult Cardiac Surgery Database is the largest cardiothoracic surgery outcomes and quality improvement database program in the world, and is viewed as the national gold standard for cardiothoracic surgery. Over 800 surgeon groups voluntarily participate in this clinical registry containing data from more than three million patient records.

This data is considered the cornerstone of quality assessment in cardiothoracic surgery and has been used to establish clearly-defined benchmarks for clinical comparisons. Many third-party payers, major corporate purchasers of healthcare, hospitals, health care systems and states now require monitoring of outcomes and participation in quality improvement programs, and involvement in the STS National Database helps fulfill this requirement.

Somanetics has pioneered many “firsts” in the regional oximetry market, including the first U.S. adult cerebral oximeter in 1996, the first pediatric cerebral oximeter in 2000 and the first simultaneous cerebral-somatic (brain and body tissue) oximeter in 2005.

About the INVOS(R) Cerebral / Somatic Oximeter

The INVOS System has a 10-year market track record and is used at more than 600 U.S. hospitals conducting a total of 150,000 procedures annually. It is the only noninvasive oximeter to provide simultaneous cerebral/somatic monitoring of changes in regional blood oxygen saturation. The INVOS System uses near infrared spectroscopy to “reflect the color of life” by measuring the color of de-oxygenated and oxygenated hemoglobin molecules within red blood cells. The resulting regional oxygen saturation (rSO2) change information is a vital sign that helps critical care teams detect and correct site-specific blood oxygenation issues that can lead to complications and poor outcomes. Cerebral/somatic monitoring via the INVOS System can be used on adult, pediatric and infant patients in any clinical setting where patients are at risk of reduced-flow or no-flow ischemia.

About Somanetics

Somanetics Corporation develops, manufactures and markets the INVOS Cerebral/Somatic Oximeter, a non-invasive patient monitoring system that continuously measures changes in the blood oxygen levels in the brain and body (i.e., somatic, or skeletal muscle tissue). Surgeons, anesthesiologists, intensive care nurses and other medical professionals can use the information provided by the INVOS System, in conjunction with other available information, to identify cerebral or somatic oxygen imbalances and take necessary corrective action, potentially improving patient outcomes and reducing the costs of care. Somanetics supports its customers through a direct U.S. sales force and clinical education team. Tyco Healthcare markets INVOS System products in Europe, Canada, the Middle East and South Africa and Edwards Lifesciences represents INVOS System products in Japan. For more information visit http://www.somanetics.com/.

Safe-Harbor Statement

Except for historical information contained herein, the matters discussed in this news release are forward-looking statements, the accuracy of which is necessarily subject to risks and uncertainties. Actual results may differ significantly from results discussed in the forward-looking statements and may be affected by, among other things, economic conditions in general and in the healthcare market, the demand for and market acceptance of our products in existing market segments and in new market segments we plan to pursue, our current dependence on the Cerebral Oximeter and SomaSensor, our dependence on distributors and independent sales representative firms for a substantial portion of our sales, our dependence on single-source suppliers, potential competition, the effective management of our growth, our ability to attract and retain key personnel, the potential for products liability claims, government regulation of our business, changes in our deferred tax assets, future equity compensation expenses, the challenges associated with developing new products and obtaining and maintaining regulatory approvals if necessary, research and development activities, the lengthy sales cycle for our products, sales employee turnover, changes in our actual or estimated future taxable income, changes in accounting rules, enforceability and the costs of enforcement of our patents, potential infringements of others’ patents and the other factors set forth from time to time in Somanetics’ Securities and Exchange Commission filings, including Somanetics’ 2006 Annual Report on Form 10-K filed on February 8, 2007 and the first and second quarter 2007 Quarterly Reports on Form 10-Q filed on April 3, 2007 and June 29, 2007 respectively.

Somanetics Corporation

CONTACT: Jane Hauser or Julia Maslen of Somanetics Corporation,+1-781-684-0770, [email protected]

Web site: http://www.somanetics.com/

By Tim Engle, The Kansas City Star, Mo.

Sep. 13–What’s Marilu Henner got against cows? Which two of her “Taxi” co-stars did she hook up with? And when you’re known as a health nut, what can you have for lunch?

Henner — also a veteran of the Burt Reynolds sitcom “Evening Shade” and Broadway’s “Chicago” — chatted with us this week from her home in L.A. The 55-year-old actress and author of Total Health Makeover will talk more Sunday afternoon when she’s in town for a Muriel I. Kauffman Women’s Heart Center event at Starlight Theatre.

Q. I’ve had the “Taxi” theme in my head all morning.

A. It’s a good thing to have. Much better than “Schlemiel! Schlemazl!” (from “Laverne & Shirley”). Not that there was anything wrong with that one.

I still think of you from “Taxi” and “Chicago,” but you’ve become almost better known as a health guru.

Well, I’m still doing both. I have a big Lifetime movie coming out in the fall (“Deadly Suspicion”) — I got to play a villain for the first time in my career. Everybody goes, “Oh, she’s so wholesome, she’s so healthy, so positive and upbeat” — well, wait till they see me in this!

But how’d you get to be Super Health Woman?

My parents both died in their 50s. My father died at 52 of a heart attack during a Christmas party at our home. I was 17. It was terrible — it was during an argument with my brother. You can imagine the effect it had on my family.

I found myself eating my feelings. I put on a lot of weight after that, got up to 174 pounds — I’m 120 now. Kept that weight on for a while, started college, etc., then went on crazy diets, would yo-yo my way up and down, became an actress. Then my mother died when she was 58 of rheumatoid arthritis.

After that I said to myself it’s not about my weight anymore, it’s really about my health. So I became a real student of health. I read everything I could get my hands on, hundreds and hundreds of books, I went to medical libraries and nutritionists, I took a human anatomy class. I just changed so much of my lifestyle.

Your first book, Total Health Makeover, came out in 1998. What was the basic concept?

It was about the 10 things I did to change my life, addressing chemicals, caffeine and smoking, sugar, meat, dairy, fat, food combining, exercise and stress, sleep and gusto. And then I wrote a chapter on reading your face and also a chapter on “What’s the Poop.” Now it’s popular to talk about it, but I was the first person to talk about it.

Didn’t Oprah do a show on poop?

Yes, I know. Oprah’s always jumping on my bandwagon (laughs). You know a lot about somebody if you check out their garbage can.

So you’re anti-dairy and vegetarian.

Well, I do have some fish once in a while, but I’m basically vegan. But no dairy, no sugar, no meat, no caffeine.

Tell me why you avoid cow’s milk.

I’ll give you my short speech about dairy. When you think about it rationally, all dairy is supposed to do is turn a 50-pound calf into a 300-pound cow in six months. That’s it. So I always say to people, if those are your aspirations, knock yourself out.

You would never make cheese (from) or drink the breast milk of your next-door neighbor, somebody you know, but you’re basically sucking the udder of a cow that you don’t know, that you have nothing to do with. You’re closer to an orangutan and yet you would never nurse from an orangutan. But we’re nursing from cows. It doesn’t make sense.

So do you drink soy milk instead?

In my family we usually do oat milk or rice milk. Or almond milk.

What did you have for breakfast this morning?

I had some oranges and some raw almonds. And for lunch I’ll probably have a brown rice sushi roll with avocado and cucumber and spicy sauce. Or cold soba noodles with a sesame sauce. Or an arugula salad or a piece of grilled fish. I’m an eater — I eat all day long. But I work out, too. I break a sweat every day doing something.

What was the hardest thing to change about your lifestyle?

I was totally addicted to dairy products. I would buy a pound of Jarlsberg cheese and chip away at it and only eat that for the day and call it my 1,600-calories-a-day diet. And then I wondered why I didn’t go to the bathroom for 17 days! Or I’d walk to unemployment in New York and stop at Zabar and buy a little baggie of cheese ends. And I’d be thinking, “Why am I fat, constipated and have pimples?” I loved cheese. I was a real dairy freak.

One of your books is I Refuse to Raise a Brat. What’s the single biggest mistake parents make?

Well-intentioned parents do so much for their kids, but they don’t know how to say no. They don’t know how to set boundaries. They don’t know that “No” is a complete sentence and the kids should have to figure it out. They shouldn’t bargain. They shouldn’t negotiate. … Kids have no school of hard knocks anymore. They have no frustration tolerance and no coping skills as a result.

I read that you can remember what you were doing on any date in the past.

I have a freaky date memory. It’s sort of photographic. It’s called eidetic memory. In fact, (a cable channel) is doing a special on me, so I can’t really talk about it too much. Name any date and I’ll tell you what day of the week it was and what I was doing that day.

OK, how about …

No, no, no! I can’t do that! I’m under a gag order right now.

In your autobiography you talk about your romances, including with Judd Hirsch and Tony Danza from “Taxi.” But I was hoping there might have been an Andy Kaufman or Christopher Lloyd hookup.

Oh, no. No, no, no. Not that they weren’t adorable. Two guys in five years is pretty good, but if I’d taken on the rest of the team, I think that would be moving into the (tramp) category.

More about Marilu Henner at her Web site, marilu.com. Her eighth book, Wear Your Life Well, is due next April.

——

NO BARBECUE FOR HER Marilu Henner says that when she takes a road trip with her two boys, 11 and 13, she checks in with happycow.com. The Web site has a searchable database of health food stores and restaurants with vegetarian options. “We found soy-cheese pizza at the Grand Canyon,” Henner says.

Her sons have never had a glass of cow’s milk. But unlike her, they do eat chicken and turkey.

——

‘HEART’ TALK WITH HENNER Who: Marilu Henner

What: Featured speaker at “A Heart in Bloom,” sponsored by the Muriel I. Kauffman Women’s Heart Center. The “Heart Healthy Woman of the Year” will be announced.

When: 1:30 p.m. Sunday

Where: Starlight Theatre in Swope Park

Cost: The ticket price of $75 includes a copy of Henner’s book Healthy Holidays. Hors d’oeuvres and cocktails will be served.

Info: Call 816-932-5624 or go to hearthealth4women.org.

To reach Tim Engle, features writer, call 816-234-4779 or e-mail [email protected].

—–

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Copyright (c) 2007, The Kansas City Star, Mo.

Distributed by McClatchy-Tribune Information Services.

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The Consortium of Independent Physician Associations (CIPA), an affiliate of Medical Advantage Group (MAG) and a collection of 38 independent physician associations (IPA), consisting of 4,000 physicians throughout the state of Michigan, has selected DrFirst(TM) as its partner in deploying Rcopia electronic prescribing technology to 1,200 of their member physicians. The initial focus will be on installing e-prescribing for primary care physicians and large group practices. This e-prescribing initiative was developed to encourage improvements in the quality and efficiency of care delivered to patients while also creating opportunities to achieve performance-based incentives for member physicians.

“Through DrFirst’s unique Rcopia Insight(TM) reporting system, CIPA will be able to observe aggregate physician prescribing behavior and to benchmark utilization and outcomes data. Our goals for the first three years of the program are to increase patient safety, cost savings, and physician office efficiency. In addition, we expect to forge new contracts with major insurers to increase generic utilization and increase formulary compliance resulting in higher incentive payments for our physician members,” said Charles Carpenter, Consultant for CIPA.

Based on results that DrFirst has achieved with similar physician organizations, CIPA anticipates 480,000 prescription changes because of drug-to-drug interaction alerts, 36,000 prescription changes because of drug allergy alerts and one to two hours per day of time saved for each physician because of the automated renewal process.

“We believe MAG and CIPA are uniquely positioned to rapidly expand the utilization of electronic prescribing across the state of Michigan because of their scope and size,” said G. Cameron Deemer, President of DrFirst. “By offering Rcopia to its member physicians, CIPA will strengthen its market presence and build its relationships with existing members through technological innovation and increased profitability.”

CIPA will subsidize first year costs for each physician and pay for a PDA or comparable credit towards other hardware. After the initial year, CIPA has contracted with DrFirst to offer the physicians the opportunity to continue the program at a discounted rate.

DrFirst’s flagship product, Rcopia, is the nation’s leading full-featured stand-alone electronic prescription management system and the leading e-prescribing tool in Michigan. Rcopia is easy to use, so clinicians can learn quickly and positively impact care. CIPA providers using e-prescribing will receive clinical alerts to patient drug allergies, drug interactions and therapeutic duplication. They can access insurance plan eligibility and formulary, authorize renewals and refills, and easily track a patient’s medication history. Rcopia operates on multiple platforms, including PDAs, desktop, laptop and tablet personal computers, allowing physicians to create legible prescriptions quickly and accurately and remembering patients’ medication dosage/interval and pharmacy of choice. In addition, staff efficiency can be increased through fewer phone calls and faxes, since prescription and renewal requests are accepted directly from and sent to pharmacy computer systems. All of these factors allow Rcopia to enhance patient safety and reduce costs with the goal of benefiting patients, physicians, pharmacies and health plans.

About DrFirst

DrFirst is a national provider of physician connectivity services through its award-winning, Surescripts GoldRx Certified Rcopia electronic prescription management system. Founded in 2000, DrFirst creates innovative services targeted to physicians in both ambulatory and acute care environments. DrFirst solutions are widely integrated with practice management and electronic medical records software through its “Open Borders” program, and the company counts among its client base not only physician practices, but major health plans, health systems, and EMR vendors. More information about DrFirst can be found at www.drfirst.com.

About The Consortium of Independent Physician Associations (CIPA)

The primary purpose of CIPA is to serve as a vehicle for physicians to maintain their independent practice of medicine yet be part of a larger entity working together to engage in physician incentive opportunities. Our mission is to encourage improvements in the quality and efficiency of care delivered to patients by engaging in opportunities which recognize and reward health care providers for performance excellence. We believe that participation in programs that recognize performance excellence with financial incentives can sustain and enhance the independent practice of medicine. CIPA is managed by Medical Advantage Group (MAG), a management service organization that provides ongoing management and administrative services to CIPA, as well as to individual physician organization members of CIPA. More information about CIPA can be found at http://www.thecipa.com.

Image Available: http://www2.marketwire.com/mw/frame_mw?attachid=574694

 DrFirst, Inc. Irene Froehlich 240-671-3320 Email Contact  CIPA Dyana Males 517-214-2465 Email Contact

SOURCE: DrFirst, Inc.

It’s time for the rowing race. The competitors position their bodies perfectly in their seats. They tighten their grip on the handles. They eye their competition. They can almost feel the wind on their faces and the lap of the water beneath their feet.

And, the race begins!

But this contest is unique because it’s a virtual race, taking place online.

WaterRower Inc., a leading designer and manufacturer of rowers for home and fitness facility use, today introduced We-Row.com, a free, interactive Web site where WaterRower owners can imagine themselves in sculling races on the river, testing their skill against other rowers and tracking their progress, all from the convenience of their own homes.

“The colder temperatures of fall and winter mean a lot of people will be bringing their workouts indoors, but not having the shared energy, motivation and support of workout partners can take its toll, even on dedicated exercisers,” said Dominik Kuprecht, director of sales and marketing, WaterRower. “With We-Row.com, WaterRower users get the best of both worlds. They can exercise in the privacy of their own home, but they still can enjoy the benefits that come from working out with others and maintain their racing skills even during the harshest winter months. The excitement of competition makes it an exhilarating way to exercise — whatever the season.”

Connecting a rowing machine to a PC and racing other rowers while online might sound futuristic, but We-Row.com is just one of the ways that technology is enhancing workouts today. “With the wide availability of training regimens and monitoring software available for iPods, GPS devices and other handheld units, consumers are increasingly using technology to infuse excitement and variety into their fitness activities,” said Kuprecht. “So we expect WaterRower users will welcome the opportunity to use the Internet to race other rowers in head-on competitions.”

After connecting the WaterRower to a PC, users log in at www.we-row.com, create a personal profile based on fitness level, weight, height and lifestyle factors, and complete a 2,000 meter row to set a benchmark fitness level. The Web site uses this information to help set personalized workout goals.

Users can participate in online races, using the Web site to invite others to row against them at specific dates and times, or in individual races where they can set the time, speed and distance and row against a virtual opponent.

Up to five WaterRower users can race at a time. During a race, the user’s PC captures speed, distance, heart rate and other data. This data is stored and continually updated each time users row, allowing them to track their progress and set new goals. Race performance is ranked against other rowers on the site, so exercisers can aim to improve their own personal workouts and measure their progress against fellow rowers.

A discussion forum is available at the We-Row Web site to all users. Online personal training with a rowing expert is $10 per month and includes customized advice and training programs designed to meet specific goals, such as building strength or increasing stamina and endurance.

We-Row.com can be used with all WaterRower machines equipped with S4 monitors, which are standard on all WaterRower units sold since May 2005. For owners of earlier models with the previous-generation S3 monitor, WaterRower offers an upgrade kit ($225) that will enable the equipment to work with We-Row.com.

“Indoor rowing machines have been the unsung heroes of cardio fitness, but more than five million Americans use them,” said Kuprecht. “They work both the upper body and lower body at the same time. They use 84 percent of muscles from the tips of the fingers to the balls of the feet, making them one of the most effective workouts for toning muscles and burning fat. For home exercisers, WaterRower and We-Row.com provide a workout solution that recreates the excitement of sculling on the river with maximum cardio, toning and weight-loss benefits.”

About WaterRower

WaterRower designs and manufacturers rowers for home and fitness facility use. The company’s patented WaterFlywheel, which uses water to provide the machine’s resistance, was designed to replicate the feel and natural dynamics of rowing on a river. Water-based resistance allows the exerciser to determine workout intensity by increasing or decreasing effort, similar to other naturally performed cardiovascular activities, such as swimming, outdoor running or ice skating. In addition, unlike resistance-based machines in which the user’s effort is high at the beginning of a stroke and decreases as the resistance is overcome, with the WaterFlywheel, the user’s effort is constant throughout the entire stroke.

Founded in 1988 in Rhode Island by WaterFlywheel inventor John Duke, WaterRower currently has eight operating units worldwide. WaterRower Inc. serves the Americas and Asia and is based in Warren. R.I.

For more information, visit www.waterrower.com.

WaterRower Inc., 560 Metacom Ave., Warren, R.I., 02885, 800-852-2210, 401-247-7742, www.waterrower.com

By Suzanne Sobotka, Pioneer Press, St. Paul, Minn.

The next time you get the urge to play the slots, maybe you should pop a vitamin instead.

A University of Minnesota study found a supplement known as N-acetyl cysteine might reduce cravings in pathological gamblers by targeting glutamate, a chemical in the brain that responds to rewards.

The eight-week study by psychiatrist Jon Grant was small. It involved 23 people who took the supplement, an antioxidant sold over-the-counter for wide-ranging health problems such as bronchitis, Alzheimer’s disease and HIV.

Sixteen participants in the trial reported decreased frequency and intensity of their cravings to gamble, and fewer disruptions in their daily lives from those cravings, Grant said.

“It looks very promising,” said Grant, whose study will be published in Saturday’s issue of Biological Psychiatry.

After the initial study, he invited the 16 whose symptoms improved to participate in a second study in which they would not know whether they would receive the supplement or a placebo. Thirteen people agreed.

In that study, 83 percent of the people who took the supplement reported a continued improvement in symptoms, compared with 29 percent in the placebo group.

Grant said these findings “trend toward significance,” but that a larger study is needed to confirm the findings.

He intends to seek federal funding soon for that study.

Grant acknowledged that the treatment might not work for everyone.

“No single treatment has worked for everyone,” he said, “but it’s important that people have options.”

Side effects of the supplement in the study were minimal. Grant said some people reported gas or bloating, but did not stop taking the supplement.

The average dose of N-acetyl cysteine given in the study was 1,400 milligrams, about two or three pills. Grant said it usually took people a few weeks at this dose to notice a difference in their cravings.

He said someone might need to take the supplement for a year or longer, along with other medications or behavioral therapy, to see a long-lasting decrease in cravings.

Grant said the supplement costs about $20 to $25 for a month’s supply.

Despite the early promise of the supplement, Grant remained cautious about its use to treat gambling behaviors.

“People need to use it cautiously and with their doctor’s knowledge,” he said. “Just because the supplement is natural does not mean taking a larger dose is better.”

Grant is also researching the effects of N-acetyl cysteine on methamphetamine addiction, and is recruiting people for the trial. Those interested can call 612-273-9736.

Grant has been involved in numerous studies identifying drugs or supplements that can affect addictions.

Last year, he reported success using naltrexone, a drug to treat alcoholism, in reducing thefts by compulsive shoplifters.

Suzanne Sobotka can be reached at 651-228-5251 or [email protected].

U.S. scientists are studying how poverty and other negative situations affect the formation of adult behaviors in children.

Duke University researchers used ethnographic studies of children and adolescents growing up in low-income families to provide insight into a seldom-studied area of child development — so-called childhood adultification — the process by which children prematurely assume adult roles.

Eldest children in a family are more likely to become adultified than their younger siblings, said study author Linda Burton. Large differences can also be seen in the types of adultified roles taken on by male and female adolescents.

She said boys are more likely to become primary or secondary breadwinners and are also more likely to become confidants to their mothers, while girls are more likely to take on homemaking and care-taking roles.

The exception, said Burton, is that African-American boys are also more likely to take on domestic roles in families compared with Hispanic and Caucasian males.

The study is detailed in the journal Family Relations.

An Oak Park man who has applied for a state license to operate the former Sangamon Care Center says the previous managers sought him out after they “could not operate this location successfully.”

Stephen Miller said the current license-holders – a group of investors operating through a Skokie-based office under the name Platinum Healthcare – haven’t been involved in management since Nov. 1.

Those investors have contracted with Miller and his associates at Oak Park-based Bridgemark Healthcare to manage the nursing home, now known as Helia Healthcare of Springfield. The home at 2800 W. Lawrence Ave. has 170 beds and serves about 90 residents. There are 110 employees.

Platinum Healthcare also operates Capitol Care Center, 555 W. Carpenter St., which, at 251 beds, is Springfield’s largest nursing home. The investor group has been involved with both nursing homes for about four years.

Ben Klein of Chicago, one of the investors, said the group had “a whole bunch of business reasons” to drop management of Helia/ Sangamon Care. For one thing, the investors felt “spread thin” by having to also concentrate on Capitol Care, Klein said.

“We couldn’t make a positive impact (at Helia) clinically,” he said. “We thought someone else could do a better job.”

Miller has said a September 2006 inspection of the nursing home by the Illinois Department of Public Health generated a “catastrophic set of survey findings” that resulted in a federal fine. He said care has improved greatly since his group took over Nov. 1. New personnel include the administrator, nursing assistants, nurses and new housekeeping and dietary managers, he said.

“The staff that we have shown to the door, in many cases, are those individuals who produced the very unfavorable survey findings in September of 2006,” Miller said.

More than 80 percent of Helia’s patients are poor and have their care paid by the state- and federally funded Medicaid program, Miller said.

(c) 2007 State Journal Register. Provided by ProQuest Information and Learning. All rights Reserved.

By Lawoyin, Taiwo O Lawoyin, Olusheyi O C; Adewole, David A

ABSTRACT Innovative and effective options toward reducing maternal mortality rates in African nations must include the active participation of all stakeholders. This study was carried out to assess men’s level of knowledge and attitude to preventing maternal deaths. In a cross-sectional, community-based survey complemented with exploratory in-depth interviews, data were collected from men from different socioeconomic areas using a two-stage cluster sampling technique. Mean age of the 316 respondents was 39.9 years (range 19-66). Nearly half (47.8%) knew someone who had died at childbirth. They blamed maternal deaths on healthcare workers not being skilled enough, financial barriers, failure to use family planning, emergency, antenatal, and delivery care services. Factors associated with knowledge and attitude to preventing maternal mortality are discussed. Healthcare reforms must be coupled with socio-economic improvements and efforts made to improve men’s attitudes and knowledge in such a way as to make them active stakeholders, more supportive of preventing maternal mortality.

Journal of Public Health Policy (2007) 28, 299-318.

doi:10.1057/palgrave.jphp.3200143

Keywords: maternal mortality, men’s attitude, facility care, skilled workers, abortion

INTRODUCTION

Maternal mortality in developing countries and economically restrained settings remains a daunting and largely unmet global public health challenge. To improve maternal health and reduce 1990 mortality rates by 75% by 2015 is a key goal among the United Nations (UN) Millennium Development Goals (MDG) (1). Progress, however, has been slow and some countries with high maternal mortality are experiencing stagnation or even reversals (2,3). Countries in sub-Saharan Africa are hardest hit by this epidemic. In Nigeria, the problem is particularly challenging. Recent epidemiological data indicate one of the highest maternal death rates, 800 per 100,000 (4,5).

The new millennium requires new thinking about the relationship between health and socio-economic development. In any African nation, creative and effective options for reducing maternal mortality rates must include the active participation of all primary stakeholders, and should include the men who are the primary decision makers in culturally driven, male-dominated societies. Men are expected to promote maternal health and prevent maternal death in their partners, yet research has not established a strong link between their behaviors and maternal mortality particularly in developing countries.

In Nigeria, where culture has been shown to be an important factor in relation to women’s access to available reproductive health facilities, little data exist on men’s views with regard to maternal deaths (6,7). This study was conducted to assess what men know and to better understand their attitudes toward maternal mortality. This understanding is important for policy-related decision making that will promote men’s effective participation in activities that advance maternal health; joining forces to reduce maternal mortality.

MATERIALS AND METHODS

Ibadan, the study area, an indigenous west African city and the capital of Oyo State, Nigeria, has a projected population of over four million (8). Politically and administratively, Ibadan municipality is divided in five local government areas (LGA): Ibadan Northwest, Ibadan Northeast, Ibadan North, Ibadan Southwest, and Ibadan Southeast. The city may also be divided into three socio- economic and cultural zones, which cut across the LGAs: a traditional inner core, a transitional, and a suburban periphery (9). The inner core areas form the old part of the city, inhabited, for the most part, by people with a low level of education. These areas are highly congested and overcrowded, have few and poor roads, limited amenities, and many public health problems. The transitional area is an interface between the inner core and elite areas. The suburban periphery is described as the elite area, containing modern low-density residential estates, occupied by professionals and other high-income groups.

This study was a community-based descriptive and exploratory one, employing both survey and qualitative inquiry. The main focus was on assessing men’s knowledge and views about maternal deaths in the country. The study was conducted in August 2006.

Both components of the study were built on the fact that Ibadan itself is stratified into three socio-economic zones. Only three LGAs – Ibadan North, Ibadan Southwest, and Ibadan Northwest – contain the full progression from inner core to suburban periphery. For the study, one of these (Ibadan North LGA) was selected by simple random sampling. The wards within each socio-economic zone were identified, and one ward per zone selected by simple random sampling. Men from each of these areas were enrolled for the in- depth interviews (n = 10) and for the questionnaire survey (n = 316). Men of 18 years and above were eligible for the study.

Study Instruments

Two instruments were used for data collection. In-depth interviews were conducted for the qualitative data collection. One of the authors administered a pre-tested, semi-structured interview guide. Respondents’ views and experiences were addressed concerning maternal death, its perceived causes, the role of abortion as one cause, and possible ways to reduce maternal deaths.

The survey instrument was a pre-tested, semi-structured questionnaire, which was administered by trained research assistants. Information collected included socio-demographic data (age at last birthday, marital status, if married how many wives, religion, occupation, and presence of children); knowledge of someone who died as a maternal death; men’s attitudes toward preventing maternal death; their knowledge of factors contributing to maternal mortality; and suggestions of ways to reduce such deaths.

Participation was voluntary and respondents were asked, as part of obtaining informed consent, if they were willing to have their answers recorded. Confidentiality was maintained; names were not required. Permission to carry out the study was obtained from the Ibadan North Local Government Secretariat.

On the knowledge scale, each of the io items received one point for a correct answer. Six items that presented both negative and positive views on preventing maternal mortality comprised the attitude scale as follows:

* A woman would die at childbirth anyway if she is destined to die and there is nothing one can do to prevent it.

* Women who are unfaithful to their husbands are more likely to die at childbirth.

* If a woman dies at childbirth, the man can now marry another woman.

* If women do not have so many children, their chances of dying at childbirth would be reduced.

* Use of family planning would help prevent more deaths in women.

* Delivery of babies in a health facility rather than at home or by the traditional birth attendant (TBA) would prevent more deaths in mothers.

Initially, we used the five-point Likert-type attitude scale, but after pre-testing it was reduced to a three-point spread: agree, neutral, and disagree. The items were scored from ? to 3 points. For the first three items above, agree was given 1 point, while for the second set of three, agree received 3 points. The resulting scores could range from 3 to 18 points. An attitude score of 13 and above was considered positive.

Data Management and Analysis

Factor analysis was used to determine the underlying constructs that explain significant portions of the variance in the questionnaire items, and to identify the factors to retain. Within a factor, negative loadings indicate that the variable is inversely associated, while positive loadings indicate direct association. Factor loadings of more than 0.30 were considered as significant.

For the multivariate logistic regression analysis, the dependent variables were the attitude and knowledge scores, each as dichotomous variables. These scores were derived from the information on whether or not the respondent reached a cutoff point. Respondents were coded “1” if they had a composite attitudinal score of 13-18 and coded “0” if the scores were less than 13. Similarly, respondents were coded “1” if they obtained a high knowledge score of 5-10, and “0” for scores less than 5. The variables were analyzed simultaneously to remove the effect of confounders and to identify significant risk factors in the study population.

A p-value of 0.05 was accepted as statistically significant for the model. Due to small numbers in the cells, some of the groups were collapsed for the purpose of regression analysis. An odds ratio of greater than one for a particular variable indicates that the study subjects in that category were more likely to have a positive attitude or high knowledge score than were subjects in the reference category. Subjects having an odds ratio of less than one were less likely to have positive attitude or high knowledge scores than were subjects in the reference category. An odds ratio of one or close to one indicates little likelihood of being different from the reference group in terms of positive attitude and high knowledge scores.

Collected data were coded and entered into the computer using SPSS version 11 and then analyzed. Quantitative data were exported into SYSTAT version 11 software for factor analysis and logistic regression analysis. An analysis of variance (ANOVA) test was used to analyze the summed responses to the attitude questions. Attitude and knowledge scores were normally distributed among study participants. Socio-economic class was classified into higher, middle, and lower, and based on a modification of the Registrar General Classification of Occupations and the more recent National Statistics Socio-Economie Classification (or NS-SEC) (10,11). This ranking is dependent on the general standing of the occupations within the community and not on a classification of individuals. The higher status occupational class includes professionals such as lawyers, physicians, and bankers, and top civil servants; the middle class includes the intermediate occupations and skilled occupations; while the lower occupations include partially skilled and unskilled workers. The classification has been used in community-based research (12).

RESULTS

In-deptb Interviews

Face-to-face, in-depth interviews were conducted with 10 men from the three different socio-economic zones of the study area. Their ages ranged between 28 and 56 years.

Men who had experienced maternal mortality either as the death of friends or family members gave a variety of reasons for the problem. Examples of culture-based factors were mentioned by a man who said that, “The death was due to spiritual powers, and could have been averted if the woman had been delivered by a traditional doctor/ herbalist.” One respondent blamed the husband for the spiritual causes by saying that, “The husband caused the wife’s death by spiritual means.” Another culture-based response was, “TBAs [traditional birth attendants] are contributing to deaths by providing sub-standard care.”

Social and economic problems related to the family were also described. One man said that, “A woman bled to death at home because the husband was not around and money was not available.””The Cesarean section was delayed because the husband/family did not make funds available on time.” Another observed that, “She should have been taken to the tertiary hospital, but they [the husband/the family] did not do that because they did not have enough money.”

Another set of problems revolved around the competency of the health system. “The health care worker was not skilled enough,” was a factor expressed by one man. Another simply observed that, “The woman died on the operating table.” An angrier response was that, “The doctors and nurses did not know what to do when the women in labor was referred from the primary care center to the secondary level facility. They [doctors and nurses on duty] did not decide on time what to do.” Finally, a respondent noted that, “Skilled workers were nonchalant and inefficient.”

The cultural concerns go beyond the immediate cause of death. Culture, according to the men, plays a major role in the way women are treated. Some men reported that in many places, where polygamy is practiced, women are treated as “baby factories” and the men “disregard their role in providing proper care and support, both financially and physically.” As a solution to this, the men wanted religious leaders reoriented so that they would be able to better promote a more positive way of living that would help stem maternal deaths. They also added that women are not adequately empowered; the standard of living is poor; and unwanted pregnancies are not prevented among teenage girls. Also, the grassroots level should be made aware of the need to use healthcare facilities. Some also said that poverty has reduced patronage of orthodox facilities “pushing more women to mission homes; into the hands of traditional birth attendants and promoting home delivery.” The men were of the opinion that something needed to be done about this.

Men saw abortion as a major factor in maternal death, but their views on abortion were divided. Some wanted it banned claiming that “abortion is killing women,” and argued that the legalization of abortion “could lead to an increase in maternal deaths.” Others preferred that abortion should be legalized as it would “remove stigma and shame, and allow women to seek skilled personnel instead of quacks.” The men claimed that unfaithful couples and those who refused to use family planning were more likely to seek abortion, while the unmarried girls would be more likely to seek an abortion because of their promiscuous behavior. They also added that there was a need for government to deal with quacks in the health profession. Men reported that abortions are usually done by unfaithful wives to conceal pregnancies that result from their unfaithful encounters. Women were to blame, according to some, and they had to stop sex work because many end up pregnant and require abortions and die in the process.

Respondents suggested ways to achieve a reduction in maternal deaths. They stressed the importance of antenatal care, and most wanted women to go for care early and to use skilled workers in well- equipped facilities. They further urged that the government assist by providing skilled health professionals, improving healthcare facilities, and promoting the awareness of antenatal care, especially in rural areas, which according to them have been neglected.

Survey Findings

An additional 316 men were enrolled and interviewed for the quantitative analysis. The mean age was 39.9 years (range 19-66 years). Most of the men were married (73.4%), in monogamous relationship (68.0%) with the wife, have children and were in middle (47.5%) or lower (34.5%) status occupations (Table 1). Christians (73.1%) were more likely to be monogamous (OR = 7.34, [2.24-25.4], p

When the respondents were asked if they knew someone who had died a maternal death – while pregnant, at delivery, or within 42 days of termination of pregnancy from a cause related to or aggravated by the pregnancy – 47.8% answered in the affirmative. When these men were further asked to identify the main cause of death and associated factors, the most commonly reported cause was obstetric hemorrhage (24.5%) followed by prolonged/obstructed labor (22.5%), and lack of access to care (19.2%). Other causes are shown in Figure 1. Only 31% of the men thought the death had been preventable.

Attitude Scores

On an attitudinal scale, the cutoff point for positive attitude was 1 3 . Mean and median attitudinal scores were 11. 6 (+-2.3) and 12 and considered poor. (Maximum attainable was 18.) Only 98 (31.0%) had a score of 13 and above – a positive attitude to preventing maternal deaths.

Mean attitudinal scores varied with socio-demographic characteristics. Married men (polygamous and monogamous) had lower scores than the unmarried (F= 12.97, p

Knowledge Scores

Mean knowledge score for the 10 questions was 5.6 ( + 2.1). The scores were quite high, with 72% scoring between 5 and 10 points.

Men who wanted abortion legalized had significantly higher mean knowledge scores than those who did not (F stat=6.i8, /7 = 0.0134), and those with positive attitude toward preventing maternal deaths had significantly higher knowledge scores than those with poor attitude (F stat = 4.41, p = 0.036). Other factors investigated are shown in Table 2.

Factor and Multivariate Analysis

Following a single-level Principal Components Analysis, a “scree” plot identified four factors. Loadings for these factors were high on 10 factors. The first group had significant contributions from sociodemographic variables; the second group had major contributions from experience with maternal deaths; the third factor had significant contributions from culture/values; and a fourth factor from knowledge about maternal mortality. These four groups accounted for 67.5% of the total variance; the socio-demographic group accounting for the maximum possible variance in the data set (24.99%). Principal component loadings are shown in Table 3.

Tables 4 and 5 show results of the multivariate logistic regression analysis, presenting predictor variables associated with positive attitude and high knowledge. Men in the higher occupational category were borderline significantly more likely than those in the lower occupational category to have high knowledge on maternal mortality (p = 0.053). Single men had significantly lower knowledge about maternal mortality than men who were married (p = 0.043). In contrast, the odds of having a positive attitude toward preventing maternal mortality increased as one went up the occupational scale. Men who did not know someone who had died during childbirth (p = 0.04) and those of Islamic religion (p = 0.002) were significantly less likely to have a positive attitude to preventing maternal deaths.

Thoughts on Abortion and Men’s Roles in Maternal Death

When the men were asked about their views on abortion in Nigeria, 159 (50.3%) thought it was not good and should be stopped and completely abolished. Fifty-three (16.8%) wanted women, parents, and teenagers educated on ways to prevent pregnancy and avoid abortions; 33 (10.4%) wanted to see more family planning counseling and promotion of condoms. Only 26 (8.2%) wanted abortion to be legalized, so it would be done professionally. They also wanted abortion clinics to be established. Another 26 (8.2%) took no stand for/against abortion; and 10 (3.2%) advocated abstinence for single men and women. Stratified analysis showed that men of Islamic and Christian affiliations had similar views concerning abortion, and religion was not a modifier (chi^sup 2^ = 0.22, p>0.05). One-fifth of men (20.9%) said that they, men, do not contribute to maternal deaths or did not know how they did. Others added that lack of child spacing by couples, not using any family planning method, husbands encouraging wife to seek abortion (3.2%), and having sex with the pregnant mother (5.7%), contribute to maternal deaths. Inability of men, because of poverty, to provide for the wife (7.6%); women living stressful lives, being overworked, and abused by her spouse (25%); and men preventing their wives from accessing facilities for antenatal care and delivery (37.3%) were additional ways men contributed to maternal deaths in Nigeria.

Suggestions for Action

Men’s views on what should be done, included government providing effective specialized (obstetric) antenatal care and making it close to the masses (14.9%). Government should help the poor, equip hospitals, train more doctors, and increase the number of clinics and health facilities (5.7%); build community awareness about maternal deaths and the need to get care at facilities (4.7%); provide free care and subsidized treatment (4.1%); and encourage family planning (2.2%). Families should support pregnant women to reduce the stress (1.5%).

Some men were of the opinion that only God can help and one had to resort to prayers (2.8%). Others said that men and women should avoid casual sex, and women avoid pregnancies at extremes of maternal age. Women should stop self-medication (3.3%). Men should be supportive of their wives. Abortions and home deliveries should stop. Emergency obstetric care should be provided. The standard of living must improve. One (0.3%) man said nothing can be done.

DISCUSSION

Developing countries may not meet the UN MDG if innovative and effective new options are not found, tried and evaluated. This study, by seeking the views of men in the community, identified factors that may affect maternal mortality. The study reveals some awareness of maternal mortality among the men interviewed, especially about the complications that lead to maternal mortality, including abortion, poverty, poorly skilled health professionals, and sub-standard care.

The multivariate analysis showed that men’s attitudes toward preventing maternal mortality were generally poor, especially among unmarried men, men in polygamous marriages, men without children, non-Christians, and men at the lower end of the socioeconomic ladder. These attitudes may eventually put women at risk of dying from childbirth-related complications. We believe it would be interesting to link these socio-demographic characteristics – for example, lower income – with stratified maternal mortality rates in a country.

Although knowledge is high in this study population, a proper understanding of maternal risk is generally lacking as some men still hold on to the notion that maternal death is caused by spiritual powers, and could have been averted if the delivery had been performed by a traditional doctor/herbalist. Some see maternal deaths as a punishment for unfaithfulness on the woman’s part, while many men believe that women die because they are destined to and believe that nothing could be done to change this. Fatalistic attitude militates against efforts to reduce maternal deaths at family level. In a study carried out in the Republic of Benin, a neighboring West African country, none of the men interviewed in a reproductive health survey thought that the number of pregnancies a woman had would affect her health. One respondent added that, “If my wife wakes up in the morning that means that she is well” (13).

One must take cognizance of the African worldview. There is no such thing as an accident in the real sense of the word to the traditional African. What appears to be an accident is, to him, the result of divine anger (14). If the world is so unfriendly, then the most reasonable thing to do is to go to the herbalist or to an expert in traditional matters for protection. The use of traditional medicine is sometimes recommended by close relatives and husbands. Furthermore, people still hold traditional beliefs about pregnancy and childbirth. These make them purposely delay seeking medical care for complications. Traditional medicine is usually sought for complications like bleeding, retained placenta, and obstructed labor. Only when these complications are serious is the woman taken to the hospital (14). Women are sometimes prevented from accessing health services in a timely manner, leading to deaths of unregistered women, that constitute a large proportion of hospital maternal deaths in Nigeria (15-17). Maternal mortality is a human rights issue. Culturally, women are still generally undervalued and this confirms earlier findings (6). A general improvement in the socio-economic milieu and education of women will help improve the standard of living and further promote women’s rights.

Fear of spiritual attack by the wicked people has been shown to promote the use of religious mission homes and the services of TBAs and herbalists (unskilled workers) for antenatal care and delivery. Many informal practitioners actually combine traditional and orthodox care to get the different forms of assurance that each offers (15,16). According to the respondents, the more important reasons for using unskilled workers were the high cost and lack of access to health facility care.

The high cost of orthodox facilities has been shown to affect in- facility delivery (18,19). There is also the need for policies to address the health inequalities. Women from lower socio-economic classes are excluded from healthcare facilities because of inadequate funds. This issue has been well highlighted by WHO (20).

In most African countries, lack of a skilled health workforce remains a public health problem. Shortage of competent human resources exacerbates maternal mortality rates in any setting. Most men in this study complained about sub-standard care and perceived this to be a problem, due perhaps to shortage of equipment rather than incompetent professionals. Health workers must be trained and provided the wherewithal to practice optimally.

Abortion is illegal in Nigeria. At least one study suggests that it is carried out more often than expected and is associated with maternal deaths (21). We found mixed views on abortion. Most men did not want abortion liberalized, as they thought it would increase the number of deaths. In another study carried out among university undergraduates in Nigeria, participants held a contrary view as only one-fifth of these respondents opposed liberalization of abortion laws (22). This difference in findings can be explained by the fact that in our study, most men were married, very few being students. In the cited study (22), most of the respondents were students and were unmarried. Another study found that over half of fatal abortions were carried out by medical personnel (23). The abortion issue continues to generate controversies, while abortion persistently claims the lives of women. Given that skilled workers are inadequate, preventing unwanted pregnancies would be a priority and probably a more viable option at this stage. In addition, care for post-abortion complications is needed. Family planning education must be more widely available and women be empowered to use reproductive health facilities. In Nigeria today, use of family planning is less expensive and safer than having an abortion for an unplanned and unwanted pregnancy. This information must be widely publicized.

As men with more knowledge had more favorable attitudes about preventing maternal deaths, public awareness of maternal mortality must be widespread and sustained so that myths are dispelled. This is most important in traditional communities who are more likely to be poor, in lower occupations, and to experience maternal deaths. Use of religious leaders, as suggested by the men would help promote awareness especially among men.

Facilities must be improved and workers trained in emergency care or the benefits of facility delivery will not be appreciated. Studies carried out in several African countries where facility delivery is quite high show that maternal mortality remains high also, informing that facility delivery alone is not enough to significantly reduce maternal deaths (24,25).

While one cannot be sure that men will act on their knowledge and attitudes, improving them is an important step toward involving men as active stakeholders in the fight against maternal mortality in Nigeria.

REFERENCES

1. UN Millennium Project. Who’s got the power? Transferring health systems for women and children. Task force on child health and maternal health UNDP 2.005.

2. WHO, UNICEF, UNFPA Maternal mortality in 2000. Estimates developed by UNICEF, WHO, UNFPA. World Health Organization, Geneva, Switzerland 2004.

3. WHO. Measuring Progress Towards the Health Millennium Development Goal, www.who.int/mdg/, date retrieved 29 September 2006.

4. UNICEF. State of the Worlds Children 2006. New York: UNICEF.

5. NPC (Nigerian Population Commission) [Nigeria] and ORC Macro. Nigerian Demographic and Health Survey 2.003: Key findings. Calverton, Maryland, USA: National Population Commission ORC, Macro; 2004.

6. Yahaya MK. Analysis of women’s reproductive health situation in Bida Emirate of Niger State, Nigeria. Afr J Reprod Health. 200256(1): 50-64.

7. Wall LL. Dead mothers and injured wives: the social context of maternal morbidity and mortality among Hausa of northern Nigeria. Stud Farn Plann. ?998;29(4):341-59.

8. Census News House magazine of National Population Commission, 1991 population census-provisional report. 1992; September 3(1):12.

9. Brieger WR, Adeniyi JD. Urban community health education in Africa. Int Quart Comm Health Edu. 198252: 109. 10. Registrar General. Statistical Review of England and Wales 1928-1968. HMSO London, Series (1968) DH3, No. 2, London.

11. Chandola T, Jenkinson C. The new UK National statistics socioeconomic classification (NS-SEC) investigating social class differences in self reported health status. / Public Health Med. 2000;22(2):182-90.

12. Lawoyin TO, Larsen U. Male sexual behavior during wife’s pregnancy and postpartum abstinence period in Oyo state, Nigeria. J Biosoc Sci. 2002;34(1):51-63.

13. Safe Motherhood Newsletter. 1996;22(3):1.

14. Okolocha C, Chiwuzie J, Braimoh S, Unigbe J, Olumeko P. Socio- cultural factors in maternal morbidity and mortality: a study of a semi-urban community in southern Nigeria. J Epidemiol Commun Health. 1998;52:293-7.

15. Opaneye AA. Towards safe motherhood. World Health Day. Profamilia. 1998;16(31):19-24.

16. Etuk SJ, Ham H, Asuquo EE. Role of the spiritual churches in antenatal clinic default in Calabar Nigeria. E Afr Med J. 1999; 76(11):639-43.

17. Harrison KA. Maternal mortality in Nigeria: the real issues. Afr J Rep Health. 1997;1(1):7-12.

18. Asowa-Omorodion FI. Women’s perceptions of the complications of pregnancy and childbirth in two Esan communities, Edo state, Nigeria. Soc Sci Med. 1997;44(12):1817-24.

19. Adamu YM, Salihu HM. Barriers to use of antenatal and obstetric care services in rural Kano, Nigeria. J Obstet Gynaecol. 2002;22(6):600-3.

20. Green A, Gerein N. Exclusion, inequality and health system development: the critical emphases for maternal, neonatal and child health. Bull World Health Organ. 2005;83(6):402.

21. Raufu A. Unsafe abortions cause 20,000 deaths a year in Nigeria. BMJ. 2002;325:988.

22. Orji EO, Adeyemi AB, Esimai OA. Liberalization of abortion laws in Nigeria. The undergraduates’ perspective. J Obstet Gynaecol. 2003; 23(1):63-6.

23. Okonofua FE, Onwudiegwu U, Odunsi OA. Illegal induced abortion: a study of 74 cases in Ile-Ife, Nigeria. Trop Doctor. 1992;22(4):175-6.

24. Grossmann KF, Filippi V, De Koninck M, Kanhonon L. Giving birth in maternity hospital, in Benin: testimonies of women. Rep Health Matter. 2001;9(18):90-8.

25. Ronsmans C, Etard JF, Walraven G, Hoj L, Dumont A, de Bernis L. et al. Maternal maternity and access to obstetric services in West Africa. Trop Med Int Health. 2003;8(10):940-8.

TAIWO O. LAWOYIN*, OLUSHEYI O. C. LAWOYIN and DAVID A. ADEWOLE

* Address for Correspondence: Community Medicine, College of Medicine, UCH, Ibadan, Oyo State, Nigeria. E-mail: [email protected]

DAVID A. Adewole, M.B. ChB, MPH is at the University College Hospital, Ibadan, Oyo state, Nigeria, [email protected]

TAIWO O. LAWOYIN, M.B. BCh, BAO, MPH, FMCPH is a Professor in Community Medicine, College of Medicine, UCH, Ibadan, Oyo state, Nigeria, [email protected]

OLUSHEYI O. LAWOYIN, B.A., MPH is at the US National Academy of Sciences, Washington, DC 21205, USA. [email protected]

Copyright Palgrave Macmillan Limited 2007

(c) 2007 Journal of Public Health Policy. Provided by ProQuest Information and Learning. All rights Reserved.

SAN DIEGO, Sept. 10 /PRNewswire/ — BioVascular, Inc., a company focused on developing therapies targeting platelet-mediated diseases, today announced that it has merged with Revitus, a privately-held company developing a first-in-class platelet count reducer, BVI-007. The announcement came as the first subject was dosed in a Phase Ia clinical trial of BVI-007, a thrombopoeitin antagonist that reduces platelet production without impacting platelet function. BVI-007 is being developed for the prevention of myocardial infarction, thrombotic stroke and death in patients who have had a previous cardiovascular event.

“BioVascular and Revitus were both focusing on novel therapeutics for platelet-mediated diseases,” noted John Parrish, CEO of BioVascular. “By merging, we created a company with two compounds in clinical development. Both compounds target platelets, but with different mechanisms of action and therapeutic applications. Together, Revitus and BioVascular are developing a synergistic portfolio of unique compounds that could potentially solve major problems in the treatment of a wide range of vascular diseases.”

As part of the merger, Stephen Hanson, Ph.D., CEO of Revitus, will join BioVascular’s board of directors. The merged company will be headquartered in San Diego. Terms of the merger were not disclosed.

Phase Ia Trial Commencement

BioVascular also completed the dosing of the first subjects in a Phase Ia clinical trial designed to evaluate the safety and pharmacokinetics of two novel controlled release formulations of BVI-007.

“Given the limited efficacy and bleeding side effects associated with current products used to prevent heart attacks, a clear need exists for improved therapies,” Dr. Hanson said. “Clinical evidence demonstrates that high numbers of circulating platelets are associated with an increased incidence of heart attack and thrombotic stroke. While most companies are developing drugs that interfere with how a platelet functions, BVI-007 simply reduces the number of circulating platelets. This novel therapeutic approach should allow for the prevention of thromboembolic events without increasing the risk of bleeding, potentially enabling safer, more effective preventative treatments for at risk patients.”

About BVI-007

BVI-007 is BioVascular’s second product candidate and acts to reduce platelet production without affecting platelet function or affecting the levels of other blood cellular components. Human clinical studies have shown that high platelet counts significantly correlate to the occurrence of secondary cardiovascular events such as myocardial infarction, thrombotic stroke and death. BioVascular has secured exclusive worldwide rights to BVI-007. After completion of the Phase Ia study to determine optimal formulation of BVI-007, a subsequent Phase Ib dose selection study is expected to start in Q4 2007.

About BioVascular, Inc.

BioVascular is a privately-held, cardiovascular and vascular disease focused company, dedicated to developing novel therapeutics for platelet-mediated disorders. Started in 2005, the company is leveraging its exclusive rights to two clinical stage cardiovascular compounds with differentiated mechanisms of action to become a leading specialty therapeutics company. BioVascular’s most advanced clinical compound, saratin, is currently being studied in two Phase I/II clinical trials for vascular graft failures due to intimal hyperplasia. The company recently acquired the full worldwide rights to BVI-007, which reduces platelet numbers without impairing platelet function.

BioVascular, Inc.

CONTACT: John Parrish, CEO of BioVascular, Inc.,+1-858-455-5000; or Carolyn Hawley, Media-Investor Relations, Porter NovelliLifeSciences, +1-619-849-5375, [email protected], for BioVascular, Inc.

CHAMPLIN, Minn., Sept. 10 /PRNewswire/ — Focusing on the “pre-disease” space of chronic and progressive diseases, and after the recent successful launch of two brands for pre-diabetes and pre-cardiovascular disease in test markets, PreEmptive Meds, Inc. (PMI) announces plans for national expansion.

Led by seasoned pharmaceutical executives, PMI is the first and fastest- growing pre-disease therapeutics company in the world. For the first time, PMI introduces evidence-based, all-natural, proprietary combination therapies exclusively to physicians, just like new prescription drugs are introduced, with fully trained sales professionals, credible peer-reviewed data on efficacy and safety and product training. PMI’s new approach is to give physicians and patients effective and safe therapeutic options for managing a variety of pre-disease states before they become irreversible in the hopes of dramatically changing the course of their disease.

Currently, with no known prescription products indicated for pre-disease usage, PMI has the opportunity to define its pre-disease space with its twice- daily formulations. While this market has always existed, there are now defined biomarkers for common chronic diseases, which are clear indicators for the impending full-blown disease. The marketplace of patients “at-risk” for developing a disease is typically five to six times larger than the market for patients who already have disease.

Launched products include PreLipid(TM) and PreLipid Plus(TM) that effectively lower cholesterol and protect cardiovascular health, and PreCrea(TM), which lowers blood sugar levels and restores balance in the pancreas. PMI also recently introduced PreMenora(TM) and PreMenora Plus(TM) for perimenopausal symptoms and bone health. Other pipeline products will include clinically proven plant-based, proprietary formulations to treat symptoms of arthritis, benign prostate enlargement, hemorrhoids, insomnia, early memory loss and a formulation to boost immunity against infections.

“We at PreEmptive Meds are delighted to have the opportunity to offer effective and safe, all natural, proprietary products to physicians for their patients, targeted exclusively for pre-disease,” stated Chuck Blitzer, PreEmptive Med’s Chief Executive Officer. We believe pre-disease is a significant area of medicine where prescription drugs play little if any role and where PreEmptive Med’s proprietary products can make an important therapeutic contribution. “

PMI only promotes its products to physicians as the Company believes that only physicians should make decisions about patients’ health and therapeutic options as only physicians are knowledgeable to review the clinical information on the products and recommend them appropriately. The scientific bases of PMI’s plant-based products are rooted in the traditional systems of medicine used for centuries in Asia, South America, Europe and the US. Today there is credible evidence from controlled studies of efficacy and safety on plant based ingredients being reported by researchers from around the world. In their proprietary combination-therapy formulations, the Company has for the first time successfully integrated ingredients based on evidence from various traditional systems.

“Most chronic diseases begin and progress because multiple patho- physiologies occur in the body” says Dr. Michael Davidson, Executive Medical Director of Radiant Research in Chicago, IL, a well known researcher and a world expert on lipids and preventive cardiology. “So in order to preempt progression of disease, one must have effective combination therapies that target the various concurrent abnormalities and physicians need to have options to effectively treat disease in their patients as generally no single agent is sufficient.” Dr. Davidson, concludes, “PMI’s combinations of plant- based ingredients are designed to target elevated cholesterol levels, one of the root causes of heart disease and could be very beneficial when used early in pre-disease. PreLipid Plus, which contains recommended doses of phytosterols, may be useful for statin-intolerant patients who have very few options to treat their cholesterol levels effectively.”

According to data from the Centers for Disease Control (CDC) 62% of Americans are taking dietary supplements and many seniors spend approximately $150-200 per month on them. And as baby boomers seek to live healthier and more active lives well into their 70s and 80s, for PMI, this is good news as the Company will find this segment of the population to be large and attractive for it’s portfolio of all-natural pre-disease products.

“PMI believes that physicians are becoming increasingly amenable to recommending alternative therapies,” says Dr. Joe Fenn, Vice President of Medical Marketing for PMI. “Our launched products have been successfully used by physicians for pre-diabetes and pre-cardiovascular disease management and many physicians are using our products even in disease states along with common prescription medicines as viable options before having to resort to increasing prescription dosages. We have also seen remarkable retention on our therapies, perhaps because our products are 100% natural and also because of our innovative compliance program.”

With standardized manufacturing techniques that allow for batch-to-batch consistency and stringent, independently-verified quality control for purity and heavy metal content, PMI is able to bring a traditional pharmaceutical manufacturing and brand management approach to the nutraceutical market.

Blitzer concludes, “Bayer(R) Aspirin, and Tylenol(R) are still leaders in their fields despite the pricing differences with competition because they are continually promoted to the physician and the first established. It is our hope that over time, PMI’s formulations and trademarks will become the “Bayer” within the pre-disease therapeutic space.”

About PreEmptive Meds, Inc.

Founded in 2006 by seasoned pharmaceutical executives, PreEmptive Meds, Inc., is a pre-disease therapeutic company that offers proprietary, branded, clinically proven, plant-based formulations to physicians. The Company has offices in Minneapolis and Las Vegas. http://www.preemptivemeds.com/.

Financing History: The Company raised $2.5mm between November 2006 and February 2007 from a group of individual (“angel”) investors with the help its investment banker, Einhorn Associates of Milwaukee. The capital raised allowed the Company to launch its first two products, in a test in Chicago and the New York City. The Company is currently raising a second angel round of capital as a prelude to a larger institutional round in the 4th quarter, for the express purpose of expanding its sales operations to over 40 territories over the next 8-12 months.

Media Contact: Andrea Martone, [email protected], 516. 944.9764, mobile: 917.929.0527

PreEmptive Meds, Inc.

CONTACT: Andrea Martone, +1-516-944-9764, mobile, +1-917-929-0527,[email protected], for PreEmptive Meds, Inc.

Web site: http://www.preemptivemeds.com/

By Jonathan Nelson, The Columbian, Vancouver, Wash.

Sep. 9–The citrus smell of Nautica cologne swept over Troy Dreiling’s former girlfriend’s senses as the Vancouver chiropractor pushed her against his office wall and closed a fist around her throat.

The 30-year-old woman, who asked that her name not be used, said she came to Dreiling’s business that August day in 2001 “to talk about the fact that we were pregnant.” He told her to leave.

She refused, he began yelling and slammed her against the wall, she said.

Dreiling, now 37, pleaded guilty to fourth-degree assault, domestic violence, for the incident. Dreiling had entered the same plea in 1999 in connection with a similar case with another woman.

The Chiropractic Quality Assurance Commission fined Dreiling $2,000 and suspended his chiropractic license for two years after investigating. The punishment, however, came not because of the assaults or the fact that Dreiling was treating both women at the same time that he was sexually involved with them. He was disciplined because he didn’t notify the governing body about the convictions. An agreement with the state allowed Dreiling to continue working as a chiropractor and president of Absolute Life Chiropractic in Vancouver during the suspension.

John McDonald, a Vancouver attorney who represented Dreiling, said the chiropractor declined to comment for this story.

McDonald said the state has never questioned Dreiling’s chiropractic abilities.

“What they went into didn’t involve negligence or omission on his part as far as the standard of care that is expected of his chiropractic care,” McDonald said.

Dreiling’s appearance before the chiropractic board wasn’t an isolated case. In 2005, he agreed to pay a $4,000 fine and serve a two-year suspension for charges that amounted to sloppy record keeping. Dreiling, again, was able to practice while serving that suspension. And he was able to get a chiropractic license despite a 1990 felony conviction for forgery.

The chiropractic commission’s handling of the case isn’t out of the ordinary when compared to other disciplinary action against Clark County health care industry workers.

The state routinely lets people who stole money from patients, assaulted patients in their care and had sex with clients keep their licenses.

In fact, the state rarely pulls a health care provider’s license.

Columbian review

The Columbian reviewed 223 disciplinary cases the Washington Department of Health handled between 2000 and April 2007. Officials revoked 41 licenses during that span. All but one of those professionals were allowed to seek reinstatement once they completed a state-mandated suspension that ranged from a year to as many as 20 years without a license.

The Department of Health’s job of meting out punishment to those who violate state laws and regulations is a fractured affair.

Within the health department is the Health Professions Quality Assurance office, which regulates nearly 300,000 health care professionals statewide that fall into 57 licensing categories.

The HPQA relies on 16 commissions and boards to oversee 34 of those licenses. Fourteen of the commissions and boards hold the power to levy fines and suspend or revoke licenses.

There is a good chance that the people handing out the punishment know the person in trouble since most of the board and commission members are professionals. For instance, doctors sit on the Medical Quality Assurance Commission and chiropractors on the Chiropractic Quality Assurance Commission.

State audit

A recently completed state audit ordered by Gov. Chris Gregoire found the system rife with flaws that include weak internal controls, spotty oversight of disciplined professionals and inadequate criminal background checks of license holders. The 13 specific findings leave the public at risk.

Rep. Tom Campbell, R-Roy, who is a chiropractor, has fought for years to toughen state laws regarding licensing requirements and the autonomy of commissions and boards that wield health care worker disciplinary authority.

“The boards are designed to protect the public,” Campbell said. “I think it’s confused. They’re protecting the professions.”

In the legislative session this year, Campbell and colleagues pushed for three bills that would have:

Allowed the state to permanently reject some applications based on past bad behavior. The law currently allows a person to reapply.

Toughened license standards for counselors.

In cases of a patient’s death or sexual misconduct, the disciplinary authority would be stripped from commissions and boards and given to the Secretary of Health.

All three bills died.

Campbell said the legislation will resurface in the 2008 session, and pressure against rogue health care providers is mounting in part due to a 2006 Seattle Times series that uncovered a system with gaping deficiencies that harbored repeat offenders. It was that series that prompted Gregoire to call for the audit.

The Times’ investigation found that one-third of the sexual misconduct complaints the Department of Health received since 1995 were dismissed without any inquiry.

The paper also found that license holders were often allowed to edit disciplinary orders by removing incriminating comments.

The health department responded to The Times’ series by implementing a series of changes that included investigating all of the sexual misconduct complaints and using emergency suspensions more frequently.

Mary Selecky, secretary of the health department, acknowledged the report has added a sense of urgency to changes under way. But Selecky said the state was already working to improve patient safety when the Times’ story appeared.

“It’s a journey we’ve been on to make sure we improve on patient safety and we’ve been working on it for a couple of years.”

Thousands of complaints

Each year the state receives 14,000 complaints, 5,000 of which become active investigations. In Clark County, there were 227 complaints filed in 2006, with 150 of those resulting in investigations.

Campbell said the structure of the agency and the autonomy of the commissions and boards put patient safety at risk. He said board members and people coming before them often went to school together, belong to the same professional organizations, know each others’ kids.

“There’s an inherent bias,” Campbell said. “They (board members) think, ‘there but for the grace of God go I.’ “

The department has attempted to remove the appearance of favoritism and uneven handling of cases by creating sanctioning guidelines, similar to the sentencing benchmarks criminal courts use. Selecky said the intention is to bring uniformity to punishing similar conduct regardless of the profession.

But of the 14 commissions that have discipline authority, only 10 have adopted the guidelines. For instance, the Medical Quality Assurance Commission, the group that oversees doctors, is the highest profile commission not to embrace the standard.

Selecky said the department is also trying to work harder at the front end of cases through a program started in 2004 that teams an investigator with a department attorney and field operative to review complaints and move the most egregious, where imminent harm is a possibility, to the top of the list.

That triaging of cases resulted in 55 summary suspensions being issued through the first half of this year compared to only 14 in 2006, according to Selecky.

Local cases

Locally, there are a number of past cases that might have drawn that more urgent response.

Robert W. Goodwin was an emergency room physician at Southwest Washington Medical Center in 2005 when he was contacted by a pharmacist who wanted pain medication for a friend who reportedly was heading overseas, according to disciplinary records. The pharmacist persuaded Goodwin to call 35-year-old Scott Piva, a Washington state trooper who was suspended from work at the time. Piva said he worked for a private company that provided para-military services and was assigned overseas and needed a six-month supply of pain pills for a back injury.

Goodwin, who never examined or met Piva, prescribed 720 tablets of the pain medication Hydrocodone and 250 pills of Xanax, a tranquilizer prescribed to relieve anxiety, documents said.

The prescription was given to Piva on March 13, 2005. Two days later, Piva’s wife, Danyel, found her husband dead in the bedroom of their Amboy home. Investigators found that 21 of the Hydrocodone pills and 30 Xanax tablets were missing. The Clark County medical examiner ruled Piva died of a heart attack.

The Medical Quality Assurance Commission reprimanded Goodwin and fined him $2,500. He resigned from Southwest on Dec. 14, 2005 and declined to renew his medical license when it expired April 1. State officials continue to investigate the open case, the specifics of which they won’t discuss. When contacted, Goodwin’s wife refused to let her husband talk about the case.

Vancouver gynecologist

Lyubov Veselkov worked as a Russian interpreter in the Vancouver office of Dr. Huong Luu and was also a patient.

On June 5, 2001, Veselkov was in the patient role when she lay down on the exam table. Luu, a gynecologist, entered the room, but left quickly, saying he forgot something, documents said. He returned and began the procedure.

Veselkov and Luu’s assistant, who was also in the exam room, saw a flash of light and heard the whir of a small motor. A few seconds later it happened again.

The assistant concluded Luu was taking pictures of Veselkov.

A couple of months later, Vancouver police took the processing unit from Luu’s computer and found that despite attempts to erase data, the doctor’s computer contained 137 pictures of female genitalia, according to documents.

Luu declined to comment on the case.

The medical commission fined Luu $3,000, suspended his license for three years and required that he undertake several evaluations. Luu continued to practice during the suspension and in 2005 successfully lobbied to remove all restrictions on his license. He continues to work in Vancouver.

State legislator Campbell said those kinds of stories keep him pushing to toughen oversight.

“Some people just shouldn’t be health care providers,” he said. “It’s a trust, it’s not a right.”

Disciplinary actions against local providers

Here are a few of the disciplinary actions the Department of Health has taken against Clark County health providers since Jan. 1. The Department of Health does not provide where the person in question practiced:

–Dentist Charles J. West was charged with unprofessional conduct for allegedly improperly setting a post for a crown during root canal treatment. –Physician Rae Wisler was charged with unprofessional conduct for allegedly failing to consider a different diagnosis of a patient, failing to adequately monitor therapeutic effects of treatment and failing to reevaluate diagnosis and treatment. –Susan D. Miller, a pharmacy technician, was charged in May with stealing money from her employer. –Gari D. Stanley, a registered counselor, was charged with unprofessional conduct for allegedly failing to comply with previous terms and conditions set against his license. –Registered counselor Glenda A. Bigalky had charges amended in connection with allegations that she caused patient harm when she accepted a friend as a patient, failed to provide written disclosure information to the patient, used substandard treatment methods and failed to maintain professional boundaries. –Pharmacist Robert S. Kellar was charged with unprofessional conduct for allegedly incorrectly filling a prescription and declining to provide counseling to a patient. –Pharmacist Jasmine T. Nguyen had her license put on probation for five years because she misrepresented her professional status to a prospective employer to obtain a higher salary and sign-on bonus. –Christina L. Cannizzaro, a registered counselor, had her license revoked because she engaged in sexual misconduct with a client. –Scott F. Koyen, a registered nurse, had his license suspended because he diverted methadone for personal use, worked while impaired and was convicted of possession of a drug without a prescription. His Nevada license is on probation for diversion of controlled substances. –Physician Michael L. Workman was charged with unprofessional conduct for allegedly allowing an unlicensed person to perform medical procedures in his office and at a facility where he was the medical director. –Mary S. Benavides, a nursing assistant, was charged with unprofessional conduct for allegedly violating a domestic violence and protection order.

Jonathan Nelson is a Columbian business writer. He can be reached at 360-759-8013 or via e-mail at [email protected].

—–

To see more of The Columbian, or to subscribe to the newspaper, go to http://www.columbian.com.

Copyright (c) 2007, The Columbian, Vancouver, Wash.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NYSE:VFC,

BEDFORD PARK, Ill., Sept. 7 /PRNewswire/ — A group of golfers received quick and very welcome relief from itch mite bites with a surprising natural remedy. Created by Earth’s Balance, Golfers Rx provided quick healing to bites that otherwise would have plagued the golfers with a week or more of constant itching.

Hundreds of Chicago area residents have been plagued by the microscopic oak leaf gall mite, also known as the itch mite. These tiny mites leave small red, pimple-like bites that can take weeks to heal. Scratching the bites can lead to infection.

Golfer’s Rx new electrolyzed oxidizing water technology for healing may be new to the USA, but the spray’s safe and effective formulation has been a proven cure for skin irritations, bee stings, mosquito and other insect bites in the Orient for years.

Golfers Rx is especially effective for pain management. Simply spray the affected area 3-4 times daily or as needed.

“The bites we are seeing do not pose a major health threat — they mostly cause an annoying, intense itch,” Dr. Eric Whitaker, director of the state public health department, said in a statement. “Do not scratch the bites, however, or you could cause an infection, which would create other health problems. I suggest using an anti-itch cream for the bites or taking oral histamine.”

Some bite sufferers find their own way of dealing with the outbreak including over-the-counter remedies and chemicals. Leo Malantis, President of Earth’s Balance, offers a natural remedy fitting with many customers’ earth friendly attitude: Natural remedies for people, pets and planet. Leo also reminds people that this problem is not just restricted to Chicago. Any Midwest state with pin oak trees can suffer from these outbreaks. Past states have included Kansas, Missouri, Nebraska and Texas. Itch mite season runs from now through November.

For additional information on Golfers Rx and learn about Earth’s Balance other natural remedies, visit http://www.earthsbalance.com/.

More Information – Leo Malantis (President) at

Earth’s Balance 708/563-0655 — [email protected]

Earth’s Balance

CONTACT: Leo Malantis, President of Earth’s Balance, +1-708-563-0655,[email protected]

Web site: http://www.earthbalance.com/

By Greg Kocher, The Lexington Herald-Leader, Ky.

Sep. 7–HIGH BRIDGE — A Nicholasville man plunged to his death yesterday after accidentally falling from a railroad bridge that spans the Kentucky River.

Timmy Williams, 18, died after falling from a platform about 75 to 100 feet below the top of High Bridge, said Jessamine County Sheriff Kevin Corman. Williams landed on the ground below, falling perhaps an additional 150 to 200 feet.

The fall was witnessed by three people accompanying Williams, Corman said.

The group had climbed down from Ky. 29, which passes beneath the Norfolk Southern railroad bridge, to a ladder that leads to the trestle’s steel superstructure, Corman said.

From there they climbed onto an X-shaped brace that extends over a limestone cliff.

“He got out on the framework of that bridge and I don’t know if he was being careless or what, but the next thing you know he fell,” Corman said.

The accident was reported about 4:30 p.m., Corman said.

For years the bridge has been a hangout for teens, young adults and thrill-seekers who like the view near the confluence of the Kentucky and Dix rivers. Some have even parachuted from the span, as three people did in November 1998.

When it opened in 1877, High Bridge was the first cantilever bridge in North America, and it was the highest bridge over a navigable stream until the early 20th century.

In 1986, the American Society of Civil Engineers designated High Bridge as an engineering landmark.

Railroad police and the Jessamine sheriff’s department patrol the area, but the bridge’s lure remains strong, even though trains rumble across the twin-track span between Jessamine and Mercer counties.

In 2000, a 33-year-old Lexington man fell or jumped from the bridge as a southbound train approached.

In 1988, a Harrodsburg High School senior fell through the crossties on the bridge and died, falling on the rocks below. Nine years before that, a University of Kentucky student was killed when he tried to climb the trestle.

The railroad put up a 12-foot-high fence with barbed wire on top in the early 1980s, and it has put up “No Trespassing” signs.

But people walk around the fences and up a steep hill to the tracks and bridge. Trespassing citations have only a temporary effect in keeping thrill-seekers away.

“Every time we get a call about somebody being down here, we come down here and cite them or, at the very least, run ’em off,” Corman said.

Reach Greg Kocher in the Nicholasville bureau at (859) 885-5775.

—–

To see more of the Lexington Herald-Leader, or to subscribe to the newspaper, go to http://www.kentucky.com.

Copyright (c) 2007, The Lexington Herald-Leader, Ky.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NYSE:NSC,

The U.S. Food and Drug Administration warned consumers about using Melanotan II , which is sold as a skin cancer preventative and tanning agent.

The FDA announced Wednesday it had issued a warning letter to the product’s manufacturer, Melanocorp Inc. of Hendersonville, Tenn., for the illegal sale and marketing of the product that isn’t FDA-approved.

This product is being mislabeled, marketed and sold illegally as a preventative against skin cancer and as a tanning agent, said Dr. Steven Galson, director of the FDA’s Center for Drug Evaluation and Research.

Melanocorp Inc. advertises the product on its Web site as an injectable tanning product that is effective in protecting against skin cancer and rosacea, a condition that causes a flushing and redness of the skin, the FDA said. Officials said the introduction and delivery of Melanotan II into interstate commerce violates federal law.

The FDA cautioned consumers about injecting any substance, particularly products that aren’t FDA-approved, into their bodies without the oversight of a licensed healthcare provider.

Consumers and healthcare providers were urged to notify the FDA about complaints or problems associated with the product.

Life Time Fitness, Inc. (NYSE:LTM), a national operator of distinctive and large health and fitness centers, today announced that the Company finalized the purchase of the White Bear Racquet & Swim club in White Bear Lake, Minnesota, on September 1, 2007. The terms of the transaction were not disclosed.

“We are excited to add the White Bear Lake club, which maintains a nearly 20-year-old, proud tradition, to our family of Life Time Fitness centers,” said Mike Gerend, Life Time Fitness chief operating officer. “In doing so, we have extended our geographic reach in the Twin Cities area, which not only delivers added flexibility and convenience to our existing members, but also, provides us with a tremendous opportunity to extend our full range of healthy-way-of-life programming, services and products to a new set of consumers in White Bear Lake and surrounding communities.”

Located at 4800 White Bear Parkway in White Bear Lake, the approximately 59,000 square foot club becomes the 25th Life Time Fitness center in the Twin Cities and the 66th nationally. Following the ownership transition, the White Bear center remains open with continued operations. Former White Bear employees have been extended opportunities for ongoing employment with Life Time Fitness.

For a complete listing of Life Time Fitness locations in the Twin Cities and nationally, please visit lifetimefitness.com.

About Life Time Fitness, Inc.

Life Time Fitness, Inc. (NYSE:LTM) operates distinctive and large sports and athletic, professional fitness, family recreation and resort/spa centers. As of September 5, 2007 the Company operated 66 centers in 15 states, including Arizona, Florida, Georgia, Illinois, Indiana, Kansas, Maryland, Michigan, Minnesota, Nebraska, North Carolina, Ohio, Texas, Utah and Virginia. The Company also operated one satellite facility and four preview locations in existing and new markets.

Life Time Fitness provides consumers with personal training consultation, full-service spas and cafes, corporate wellness programs, health and nutrition education, the healthy lifestyle magazine, Experience Life, athletic events, and nutritional products and supplements. Life Time Fitness is headquartered in Eden Prairie, Minnesota (www.lifetimefitness.com).

LIFE TIME FITNESS, the LIFE TIME FITNESS logo, and EXPERIENCE LIFE are registered trademarks of Life Time Fitness, Inc. All other trademarks or registered trademarks are the property of their respective owners.

By Stanopoulos, I Manolakoglou, N; Pitsiou, G; Trigonis, I; Et al

SUMMARY We report three cases of mechanically ventilated chronic obstructive pulmonary disease patients who were intubated due to an exacerbation of their disease and who presented with repeated spontaneous breathing trial failures. Patients were given 50 mg of sildenafil through the nasogastric tube, under close monitoring of haemodynamic and ventilatory parameters. After sildenafil, pulmonary artery pressure, pulmonary artery occlusion pressure, the respiratory frequency to tidal volume ratio and the P^sub a^CO^sub 2^-P^sub Et^CO2 (arterial minus end-tidal carbon dioxide pressure) decreased. Cardiac output increased in two of the patients, while all of them were successfully extubated. This is the first report of successful extubation after sildenafil use.

Key Words: sildenafil, COPD, mechanical ventilation

Discontinuation of ventilatory support can be difficult in about one third of mechanically ventilated patients’. The highest rate of weaning failure has been reported in chronic obstructive pulmonary disease (COPD) patients’2 and may result in prolonged mechanical ventilation, reintubation, tracheostomy and the associated complications that increase morbidity and mortality. A treatment preventing the pathophysiological mechanisms which lead to weaning failure could prove of significant clinical benefit in this group of patients.

The pathophysiology of weaning failure in COPD patients has been associated with worsening of lung mechanics that lead to inefficient ventilation’. Increased ventilatory requirements during weaning in COPD patients may result in dynamic hyperinflation and mechanical disadvantage for the respiratory muscles. Hyperinflation increases pulmonary artery pressure, impeding right ventricular ejection and increasing deadspace4. Large swings in intrathoracic pressure during unassisted breathing increase venous return and both right and left ventricular afterload5″ and may lead to inadequate oxygen supply to the respiratory muscles7. Currently, there is limited data on pharmacotherapy which may facilitate weaning in mechanically ventilated COPD patients; the only available data is on diuretics, which have been shown to be beneficial in weaning COPD patients with left heart disease5.

The current report was based on the observation that pulmonary artery pressure (PAP) is elevated in most COPD patients, during spontaneous breathing trials. Sildenafil has been recently approved in patients with pulmonary hypertension, due to its selective vasodilatory effects on the pulmonary circulation. Our hypothesis was that sildenafil could reduce right ventricular afterload, preventing an interdependence effect on left ventricular performance; by increasing lung perfusion, sildenafil might also improve ventilatory efficiency and attenuate hyperinflation. The magnitude of negative inspiratory pressure swings might thus decrease, preventing an increase in left ventricular afterload. Based on this hypothesis, we evaluated the effects of sildenafil in three male COPD patients who repeatedly failed weaning trials.

CASE HISTORIES

Three male COPD patients were mechanically ventilated in the Respiratory Failure Unit of our hospital, after they presented with hypercapnic respiratory failure during an exacerbation of their disease. There was no indication of pneumonia or pulmonary oedema on their chest X-ray and none of them had a known history of coronary artery disease. The first patient was 45 years old and had a? – antitrypsin deficiency. The other two were 67 and 73 years old, correspondingly. All three patients, who have given their free consent for the preparation of this manuscript, were in an advanced stage of COPD, had emphysema, had been hospitalised at least once during last year and were on long-term home oxygen therapy.

While on mechanical ventilation, patients were treated with bronchodilators and antibiotics. In order to avoid fluid overload and oedema, they received intravenous frusemide. After a period of nine days for the first patient, five days for the second and three days for the third, sedation was stopped and ventilatory support gradually reduced, provided that the patients were haemodynamically stable without vasopressors, afebrile and without severe bronchospasm. When they were fully awake and cooperative, they underwent a spontaneous breathing trial through the endotracheal tube (T-piece) with oxygen supplementation, to ensure adequate oxygenation. All three patients had at least two failed T-piece trials in two consecutive days, characterised by dyspnoea, tachypnoea, accessory respiratory muscle recruitment, diaphoresis and worsening respiratory acidosis.

All patients were catheterised with a pulmonary artery catheter (Swan-Ganz) during support ventilation and baseline haemodynamic parameters were measured during the first 15 minutes of a new T- piece trial. The respiratory frequency to tidal volume index (f/VT) was calculated during spontaneous ventilation using a Wright respirometer and end-tidal CO2 was measured with a capnometer (Capnocheck, BCI International). After measurements were completed, patients were reconnected to the ventilator in a comfortable pressure support mode and a tablet of 50 mg sildenafil citrate (Viagra, Pfizer CO) was given through the nasogastric tube. Ninety minutes after sildenafil administration, patients underwent a new T- piece trial and haemodynamic and ventilatory measurements were repeated during the first 15 minutes.

Values of basic haemodynamic and respiratory parameters during T- piece trials before and 90 minutes after sildenafil administration for each patient are shown in Table 1. After receiving sildenafil, they completed at least one hour of spontaneous breathing without clinical deterioration and were extubated; they continued treatment with sildenafil 50 mg t.d.s. and were eventually discharged from the hospital.

DISCUSSION

In this case report we present three COPD patients with repeated spontaneous breathing trial failures, who were successfully extubated after receiving sildenafil. The results demonstrated a beneficial effect of sildenafil on the pulmonary circulation, indicating a possible therapeutic role of the phosphodiesterase type 5 inhibitors in such cases.

The common mechanism underlying weaning failure is inequality between respiratory muscles’ energy demand and supply. The increased work of spontaneous breathing in COPD patients is associated with a high rate of weaning failure. In a group of COPD patients who failed a weaning trial, development of rapid shallow breathing with high dynamic lung elastance and intrinsic positive end-expiratory pressure (PEEPi) was observed, suggestive of dynamic hyperinflation as the dominant pathophysiological mechanism. Such an increase in lung elastance during weaning may also be due to microatelectasis from tidal volume decrease and pulmonary oedema from left ventricular (LV) dysfunction3.

Cardiopulmonary interactions may significantly influence weaning outcome. Large swings in intrathoracic and abdominal pressure during spontaneous breathing increase venous return and may contribute to weaning failure in COPD patients with left heart disease5. Negative inspiratory swings can also increase afterload, as was suggested by a decrease in LV ejection fraction during weaning in COPD patients in whom myocardial ischaemia was excluded”. Alternatively, myocardial ischaemia may complicate weaning in some patients with coronary artery disease”. In a study including COPD patients, elevated right and left ventricular afterload was associated with inability to increase O, transport during unsuccessful weaning and this was reflected in a progressive decrease in venous oxygen saturation SvO^sub 2^(7).

In our report, during the first T-piece trial in all three patients, PAP and pulmonary artery occlusion pressure (PAOP) were both elevated (Table 1). This increase in PAP was probably related to dynamic hyperinflation (alveolar vessel compression), although worsening hypoxaemia (microatelectasis) and increase in venous return may have also contributed. As transmural PAOP was not measured, the increase in PAOP could either indicate acute left ventricular dysfunction or represent an effect of hyperinflation and PEEPi. Myocardial ischaemia seems not to be the case, as all patients had a medical history free of coronary artery disease and there were no electrocardiographic changes during or after spontaneous breathing. In concert, systemic haemodynamics did not worsen during the observation period.

There is limited data in the literature on the medical management of weaning failure in COPD patients”. By decreasing preload, after 10 days of frusemide treatment, Lemairc5 successfully weaned nine of 15 failed COPD patients with left heart disease. The beneficial effect of diuretics on left ventricular function was documented by a significant reduction in transmural PAOP5. Although our patients were receiving frusemide continuously to prevent fluid overload, a temporary increase in venous return elevating PAP and PAOP cannot be excluded. However, acute diuretic administration in hyperinflated COPD patients with a negative fluid balance might have increased deadspace and P^sub a^CO^sub 2^.

Sildenafil is a potent phosphodiesterase type 5 inhibitor, with a proven vasodilatory effect on pulmonary circulation, improving exercise capacity and haemodynamics in patients with pulmonary arterial hypertension”. It has minimal effects on systemic circulation during exercise”1 and improves gas exchange in patients with lung fibrosis, acting selectively in well ventilated areas of the lung”. In the ICU setting phosphodiesterase type 5 inhibitors have proven to be effective; sildenafil was substituted for inhaled nitric oxide successfully in a mechanically ventilated patient with right ventricular dysfunction and pulmonary hypertension secondary to obesity, COPD and sleep-disordered breathing12, while vardenafil use allowed nitric oxide withdrawal in a mechanically ventilated patient with pulmonary hypertension secondary to ARDS”. In a recent study of six COPD patients with pulmonary hypertension, PAP and pulmonary vascular resistance were significantly reduced one hour after administration of 50 mg of intravenous sildenafil14. In this report, systemic arterial pressure changes were clinically insignificant in all patients, PAP and PAOP decreased, SvO, remained unchanged, while cardiac output increased in two patients; the cardiac output decrease observed in the other patient was possibly related to a decrease in catecholamine levels. Since transmural PAOP was not measured, the decrease in PAOP could be either the result of a lower PEEPi or an improvement in left ventricular function. The latter could be caused by preventing RV dilation and interventricular septal shift and/or by a modest systemic vasodilation caused by sildenafil.

The effect of sildenafil on ventilatory parameters was evaluated by simple bedside measurements and this is a limitation in our report. However, sildenafil decreased the f/VT ratio of spontaneous breathing, which is a reliable predictor of weaning outcome”, probably by improving lung mechanics. Sildenafil also decreased P^sub a^CO^sub 2^-P^sub ET^CO^sub 2^, indicating a reduction in VD/ VT16. Although a possible bronchodilatory action of sildenafil has been reported17, it should be clinically insignificant in patients already receiving high doses of bronchodilators. By increasing lung perfusion preferably to high V/Q areas11, sildenafil probably improved ventilatory efficiency and attenuated hyperinflation; sildenafil has been shown to improve ventilatory efficiency in chronic heart failure patients during exercise, as was suggested by a significant reduction of VE/VC02 slope18. However, the mechanism of improvement may differ in this group of patients.

In conclusion, this is the first case series to indicate that sildenafil may facilitate weaning of mechanically ventilated COPD patients, by reducing right ventricular afterload and improving ventilatory efficiency, while a reduction in left ventricular afterload may also contribute. A well designed study of the ventilatory and haemodynamic effects of sildenafil in COPD patients who fail weaning is justified, in order to provide further and solid evidence of the proposed mechanism of action.

REFERENCES

1. Lemaire F. Difficult weaning. Intensive Care Med 1993; 19: S69- S73.

2. Vallverdu I, Calaf N, Subirana M, Net A, Benito S, Mancebo J. Clinical characteristics, respiratory functional parameters, and outcome of a two-hour T-piece trial in patients weaning from mechanical ventilation. Am J Respir Crit Care Med 1998; 158:1855- 1862.

3. Jubran A, Tobin M. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med 1997; 155:906-915.

4. Pinsky MR. Cardiovascular issues in respiratory care. Chest 2005; 128:592S-597S.

5. Lemaire F, Teboul JL, Cinotti L, Giotto G, Abrouk F, Steg G et al. Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology 1988; 69:171-179.

6. Richard C, Teboul JL, Archambaud F, Hebert JL, Michaut P, Auzepy P. Left ventricular function during weaning of patients with chronic obstructive pulmonary disease. Intensive Care Med 1994; 20:181-186.

7. Jubran A, Mathru M, Dries D, Tobin M. Continuous recordings of mixed venous oxygen saturation during weaning from mechanical ventilation and the ramifications thereof. Am J Respir Crit Care Med 1998; 158:1763-1769.

8. Chatila W, Ani S, Guaglianone D, Jacob B, AmoatengAdjepong Y, Manthous CA. Cardiac ischemia during weaning from mechanical ventilation. Chest 1996; 109:1421-1422.

9. Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353:2148-2157.

10. Stanopoulos I, Hatzichristou D, Tryfon S, Tzortzis V, Apostolidis A, Argyropoulou P. Effects of sildenafil on cardiopulmonary responses during stress. J Urol 2003; 169:1417- 1421.

11. Ghofrani HA, Wiedermann R, Rose F, Schermuly RT, Olschewski H, Weissmann N et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet 2002; 360:895-900.

12. Ng J, Finney SJ, Shulman R, Bellingan GJ, Singer M, Glyme PA. Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil? Br J Anaesth 2005; 94:774- 777.

13. Giacomini M, Borotto E, Bosotti L, Denkewitz T, Reali- Forster C, Carlucci P et al. Vardenafil and weaning from inhaled nitric oxide: effect on pulmonary hypertension in ARDS. Anaesth Intensive Care 2007; 35:91-93.

14. Alp S, Skrygan M, Schmidt WE, Bastian A. Sildenafil improves hemodynamic parameters in COPD – an investigation of six patients. PuIm Pharmacol Ther 2006; 19:386-390.

15. Vassilakopoulos T, Routsi C, Sotiropoulou C, Bitsakou C, Stanopoulos I, Roussos C et al. The combination of the load/ force balance and the frequency/tidal volume can predict weaning outcome. Intensive Care Med 2006; 32:684-691.

16. Yamanaka MK, Sue DY. Comparison of arterial-end-tidal PCO, difference and dead space/tidal volume ratio in respiratory failure. Chest 1987; 92:832.

17. Charan NB. Does sildenafil also improve breathing? Chest 2001; 120:305-306.

18. Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol 2004; 44:2339-2348.

I. STANOPOULOS*, N. MANOLAKOGLOU[dagger], G. PITSIOU*, I. TRIGONIS[dagger], E. A. TSIATA[dagger], A. K. BOUTOU[double dagger], R K. KONTOU[dagger], R ARGYROPOULOU[section]

Respiratory Failure Unit, Aristotle University, G. Papanikolaou Hospital, Thessaloniki, Greece

* M.D., Ph.D., Pneumonologist and Critical Care Medicine Specialist.

[dagger] M.D., Pncumonology and Critical Care Medicine Trainee.

[double dagger] M.D., M.Sc. Pncumonology and Critical Care Medicine Trainee.

[section] M.D., Ph.D., Professor. Pneumonologist and Critical Care Medicine Specialist.

Address for reprints: Dr A. K. Boutou, 3ft. Ag Vasileiou str.. Kalamaria. 55133, Thessaloniki. Greece.

Accepted for publication on April 2ft. 2007.

Copyright Australian Society of Anaesthetists Aug 2007

(c) 2007 Anaesthesia and Intensive Care. Provided by ProQuest Information and Learning. All rights Reserved.

NationsHealth, Inc. (Nasdaq: NHRX) today announced that it has acquired Diabetes Care & Education, Inc. (DC&E), a leading provider of insulin pumps, pump supplies and blood glucose monitoring equipment. Susan Hill, the founder and President of DC&E, is a certified diabetes educator and a registered dietician, who will lead NationsHealth’s and DC&E’s combined insulin pump and diabetes education programs. Ms. Hill has been an active member of the American Diabetes Association (ADA) for 25 years, where she served as President of the South Carolina affiliate of the ADA, and is currently serving on the ADA’s Leadership Council in Louisville, Kentucky.

Under the terms of the agreement, NationsHealth purchased all of the issued and outstanding capital stock of DC&E for $2.5 million in cash and $0.5 million in shares of unregistered common stock of the Company. NationsHealth may also pay additional cash amounts based on annual revenue targets associated with DC&E’s pump and education operations in 2008, 2009 and 2010.

Glenn Parker, M.D., NationsHealth’s Chief Executive Officer stated, “We are very excited about our acquisition of Diabetes Care & Education which supports our long-term goal of expanding our business into new areas of the diabetes patient market, as well as expanding our current product offerings to our customers. Furthermore, through diabetes education, we will seek to partner with physicians thereby giving us greater access to future patient acquisition channels.

“We have now completed seven acquisitions since May 2007, and have used substantially all of the $5.5 million available to us under our term loan, which has provided NationsHealth access to over 13,000 new diabetes patients.”

Ms. Hill, who signed a long-term employment agreement, commented, “I am delighted that DC&E will become part of the NationsHealth family and look forward to leading NationsHealth’s entrance into diabetes education and disease management.”

The addition of DC&E allows NationsHealth to expand its diabetes related offerings to its existing and future patient base, including its managed care customers, and offer blood glucose testing supplies to DC&E’s patient base. Management expects the acquisition to add over $10.0 million of revenue to NationsHealth in 2008.

About NationsHealth, Inc.

NationsHealth seeks to improve the delivery of healthcare to Medicare and managed care beneficiaries by providing medical products and insurance related services. NationsHealth provides home delivery of diabetes supplies, medications and other medical products to patients across the nation. In addition to its medical products business, NationsHealth also provides education, marketing, enrollment and patient service to insurers offering Medicare Part D prescription drug plans and other Medicare insurance coverage. NationsHealth has an agreement with CIGNA to service its Medicare Part D prescription drug plans nationally. For more information please visit http://www.nationshealth.com.

About Diabetes Care & Education, Inc.

DC&E is a leading provider of insulin pumps, pump supplies and blood glucose monitoring equipment through its three facilities in Kentucky, North Carolina and South Carolina. DC&E also offers diabetes education to individuals with diabetes through its American Diabetes Association recognized education programs.

This press release contains forward-looking statements about NationsHealth, including statements regarding management initiatives and new product and market opportunities, none of which should be construed in any manner as a guarantee that such results will in fact occur. In addition, other written or oral statements that constitute forward-looking statements may be made by us or on our behalf. Forward-looking statements are statements that are not historical facts, and in some cases may be identified by the words “anticipate,””project,””expect,””plan,””intend,””may,””should,””will,” and similar words or phrases. Such forward-looking statements, based upon the current beliefs and expectations of NationsHealth’s management, are subject to risks and uncertainties, which could cause actual results to differ from the forward-looking statements. The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the ability to realize the benefits from the DC&E acquisition; the ability to effectively integrate NationsHealth and DC&E’s operations, changes in Medicare, Medicaid and any other state or national-based reimbursement program, including competitive bidding for durable medical equipment and supplies; our ability to maintain our existing customer base; our ability to raise the capital we will need to sustain our operations; and our dependence on Medicare reimbursement and other risks and uncertainties described in NationsHealth’s Annual Report on Form 10-K for the year ended December 31, 2006, and in NationsHealth’s other reports filed with the Securities and Exchange Commission. The information set forth herein should be read in light of such risks. NationsHealth cautions investors not to place undue reliance on the forward-looking statements contained herein. These statements speak only as of the date of this press release and, except as required by applicable law, NationsHealth assumes no obligation to update the information contained herein.

WASHINGTON, Sept. 4 /PRNewswire/ — From Washington, DC to Dothan, Alabama, the BET Foundation (BETF) is on the road to healthy living. In partnership with sponsors General Mills, State Farm and Merck, BET Foundation heads to the Greater Beulah Baptist Church in Dothan, AL on Sept. 7-8, 2007 for an for an exciting and enlightening Symposium to address health disparities affecting women of color.

The two-day health Symposium will kick off on Friday, Sept. 7 with T.E.A. Talk, a relaxing forum co-hosted by the National Medical Association, for ladies to listen to and talk with health experts. The Women’s Health Symposium will feature free health screenings; fitness exercises; healthy cooking demonstrations; expert panelists and speakers including renowned gynecologic oncologist Groesbeck Parham, MD; Gwendolyn Lipscomb, Director, Office of Minority Health and Jessica Hardy, Director, Office of Women’s Health. Dothan Commissioner Larry Matthews and the Honorable Vicki Moore, Mayor of Slocomb will be on hand to make special presentations at the Symposium. As one of the Symposium’s many highlights, attendees will be treated to an inspiring special performance by evangelist and national gospel artist Karen Clark Sheard.

National health data shows that among African-American women, heart disease is the leading cause of death; 1 in 4 over 55 has diabetes and they account for 71% of the 4500 newly diagnosed HIV cases. The dialogue in Dothan is part of an ongoing BET Foundation initiative to encourage healthy lifestyles and share information on common preventable obesity-related health risks such as diabetes, hypertension, stoke, heart disease, certain forms of cancers and mental illness through women’s health forums.

“The BET Foundation is committed to traveling the U.S. and sharing our healthy lifestyle message. Our goal is to make the African-American community healthy, one city at time,” says Executive Director Lynda Dorman. “We work primarily with women because health disparities rates among African-American women are higher compared to other groups, but also because they can educate and encourage healthier choices in their respective households.”

The Symposium is free and open to women ages 18 and older; however advanced registration is required as capacity is limited. Interested individuals can register for the event by visiting http://www.ahealthybet.com/ or call 1-800-626-9911, ext 2341 for more information.

   WHAT:  The BET Foundation, A Healthy BET: Women's Health Symposium          "Remembering Our Health"    WHEN:  Fri, Sept. 8, T.E.A. Talk            - 5:30 p.m. to 9:00 p.m.           Sat, Sept. 9 Symposium            - 7:30 a.m. Check-in;            - 7:45 a.m. Master fitness class; and 8 a.m. free health                         screenings begin.            - 10:00 a.m. Panel of Experts            - 1:45 p.m. Healthy Cooking Demonstrations            - 3:15 p.m. Performance by Evangelist Karen Clark Sheard    WHERE:  Greater Beulah Baptist Church,           254 Headland Avenue, Dothan, AL    ABOUT BET FOUNDATION  

The BET Foundation is a non-profit organization created to raise public awareness to the numerous health-related challenges within African-American communities. Established in 2003, the Foundation takes a pioneering step in addressing one of the leading behavioral-attributed health concerns among African-American women and families, obesity-related health concerns. Through specifically tailored initiatives and targeted campaigns, the BET Foundation aims to insure that African Americans live longer and healthier lives. The BET Foundation includes public service announcements (PSAs); targeted programming segments; seminars and health forums; health brochure materials; a dedicated toll-free hotline and website; and a nationwide Healthy BET Fitness Challenge contest to provide the tools and knowledge necessary for communities to develop long lasting healthy lifestyle habits. For more information, please visit http://www.ahealthybet.com/.

ABOUT GENERAL MILLS

General Mills, with annual net sales of $10.8 billion, is a leading global manufacturer and marketer of consumer food products. Its global brand portfolio includes Betty Crocker, Pillsbury, Green Giant, Haagen-Dazs, Old El Paso and more. It also has more than 100 U.S. consumer brands, more than 30 of which generate annual retail sales in excess of $100 million. General Mills is also a leading supplier of baking and other food products to foodservice and commercial baking industries.

ABOUT STATE FARM

State Farm was founded in 1922 and built on face-to-face Good Neighbor service. State Farm(R) insures more cars than any other insurer in North America and is the leading U.S. home insurer. State Farm’s 17,000 agents and 68,000 employees serve over 75 million auto, fire, life and health policies in the United States and Canada, and more than 1.6 million bank accounts. State Farm Mutual Automobile Insurance Company is the parent of the State Farm family of companies. State Farm is ranked No. 31 on the Fortune 500 list of largest companies.

ABOUT MERCK & CO., INC.

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service.

BET Foundation

CONTACT: Dedra Owens, +1-202-491-0845, [email protected],for BET Foundation

Web site: http://www.ahealthybet.com/

Formedic, the nation’s leading provider of patient record forms, introduces the Medical History Questionnaire (www.FormedicMHQ.com), a free, easy-to-use electronic patient interview that helps physicians save money and time, and requires no technical expertise to setup or use.

“Medical History Questionnaire (MHQ) helps doctors conduct a more focused exam and maintain better documentation to code at appropriate levels and enhance reimbursement,” says Formedic General Manager for MHQ Bruce Rowan. “The system also expedites the patient care process, saving valuable physician time — an average of four minutes per visit, enabling them to increase volume and improve profitability.”

The point-and-click system captures the patient’s history and current symptoms prior to their visit. Running on a standard PC in the waiting area or exam room, or accessible online from a patient’s home or office, MHQ prompts patients through a series of specialty-specific questions based on their chief complaint.

MHQ has the ability to access up to 5,000 unique symptom-based question sets, driven by a series of algorithms. It then turns the patient’s answers into familiar clinical terminology, organizes the positive and negative findings by body organ system, and generates a complete subjective history note.

Developed with input from a variety of physicians including doctors affiliated with the nation’s most prestigious medical institutions, MHQ works for episodic visits, chronic disease visits, annual exams and new patients.

“MHQ is a truly innovative communication tool that links the patient and the physician,” says Rowan. “It improves practice management and enhances the dialogue between both parties because the doctor walks into the exam room better informed and prepared.”

Formedic’s novel system requires no special equipment or technology expertise. MHQ is compatible with electronic medical records (EMRs) and can send patients’ reports to physicians electronically. Physicians can start using the system by visiting www.FormedicMHQ.com.

Ideal for practices of any size, MHQ has capabilities to address the needs of numerous medical specialties including primary care physicians, pediatricians, obstetricians and gynecologists, dermatologists, gastroenterologists, as well as cardiologists, allergists, nephrologists, rheumatologists and other specialties.

Just like the company’s complete line of customized, professional medical forms used by more than 188,000 physicians across the United States, Formedic never charges medical professionals for use of its products. The system is funded by sponsorships from healthcare companies. For more information or to begin using MHQ, visit www.FormedicMHQ.com

About Formedic

Formedic www.formedic.com is the innovator behind MHQ and, for over a quarter century, has been the nation’s leading provider of patient record forms. Founded in 1981, Formedic has led the industry in providing customized, professional medical forms serving more than 188,000 physicians across the United States. Among the free services the company provides to physicians, NPs and PAs are the new Medical History Questionnaire (MHQ) (www.FormedicMHQ.com), a PC-based patient interview system offering time- and money-saving opportunities to physicians. The company also produces patient record forms, prescription pads, telephone message pads, referral forms, work/school slips and appointment cards.

By Carla McClain, The Arizona Daily Star, Tucson

Sep. 1–The death of Tucson attorney Kimberley A. Taylor after undergoing cosmetic surgery was caused by a failed attempt to intubate her when she stopped breathing during the operation, a lawsuit filed by the family says.

The suit, claiming “malpractice and gross negligence,” was filed in Pima County Superior Court in August against Taylor’s plastic surgeon, Dr. Armando Alfaro, and his nurse anesthetist, Elizabeth Kayser.

Taylor, who was 53 when she died, was undergoing two minor cosmetic procedures — liposuction and tightening of the jaw line — in Alfaro’s office on Dec. 28 when the emergency occurred. Kayser had placed Taylor under conscious sedation — a form of anesthesia that does not require putting the patient on a breathing machine.

At some point during the surgery, Taylor’s breathing slowed and ultimately stopped. To revive her, Alfaro and Kayser intubated her — inserted an endotracheal tube down her throat — but inserted it into the esophagus instead of the lungs, the suit says.

That meant Taylor was getting no oxygen to her brain. Paramedics called to Alfaro’s office noted the improper placement of the breathing tube and tried to revive Taylor with bag ventilation. But she already had suffered severe brain damage by the time they arrived, according to the suit.

She was transported comatose to Tucson Medical Center’s emergency room and placed on life support. Taylor died 10 days later, on Jan. 6.

Doctors performing these kinds of procedures are required to have a device that indicates where the breathing tube should be placed in such an emergency, according to the Taylor family’s attorney, Ted Schmidt. Medical records show that Alfaro did have such a device in his office but did not use it when he tried to intubate Taylor, Schmidt said.

“This is a terribly sad and tragic story,” Schmidt said in a statement released Friday afternoon. “A perfectly healthy 53-year-old woman going in for rather routine outpatient plastic surgery should not die. Had the usual reasonable procedures and equipment been in place and used when needed in Kim’s care she would be with us today.

“She was extremely close to her two college-age daughters and mother. To have their mother and daughter taken from them so abruptly, unexpectedly and untimely will touch them deeply forever.”

The suit seeks unspecified damages for Taylor’s mother and her two grown daughters, Alexis and Lauren Cheadle. Relatives declined to comment Friday afternoon, Schmidt said.

Attempts to contact Alfaro and his attorney, Tom Slutes, were unsuccessful.

Kayser’s attorney, Edwin Gaines, said that Kayser has practiced as a certified nurse anesthetist for more than 30 years and has never had a problem before this.

“Liz is a very skilled nurse anesthetist who has done anesthesia for Dr. Alfaro for a number of years,” he said. “Kim (Taylor) had had a number of cosmetic procedures before this with no problems. Anesthesia always poses some risk, in any surgery.

“But an adverse outcome does not mean anyone fell below the standard of care. This is a tragic, tragic event, and I feel for Kim’s kids.”

Taylor’s death here brought attention to the nationwide controversy about the popular trend among cosmetic surgeons to increasingly perform these elective surgeries in their offices, rather than in hospitals fully equipped and staffed for emergencies.

A high rate of deaths in office settings uncovered in several states has resulted in the passage of stricter safety standards and inspections, and mandates to use physician anesthesiologists rather than nurse anesthetists in those states.

In response to the Taylor death and other bad outcomes in Arizona, the Arizona Medical Board has proposed new rules regulating office-based surgeries. The proposals — now under review by the governor — require doctors who perform these surgeries have specific monitoring and emergency equipment for all levels of anesthesia and sedation, from “minimal” to “deep.”

They also require specialized staff training and that patients be informed of the risks of having surgery in an office setting.

–Contact reporter Carla McClain at 806-7754 or at [email protected].

—–

To see more of The Arizona Daily Star, or to subscribe to the newspaper, go to http://www.azstarnet.com.

Copyright (c) 2007, The Arizona Daily Star, Tucson

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

CLEVELAND, Aug. 31 /PRNewswire/ — Cleveland-based The ScottCare Corporation, a leader in non-invasive external counterpulsation (ECP) therapy and cardiopulmonary rehabilitation telemetry, announced today that the company has completed the previously announced acquisition of the operations of Rozinn Electronics, Inc., a privately-held market leader in cardiovascular diagnostic equipment based in Glendale, NY.

“We are very pleased to welcome the customers, employees and vendors of Rozinn to ScottCare,” said Ken Zajaczkowski, General Manager of The ScottCare Corporation. “We are excited about the opportunities created by adding Rozinn’s leading portfolio of diagnostic products and distribution network. ScottCare can now provide products across the spectrum of cardiac care – diagnosis, treatment and rehabilitation, meeting the needs of cardiology customers worldwide.”

The acquisition strengthens ScottCare’s position in non-invasive and diagnostic cardiology device markets around the world. ScottCare will accelerate development, marketing and support for Rozinn’s diagnostic product suite including Holter for Windows+(R), Pacemaker and Event Monitoring Products. In addition, ScottCare will expand the availability of its leading cardiac rehab telemetry and ECP therapy products outside North America through Rozinn’s extensive international network of dealers.

Rozinn key personnel, including Mark Rosoff, Karl Ziemann, Sneh Merchant and George Falcone, will continue to play a key roll in the further development and growth of Rozinn’s diagnostic product line.

For more information, call 1-800-243-9412, ext. 133 or visit http://www.scottcare.com/.

About The ScottCare Corporation

Since 1989, The ScottCare Corporation has developed, manufactured and marketed quality medical devices for non-invasive cardiology therapy and cardiopulmonary rehabilitation professionals. ScottCare is committed to providing the most advanced systems, unparalleled customer service and training, and software solutions to meet the unique and practical needs of clinicians, researchers, patients and other constituents within cardiac care, all in a cost-effective manner.

Based in Cleveland, Ohio, The ScottCare Corporation is a subsidiary of The Scott Fetzer Company, the flagship company of a diversified group headquartered in Westlake, Ohio and wholly-owned by Berkshire Hathaway Inc. Visit ScottCare on the web at: http://www.scottcare.com/.

About Rozinn Electronics

Based in Glendale, New York, Rozinn was established in 1979 by Mark Rosoff and Karl Ziemann, and has enjoyed 28 years of steady growth as a result of innovative products and attentive customer service. Rozinn’s market-leading product portfolio includes Holter for Windows+(R), and a market-leading cardiac diagnostic suite including Pacemaker and Event Monitoring employed in doctor’s offices, clinics, scanning services, community hospitals, university medical centers and advanced pharmaceutical and bio-device research centers around the world. Visit Rozinn on the web at: http://www.rozinn.com/.

The ScottCare Corporation

CONTACT: Bill Kulp, Director of Sales and Marketing of ScottCareCorporation, +1-216-362-0550, ext. 133

Web site: http://www.scottcare.com/http://www.rozinn.com/

By Verdier-Sevrain, S

ABSTRACT Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens prevent skin aging. They increase skin thickness and improve skin moisture. Beneficial effects of hormone replacement therapy (HRT) on skin aging have been well documented, but HRT cannot obviously be recommended solely to treat skin aging in menopausal women. Topical estrogen application is highly effective and safe if used by a dermatologist with expertise in endocrinology. The question of whether estrogen alternatives such as phytoestrogens and selective estrogen receptor modulators are effective estrogens for the prevention of skin aging in postmenopausal women remains unanswered. However, preliminary data indicate that such treatment may be of benefit for skin aging treatment.

Key words: SKIN AGING, HORMONE REPLACEMENT THERAPY, TOPICAL ESTROGEN, PHYTOESTROGENS, SELECTIVE ESTROGEN RECEPTOR MODULATORS

INTRODUCTION

There are approximately 40 million postmenopausal women in the United States, contributing to 17% of the total population1. As the population of older women continues to grow at a rapid rate, the challenges of learning more about the health-care concerns and priorities of this group of patients become apparent. The skin is one of the largest organs of the body in which aging-related changes are visible and women are concerned by the deterioration of their skin’s appearance. Skin aging is influenced by genetic, environmental and hormonal factors. Numerous reviews have adequately described the difference between normal cutaneous aging, due to the passage of time, and damage from solar exposure. The prior is referred to as intrinsic aging, and the latter as photoaging. Intrinsic aging is characterized by smooth, pale, finely wrinkled skin and dryness2. Photoaging is characterized by severe wrinkling and pigmentary changes such as solar lentigo and mottled pigmentation . Estrogens affect several skin functions and the estrogen deprivation that accompanies menopause contributes to, and exacerbates, the deleterious effects of age on the skin. Since its first use in the 1940s, systemic estrogen therapy has been known to have an obvious, visible effect on the skin and to be efficient in combating the phenomenon of skin aging4,5.

In this article, we review the effects of estrogen on skin biology and particularly its ability to prevent skin aging. We examine the role of estrogen therapy in skin aging treatment, discussing successively the indications of hormone replacement therapy (HRT), topical estrogen treatment, and new drugs called selective estrogen receptor modulators (SERMs).

BIOLOGY OF ESTROGENS IN SKIN

Estrogens affect several skin functions such as elasticity6, water-holding capacity7, pigmentation8 and vascularity . Estrogens prevent skin aging by influencing skin thickness, skin wrinkling and skin moisture10. Not just the skin but also skin appendages, such as hair follicles, are influenced by estrogens11.

Estrogen effects on skin thickness and collagen content

Collagen is a main constituent of the skin and provides the major support for skin resistance. It was first noticed in 1941 by Albright and colleagues that postmenopausal women with osteoporosis had skin that was noticeably atrophied. Then, Brincat and colleagues13 demonstrated that there was a decrease in skin thickness and skin collagen content, corresponding to a reduction in bone mineral density, in the years following menopause, particularly in the initial postmenopausal years. More recently, Affinito and colleagues14 showed that skin collagen decline was closely correlated to years following menopause. They showed that postmenopausal women had decreased amount of types I and III collagen, as well as a decreased type III/I ratio in comparison to premenopausal women. With the correlation noted between skin collagen decline and postmenopausal years, studies have attempted to decipher the effects of estrogens on skin collagen. Several controlled studies have reported that estrogen therapy had a beneficial effect on collagen content and skin thickness15-19 (see Table 1).

Table 1 Estrogen effects on skin collagen or skin thickness in human (results from controlled studies)

Estrogen effects on skin moisture

The ability of the skin to hold water is related to the stratum corneum lipids which play a predominant role in maintaining the skin barrier function and also to the dermal glycosaminoglycans, which have a high water-holding capacity21.

It has been demonstrated that postmenopausal women who were not taking hormone replacement therapy were significantly more likely to experience dry skin compared with those postmenopausal women taking estrogen22. Pierard-Franchimont and colleagues7 showed that transdermal estrogen therapy leads to significantly increased water- holding capacity of the stratum corneum, suggesting that estrogen may play a role in the stratum corneum barrier function. Denda and colleagues23 demonstrated changes in the stratum corneum sphingolipids with aging and suggested a possible hormonal influence. Estrogens also affect dermal water-holding capacity: studies in animal have demonstrated marked increases in glycosaminoglycans within 2 weeks of estrogen therapy and studies in human have shown estrogens to increase dermal hydroscopic qualities.

Estrogen effects on skin wrinkling

Wrinkles are modifications of the skin associated with cutaneous aging, appearing preferentially on sun-exposed areas (actinic aging). Moreover, they can be increased by various intrinsic (heredity, ethnic, hormonal and pathological) or extrinsic factors (irradiation, pollution, temperature, humidity). Histological studies of wrinkles have shown alterations of dermal component with atrophy of dermal collagen, alterations of elastic fibers and marked decrease in glycosaminoglycans26. Creidi and colleagues27 showed that a conjugated estrogen cream applied to the facial skin of postmenopausal women resulted in significant improvement in fine wrinkles, as clinically evaluated by dermatologists. Dunn and colleagues22 pointed out that postmenopausal women using estrogen were significantly less likely to develop skin wrinkles. As noted earlier, estrogens cause an increase in collagen and glycosaminoglycans in the dermis15,24, which may explain the decrease in skin wrinkling with estrogen treatment. Decreased skin elasticity has been demonstrated in women after menopause28, and changes in the skin elastic fibers have also been reported after application of estriol ointments to the skin of postmenopausal women29.

Estrogen effects on hair growth

Hair growth encompasses three stages, all known to be influenced by estrogens: growing (anagen), structural regression (catagen) and resting (telogen) . High systemic estrogen levels during pregnancy prolong the anagen phase of the hair follicle, and the plummeting estrogen levels postpartum are thought to cause this excess number of anagen follicles to enter the telogen phase simultaneously, sometimes resulting in clinically significant hair loss, the so- called telogen effluvium31. Androgenetic alopecia also known as female pattern alopecia, is the most common hair loss in women and is most frequently observed after menopause , suggesting a role of estrogens or the estrogen : androgen ratio. In men, androgenetic alopecia is a dihydrotestosterone-mediated process, characterized by continuous miniaturization of androgen-sensitive hair follicles33. Indeed, it is usually treated with systemic antiandrogens such as cyproterone acetate34 in women, or steroidogenic enzyme inhibitors such as finasteride in men. Topical estrogen is also used as treatment in women, especially in Europe36. The mechanism involved in estrogen-mediated induction of hair growth in androgenetic alopecia is not well understood. Some studies have shown an increased anagen and decreased telogen rate after estrogen treatment, as compared to placebo37. Niiyama and colleagues38 have demonstrated the ability of estrogen to modify androgen metabolism in dermal papillae of hair follicles.

MOLECULAR MECHANISMS OF ESTROGEN EFFECTS IN SKIN

Estrogens regulate cell function by binding two nuclear receptors: the estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta)39. In addition, the existence of a cell- surface form of estrogen receptor (membrane estrogen receptor) has been recently demonstrated40. The mechanism of estrogen action in skin is not well known and there are still some controversies regarding the expression of ER-alpha and ER-beta. Thornton and colleagues41 found that ER-beta is the predominant receptor in skin. Others42 found that both receptors are expressed and demonstrated the existence of a membrane receptor in the epidermis.

ESTROGEN THERAPY FOR SKIN AGING

Hormone replacement therapy

HRT consists of two components: estrogen and progestogen. The use of estrogen alone (unopposed estrogen) is associated with an increased risk of endometrial hyperplasia and/or carcinoma. In order to avoid this effect, in women with intact uterus and treated with estrogens, progestogens should be used to protect the endometrium. As the estrogen component, natural 17beta-estradiol is often used in Europe, whereas the conjugated equine estrogen (CEE) derived from pregnant mare’s urine is the preferred product in the US. HRT carries a small increased risk of serious complications, and the risk increases with duration of the therapy. Recently, recognized experts have provided practical guidelines for postmenopausal HRT and have reviewed the risk of complications43-46. Endometrial cancer occurs up to four times more frequently in women with a uterus who take unopposed estrogen than in non-users. The risk may be reduced by adding a progestogen. Breast cancer risk increases slightly with HRT prescribed longer than 5 years. Venous thromboembolism is rare but increases with estrogen use.

The indication for HRT is the treatment of menopausal symptoms (hot flushes, sweating, insomnia, fatigue, depressed mood and urogenital atrophy). The dose and regimen of HRT need to be individualized, based on choosing the lowest appropriate dose in relation to the severity of symptoms and on the menopausal age. The standard higher doses used in the past (0.625 mg CEE or 2 mg 17beta- estradiol) are not recommended today. Lower-dose HRT (0.3 mg CEE or 1 mg 17beta-estradiol) has been shown to be effective and minimizes the side-effects47. Usually, after 3-4 years of hormonal treatment, it is possible to stop HRT with no recurrence of menopausal symptoms. Currently, experts believe that limited, short-term use of HRT (

Beneficial effects of HRT on skin aging have been documented by several studies. An analysis of a large cohort of 3875 postmenopausal women aged 40 and more showed that HRT prevents dry skin and wrinkling. Women under long-term substitution had one- third fewer wrinkles than non-substituted patients22. A pilot study of 24 menopausal women examined the effects of different regimens of HRT on skin aging . Patients were assigned to three groups: transdermal estrogen only (Estraderm TTS(R) 50), transdermal estrogen and progesterone (Estraderm TTS(R) 50 and 0.4 mg progesterone vaginal suppository), and oral estrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository). One group served as control. Treatment was continued for 6 months. Epidermal moisture, skin elasticity and skin thickness were significantly improved in all treated groups. A comparison of epidermal hydration and skin elasticity revealed no significant differences between ultraviolet-exposed and nonexposed measurements sites, suggesting that both intrinsic and photoaging may be improved by HRT.

A leading parameter of skin aging is skin thickness, which reflects the status of collagen tissue. As previously reviewed, many studies have demonstrated beneficial effects of HRT on skin collagen content (Table 1). HRT also affects skin elasticity; it has been reported that HRT limits the age-related increase in cutaneous extensibility, thereby exerting a preventive effect on skin slackness6. Despite such beneficial effects of HRT on skin aging, HRT cannot obviously be recommended solely to treat skin aging in menopausal women. Prevention of skin aging with HRT should be regarded as an additional benefit for menopausal women who receive this treatment for other menopausal symptoms.

Topical estrogen treatment

Studies have showed that topical estrogen may prevent skin aging, as seen with HRT. Schmidt and colleagues4 examined the effects of 6- month treatment with topical 0.01% estradiol and 0.3% estriol on skin aging on the face of perimenopausal women. They found improvement similar to that seen in the studies using HRT. Both treatment groups showed increased skin moisture and improvement of elasticity and firmness of the skin with decreased wrinkle depth. No hormonal side-effects were noted, either clinically or by hormone monitoring. Serum hormone levels and the appearance of vaginal smears showed no significant change as compared to before treatment.

Creidi and colleagues27 examined the effect of a topically applied conjugated estrogen cream (Premarin(R) 0.625 mg/g of cream) in 54 women. After a 24-week treatment period, they found that Premarin cream produced better results than the placebo cream; the difference was statistically significant for skin thickness and fine wrinkles. Premarin cream was well tolerated locally. The general safety of Premarin cream was also excellent; no women had any serious drug-related study events. However, in contrast to the previous study, a modification of the vaginal maturation index was seen in women using the Premarin cream, demonstrating that the CEE has permeated the skin and exerted its effect on the vaginal mucosa. Indeed, it is known that CEE and 17beta-estradiol differ in their total estrogenic potency, with CEE possessing greater estrogenic potency . This suggests that estradiol creams may provide a safer therapy for skin aging compared to CEE creams, since they seem not to induce systemic effects.

It is clear that topical estrogen is an effective treatment for skin aging. Menopausal women who are not receiving HRT and who do not have any contraindications to HRT would be candidates for topical estrogen therapy.

Since studies have demonstrated a sharp decline in skin thickness and collagen in the years following menopause, particularly in the initial postmenopausal years13, it would be critical to begin the treatment within the first postmenopausal years. Additional studies are needed to definitively demonstrate the safety of this treatment. Further investigations should determinate the highest effective concentration of estrogens that can be used without the risk of possible systemic side-effects. Based on previous work on the use of topical estrogen for vaginal atrophy in postmenopausal women, it is expected that a short-term use of topical estrogen (

Such topical estrogen treatment for skin aging will need to be administered by a dermatologist experienced in endocrinology, given that concentration and application areas must be observed in order to avoid systemic sideeffects.

Selective estrogen receptor modulators

SERMs act at the level of the estrogen receptor; they bind to ER- a and ER-/?. They appear to have either estrogenic or antiestrogenic effects, depending on the tissue. In some tissues such as bone, they mimic the effects of estrogen, while in others they act as antiestrogens and block unwanted estrogenic effects on uterine and breast tissues. Because of this tissue specificity activity, SERMs are potentially a versatile drug class that offers the prospect of developing individualized, targeted treatments for menopause- associated morbidity. SERMs and estrogen agonist molecules that are currently available and currently in development are shown in Table 2.

The question of whether estrogen alternatives such as phytoestrogens and SERMs are effective estrogens for the prevention of skin aging in postmenopausal women remains unanswered. However, preliminary data indicate that such treatment may be of benefit for skin aging treatment.

Effects of phytoestrogenic SERMs on skin aging

Phytoestrogens are plant-derived molecules that structurally resemble endogenous estrogens, containing a diphenolic chemical structure that can directly bind to estrogen receptor5 . They have a relative greater affinity for ER-beta than for ER-alpha. Phytoestrogens exhibit some estrogen agonist-like properties5 but can also act as partial estrogen receptor antagonists55. Because of their mixed agonist/antagonist estrogen receptor profile, phytoestrogens have received considerable attention as potential alternatives to estrogen. Studies have demonstrated that genistein may prevent photoaging in human skin56. Other studies have reported that genistein and daidzein stimulate hyaluronic acid production in human keratinocyte culture57. A recent European study had examined the effect of a cosmetic cream preparation including isoflavone (Novadiol(R)) in 234 postmenopausal women and had showed improvement in skin dryness and wrinkles after 12 weeks of treatment58.

Effects of SERMs on skin aging

An effective SERM for the skin would exert estrogen agonist action in skin and estrogen antagonist action in breast and uterus. The ideal SERM for skin would also exert estrogen action in brain, bone and in the vagina. Among different SERMs currently available or under development, only raloxifene has been studied for its effects in skin. Raloxifene is used in prevention and treatment of postmenopausal osteoporosis59. It also decreases the risk of breast cancer60 and does not stimulate the endometrium 1. Recent studies have demonstrated that raloxifene exerts stronger stimulative effects on collagen biosynthesis than estradiol in human skin fibroblasts and might reverse some of the postmenopausal changes in skin62. Table 2 Selective estrogen receptor modulators (SERMs) currently available or under development

CONCLUSION

The skin is an estrogen-responsive tissue. A better understanding of the hormonal regulation of skin physiology and skin aging may provide the basis for development of new hormonal treatment for skin aging. HRT cannot be recommended solely to treat skin aging in menopausal women but may be considered as an additional benefit in the treatment of menopausal symptoms. Topical estrogen application is highly effective and safe if used by a dermatologist with expertise in endocrinology. Phytoestrogens appear to be effective but their possible side-effects have not been well investigated. SERMs are drugs that offer exciting opportunities for the future treatment of skin aging but, while great strides have been made in developing effective SERMs for menopausal symptoms such as osteoporosis, the challenge of developing an effective estrogen alternative for skin aging treatment remains.

Conflict of interest The author declares having no conflict of interest capable of influencing her judgment.

Source of funding Nil.

Received 27-10-06

Revised 15-02-07

Accepted 23-02-07

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S. Verdier-Sevrain

Bio-Hybrid, LLC, West Palm Beach, Florida, USA

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Copyright Taylor & Francis Ltd. Aug 2007

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