In a study published May 20 in the journal Addiction, researchers have determined that treatment for smoking dependence is as effective among people with severe mental illnesses as it is for the general population. Importantly, they also found that offering such treatments does not appear to cause deterioration in mental health.

This is good news: people with severe mental illnesses (SMI) such as schizophrenia have some of the worst physical health of any section of the population. They are two to three times more likely to smoke, and smoking-related illnesses contribute significantly to their high sickness and death rates. Mortality rates for those with SMI are three times that of the rest of the population.

Although treatment for smoking dependence would improve the physical health of people with SMI, the medical community has traditionally ignored health promotion and worried that such treatments would worsen people’s mental states.

The authors brought together the most rigorous evidence on smoking cessation treatment among people with SMI. They were able to determine the effectiveness of smoking cessation treatment and chart any predictable adverse effects. In general, people with SMI responded well to pharmaceutical and behavioral treatments, which doubled their chance of quitting.

Because most of the studies focused on people with well controlled psychiatric conditions, it was not possible to state how well people with acute mental illness (such as those who have experienced recent hospitalization) would respond to smoking cessation treatment.

Professor Simon Gilbody from the University of York & Hull York Medical School, who co-authored the review, commented that “schizophrenia is a devastating condition which causes people to die 25 years earlier than the rest of the population. This is a huge health inequality, and it is largely due to smoking-related illness rather than schizophrenia itself.”

Dr Lindsay Banham, who led the review, added “what this review suggests is that quit-smoking treatments like nicotine replacement therapy may work just as well for people with disorders like schizophrenia. Smoking by those with SMI has largely been ignored and people with schizophrenia are not consistently offered treatment or services. We found evidence that smoking cessation treatments are effective and safe. We hope our research leads to better services for this neglected population.”

Professor Gilbody concluded, “Despite huge expansion in smoking cessation services in recent years, people with severe mental illness have been left behind. The challenges for health services are to ensure people with schizophrenia are offered these treatments, and that services reflect the needs of this population.”

Reference: Banham L. and Gilbody S. Smoking cessation in severe mental illness: What works? Addiction 2010; 105: doi:10.1111/j.1360-0443.2010.02946.x

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On the Net:

• Addiction

Patients with chronic kidney disease who have been diagnosed with depression are twice as likely to be hospitalized, progress to long-term dialysis treatments or die within a year as those who are not depressed, UT Southwestern Medical Center researchers have found.

In the study, published in the May 19 issue of the Journal of the American Medical Association, researchers monitored for one year 267 patients with chronic kidney disease ““ 56 of them with a diagnosis of a current major depressive episode, referred to here as depression, based on the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV).

Nearly 61 percent of patients with depression compared to 44 percent without depression either died, progressed to long-term dialysis, or were hospitalized within a year of observation; 55 percent of depressed patients were hospitalized compared to 40 percent of patients who were not depressed; 27 percent of depressed patients needed to start regular dialysis treatments compared to 11 percent without depression; and 9 percent of depressed individuals died compared to 6 percent without depression.

“Chronic kidney disease patients with depression have poorer health outcomes than those without depression, even after adjusting for other factors that determine poor outcomes in these patients, such as other medical diseases, anemia and low albumin levels,” said Dr. Susan Hedayati, assistant professor of internal medicine at UT Southwestern, staff nephrologist at the Dallas VA Medical Center and lead author of the study. “Clinicians should consider screening chronic kidney disease patients for depression, especially since depression is also associated with poor quality of life.”

Twenty-six million people in America have chronic kidney disease and millions more are at an increased risk, according to the National Kidney Foundation. If treatment does not begin early, the condition progresses to end-stage renal disease. At that point, a patient’s kidneys have failed to the point where dialysis ““ a filtering of toxic chemicals in the blood and removal of fluid to help control blood pressure ““ or a kidney transplant is needed.

In 2007 an estimated $24 billion, about 6 percent of the entire Medicare budget, was spent on dialysis-related health care in patients with chronic kidney disease, according to the U.S. Renal Data System 2009 Annual Report.

This JAMA study is the first to look at outcomes as they relate to an association between chronic kidney disease and depression in patients prior to starting regular dialysis. In previous reports, Dr. Hedayati has found that one in five chronic kidney disease patients is depressed before beginning long-term dialysis therapy and that patients already on dialysis who have been diagnosed with depression are nearly twice as likely to be hospitalized or die within a year than those who are not depressed.

For the current study from May 2005 to November 2006, researchers invited patients at the Dallas VA Medical Center who were visiting the clinic for chronic kidney disease appointments to join the study. Patients who agreed to participate then underwent a structured clinical interview to determine if they had a current major depressive episode, based on the DSM-IV definition which is considered the gold-standard in evaluating depression.

Fifty-six patients were found to be depressed. The mean age of patients was about 65; two were women; and nearly 56 percent were white. All patients were veterans.

The association between chronic kidney disease, depression and poorer health outcomes held after adjusting for age, race and other current medical conditions.

“Our results support the need for well-designed clinical trials to investigate if antidepressant treatment is efficacious and safe in this vulnerable population. Patients with advanced kidney disease have been previously excluded from larger randomized trials of antidepressant medication treatment,” said Dr. Hedayati, who is now conducting the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) to determine whether antidepressant medication would be tolerated in kidney-disease patients and whether such treatments can improve depression and quality of life.

Other UT Southwestern researchers participating in this study were Dr. Abu Minhajuddin, assistant professor of clinical sciences; Dr. Masoud Afshar, a postdoctoral fellow in nephrology; Dr. Robert Toto, professor of internal medicine and clinical sciences; and Dr. Madhukar Trivedi, professor of psychiatry.

The study was supported by UT Southwestern’s George M. O’Brien Kidney Research Core Center, the National Institutes of Health and the Department of Veterans Affairs.

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On the Net:

• UT Southwestern Medical Center
• Journal of the American Medical Association

Boston University biomedical engineers develop new nanopore method for DNA sequencing

Sequencing DNA could get a lot faster and cheaper ““ and thus closer to routine use in clinical diagnostics ““ thanks to a new method developed by a research team based at Boston University. The team has demonstrated the first use of solid state nanopores “” tiny holes in silicon chips that detect DNA molecules as they pass through the pore “” to read the identity of the four nucleotides that encode each DNA molecule. In addition, the researchers have shown the viability of a novel, more efficient method to detect single DNA molecules in nanopores.

“We have employed, for the first time, an optically-based method for DNA sequence readout combined with the nanopore system,” said Boston University biomedical engineer Amit Meller, who collaborated with other researchers at Boston University, and at the University of Massachusetts Medical School in Worcester. “This allows us to probe multiple pores simultaneously using a single fast digital camera. Thus our method can be scaled up vastly, allowing us to obtain unprecedented DNA sequencing throughput.”

The research is detailed in Nano Letters. The National Institutes of Health are currently considering a four-year grant application to further advance Meller’s nanopore sequencing project.

This low-cost, ultra-fast DNA sequencing could revolutionize both healthcare and biomedical research, and lead to major advances in drug development, preventative medicine and personalized medicine. By gaining access to the entire sequence of a patient’s genome, a physician could determine the probability of that patient developing a specific genetic disease.

The team’s findings show that nanopores, which can analyze extremely long DNA molecules with superior precision, are uniquely positioned to compete with current, third-generation DNA sequencing methods for cost, speed and accuracy. Unlike those approaches, the new nanopore method does not rely on enzymes whose activity limits the rate at which DNA sequences can be read.

“This puts us in the unique advantageous position of being able to claim that our sequencing method is as fast as the rapidly evolving photographic technologies,” said Meller. “We currently have the capability of reading out about 200 bases per second, which is already much faster than other commercial third-generation methods. This is only the starting point for us, and we expect to increase this rate by up to a factor of four in the next year.” Licensing intellectual property from Boston University and Harvard University, Meller and his collaborators recently founded NobleGen Biosciences to develop and commercialize nanopore sequencing based on the new method.

“I believe that it will take three to five years to bring cheap DNA sequencing to the medical marketplace, assuming an aggressive research and development program is in place,” said Meller.

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On the Net:

• Boston University College of Engineering
• Nano Letters

Patients Over 40 Once Unheard-of Now a Growing Segment of the Population

An emerging population of middle-aged cystic fibrosis patients contains significantly more females and includes a large proportion of patients who lived for decades without a diagnosis or specialized care, according to research published by researchers at National Jewish Health. The comprehensive analysis of this over-40 cohort, published online May 20 in the American Journal of Respiratory and Critical Care, may help guide future treatment of cystic fibrosis as survival past 40 becomes increasingly common.

“As both care and diagnosis have improved, cystic fibrosis has been transformed from a uniformly fatal childhood disease to a condition where survival to middle age and older is possible,” said National Jewish Health pulmonologist and lead author Jerry Nick, MD. “We were surprised to discover that the majority of patients diagnosed as adults were females, representing a striking reversal of the “gender gap” in cystic fibrosis, and that they have delayed, but equally severe disease.”

Cystic fibrosis (CF), an inherited disease of the lungs and digestive system, affects about 30,000 people in the United States and is the most common genetic disease among Caucasians. A single defective gene causes a missing or non-functional channel for chloride to travel into and out of cells. Lack of this channel disrupts the water balance in the lungs of CF patients, causing the development of thick, dehydrated mucus, which serves as a fertile environment for bacterial growth. Most patients die of respiratory failure brought on by repeated severe bacterial infections in the lungs.

In 1962 the median predicted survival for children with cystic fibrosis was 10 years. Today, it is 37, and children diagnosed today can expect to live into their 50s. Improved care is helping patients live longer. In addition, many more patients with non-traditional symptoms are being diagnosed for the first time as adults.
These two groups – those diagnosed as children and those diagnosed for the first time as adults – comprise two distinct populations of CF patients over 40. Those diagnosed as adults usually have a genetic mutation that produces a partially functional gene and a slightly different set of symptoms from those diagnosed as children. Most commonly, they have functional pancreases and fewer digestive problems.

Dr. Nick and his colleagues analyzed epidemiological and health data on 156 CF patients over 40 year of age who receive care at National Jewish Health, the largest adult cystic fibrosis clinic in the nation. In addition, data were analyzed on nearly 3,000 patients from around the nation who were included in the Cystic Fibrosis Foundation Patient Registry from 1992-2007.

The researchers found that the fate of females changes considerably in the older CF population. It has long been recognized that a “gender gap” is present in CF, favoring males. Historically, females have been diagnosed later, had a poorer prognosis, and survived fewer years than males.

Accordingly, Dr. Nick’s analysis showed that fewer females diagnosed as children survived to age 40. However, among those diagnosed as adults, females represented a significant majority, accounting for 72 percent of patients in Colorado and 54 percent nationally. Among the adult diagnosed patients, females survived on average 9 to 14 years longer than males.

The complex factors that account for the differential fate of female CF patients is not understood, although Dr. Nick believes it could be a mixture of behavioral and biological factors.

Dr. Nick’s findings also indicate that patients diagnosed as adults do not really have milder diseases — as is commonly believed — just a delayed onset of an equally severe form of the disease. Although patients diagnosed as adults live longer than those diagnosed as children, the adult-diagnosed patients lose lung function as rapidly those diagnosed in childhood, and approximately 85% die of respiratory failure or post-transplant complications.

Dr. Nick believes there is a significant number of adults whose CF remains undiagnosed. His analysis indicates that once those patients are accurately diagnosed, proper care can significantly improve their health. Patients diagnosed as adults and subsequently followed at a CF center reversed progressive lung function decline and improved their lung function for at least four years.
Older patients commonly do not get specialized CF care. It is generally recognized that the team approach to treatment provided by the 112 CF Foundation-accredited Care Centers results in better clinical outcomes. However, less than half of long-term CF survivors continued to be seen at CF Centers as they pass 40 years, with the fewest among the adult-diagnosed patients.

“In the coming years, more and more cystic fibrosis patients will be living into their 40s, 50s and beyond,” said Dr. Nick. “Our findings concerning the role of gender, in survival, progression of disease, and type of care in current long-term survivors provides important insights that will help us prepare for better treatment of the steadily aging CF population.”

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On the Net:

• National Jewish Health
• American Journal of Respiratory and Critical Care

Spanish researchers have employed for the first time adult cells extracted from a human heart to turn stem cells from adipose tissue into cardiac myocytes. In other words, they achieved to “reprogram” adult stem cells, which might improve treatments for heart disease therapeutical.

At present, the use of stem cells in treatments for heart disease is one of the most common practices. However, working with stem cells without targeting heart tissue negatively affects the efficacy of treatments. Therefore, inducing cell differentiation into cardiac muscle (cardiomyocytes) may be one of the best options in the treatment of these pathologies.

For the purpose of this study, researchers isolated adult human stem cells from lipoaspiration. Subsequently, these cells were temporarily permeabilized and exposed to a human-auricle cell extract. Then, these cells were recovered in culture.

Morphological Changes

After 21 days in culture, the cells differentiated towards a cardiac myocyte phenotype, which was demonstrated by expression of morphological changes (appearance of binuclear cells with striated fibers and ramifications), detection of cardiospecific markers through inmunofluorescence, and the presence of cardiac muscle-related genes that were analyzed through RT-PCR; and finally, by expression of reverse transcription. Thus, mesenchimal stem cells acquired a cardiac phenotype.

This study was conducted by Macarena Perán, Juan A. Marchal, Elena L³pez, Manuel Jim©nez-Navarro, Houria Boulaiz, Fernando Rodríguez-Serrano, Esmeralda Carrillo, Gema Sánchez-Espín, Eduardo de Teresa, David Tosh y Antonia Aránega, researchers from the University of Jaen (Spain), the University of Granada, the Hospital Clínico Universitario of Malaga and the University of Bath (United Kingdom). It is going to be published on the Journal Cytotherapy, the official reporting organ of the International Society for Cellular Therapy (ISCT).

This technique could be used in the future for regeneration of cardiac muscles through the use of cells directly extracted from the patient. However, physicians have remarked that, at present, this research is in its earlier stages, and it will be a long time until it has any therapeutical use.

Currently, researchers are preparing a new approach for introducing the cell extract into the target cell (by using a cell microinjector) that will allow them to obtain a larger number of viable differentiated cells, which is essential for their having any therapeutical use. The following step is to use animal models to validate differentiated cells’ functionality. Finally, a number of clinical trials should be conducted to assess the viability of this technique in human patients.

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On the Net:

• Cytotherapy

A relatively simple electronic gadget could speed up HIV/AIDS diagnostics and improve accuracy particularly in parts of the world with very limited access to healthcare workers. The device is described in the International Journal of Biomedical Engineering and Technology.

Ali El Kateeb of the Electrical and Computer Engineering Department, at the University of Michigan, in Dearborn, explains that rapid blood tests for diagnosing HIV have become widely available but are prone to human error in reading the results. The currently available kits require a drop of blood placed in a well containing reactant test chemicals. A positive test produces a colored band perpendicular to a “control” bar that appears only if the test procedure was carried out correctly. El Kateeb points out that even such an apparently simple test must be carried out by a trained technician and in a clinic or laboratory.

Unfortunately, errors in reading the test pattern can occur and are particularly common in parts of the world where there is a dearth of qualified technicians. The result is that false positives that have a negative psychological effect on patients are common while false negatives mean patients thinking they are free of the virus will continue to infect others unwittingly.

Previously, El Kateeb had developed a static imaging device -, akin to a simple digital camera, that could be used to identify valid and positive test results using a built-in computer chip modified to run a dedicated pattern recognition program. The static approach was not entirely successful because it relies on precise manufacture of the test kit as well as accurate placement of the “eye” of the imaging device above the test kit. Now, El Kateeb has developed a “dynamic” version of the device that overcomes this significant drawback.

In the dynamic approach, the built-in software embedded on a Reconfigurable System-On-Chip, first determines the relative position of the detector’s 384 Ö 288 pixel eye relative to the test kit well, illuminated by four LEDs, using a rapid analysis of pixel density in the captured image. The software then identifies the control bar and detects whether or not the perpendicular test bar is present regardless of their exact positioning within the well.

El Kateeb says this dynamic detection technique is 100% accurate in laboratory testing. The device is inexpensive, portable and self-contained and so could be made available to small clinics and pharmacies at low cost. Moreover, it requires no technician intervention, which will make it useful for rural areas in the developing world.

“An accurate dynamic testing approach for analyzing images produced by quick HIV kits” in Int. J. Biomed. Eng. Technol., 2010, 4, 151-160

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On the Net:

• Journal of Biomedical Engineering and Technology

Duodenocaval fistula (DCF) is an uncommon but lethal clinical entity. The high mortality has been attributed to the difficulty of diagnosis before attempts at definitive therapy.

A case report and review of literature to be published on May 14, 2010 in the World Journal of Gastroenterology addresses the diagnostic significance of computed tomography (CT) and magnetic resonance imaging (MRI) for DCF.

During a 2-mo stay in hospital, a small, low-density air bubble appeared in the inferior vena cava (IVC) and gradually enlarged on follow-up CT scans. MRI clearly demonstrated the high-signal enteric contrast medium or thrombus and signal-void air bubbles in the IVC. However, cavography did not reveal the thrombus in the IVC. The authors deemed that the thrombus was flushed out by the high-pressure injection of intravenous contrast medium. Noninvasive CT and MRI are suggested as a first-line investigation for diagnosis of DCF.

Reference: Guo Y, Zhang YQ, Lin W. Radiological diagnosis of duodenocaval fistula: A case report and literature review. World J Gastroenterol 2010; 16(18): 2314-2316

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On the Net:

• World Journal of Gastroenterology Article

Study suggests that treating serious gum disease in diabetics could mitigate risks

A study to be published in the latest issue of The Cochrane Library and led by researchers at the University of Edinburgh and supported by colleagues at the Peninsula Dental School, the University of Ottawa and UCL Eastman Dental Institute, suggests that the treatment of serious gum (periodontal) disease in diabetics with Type 2 diabetes may lower their blood sugar levels.

The research team analyzed randomized controlled trials of people with Type 1 and Type 2 diabetes who had also been diagnosed with periodontal disease. The team looked at 690 papers and included seven studies in the review that fulfilled pre-specified criteria for inclusion.

Their findings suggest that the treatment of periodontal disease can reduce blood sugar levels in Type 2 diabetes, although there was not enough available evidence to support the same benefit for those with Type 1 diabetes.

Current belief is that, when bacteria infect the mouth and cause inflammation, the resulting chemical changes reduce the effectiveness of insulin produced in the body, thus making it more difficult for diabetics to control their blood sugar.

The findings are key because many patients and health care professionals do not necessarily make the association between the treatment of gum disease and the control of blood sugar levels. The study suggests that the effective treatment of gum disease could have a positive impact on diabetic patients, especially those with Type 2 diabetes, because it good blood sugar control contributes to lowering the risk of serious complications linked to the condition, such as eye problems and heart disease.

Terry Simpson, lead author at the Edinburgh Dental Institute, said: “It would be wise to advise patients of the relationship between treating periodontal disease and the possibility of lowering their blood sugar levels. Additionally, an oral health assessment should be recommended as part of their routine diabetes management.”

David Moles, Professor of Oral Health Research and Director of Postgraduate Education and Research at the Peninsula Dental School, added: “In this study we have helped confirm a link between the effective treatment of gum disease and lower blood sugar levels in those with Type 2 diabetes. Now what are required are larger randomized trials to further study dental treatment and its long term outcomes for those with diabetes, including the possibility of marrying dental care for diabetics with wider diabetes support and treatment networks and closer collaboration between doctors and dentists.”

Type 1 diabetes is the type of diabetes that typically develops in children and young adults. In Type 1 diabetes the body stops making insulin and the blood glucose level goes very high. Treatment to control the blood glucose level is with insulin injections and a healthy diet. Other treatments aim to reduce the risk of complications and include reducing blood pressure if it is high, and to lead a healthy lifestyle.

Type 2 diabetes occurs mainly in people aged over 40, although it is affecting a growing number of younger people. The ‘first-line’ treatment is diet, weight control and physical activity. If the blood glucose level remains high despite these measures, then tablets to reduce the blood glucose level are usually advised. Insulin injections are needed in some cases. Other treatments include reducing blood pressure if it is high, lowering high cholesterol levels and also other measures to reduce the risk of complications.

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On the Net:

• The Cochrane Library

A joint clinical trial conducted by the University Hospital and the University of Gothenburg, Sweden, found that an element in human blood, fibrinogen, is likely more vital to the blood’s clotting ability in connection with heart surgery than previously considered. If the patients also receive a dose of fibrinogen prior to the procedure, this reduces the risk of hemorrhage during and after surgery. These results may open the door to new strategies in reducing bleeding complications in cardiac surgery.

Each year over 7,000 Swedes undergo open-heart surgery, most commonly a coronary artery bypass or a valve replacement. It’s a major procedure during which the heart and lungs are stopped and their functions are temporarily replaced by a heart-lung machine, or CPB pump.

“But the use of a CPB pump has negative effects on the blood’s clotting ability, and those effects last a few hours after the operation,” says Dr Martin Karlsson at Sahlgrenska Academy at the University of Gothenburg, author of the thesis. “This leads to a risk of bleeding. It’s unclear why certain patients have more problems than others, but several factors may be involved.”

Fibrinogen is one of the most important coagulation proteins in our blood, and the thesis shows that the amount of fibrinogen in the blood is more important than previously thought to ensure clotting after heart surgery.

“We found that the amount of fibrinogen in the patient’s blood immediately prior to bypass surgery is directly related to how much the patient bleeds afterwards, and also to the need for blood transfusions after surgery. As a rule, patients with lower levels of fibrinogen in their blood prior to surgery bleed more, even if they have levels that were previously perceived as normal and sufficient.”

In one part of the trial, bypass patients with low levels of natural fibrinogen in their blood were pre-treated with fibrinogen concentrate before the operation. This reduced the amount of bleeding and the need for transfusions during and after surgery compared with a control group, and the pre-treated patients showed no signs of side effects.

“Treatments such as this have never been tried on patients before, and this trial was only a pilot study, with a small number of patients,” Karlsson explains. “So it’s too early to draw any real conclusions, but the results are promising and larger trials have already begun.”

Karlsson hopes that if the results of the pilot study can be confirmed, then fibrinogen concentrate could be used as a preventive therapy for patients about to undergo a surgical procedure and in other instances where the risk of hemorrhage is high. This would offer a new treatment option for the large number of patients undergoing cardiac surgery each year, possibly also for other surgical procedures.

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On the Net:

• University of Gothenburg

In people with insulin resistance or full-blown diabetes, an inability to keep blood sugar levels under control isn’t the only problem by far. A new report in the May issue of Cell Metabolism, a Cell Press publication, shows that our arteries suffer the effects of insulin resistance, too, just for entirely different reasons.

“We think about insulin resistance in liver, muscle, and fat, but insulin also works on vascular cells,” said Christian Rask-Madsen of the Joslin Diabetes Center in Boston.

And what insulin does in our arteries sends a signal that helps prevent the buildup of fatty plaques that can cause arteries to harden, new research in mice shows.

Earlier studies showed that in the context of systemic insulin resistance, blood vessels become resistant, too. Doctors also knew that insulin resistance and the high insulin levels to which it leads are independent risk factors for vascular disease. But it wasn’t clear if arteries become diseased because they can’t respond to insulin or because they get exposed to too much of it.

Now comes evidence in favor of the former explanation. Rask-Madsen along with George King and their colleagues find that mice prone to atherosclerosis fare much worse when the linings of their arteries can’t respond to insulin. The animals’ insulin-resistant arteries develop plaques that are twice the size of those on normal arteries.

Insulin-resistant blood vessels don’t open up as well, and levels of a protein known as VCAM-1 go up in them, too.

VCAM-1 belongs to a family of adhesion molecules, Rask-Madsen explained. “It sits on the endothelium and binds white blood cells.” Those cells can enter the artery wall, where they start taking up cholesterol, and an early plaque is born.

“The results provide definitive evidence that loss of insulin signaling in the endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis,” the researchers conclude.

The findings should come as good news to those on insulin therapy, since they suggest the hormone itself should not cause harm to arteries, as some had feared. “If anything, it should be beneficial in preventing atherosclerosis,” Rask-Madsen said.

The results also suggest drugs specifically designed to treat insulin resistance in the vasculature might prevent cardiovascular complications in people with insulin resistance or type 2 diabetes, the researchers say.

While the researchers emphasize that it will remain critical to keep blood sugar in check with more traditional therapies, new treatments aimed at blood vessels could mean big gains for those with diabetes. After all, atherosclerosis is responsible for many of diabetes’ worst complications””heart disease, stroke, and leg amputations among them.

“Atherosclerosis is the main reason for shorter life spans in diabetes patients,” Rask-Madsen said.

The researchers include Christian Rask-Madsen, Joslin Diabetes Center, Boston, MA; Qian Li, Joslin Diabetes Center, Boston, MA; Bryn Freund, Temple University School of Medicine, Philadelphia, PA; Danielle Feather, Temple University School of Medicine, Philadelphia, PA; Roman Abramov, Joslin Diabetes Center, Boston, MA; I-Hsien Wu, Joslin Diabetes Center, Boston, MA; Kai Chen, Joslin Diabetes Center, Boston, MA; Junko Yamamoto-Hiraoka, Joslin Diabetes Center, Boston, MA; Jan Goldenbogen, Joslin Diabetes Center, Boston, MA; Konstantinos B. Sotiropoulos, Joslin Diabetes Center, Boston, MA; Allen Clermont, Joslin Diabetes Center, Boston, MA; Pedro Geraldes, Joslin Diabetes Center, Boston, MA; Claudia Dall’Osso, Joslin Diabetes Center, Boston, MA; Amy J. Wagers, Joslin Diabetes Center, Boston, MA; Paul L. Huang, Massachusetts General Hospital, Boston, MA; Mark Rekhter, Lilly Research Laboratories, Indianapolis, IN; Rosario Scalia, Temple University School of Medicine, Philadelphia, PA; C. Ronald Kahn, Joslin Diabetes Center, Boston, MA; and George L. King.

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On the Net:

• Cell Metabolism

Rush Center for Urban Health Equity will focus on disparities in heart and lung disease

Rush University Medical Center has been awarded a $10 million grant from the National Institutes of Health (NIH) to establish the Rush Center for Urban Health Equity. The aim of the Center is to find ways to promote changes to eliminate the disparities in heart and lung disease affecting inner city residents, in particular those who are low-income persons of color.

“Health disparities have persisted or worsened in the past two decades, despite efforts to narrow the gap. In Chicago alone, if the mortality rate for blacks was the same as for whites, then 4,000 fewer black people would die each year,” said Lynda H. Powell, PhD, the director of the Center and the chairperson of the Department of Preventive Medicine at Rush.  “We must find a way to change this situation.”

The Rush Center for Urban Health Equity is based on the principle that continued documentation of avoidable deaths and disabilities from health disparities in observational studies in insufficient. Instead, the Center is dedicated to preventing health disparities by conducting rigorous behavioral clinical trials and testing interventions across the spectrum from children to the elderly. These interventions, if effective, will have an immediate impact.

The first three research projects will focus on heart failure, depression, and pediatric asthma with co-morbid obesity.

A clinical trial led by Powell and Dr. James Calvin, director of the Section of Cardiology at Rush, aims to reduce repeated hospitalizations in low-income heart failure patients by improving doctor’s prescription of evidence-based medicine and patients’ adherence to the medicines that have been prescribed.

A second study, the BRIGHTEN Heart (Bridging Resources of a Geriatric Health Team via Electronic Networking ““ Heart) program will use “virtual” teams to coordinate care for older adults with co-morbid depression and metabolic syndrome. The study will be led by Dr. Steven Rothschild, associate center director and a family practice physician at Rush, and Erin Emery, PhD, director of Geriatric & Rehabilitation Psychology at Rush.

A third clinical trial is one of the first attempts to simultaneously control both asthma and obesity in high-risk children. The team, led by Dr. Molly Martin, a pediatrician and assistant professor in the Department of Preventive Medicine at Rush, has developed strong partnerships with local organizations in the Humboldt Park neighborhood with the aim of targeting the influences of schools, family and caregivers on weight and self-management of asthma.

Community partnerships are at the core of the Center’s vision and values. Residents will become active participants in the design and conduct of all of the interventions to improve their health.

“It’s critical to develop and conduct these programs in the community where people live in order to promote sustained change. Studies conducted at hospitals or research labs may produce short-term results, only to see those changes reversed when people return to the challenging environments within which they live,” said Rothschild.

The Center will involve a dynamic multi-disciplinary team representing basic and clinical research, cardiology, behavioral sciences, gerontology, endocrinology, epidemiology and pulmonary medicine to address risk a variety of levels of risk factors, including the community, family, social network, and individual psychology and risk behaviors.

“Efforts to isolate a single risk factor and to intervene on it alone have had only modest effectiveness.  Our Center has convened a group of medical and social science investigators and community residents to provide a multi-level approach to address the many simultaneous contributors to these disparities,” said Powell.

Unique to the Center is the involvement of a specialist in post-traumatic stress, Stevan Hobfoll, PhD, professor and chairperson of the Department of Behavioral Sciences at Rush.

Although research on health disparities has at times focused on major life stress, there has been relatively little focus on traumatic stress. Low income and ethnic minority populations are much more likely than higher income and majority population members to be exposed to traumatic stressors, such as murder, serious injury, sexual or physical assault.

“Major life and traumatic stressors may both indirectly affect physical health through their influence on behaviors, including drug and alcohol use, smoking, sleep disturbances, avoidance of exercise, as well has directly affect health by compromising the immune system or inflammatory responses,” said Hobfoll.

The Center will place a priority on training the next generation researchers who will foster health equity in the future. This will include supporting initiatives in Chicago Public Schools to promote health careers and progression to college programs with minority serving institutions such as Chicago State University and Malcolm X College.  Training fellowships and post-doctoral training will also be offered.

“Progress on health disparities has been slow in the United States. In fact, in Chicago black/white health disparities continue to get worse over time,” said Powell.  “We refuse to sit idly by and watch this happen. We want to eliminate the health disparities that are cutting short the lives and livelihoods of our family, friends, and neighbors.”

The Rush Center will be a designated Centers for Population Health and Health Disparities (CPHHD) program. The National Cancer Institute and the National Heart, Lung and Blood Institute and the Office of Behavioral and Social Sciences Research at the National Institutes of Health (NIH) are partnering to provide funds to continue the CPHHD program. This program responds to a strategic priority at the NIH to address disparities and inequities in the prevalence and outcomes of several diseases, particularly cancer and heart disease. The CPHHD program requires transdisciplinary research involving social, behavioral, biological, and genetic research to improve knowledge of the causes of health disparities and devise effective methods of preventing, diagnosing and treating disease and promoting health. For more information on the CPHHD program, visit http://cancercontrol.cancer.gov/populationhealthcenters/cphhd/

Theme issue of Archives of Pediatrics & Adolescent Medicine highlights dangers during early development, interventions to improve long-term health

Experiences between birth and age 5 matter significantly to children’s long-term emotional and psychological health, and changing these experiences for the better pays dividends, according to an editorial and several new reports in the May issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

This month’s journal is a theme issue devoted to the science of early life experience. The articles provide “key, actionable evidence of how we can manipulate the early environment of children and make a tangible difference in their health,” write Dimitri A. Christakis, M.D., M.P.H., and Frederick P. Rivara, M.D., M.P.H., both of the University of Washington and Seattle Children’s Research Institute as well as associate editor and editor of the Archives, in the editorial.

“This research needs to be translated into action,” they continue. “In the new austerity that has been spawned by the national fiscal crisis, states are cutting back broadly on services. In many cases, children are being hit the hardest. Given the importance of early childhood experiences on the entire life course, we can only hope that the people who make decisions about where monies are saved are mindful of the effect those decisions can have.”

(Arch Pediatr Adolesc Med. 2010;164[5]:491-492)

Prenatal Nicotine, Antidepressant Exposure Associated With Childhood Difficulties

Children whose mothers smoked during pregnancy appear to have more sleep problems throughout the first 12 years of life, and those whose mothers took a certain type of antidepressant may be more likely to have some behavior problems at age 3, according to two reports in the theme issue.

In one study, Kristen C. Stone, Ph.D., of the Brown Center for the Study of Children at Risk, Women and Infants Hospital, Providence, R.I., and colleagues assessed 808 children whose mothers provided information about prenatal care, sociodemographics and their children’s sleep and behavior problems, as well as substance exposure during pregnancy.

Of the five substances assessed””cocaine, opiate, marijuana, alcohol and nicotine””only prenatal exposure to nicotine was associated with sleep problems in children. “Higher levels of prenatal nicotine exposure predicted more sleep problems, specifically difficulty falling and staying asleep from one month to 12 years,” the authors write.

“Targeting of this group of children for educational and behavioral efforts to prevent and treat sleep problems is merited given that good sleep may serve as a protective factor for other developmental outcomes,” they conclude.

In another report, Tim F. Oberlander, M.D., F.R.C.P.C., and colleagues at University of British Columbia, Vancouver, studied 75 mothers and their 3-year-old children. Of these, 33 mothers took selective serotonin reuptake inhibitors (SSRIs) during pregnancy and 42 did not. Mothers’ moods were assessed during the third trimester, three months after birth and at the three-year follow-up.

“Prenatal SSRI exposure and higher current maternal anxiety contributed to increased internalizing behaviors [withdrawal, anxiety and depression] in 3-year-old children,” the authors write. “Increased levels of externalizing behaviors were also observed, but they were associated with current levels of three-year postpartum maternal mood.” Genetic factors, including an altered version of a gene in the serotonin processing system, moderated the effect of a mothers’ mood on her child.

“Even with prenatal maternal SSRI treatment, mothers continue to be symptomatic, and child behavior at 3 years of age continues to be at risk,” the authors conclude.

In an editorial accompanying both papers, Gideon Koren, M.D., and Irena Nulman, M.D., of the Hospital for Sick Children, Toronto, write that “since the thalidomide era, there are concerns regarding potential adverse effects of drug and chemical exposure on the developing fetus in pregnancy, causing physicians and expectant mothers high levels of anxiety toward drugs, even in life-threatening conditions.”

“Because pregnant women will never be randomized to exposure to antidepressants or recreational drugs, high-quality observational investigations, such as those by Oberlander and colleagues and Stone and colleagues, will be critical in distinguishing associations from causation in the field of maternal-fetal toxicology,” they conclude.

(Arch Pediatr Adolesc Med. 2010;164[5]:452-456, 444-451, 494-495.)

Early Childhood Television Exposure Associated With Academic, Lifestyle Risks in Fourth Grade

Children who are exposed to more television at 29 months of age appear to have more problems in school and poorer health behaviors in fourth grade. Linda S. Pagani, Ph.D., of Universit© de Montr©al, Canada, and colleagues studied 1,314 children in this age group whose parents reported their weekly hours of television exposure.

The researchers assessed parent and teacher reports of the children’s academic, psychosocial and health behaviors as well as their body mass index (BMI) in fourth grade. Each additional hour of television in early childhood corresponded to a 7 percent unit decrease in classroom engagement, 6 percent unit decrease in math achievement, 10 percent unit increase in victimization by classmates, 13 percent unit decrease in time spent doing weekend physical activity, 9 percent unit decreases in activities involving physical effort, 9 percent higher scores for consumption of soft drinks and 10 percent higher scores for consumption of snacks, as well as a 5 percent unit increase in BMI.

“The long-term risks associated with higher levels of early exposure may chart developmental pathways toward unhealthy dispositions in adolescence,” the authors conclude. “A population-level understanding of such risks remains essential for promoting child development.”

(Arch Pediatr Adolesc Med. 2010;164[5]:425-431.)

Home Visits by Nurses Benefit Mothers, Children Through Age 12

Home visits by nurses during pregnancy and the child’s infancy appear to improve mothers’ life course, reduce some behavior problems in children and decrease government spending in aid programs through age 12, according to two reports in the theme issue.

In the first, Harriet J. Kitzman, R.N., Ph.D., of University of Rochester, N.Y., and colleagues studied 613 12-year-old children, 228 of whose mothers were randomly assigned to receive home visits by nurses during the prenatal period and until the child was age 2. The other mothers received prenatal care and developmental screening and referral for the children, but no home visits.

“Through age 12, the program reduced children’s use of substances and internalizing mental health problems and improved the academic achievement of children born to mothers with low psychological resources,” the authors write.

In the second paper, David L. Olds, PhD, University of Colorado Denver Anschutz Medical Campus, and colleagues assessed partner relationships, fertility, economic self-sufficiency and government spending among the mothers in the study. By the time the child was age 12, nurse-visited mothers as compared with control mothers reported less role impairment due to substance use (0 percent vs. 2.5 percent), longer partner relationships (59.6 months vs. 52.6 months) and a greater sense of mastery.

During the 12-year period, the government spent less through aid programs on nurse-visited families ($8,772 vs. $9,797); this represents $12,300 in discounted savings compared with the program cost of $11,511.

“In general, these findings support the effectiveness of the Nurse-Family Partnership,” the program providing the nurse visits, the authors write. “The partnership offers a means of reducing government spending and family poverty, improving children’s health and development and grounding policy based on the results of replicated randomized controlled trials.”

(Arch Pediatr Adolesc Med. 2010;164[5]:412-418, 419-424.)

Repetitive Movements Common in Children With a History of Institutional Care

Stereotypies””repetitive, unchanging movements with no obvious goal or function””appear common among children who have a history of early institutional care. Karen J. Bos, of Children’s Hospital Boston and Harvard Medical School, Boston, and colleagues studied 136 children from institutions in Bucharest, Romania.

After a baseline assessment, half of the children remained in their institutions, whereas the other half were assigned to be placed in foster care. At the initial assessment, more than 60 percent of children in institutional care exhibited stereotypies. At follow-up assessments 30 months, 42 months and 54 months later, children placed in foster care experienced a reduction in stereotypies, with earlier and longer placements resulting in larger reductions.

“Children who continue to exhibit stereotypies after foster care placement are significantly more impaired on outcomes of language and cognition than children without stereotypies and thus may be a target for further assessments or interventions,” the authors write. “These findings have implications beyond the unique population of children in orphanages, as the extreme example of institutional care can help us to better understand the impact of deprivation on children in many settings.”

(Arch Pediatr Adolesc Med. 2010;164[5]:406-411.)

Living With Birth Parents After Maltreatment Associated With Altered Cortisol Levels

Children who continue to live with their birth parents after the involvement of Child Protective Services appear to have different daily patterns in production of the stress hormone cortisol than do children who are placed in foster care. Kristin Bernard, M.A., and colleagues at the University of Delaware, Newark, studied 339 children at 2.9 to 31.4 months, 155 of whom were living with birth parents and 184 of whom were placed in foster care following an incident requiring the involvement of Child Protective Services.

The children’s salivary cortisol levels were measured at waking and bedtime on two days. Children who still lived with their parents had different patterns of cortisol production than those in foster care, with flatter slopes in waking to bedtime values.

“A blunted pattern of cortisol production appears to confer risk for later psychiatric disorders, most especially psychopathy and substance abuse problems,” the authors write. “Although it is premature to suggest specific implications for neglected children, the findings are concerning.”

“Foster care may have a regulating influence on children’s cortisol among children who have experienced maltreatment,” they conclude.

(Arch Pediatr Adolesc Med. 2010;164[5]:438-443.)

Editorial: Behavioral Interventions Should Target Caregiver Relationships

“We live in a universe where the disruptive behaviors so often exhibited by children in child welfare are easily ascribed to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnoses of attention-deficit, bipolar or oppositional defiant disorders,” write David Rubin, M.D., M.S.C.E., and Kathleen Noonan, J.D., of The Children’s Hospital of Philadelphia, in an accompanying editorial.

“Missing from that discussion is that at the heart of many of these disruptive behaviors are the biological effects of failed relationships, failed attachment and multiple traumatic disruptions,” they write. “The strength of the Bernard et al and Bos et al articles in this month’s Archives is that they demonstrate that such injuries produce neurobiological alterations whose treatment is more likely to be successful with interventions that target attachment failure than the symptoms of disruptive behaviors targeted by medications.”

“The work ahead is in understanding and supporting secure and functional caregiver relationships that lead to the sustained changes in the brain that will promote resiliency in children,” they conclude.

(Arch Pediatr Adolesc Med. 2010;164[5]:492-493.)

Twin With Higher Birth Weight Has More Conduct Problems

Among twin pairs in which there is a 20 percent or greater difference in birth weight, the twin who weighs more appears more likely to have conduct problems at age 3 to 4 years. David Mankuta, M.D., of Hadassah Hebrew University Hospital, Jerusalem, and colleagues identified 112 Israeli families with twins born at unequal weights in 2004 and 2005.

According to mothers’ reports, the twin with the higher birth weight had more conduct problems in 41 percent of twin pairs, whereas the twin with lower birth weight had more conduct problems in 21 percent of twin pairs. This association tended to be stronger in dizygotic (fraternal) vs. monozygotic (identical) twins.

“The findings suggest an effect of birth weight differences on development of subsequent conduct problems,” the authors write. “Further studies are needed to clarify the mediating factors of this effect.”

(Arch Pediatr Adolesc Med. 2010;164[5]:457-461.)

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On the Net:

• Archives of Pediatrics & Adolescent Medicine

Norwegian researchers say that pregnant women are three times more likely to suffer from severe morning sickness if their mothers did.

About 2 percent of women suffer from excessive nausea and vomiting in pregnancy, which can require hospital treatment.

However, a study of 2.3 million births showed threefold higher numbers if mothers had moms that suffered the same condition.

Experts said the results might help women better understand their risk.

Hyperemesis is an excessive sickness that starts before the 22nd week of pregnancy, which can lead to dehydration and weight loss.

This is the most common cause of admission to hospital in early pregnancy and can lead to low birth weight and premature birth.

Previous studies have attributed the condition to “psychological causes,” according to the researchers.

The researchers analyzed birth records from 1967 to 2006, which included information on pregnancy complications.

The study found that daughters of women who had the condition during their pregnancy had a 3 percent higher risk, compared with 1 percent in those whose mothers did not have it.

However, there was no increased risk to the female partners of sons that had mothers with previous conditions.

The team said that even though the results found a genetic link between mothers and daughters, it is also possible there are lifestyle or environmental factors that are shared between mothers and daughters that increase the risk.

The researchers said the study “shed a new light” on the causes of hyperemesis in pregnancy.

“It might lead to a better appreciation of the underlying biology,” they added.

Catherine Nelson-Piercy, a consultant obstetric physician at Guy’s and St. Thomas’ Foundation Trust in London, told BBC News that clinicians might benefit from a better understanding of the genetic risks of hyperemesis when counseling women about the risk of recurrence in future pregnancies.

She said most women were under-treated due to the legacy of thalidomide, despite the availability of safe drugs.  Thalidomide is a drug given for morning sickness in the 1960s that caused birth defects.

“It can be extremely debilitating, women can’t work, can’t look after their families and they need to be admitted to hospital,” Piercy told BBC.

“It is safe to take anti-sickness drugs and it’s better for the baby and the pregnancy to treat this condition than let the woman get very severely ill and risk complications.”

The spokesman for the Royal College of Obstetrics and Gynecology, Patrick O’Brien, said the study showed growing evidence that many conditions in pregnancy, like diabetes or high blood pressure, were linked to a “genetic predisposition.”

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On the Net:

• BMJ

Children normally experience flights of fancy, including imaginary friends and conversations with stuffed animals, but some of them are also having hallucinations and delusions which might be the early signs of psychosis.

A study of British 12-year-olds that asked whether they had ever seen things or heard voices that weren’t really there, and then asked careful follow-up questions, has found that nearly 6 percent may be showing at least one definite symptom of psychosis.

The children who exhibited these symptoms had many of the same risk factors that are known to correlate with adult schizophrenia, including genetic, social, neurodevelopmental, home-rearing and behavioral risks.

“We don’t want to be unduly alarmist, but this is also not something to dismiss,” said co-author Terrie Moffitt, the Knut Schmidt Nielsen professor of psychology and neuroscience and psychiatry & behavioral sciences at Duke University. The study appears in the April issue of Archives of General Psychiatry.

The children were participants in the long-term Environmental Risk Longitudinal Twin Study in Britain, which includes 2,232 children who have been tracked since age 5 and reassessed at 7, 10 and 12.

The British study is an outgrowth of research that the same group did earlier with a long-term cohort in Dunedin, New Zealand. At age 11, those children were asked about psychotic symptoms, but the researchers waited 15 years to see how, as adults, their symptoms matched what they reported at 11. By age 26, half of the people who self-reported symptoms at age 11 were found to be psychotic as adults.

“It looks like a non-trivial minority of children report these symptoms,” said co-author Avshalom Caspi, the Edward M. Arnett professor of psychology and neuroscience and psychiatry & behavioral sciences at Duke.

The findings provide more clues to the development of schizophrenia, but don’t solve any questions by themselves, said co-author Richard Keefe, director of the schizophrenia research group in the department of psychiatry and behavioral sciences at Duke.

Schizophrenia often goes undetected until adolescence, when the first overt symptoms ““ antisocial behavior, self-harm, delusions ““ begin to manifest in an obvious way. But nobody knows whether the disease is triggered by the process of adolescence itself, or brain development or hormone changes. “It’s my impression that all of those things interact,” Keefe said.

Psychotic symptoms in childhood also can be a marker of impaired developmental processes, and are something caregivers should look for, Moffitt said. “There is not much you can do except monitoring and surveillance,” Moffitt said. “But we feel we should be alerting clinicians that there’s a minority to pay attention to.”

While the incidence of psychotic symptoms in this study was around 5 or 6 percent, the adult incidence of schizophrenia is believed to be about 1 percent, Keefe added. There are some recent findings however, that many more people experience hallucinations and delusions without being diagnosed as psychotic, he said.

The research was supported by the U.S. National Institutes of Health, UK Medical Research Council, The National Alliance of Research on Schizophrenia and Depression, the Health Research Board of Ireland and the William T. Grant Foundation.

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On the Net:

• Duke University
• Etiological and Clinical Features of Childhood Psychotic Symptoms, Guilherme Polanczyk et al, Archives of General Psychiatry, April 2010

Medicine and mathematics are being combined to develop powerful new scientific weapons to combat killer diseases.

This year’s ‘Science at the Shine Dome’ Symposium brings together some of the finest minds from Australia and around the world to explore how medicine and mathematics are working together to throw new light on the complex genetics that underlie diseases such as cancer.

The Symposium, entitled Genomics and Mathematics, will be held at the Australian Academy of Science’s Shine Dome, on 7 May 2010. Media are welcome to attend and interview participants.

‘In a number of diseases ““ cancer, for example ““ we’re beginning to discover that some of the genes that many of us carry make us more susceptible and to see possible treatments based on our knowledge of the genetic changes that appear to be major causal factors. But we’ve only scratched the surface of these kinds of analyses,’ explains symposium organizer Professor Peter Hall.

‘The real challenge is to discover which genetic features are linked to which disease, and how. In this process of discovery, mathematics and statistics are working hand in hand with medicine and biology, allowing scientists to quantify not just the existence of connections between genes and disease, but also the strength of these associations.’

‘Applying exciting new mathematical and statistical tools in medicine enables us to explore the genetic basis of disease far more than we could using more conventional methods. This reveals patterns that would not otherwise be detectable. And these in turn can potentially lead to better approaches to diagnosis and treatment.’

Highlights of the symposium include:
“¢ Professor Terry Speed, of the Walter and Eliza hall Institute will talk about the spectacular growth in genome data in the last two years and its implications for understanding and treating all kinds of disease.

“¢ Professor Simon Tavar© of the Department of Oncology, University of Cambridge, UK, will speak about ‘Combining genomics and mathematics to learn about cancer’.

“¢ Professor Susan Clark of the Garvan Institute of Medical Research will speak about ‘Epigenetics & Genetics: Discovery of layers of change in the cancer genome’.

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On the Net:

• Details of the Symposium program are at: http://www.science.org.au/events/sats/sats2010/symposium.html