Baclofen, esomeprazole investigated as treatments

The impact of upper GI conditions, like gastroesophageal reflux disease (GERD) and functional dyspepsia, on sleep””and treatments aimed at providing relief to heartburn/acid reflux patients who suffer from disordered sleep””were explored in three new studies related to sleep dysfunction presented today at the American College of Gastroenterology’s (ACG) 75th Annual Scientific meeting in San Antonio, Texas.

Functional dyspepsia is a common, but poorly understood, upper GI condition affecting approximately 10 percent of U.S. adults. The condition is described as chronic abdominal pain and a sensation of fullness, pressure or discomfort in the upper abdomen. This sensation is associated with eating as symptoms usually worsen after meals.

While the prevalence of disordered sleep in patients with functional dyspepsia is unknown, a new study unveiled today found that disordered sleep is significantly more common in functional dyspepsia patients than in healthy controls.

Patients with functional dyspepsia were 3.25 times more likely to have disordered sleep compared to healthy controls, according to the study, “Functional Dyspepsia: A Risk Factor for Disordered Sleep,” which also found that women with functional dyspepsia were 2.3 times more likely to have disordered sleep than men with this same condition. While gender tended to be associated with disordered sleep, age, tobacco and alcohol use was not a factor. The study also found that mental and physical factors were related to disordered sleep in patients with functional dyspepsia.

Routine exercise, for instance, appeared to decrease the likelihood of a patient suffering from sleep disorders. Functional dyspepsia patients also had higher scores for anxiety and depression, according to the study, suggesting that depression may be a contributing factor to functional dyspepsia symptom generation.

“Fatigue changes the sensation for pain, said Brian Lacy, M.D., Ph.D., associate professor of medicine, Dartmouth Medical School who presented the results of the study. “The key finding here is that disordered sleep may affect nerve function in upper GI tract which could lead to worsening dyspepsia, creating a vicious cycle leading to more pain and more insomnia,” said Dr. Lacy. He added that, “future clinical trials for functional dyspepsia should include validated measures of sleep, as improvements in functional dyspepsia symptoms may be mirrored by improvements in sleep.”

Esomeprazole Reverses Driving Impairment in GERD Induced Sleep Disorders

GERD”Âinduced sleep dysfunction has a previously unrecognized and significantly adverse affect on simulated driving performance, which improved with esomeprazole, according to the results of another study, “GERD”ÂInduced Sleep Disorders and a Reversible Driving Impairment with Esomeprazole”ÂA Prospective Pilot Study.”

Dr. David A. Johnson, Chief of Gastroenterology and Professor of Medicine at Eastern Virginia Medical School in Norfolk, Va., presented the findings from this prospective”Âpilot study that evaluated 11 healthy patients with well”Âestablished GERD with nocturnal symptoms.

Testing was done in a validated commercial driving simulator that responds to driver inputs (steering, throttle, brake) and generates realistic roadway images. Driving performance (standard deviation of lane variation SDLP) was compared across six consecutive 10″Âminute driving periods while subjects were on and off the drug.

According to the study, SDLP increased over time (p=0.0002) and improved with esomeprazole. Patients on esomeprazole had an overall average 62.5 percent decrease in the number of sleep disordered nights vs. a 9.5 percent decrease without the drug. The Epworth Sleepiness Scale, used to determine the level of daytime sleepiness, decreased to 5.9 and 3.5 from 7.9 and 2.5 and GERD symptom score decreased from 2.10 to 0.33.

“The improved ESS score suggests that reduced sleepiness contributed to improved performance,” said Dr. Johnson. “We know that GERD impairs sleep quality and next day function as measured by quality of life and work productivity assessments. Furthermore, sleep dysfunction (such as sleep apnea) has been linked to impaired psychomotor function including worsening driving simulator performance.

Therefore, appropriate treatment for patients with GERD and nocturnal symptoms may have potentially new and life”Âsaving implications.”

Dr. Johnson also noted that further prospective blinded controlled trials are warranted to validate these findings.

Baclofen Decreases Reflux, Improving Sleep Quality for Nighttime Heartburn Sufferers

Nighttime heartburn sufferers also may get relief “”and better sleep quality, from the muscle”Ârelaxant and antispastic drug, baclofen, according to results of another new study unveiled today, “Baclofen Decreases Reflux and Improves Sleep Quality in Individuals with Nighttime Heartburn.”

While baclofen has been shown to reduce episodes of GERD, this new study found that in addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GERD and sleep disturbances.

“About 70 percent of individuals who have GERD also suffer from nighttime heartburn, and 40 percent of those people say they experience disturbed sleep at night,” said study co”Âauthor Dr. William Orr, president and CEO of the Lynn Health Science Institute and a clinical professor of medicine at the University of Oklahoma Health Sciences Center. “They don’t feel good the next day and they don’t perform as well.”

Approved by the FDA in 1977, bacolfen is typically used by neurologists to treat uncontrolled movements, such as shakes and tremors. The drug inhibits nerve activity within the part of the brain that controls the contraction and relaxation of skeletal muscles.

“In this study, we found that bacolfen significantly reduces the amount of waking which occurs after the onset of sleep,” said Dr. Orr. “Baclofen addresses the physiological causes of reflux, by preventing the relaxation of the lower esophageal sphincter and preventing the stomach acid from entering the esophagus. Few drugs inhibit the occurrence of reflux and 40 to 50 percent of those taking PPIs don’t get satisfactory relief, especially at nighttime,”

Baclofen reduced the number of reflux events compared to a placebo (4 events vs. 1.3). Patients on baclofen also had more sleep time (434 minutes vs. 379 minutes) and greater sleep efficiency (91 percent vs. 79 percent), according to the study. “The results of this study suggest that baclofen could be a useful adjunct therapy to proton pump inhibitors in patients with nighttime heartburn and sleep disturbance,” said Dr. Orr.

—

On the Net:

• American College of Gastroenterology

Yale University researchers have found a gene that seems to be a key contributor to the onset of depression and is a promising target for a new class of antidepressants, they report Oct. 17 in the journal Nature Medicine.

“This could be a primary cause, or at least a major contributing factor, to the signaling abnormalities that lead to depression,” said Ronald S. Duman, professor of psychiatry and pharmacology at Yale and senior author of the study.

Scientists have had a difficult time pinning down the cause of depression, which afflicts almost 16 percent of Americans in any given year and carries an annual economic burden of $100 billion.

Symptoms of depression vary widely among individuals. Most now believe that multiple physiological processes are involved in major depressive disorder. That explains why people respond differently to most commonly prescribed antidepressants, which work by manipulating the uptake of the neurotransmitter serotonin. However, as many as 40 percent of depressed patients do not respond to currently available medications, which take weeks to months to produce a therapeutic response.

Duman’s team did whole genome scans on tissue samples from 21 deceased individuals who had been diagnosed with depression and compared gene expression levels to those of 18 individuals who had not been diagnosed with depression. They found that one gene called MKP-1 was increased more than two-fold in the brain tissues of depressed individuals.

This was particularly exciting, say the researchers, because the gene inactivates a molecular pathway crucial to the survival and function of neurons and its impairment has been implicated in depression as well as other disorders. Duman’s team also found that when the MKP-1 gene is knocked out in mice, the mice become resilient to stress. When the gene is activated, mice exhibit symptoms that mimic depression.

The finding that a negative regulator of a key neuronal signaling pathway is increased in depression also identifies MKP-1 as a potential target for a novel class of therapeutic agents, particularly for treatment resistant depression.

—

On the Net:

• Yale University
• Nature Medicine

A study that includes data on more than 100,000 patients who underwent coronary artery bypass graft surgery finds that there is wide variability among hospitals in the U.S. on the use of blood transfusions, without a large difference in the rate of death, suggesting that many transfusions may be unnecessary, according to a study in the October 13 issue of JAMA. Another study in this issue of JAMA examines the effect of a restrictive transfusion strategy on outcomes after cardiac surgery.

“Patients who undergo cardiac surgery receive a significant proportion of the 14 million units of allogeneic [taken from a different individual] red blood cells (RBCs) transfused annually in the United States,” the authors write. “Perioperative [around the time of surgery] blood transfusions are costly and have safety concerns. As a result, there have been multiple initiatives to reduce transfusion use. However, the degree to which perioperative transfusion rates vary among hospitals is unknown.”

Elliott Bennett-Guerrero, M.D., of Duke University Medical Center, Durham, N.C., and colleagues conducted a study to assess the use of RBC, fresh-frozen plasma, and platelet transfusions in coronary artery bypass graft (CABG) surgery in current practice, and to determine the degree to which transfusion practices vary among U.S. hospitals. The study included 102,470 patients undergoing CABG surgery during 2008 at 798 sites in the United States.

The researchers found significant variability in the observed hospital-specific transfusion rates for all 3 blood products among the patients and hospitals included in the study. To ensure that between-center differences would not be dominated by random statistical variation, the researchers also analyzed the subset of hospitals performing at least 100 eligible on-pump CABG operations during the year. At these 408 sites (n = 82,446 cases), the frequency of blood transfusion rates ranged from 7.8 percent to 92.8 percent for RBCs, 0 percent to 97.5 percent for fresh-frozen plasma, and 0.4 percent to 90.4 percent for platelets.

“Multivariate analysis including data from all 798 sites (102,470 cases) revealed that after adjustment for patient-level risk factors, hospital transfusion rates varied by geographic location, academic status, and hospital volume. However, these 3 hospital characteristics combined only explained 11.1 percent of the variation in hospital risk-adjusted RBC usage,” the authors write.

There was no significant association between hospital-specific RBC transfusion rates and all-cause mortality.

“As is the case in other areas of medicine, the degree of variability in clinical practice we observed represents a potential quality improvement opportunity. This is particularly complex in relation to transfusion practice in CABG surgery. The decision to transfuse has multiple triggers, resulting from a wide array of clinical scenarios and the consequent inability to apply standardized algorithms. The multiplicity of health care practitioners in CABG surgery care generates differences of opinion about safety and efficacy. Transfusion thresholds will change during the course of care; the threshold for a rapidly bleeding patient is different than for a stable patient postoperatively. Improvement in quality related to transfusion practice in CABG surgery is a multifactorial, complex but critically important, challenge,” the researchers write.

(JAMA. 2010;304[14]:1568-1575. Available pre-embargo to the media at www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Blood Transfusion as a Quality Indicator in Cardiac Surgery

In an accompanying editorial, Aryeh S. Shander, M.D., of Englewood Hospital and Medical Center, Englewood, N.J., and Lawrence T. Goodnough, M.D., of the Stanford University School of Medicine, Stanford, Calif., write that this study provides a snapshot of transfusion practices in a subset of patients undergoing cardiac surgery across the United States.

“The data showing highly variable transfusion rates are disconcerting. Yet despite magnitudes of differences between hospitals in terms of RBC transfusion rates, there were no significant differences in mortality rates between the hospitals. The absence of differences in mortality among centers with varying transfusion rates strongly suggests inappropriate transfusions.”

(JAMA. 2010;304[14]:1610-16111. Available pre-embargo to the media at www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

—

On the Net:

• JAMA and Archives Journals

In a Canadian first, the Peter Munk Cardiac Centre used a new kind of left ventricular assist device (LVAD) to treat a patient with advanced heart failure. The new device is longer lasting than older generation LVADs and may eliminate the need for a second LVAD ““ a major drawback with the old technology.

The patient, 61-year-old Marva Lorde of Mississauga, suffered a heart attack in 2007 and underwent several treatments for heart failure ““ including a 10-day intensive care unit stay, angioplasty and pacemaker implantation ““culminating in a cardiac arrest in June 2008.

“I would have died in my sleep if the nurse hadn’t checked my heart monitor,” says Marva who is at home after receiving her LVAD on July 29, 2010. “Before the LVAD, I had trouble climbing the stairs to my bedroom, but now I’m back to my usual activities, including regular walks, and the stairs don’t give me trouble anymore.”

Marva’s LVAD, known as the DuraHeart, is designed for long-term cardiac support and reduces the risk of complications including strokes, infection and device failure ““ all of which can happen in mechanical heart devices. The device’s central pump is powered by magnetic levitation technology, which means its moving parts are held in place with magnets instead of bearings, eliminating wear and tear on the device. This technology enables blood to flow through the pump smoothly, which extends the life of the device and the life of the patient.

“With access to eight different types of cardiac assist devices, including the Duraheart, we have the most diverse array of circulatory support technology in Canada to best manage patients with end stage heart failure,” says Dr. Vivek Rao, Surgical Director of the Heart Transplant Program at the Peter Munk Cardiac Centre (PMCC), Toronto General Hospital.

Heart failure is the most common cause of hospitalization in North American adults and over 50,000 are treated for advanced heart failure annually. Transplantation is the only long-term treatment for end-stage heart failure patients and the long wait times for a matching donor organ make it necessary to find other alternatives.

Marva is currently on the heart transplant waiting list along with 36 other GTA residents, and her LVAD is her lifeline since her weak heart needs support until a new heart becomes available. This “bridge to life” is an innovative approach pioneered in Canada by Dr. Vivek Rao.

“Part of the centre’s mandate is to evaluate new technologies such as the Duraheart to help determine which patients are best suited to a specific device,” says Dr. Rao who’s team has implanted approximately 70 LVADs since 2004, giving hope to many patients and families.

The Duraheart device has been used in patients in Germany and the United States.

—

On the Net:

• University Health Network

A deficiency in one of the immune system’s enzymes affects the severity of autoimmune diseases such as MS, and explains why the course of these diseases can vary so much. New findings give an insight into how this enzyme deficiency can be diagnosed, and could lead to new medicines, reveals a thesis from the Sahlgrenska Academy.

Multiple sclerosis (MS) and Guillain-Barr© syndrome (GBS) ““ the two autoimmune diseases covered by the thesis ““ can follow vastly different courses, with symptoms ranging from insignificant to life-threatening, the reason for which has been largely unknown. In the thesis the researchers have now found a factor in the immune defence that can explain this mechanism.

The immune system’s white blood cells play an important role in the fight against invading micro-organisms. They contain an enzyme called NADPH oxidase, which converts oxygen into reactive oxygen radicals. It has long been known that these oxygen radicals stop infections by breaking down micro-organisms. New studies using animal models have shown that inadequate production of oxygen radicals can lead to the development of autoimmune diseases, where a patient’s immune system attacks the body’s own tissues. This would indicate that oxygen radicals are important for preventing the occurrence of autoimmune diseases.

“We wanted to look at this in humans, and examined the NADPH oxidase in the white blood cells of patients with MS, GBS and recurring GBS (RGBS),” says Natalia Mossberg, doctoral student at the Institute of Neuroscience and Physiology at the Sahlgrenska Academy. “The results show that patients with more severe forms of the illness have lower levels of oxygen radical production in their white blood cells as a result of deficient NADPH oxidase function.”

The researchers discovered that the body’s ability to produce reactive oxygen radicals at an early stage in the immune defence against infections has a major impact on how these illnesses develop. “We’ve shown that a strong but controlled production of oxygen radicals by the immune system is important for subduing illnesses such as MS and GBS,” says Mossberg.

The researchers think that this method of measuring oxygen radical production in white blood cells can be used for investigating other autoimmune diseases and for diagnosing the severity of these illnesses. The discovery could also lead to a new approach to the treatment of MS in its early stages with medicines that trigger the production of NADPH oxidase or a vaccination for people at risk of developing this type of illness.

—

On the Net:

• University of Gothenburg

Twenty-two physical symptoms associated with cancer ““ symptoms often unrecognized and undertreated ““ are prevalent in all types of cancers regardless of whether the patient is newly diagnosed, undergoing treatment or is a cancer survivor, according to researchers from the Regenstrief Institute and the Indiana University schools of medicine and nursing.

Common symptoms include fatigue, pain, weakness, appetite loss, dry mouth, constipation, insomnia and nausea. These physical symptoms are associated with substantial functional impairment, disability and diminished quality of life.

The study of 405 patients was reported in the Oct. 11, 2010, issue of the Archives of Internal Medicine. Numerous physical symptoms, rather than just a few, were prevalent in patients with cancer and this prevalence did not diminish after completion of therapy.

“We found that regardless of where they are in the course of their diseases, many individuals with cancer have a high symptom burden,” said Kurt Kroenke, M.D., the study’s principal investigator and first author. Dr. Kroenke is a Regenstrief Institute investigator and a Chancellor’s Professor of Medicine in the IU School of Medicine.

“These symptoms impact them at home and at work throughout their lives,” he said.

Study participants, all of whom had pain, depression or both, experienced substantial disability, reporting on average 17 of the past 28 days as either bed days or days in which they had to cut down on activities by at least 50%. Almost all patients reported feeling tired (97.5%) and most (78.8%) were bothered “a lot” by this symptom. Of the 22 symptoms studied, 15 were reported by more than half of the study participants.

In spite of high symptom prevalence, the researchers did not uncover greater use of the health care system. There may be several explanations for this including patients’ inclinations to focus on cancer treatment while with their physicians or to accept the symptoms as an inevitable result of the disease or its treatment. Alternatively, the explanation may lie with the fact that those in the study, as cancer patients or former patients, were already frequently interacting with many parts of the health care system.

“Patients and their families should be encouraged to bring up symptoms like pain or insomnia with physicians. But because oncologists are necessarily focused on treatment of the cancer itself, they often have insufficient time to optimally evaluate and manage symptoms and other factors impacting quality of life. We have shown in an earlier study that one effective solution might be a partnership between a telephone-based symptom management team and community-based oncology practices,,” said Dr. Kroenke, who is a research scientist with the Center for Implementing Evidence-Based Practice at the Richard Roudebush VA Medical Center and an Indiana University Melvin and Bren Simon Cancer Center member.

The previous study, published earlier in 2010 in the Journal of the American Medical Association, reported that an economical, centralized approach is feasible to conduct and significantly improved symptoms of pain and depression in patients in any phase of cancer. That approach gave patients, many of whom lived in underserved rural areas, one-stop assistance they probably wouldn’t have had access to unless they went to a major cancer center, Kroenke said.

Recognizing and managing physical symptoms such as fatigue, pain, nausea, and insomnia may make a significant difference regardless of type or phase of cancer. The researchers plan to investigate medical and behavioral strategies and combinations of both approaches to control these symptoms.

—

On the Net:

• Indiana University School of Medicine
• Archives of Internal Medicine

Black Death, one of the deadliest pandemics in human history, has been confirmed by anthropologists to have been caused by a germ called Yersinia pestis.

Researchers studied tooth and bone samples from 76 skeletons discovered in “plague pits” in France, Germany, Italy and the Netherlands and found DNA evidence that Y. pestis was to blame for the plague that wiped out nearly a third of Europe’s population during the Middle Ages.

It was believed for more than a century that Y. pestis was the source of the so-called Black Death, which plagued Europe from the 1300s to the 1700s and possibly early 1800s. But scientific data to prove the bacterium was the actual culprit has been sketchy at best.

Because of this, many rival theories have come about, including opinions that an Ebola-style virus or the anthrax germ was to blame.

The new evidence also sheds light on the geographical route the germ took, which is believed to have originated in central or southern Asia before making its way into Europe through trade routes.

In the samples that researchers found Y. pestis genes, they ran a test for 20 DNA markers to identify a particular bacterial strain.

They wanted to know if it matched either of the other two Y. pestis strains that are floating around today, mostly in Africa, America, the Middle East and Russia. But neither of the two modern types, Orientalis and Medievalis, showed up.

Instead, two previously unknown types were found, both of them older than today’s strains and different from each other.

“The history of this pandemic is much more complicated than we had previously thought,” said Stephanie Haensch, a co-leader of the research, at Johannes Gutenberg University in Mainz, Germany.

Y. pestis showed up in Western Europe in November 1347, believed to be driven by fleas living on rats which made it to land from a merchant ship docked at the Mediterranean French port of Marseille.

After making landfall, it took six years for it to spread through western France to northern France and then over to England, again through commerce.

However, a different strain was discovered in a mass burial site in Bergen op Zoom, a port in the southern Netherlands, suggesting that Y. pestis also made entry from the north, perhaps from Norway via the Dutch province Friesland.

After its initial surge in 1347, the pandemic progressively spread around Europe, reducing the population by as much as 60 percent throughout its 4 century run, and causing far-reaching social and political impacts.

The findings were published in the open-access journal PLoS Pathogens.

—

Image Caption: A scanning electron microscope micrograph depicting a mass of Yersinia pestis bacteria. Credit: Rocky Mountain Laboratories, NIAID, NIH

—

On the Net:

• Johannes Gutenberg University
• PLoS Pathogens

(Ivanhoe Newswire) — A recent study pulls down the covers on contemporary American’s sexual behaviors.  The findings — with reference to 5,865 adolescent and adults ages 14 to 94 — include a description of more than 40 combinations of sexual acts that people perform when the lights go out, patterns of condom use by adolescence and adults, and the percentage of Americans participating in same-sex encounters.

The National Survey of Sexual Health and Behavior (NSSHB), one of the most inclusive studies on sexual behavior in roughly two decades, was conducted by researchers from the Center for Sexual Health Promotion (CSHP) in Indiana University’s School of Health, Physical Education, and Recreation (HPER).

“This survey is one of the most expansive nationally representative studies of sexual behavior and condom use ever conducted, given the 80-year span of ages,” which Michael Reece, director of the Center for Sexual Health Promotion, was quoted as saying.  “These data about sexual behaviors and condom use in contemporary America are critically needed by medical and public health professionals who are on the front lines addressing issues such as HIV, sexually transmissible infections and unintended pregnancy.”
The initial findings of the survey show that one of four acts of vaginal intercourse are condom protected in the United States (one in three among singles).

“These data, when compared to other studies in the recent past, suggest that although condom use has increased among some groups, efforts to promote the use of condoms to sexually active individuals should remain a public health priority,” Reece added.

“People are often curious about others’ sex lives,” which Debby Herbenick, associate director of the CSHP, was quoted as saying. “They want to know how often men and women in different age groups have sex, the types of sex they engage in, and whether they are enjoying it or experiencing sexual difficulties. Our data provide answers to these common sex questions and demonstrate how sex has changed in the nearly 20 years since the last study of its kind.”

The study helps promote awareness apropos patterns of condom use across different stages of people’s relationships and across ages for both the public and professionals alike.  Herbenick added that these “findings show that condoms are used twice as often with casual sexual partners as with relationship partners, a trend that is consistent for both men and women across age groups that span 50 years.”

Furthermore, there is vast variability in the sexual repertoires of the U.S. adults now, and adult men and women seldom engage in merely one sexual act when they have sex.  When it comes to sex, responsibility is just as important as pleasure is.  Condom use was reported being highest among African-Americans as well as Hispanic-Americans, compared to Caucasians and other racial groups.

“Many surveys of adolescent sexual behavior create an impression that adolescents are becoming sexually active at younger ages, and that most teens are sexually active,” which Dennis Fortenberry, M.D., professor of pediatrics in the IU School of Medicine, was quoted as saying.  “Our data show that partnered sexual behaviors are important but by no means pervasive aspects of adolescents’ lives.  In fact, many contemporary adolescents are being responsible by abstaining or by using condoms when having sex.”

Additional key findings highlighted in the collection of papers include:

“¢ There is enormous variability in the sexual repertoires of U.S. adults, with more than 40 combinations of sexual activity described at adults’ most recent sexual event.

“¢ Many older adults continue to have active pleasurable sex lives, reporting a range of different behaviors and partner types; however adults over the age of 40 have the lowest rates of condom use. Although these individuals may not be as concerned about pregnancy, this suggests the need to enhance education efforts for older individuals regarding STI risks and prevention.

“¢ About 85 percent of men report that their partner had an orgasm at the most recent sexual event; this compares to the 64 percent of women who report having had an orgasm at their most recent sexual event. (A difference that is too large to be accounted for by some of the men having had male partners at their most recent event.)

“¢ While about 7 percent of adult women and 8 percent of men identify as gay, lesbian or bisexual, the proportion of individuals in the U.S. who have had same-gender sexual interactions at some point in their lives is higher.

“¢ At any given point in time, most U.S. adolescents are not engaging in partnered sexual behavior. While 40 percent of 17 year-old males reported vaginal intercourse in the past year, only 27 percent reported the same in the past 90 days.

“¢ Adults using a condom for intercourse were just as likely to rate the sexual extent positively in terms of arousal, pleasure and orgasm than when having intercourse without one.

SOURCE: The Journal of Sexual Medicine, October 2010

(Ivanhoe Newswire) ““ Poverty and the stresses that come along with it have long been correlated to neglect and child abuse, but this study shows that unemployment leads to maltreatment of children only one year later. With the increasing rates of unemployment in the U.S. it is important to not let the stress of life affect innocent children.

The researchers reviewed state-level unemployment statistics from the Bureau of Labor Statistics, and compared them with child maltreatment data from the National Child Abuse and Neglect Data System (NCANDS), during the years 1990 to 2008. Each 1 percent increase in unemployment was associated with at least a 0.50 per 1,000 increase in confirmed child maltreatment reports one year later. In addition, higher levels of unemployment appeared to raise the likelihood of child maltreatment, as it was not only the lagged change in unemployment, but also the previous year’s unemployment level that influenced the number of child abuse cases.

According to the study, the rise in unemployment lasting for years, not only affects the economy of our country but also the physical and mental health of children. These children suffer the immediate physical and emotion abuse associated with a lost job. These kids have to deal with physical injury, mental and emotional abuse, neglect, and sometimes even death. It has been proven that these children and at an increased risk of physical and mental health effects that usually last their entire lives.

“When times are bad, children suffer,” study author Robert Sege, MD, PhD, FAAP, professor of pediatrics, Boston University School of Medicine, and director, Division of Ambulatory Pediatrics, Boston Medical Center was quoted as saying. “These results suggest that programs to strengthen families and prevent maltreatment should be expanded during economic downturns.”

SOURCE: The American Academy of Pediatrics (AAP) National Conference and Exhibition, held in San Francisco, October 2010

Doctors provide strategy to improve outcomes

Almost 50 percent of patients undergoing orthopedic surgery have vitamin D deficiency that should be corrected before surgery to improve patient outcomes, based on a study by researchers at Hospital for Special Surgery (HSS) in New York City. Vitamin D is essential for bone healing and muscle function and is critical for a patient’s recovery. The study appears in the October issue of The Journal of Bone and Joint Surgery.

“In the perfect world, test levels, fix and then operate,” said Joseph Lane, M.D., professor of Orthopedic Surgery and chief of the Metabolic Bone Disease Service at HSS, who led the study. “If you put people on 2,000-4,000 [milligrams] of vitamin D based on what their deficient value was, you can usually get them corrected in four to six weeks, which is when you are really going to need the vitamin D. If you are really aggressive right before surgery, you can correct deficient levels quickly, but you have to correct it, measure it, and then act on it.”

According to Dr. Lane, bone remodeling or bone tissue formation, a part of the healing process, occurs about two to four weeks after surgery. This is the critical stage when your body needs vitamin D.

For their study, investigators conducted a retrospective chart review of 723 patients who were scheduled for orthopedic surgery between January 2007 and March 2008 at HSS. They examined the vitamin D levels, which had been measured in all patients before their surgery, and found that 43 percent had insufficient vitamin D and 40 percent had deficient levels.

Vitamin D inadequacy was defined as <32 ng/mL, vitamin D insufficiency was defined as 20 to <32 ng/mL, and vitamin D deficiency was defined at <20 ng/mL. Problems were more prevalent in younger patients, men and individuals with dark skin””blacks and Hispanic.

The highest levels of deficiency were seen in patients in the trauma service, where 66 percent of patients had insufficient levels and 52 percent had deficient levels. Of the patients undergoing foot and ankle surgery, 34 percent had inadequate levels and of patients undergoing hand surgery, 40 percent had insufficient levels.

In the Sports Medicine Service, 52.3 percent had insufficient levels and of these, one-third of these or 17 percent of the total had deficient levels. “We frequently see stress fractures in the Sports Medicine Service and if you want to heal, you have to fix the calcium and vitamin D,” Dr. Lane said.

In the Arthroplasty Service, which conducts hip and knee replacements, 38 percent had inadequate levels and 48 percent had deficient levels. “With arthroplasty, there is a certain number of patients that when you put in the prothesis, it breaks the bone adjacent to the protheses, which can really debilitate patients.” This could be prevented or minimized by rectifying vitamin D levels. Dr. Lane also explained that they now perform procedures where they grow a bone into a prosthesis without using cement. “In those people, it would be an advantage to have adequate vitamin D, because it matures the bone as it grows in, it is really healing into the prosthesis,” he said.

“The take home message is that low vitamin D has an implication in terms of muscle and fracture healing, it occurs in about 50 percent of people coming in for orthopedic surgery, and it is eminently correctable,” Dr. Lane said. “We recommend that people undergoing a procedure that involves the bone or the muscle should correct their vitamin D if they want to have an earlier faster, better, result. What we are saying is ‘wake up guys, smell the coffee; half of your patients have a problem, measure it, and if they are low, then fix it.'”

In recent years, vitamin D deficiency has been recognized as a common phenomenon and is caused by many factors. It is difficult to get from foods, except, for example, cod liver oil and fish. Until recently, the recommended daily allowance was set too low so foods were not supplemented with adequate doses. And third, while people can absorb vitamin D from sunlight, people these days often work long hours and often use sunscreen that impedes vitamin D intake.

—

On the Net:

• Hospital for Special Surgery
• The Journal of Bone and Joint Surgery

In this week’s PLoS Medicine, Gabriel Leung from the Government of the Hong Kong SAR and Angus Nicoll from the European Centre for Disease Prevention and Control offer their reflections on the international response to the 2009 H1N1 influenza pandemic, including what went well and what changes need to be made on the part of global and national authorities in anticipation of future flu pandemics.

—

On the Net:

• Public Library of Science
• PLoS Medicine

Researchers of the University of Granada, in collaboration with the Centre for Sensory-Motor Interaction of the University of Aalborg, Denmark, and the University Rey Juan Carlos, Madrid, conducted a research on chronic impingement syndrome. The study revealed that excessive activation of specific neck and shoulder muscles during daily life or while playing sports ““as swimming”“ is the cause of a high number of injury and shoulder.

A Common Pain

The pattern of the pain originated in these muscles ““sometimes in regions far from the shoulder”“ coincides with most of the symptoms suffered by patients attending health care centers for this type of problem. 25 out of 1,000 visits to the family doctor are related to shoulder pain, and the causes of this problem are several. The chronic impingement syndrome is considered the main cause for shoulder pain and disability.

The study conducted by Amparo Hidalgo-Lozano, Ph.D candidate of the department of Physiotherapy of the University of Granada, under the supervision of professor Manuel Arroyo Morales, opens the door to future tests to the efficacy of Physiotherapy as a non-invasive treatment for shoulder injury. Shoulder injury is the cause of 13% of sick leaves and implies a cost of 7 billion dollars in the USA.

This research was published in the last issue of the prestigious journal Experimental Brain Research.

—

On the Net:

• University of Granada
• Experimental Brain Research

Patients with triple negative breast cancer that also have mutations in the BRCA gene appear to have a lower risk of recurrence, compared to those with the same disease without the deleterious genetic mutation, according to researchers at The University of Texas MD Anderson Cancer Center.

The findings may offer a direction for study of personalized therapy in this select group of triple negative breast cancer patients, as well as highlight the unique need for genetic testing in a patient population. Ana M. Gonzalez-Angulo, M.D., associate professor in MD Anderson’s Departments of Breast Medical Oncology and Systems Biology presented the findings in advance of the 2010 Breast Cancer Symposium.

“There is data on the number of breast cancer patients with BRCA mutations, as well as those that have triple negative disease. However, there is no understanding of the incidence of BRCA1 and 2 mutations in unselected patients with triple negative breast cancer,” said Gonzalez-Angulo, the study’s first and corresponding author. “Now, there are new drugs that appear to be more effective in treating triple negative breast cancer and BRCA status may be an important way of selecting patients that may respond to these therapies.”

Triple negative disease – breast cancer that is estrogen, progesterone and HER2-neu receptor negative – accounts for about 15 percent of all breast cancers. Currently, it’s an area of much research focus in the breast cancer community because: it lacks effective targets effective for anti-cancer therapies; chemotherapy is only effective in about 40 percent of patients; and in those that do relapse, the disease is highly resistant and patients die quickly.

PARP inhibitors, a class of drugs of growing interest in cancer research, have shown promise in both patients with BRCA and triple negative disease. PARPs appear to be more effective in patients with BRCA mutations, as both PARP enzymes and proteins produced by the BRCA genes are involved in the repair of DNA. Therefore, the MD Anderson finding may provide an early idea of how to select those triple negative breast cancer patients that may respond best to therapy.

For this study, part of Gonzalez-Angulo’s ongoing laboratory project, Molecular Characterization of Triple Negative Breast Cancer, the researchers sent both tumor and normal tissue of 77 women with triple negative disease to Myriad Genetics Inc. to identify germline (inherited) and somatic (in tumor only) BRCA mutations. Of those 77 patients, 15 (19.5 percent), were found to have mutations (14 germline, one somatic) -12 (15.6 percent) with BRCA1 and three (3.9 percent) with BRCA2.

The triple negative breast cancer patients were treated at MD Anderson between 1987 and 2006, and all but one received the same adjuvant chemotherapy regimen. The median follow-up was 43 months. The five-year relapse-free and five-year overall survival of the patients with either BRCA mutation, was 86,2 percent, and 73.3 percent, respectively, compared to 51.7 percent and 52.8 percent, respectively, in patients lacking mutations.

The researchers were surprised by the findings, however, Gonzalez-Angulo notes that prior studies conducted were case-controlled looking at BRCA mutations carriers with all types of breast cancer. The MD Anderson study is the first to look exclusively at women with triple negative breast cancer, an unselected population.

Also surprising, the incidence of BRCA mutations in the triple negative breast cancer population was higher than expected, said Gonazlez-Angulo.

“It was interesting to find that a good portion of these women were not sent to genetic counseling – some didn’t meet the criteria to be sent for testing, however they still had BRCA mutations,” said Gonazlez-Angulo. “Perhaps we need to lower our threshold for patients with triple negative breast cancer for genetic counseling and to assess for mutation status – especially those under age 50 – despite not having the significant family history as others.”

As a follow up, Gonzalez-Angulo plans to continue her ongoing laboratory research, with signaling pathways, RNA, DNA, and other mutations of the disease.

—

On the Net:

• University of Texas M. D. Anderson Cancer Center

In recent human trials for a promising new class of drug designed to target the hepatitis C virus (HCV) without shutting down the immune system, some of the HCV strains being treated exhibited signs of drug resistance.

In response, an interdisciplinary team of Florida State University biologists, chemists and biomedical researchers devised a novel genetic screening method that can identify the drug-resistant HCV strains and the molecular-level mechanisms that make them that way ““”“ helping drug developers to tailor specific therapies to circumvent them.

The potentially life-saving technology also works when screening other viruses with drug-resistance issues, notably human immunodeficiency virus (HIV) and influenza.

More than 170 million people worldwide are infected with HCV, which leads to both acute and chronic liver diseases.

“In collaboration with pharmaceutical firm Gilead Sciences and researchers from the University of Heidelberg (Germany), what our research team discovered was how the latest drug for HCV works and what changes in the virus that makes it resistant to this unique therapy,” said Hengli Tang, a Florida State University molecular biologist.

“This is knowledge that is essential to drug developers focused on HCV,” said Tang, “but equally important is that our method, which we call “ËœCoFIM’ (Cofactor-independent mutant) screening, can also be applied to other drug targets and other viruses.

“And, since we now understand how this latest class of drug works and what causes resistance to it, we can better select other classes of drugs with distinct mechanisms ““”“ in other words, those that target other parts of the virus ““”“ in order to craft a combination therapy, which is the future of HCV therapy and the key to overcoming drug resistance.”

The groundbreaking research is described in a paper published online in the September 2010 issue of the journal PLoS Pathogens.

Florida State biology doctoral student Feng Yang led the research team. The award-winning scholar earned her Ph.D. in August 2010 and is now a postdoctoral associate at Yale University. Yang designed the CoFIM screening methodology with fellow FSU graduate students, postdoctoral associates and distinguished faculty colleagues ““”“ including Associate Professor Tang; chemistry/biochemistry Professor Timothy M. Logan, director of FSU’s Institute of Molecular Biophysics; and Research Assistant Professor Ewa A. Bienkiewicz, of the FSU College of Medicine, where she directs the Biomedical Proteomics Laboratory.

Driving the team’s development of CoFIM screening was the need to identify key “cellular cofactors” and their mechanisms of action ““”“ a fundamental aspect of virus-host interaction research.

“‘Cellular cofactors’ are proteins that normally exist in host cells that have been hijacked by viruses to facilitate viral replication.” Tang said. “They became accomplices to the invading viruses.

“Our research team was the first to show that “Ëœcyclophilin A’ (CyPA) is an essential cellular cofactor for hepatitis C virus infection and the direct target of a new class of clinical anti-HCV compounds, which include cyclosporine A (CsA)-based drugs that are devoid of immunosuppressive function,” Tang said.

“In addition, we went a step further than other research teams by employing our newly developed CoFIM screening method, which we used to demonstrate not only HCV’s dependence on cellular cofactor cyclophilin A and susceptibility to cyclosporine A drugs but also to uncover the molecular-level regulators that determine those two traits in the virus.”

Those molecular-level regulators are known as “small interfering RNA libraries” ““”“ collections of molecules so named for their size and ability to suppress gene expression. They act to individually suppress every gene in the cell, resulting in different consequences depending upon which gene is suppressed by a given member in the library.

The CoFIM screening method involves inducing or “coaxing” the HCV virus to mutate by itself, in vitro, absent the replication assistance it normally receives from a particular cellular cofactor. Then, CoFIM tracks the changes in the virus’s response both to CsA-based drugs and any other drug designed to inhibit the cofactor.

Funding for the research conducted at Florida State University came in largest part from a $1.4 million grant awarded by the National Institutes of Health (NIH). And, because chronic liver disease caused by HCV can lead to liver cancer, a grant from the American Cancer Society provided additional support.

—

On the Net:

• The Florida State University
• PLoS Pathogens

Federal funding of embryonic stem cell research will be allowed to continue for the time being, the U.S. Court of Appeals in the Washington, D.C. Circuit ruled on Tuesday.

The decision lifts an injunction put into place by Chief Judge Royce Lamberth on August 23.

According to Reuters, the three-judge panel ruled in favor of those supporting the National Institutes of Health (NIH) guidelines, stating that they had “satisfied the standards required for a stay pending appeal.” That “unusually quick” decision, in the words of AP writer Nedra Pickler, came just one day after the judges heard arguments from both sides on Monday.

Lamberth had previously ruled that the Obama administration’s policy regarding the funding violated the Dickey-Wicker amendment, a federal law barring the use federal tax funds to sponsor research that would cause human embryos to be destroyed.

“Congress remains perfectly free to amend or revise the statute,” Lamberth had written in a September 9 order upholding the injunction. “This court is not free to do so.”

During Monday’s testimony, Deputy Assistant Attorney General Beth Brinkmann told the appeals court judges that the injunction would stop funding to 24 research projects at the NIH–projects which, she said, had already received more than $60 million in taxpayer funds.

When challenged on her claims by Judge Thomas Griffith, who asked whether or not the work for be irreparably harmed due to the injunction, she responded that it would “be a setback” and that biological materials would have to be destroyed as a result.

Joining Griffith on the panel were justices Judith Rodgers and Brett Kavanaugh. Rodgers was appointed by former President Bill Clinton, while both Griffith and Kavanaugh were appointees of former President George W. Bush.

Federal funding of embryonic stem cell research was banned by the Bush administration in 2001. Current President Barack Obama overturned that ban in March 2009, who according to CNN said at the time that he was convinced that the government had been “forced” into “what I believe is a false choice between sound science and moral values.”

“President Obama made expansion of stem cell research and the pursuit of groundbreaking treatments and cures a top priority when he took office,” White House spokesman Robert Gibbs said in a statement following Tuesday’s ruling. “We’re heartened that the court will allow NIH and their grantees to continue moving forward while the appeal is resolved.”

However, as Jeremy Pelofsky of Reuters points out in a Wednesday morning article, “Even with funding allowed to continue, possibly only temporarily, the White House could turn to Congress in hopes lawmakers will rewrite the law to be clearer on the issue”¦ NIH could also try to rewrite its guidelines to conform with the law, or the White House could appeal to the Supreme Court if the appeals court rules against it on the merits of the case.”

—

On the Net:

• Court of Appeals, Washington, D.C. Circuit
• White House
• Chief Judge Royce Lamberth

Using a novel aptamer-based proteomics array technology, researchers and collaborators have identified biomarkers and protein signatures that are hallmarks of cancer at an early stage for two of the most aggressive and deadly forms of cancer “” pancreatic and mesothelioma.

This technology would enable better clinical diagnosis at an earlier stage and may provide insight into new therapeutic targets, said Rachel Ostroff, Ph.D., clinical research director of Somalogic Inc.

“Currently these cancers are detected at an advanced stage, where the possibility of cure is minimal,” said Ostroff. “Detection of these aggressive cancers at an earlier stage would identify patients for early treatment, which may improve their survival and quality of life.”

Ostroff presented results of this ongoing study at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

Discovered about 20 years ago, aptamers are nucleic acid molecules that bind to specific proteins. SomaLogic has developed the next generation of aptamers, SOMAmers (Slow Off-rate Modified Aptamers), which have superior affinity and specificity. SOMAmers enable a highly multiplexed proteomic platform used for simultaneous identification and quantification of target proteins in complex biological samples.

The goal of this study was to determine if this proteomics technology could identify blood-based biomarkers for pancreatic cancer or mesothelioma in people diagnosed, but not yet treated, for cancer.

Participants in the control group had symptoms that resembled these cancers, but were benign (i.e. pancreatitis or lung fibrosis).

Ostroff and colleagues tested blood from participants to discover the biomarkers specific to those with cancer, which would then be used to identify these diseases at an early stage, where the potential for effective treatment is much higher than in disease that has progressed.

For both forms of cancer, the researchers discovered biomarkers and developed a signature with high accuracy for detection of each form of cancer. Equally important, they found high specificity, meaning few people without disease will be incorrectly diagnosed and thus avoid unnecessary tests or treatments.

“Validation studies are underway, which we hope will lead to the development of diagnostic tests that hold clinical benefits for patients,” Ostroff said.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Mesothelioma is an asbestos-related pulmonary cancer that causes an estimated 15,000 to 20,000 deaths per year worldwide.

—

On the Net:

• American Association for Cancer Research