Just under one percent of the general population suffers from schizophrenia. The economic burden of the disease was estimated at $33 billion per year in the early 1990s. Much of that cost can be attributed to the consequences of psychotic relapse, which is common among schizophrenic patients.

Past studies of antipsychotic drugs tended to be short-term trials, lasting four to eight weeks. They had shown that second-generation drugs helped reduce psychotic symptoms, but longer-term studies were needed in order to determine their long-term effects on the disorder, especially on relapse.

“Schizophrenia is a chronic, psychiatric illness,” explains John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry at Washington University School of Medicine in St. Louis and the study’s principal investigator. “Relapse is common even under the best of circumstances, with an average patient relapsing at least once every one to two years. Because of the chronic nature of the illness, it is very important to determine whether newer drugs can diminish the relapse rate. Relapse prevention is the most important indicator of therapeutic success over the long term.”

The study involved nearly 400 patients with schizophrenia. They were treated at 40 sites around the United States. All study patients had records of having relapsed within the 24 months prior to the start of the study. Investigators spent two years comparing the rate of relapse in patients taking risperidone, a second-generation antipsychotic medication, to patients taking an older drug, haloperidol. Since its discovery in the 1950s, haloperidol has been one of the most commonly prescribed drugs in patients with schizophrenia and other psychotic disorders.

“At the time this study began, haloperidol was the most commonly used antipsychotic drug in the United States,” says Csernansky. “In any way one could measure it, haloperidol was the industry standard.”

When the study was completed, Csernansky and colleagues found that the one-year rate of relapse for patients on haloperidol was about 50 percent. But the rate of relapse for patients taking risperidone was only about 25 percent, about half of what was observed in patients taking the older drug.

“Reducing the rate of relapse is a tremendous benefit to the patient, but it’s also a benefit for the family and the system of care that has to pay for the hospitalization that often goes along with relapse,” Csernansky says. “Most importantly, however, patients who relapse face many months of difficulty. Hospitalization can last from seven to 21 days, but even after discharge it may take weeks, if not months, to restore work relationships and social relationships a patient had established prior to relapse.”

Haloperidol and other traditional antipsychotic drugs block activity in brain cells at the neuron’s dopamine receptor. Newer drugs like risperidone block the dopamine receptor, but they also act at other receptors, such as the serotonin receptor. Past studies have shown the newer drugs seem to be more effective and cause fewer side effects, at least in the short term. This study, however, followed patients for at least a year — with some participating in the study for two years. The goal was to determine whether psychotic symptoms were controlled and side effects minimized during a longer time period.

Antipsychotic drugs can have side effects on the central nervous system. After years on such drugs, some patients develop symptoms similar to Parkinson’s disease. Over many years, some even develop a chronic movement disorder called tardive dyskinesia, a condition that resembles Huntington’s chorea. The newer drugs, such as risperidone, have fewer neurological side effects.

Despite the dramatic change in rates of relapse, Csernansky says more immediate differences observed in study patients were subtle. “Risperidone had benefits in terms of causing a modest reduction in symptoms and side effects, but it’s interesting that those benefits were relatively small. One wouldn’t necessarily notice a large change in symptoms, at least in the short term,” he says.

Csernansky says more needs to be done to cut relapse rates, but he believes the reduction offered by risperidone is a very positive development. Unfortunately, he says the cost difference between the two drugs may influence some clinicians and managed care plans to continue to favor the older drug, but he says the cost of relapse also must be included in the equation.

“In general, a hospitalization for schizophrenia lasts about two weeks and costs in the neighborhood of $500 per day, so cutting the relapse rate by half could have significant economic benefits,” he says.

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John G. Csernansky, et. al., “A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia,” New England Journal of Medicine, Jan. 3, 2002.

This research was supported by grants from the Janssen Research Foundation. The investigators also received honoraria for delivering lectures from the Janssen Research Foundation, Eli Lilly, AstraZeneca Pharmaceuticals and Pfizer Pharmaceuticals

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

The study is scheduled for the December 1 issue of ACS’ Molecular Pharmaceutics, a bi-monthly journal.

In the new study, Ram Mahato, Guofeng Cheng, and Lin Zhu point out that transplantation of the pancreas’s insulin producing cells, called islet cells, has great potential for treating patients with insulin-dependent diabetes.

However, the procedure currently is ineffective for most people due to a tendency of the body’s immune system to reject transplanted cells. Studies by others indicate that a specific enzyme, caspase-3, plays a key role in carrying-out this destructive process.

To address this problem, the scientists genetically modified islet cells in the laboratory to turn off, or "silence" the gene responsible for producing caspase-3. When the modified cells were transplanted into the kidneys of mice with insulin-dependent diabetes, the blood glucose levels of the mice became normal for up to 32 days, the scientists say.

When the cells were removed, the blood glucose levels of the mice returned to high levels similar to pre-transplantation levels, confirming that the transplanted cells were functional and effective, the researchers say.

The study, authored by Rebecca A. Bernert, of Florida State University, focused on 322 college undergraduates between 19-24 years of age. The following symptom measures were administered: Pittsburgh Sleep Quality Index (PSQI); Insomnia Severity Index (ISI); Beck Depression Inventory (BDI); and Beck Scale for Suicide Ideation (BSS).

According to the results, consistent with past research, PSQI and ISI total scores were significantly associated with greater BDI scores. Elevated scores on the BSS were significantly predicted by higher scores on the ISI and the PSQI, although the latter emerged only as a non-significant trend. Importantly, after BDI scores were entered into the model as a co-variate, ISI and PSQI scores jointly predicted greater BSS scores, though they failed to significantly predict these symptoms independently.

"This investigation attempted to clarify whether self-reported sleep disturbances serve as a risk factor for suicide ideation in a nonclinical sample of young adults," said Bernert. "We found that insomnia and poor sleep quality jointly predicted elevated suicidal symptoms, even after controlling for depression. However, these sleep complaints failed to individually predict increased risk for suicide. This suggests that, within a less severe sample, multiple indices of sleep disturbances may be necessary to assess suicide risk and guide clinical decision-making. These findings may inform both intervention efforts and suicide risk assessment models."

Insomnia is a classification of sleep disorders in which a person has trouble falling asleep, staying asleep or waking up too early. It is the most commonly reported sleep disorder. About 30 percent of adults have symptoms of insomnia.

It is recommended that adults get between seven and eight hours of nightly sleep.

Cervical cancer is one of the major causes of death from cancer for women worldwide. But in countries with organised screening programmes for cervical cancer, incidence rates and deaths drop significantly.

The study looked at the long-term risks of cervical and other cancers for women after treatment to remove pre-cancerous lesions, a procedure called cervical intraepithelial neoplasia (CIN). The treatment removes abnormal cells that, if left untreated over a period of time, might turn into cancer.

Researchers studied 7,564 women treated for CIN during 1974 and 2001, and followed this up through the Finnish cancer registry until 2003.

Over the period, the researchers identified 448 new cases of cancer among the women, which was 96 more than they anticipated when considering average rates among the female population.

Of those new cases, 22 had developed invasive cervical cancer and showed that women were at more than average risk in the first and second decades after their CIN treatment.

The authors say their findings are in contrast to previous studies that said the risk of cancer did not increase after eight years follow-up after CIN treatment.

There are three types of CIN — mild, moderate and severe. The authors found that the risk of cervical cancer was higher for women previously treated for the mild or moderate type of CIN, possibly because people with less serious lesions tended to have less systematic follow-up checks than those who had experienced the more severe form of CIN.

Despite this, the authors say the treatment of CIN is still effective and that an estimated 28-39% of cases without treatment would progress to invasive cancer.

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Citation: Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study, BMJ Volume 331, pp1183-5

Work setting also appears to play a role in predicting the risk of injury, with food service and construction industry jobs topping the list of hazardous employment in this age group.

The review appears in the February issue of the American Journal of Preventive Medicine.

"These studies provide sufficient evidence that the type of work setting, in particular restaurant work and manual labor jobs, was independently associated with work injury," said lead author F. Curtis Breslin, Ph.D., a scientist at the Institute for Work & Health in Toronto.

Breslin and his colleagues analyzed nine studies published between 1997 and 2005 that examined nonfatal injuries among 12- to 24-year-old workers.

The review focused only on youth performing paid nonagricultural jobs, such as those in the retail, food service or construction industries. The review also included self-employed teens, such as those performing babysitting or yard work.

Through telephone and written questionnaires, the workers reported characteristics of their employment and the type and severity of any on-the-job injuries they experienced.

Six studies took place in the United States and three were conducted in Canada and Australia.

Previous research had indicated that young male workers sustain injuries at about twice the rate of female workers. However, although six review studies compared injuries between the sexes, only one found that young males had a higher risk for injury, after taking into account work setting, on-the-job hazards and work hours.

"We found that when males and females are working similar jobs, they have a similar risk for work injury," Breslin said. "Even though you have males having higher injury rates, it seems to be attributable to them being in more dangerous jobs like construction," he said, not to factors specifically associated with gender.

Minority status appeared to be a significant predictor of increased injury risk, after taking work setting and work hours into account. In one study, the prevalence of work injury among Hispanic, black and other minorities was 67 percent higher than among young white workers. In another, the prevalence of on-the-job injury was 60 percent higher in Hispanic teens, compared to white teens.

"We didn’t necessarily expect that [finding] going into it," Breslin said. "It seems to be more the job they’re doing, not the characteristics of the kids themselves" that affects injury risk, Breslin said.

"This finding raises more questions than it answers," said Carol Runyan, Ph.D., director of the Injury Prevention Research Center at the University of North Carolina at Chapel Hill.

"I would want to know more about whether there are differences in the types of environments in which minority versus majority workers are employed, [such as] environmental safety factors, differences in training or supervision, safety of neighborhoods and risk of assault at work," she said.

Runyan suggested that for some Hispanic workers, there may also be language barriers between workers and supervisors that could impinge on the success of training and supervision practices associated with maintaining safe work practices.

The review results also showed that the frequency and number of on-the-job hazards was significantly associated with teens’ risk of injury. Common on-the-job hazards included using knives, climbing ladders or scaffolding and operating fryer machines, grills and ovens.

Unsurprisingly, the more hazards workers were exposed to, the greater their likelihood of injury.

A consistently increased risk of injury also existed among youth who reported feeling overloaded or pressured to maintain a certain pace at work.

Breslin said that part of the problem may lie in the difference in social norms in the workplace versus schools and home environments. Parents and educators may teach work safety education techniques that aren’t necessarily being used on the job, he said.

In 2004, almost 180,000 U.S. teens were severely injured at work. Between 15 percent and 26 percent of injured teen workers report permanent health problems as the result of on-the-job injuries.

"I think it is critically important that parents talk with their children about what they are doing at work, including issues of supervision and training and the kinds of tasks and equipment they are involved with," Runyan said.

Runyan also suggested that parents meet the supervisors of their children to let them know they are aware of the work environment and to try to determine if the supervisor is managing them in a responsible way.

For more information about youth work laws by state, visit the U.S. Department of Labor website at dol/dol/topic/youthlabor/

Reference: Breslin CF, et al. Non-agricultural work injuries among youth: a systematic review. Am J Prev Med 32(2), 2007.

The study is the first to examine whether fish intake affects atrial fibrillation (AF). It’s also the first to focus on the kind of fish meals eaten, said Dariush Mozaffarian, M.D., M.P.H., the study’s lead author. “The results suggest that regular intake of tuna or other broiled or baked fish may be a simple and important deterrent to AF among older men and women,” said Mozaffarian, instructor of medicine and researcher in the Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School in Boston.

AF affects more than 2 million Americans. A chronic condition that causes disability through fatigue, shortness of breath and reduced exercise tolerance, it occurs when the heart’s two upper chambers (the atria) quiver instead of beating effectively. Blood isn’t pumped completely out of the chambers, so it may pool and clot.

If a blood clot leaves the heart and becomes lodged in an artery in the brain, a stroke results. About 15 to 20 percent of strokes occur in people with atrial fibrillation. The incidence of AF increases with age, rising to approximately 2 percent per year after age 65. Researchers analyzed data from the National Heart, Lung, and Blood Institute-funded Cardiovascular Health Study, a prospective, population-based, multicenter study on 4,815 people over age 65 whose usual dietary intake was assessed in 1989–90. During 12 years of follow-up, doctors diagnosed 980 cases of AF.

An analysis found that higher consumption of tuna fish (fresh or canned) or other fish that was broiled or baked was associated with lower incidence of AF. People who reported eating those fish one to four times per week had a 28 percent lower risk of AF, while those who had five or more servings had a 31 percent lower risk compared to those who ate fish less than once a month. In contrast, researchers found that eating fried fish or fish sandwiches (fish burgers) was not associated with lower risk of AF.

Differences in AF risk based on the kinds of fish eaten persisted after adjusting for other risk factors, including smoking, diabetes, prior stroke and high blood pressure.

Researchers assessed dietary intake through a questionnaire about usual fish consumption during the past year. In an earlier study on a subgroup of this patient population, the researchers discovered that eating tuna or other broiled and baked fish correlated to increased biomarkers of long-chain n-3 fatty acids (also called omega-3 fatty acids) in the blood while eating fried fish or fish sandwiches did not. Long-chain n-3 fatty acids are plentiful in fatty fish such as salmon, tuna, mackerel and sardines.

“The lack of correlation between fried fish and fish sandwich intake and n-3 fatty acid levels suggests that these fish meals were either mostly lean (white) fish or that the preparation method affected the n-3 fatty acid content,” Mozaffarian said. “The former may be more likely because, on average, most fried fish or fish sandwiches eaten in the United States are lean (white) fish such as cod, pollock, etc.”

Mozaffarian said the relationship between intake of tuna or other broiled or baked fish and AF risk should be confirmed in other studies.

The potential mechanisms of this relationship – such as effects on blood pressure, left ventricular function, inflammation, or direct anti-arrhythmic effects – should be evaluated further, he said.

Co-authors are Bruce M. Psaty, M.D., Ph.D.; Erick B. Rimm, Sc.D.; Rozenn N. Lemaitre, Ph.D., M.P.H.; Gregory L. Burke, M.D., M.S.; Mary F. Lyles, M.D.; David Lefkowitz, M.D.; and David S. Siscovick, M.D., M.P.H. The National Heart, Lung, and Blood Institute funded the research.

"The goal is a public information and awareness system for pandemic with the same level of credibility, timeliness and visibility as storm-warning icons presented on television screens," said Barrett Caldwell, a Purdue University associate professor of industrial engineering.

The system works by monitoring "event phases" of human behavior leading up to a pandemic, such as an increase in people purchasing flu-related medications or "foraging" on the Internet for certain types of information related to the flu.

Understanding these phases might be a way to overcome a fundamental hurdle in controlling pandemic: Conventional approaches require public-health officials to know when certain events leading to pandemic begin, Caldwell said.

"The problem with this requirement is that by the time you know an event has happened, it’s often too late to do much about it," he said.

Caldwell and former Purdue industrial engineering doctoral student Sandra K. Garrett have proposed a new approach to warn the public of an impending pandemic.

"If you can recognize the triggers, the signals suggesting an event is likely to occur, you can start responding to it, gathering resources, preparing and mobilizing people," said Garrett, an assistant professor of industrial engineering at Clemson University. "Our basic research idea could be used for any pandemic, or even other types of disasters."

Garrett and Caldwell detailed the findings in a paper that will be presented June 2 at the Industrial Engineering Research Conference in Miami.

The paper shows how pre-pandemic events are separated into four categories of "human factors," or social behavior: a period during which it is first possible to detect signals of an emerging pandemic; a time when it is possible to begin early efforts to prevent or mitigate spread; a time when it is critical to implement such measures; and a period when it is time to complete mitigation steps.

The method is an elaboration of "signal-detection theory," conceived decades ago.

"Normally, when psychologists study signal detection, they are looking at very rapid changes, like whether a tone changes, whether a light changes color or turns on and off," Caldwell said.

The new approach proposes to make signal detection sensitive to more gradual events that are slower to develop.

"This is important because a pandemic is not a single point in time but a scenario that may take place in several waves over a period of months," he said. "One of the challenges is that the way influenza spreads, you don’t know that someone’s sick until several days later, and by then they have had the opportunity to infect other people. At that point you have to project backward to see where people have first been sick and where certain flu-related events have happened. You are reactive, rather than proactive."

The researchers envision a system that uses icons similar to those used to alert the public about an impending blizzard, hurricane or tornado. The new approach would enable public health officials to properly manage "event deadlines," or respond to a problem before it’s too late.

"For example, by now we have many cases in the United States, so the event deadline for closing travel boarders with Mexico has already passed," Caldwell said.

The method also would enable officials to recognize a critical "trigger" that marks when people are prompted to act in certain ways based on a mental preview of what they think may happen in the near future.

"This trigger could be that something has already happened or you think that something is going to happen so you are doing something to prepare yourself," Caldwell said. "There are no swine flu cases yet, but you think there might be cases near where you live. You go out and buy cans of food and extra juice, and so on."

A need for such a warning system can be seen in the World Health Organization’s unexpectedly rapid response to swine flu, Caldwell said.

"Health officials were very surprised that the World Health Organization went from a phase 3 pandemic alert to phase 5 in 48 hours," he said. "The pandemic preparation materials produced a few years ago stated that these sorts of decisions could be expected to evolve over several days to maybe two weeks, but not two days. So the events have unfolded much faster than people were expecting."

The research was funded by a grant from the Indiana State Department of Health through Purdue’s Healthcare Technical Assistance Program, based at Purdue’s Discovery Park, which strives to improve health-care performance and delivery.

In related work, the researchers have collaborated with health officials and hospitals in Indiana to determine an "alternative care system" that may need to be activated once a pandemic reaches the local area.

"A pandemic flu alternative care system is designed to respond to concerns that the existing hospital structures may not have the capacity to respond to the number of flu cases," Caldwell said. "One of the problems that we uncovered in research was that a really complex alternative care system requires even more advance planning and even more coordination of signals to know when and how to activate. Something that starts out with just a flu-information telephone number isn’t bad, but we had looked at systems all the way up to temporary satellite hospitals that just handled incoming flu patients."

Previous research emphasized that counties should recognize when and what type of alternative care system would be required based on the signals officials received, determining when to activate the system based on where cases were being reported.

According to study chairman, Fred D. Lublin, M.D., Saunders Family Professor of Neurology at Mount Sinai School of Medicine-Corinne Goldsmith Dickinson Center for Multiple Sclerosis, "This is a very important trial because, if effective, combination therapy will allow us to take advantage of these agents that have different and complementary mechanisms of action to slow or halt progression of MS."

An estimated 400,000 Americans suffer from MS, a chronic neurological disease that affects the central nervous system. MS is most commonly diagnosed in young adults. Relapsing-remitting MS, the most common form of new cases of the disease, is characterized by episodes of attacks of neurologic dysfunction, which occur over many years.

Approximately 130,000 MS patients are receiving either FDA-approved interferon beta-1a weekly (Avonex®) or glatiramer acetate daily (Copaxone®) to treat relapsing forms of MS. However, because these agents provide only a partial amelioration of the risk for additional attacks and development of disability, there is a major and continuing need for better therapies. As yet, there is no cure for MS.

CombiRx will determine whether the combination of these treatments is more effective than either treatment alone. This trial is unique among placebo controlled studies, in that none of the participants will receive placebo alone. All participants will receive at least one active, FDA-approved treatment. Specifically, 50% will receive the combined investigational therapy, 25% will receive interferon beta 1-a weekly plus a daily placebo, and 25% will receive glatiramer acetate daily plus a weekly placebo.

In addition to CombiRx, participants will be offered the opportunity to volunteer for another study known as Biomarkers in MS. This study is designed to determine if there are specific genes and proteins that can predict the course and progression of MS. More importantly, this study may allow identification of markers that may be useful in distinguishing which MS patients may respond to specific treatments. According to Dr. Henry McFarland, Clinical Director, NINDS, "As with the data from the CombiRx Trial, the implications of the Biomarkers in MS Study could be enormous, both for the individual patient as well as for the costs associated with MS treatment and hence the health care providers and the general public."

One thousand patients are being recruited for these studies at approximately 80 sites across the US and Canada.

Men and women between 18 and 60 years of age who have been diagnosed with relapsing-remitting MS and who have not previously taken interferon beta-1a weekly (Avonex®) or glatiramer acetate daily (Copaxone®) may be eligible to participate in both studies. Participants will be randomly assigned to one of the three study groups and will receive treatment over 36 months. Clinic visits will be scheduled every three months throughout the treatment period to assess the impact of treatment.

To learn more about the CombiRx trial, please call (866) 848-3088.

The guidelines are available free online at liebertpub/thy

"Following careful peer review, Thyroid has published the first comprehensive set of clinical guidelines for the treatment of all medullary thyroid carcinoma (MTC) disorders," says Charles H. Emerson, MD, Editor-in-Chief of the Journal and Professor Emeritus at University of Massachusetts Medical School, in Worcester. "This form of thyroid cancer is especially important because of its high mortality, strong inheritance patterns, and associations with other serious glandular disorders. These evidence-based guidelines will become a benchmark for patient management and clinical research, as they illuminate the diagnostic and therapeutic strategies required when caring for gravely ill patients and those in the anxiety-ridden early stages of the disease, and when offering testing and counseling to family members."

MTC is a complex disease that accounts for about 4% of all thyroid cancer cases in the United States. Nearly 25% of cases worldwide are familial and present as an autosomal inherited disorder. In individuals with the inherited form of MTC, a preneoplastic lesion called C-cell hyperplasia will first develop and then progress to an invasive, life-threatening malignancy.

The American Thyroid Association (thyroid) has compiled 122 evidence-based recommendations that cover a range of clinical topics, including diagnosis and therapy for early disease, genetic testing, surgical management, post-surgical treatment and monitoring, management of persistent or recurrent MTC and metastatic disease, and long-term follow-up. The guidelines also propose directions for future research on MTC.

"Medullary thyroid cancer is a rare and fascinating disease that few health care professionals ever master," says Richard T. Kloos, MD, Chair of the ATA Guidelines Task Force, Secretary and Chief Operating Officer of the American Thyroid Association, and Co-Director of the Ohio State University Thyroid Cancer Unit. "The ATA guidelines promote optimal medical care that is grounded in an evidence-based review of the literature by an international and multidisciplinary panel. It is our hope that they will serve all the professionals that care for these patients, including those in the fields of endocrinology, genetics, pediatrics, radiology, nuclear medicine, surgery, and oncology."

Croup is characterized by a loud cough that may sound like the barking of a seal. It may be accompanied by fast or difficult breathing, and sometimes a grunting noise or wheezing while breathing. The symptoms of croup can be very upsetting to parents and caregivers, as they may be mistaken for choking or other serious airway issues.

It has been commonly believed that croup is caused by a virus, however, upper airway complications have also been suggested. Researchers did an airway evaluation on 80 children who had recurrent croup to see if there had been any narrowing in the upper airways which could indicate reflux. Of the patients who had narrowing in the airway (33 percent), 19 of those (73 percent) also manifested laryngopharyngeal reflux.

Researchers noted many episodes of croup could be averted if it was determined that reflux was a component of the patient’s diagnosis and proper preventive treatment could be prescribed.

*Title: Etiology of Pediatric Recurrent Croup. Presenters: Harlan R Muntz, MD; Ryan VanWoerkom, MD. Date: September 21, 2008, 10:30 am – 12:00 pm (all times CDT)