SCIENCE NEWS: STARTING DIALYSIS EARLIER MAY BE HARMFUL FOR SOME PATIENTS
ScienceDaily (Nov. 9, 2010) -
Beginning dialysis therapy earlier in the development of advanced kidney disease appears to be associated with a greater risk of death for some patients in the following year, according to a report posted online that will be published in the March 14 print issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Dialysis -- a procedure in which a machine performs the blood-filtering functions of the kidneys -- should help patients with advanced kidney disease live longer, reduce their illness burden and improve their quality of life, according to background information in the article. "The appropriate timing for initiating hemodialysis relative to estimated levels of residual renal function is an important, but as yet unresolved, question having considerable patient outcome and financial consequences," the authors write. Since 1996, more U.S. patients have begun dialysis early as indicated by their estimated glomerular filtration rate (eGFR, a measure of kidney function).
Steven J. Rosansky, M.D., of Wm. Jennings Bryan Dorn Veterans Hospital and the University of South Carolina, Columbia, and colleagues analyzed data from 81,176 patients age 20 to 64 who began dialysis between 1996 and 2006. They assessed only patients who did not have diabetes or any other co-occurring illness besides high blood pressure.
Overall, 9.4 percent of patients died within the first year and 7.1 percent died the second year. Patients who had an early start to dialysis based on their eGFR were more likely to die in the first year than were those who started later (20.1 percent vs. 6.8 percent).
Patients with the lowest levels of albumin -- a protein made by the liver -- also had an increased risk of death in the first year compared to those with the highest albumin levels (21 percent vs. 4.7 percent). Other factors associated with increased risk of death included increasing age, being black or male and having a lower body mass index (BMI), whereas having higher levels of hemoglobin (a protein in red blood cells that contains iron), being treated in a later year, being Asian and having certain types of kidney disease (polycystic kidney disease or glomerular disease) were associated with survival.
The higher death rate among those starting dialysis early "raises a concern that hemodialysis may be providing more harm than benefit," the authors write. Possible mechanisms for this harm include sudden cardiac death or recurring myocardial ischemia (cutoff of blood flow to the heart), which can lead to lasting defects in the heart's left ventricle.
"Hemodialysis is an invasive, lifelong, potentially dangerous intervention," the authors conclude. These results and those of other recent studies have failed to find benefit in early dialysis and suggest the potential of harm. "Initiation of hemodialysis should not be based on an arbitrary level of eGFR or serum creatinine level unless this measure is accompanied by definitive end-stage renal failure-related indications for hemodialysis."
Time to Rethink Dialysis Timing
"Over the past 15 years, dialysis has been initiated at progressively higher levels of estimated kidney function," writes Kirsten L. Johansen, M.D., of San Francisco VA Medical Center and the University of California, San Francisco, in an accompanying editorial.
"I believe that recent studies should make us think carefully about the timing of dialysis initiation," Dr. Johansen writes. "I am not advocating that we require months of nausea and vomiting before initiating dialysis, but I am suggesting that (in the absence of urgent indications) we shift our paradigm to consider starting dialysis when the symptoms are worse than the anticipated lifestyle burden and effects of dialysis, which are considerable and include a substantial time commitment, frequent fatigue and infections, among other things."
"This will require close follow-up and ongoing discussions with our patients," she concludes. "From a research perspective, we need to focus our efforts on examining the quality-of-life implications of timing of dialysis initiation."
Journal References:
Steven J. Rosansky; Paul Eggers; Kirby Jackson; Richard Glassock; William F. Clark. Early Start of Hemodialysis May Be Harmful. Arch Intern Med, 2010; DOI: 10.1001/archinternmed.2010.415
Kirsten L. Johansen. Time to Rethink the Timing of Dialysis Initiation. Arch Intern Med, 2010; DOI: 10.1001/archinternmed.2010.413
SCIENTISTS IDENTIFY GENE VARIANTS ASSOCIATED WITH EATING DISORDER
Scientists at The Children's Hospital of Philadelphia have identified both common and rare gene variants associated with the eating disorder anorexia nervosa. In the largest genetic study of this psychiatric disorder, the researchers found intriguing clues to genes they are subjecting to further investigation, including genes active in neuronal signaling and in shaping interconnections among brain cells.
Anorexia nervosa (AN) affects an estimated 9 in 1000 women in the United States. Patients have food refusal, weight loss, an irrational fear of weight gain even when emaciated, and distorted self-image of body weight and shape.
Women are affected 10 times more frequently than men, with the disorder nearly always beginning during adolescence. AN has the highest mortality rate of all psychiatric disorders, and successful treatment is challenging.
Twin studies and other family studies have suggested that AN is strongly heritable. "However, despite various genetic studies that identified a handful of candidate genes associated with AN, the genetic architecture underlying susceptibility to AN has been largely unknown," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. The research appeared online in Molecular Psychiatry on Nov. 16.
"This is the first genome-wide association study on a large anorexia cohort, as well as the first study of copy number variations in the disorder," said Hakonarson. Genome-wide association studies (GWAS) search for single-nucleotide polymorphisms, or SNPs - common gene variants that typically act as pointers to a gene region with a small effect on raising disease risk. The study team also performed a parallel search for copy number variations (CNVs), rarer variants that usually have a stronger impact on disease risk.
The sample size was the largest used in an AN gene study - DNA came from 1,003 AN patients, all but 24 of them female, from various sources, having an average age of 27 years. For comparison, there was a control group of 3,733 pediatric subjects (average age of 13), drawn from the Children's Hospital pediatric network.
"We confirmed results of previous studies of anorexia nervosa: SNPs in the gene OPRD1 and near the gene HTR1D confer risk for the disease," said Hakonarson. "We did not detect other obvious candidate genes, but we did generate a list of other genes that we are analyzing in follow-up studies." One SNP is between the CHD10 and CHD9 genes, a region that Hakonarson associated with autism spectrum disorders in 2009. Called cadherin genes, CHD10 and CHD9 code for neuronal cell-adhesion molecules - proteins that influence how neurons communicate with each other in the brain.
The current anorexia study also investigated CNVs - deletions or duplications of DNA sequences. Previous research by Hakonarson and others has shown that CNVs play a significant role in other neuropsychiatric disorders, such as schizophrenia, bipolar disorder and autism.
The current study suggests that CNVs may play a less important role in anorexia than they do in schizophrenia and autism. Nonetheless, the researchers identified several rare CNVs that occurred only in AN cases, including a deletion of DNA on a region of chromosome 13.
"Our study suggests that both common SNPs and rare CNVs contribute to the pathogenesis of anorexia nervosa," said Hakonarson. "The gene variants we discovered are worthy of further analysis in independent cohorts. However, the relatively modest number of anorexia cases explained by these results we found suggests that many other candidate genes remain unknown. Future studies will require much larger sample sizes to detect additional gene variants involved in this complex disorder."
Support for this research came from an Institute Development Award from The Children's Hospital of Philadelphia, as well as from the Price Foundation, the Klarman Family Foundation, and the Scripps Translational Science Institute of La Jolla, Calif. Hakonarson's co-authors were from the University of Pennsylvania, the Scripps Translational Science Institute, the Scripps Research Institute, the University of California, San Diego, and the Price Foundation Collaborative Group.
SOURCE: The Children's Hospital of Philadelphia
OBESITY, WEIGHT GAIN IN MIDDLE AGE ASSOCIATED WITH INCREASED RISK OF DIABETES AMONG OLDER ADULTS
ScienceDaily (June 24, 2010) - For individuals 65 years of age and older, obesity, excess body fat around the waist and gaining weight after the age of 50 are associated with an increased risk of diabetes, according to a study in the June 23/30 issue of JAMA.
"Incidence of diabetes in the United States has doubled in the past 15 years, and is highest among adults 65 to 79 years of age. Approximately 70 percent of U.S. men and women 60 years of age and older are overweight or obese [BMI -- body mass index 25 or greater]. Adiposity [body fat] is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, however, the relationships between different measures of body composition and diabetes in older adults [65 years of age or older] are not well described," the authors write.
Mary L. Biggs, Ph.D., of the University of Washington, Seattle, and colleagues examined the relationship between measures of overall body fat, fat distribution, changes in these measures, and diabetes risk among 4,193 men and women 65 years of age and older. Measures of adiposity were determined when participants entered the study, and repeated 3 years later. The incidence of diabetes was ascertained based on use of antidiabetic medication or a fasting blood glucose level of 126 mg/dL or greater.
Over a median (midpoint) follow-up of 12.4 years, 339 new cases of diabetes were diagnosed among the study participants. The researchers found that BMI at baseline, BMI at 50 years of age, weight, fat mass, waist circumference, waist-hip ratio, and waist-height ratio were all strongly related to the risk of diabetes. "For each measure, there was a graded increase in the risk of diabetes with increasing quintiles of adiposity. Participants in the highest category of adiposity had an approximately 2- to 6-fold increased risk of developing diabetes compared with those in the lowest category. We found no evidence of significant statistical interaction by sex or race," the authors write.
Also, compared with participants whose weight remained stable (plus or minus 4.4 lbs.) over the time period, those who gained 20 lbs. or more between the age of 50 years and study entry had an approximately 3-fold greater risk of developing diabetes during follow-up, regardless of their BMI at 50 years of age. Participants who were obese (BMI 30 or greater) at 50 years of age and who experienced the most weight gain (more than 20 lbs.) between the age of 50 years and study entry had 5 times the risk of developing diabetes compared with weight-stable participants with normal BMI (less than 25) at 50 years of age.
The researchers also found that participants in the highest categories of both BMI and waist circumference had more than 4 times the risk of those in the lowest category of both measures. Participants with a greater than 4 inch increase in waist size from baseline to the third follow-up visit had a 70 percent higher risk of type 2 diabetes compared with those who gained or lost 0.8 inches or less.
"Results of this study affirm the importance of maintaining optimal weight during middle age for prevention of diabetes and, while requiring confirmation, suggest that weight control remains important in reducing diabetes risk among adults 65 years of age and older," the authors conclude.
Though this study was done in the US and the participant volunteers are also American we may safely say that the same trend will hold true in most parts of the world to some extent more or less.
REGULAR WALKING MAY SLOW DECLINE OF ALZHEIMER'S
Researchers also find that walking 6 miles a week can help prevent onset of disease.
New research suggests that walking about five miles a week may help slow the progression of cognitive illness among seniors already suffering from mild forms of cognitive impairment or Alzheimer's disease.
In fact, even healthy people who do not as yet show any signs of cognitive decline may help stave off brain illness by engaging in a similar level of physical activity, the study team noted.
An estimated 2.4 million to 5.1 million people in the United States are estimated to have Alzheimer's disease, which causes a devastating, irreversible decline in memory and reasoning, according to National Institute on Aging.
The researchers were slated to present the findings Monday in Chicago at the annual meeting of the Radiological Society of North America (RSNA).
"Because a cure for Alzheimer's is not yet a reality, we hope to find ways of alleviating disease progression or symptoms in people who are already cognitively impaired," lead author Cyrus Raji, of the department of radiology at the University of Pittsburgh, said in a RSNA news release.
"We found that walking five miles per week protects the brain structure over 10 years in people with Alzheimer's and MCI, especially in areas of the brain's key memory and learning centers," he said. "We also found that these people had a slower decline in memory loss over five years."
To assess the impact that physical exercise might have on Alzheimer's progression (as well as that of less severe brain illnesses), the researchers analyzed data from an ongoing 20-year study that gauged weekly walking patterns among 426 adults.
Among the participants, 127 were diagnosed as cognitively impaired -- 83 with mild cognitive impairment (MCI), and 44 with Alzheimer's. About half of all cases of MCI eventually progress to Alzheimer's. The rest were deemed cognitively healthy, with an overall average age of between 78 and 81.
A decade into the study, all the patients had 3-D MRI scans to assess brain volume. In addition, the team administered a test called the mini-mental state exam (MMSE) to pinpoint cognitive decline over a five-year period.
After accounting for age, gender, body-fat composition, head size and education, Raji and his colleagues determined that the more an individual engaged in physical activity, the larger his or her brain volume. Greater brain volume, they noted, is a sign of a lower degree of brain cell death as well as general brain health.
In addition, walking about five miles a week appeared to protect against further cognitive decline (while maintaining brain volume) among those participants already suffering from some form of cognitive impairment.
This indication was bolstered by the mini-mental state exam results, which revealed that cognitively impaired patients who met the walking threshold experienced only a one-point drop in cognition scores over a five-year period. By contrast, those who didn't walk sufficiently experienced an average decline of five points.
Physical activity had a similar impact on the protection of cognitive abilities in healthy adults, although their exercise threshold was deemed to be about six miles per week of walking.
"Alzheimer's is a devastating illness and, unfortunately, walking is not a cure," Dr. Raji said. "But walking can improve your brain's resistance to the disease and reduce memory loss over time."
Dr. Robert Friedland, chairman of the neurology department at the University of Louisville's School of Medicine in Kentucky, expressed little surprise at the findings, but cautioned against inferring a direct cause-and-effect link between walking and protection against cognitive decline.
"In an observational study like this, undoubtedly people who are developing cognitive disease or are likely to be in the early stages are also likely to become less active," he noted. "So, it's not possible to be sure that they're observing a direct effect of walking on the disease, because diminished walking in the group that is progressing more rapidly could have been a direct result of the disease itself."
"But that's not to say that I don't think walking is a good idea," Friedland added. "Many people, including my group, have shown that physical as well as mental activity may be protective against developing disease during midlife -- that is, between [ages] 20 and 60. And I'm sure that this is also true in later life."
"And there are many reasons why: physical activity improves blood flow to the brain, and it changes neurotransmitters and improves cardiac function," he said. "It lessons the risk of obesity, improves insulin resistance and lowers the risk of diabetes, and lowers your blood pressure. And all of these things are risk factors for Alzheimer's disease."
"So, I would say that everyone at all ages should be encouraged to get as much physical exercise as they can tolerate," Friedland concluded. "Of course, we don't want people to exercise excessively if they have heart disease, for example. But with a physician's advice and supervision, walking is an excellent form of activity."
Since the research was presented at a medical meeting, the data and conclusions should be seen as preliminary until published in a peer-reviewed journal.
BPA
BPA Can Rub Off From Receipts, Money, Study Finds. Environmental Group Suggests Less Handling of Receipts, but Industry Says Chemical Exposure Is Low. By Kathleen Doheny - WebMD Health News
Dec. 8, 2010 -- Bisphenol A or BPA, a common chemical found in plastics and other consumer products that's been linked to reproductive harm and other ills, can also be transferred to the skin from cash register receipts and dollar bills, according to a new investigation by two environmental advocacy groups.
"BPA is a developer used in the thermal paper," says Erika Schreder, a staff scientist at the Washington Toxics Coalition and author of the new report, "On the Money: BPA on Dollar Bills and Receipts." It's found in the receipts used by probably 95% of stores, she tells WebMD.
Together with the Safer Chemicals, Healthy Families coalition, the Washington Toxics Coalition researched the extent to which thermal paper containing BPA has permeated the market, whether BPA also escapes onto money that is usually close to those receipts in the wallet, and whether the chemical easily transfers to skin.
As a result of the investigation, Schreder recommends people handle receipts as little as possible. But a spokesperson for the Polycarbonate/BPA Global Group says there is no reason to worry. A Closer Look: BPA in Receipts and Money
For the study, researchers collected 22 receipts made with thermal paper from 22 retailers in 10 states and Washington, D.C. The sites included grocery stores, home improvement, discount, and retail stores.
Researchers also collected dollar bills from 18 states and D.C., testing 22 in all.
BPA was found in what Schreder calls very large quantities in 11 of the 22 receipts -- in amounts up to 2.2% of the total weight.
BPA was found in 21 of the 22 bills tested.
Because the BPA used in thermal paper is not chemically bound, it is a concern, Schreder says. "We are definitely concerned about these levels of BPA in receipts because BPA is present in an unbound form, where it can easily transfer to our skin."
To see how easily it may transfer, researchers conducted tests mimicking a typical handling of receipts. BPA was transferred from receipts to fingers. Just 10 seconds of holding a receipt resulted in a transfer of up to 2.5 micrograms, the researchers found.
And rubbing the receipt -- similar to scrunching it or fiddling with it -- transferred about 15 times that amount.
"BPA is a hormone-disrupting chemical," Schreder says, capable of causing problems such as reproductive harm, early puberty, and infertility.
The big concern is overall exposure, she says, with BPA from receipts and money adding to the total.
BPA Industry Responds
''Some receipts made from thermal paper can contain low levels of bisphenol A (BPA)," Steven G. Hentges, PhD, senior director of the Polycarbonate/BPA Global Group, says in a statement.
However, he says, there is no reason for concern. "Recent scientific studies indicate that to the limited extent BPA is absorbed through the skin, it is converted to a biologically inactive metabolite that is rapidly eliminated from the body."
And, he says, the trace levels of BPA claimed to be present on dollar bills are not significant.
The new report ''shows that a significant amount of BPA comes off the receipt and onto the skin," says Ted Schettler, MD, MPH, science director of the Science and Environmental Health Network, a public and environmental health advocacy group. He conducted an editorial review of the report for the researchers.
More research is needed, he and Schreder say.
''It could turn out that skin exposure could be an important pathway," Schettler says.
BPA Exposure: How to Minimize
What's needed, in Schreder's view, is for Congress to make reform of the Toxic Substances Control Act a top priority. Bills have been introduced in the House and the Senate to update the law, she says.
Her organization is calling for immediate action to reduce exposure to the most hazardous chemicals.
"BPA is on that list," she tells WebMD.
Meanwhile, she suggests minimizing exposure to receipts. "Refuse it if you can," she says. If not, store the receipts separately in your wallet, away from your currency.
Keep receipts away from young children, and wash your hands after handling," she says.
