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Latest Research


A summary of the "must-read" articles from the journals in that pile on your desk.

Folic Acid Does Not Reduce Colorectal Adenoma Risk

Supplementation may even increase risk for some types of tumors

Supplementation with folic acid does not reduce the risk of colorectal adenomas and may in fact increase the risk for some types of colorectal cancer, according to study findings published in the June 6 issue of the Journal of the American Medical Association.

Bernard F. Cole, Ph.D., of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues conducted a double-blind, placebo-controlled study of 1,021 subjects who were randomized to receive 1 mg/day of folic acid or placebo. They also received 81 mg/day or 325 mg/day of aspirin or placebo. The subjects were followed-up with colonoscopy at three years and again at three to five years later.

At the first follow-up, 221 subjects in the folic acid group and 206 in the placebo group (44.1 percent and 42.4 percent, respectively) had at least one colorectal adenoma. Advanced lesions were detected in 57 subjects in the folic acid group (11.4 percent) and 42 in the placebo group (8.6 percent).

Of the 607 subjects who underwent the second follow-up, advanced lesions were detected in 35 (11.6 percent) of the folic acid group and 21 (6.9 percent) of the placebo group.

"Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia," the authors conclude.

AbstractFull TextEditorial

Financial Incentives Don't Boost Hospitals' Heart Care

Limited impact on processes of care or outcomes

Hospitals that participated in a voluntary quality-improvement scheme with performance-related pay did not show any improvement in the care of patients with acute myocardial infarction, according to the results of a study published in the June 6 issue of the Journal of the American Medical Association.

Seth W. Glickman, M.D., of the Duke University Medical Center in Durham, N.C., and colleagues analyzed data on 105,383 patients with acute non-ST-segment elevation myocardial infarction who were admitted to 54 hospitals participating in the quality-improvement initiative and 446 control hospitals.

In hospitals under the quality-improvement initiative, the rate of improvement for two of the six targeted therapies (smoking cessation counseling and prescription of aspirin at discharge) was slightly higher than in the control hospitals. However, the composite measure of the six targeted therapies showed no difference between the two groups of hospitals.

"Overall, there was no evidence that improvements in in-hospital mortality were incrementally greater at pay-for-performance sites," the authors conclude. "Conversely, we did not find evidence that pay for performance had an adverse impact on improvement in processes of care that were not subject to financial incentives."

AbstractFull Text (subscription or payment may be required)

ASCO: Study Sheds Light on Hereditary Gastric Cancer

Nearly 40 percent of families with hereditary diffuse gastric cancer have mutation in CDH1 gene

Many families with hereditary diffuse gastric cancer have mutations in the epithelial cadherin (CDH1) gene that occur independently or due to a founder effect, according to a study published in the June 6 issue of the Journal of the American Medical Association. In particular, a number of cases in Newfoundland are thought to be due to a founder mutation. The findings were also presented Sunday at the annual meeting of the American Society of Clinical Oncology in Chicago.

Pardeep Kaurah, M.Sc., of the British Columbia Cancer Agency in Vancouver, Canada, and colleagues studied 38 families with clinically diagnosed hereditary gastric cancer. In 26 families there were at least two cases of gastric cancer and one case of diffuse gastric cancer among people aged below 50, while 12 families had a member aged below 35 diagnosed with diffuse gastric cancer or multiple cases of diffuse gastric cancer among family members aged above 50.

Forty percent of the families had one of 13 mutations, including six novel ones, in CDH1. Four families from Newfoundland shared a common haplotype, suggestive of a founder effect. Male members of these four families who were mutation carriers had a 40 percent risk for clinically detected gastric cancer by age 75, while the risk for female carriers was 63 percent. The risk of breast cancer for females carrying the mutation was 52 percent.

"Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported," the authors conclude.

AbstractFull TextEditorial

Drug Benefits Patients with Amyloid A Amyloidosis

Improves disease but had no significant effect on risk of end-stage renal disease or death

Eprodisate improves disease in patients with amyloid A (AA) amyloidosis though it has no significant effect on the risk of end-stage renal disease or death, according to two reports in the June 7 issue of the New England Journal of Medicine.

Laura M. Dember, M.D., from Boston University School of Medicine, and colleagues randomized 183 patients with AA amyloidosis and renal involvement to eprodisate or placebo for 24 months. The disease worsened in significantly fewer patients from the eprodisate group (27 percent versus 40 percent, hazard ratio 0.58). However, eprodisate had no significant effect on the risk of progressing to end-stage renal disease or death.

The study was partially funded by Neurochem.

Helen J. Lachmann, M.D., and colleagues from the Royal Free and University College Medical School in London, U.K., followed the natural history of AA amyloidosis and its response to treatment in 374 patients for a median of 86 months. Median survival was 133 months after diagnosis, with renal dysfunction as the primary disease manifestation. The risk of death was correlated with serum amyloid A protein, and patients with levels less than 4 mg per liter had relatively favorable outcomes.

The trial of eprodisate "is a milestone in which hypothesis-driven, direct targeting of amyloid fibrils has shown some benefit," state the authors of an accompanying editorial.

AbstractFull Text (subscription or payment may be required)AbstractFull Text (subscription or payment may be required)Editorial

Drop in Heart Deaths Due to Treatment, Risk Factors

Partially offset by increases in body mass index and diabetes

About half the drop in deaths from coronary heart disease in the United States from 1980-2000 can be explained by treatment, and about half by reductions in risk factors, although this is partially offset by increases in body mass index and diabetes, according to a report in the June 7 issue of the New England Journal of Medicine.

Simon Capewell, M.D., from the University of Liverpool in the United Kingdom, and colleagues used a statistical model to examine factors explaining the drop in deaths from coronary heart disease among U.S. adults from 1980-2000. The age-adjusted death rate dropped from 542.9 to 266.8 per 100,000 in men and 263.3 to 134.4 per 100,000 in women over this period.

About 47 percent of the decrease could be explained by treatments such as those administered after myocardial infarction or revascularization. About 44 percent could be explained by changes in risk factors such as lower total cholesterol and lower systolic blood pressure. However, the researchers note that increases in body mass index increased deaths by 8 percent and an increase in the prevalence of diabetes increased deaths by 10 percent.

"Approximately half the decline in U.S. deaths from coronary artery disease from 1980 through 2000 may be attributable to reductions in major risk factors and approximately half to evidence-based medical therapies," Capewell and colleagues conclude.

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Mitotane Beneficial After Adrenal Cancer Surgery

Prolongs recurrence-free survival

Adjuvant mitotane significantly prolongs recurrence-free survival in patients with adrenocortical carcinoma who have undergone radical resection, according to a study published in the June 7 issue of the New England Journal of Medicine.

Massimo Terzolo, M.D., from the Universita di Torino in Turin, Italy, and colleagues retrospectively compared recurrence-free survival in 177 Italian and German patients with adrenocortical carcinoma who had undergone radical surgery. Of these, 47 Italian patients had received adjuvant mitotane while 55 Italian patients and 75 German patients did not and acted as controls.

The researchers found that patients receiving mitotane had significantly longer recurrence-free survival (42 months versus 10 months for the Italian controls and 25 months for the German controls). This translated to hazard ratios of 2.91 and 1.97, respectively. The adverse events of mitotane were mainly low grade, although 13 percent of patients required a temporary dose reduction.

"The study provides a compelling rationale for the use of low-dose mitotane as adjuvant therapy in patients presenting with stages I, II, and III adrenocortical carcinoma whose surgical resection has been macroscopically complete," David E. Schteingart, M.D., from the University of Michigan Medical Center in Ann Arbor, writes in an accompanying editorial.

AbstractFull Text (subscription or payment may be required)Editorial

New Bartonella Bacterial Species Identified

Species identified from woman who had recently traveled to Peru

A new bartonella species has been identified from a woman who developed a fever and splenomegaly after traveling to Peru, according to a report in the June 7 issue of the New England Journal of Medicine.

Jane E. Koehler, M.D., from the University of California San Francisco, and colleagues describe the case of a 43-year-old American woman who presented with fever, splenomegaly, anemia and a history of insect bites after traveling to Peru. The illness resolved after treatment with levofloxacin.

The researchers cultured a bartonella-like bacterium from the patient's blood whose appearance was indistinguishable from B. bacilliformis, which causes Oroya fever. However, DNA sequences from the bacterium showed that it was a new bartonella species, which they named B. rochalimae, that was phylogenetically closest to B. clarridgeiae. Protein profiles also confirmed that the new species was distinct, and the bacterium could cause fever and sustained bacteremia in a rhesus macque.

"In conclusion, we have identified a new bartonella species that caused an illness with features resembling Oroya fever in a patient who had recently traveled to Peru," Koehler and colleagues write. "Whether a zoonotic reservoir exists and the mechanism by which human infection occurs are currently unknown."

AbstractFull Text (subscription or payment may be required)Editorial

Study Re-Evaluates Avandia, But Jury Still Out on Safety

Interim analysis suggests that the drug may not increase cardiovascular events in diabetics

In contrast to a recent meta-analysis showing an increased cardiovascular risk in type 2 diabetics treated with rosiglitazone, new evidence suggests that such treatment may not be inferior to non-rosiglitazone regimens, according to a study published online June 5 in the New England Journal of Medicine. However, experts said the new study did not allay their concerns about the drug.

Philip D. Home, D.M., D.Phil., of Newcastle Diabetes Centre and Newcastle University in Newcastle upon Tyne, U.K., and colleagues conducted an unplanned interim analysis of an open-label, non-inferiority trial involving 4,447 patients who had failed treatment with metformin or sulfonylurea. The patients were randomly assigned to receive either add-on rosiglitazone or a combination of metformin plus sulfonylurea.

After a mean follow-up of 3.75 years, the researchers found that 217 rosiglitazone patients and 202 control patients were either hospitalized or suffered death from cardiovascular causes (hazard ratio, 1.08). Although there were no significant group differences in myocardial infarction and death from cardiovascular causes or any cause, the researchers found that heart failure was more common in the rosiglitazone group (HR, 2.15).

"The clinical impact of these data needs to be clarified," the NEJM editors write. "To do so, we asked a diabetologist, a cardiovascular epidemiologist, and a drug-safety expert to give their interpretations, which can be found in the accompanying editorials. Both editorials express uncertainty about the safety of rosiglitazone."

AbstractFull TextEditorial - DrazenEditorial - NathanEditorial - Psaty

Loss of Insurance Causes Drop in Health Expenditures

Health care expenditures correlate to a person's medical coverage and are highest among the insured

When uninsured patients gain medical coverage, their health care expenditures tend to rise to the level of those who are continuously insured, and vice versa, researchers report in the June 5 issue of the Annals of Internal Medicine.

Lisa Ward, M.D., of the University of California San Francisco, and Peter Franks, M.D., of the University of California-Davis, found that insured people use predictable amounts of health care regardless of whether they had medical coverage in the past. The investigators based their results on a longitudinal study evaluating the association between health insurance status and expenditures for 20,848 adults who participated in the 2000-2003 Medical Expenditure Panel Surveys (MEPS).

The researchers compared data over two years for four subgroups of the MEPS cohort: those continuously uninsured; those with continuous coverage; people who had insurance one year but lost it the next; and people who were uninsured the first year and obtained coverage the second. Health expenditures rose or fell in a predictable manner depending on the insurance status.

"Because we did not examine outcomes, it is unclear whether changes in service utilization translate into changes in health care outcomes," the authors write. "However, emerging evidence suggests that improved access associated with insurance coverage is associated with potentially beneficial changes in care."

AbstractFull TextEditorial

Antipsychotic Drugs Risky for Dementia Patients

Use of antipsychotic drugs increases mortality risk in older adults with dementia

Treating adult dementia patients with antipsychotic drugs for irritation or behavioral problems is risky and should be avoided if other therapies are available, researchers report in the June 5 issue of the Annals of Internal Medicine.

Sudeep Gill, M.D., of St. Mary's of the Lake Hospital in Ontario, Canada, and colleagues used population-based data to determine that mortality risk increased significantly among older adults with dementia treated with antipsychotic drugs in community settings and long-term care facilities.

The researchers found the risk of death was slightly higher from use of conventional antipsychotic drugs such as chlorpromazine, flupenthixol, fluphenazine, haloperidol and loxapine than use of newer, atypical drugs such as olanzapine, quetiapine and risperidone.

"These findings highlight the need to carefully balance potential risks and benefits when considering antipsychotic treatment for older adults with dementia and emphasize the need to limit use of these drugs to situations in which non-pharmacologic measures have provided an inadequate response," the authors write.

One researcher was supported by a grant from Eli Lilly, while several are consultants for various drug companies.

AbstractFull Text

Exercise, Advice Can Bring Short-Term Help for Back Pain

A combination of exercise and psychological advice can provide relief for subacute low back pain

A regimen of aerobic, stretching and endurance exercises combined with behavioral advice may lead to short-term benefits for patients with mild to moderate lower back pain, according to a report in the June 5 issue of the Annals of Internal Medicine.

Christopher G. Maher, Ph.D., of the University of Sydney in Australia, and colleagues conducted a randomized, placebo-controlled study of 259 people with subacute lower back pain to test how exercise and advice interventions might improve outcomes after six weeks, three months and one year.

At six weeks, those given a real set of exercises and real personal advice sessions had better outcomes for pain, perceived effect of treatment and functional ability than participants in three other groups that used a placebo factor. However, these benefits were reduced at three months and appeared to be negligible at 12 months.

"Our study provides evidence that exercise and advice are slightly more effective than placebo in improving pain at six weeks in persons with subacute low back pain," the authors write. "When both treatments were administered together, the effects were large enough that they could be considered clinically worthwhile by some participants at six weeks."

AbstractFull Text

Electronic Medical Records May Not Improve Diabetes Care

Electronic practices found to have lower adherence to diabetes quality of care measures

The use of an electronic medical record does not guarantee higher quality diabetes care, researchers report in the May/June issue of the Annals of Family Medicine.

Jesse C. Crosson, Ph.D., of the UMDNJ-New Jersey Medical School in Newark, N.J., and colleagues assessed the quality of care of 927 diabetic patients in 50 primary care practices, including 13 practices that used an electronic medical record, or EMR, and 37 that did not.

After adjusting for other factors, the researchers found that patient care at practices that did not use an EMR was more likely than practices using an EMR to meet guidelines for process (odds ratio, 2.25), treatment (OR, 1.67) and intermediate outcomes (OR, 2.68).

"The findings presented here suggest that national policy makers and primary care practice owners should pay renewed attention to maintaining and improving quality in primary care settings during and after EMR implementation," the authors write. "EMR vendors should be encouraged to address existing recommendations to develop products that provide more than a means to enhance billing for clinician services. They should include, or make more easily usable, features that can support improved health care quality (such as developing a chronic illness registry capable of identifying patients for whom treatment intensification would be warranted or offering real-time clinical guidelines support)."

AbstractFull Text

Evidence Scarce for Statin-CoQ10 Link in Myopathy

Few studies support reduction in muscle coenzyme Q10 as etiologic factor in statin-associated myopathy

There is insufficient evidence to support the effect of statins on coenzyme Q10 (CoQ10) levels as the primary mediator of statin-associated myopathy, according to a literature review in the June 12 issue of the Journal of the American College of Cardiology.

To determine if CoQ10 is an etiologic factor in statin-mediated myopathy, Leo Marcoff, M.D., of Yale University School of Medicine in New Haven, Conn., and a colleague conducted a systematic review of English-language articles published through August 2006. Statins have previously been shown to reduce levels of the fat-soluble quinone, potentially affecting mitochondria and muscle function.

The investigators confirm that many studies of statin use show significant reductions of CoQ10 in blood, plasma and serum. However, few studies have addressed the use of statins on intramuscular CoQ10. Of four studies identified, one showed a non-significant 33 percent decrease in skeletal muscle CoQ10, while another showed a significant 46 percent increase. Few studies have addressed CoQ10 supplementation during statin use as well.

"We conclude that there is insufficient evidence to prove the etiologic role of CoQ10 deficiency in statin-associated myopathy and that large, well-designed clinical trials are required to address this issue," the authors write. "The routine use of CoQ10 cannot be recommended in statin-treated patients."

The authors received research support and speaking honoraria from, or own stock in, Merck, Pfizer, AstraZeneca, Schering-Plough, and Kos.

AbstractFull Text (subscription or payment may be required)

Patch Improves Remodeling of Rats' Damaged Heart Muscle

Treated rats show improved muscle structure after eight weeks

A novel, biodegradable polyester urethane urea (PEUU) cardiac patch that is implanted on infarcted heart muscle promotes contractile smooth muscle tissue formation, improved cardiac remodeling and improved contractions, researchers report in the June 12 issue of the Journal of the American College of Cardiology.

William Wagner, Ph.D., of the University of Pittsburgh, and colleagues examined cardiac remodeling and performance in 14 rats treated with an implantable PEUU cardiac patch two weeks after coronary ligation. Twelve rats subjected to sham surgery were used as controls.

Rats treated with the patch showed stable end-diastolic left ventricular cavity area and increased fractional area change, as well as abundant smooth muscle bundles, increased contractility and a thicker left ventricular wall within eight weeks compared to control rats. The patch was largely resorbed by this time.

"Implantation of a novel biodegradable PEUU patch onto a subacute myocardial infarction promoted contractile phenotype smooth muscle tissue formation and improved cardiac remodeling and contractile function at the chronic stage," the authors write. "Our findings suggest a new therapeutic option against post-infarct cardiac failure."

AbstractFull Text (subscription or payment may be required)

Enoxaparin May Be Safe and Effective After STEMI

Significant reduction in death, recurrent MI, angioplasty compared with unfractionated heparin

Enoxaparin may reduce the need for angioplasty and reduce risk of death or recurrent myocardial infarction (MI) in patients with ST-segment elevation myocardial infarction (STEMI), without increasing the risk for bleeding, according to research published in the June 12 issue of the Journal of the American College of Cardiology.

Elliott Antman, M.D., of Brigham and Women's Hospital and Harvard Medical School in Boston, and the ExTRACT-TIMI 25 investigators asked whether enoxaparin is better than unfractionated heparin (UFH) as adjunctive therapy for patients with STEMI receiving fibrinolytic therapy. A total of 20,479 STEMI patients were randomized to either enoxaparin while hospitalized, or UFH for at least 48 hours.

The investigators found a significant reduction in the number of patients undergoing percutaneous coronary intervention (PCI) within 30 days in the enoxaparin group compared with the UFH group (22.8 versus 24.2 percent, respectively). The primary endpoint of death or recurrent MI was also lower in the enoxaparin group (10.7 versus 13.8 percent). Bleeding rates were similar between the two groups, at around 1.5 percent.

"Low molecular-weight heparin may ultimately prove to be safe and efficacious as an adjunct to PCI after fibrinolytic therapy for STEMI," states an accompanying editorial, which adds that replacing UFH with enoxaparin requires further study. "These results are important, given that antithrombin therapy after successful fibrinolysis is often selected by physicians who are not involved in the subsequent invasive cardiac care of the patient."

AbstractFull Text (subscription or payment may be required)Editorial

After Cardiac Arrest, Induced Hypothermia Effective in Field

Cooled saline in the field lowers body temperature, improves survival following cardiac arrest

Induction of mild hypothermia appears to be a safe and effective treatment for patients resuscitated following cardiac arrest outside the hospital, according to a report published online June 4 in Circulation: Journal of the American Heart Association.

Francis Kim, M.D., of Harborview Medical Center in Seattle, and colleagues treated 125 individuals who experienced cardiac arrest outside the hospital and were subsequently resuscitated with standard care alone, with or without induction of mild hypothermia by infusion of up to 2 liters of saline at 4 degrees Celsius.

Patients who received cooled saline had a mean hospital-measured esophageal temperature that was 1.24 degrees C lower than in the field, while those in the control group had temperature readings 0.10 degrees C higher than in the field. The greatest effect was observed when the amount of saline infused was between 500 mL and 2 L. Safety parameters were largely identical in both groups, except that the cooled patients had a higher first heart rate reading, lower pH and lower incidence of cardiomegaly. Those who were cooled and whose initial rhythm was ventricular fibrillation tended to survive to hospital discharge (66 percent versus 45 percent who were not cooled).

"The infusion of 4 degree C normal saline in the field appears to be an effective method for inducing mild hypothermia in resuscitated out-of-hospital cardiac arrest patients," the authors write.

AbstractFull Text (subscription or payment may be required)

Secondhand Smoke Lowers Pediatric Vascular Function

Dose-dependent relationship seen between increasing nicotine exposure and decreasing vascular function

Pediatric exposure to secondhand smoke adversely affects vascular function, according to a report published online June 4 in Circulation: Journal of the American Heart Association.

Katariina Kallio, M.D., of the University of Turku in Finland, and colleagues examined levels of cotinine (a nicotine metabolite) and arterial endothelial function (by ultrasound) in 402 healthy, non-smoking 11-year-old children.

Of 327 children for whom four cotinine measurements (from age 8 to 11) and ultrasound data were available, peak flow-mediated dilation and area under the curve values consistently decreased with increasing nicotine exposure. Flow-mediated dilation values dropped from a mean 9.14 percent for those with consistently low cotinine, to 7.14 percent for those with consistently high cotinine levels. Temporal development of the flow-mediated dilation responses also differed between groups, with those in the consistently high cotinine group showing the poorest response.

"The present data suggest that passive smoking alters endothelial function in childhood, and thus has a role in the development of early atherosclerosis," the authors write.

AbstractFull Text (subscription or payment may be required)

Prepared jointly by the editors of Medical Economics and HealthDay's Physicians' Briefing (www.physicianbriefing.com)

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