Latest Research

Antifolate, Combo Therapy Effective in Fighting Malaria

Studies outline best treatment options in Uganda and South Asia

Antifolates proved effective against P. vivax malaria in South Asia, while an artemether-lumefantrine combination was helpful in treating uncomplicated malaria in Uganda, according to two studies in the May 23/30 issue of the Journal of the American Medical Association.

Toby Leslie, M.Sc., of the London School of Hygiene and Tropical Medicine in London, U.K., and colleagues screened 20,410 patients aged over 3 years in eastern Afghanistan and northwestern Pakistan, of whom 767 patients had Plasmodium vivax malaria. They were randomized to receive chloroquine, or one of two antifolate drugs -- sulfadoxine-pyrimethamine or chlorproguanil-dapsone.

"Although chloroquine remains the drug of choice, antifolates are effective against P. vivax malaria in South Asia. These drugs may be appropriate for unified treatment where species-specific diagnosis is unavailable, most likely in combination with other drugs," the authors conclude.

Grant Dorsey, M.D., Ph.D., of the University of California San Francisco, and colleagues conducted a study of three combination treatment options for uncomplicated malaria among 329 children in Kampala, Uganda, diagnosed with at least one episode of Plasmodium falciparum malaria. The most effective treatment was an artemether-lumefantrine combination.

"With all study regimens, the provision of prompt and reasonably effective facility-based treatment was associated with good outcomes in long-term health measurers," the authors conclude.

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Imported Malaria Requires Vigilance By U.S. Docs

With 1,200 cases imported yearly, physicians must be familiar with symptoms and treatment

As more Americans travel to areas where malaria is endemic, U.S. doctors should be familiar with the symptoms and treatment of the disease, which infects an average 1,200 people in the United States yearly, according to a report in the May 23/30 issue of the Journal of the American Medical Association.

Kevin S. Griffith, M.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues reviewed management recommendations for uncomplicated and severe malaria published between 1966 and 2006. They found that there are a range of measures that physicians should take, including considering a patient's travel history when diagnosing the cause of fever, prompt diagnosis and timely treatment.

For Plasmodium falciparum acquired in areas without chloroquine-resistant strains of the disease, the researchers found that the optimum treatment is still chloroquine. Treatment for malaria acquired in chloroquine-resistant strain areas comprises a combination of atovaquone and proguanil, or quinine plus tetracycline, doxycycline or clindamycin. The authors also spell out optimum treatment measures for other strains of malaria.

"Malaria remains a diagnostic and treatment challenge for U.S. clinicians," the authors write. "A strong evidence base exists to help clinicians rapidly initiate appropriate therapy and minimize the major mortality and morbidity burdens caused by this disease."

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DNA Changes in Stromal Cells Linked to Breast Tumor Grade

Researchers use whole genome technique to identify DNA regions in stromal cells surrounding tumors

Genetic markers found in the stromal and epithelial cells surrounding primary sporadic breast cancers are associated with tumor grade, metastases and other clinicopathological features, such as the presence of progesterone receptors, according to a report in the May 16 issue of the Journal of the American Medical Association.

Charis Eng, M.D., Ph.D., of the Cleveland Clinic Genomic Medicine Institute in Ohio, measured loss of heterozygosity and allelic imbalances by whole genome genotyping in stromal and epithelial cells from 220 primary sporadic invasive breast carcinomas.

The investigators found two markers on chromosome 14 in epithelial cells that were associated with progesterone-receptor expression, and genomic instability on seven chromosomes (1, 2, 5, 11, 18, 20, 22) in stromal cells that were linked to either tumor grade or the presence of lymph node metastases. The "hot spots" included regions near the ATM and TP53 genes, but did not include the HER2 gene, perhaps because of low resolution.

"Genetic changes acquired in the stroma adjacent to transformed epithelial cells contribute an additional dimension of progression modulation beyond that contributed by the carcinoma cells themselves. The combination of stromal and epithelial genetic changes produces a greater range of outcome scenarios than can otherwise be explained by carcinoma cell genotype alone," the authors conclude. The data should be validated in larger trials with longer follow-ups, they add.

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Even Minimal Exercise Helps Overweight Women

Three days per week can increase fitness by 4.2 percent over sedentary control

As little as 72 minutes of physical activity per week can help improve the fitness of sedentary postmenopausal women who are overweight or obese, researchers report in the May 16 issue of the Journal of the American Medical Association.

Timothy S. Church, M.D., Ph.D., of Louisiana State University in Baton Rouge, and colleagues randomized 464 women with elevated blood pressure and a body mass index between 25 and 43, to six months of physical activity at 50, 100 and 150 percent of the weekly energy expenditure recommended by the NIH Consensus Development Panel.

The investigators found a graded response in overall fitness, measured as absolute oxygen consumption on a cycle ergometer, that reached 8.2 percent over control for the highest energy expenditure. The study authors note that even the lowest physical activity group, accounting for 4-kcal/kg or 72 minutes of exercise per week over three days, showed a 4.2 percent improvement over the control group. There were no effects on systolic or diastolic blood pressure, however.

The study provides "important information on the dose of physical activity to improve physical fitness, a strong predictor of chronic disease and premature mortality," according to an editorial by I-Min Lee, of Brigham and Women's Hospital and Harvard Medical School in Boston. "This may be succinctly summarized for patients and clinicians as 'Even a little is good; more may be better!'"

The authors report receiving compensation in the form of consulting fees, lecture fees, honoraria, or royalties from Trestle Tree, Inc., and Jenny Craig, among others.

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Low-Glycemic Diet Improves Weight Loss for Some Dieters

Those with high insulin secretion may achieve better weight loss with low-glycemic load diet

Overweight individuals with high insulin secretion may achieve greater weight loss by selecting diets with a low-glycemic load rather than diets that are low in fat, according to the results of a randomized trial published in the May 16 issue of the Journal of the American Medical Association.

Cara B. Ebbeling, Ph.D., of Children's Hospital Boston, and colleagues randomized 73 obese adults, aged 18 to 35 years, to six months of either a low-glycemic load diet (consisting of 40 percent carbohydrate and 35 percent fat) or a low-fat diet (consisting of 55 percent carbohydrate and 20 percent fat), and compared weight loss from each diet as a function of baseline insulin secretion.

Overall, both diet groups achieved the same reductions in weight and body fat composition, losing about 4 kg and about 1.3 percent of body fat at six months. However, those individuals with baseline insulin secretion above the median achieved greater decreases in body weight (5.8 versus 1.2 kg) and body fat percentage (2.6 versus 0.9 percent) than the low-fat dieters.

"Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion," the authors conclude. "Regardless of insulin secretion, a low-glycemic load diet has beneficial effects on concentrations of high-density lipoprotein cholesterol and triglycerides but not on low-density lipoprotein cholesterol."

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For Infants in Neonatal ICUs, Mortality Varies with Care

Lower mortality in NICUs with high level of care, high volume of very low birth weight infants

Very low birth weight infants born in hospitals with neonatal intensive care units (NICUs) with a high level of care and high volume of such infants have a lower risk of death than infants born in lower quality and lower volume hospitals, according to a report in the May 24 issue of the New England Journal of Medicine.

Ciaran S. Phibbs, Ph.D., from Stanford University School of Medicine in Stanford, Calif., and colleagues compared neonatal mortality in 48,237 very low birth weight infants (under 1,500 g) in California NICUs in the 1990s based on the hospital's level of care and volume of such infants.

The researchers found that very low birth weight infants in NICUs with lower levels of care and lower volumes had a higher risk of death than infants in NICUs with higher levels of care and higher volumes (more than 100 per year, odds ratio 1.19-2.72). Fewer than one-quarter of NICUs were classified as high-level care and high-volume, and 92 percent of deliveries occurred in urban areas with high-volume NICUs.

"Mortality among very low birth weight infants was lowest for deliveries that occurred in hospitals with NICUs that had both a high level of care and a high volume of such patients," Phibbs and colleagues conclude. "Our results suggest that increased regionalization of perinatal care might reduce mortality among very low birth weight infants."

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Aspirin Reduces COX-2 Expression in Colon Cancer

COX-2 promotes inflammation, cell proliferation

Among colon cancer patients, regular aspirin use reduces the risk of having tumors that overproduce cyclooxygenase-2 (COX-2), an enzyme that promotes inflammation and cell proliferation, according to the results of a study in the May 24 issue of the New England Journal of Medicine.

Andrew T. Chan, M.D., from Massachusetts General Hospital in Boston, and colleagues examined the association between aspirin use and COX-2 expression in 636 colorectal cancer specimens. Patients provided data on aspirin use every two years and COX-2 expression was assessed by immunohistochemistry.

The researchers found that 67 percent of specimens had moderate or strong COX-2 expression. Patients who took aspirin regularly were less likely to have tumors that overproduced COX-2 (multivariate relative risk, 0.64) but were equally likely to have tumors with weak or no expression of COX-2 (multivariate relative risk, 0.96). Regular aspirin users had an age-standardized incidence of 37 per 100,000 person-years for cancers that overproduced COX-2, compared with 56 per 100,000 for those who did not use aspirin regularly.

"The findings…provide powerful support for the role of COX-2 as a key mediator in the development of colon cancer and now pose important questions about the biologic basis and clinical implications of discovering differences between colon cancers that express high or low levels of COX-2," states an accompanying editorial.

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Adding Advanced Life Support to EMS Reduces Mortality

Death rate reduced by about 2 percent in patients with respiratory distress

Adding measures such as endotracheal intubation and intravenous drugs to the basic life support provided by emergency medical services (EMS) reduces the death rate in patients with respiratory distress by about 2 percent, researchers report in the May 24 issue of the New England Journal of Medicine.

Ian G. Stiell, M.D., from the University of Ottawa in Canada, and colleagues examined whether adding advanced life support to basic life support in EMS could reduce out-of-hospital respiratory distress. The study was conduced in 15 cities in Ontario, Canada, and involved 8,138 patients, of which 3,920 were in the basic life support phase (January 1995 to February 1998) and 4,218 were in the advanced life support phase (February 1998 to November 2000).

During the second phase, 56.6 percent of patients received advanced life support. Of these, 1.4 percent received endotracheal intubation and 15 percent received intravenous drugs. The use of nebulized salbutamol and sublingual nitroglycerin for symptom relief increased from 15.7 percent to 59.4 percent. After the addition of advanced life support, the death rate fell from 14.3 percent to 12.4 percent (adjusted odds ratio, 1.3).

"The addition of a specific regimen of out-of-hospital advanced-life-support interventions to an existing EMS system that provides basic life support was associated with a decrease in the rate of death of 1.9 percentage points among patients with respiratory distress," Stiell and colleagues conclude.

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Rosiglitazone May Increase Risk of Myocardial Infarction

FDA issues safety alert on Avandia

Patients with type 2 diabetes who are treated with rosiglitazone (Avandia) may have an increased risk of myocardial infarction and possibly cardiovascular-related death compared to those not treated with the drug, according to a meta-analysis of 42 trials published early online May 21 in the New England Journal of Medicine. The U.S. Food and Drug Administration issued a safety alert on Avandia on Monday.

Steven Nissen, M.D., and Kathy Wolski, M.P.H., from the Cleveland Clinic in Ohio, analyzed data from the U.S. Food and Drug Administration and GlaxoSmithKline's clinical trials registry. They included 42 of 116 possible studies that lasted longer than 24 weeks, had a randomized, non-rosiglitazone control group and data on myocardial infarctions and cardiovascular mortality.

The investigators found that the odds ratio for myocardial infarction was 1.43 in rosiglitazone-treated patients compared with controls. The odds ratio for cardiovascular mortality was 1.64, but the finding was of borderline statistical significance.

The analysis has a number of weaknesses and a "few events either way might have changed the findings for myocardial infarction or for death from cardiovascular causes," according to an editorial by Bruce Psaty, M.D., Ph.D., and Curt Furberg, M.D., Ph.D. "In this setting, the possibility that the findings were due to chance cannot be excluded. In their discussion, the authors properly emphasize the fragility of their findings."

"Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes," according to the FDA.

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AUA: Sling Better Than Burch for Stress Incontinence

Head-to-head study shows sling procedure more effective than Burch, but has more complications

Pubovaginal sling surgery is more effective than the Burch colposuspension method for treating stress incontinence in women, however the sling procedure has a higher rate of complications, according to the results of a new head-to-head trial presented at the annual meeting of the American Urological Association in Anaheim, Calif. The findings will also appear in the May 24 issue of the New England Journal of Medicine.

Michael E. Albo, M.D., of the University of California San Diego, and colleagues randomized 655 women to undergo either the sling or the Burch procedure to treat stress incontinence.

At 24 months, 47 percent of the women who underwent the sling procedure were successful overall compared with 38 percent of the women who underwent the Burch colposuspension procedure. What's more, 66 percent of women who underwent the sling procedure had success with stress-specific leakage, compared with 49 percent of women who had the Burch procedure. More women who had the sling procedure reported being satisfied with the surgery.

Women in the sling group did have higher rates of complications, namely voiding problems, urgency symptoms, urinary tract infection and repeat operations to address voiding issues.

The findings "greatly advance our ability to counsel patients and effectively compare surgical options for treatment of stress incontinence," writes Kris Strohbehn, M.D., of Dartmouth Medical School in Lebanon, N.H., in an editorial accompanying the new report.

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Corticosteroids for Mild Asthma Can Be Stepped-Down

Changes in treatment regimen allow corticosteroid dose to be reduced without treatment failure

Patients with mild, persistent asthma that is well controlled can step down their inhaled corticosteroids and use a beclomethasone/albuterol inhaler as needed without risking treatment failure, according to two reports in the May 17 issue of the New England Journal of Medicine.

In the first study, Janet Holbrook, Ph.D., of Johns Hopkins University in Baltimore, and members of the American Lung Association Asthma Clinical Research Centers conducted a randomized step-down study in 500 patients with asthma that was well controlled with twice-daily inhaled fluticasone, and found that once daily fluticasone with salmeterol was just as effective while reducing the total corticosteroid dose. Once-daily montelukast was associated with higher treatment failure.

In the second study, Leonardo Fabbri, M.D., of the Universita di Modena in Italy, and the BEST study group found in a six-month, randomized, double-blind study that patients with mild asthma could use a beclomethasone/albuterol inhaler as needed and achieve the same effectiveness as regular use of beclomethasone while reducing the cumulative dose of inhaled corticosteroid.

A discussion of three treatment options for mild persistent asthma is presented in an accompanying Clinical Decisions interactive article, a new forum designed to understand the decisions physicians make everyday at the bedside and in the office. Readers are encouraged to participate online by voting for a treatment option and, if they like, to comment on their decision.

Financial disclosures are included with each article.

Abstract - HolbrookFull Text (subscription or payment may be required)Abstract - FabbriFull Text (subscription or payment may be required)Editorial

Very Low Birth Weight Linked to Poor Glucose Regulation

Preterm infants with very low birth weight develop poor glucose regulation as young adults

Infants born with a very low birth weight, less than 1,500 grams, have a higher risk of insulin resistance and glucose intolerance as young adults than those born with normal weight, according to a report in the May 17 issue of the New England Journal of Medicine.

Petteri Hovi, M.D., of the National Public Health Institute in Helsinki, Finland, and colleagues performed a 75-g oral glucose test in 163 young adults born preterm with a birth weight less than 1,500 g, and in 169 young adults born with normal birth weights. Insulin and glucose levels were measured at baseline and at 120 minutes.

The investigators found that very low birth weight subjects had two-hour glucose concentrations that were 6.7 percent higher than control subjects. Also, insulin concentrations in these subjects were 16.7 percent higher while fasting and 40 percent higher after two hours than their matched controls, giving an 18.9 percent higher insulin-resistance index. In addition, very low birth weight subjects had an average systolic blood pressure that was 4.8 mm Hg higher than controls.

The results suggest "that persons with very low birth weight might be more vulnerable to disorders such as type 2 diabetes and cardiovascular disease later in life," the authors conclude. "Lifestyle interventions are effective in preventing these disorders, and the identification of persons at increased risk early in life provides an important opportunity for disease prevention."

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HPV Vaccine Protects Against Vulval and Vaginal Cancers

Vaccine halves incidence of high-grade lesions caused by human papillomavirus

In addition to offering protection against cervical cancer, the quadrivalent human papillomavirus (HPV) vaccine also offers women protection against vulval and vaginal cancers, researchers report in the May 19 issue of The Lancet.

Jorma Paavonen, M.D., of the University Central Hospital in Helsinki, Finland, and colleagues conducted a study of 18,174 women, aged 16 to 26 years, who were randomized to receive three doses of either quadrivalent HPV6/11/16/18 vaccine or placebo, and who were then followed-up for a mean three years.

In terms of protection against high-grade vulval intraepithelial neoplasia and vaginal intraepithelial neoplasia associated with HPV16 and HPV18, the vaccine was 100 percent effective in women who were not infected with either of the strains during the six-month vaccination period and one month after. Efficacy was 71 percent in women with previous exposure to the virus strains and the vaccine conferred 49 percent protection against incidence of the two cancers regardless of the presence or absence of HPV DNA.

"The maximum effect of vaccination is expected in girls who are vaccinated in early adolescence, before exposure. The effect of vaccination in the general population of sexually experienced young women is expected to be lower initially, due to prevalent HPV infection," the authors conclude. "This intervention could greatly reduce the morbidity, mortality and health-care costs associated with these diseases."

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Hormone Agonists Helpful in Premenopausal Breast Cancer

Ovarian suppression may help treat patients if used in combination with standard therapies

When used in combination with chemotherapy and tamoxifen, luteinizing-hormone-releasing hormone (LHRH) agonists are effective in treating hormone-receptor-positive breast cancer in premenopausal women, according to a meta-analysis published in the May 19 issue of The Lancet.

Jack Cuzick, Ph.D., of the University of London in the United Kingdom, and colleagues in the LHRH Agonists in Early Breast Cancer Overview group reviewed data from 16 trials comprising 11,906 premenopausal women with early breast cancer.

Used alone, the hormone agonists did not reduce recurrence or death after recurrence, but when used in combination with tamoxifen, chemotherapy or both, the agonists reduced recurrence by 12.7 percent and death after recurrence by 15.1 percent. The LHRH agonists had no effect on hormone-receptor-negative breast cancer.

"The results of our analysis show that LHRH agonists provide an effective additional class of agents for the treatment of premenopausal women with hormone-sensitive breast cancer," the authors conclude.

Chemotherapy followed by tamoxifen should remain the standard approach for women with higher-risk disease, but the addition of LHRH agonists for premenopausal women is worth considering, according to the authors of an accompanying editorial. "A century of research has taught us much about endocrine therapy for breast cancer, but the most important lessons about adjuvant ovarian suppression will be learnt over the next decade," they write.

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Study Finds No Cancer Risk from Blood Transfusions

Blood from donors with undiagnosed cancer does not appear to pose risk to recipients

There is no evidence that blood from donors with undiagnosed cancer can increase the risk of cancer in recipients, according to the results of a study published in the May 19 issue of The Lancet.

Olof Nyrén, M.D., of the Karolinska Institute in Stockholm Sweden, and colleagues analyzed data from 354,094 patients who had received blood transfusions, of whom 12,012 (3 percent) were exposed to blood products from donors later diagnosed with cancer.

When data on recipients from pre-cancerous and non-cancerous donors were compared, the investigators found no difference in terms of cancer risk in the recipients.

"Although our findings should not be over-interpreted, the overall consistency of the negative results does not support the hypothesis that allogenic transfusion of single malignant cells can lead to engraftment and subsequent development of clinical malignancies in human transfusion recipients," the authors conclude.

"Blood is an immensely complex and biologically active substance. Although the potential for standard allogenic blood transfusion to save lives is incontrovertible, our understanding of the full consequences of transfusion is rudimentary," writes Garth Utter, M.D., of the University of California-Davis, in an editorial. He adds that the authors "have taken an important stride forward in evaluating one of these potential long-term risks of blood transfusion."

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Aspirin Modestly Reduces Risk of Preeclampsia

Also reduces risk of premature delivery and adverse pregnancy outcomes

Aspirin modestly reduces the risk of preeclampsia, premature delivery and serious adverse pregnancy outcomes in at-risk women, according to a meta-analysis published online May 17 in The Lancet.

Lisa M. Askie, Ph.D., from the University of Sydney in Australia, and colleagues performed a meta-analysis of 31 randomized clinical trials of anti-platelet agents to prevent preeclampsia. The trials involved 32,217 women and 32,819 infants, and 98 percent of women were in trials of 50 mg to 150 mg aspirin alone per day.

The researchers found that women receiving anti-platelet agents had a reduced risk of preeclampsia (relative risk, 0.90), a reduced risk of delivering before 34 weeks (RR, 0.90), and a reduced risk of having a serious adverse outcome (RR, 0.90). Anti-platelet agents did not significantly affect the risk of death in fetus or infant, having a small-for-gestational-age infant, or bleeding in the women or their infants.

"There are certain settings in which preeclampsia is almost a certainty, including women with preeclampsia in more than one pregnancy or women with chronic hypertension and preeclampsia in a previous pregnancy," James M. Roberts, M.D., and Janet M. Catov, Ph.D., of the University of Pittsburgh, write in an accompanying editorial. "In these settings, aspirin is justified."

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Premature Infants May Benefit from Probiotics

'Good bacteria' could help reduce risk of necrotizing enterocolitis

The use of probiotics in premature infants may reduce the risk of necrotizing enterocolitis, according to study findings published in the May 12 issue of The Lancet.

Sanjay Patole, Dr.P.H., of the King Edward Memorial Hospital for Women in Western Australia, and colleagues conducted a systematic review of seven controlled trials comprising 1,393 preterm newborns with very low birth weight who were randomized to receive or not receive probiotic supplementation.

Supplementation with probiotics reduced the risk of developing necrotizing enterocolitis by 64 percent, and reduced the mortality risk by 53 percent, compared to the control groups. Risk of sepsis was similar between the two groups.

"The usual measures for the prevention of necrotizing enterocolitis are feeding with breast milk and delaying preterm delivery," writes Carlo Caffarelli of the University of Parma, Italy, in an editorial. "The overview by [Patole] and colleagues is an important step towards an evidence-based use of probiotics. However, further large controlled trials are needed before recommending these promising agents."

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Daily Aspirin May Reduce Risk of Colorectal Cancer

But risks rule it out as population-wide chemopreventive drug

Taking at least 300 mg/day of aspirin for five years confers protection against colorectal cancer, but the risks of taking the drug outweigh the benefits in the population as a whole, according to a report published in the May 12 issue of The Lancet.

Enrico Flossmann, D.Phil., and Peter M. Rothwell, F.R.C.P., of Radcliffe Infirmary in Oxford, U.K., analyzed data from two large randomized trials with more than 20 years of follow-up. The first trial comprised 5,139 subjects, of whom two-thirds took 500 mg/day of aspirin for five years while the remaining third were control subjects. The second trial comprised 2,449 subjects, two-thirds of whom took 300 mg/day or 1,200 mg/day of aspirin for one to seven years, and one-third of whom took placebo.

While subjects in the aspirin groups had lower incidence of colorectal cancer in both trials, the effects were only observable after 10 years and was greatest 10 to 14 years after the trials began.

However, the risks outweigh the benefits for the general population. "With the concerns about the potential risks of long-term aspirin use and the availability of alternative prevention strategies (e.g., screening), these findings are not sufficient to warrant a recommendation for the general population to use aspirin for cancer prevention," writes Andrew Chan, M.D., of Massachusetts General Hospital in Boston, in an editorial.

Rothwell has received honoraria from several pharmaceutical companies but none in support of this work.

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Good News, Bad News for Oral Smokeless Tobacco

Product doubles the risk of pancreatic cancer, but may be a relatively safe approach to quitting smoking, too

Snus, a smokeless, moist oral tobacco sold in Scandinavia, can double the risk of pancreatic cancer in men who use the product compared to those who have never used tobacco, according to a report published online May 10 in The Lancet. However, a second report suggests that smokers may gain some benefits by switching from cigarettes to snus in an effort to quit tobacco altogether.

Olof Nyren, M.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues followed nearly 280,000 men for an average 20 years to measure the effect of snus on the incidence of oral, lung and pancreatic cancers. They found that snus use doubled the risk of pancreatic cancer relative to those who never used any tobacco. No increase in risk was observed for oral or lung cancers.

Wayne Hall, Ph.D., of the University of Queensland in Australia, and colleagues computed the health-adjusted life expectancy in Australia among current smokers who either continued to smoke, switched to snus or quit tobacco altogether; and in people who used snus yet never smoked. The difference in male health-adjusted life expectancy was 2.4 to 5 years (depending on age) lower in current smokers compared with never smokers. However, the life expectancies were closer in never users and current snus users who never smoked (0.2- to 0.5-year difference) and in smokers who quit all tobacco and those who switched to snus. (0.1- to 0.3-year difference for men).

These findings "indicate that we should not delay in allowing snus to compete with cigarettes for market share, and we should be prepared to accurately inform smokers about the relative risks of cigarettes, snus and approved smoking-cessation medications," write the authors of an accompanying editorial.

Abstract -- NyrenFull Text (subscription or payment may be required)Abstract -- HallFull Text (subscription or payment may be required)Editorial

Personalized Pharmacy Care Benefits Heart Failure Patients

Patient-centered pharmacist care improves medication adherence, outcomes

Heart failure patients who receive one-on-one personalized care from their pharmacists are more likely to take their medications as prescribed and tend to make fewer trips to the hospital than their counterparts who receive usual care from pharmacists, according to a new study in the May 14 issue of the Annals of Internal Medicine.

Michael D. Murray, PharmD, M.P.H., of the University of North Carolina at Chapel Hill, and colleagues investigated 314 low-income heart failure patients randomized to a usual-care control group or an intervention group in which pharmacists took medication histories and provided verbal instructions and written materials to patients. The written materials were aimed at patients with low health literacy.

Patients who received care from specially trained pharmacists during the nine-month study took their medications 11 percent more consistently than patients in the control group. These differences faded within three months of stopping the intervention. Patients in the intervention group had 19 percent fewer emergency department visits and hospitalizations than their counterparts who received usual care from pharmacists.

"Ongoing educational intervention by a pharmacist can improve medication adherence and outcomes in patients with heart failure," the study authors conclude.

AbstractFull Text

Better Depression Care Cuts Mortality Risk in Elderly

Algorithm-based depression care program can reduce risk of cancer death

Older patients with depression who are enrolled in a primary care program to improve depression management may live longer than their counterparts who do not take part in such a program, according to a report in the May 15 issue of the Annals of Internal Medicine.

Joseph J. Gallo, M.D., of the University of Pennsylvania in Philadelphia, and colleagues evaluated whether an intervention designed to improve depression care affected risk of death among 1,226 older adults from 20 primary care practices. The intervention consisted of a depression care manager who worked with the primary care doctor to provide algorithm-based care.

There was a 45 percent reduction in risk of death among patients with major depression who were cared for in practices that implemented the practice-based depression model. For reasons that are unclear, the reduction was mainly due to death from cancer.

"If we are to prepare for the increasing need for mental health services among older persons and to ease the burden of disability associated with depression, we must engage primary care practices as partners in developing services that interrupt the pathway from depression to death," the study authors conclude.

AbstractFull Text

Cereal Fiber, Magnesium May Stave Off Type 2 Diabetes

High intake of cereal fiber and magnesium may protect against type 2 diabetes

A diet rich in fiber from grains as well as magnesium may help lower the risk of type 2 diabetes, according to new research published in the May 14 issue of the Archives of Internal Medicine.

Matthias B. Schulze, Dr.P.H., of the German Institute of Human Nutrition Potsdam-Rehbruecke in Nuthetal, Germany, and colleagues followed 9,702 men and 15,365 women, aged 35 to 65, for an average of seven years. They also conducted a meta-analysis of how fiber intake and magnesium affect diabetes risk.

A total of 844 subjects developed type 2 diabetes. Participants who ate the most amount of fiber from any source had a 27 percent lower risk of developing diabetes than those who ate the least amount of fiber. Magnesium intake was not associated with diabetes risk.

In the meta-analysis, individuals who consumed the most cereal fiber has a 33 percent lower risk of developing diabetes than their counterparts who ate the least amount. Participants who consumed the most magnesium had a 23 percent lower risk for diabetes, compared with those who consumed the least.

"The evidence from our study and previous studies, summarized by means of meta-analysis, strongly supports that higher cereal fiber and magnesium intake may decrease diabetes risk," the study authors conclude.

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Calcium and Vitamin D Cut Postmenopausal Weight Gain

Women's risk of weight gain 11 percent lower with the supplements than with placebo

Women who take calcium and vitamin D supplements after menopause are less likely to gain weight than women who take a placebo, particularly women who have an inadequate intake of calcium in their diet, according to the results of a randomized trial published in the May 14 issue of the Archives of Internal Medicine.

Bette Caan, Ph.D., of Kaiser Permanente Northern California in Oakland, and colleagues analyzed annual body weight changes in 36,282 postmenopausal women, aged 50 to 79, who were involved in the Women's Health Initiative trial. The women were randomly assigned to take a daily placebo or 400 International Units of cholecalciferol (vitamin D) and 1,000 milligrams of elemental calcium.

Women who took calcium and vitamin D experienced smaller weight gain over the seven-year study, and their mean weight was 0.13 kilograms lower than the placebo group. Women consuming less than 1,200 milligrams of calcium a day at baseline who took the supplements had an 11 percent lower risk of gaining 1 to 3 kilograms and 11 percent lower risk of gaining more than 3 kilograms after three years than those taking a placebo.

"Our findings do not alter current dietary recommendations. Postmenopausal women should continue to be advised to consume 1,200 mg/d of calcium as recommended by the Food and Nutrition Board of the National Academy of Sciences," the authors write.

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Sleep Apnea May Increase Risk of Heart Failure Death

Study shows risk of death doubles for heart failure patients with central sleep apnea

A number of factors are associated with an increased risk of death in patients with systolic heart failure, including central sleep apnea, right ventricular systolic dysfunction and low diastolic blood pressure, researchers report in the May 22 issue of the Journal of the American College of Cardiology.

Shahrokh Javaheri, M.D., of the Veterans Affairs Medical Center in Cincinnati, Ohio, and colleagues followed 88 patients with systolic heart failure (defined by a left ventricular ejection fraction of 45 percent or less) for an average of 51 months to determine if central sleep apnea increases mortality for heart failure patients. The average age of patients was 62 years for those with an apnea-hypopnea index (AHI) of less than 5 per hour and 67 years for those with an AHI of 5 or greater per hour.

The mean AHI for patients with sleep apnea was 34 per hour compared to 2 per hour for those without. Survival of patients with sleep apnea was approximately 45 months compared to 90 months for those without sleep apnea, resulting in a hazard ratio for death of 2.14. Low diastolic blood pressure and right ventricular systolic dysfunction also contributed to poor survival.

The authors emphasize that the link between sleep apnea and mortality in this group remained high, even after adjustment for strong confounders of heart failure including left ventricular ejection fraction, New York Heart Association functional class, and age, among others. The question remains as to "whether the effective treatment of central sleep apnea is associated with improved survival" in patients with heart failure," the authors note.

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Anxiety Associated with Poor Heart Disease Outcome

Authors find higher risk in those with highest stress level versus lowest

Anxiety is associated with an increased risk of myocardial infarction or death in patients who have been diagnosed with coronary artery disease, according to a report in the May 22 issue of the Journal of the American College of Cardiology.

Charles M. Blatt, M.D., of Lown Cardiovascular Center in Brookline, Mass., and colleagues conducted a prospective cohort study of 516 patients with coronary artery disease. They used annual questionnaires to determine the effect of anxiety on a combined outcome of non-fatal myocardial infarction and all-cause mortality.

The study identified 44 non-fatal myocardial infarctions and 19 deaths during an average follow-up of 3.4 years and found that anxiety was significantly associated with the primary outcome. After dividing the cohort into thirds based on anxiety level, the investigators found that patients in the highest tertile of anxiety had a 1.97-fold higher risk for myocardial infarction or death compared with those in the lowest tertile. Multivariate adjustments reduced the risk to a lower but still significant 1.06-fold.

"Repeated measures of anxiety predicted the composite outcome of non-fatal myocardial infarction or death in patients with stable coronary artery disease," the authors write. "Baseline anxiety scores failed to predict these outcomes, suggesting that assessing anxiety regularly over the long term is necessary."

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Early Risk Factors Predict Coronary Artery Calcium

Above optimal risk factors in young adults linked to twofold to threefold odds for coronary artery calcium

Although young adults have relatively low levels of modifiable risk factors for cardiovascular disease, these risk factors are better predictors of coronary artery calcium in middle age than subsequent risks, according to a report in the May 22 issue of the Journal of the American College of Cardiology.

Catherine M. Loria, Ph.D., from the National Heart, Lung, and Blood Institute in Bethesda, Md., and colleagues used data collected from the prospective CARDIA (Coronary Artery Risk Development in Young Adults) study to determine if established, modifiable risk factors for cardiovascular disease (e.g., cholesterol levels, blood pressure, smoking) measured in 18- to 30-year-olds predicts coronary artery calcium (CAC) and other risk factors at ages 33 to 45.

Overall, 9.6 percent of subjects had CAC, with a greater prevalence in males, whites and older subjects. Baseline levels of risk factors predicted CAC as well as 15-year average levels and better than concurrent levels. Risk factors increased the odds for CAC from 1.2-fold per 15-mg/dL glucose to as much as 1.5-fold per 10 cigarettes or 30 mg/dL low-density lipoprotein cholesterol. Young adults with above-optimal risk factor levels at baseline were two to three times more likely to have CAC.

"Early adult levels of modifiable risk factors, albeit low, were equally or more informative about odds of CAC in middle age than subsequent levels," the authors write. "Earlier risk assessment and efforts to encourage young adults to achieve and maintain optimal levels may be needed to prevent or delay coronary calcification, which has been shown to predict subsequent coronary heart disease."

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