Latest Research

Abnormal Electrocardiogram Predicts Future Risk in Women

Minor, major abnormalities linked to higher risk of future cardiovascular events in postmenopausal women

Postmenopausal women without symptoms of cardiovascular disease but who have minor or major abnormalities on an electrocardiogram are more likely to have a future cardiovascular event compared to those with normal results, according to study findings published in the March 7 issue of the Journal of the American Medical Association.

Pablo Denes, M.D., of the Northwestern University Feinberg School of Medicine in Chicago, and colleagues analyzed data on 14,749 postmenopausal women, of whom 9,744 had no electrocardiogram abnormalities, 4,095 had minor abnormalities and 910 had major abnormalities. Among the normal electrocardiogram group, there were 118 cardiac events. There were 91 events among the minor abnormalities group and 37 among those with major abnormalities, generating an incidence rate per 10,000 women of 21, 40 and 75 for the three groups, respectively.

All the subjects were taking hormone therapy or a matching placebo, and the hormone therapy did not affect the risk prediction ability of the electrocardiogram results.

"Given the low cost, wide availability and ease of interpretation, the electrocardiogram may be a useful tool for assisting in the prediction of future cardiovascular events in asymptomatic postmenopausal women. The presence of electrocardiogram abnormalities should prompt physicians to consider further risk stratification, more intensive therapeutic interventions, or both, on modifiable risk factors for primary prevention of cardiovascular events," the authors conclude.

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Study Compares Four Diet Plans in Overweight Women

Women on Atkins diet lose more than those on three other diet programs

The Atkins diet may be the best at helping overweight premenopausal women lose weight, according to the results of a head-to-head competition with three other diet programs published in the March 7 issue of the Journal of the American Medical Association.

Christopher D. Gardner, Ph.D., of Stanford University Medical School in Stanford, Calif., and colleagues examined the year-long effect of four diet plans on weight loss in 311 overweight or obese premenopausal women. The diets were Atkins (very low in carbohydrates); Zone (low in carbohydrates); LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition, which is a low-fat, high-carbohydrate diet based on national guidelines); and Ornish (high in carbohydrates).

Women on the Atkins diet lost an average of 10.4 pounds after 12 months, compared with 3.5 pounds for Zone, 5.7 pounds for LEARN and 4.8 pounds for Ornish. Lipid, insulin and glucose levels, as well as blood pressure measurements, were comparable or more favorable with the Atkins diet than with the other diets.

"Concerns about adverse metabolic effects of the Atkins diet were not substantiated within the 12-month study period," the authors write. "As with any diet, physicians should caution patients that long-term success requires permanent alterations in energy intake and energy expenditure, regardless of macronutrient content."

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CT Screening Does Not Reduce Lung Cancer Deaths

Screening has no impact on diagnosis of advanced-stage lung cancer or death

While routine computed tomography (CT) screening can help detect lung cancer earlier in current and former smokers, it has no effect on diagnosis of advanced-stage lung cancer or death from lung cancer in this group, researchers report in the March 7 issue of the Journal of the American Medical Association.

Peter B. Bach, M.D., of Memorial Sloan-Kettering Cancer Center in New York City, and colleagues measured the frequency of lung cancer detection, resection, advanced-stage lung cancer diagnosis and death from lung cancer in 3,246 asymptomatic current or former smokers undergoing yearly CT screening compared with predicted results from no screening.

The investigators found that patients monitored by CT screening were three times as likely to be diagnosed with lung cancer and 10 times more likely to undergo lung cancer surgery: 144 diagnoses and 109 surgeries occurred compared with the expected rate of 44 diagnoses and 11 surgeries. However, the routine screening did not help reduce the rate of diagnosis of advanced-stage lung cancer or the number of deaths as a result of lung cancer, compared to the predicted values.

"Although expensive and time-consuming, rigorous trials of cancer screening are far more cost-effective than what might be the alternative -- widespread adoption of costly screening interventions that cause more harm than good," write the authors of an accompanying editorial.

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Revascularizations Up in Areas with Cardiac Specialty Units

Rates twice as high as in areas with no units or in areas where units were added to hospitals

Coronary revascularization rates are up to twice as high in regions where cardiac specialty hospitals have opened, many of which are owned by physicians, compared to regions where there are no specialty units or where cardiac programs were added to existing hospitals, according to a report in the March 7 issue of the Journal of the American Medical Association.

Brahmajee K. Nallamothu, M.D., M.P.H., of the University of Michigan Medical School in Ann Arbor, and colleagues calculated annual population-based rates for total revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG), in Medicare beneficiaries from 1995 through 2003. Rates in regions opening specialty hospitals were compared to rates where programs were opened at existing hospitals, or where none were opened.

Four years after the opening of a specialty hospital, total revascularization rates were twofold higher than in regions where cardiac programs were added or where no new programs were opened. Rates were similar when CABG or PCI were considered individually.

"As specialty hospitals evolve, vigilance will be needed to determine if benefits are being delivered as promised and if untoward effects on the delivery system are emerging," write Peter Cram, M.D., M.B.A., and a colleague from the University of Iowa, Iowa City, in an accompanying editorial.

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Discharge Data Not Reaching Primary Care Physicians

Traditional discharge summaries and letters often incomplete, and sometimes never arrive

Effective communication between discharging and primary care physicians is relatively rare, according to a report published in the Feb. 28 issue of the Journal of the American Medical Association.

Sunil Kripalani, M.D., of Emory University School of Medicine in Atlanta, and colleagues performed a meta-analysis of 73 published studies involving communications between the discharging physicians at hospitals and primary care physicians. The dataset included 55 observational studies and 18 controlled interventions.

Communication between discharging physicians and primary care doctors was rare: 3 percent of primary care physicians said they were involved in discharge discussions, and about 20 percent reported being notified about discharges, most commonly in the form of either discharge summaries or discharge letters. In up to 53 percent of cases, patients see their primary care physician before the doctor receives a discharge letter. Many discharge summaries never reached their targets, and a large fraction of those that did were missing key data such as diagnostic test results (33-63 percent) and tests pending at discharge (65 percent).

"According to the results of this review, we suggest several steps to improve communication between inpatient and outpatient physicians at hospital discharge," Kripalani and colleagues write. The authors offer advice on key findings that should be included in the summary, tips for structuring the document for clarity, and suggest that hospitals use information technology for rapid and accurate completion of discharge summaries.

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HPV Affects 25 Million Women in United States

One in four women aged 14 to 59 tests positive for human papillomavirus

One-quarter of American women between the ages of 14 and 59 are infected with human papillomavirus (HPV), according to a report published in the Feb. 28 issue of the Journal of the American Medical Association. Nearly half of sexually active women in their early 20s are infected.

Eileen F. Dunne, M.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues used polymerase chain reaction to test for cervicovaginal HPV in 1,921 women, aged 14 to 59, who participated in the National Health and Nutrition Examination Survey 2003-2004.

Overall, 26.8 percent of samples collected during the survey were positive for HPV, corresponding to some 25 million U.S. women. Women aged 20 to 24 had the highest rate of infection (44.8 percent), with infection rates rising between ages 14 and 24, and then gradually declining. Half (49.3 percent) of sexually active women between 20 and 24 were HPV-positive, followed by women aged 14 to 19 (39.6 percent). The most widely detected serotypes were HPV-62 and HPV-84 (3.3 percent); the most prevalent high-risk form was HPV-53 (2.8 percent). Just over 3 percent of participants were infected with any of the four HPV strains included in the new HPV vaccine.

"Our data indicate that the burden of prevalent HPV infection among women was higher than previous estimates," the authors write.

The study was funded by the CDC.

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Behavioral Therapy Effective for PTSD in Female Veterans

Prolonged exposure more effective than present-centered therapy

A type of cognitive behavioral therapy, prolonged exposure, is about twice as effective as present-centered therapy in treating post-traumatic stress disorder (PTSD) in female veterans and active-duty military personnel, according to the results of a study published in the Feb. 28 issue of the Journal of the American Medical Association.

Paula P. Schnurr, Ph.D., of Dartmouth Medical School in Lebanon, N.H., and colleagues randomly assigned 284 female veterans and active-duty personnel with PTSD to prolonged exposure or present-centered therapy. Prolonged exposure therapy focused on helping patients to face trauma memories and associated situations. Present-centered therapy focused on current life situations as a manifestation of PTSD. Therapy was given in 10 weekly 90-minute sessions and patients were followed for six months.

The researchers found a significant reduction in PTSD symptoms in women in the prolonged exposure group. This group was also significantly more likely to no longer be diagnosed with PTSD (odds ratio 1.80) and to achieve total remission (OR, 2.43).

"Prolonged exposure is an effective treatment for PTSD in female veterans and active-duty military personnel," Schnurr and colleagues conclude. "It is feasible to implement prolonged exposure across a range of clinical settings."

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Antioxidant Supplements Linked with Higher Mortality Risk

Study implicates beta-carotene, vitamins A and E; vitamin C and selenium effects insignificant

Antioxidant supplements such as beta-carotene, vitamin A and vitamin E may increase the risk of mortality, according to a meta-analysis in the Feb. 28 issue of the Journal of the American Medical Association.

Goran Bjelakovic, M.D., of the University of Nis in Serbia, and colleagues performed a meta-analysis of 385 published reports, based on 68 randomized trials. The studies examined the effects of beta-carotene (25 trials), vitamin A (16), vitamin C (34), vitamin E (55) or selenium (21) -- either alone or in combination -- on mortality in adults. In total, some 233,000 individuals were included in the analysis.

After excluding selenium trials and "high-bias risk" trials (about one-third of the studies), beta-carotene, vitamin A and vitamin E, used either singly or with other supplements, were associated with a higher risk of mortality (relative risks of 1.07, 1.16 and 1.04, respectively). Neither vitamin C nor selenium had any mortality effect, either positively or negatively. When high- and low-bias trials were combined, there was no effect on mortality (RR, 1.02).

"Our findings contradict the findings of observational studies, claiming that antioxidants improve health," the authors write. "Considering that 10 percent to 20 percent of the adult population (80-160 million people) in North America and Europe may consume the assessed supplements, the public health consequences may be substantial."

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Antiplatelet Antibodies Linked to Vancomycin

One-third of patients with antibodies experience severe bleeding

Patients treated with vancomycin can develop antiplatelet antibodies that can cause thrombocytopenia and severe bleeding, according to study findings published in the March 1 issue of the New England Journal of Medicine.

Richard H. Aster, M.D., of the Medical College of Wisconsin and the BloodCenter of Wisconsin in Milwaukee, and colleagues analyzed patients from around the United States who were suspected of having vancomycin-triggered thrombocytopenia. Thirty-four patients, about 20 percent of the referred sample, had drug-dependent and platelet-reactive IgG and IgM antibodies, while 25 vancomycin-treated patients who did not develop thrombocytopenia did not have these antibodies.

Severe bleeding occurred in 10 of the 29 patients (34 percent) where clinical follow-up information was available, and these patients were found to have a mean platelet count that was 13,600 per cubic millimeter. Platelet levels returned to baseline when vancomycin was discontinued.

"Laboratory detection of drug-dependent antibodies can be invaluable," writes Theodore E. Warkentin, M.D., of McMaster University in Hamilton, Ontario, Canada, in an accompanying editorial. "Detection of drug-dependent (or drug metabolite-dependent) binding of antibodies to platelet glycoproteins has high specificity but only moderate sensitivity, perhaps because relevant drug metabolites may not be present within the test system."

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Intense Periodontal Treatment Helps Endothelial Function

Short-term effect is negative, but endothelial function better in long-term

While intensive treatment of severe periodontitis may have a negative effect on endothelial function in the short-term, in the long-term it helps to improve endothelial function more than standard treatments, according to a report in the March 1 issue of the New England Journal of Medicine.

Maurizio S. Tonetti, D.M.D., Ph.D., of the University of Connecticut Health Center in Farmington, and colleagues randomly assigned 120 patients with severe periodontitis to community-based treatment (including standard teeth cleaning), or intensive treatment with removal of damaged teeth and subgingival dental plaque biofilms under anesthesia, and placement of minocycline microspheres in periodontal pockets. Patients were removed from the study and treated by a specialist if periodontitis progressed.

Flow-mediated dilation was lower in the intensive group than in the control group 24 hours after treatment, while markers of inflammation and coagulation, including C-reactive protein and von Willebrand factor, were higher. However, endothelial function improved and biomarkers were lower in the treatment group compared with the control group after 60 and 180 days of therapy. The improvement correlated with the decline in periodontal disease.

"It is likely that periodontitis of the severity seen in the patients in this study affects about 0.5 to 1.0 percent of the adult population in the United States, about 3 million people in all," the authors write. "Further studies are required to determine whether the treatment of severe periodontitis could contribute to the prevention of atherosclerosis and cardiovascular events in adults."

Some of the authors received support from or are current employees of Johnson & Johnson, ITI Biologics, Thommen Medical or GlaxoSmithKline.

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Vaccine Prevents Hepatitis E in High-Risk Population

Three-dose regimen shows 95 percent efficacy in volunteers from Nepalese Army

A recombinant hepatitis E vaccine, previously shown to be effective in monkeys, has now been shown to be safe and effective in preventing infection in a high-risk human population, researchers report in the March 1 issue of the New England Journal of Medicine. It is estimated that one-third of the world's population has been infected with hepatitis E.

Bruce Innis, M.D., of GlaxoSmithKline in King of Prussia, Penn., and colleagues conducted a randomized, double-blind phase 2 trial of a recombinant hepatitis E vaccine in volunteers from the Nepalese Army, a population at high risk for infection.

A total of 1,794 subjects were randomized to either three doses of the vaccine or placebo at 0, 1 and 6 months, and followed for a median of 804 days. The investigators found that 66 of the 69 subjects who developed hepatitis E during the follow-up period were in the placebo group, giving a vaccine efficacy of 95.5 percent. Injection-site pain was slightly increased in the vaccine group.

"It will be important to define how this vaccine may affect the reservoir and transmission of HEV, thus determining the overall public health benefit," writes Krzysztof Krawczynski, M.D., Ph.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, in an accompanying editorial. "The cost of the vaccine will be an important factor in determining its availability in the developing world, where it is most needed."

GlaxoSmithKline Biologicals partly funded the study and has intellectual property rights to the vaccine.

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Mutations in Mitochondria Cause Hearing Loss Syndrome

Mutations lead to increased production of reactive oxygen species

Patients with Bjornstad syndrome as well as complex III deficiency and the GRACILE syndrome, which lead to hearing loss and multisystem organ failure, respectively, have mutations in a gene that disrupts mitochondria and causes increased production in reactive oxygen species, according to the results of a study published in the Feb. 22 issue of the New England Journal of Medicine.

Christine E. Seidman, M.D., of Harvard Medical School in Boston, and colleagues identified a single nucleotide variant of the BCS1L gene in affected members of a family with Bjornstad syndrome. Mutations in the gene were also found in four additional unrelated probands with Bjornstad syndrome as well as individuals with complex III deficiency and the GRACILE syndrome.

Characterization of the BCS1L gene showed that it belonged to the family of ATPases necessary to assemble complex III in mitochondria, according to the researchers. Biochemical experiments showed that mutations in the gene led to disrupted assembly of complex III, reduced activity of the mitochondrial electron-transport chain, and increased production of reactive oxygen species. Mutations associated with complex III deficiency also increased mitochondrial content, leading to even higher production of reactive oxygen species, the investigators found.

"We conclude that BCS1L mutations that affect ATP binding or hydrolysis and severely disrupt complex III assembly cause disease by attenuating electron-transport-chain activity and markedly increasing the production of reactive oxygen species," Seidman and colleagues write. "Mutations that cause the Bjornstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species."

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Herpes Simplex Virus Therapy Reduces HIV-1 RNA Levels

In co-infected women, valacyclovir significantly decreases genital and plasma HIV-1 RNA levels

In women who are co-infected with HIV-1 and herpes simplex virus type 2 (HSV-2), HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels, according to research published in the Feb. 22 issue of the New England Journal of Medicine.

Nicolas Nagot, M.D., of the London School of Hygiene and Tropical Medicine in London, U.K., and colleagues recruited 140 women in Burkina Faso who were ineligible for highly active antiretroviral therapy. They randomly assigned the women to receive either 500 milligrams of valacyclovir twice daily or placebo for 12 weeks.

The researchers found that the valacyclovir was associated with significant decreases in the frequency of genital HIV-1 RNA (odds ratio, 0.41), the mean quantity of the virus (log10 copies per milliliter, −0.29), and the mean plasma HIV-1 RNA level (log10 copies per milliliter, −0.53).

"The study by Nagot et al. highlights the potential benefit that screening and treating subclinical HSV-2 infection may offer to patients with HIV infection," states the author of an accompanying editorial. "Many questions about the interaction between these two organisms remain, and larger studies with defined clinical end points are needed to move the medical literature on this interaction into more effective clinical and population-based management. In the meantime, clinicians may want to incorporate more routine HSV-2 testing into the initial evaluation of HIV-seropositive patients."

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COPD Survival Unaffected by Combination Therapy

Study finds no statistically significant survival benefit from salmeterol-fluticasone combination

In patients with chronic obstructive pulmonary disease, or COPD, combination treatment with salmeterol and fluticasone does not significantly reduce the risk of death from all causes compared to placebo but does improve health status and lung function, according to study findings published in the Feb. 22 issue of the New England Journal of Medicine.

Peter M.A. Calverley, M.D., of University Hospital Aintree in Liverpool, U.K., and colleagues randomly assigned 6,112 patients to receive 50 micrograms of salmeterol plus 500 micrograms of fluticasone propionate twice a day, salmeterol alone, fluticasone propionate alone, or placebo.

After three years, 875 patients had died. The researchers found that all-cause mortality rates were 12.6 percent in the combination-therapy group, 13.5 percent in the salmeterol-only group, 16 percent in the fluticasone-only group and 15.2 percent in the placebo group. They also found that combination therapy was associated with a lower annual rate of exacerbations and improved health and spirometric values.

"The clinical guidance is obvious: monotherapy with corticosteroids should not be advocated for patients with COPD, monotherapy with a long-acting bronchodilator appears to be safe, and the combination therapy offers no statistically significant additional survival benefit," states the author of an accompanying editorial.

This study was supported by GlaxoSmithKline.

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DNA Repair Enzymes May Boost Lung Cancer Survival

High expression of RRM1 and ERCC1 benefit patients with non-small-cell lung cancer

In patients who receive surgical treatment for early-stage non-small-cell lung cancer, survival is significantly improved in those with high expression of two enzymes involved in DNA synthesis and repair: ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation group 1 (ERCC1), according to a report published in the Feb. 22 issue of the New England Journal of Medicine.

Zhong Zheng, M.D., Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and colleagues measured RRM1 and ERCC1 expression in histologic specimens from 187 patients and compared the results with clinical outcomes.

RRM1 was found to be correlated with ERCC1, but not with another relevant protein: phosphatase and tensin homologue. High expression of RRM1 in tumors was associated with a median disease-free survival of 120 months (versus 54.5 months in those with low expression) and a median overall survival exceeding 120 months (versus 60.2 months in those with low expression). Survival benefit was limited to the 30 percent of patients who had high expressions of both RRM1 and ERCC1.

"Knowledge of these two gene markers could affect two major aspects of the management of non-small-cell lung cancer: the selection of patients with resected early-stage tumors who do not require adjuvant therapy and the selection of patients who are not likely to benefit from conventional chemotherapy for advanced cancer," states the author of an accompanying editorial.

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Future Global Diabetes Predictions Likely Too Low

Current diabetes prevalence in Ontario, Canada, already exceeds estimates

The prevalence of diabetes in Ontario, Canada rose 69 percent between 1995 and 2005, already exceeding the World Health Organization's predicted 39 percent rise in global diabetes prevalence from 2000 to 2030, according to the results of a study published in the March 3 issue of The Lancet. The findings suggest that the worldwide rise in diabetes may be greater than previously thought.

Lorraine L. Lipscombe, M.D., and Janet E. Hux, M.D., from the University of Toronto in Ontario, Canada, examined diabetes trends in Ontario using data on prevalence, mortality and incidence in adults at least 20 years old.

The researchers found that the age- and sex-adjusted diabetes prevalence increased by 69 percent (from 5.2 to 8.8 percent of the population) between 1995 and 2005. The rate of increase was highest among those aged 20 to 49 years, even though the prevalence was still highest in those over 50 years old. The incidence of diabetes increased by 31 percent between 1997 and 2003, and adjusted diabetes mortality fell by 25 percent between 1995 and 2005.

"The increasing incidence observed in ethnic minorities and the young, coupled with decreasing mortality rates and extended life expectancy, means that prevention is the best method of reducing the global burden of diabetes," according to the journal's editors. "A one-size-fits-all approach is not optimal for the treatment of a disease that affects subpopulations differently."

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'Mild' IVF As Successful As Standard IVF for Live Births

Shorter treatment and single embryo transfer produces fewer multiple pregnancies and costs less

A "mild" version of in vitro fertilization with shorter ovarian stimulation treatment and a single embryo transfer can be as successful as standard IVF in producing live births, but with fewer multiple pregnancies and lower costs, researchers report in the March 3 issue of The Lancet.

Bart C.J.M. Fauser, M.D., from University Medical Center in Utrecht, the Netherlands, and colleagues randomized 404 patients to mild IVF or standard IVF. Mild IVF consisted of shorter ovarian stimulation using co-treatment with gonadotropin-releasing hormone antagonist and transfer of one embryo, while standard IVF consisted of long stimulation with the antagonist and transfer of two embryos.

The researchers found a similar percentage of pregnancies leading to live births with mild and standard treatments after one year (43.4 and 44.7 percent, respectively). However, mild treatment resulted in significantly fewer multiple pregnancies (0.5 percent versus 13.1 percent) and a significantly lower mean total cost (8,333 versus 10,745 euros). The two treatments were similar in terms of patient discomfort, the report indicates.

"Governments should recognize the long-term benefits to patients, to neonatal and postnatal care, and to the public purse of implementing a policy of single embryo transfer and encouraging adoption of the policy with increased funding for such treatments," William L. Ledger, M.D., from the University of Sheffield in the United Kingdom, writes in an accompanying editorial.

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Direct-to-Consumer Ads Should Spur Doc-Patient Discussions

Essayists discuss direct-to-consumer advertising, patient empowerment, effects on medical practice

Direct-to-consumer drug ads should be a topic of discussion between physicians and patients, including the expectations and misperceptions that can result from such advertising, according to a Michigan physician. The "medicalization" of society, represented by direct-to-consumer drug ads, patient empowerment and changing perceptions of illness, is the subject of six essays published Feb. 24 in a special section of The Lancet.

Jonathan Metzl, M.D., Ph.D., of the University of Michigan Medical School in Ann Arbor, wrote or co-wrote two of the essays. Metzl describes ads showing Levitra-invigorated men who throw footballs through tires and antidepressant-treated women who become better mothers, in his essay "If direct-to-consumer advertisements come to Europe: lessons from the USA."

"More nuanced clinical conversations about prescription drugs are needed between doctors and patients," Metzl writes. "Instead of feeling pressure or viewing prescription interactions solely as yes or no decisions, physicians should become more aware of, and constructively address, the intended and unintended expectations and misperceptions raised by direct-to-consumer advertisements."

Other essay authors include Rebecca M. Herzig, Ph.D., of Bates College in Maine; Nancy Tomes, of the State University of New York at Stony Brook; Nikolas Rose, Ph.D., of the London School of Economics; Troy Duster of New York University; and Cindy Patton, Ph.D., of Simon Fraser University in Vancouver, Canada.

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Aspirin Not Advised to Prevent Colon Cancer in Most People

U.S. Preventive Services Task Force also advises against NSAIDs, COX-2 due to possible harms

Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors reduce the incidence of colorectal adenomas or colorectal cancers, but the gastrointestinal and cardiovascular risks do not favor their use in average-risk individuals, according to new recommendations from the U.S. Preventive Services Task Force. The recommendations and two reviews of the data are published in the March 6 Annals of Internal Medicine.

Alaa A. Rostom, M.D., M.Sc., from the University of Calgary Medical Clinic in Alberta, Canada, and colleagues surveyed published literature for studies examining the preventive effect of aspirin on colorectal cancer.

Aspirin reduced the incidence of colonic adenomas in randomized controlled trials, case-control studies and cohort studies (relative risks 0.72-0.87). Aspirin was most effective when used at high doses for longer than 10 years, but it also increased the incidence of gastrointestinal complications in a dose-dependent manner.

Rostom and colleagues also surveyed published literature for studies examining the benefits and harms of non-aspirin NSAIDs and COX-2 inhibitors in the prevention of colorectal cancer and adenoma.

NSAIDs reduced the incidence of colorectal cancer in cohort and case-control studies (relative risk 0.61, 0.70, respectively) and colorectal adenoma (relative risk 0.64, 0.54, respectively). COX-2 inhibitors also reduced the incidence of colorectal adenoma in randomized controlled trials (relative risk 0.72). The rate of ulcer complications was 1.5 percent per year for NSAIDs, which was reduced by COX-2 inhibitors, but long-term use still increased this risk over placebo. Both drug classes, with the exception of naproxen, were associated with an increased risk of serious cardiovascular events.

"The balance of benefits to risk does not favor chemoprevention in average-risk individuals," the authors conclude.

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Internists Perform Smaller Number, Variety of Procedures

Dramatic reduction since 1986

General internists currently perform a dramatically smaller number and variety of medical procedures compared with those performed in 1986, according to a report in the March 6 issue of the Annals of Internal Medicine.

Robert S. Wigton, M.D., from the University of Nebraska Medical Center College of Medicine in Omaha, and Patrick Alguire, M.D., from the American College of Physicians in Philadelphia, surveyed 990 general internists in 2004 regarding the number and types of procedures they perform.

Compared with a similar survey in 1986, the researchers found that, on average, less than half the percentage of internists currently perform each of the 40 procedures surveyed. The average number of procedures also fell from 16 to seven. Similar to the earlier survey, internists practicing in smaller towns and hospitals did, on average, twice as many procedures. Internists who spent more time in total patient care performed a greater number and variety of procedures, the report indicates.

"Internists are capable of learning many procedures, but what we should do depends on how we fit into our particular practice system to best serve our patients," state the authors of an accompanying editorial. "All internists should have access to the training needed to expertly pass needles, catheters, lines and tubes to diagnose and treat illnesses and to learn how to use new technology."

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One-Fifth of Primary Care Patients May Have Anxiety

About 40 percent not receiving treatment

About one-fifth of patients in primary care have an anxiety disorder, but about 40 percent of these patients are not receiving treatment, researchers report in the March 6 issue of the Annals of Internal Medicine.

Kurt Kroenke, M.D., from the Regenstrief Institute for Health Care in Indianapolis, and colleagues surveyed 965 randomly sampled patients in primary care clinics regarding anxiety, using a self-report questionnaire and a follow-up telephone interview with a mental health professional.

The researchers found that 19.5 percent of patients had one or more of four anxiety disorders: post-traumatic stress disorder; a generalized anxiety disorder; a panic disorder; or a social anxiety disorder. All were associated with substantial impairment. However, 41 percent of patients with an anxiety disorder were not receiving treatment. The seven-item Generalized Anxiety Disorder scale and its two core components were useful in detecting all four disorders, the report indicates.

The authors "have performed a large, descriptive study that shines a spotlight on a largely neglected disorder," Wayne Katon, M.D., and Peter Roy-Byrne, M.D., from the University of Washington School of Medicine in Seattle, write in an accompanying editorial.

The study was supported by Pfizer.

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Combination Therapy Improves COPD Quality of Life

However, adding fluticasone and salmeterol to tiotropium does not reduce exacerbations

While adding fluticasone and salmeterol to tiotropium may not decrease exacerbations among patients with chronic obstructive pulmonary disease (COPD), the trio does improve lung function and quality of life as well as decrease risk of hospitalization, according to the results of a study released online Feb. 20 in the Annals of Internal Medicine. The findings are to be published in the April 17 issue of the journal.

Shawn D. Aaron, M.D., of the Ottawa Hospital in Ontario, Canada, and colleagues randomized 449 adults with moderate to severe COPD to treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol for one year. There were no significant differences among the groups in terms of COPD exacerbations (63 percent in the tiotropium/placebo group, 65 percent in the tiotropium/salmeterol group and 60 percent in tiotropium/fluticasone-salmeterol group).

Patients in the tiotropium plus fluticasone-salmeterol group, however, did show improvements in lung function and quality of life compared with patients in the other two groups. Moreover, patients in the tiotropium plus fluticasone-salmeterol group also had decreased risk of being hospitalized for COPD. The study's main limitation is that many patients stopped taking their medication.

"Further methodologically rigorous large studies are required to support our findings and determine whether combined therapy with fluticasone-salmeterol plus tiotropium leads to definitive improvements in rates of COPD exacerbation," the researchers conclude.

The study was not funded by a pharmaceutical company.

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New Model Predicts Risk of Kidney Disease

Researchers call for mass screening using simple scoring method

A novel prediction model known as SCORED (Screening for Occult Renal Disease) that utilizes readily available demographic and medical information may help identify patients at high risk for chronic kidney disease, according to a report in the Feb. 26 issue of the Archives of Internal Medicine.

Heejung Bang, Ph.D., of Weill Medical College of Cornell University in New York City, and colleagues tested the scoring system on 8,530 adults from the National Health and Nutrition Examination Surveys. The model assigns points based on the presence of risk factors including age, sex, blood pressure, diabetes and cardiovascular disease history. Chronic kidney disease was defined as glomerular filtration rate less than 60 mL/min per 1.73 m2.

Overall, 601 adults had kidney disease (5.4 percent). The researchers report that the new model demonstrates a 92 percent sensitivity and 99 percent negative predictive value when using a cutoff score of 4 or higher. The specificity and positive predictive value are low.

The authors call for mass public and private screenings, public education initiatives and Web-based information and questionnaires. "Among individuals scoring 4 or higher in any of these settings, confirmatory testing could then be obtained using a common and relatively inexpensive measurement, serum creatinine concentration," they suggest.

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Smoking May Increase Risk of Tuberculosis

Meta-analysis suggests more than 500,000 annual deaths may be attributed to smoking

People who smoke may be at higher risks for both tuberculosis infection and disease, according to a report published Feb. 26 in the Archives of Internal Medicine.

Kirk Smith, Ph.D., of the University of California, Berkeley, School of Public Health, and colleagues performed a meta-analysis of 24 published studies investigating the relationship between smoking and tuberculosis (TB) infection (six studies), TB disease (13 studies), and TB mortality (five studies).

Smoking increases the relative risk of TB infection by 73 percent (RR, 1.73), and more than doubles the risk of disease (RR, 2.33 when including ex-smokers, 2.66 when ex-smokers are excluded). The summary relative risk for TB mortality was 1.6, but as this was below the risk for disease, the authors suggest that smoking adds no additional risk for mortality. The risk of developing TB when smoking, independent of infection, is estimated to be between 1.4 and 1.6.

Based on a model in which 30 percent of the at-risk population smokes and using a relative risk of 2.5 for developing TB disease and smoking, "Simple attributable proportion calculations suggest that 31 percent of TB cases and TB deaths are attributable to smoking," the authors write. "Because worldwide there are approximately 9 million new TB cases and 1.7 million TB deaths each year, this proportion equates to an annual global burden of 2.79 million new TB cases and 527,000 deaths."

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Blood Pressure Higher in Right Arm, Even in the Left-Handed

Routine second arm readings don't improve accuracy in persons without obstructive arterial disease

Despite right- or left-handedness, hypertensives without obstructive arterial disease have systolic and diastolic blood pressures readings consistently 2 to 3 mm Hg higher in the right arm, researchers report in the Feb. 26 Archives of Internal Medicine.

Kazuo Eguchi, M.D., of Columbia University Medical College in New York City, and colleagues analyzed blood pressure readings from 147 hypertension patients. Three sets of three blood pressure readings were recorded using two oscillometric devices simultaneously in both arms, then three sequential readings were taken with a standard sphygmomanometer; the third set repeated the protocol for the first set.

Large inter-arm systolic blood pressure differences were only seen in two obstructive arterial disease patients. In the remaining patients, systolic blood pressure and diastolic blood pressure, respectively, were 2 to 3 mm Hg higher in the right arm and 1 mm Hg higher for all three sets. For systolic and diastolic blood pressure, respectively, 11 patients (7.5 percent) and four patients (2.7 percent) had a mean inter-arm difference more than 5 mm Hg. Of the 91 patients who repeated the test later, none had consistent inter-arm differences more than 5 mm Hg.

The authors conclude that "routinely taking measurements on a second arm does not improve the accuracy of the measurement in persons without significant obstructive arterial disease. On the other hand, marked and persistent inter-arm blood pressure disparity should prompt an investigation for occlusive arterial disease."

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Strenuous Long-Term Exercise Lowers Breast Cancer Risk

Invasive cancers that develop are less likely to be estrogen receptor-negative

Women who perform strenuous recreational exercise over the long term have a lower risk of in situ and invasive breast cancer, and are less likely to develop estrogen receptor-negative invasive cancers than women who are more sedentary, researchers report in the Feb. 26 issue of the Archives of Internal Medicine.

Leslie Bernstein, Ph.D., of the University of Southern California in Los Angeles, and colleagues prospectively studied 110,599 women, aged 20 to 79 years, with no history of breast cancer at study entry in 1995-1996. Physical activity was assessed from high school to the current age or age 54, as well as in the past three years. By the end of 2002, 2,649 women had been diagnosed with invasive breast cancer and 593 had been diagnosed with in situ breast cancer.

Compared with inactivity (0.5 hours/week per year or less), strenuous long-term physical activity (more than 5 hours/week per year) was associated with a lower risk of invasive breast cancer (relative risk 0.80) and in situ breast cancer (relative risk 0.69). Long-term moderate and strenuous physical activity lowered the risk of estrogen receptor-negative invasive breast cancer, but not estrogen receptor-positive cancer.

"These results support a protective role of strenuous long-term exercise activity against invasive and in situ breast cancer and suggest differing effects by hormone receptor status," Bernstein and colleagues conclude.

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Study Finds No Lipid Benefit to Garlic Supplements

Garlic may have other medicinal properties, but doesn't appear to lower cholesterol

Neither raw garlic nor garlic supplements have a statistically significant effect on serum cholesterol levels, according to a report published in the Feb. 26 issue of the Archives of Internal Medicine.

Christopher Gardner, Ph.D., of Stanford University Medical School in Stanford, Calif., and colleagues studied the effect of raw garlic and two garlic formulations on total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins in 192 adults with moderate hypercholesterolemia (LDL-C; 130-190 mg/dL) over a six-month period.

Subjects were divided into four treatment arms: raw garlic, powdered garlic supplement, aged garlic extract supplement, or placebo. The first three groups received the equivalent of a single clove of garlic per day. There were no statistically significant changes in any measured lipid value over six months in any of the treatment arms. Net change in LDL-C levels at six months for the four groups were 0.4, 3.2, 0.2, and -3.9 mg/dL, respectively.

"Based on our results and those of other recent trials, physicians can advise patients with moderately elevated LDL-C concentrations that garlic supplements or dietary garlic in reasonable doses are unlikely to produce lipid benefits," the authors conclude.

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Frequent Analgesic Use Linked to Hypertension Risk

Risk of high blood pressure up 38 percent in males taking NSAIDs six to seven times per week

Frequent use of analgesics, including aspirin, acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), is associated with an increased risk of hypertension, according to a report published Feb. 26 in the Archives of Internal Medicine.

John Forman, M.Sc., M.D., of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues studied the effects of aspirin, acetaminophen and NSAIDs on the rate of hypertension among 16,031 male health professionals from the Health Professionals Follow-up Study. Data were collected using biennial questionnaires over four years. None of the study participants had a history of hypertension at baseline.

Study subjects reported 1,968 new diagnoses of hypertension during the study period. Compared to subjects taking no analgesics, patients taking NSAIDs six to seven times per week had a multivariate-adjusted relative risk of 1.38. The relative risk for acetaminophen was 1.34 and for aspirin was 1.26. Controlling for baseline blood pressure values did not change the risk. Obesity affected the risk of hypertension among those using acetaminophen and NSAIDs, but not aspirin. The link between acetaminophen use and hypertension was greatest among individuals with a body mass index (BMI) below 25; the association between NSAID use and hypertension was greatest with BMI above 25. Age had no statistically significant effect on risk.

"Given their common consumption and the high prevalence of hypertension, our results may have substantial public health implications, and suggest that these agents be used with greater caution," the authors conclude.

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Second Twins Born at Term at Higher Risk of Death

A higher risk of death from anoxia in at-term second twins delivered vaginally

Second twins born at term have a more than twofold higher risk of death compared with first twins, primarily due to labor and delivery complications, according to a report published online March 2 in BMJ. Second twins born at term and delivered by Caesarean section have a lower risk of death from anoxia compared with those born vaginally.

Gordon C.S. Smith, M.D., Ph.D., of Cambridge University in the United Kingdom, and colleagues estimated the risk of perinatal death based on birth order in 1,377 twin pregnancies between 1994 and 2003. In each pregnancy studied, there was one perinatal death from causes other than congenital abnormality and one surviving infant.

The researchers found that although birth order had no effect on the overall risk of death, second twins born at term had a significantly higher risk of death (odds ratio 2.3), "principally because of complications of labor and delivery." For twins born at term, second twins born vaginally rather than by Caesarean tended to be at greater risk of death from anoxia (OR, 4.1 versus 1.8).

"In this cohort, compared with first twins, second twins born at term were at increased risk of perinatal death related to delivery," Smith and colleagues conclude.

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Carvedilol Superior to Metoprolol in Heart Failure Study

Large-scale study finds significantly lower risk of adverse cardiovascular events

In patients with heart failure, treatment with carvedilol is associated with improved vascular outcomes compared to treatment with metoprolol, according to a report published in the March 6 issue of the Journal of the American College of Cardiology.

Willem J. Remme, M.D., Ph.D., of the Sticares Cardiovascular Research Institute in Rhoon, the Netherlands, and colleagues randomly assigned 3,029 patients with either ischemic (51 percent) or idiopathic (44 percent) cardiomyopathy to receive either carvedilol (1,511 patients) or metroprolol (1,518 patients) for 58 months.

The researchers found that that carvedilol group had fewer myocardial infarctions than the metoprolol group (hazard ratio 0.71). They also found that the carvedilol group had a lower risk of cardiovascular death or non-fatal myocardial infarction combined (HR, 0.81), unstable angina (HR, 0.71), stroke (HR, 0.79), fatal myocardial infarction or stroke (HR, 0.46), and death after a non-fatal myocardial infarction or stroke (HR, 0.66).

"The anti-ischemic properties of carvedilol can be explained by several mechanisms contributing to vasculo-protection by the drug," the authors conclude. "These effects are clinically relevant, and likely to contribute to the superior therapeutic profile of this beta-blocker in the treatment of heart failure."

The Carvedilol or Metoprolol European Trial (COMET) study was funded by F. Hoffmann- La Roche and GlaxoSmithKline.

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Imaging May Help in Diagnosis of Chest Pain

Multi-slice computed tomography is faster, cheaper than standard care

Multi-slice computed tomography (MSCT) can determine whether coronary disease is the source of chest pain in 75 percent of patients and is significantly faster and cheaper than standard care, researchers report in the Feb. 27 issue of the Journal of the American College of Cardiology.

Gilbert L. Raff, M.D., and colleagues from William Beaumont Hospital in Royal Oak, Mich., randomized 197 patients with low-risk acute chest pain to MSCT or standard of care diagnostic work-ups. Patients with normal MSCT scans were eligible for immediate discharge, those whose scan showed severe stenosis (over 70 percent) underwent invasive angiography, and those whose scan showed intermediate lesions or an unclear diagnosis underwent nuclear stress scans. Patients receiving standard of care underwent nuclear stress scans.

The researchers found that MSCT was able to determine whether coronary disease was the source of chest pain in 75 percent of patients. MSCT diagnosis was also significantly faster (3.4 hours versus 15 hours) and significantly cheaper ($1,586 versus $1,872), and fewer patients undergoing MCST required further evaluations for recurrent chest pain (2 percent versus 7 percent).

"Multi-slice computed tomographic coronary angiography can definitely establish or exclude coronary disease as the cause of chest pain," Raff and colleagues conclude. "However, inability to determine the physiological significance of intermediate severity coronary lesions and cases with inadequate image quality are present limitations."

This work was supported in part by a grant from Minestrelli Advanced Cardiac Research Imaging.

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Latin American Myocardial Infarction Risks Modifiable

Smoking, obesity and high cholesterol account for 88 percent of risk

Over four-fifths of myocardial infarctions in Latin America are attributable to three risk factors -- abdominal obesity, abnormal lipid profiles and smoking, according to a report published in the March 5 issue of Circulation: Journal of the American Heart Association.

As part of the INTERHEART Latin America Study, Fernando Lanas, M.D., of Universidad de la Frontera, Temuco, Chile, and colleagues analyzed data from 1,888 controls and 1,237 patients presenting with a first myocardial infarction in Argentina, Brazil, Colombia, Chile, Guatemala and Mexico. A range of myocardial infarction risk factors were noted, including smoking history, diet, alcohol consumption, exercise, hypertension and diabetes mellitus.

There was a higher risk of acute myocardial infarction among those under persistent stress, with a history of hypertension or diabetes, or who were current smokers. Other significant risk factors were increased waist-to-hip ratio and a higher ratio of apolipoprotein B to A-1.

"The majority of risk of acute myocardial infarction in Latin America can be explained by tobacco use, abnormal lipids, abdominal obesity and hypertension. Given that all these factors are modifiable, the INTERHEART Latin America Study provides a scientific basis to develop preventive strategies that are practical and generally similar in all countries in the entire region," the authors conclude.

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Rise in Fasting Glucose Linked to Heart Failure Risk

Risk of heart failure hospitalization increases 1.10 times for every millimole per liter increase in fasting plasma glucose

Even incremental increases in fasting glucose levels are associated with an increased risk of congestive heart failure in diabetic and other high-risk patients, according to a report published online March 5 in Circulation: Journal of the American Heart Association.

Claes Held, M.D., Ph.D., of the McMaster Clinic in Hamilton, Ontario, Canada, and an international group of researchers examined heart failure risk and fasting glucose levels in 31,546 high-risk patients involved in two parallel randomized controlled studies. Overall, 37 percent of patients were diabetic, but none had heart failure at baseline.

The studies evaluated the effect of telmisartan, ramipril, a combination of both, or placebo in 25,620 participants; and the effect of telmisartan versus placebo in 5,926 angiotensin-converting enzyme-intolerant heart patients. During follow-up, 668 subjects developed congestive heart failure.

The researchers found that participants had a 1.10-fold increase in the risk of heart failure hospitalization for every 1 millimole per liter increase in fasting plasma glucose from baseline, after adjusting for age, diabetes and other factors.

"Fasting plasma glucose is an independent predictor of hospitalization for congestive heart failure in high-risk subjects," the authors write. "These data provide theoretical support for potential direct beneficial effects of glucose lowering in reducing the risk of congestive heart failure."

One author has received a research grant for studies on insulin to reduce cardiovascular events and is a consultant for Sanofi-Aventis.

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Pain Guidelines Advise Reduced Use of COX-2 Inhibitors

Non-pharmacological treatment, analgesics and non-selective COX inhibitors should be used first

To minimize the risk of adverse events, patients with or at risk for heart disease who are in chronic pain should first be treated by non-pharmacological approaches, followed by analgesics and non-selective cyclooxygenase (COX) inhibitors, with COX-2 inhibitors only prescribed as a last resort, according to updated guidelines published online Feb. 26 in Circulation: Journal of the American Heart Association.

A meta-analysis has shown that compared with placebo, selective COX-2 inhibitors increase the risk of myocardial infarction by 86 percent, according to the recommendations. Diclofenac and ibuprofen, which have been thought to be non-selective, also appear to increase the risk of cardiovascular disease.

Rather than prescribing a COX-2 inhibitor as a first-line treatment for chronic pain, the guidelines advise non-pharmacological treatments such as physical therapy and exercise, weight loss to reduce joint stress, and heat or cold therapy. If these are ineffective, acetaminophen, aspirin or even short-term narcotic analgesics should be prescribed based on the patient's medical history.

"We believe that some physicians have been prescribing the new COX-2 inhibitors as the first line of treatment. We are turning that around and saying that, for chronic pain in patients with known heart disease or who are at risk for heart disease, these drugs should be the last line of treatment," said Elliott M. Antman, M.D., in a statement.

The guidelines are an update from two years ago and were developed by a committee chaired by Antman, who is at Harvard Medical School in Boston.

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