Latest Research

Ranolazine Does Not Reduce Major Cardiovascular Events

But drug does reduce recurrent ischemia by 13 percent

The piperazine derivative ranolazine is a safe and effective anti-anginal treatment for some patients with non-ST-segment elevation acute coronary syndrome, but is not effective in reducing major cardiovascular events, according to a report in the April 25 Journal of the American Medical Association.

David Morrow, M.D., of Brigham and Women's Hospital in Boston, and the MERLIN-TIMI 36 Trial Investigators measured cardiovascular death, myocardial infarction, or recurrent ischemia in 6,560 patients in multiple countries with non-ST-elevation acute coronary syndrome who were randomized to ranolazine or placebo for a median of 348 days.

While the combined outcomes from ranolazine treatment were similar to placebo, the treatment significantly reduced recurrent ischemia by 13.9 percent. The drug did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia.

"Ranolazine does not significantly improve acute or downstream prognosis; therefore, it should not be routinely added to treatment following an acute coronary event," write the authors of an accompanying editorial.

CV Therapeutics supported the trial and provided grant support, honoraria, or consulting fees to the editorialists.

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Non-PCV7 Pneumococcal Serotypes Emerging in Alaska

Results suggest invasive pneumococcal disease target is 'moving'

Non-vaccine serotypes of invasive Streptococcus pneumoniae are emerging in Alaska Native children where 7-valent pneumococcal conjugate vaccine (PCV7) coverage is high, researchers report in the April 25 issue of the Journal of the American Medical Association.

Rosalyn Singleton, M.D., of the Arctic Investigations Program of the Centers for Disease Control and Prevention in Anchorage, Alaska, and colleagues measured the incidence and types of pneumococcal disease in Alaska Native children younger than 2 years old after introduction of PCV7 in 2001.

While introduction of PCV7 caused a 67 percent reduction in invasive pneumococcal disease by 2003, the incidence increased again, rising 82 percent from 2003 to 2006. This was accompanied by both a 96 percent decrease in PCV7 serotypes and a 140 percent rise in non-vaccine serotypes, over a quarter of which were marked as serotype 19A. Emerging serotypes were not found in non-Native Alaskan children.

"Surveillance of pneumococcal colonization and disease is important to public health and is informing vaccine redesign," write Timothy Peters, M.D., and a colleague at Wake Forest University in Winston-Salem, N.C., in an editorial. "The target is moving. An adaptable vaccine strategy must also move to protect children worldwide and defend the idea that humankind will ultimately be free of pneumococcal disease."

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Gene Variations Linked to Macular Degeneration

Two polymorphisms plus smoking and overweight increases risk of age-related macular degeneration

The combination of two single-nucleotide polymorphisms, smoking and body mass index of 25 of greater increases the risk for age-related macular degeneration (AMD) by 19-fold, according to a report in the April 25 issue of the Journal of the American Medical Association.

Johanna Seddon, M.D., of Tufts-New England Medical Center in Boston, and colleagues measured the incidence of dry and neovascular advanced AMD in 1,466 subjects enrolled in the Age-Related Eye Disease Study (AREDS) to confirm previous reports that single-nucleotide polymorphisms in the CFH and LOC387715 genes are linked to disease progression.

CFHY402H and LOC387115A69S polymorphisms were associated with an odds ratio for AMD of 2.6 and 4.1, respectively, even after controlling for demographic factors, smoking, body mass index and AREDS vitamin-mineral treatment assignment. The presence of both polymorphisms plus smoking and body mass index of 25 or greater was linked to a 19-fold increased odds for AMD.

Although the authors believe it is premature to use genotyping for AMD assessment, "a risk profile that includes genetic and environmental factors, such as the one calculated herein, may ultimately lead to targeted screening and closer monitoring of individuals who are at higher risk of visual loss due to AMD progression," they write.

Seddon is an inventor on a patent application for use of biomarkers in detecting AMD.

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Study Supports Pediatric Antidepressant Treatment

Researchers find that benefits outweigh risks, including an insignificant risk of suicidal ideation

Antidepressant treatment is associated with more benefits than risks in children and adolescents with depression and anxiety disorders, and the increased risk of suicidal ideation and suicide attempts is statistically insignificant, according to a meta-analysis in the April 18 issue of the Journal of the American Medical Association.

Jeffrey A. Bridge, Ph.D., of Ohio State University in Columbus, and colleagues conducted a meta-analysis of 15 randomized controlled trials of antidepressants for major depressive disorder, six for obsessive compulsive disorder, and six for non-OCD anxiety disorders.

The researchers found evidence supporting the efficacy of antidepressants in all three disorders. Although they identified an increased risk of 0.7 percent for suicidal ideation/suicide attempt in patients taking antidepressants compared to those taking placebo, they found that the pooled risk differences (0.9 percent for major depressive disorder, 0.5 percent for obsessive compulsive disorder and 0.7 percent for non-OCD anxiety disorders) were not significant.

"Some may argue that any risk of suicidal ideation/suicide attempt cannot possibly justify treatment with antidepressants for children and adolescents," the authors concluded. "Instead, we believe that the strength of evidence presented here supports the cautious and well-monitored use of antidepressant medications as one of the first-line treatment options, with the recognition that efficacy appears greatest for non-OCD anxiety disorders, intermediate for OCD, and more modest for major depressive disorder."

The study was funded by a grant from the National Institute of Mental Health.

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For-Profit Dialysis Centers May Have Over-Used Epoetin

Patients with low hematocrit levels received three times as much epoetin at for-profit facilities

End-stage renal disease patients treated at large, for-profit dialysis facilities may have received high amounts of red cell-boosting epoetin regardless of anemia status, according to a study published in the April 18 issue of the Journal of the American Medical Association. The U.S. Food and Drug Administration recently issued a warning recommending that the use of such erythropoiesis-stimulating agents be limited due to the potential risks of the drugs.

Mae Thamer, Ph.D., of the Medical Technology and Practice Patterns Institute in Bethesda, Md., and colleagues analyzed 2004 data from the U.S. Renal Data System on 159,522 Medicare-eligible patients, including 106,116 at large for-profit dialysis chain facilities and 28,199 at nonprofit dialysis facilities.

The researchers found that patients at for-profit facilities with hematocrit levels of less than 33 percent received three times the dosage of epoetin compared to their counterparts at nonprofit facilities. They also found that patients at for-profit facilities with hematocrit levels in the recommended 33 percent to 36 percent range received higher dosages of epoetin. The authors suggested that reimbursement policy and clinical performance measures may give for-profit facilities an incentive to target hematocrit levels exceeding those recommended by clinical guidelines.

"These discrepancies help to explain the explosion in the cost of epoetin therapy for dialysis patients," stated the author of an accompanying editorial. "Between 1998and 2004, annual Medicare payments for erythropoiesis-stimulating agents (epoetin and darbepoetin) in patients with end-stage renal disease increased 115 percent from $840 million to $1.8 billion while patient volume increased just 33 percent."

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Fission Gene Defect Can Be Lethal in Infancy

Gene involved in fission of peroxisomes and mitochondria

A mutation in a gene involved in the fission of peroxisomes and mitochondria can lead to serious neurological problems and death, according to a case report in the April 26 issue of the New England Journal of Medicine.

Hans R. Waterham, Ph.D., from Academic Medical Center in Amsterdam, the Netherlands, and colleagues describe the case of a newborn white British female who presented with microcephaly, optic atrophy, abnormal brain development, lactic acidemia in plasma and cerebrospinal fluid, and elevated plasma levels of very-long-chain fatty acids. The infant died suddenly at 37 days.

The researchers found no abnormalities in a muscle-biopsy specimen, but an examination of skin fibroblasts showed few peroxisomes and abnormal mitochondria. Amplification and sequencing of the dynamin-like protein 1 (DLP1) gene revealed a heterozygous point mutation that was not present in control fibroblasts, producing a protein that blocked the function of the normal protein.

"Our findings are representative of a class of disease characterized by defects in both mitochondria and peroxisomes," Waterham and colleagues conclude.

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Physician-Industry Relationships Common

Many reimbursed for professional meetings, paid for consulting

Nearly all physicians have some relationship with industry, with about one-third being reimbursed for professional meetings or continuing medical education and more than one-quarter receiving payments for consulting and other activities, according to the results of a nationwide survey published in the April 26 New England Journal of Medicine.

Eric G. Campbell, Ph.D., from Harvard Medical School in Boston, and colleagues surveyed 3,167 physicians (in anesthesiology, cardiology, family practice, general surgery, internal medicine and pediatrics) regarding their financial links to industry.

The researchers found that 94 percent of physicians reported a relationship with the pharmaceutical industry, mostly receiving drug samples or food in the office. Thirty-five percent were reimbursed for professional meetings or continuing medical education. Twenty-eight percent reported being paid for consulting, giving lectures or enrolling patients in clinical trials, which was more than twice as common among cardiologists as family practitioners. Family practitioners met with industry representatives most frequently, as did physicians in individual or group practices compared with physicians in hospitals and clinics.

"The results of this national survey indicate that relationships between physicians and industry are common and underscore the variation among such relationships according to specialty, practice type and professional activities," Campbell and colleagues conclude.

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Protease Inhibitors Increase Risk of Myocardial Infarction

Increase modest, partly due to dyslipidemia

Protease inhibitors modestly increase the risk of myocardial infarction in HIV-infected individuals and is partly due to dyslipidemia, according to study findings published in the April 26 issue of the New England Journal of Medicine.

Jens D. Lundgren, M.D., from the University of Copenhagen in Denmark, and colleagues examined the risk of myocardial infarction in 23,437 HIV-infected individuals based on whether they were treated with protease inhibitors or non-nucleoside reverse-transcriptase inhibitors.

After a median of 4.5 years, the researchers observed 345 myocardial infarctions. After adjusting for cardiovascular risk factors and exposure to other drug classes, protease inhibitor treatment increased the risk of myocardial infarction by 16 percent per year compared with an increased risk of 5 percent per year for non-nucleoside reverse-transcriptase inhibitors. The risk was reduced to 10 percent and 0 percent, respectively, after adjusting for serum lipid levels.

Although the study conclusions are sound, "it is critically important to recognize that the magnitude of increased cardiovascular risk observed with protease inhibitors is not high, especially as compared with the effect of other cardiovascular risk factors" such as increasing age, male gender, current smoking and cardiovascular disease history, writes editorialist James H. Stein, M.D., of the University of Wisconsin School of Medicine and Public Health in Madison.

Several authors report receiving lecture or consulting fees, as well as grants, from various drug companies.

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Sodium Butyrate Stops Seizures in Child With GPI Deficiency

Treatment relieves suppression of PIGM gene

Sodium butyrate can stimulate expression of the PIGM gene and may cause complete cessation of intractable seizures in patients with inherited glycosylphosphatidylinositol (GPI) deficiencies, according to a pediatric case study in the April 19 issue of the New England Journal of Medicine.

Antonio M. Almeida, M.D., Ph.D., of Imperial College London, U.K., and colleagues found that inherited GPI deficiencies can be caused by reduced PIGM expression due to a suppressive mutation in its promoter. The group then treated a 14-year-old girl with GPI deficiency and a history of seizures with sodium butyrate, a histone deacetylase inhibitor, in an effort to stimulate PIGM expression.

The authors found that sodium butyrate treatment of lymphoblastoid cells caused changes in histone acetylation at the PIGM promoter that correlate with gene activation. In the patient, sodium butyrate treatment caused an increase in PIGM mRNA levels by a factor of 70 and increased cell-surface GPI expression in whole blood.

Within two weeks of treatment, the seizures ceased, and the patient eventually began to walk, interact, and feed herself -- activities she had not done in two to three years. The authors concluded that sodium butyrate is of "great therapeutic value" and could be used in other diseases that are caused by suppressive mutations.

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U.S. Breast Cancer Cases Sharply Declined in 2003

Report says 6.7 percent decline may be linked to 2002 Women's Health Initiative findings

Breast cancer incidence in the United States declined sharply in 2003, possibly because many postmenopausal women stopped using hormone-replacement therapy after the 2002 Women's Health Initiative study found it increased the risk of heart disease and breast cancer. The findings are published in the April 19 issue of the New England Journal of Medicine.

Peter M. Ravdin, Ph.D., M.D., of the M.D. Anderson Cancer Center in Houston, and colleagues analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries.

The researchers found that the age-adjusted incidence rate of breast cancer decreased by 6.7 percent in 2003 and leveled off in 2004. They also found that the drop applied only to women age 50 or older and was more common for estrogen-receptor-positive cancers than for estrogen-receptor-negative cancers. According to their regression analysis, the decrease began in mid-2002, and began to level off by mid-2003

"We believe that the data are most consistent with a direct effect of hormone-replacement therapy on preclinical disease, but this conclusion does not rule out some contribution from changes in screening mammography," the authors wrote. "In any case, attempts to understand the rapid reduction in incidence using theoretical models of breast cancer evolution and the effects of screening and treatment-- such as those of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network -- may lead to new insights into the development and prevention of breast cancer."

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Omeprazole Before Endoscopy Cuts Ulcerative Bleeding

Patients treated with omeprazole tend to leave hospital earlier than those who are not

Patients with gastrointestinal bleeding who have a high-dose infusion of the proton-pump inhibitor omeprazole before endoscopy are less likely to have ulcerative bleeding or need endoscopic therapy, according to a report in the April 19 issue of the New England Journal of Medicine.

Neutral pH is critical for clot formation, so the authors hypothesized that omeprazole would have a therapeutic effect on bleeding ulcers. Over a period of 17 months, James Y. Lau, M.D., of The Chinese University in Hong Kong, China, and colleagues enrolled 638 consecutive patients admitted with gastrointestinal bleeding to receive an 80-mg bolus of omeprazole plus 8-mg per hour or placebo until the endoscopic procedure the following morning.

The authors found that 19.1 percent of the omeprazole group needed endoscopic treatment compared with 28.4 percent of the placebo group. More patients in the treatment group were released within three days (60.5 percent vs. 49.2 percent). There were no differences in mean amount of blood transfused, recurrent bleeding, number of emergency surgeries, or 30-day mortality between the two groups.

"We do not propose using high-dose proton-pump inhibitors as a replacement for early endoscopy," the authors wrote. "However, we recommend the preemptive use of high-dose intravenous omeprazole."

Some of the authors had received lecture fees or grant support from AstraZeneca, Pfizer, Takeda, TAP Pharmaceuticals, or GlaxoSmithKline.

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Fewer Transfusions OK in Critically Ill Children

Reducing transfusion exposure by setting lower hemoglobin limits does not increase adverse outcomes

A strategy of using a lower hemoglobin threshold before the infusion of red blood-cells can decrease transfusions without increasing adverse outcomes in stable, critically ill children, according to a report in the April 19 issue of the New England Journal of Medicine.

Jacques Lacroix, M.D., of Université de Montréal, Québec, Canada, and colleagues randomly assigned 637 stable but critically ill children with hemoglobin concentrations below 9.5 g/dL to infusion of leukocyte-reduced packed red cells. In one group, they used a restrictive strategy, setting a threshold of 7 g/dL before transfusion, and, in the other, they used a liberal strategy, with a threshold of 9.5 g/dL.

Patients in the restrictive strategy group received 44 percent fewer transfusions and had hemoglobin concentrations of 2.1 g/dL lower than the liberal strategy group. In fact, 54 percent in the restrictive group did not receive any transfusions compared with 2 percent in the liberal group. About 12 percent in each group had multiple organ dysfunction syndrome, and 14 patients died in each group.

"A transfusion trigger of 7.0 g per deciliter for most critically ill adults and children appears to be appropriate," according to Howard L. Corwin, M.D., of Lebanon, N.H., and a colleague in an accompanying editorial. "Red-cell transfusion should no longer be regarded as 'may help, will not hurt' but, rather, should be approached as 'first, do no harm.' "

Some of the authors had received support from Johnson & Johnson/Ortho Biotech, Novo Nordisk, Amgen, Baxter, Xoma, or Eli Lilly.

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Botulinum Toxin Can Resolve Hyperhidrosis of the Hand

Treatment is well tolerated in 23-year-old patient with lifelong hyperhidrosis

Intradermal injections with botulinum toxin resolved severe hyperhidrosis of the hand and forearm in a 23-year-old girl, according to a report in the April 21 issue of The Lancet.

Daniela Bruch-Gerharz, M.D., from University Hospital in Dusseldorf, Germany, and colleagues describe the case of a woman who presented with hyperhidrosis in her right forearm and the back of her right hand. Starting in childhood, the woman's hand periodically dripped with sweat, and the events were occuring an average of five times a day for 30 minutes. Previous treatment with topical aluminum chloride and tap water iontophoresis was ineffective.

A skin biopsy showed that the cause of her hyperhidrosis was eccrine nevus, the researchers found. Intradermal injections with botulinum toxin resolved the problem.

"The treatment was well-tolerated, and the patient's quality of life appreciably improved," Bruch-Gerharz and colleagues wrote. "In recent years, botulinum toxin has been used as a therapeutic option for hyperhidrosis."

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Low Molecular Weight Heparin Cuts Post-Stroke Clot Risk

Reduces the risk of venous thromboembolism by 43 percent compared with unfractionated heparin

The low molecular weight heparin enoxaparin reduces the risk of developing a venous thromboembolism after an acute ischemic stroke by 43 percent compared with unfractionated heparin, according to a study in the April 21 issue of The Lancet.

David G. Sherman, M.D., from the University of Texas Health Science Center in Houston, and colleagues randomized 1,762 acute ischemic stroke patients to either enoxaparin once a day or unfractionated heparin twice a day within 48 hours of the cardiovascular event. The patients were unable to walk without assistance.

The researchers found that the risk of developing venous thromboembolism was 43 percent lower in the enoxaparin group. The reduction was observed regardless of stroke severity. The frequency of symptomatic intracranial hemorrhage was the same in both groups (1 percent), but the frequency of symptomatic extracranial hemorrhage was significantly higher in the enoxaparin group (1 percent vs. 0 percent).

"Our results suggest that for patients with acute ischemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration," Sherman and colleagues concluded.

The study was sponsored by Sanofi-Aventis.

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Hormone Replacement May Raise Ovarian Cancer Risk

Additional risk disappears when therapy is stopped

Women who use hormone replacement therapy (HRT) may be at increased risk of developing ovarian cancer, and its use in the United Kingdom may have resulted in an additional 1,000 deaths from the disease since 1991, according to a study published online April 19 in The Lancet.

Valerie Beral, of Cancer Research U.K., Oxford, U.K., and colleagues analyzed data from the Million Women Study, including 948,576 postmenopausal women with no previous history of cancer or bilateral oophorectomy. The women were followed for an average of 5.3 years for incident ovarian cancer (2,273 cases) and 6.9 years for death (1,591 subjects) during the follow-up.

Overall, 30 percent of the women were current HRT users, and 20 percent were past users. Current users had a 1.2-fold greater risk of incident ovarian cancer and a 1.23-fold greater risk of ovarian cancer death than never-users. There was no difference based on the type of HRT, and past users were not at increased risk. The highest risk was for serous tumors in women with epithelial cancer, with current users at 1.53 times the risk as never users.

Among current users of HRT there was an estimated one extra case per 2,500 users and one extra death per 3,300 users. "If this association is causal, use of HRT since 1991 has resulted in roughly 1,300 extra cases of ovarian cancer and 1,000 extra deaths from the malignancy in the U.K.," the authors wrote.

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HIV-1 Integrase Inhibitor Safe, Potent in Advanced HIV

Raltegravir may become an important part of salvage therapy in advanced HIV

Raltegravir, an experimental HIV drug that targets the integrase enzyme, appears promising in a randomized phase II trial of treatment-resistant patients, according to a report in the April 14 issue of The Lancet. The drug is under development by Merck Research Laboratories in North Wales, Penn.

Beatriz Grinsztejn, M.D., of the Evandro Chagas Clinical Research Institute/Oswaldo Cruz Foundation in Rio de Janiero, Brazil, and colleagues assessed the safety and efficacy of raltegravir when added to optimized background combination therapies in 178 patients with advanced HIV who were failing their existing therapies. Patients received placebo or 200, 400 or 600 mg of raltegravir twice daily with background treatment for 24 weeks.

At 24 weeks, patients who received raltegravir showed a 98 percent drop in HIV RNA, on average, compared with 45 percent among their counterparts in the placebo group. Moreover, the number of CD4 cells was also increased in patients taking the novel HIV drug. Raltegravir was safe and well-tolerated in most study participants.

"If no long-term unexpected side-effects or resistance issues emerge, raltegravir will have a major role in salvage therapy," write Pedro Cahn, M.D., Ph.D., and Omar Sued, M.D., of the Fundación Huesped in Buenos Aires, Argentina, in an editorial.

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Bovine TB Can Spread Via Person-to-Person Contact

Five cases in England in 2005 traced to index case of Mycobacterium bovis

Bovine tuberculosis can be spread from person to person, according to a study of six patients from central England who developed tuberculosis caused by Mycobacterium bovis in 2005. The findings are published in the April 14 issue of The Lancet.

Jason T. Evans, M.Sc., of Birmingham Heartlands Hospital in Birmingham, U.K., and colleagues report on the cluster, including five who had pulmonary disease and one who died due to bovine tuberculosis-related meningitis. Four patients had factors predisposing them to tuberculosis including use of steroids, alcohol misuse, HIV and insulin-dependent diabetes.

All of the patients had social ties to one another through visits to bars in two areas. Only the first patient was exposed to bovine disease via infected cattle or consumption of unpasteurized milk, which points to human to-human contact. Transmission was likely due to a combination of host of environmental factors, the researchers suggest. Health professionals set up measures to prevent against further transmission in this case.

"Investigations are needed to elucidate the relative importance of M. bovis in the worldwide tuberculosis problem in human beings, especially in developing countries," write Charles O. Thoen, DVM, Ph.D., of Iowa State University in Ames, Iowa, and Philip A. LoBue, M.D. of the U.S. Centers for Disease Control and Prevention in Atlanta, in an accompanying editorial.

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Monovalent Oral Polio Vaccine Shows Improved Efficacy

Monovalent vaccine is more effective than standard trivalent vaccine in study conducted in India

A monovalent oral vaccine against type 1 poliovirus introduced in 2005 is almost three times as effective as the standard trivalent vaccine in preventing persistent poliovirus transmission in India, one of the last remaining infected countries, according to a report published online April 12 in The Lancet.

Nicholas C. Grassly, D.Phil., from Imperial College London in the United Kingdom, and colleagues examined the efficacy of monovalent oral type 1 poliovirus vaccine (mOPV1) by looking at 2,076 matched case-control pairs of confirmed poliomyelitis caused by type 1 wild poliovirus and non-polio flaccid paralysis in the state of Uttar Pradesh in India. The efficacy was determined by estimating vaccine coverage from data on cases of non-polio paralysis. Comparisons were made with the standard trivalent poliovirus vaccine.

The researchers estimated that the mOPV1 vaccine had a protective efficacy of 30 percent against type 1 paralytic disease compared with 11 percent for the trivalent vaccine. At the end of 2006, after the mOPV1 vaccine became available, an estimated 76 percent to 82 percent of children under 2 years old were protected by vaccination compared with 59 percent at the end of 2004, before mOPV1 was available.

"The demonstration of superior effectiveness of mOPV vaccine adds to the evidence that termination of wild poliovirus transmission is technically feasible, given enough time, continued funding, political stability, and continued political support in the affected areas of the world," state the authors of an accompanying editorial.

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Sequential Antibiotics May Be Better for Peptic Ulcer

Particularly effective for some antibiotic-resistant strains

Four antibiotics given sequentially are more effective than three antibiotics together in eradicating Helicobacter pylori infection in patients with dyspepsia or peptic ulcers, particularly for certain antibiotic-resistant strains, according to a study in the April 17 issue of the Annals of Internal Medicine.

Dino Vaira, M.D., from S. Orsola Hospital in Bologna, Italy, and colleagues randomized 300 patients with dyspepsia or peptic ulcers to a sequential 10-day antibiotic regimen (pantoprazole and amoxicillin twice a day for 5 days, then pantoprazole, clarithromycin, and tinidazole twice a day for 5 days) or the standard 10-day regimen (pantoprazole, clarithromycin, and amoxicillin twice a day).

The researchers found that the sequential regimen was significantly better in eradicating H. pylori infection (89 percent vs. 77 percent) and was significantly more effective in eradicating the infection in patients with clarithromycin-resistant strains (89 percent vs. 29 percent). The two groups had a similar incidence of side effects, according to the study.

"Sequential therapy is statistically significant compared with standard therapy for eradicating H. pylori infection and is statistically significantly more effective in patients with clarithromycin-resistant strains," Vaira and colleagues concluded.

One author of the study was financially compensated by Altana Pharma, makers of pantoprozole.

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Study Finds Chondroitin Not Beneficial for Arthritis Pain

Pooled analysis indicates no increased risk of adverse events

A pooled analysis of well-designed trials examining the use of chondroitin to treat osteoarthritis pain has shown that chondroitin has no clear benefit but does not increase the risk of adverse events, according to a study in the April 17 issue of the Annals of Internal Medicine.

Peter Juni, M.D., from the University of Bern, Switzerland, and colleagues identified and performed a meta-analysis of 20 clinical trials involving 3,846 patients examining the effect of chondroitin on pain in osteoarthritis.

The researchers found that the trials tended to be heterogeneous, and small trials, those with poor allocation concealment, and those not analyzed based on intent-to-treat principles showed a greater benefit of chondroitin. An analysis of three trials with large sample sizes and an intent-to-treat analysis showed no clear benefit of chondroitin. An analysis of 12 trials showed that chondroitin did not increase the risk of adverse events.

"Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent," Juni and colleagues concluded. "Use of chondroitin in routine clinical practice should therefore be discouraged."

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Helicobacter pylori May Lower Asthma and Allergy Risks

Association stronger in children

Children who acquire the stomach bacterium Helicobacter pylori before age 10 may have a lower risk of allergy and asthma than other children, researchers report in the April 23 issue of the Archives of Internal Medicine.

Yu Chen, Ph.D., of the New York University Cancer Institute in New York City, and colleagues analyzed the connection between allergen-specific skin sensitization, allergy and asthma status in 7,663 adults, comparing results for those who tested seropositive for two strains of H. pylori with those who tested negative for the bacterium.

The researchers found that exposure to H. pylori was associated with a reduced risk of asthma (odds ratio 0.79). For those who tested seropositive for the cagA strain of the bacterium, the risk of developing asthma by age 15 (OR, 0.63) was lower than that of developing asthma as adults (OR, 0.97).

The bacterium was also linked to a reduced risk of allergic rhinitis, particularly in children (OR, 0.55), and fewer pollen and mold sensitivities and allergies in the past year.

"These observations support the hypothesis that childhood acquisition of H. pylori is associated with reduced risks of asthma and allergy," the authors conclude.

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Obesity May Have Economic Toll in Workplace

Linear relationship between body mass index and employer cost observed

Overweight individuals file more workers' compensation claims, miss more work and have costlier claims than do individuals with a recommended weight, researchers report in the April 23 issue of the Archives of Internal Medicine. A second study, however, finds that people over age 65 who have a slightly higher body mass index (BMI) have a lower mortality and risk of injury than those with the lowest and highest BMIs.

Truls Ostbye, M.D., Ph.D., of Duke University Medical Center in Durham, N.C., and colleagues studied 11,728 university employees and health care workers, most younger than 55, and observed BMI-related increases in the number of claims (11.65 for the most obese individuals versus 5.8 for recommended weight), lost workdays (183.63 versus 14.19), medical claims costs ($51,091 versus $7,503) and indemnity claims costs ($59,178 versus $5,396).

Soham Al Snih, M.D., Ph.D., of the University of Texas Medical Branch in Galveston, and colleagues studied 12,725 non-disabled individuals older than 65 and discovered that a BMI at baseline of less than 18.5 or 30 or higher was associated with the highest risk of disability. A BMI between 25 and 34 was linked to a lower risk of mortality compared to a BMI under 25 or 35 or greater. The greatest disability-free life expectancy occurred with a BMI between 25 and 30.

"Considering the trade-off between total and disability-free life expectancy, it would seem that becoming slightly overweight as we grow older may not be so bad," according to the authors of an accompanying editorial.

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No Link Between Breast Cancer Risk, Abortion

Among premenopausal women, neither spontaneous nor induced abortion linked to breast cancer

Although women have a lifetime reduction in breast cancer risk if they have a full-term pregnancy before the age of 35, those who have a spontaneous or induced abortion are not at higher risk of developing the disease compared with the general female population, according to the results of a study published in the April 23 issue of the Archives of Internal Medicine.

Karin B. Michels, Ph.D., of Harvard Medical School and Brigham and Women's Hospital in Boston, and colleagues conducted a study of 105,716 women aged 29 to 46 years old who were followed up from 1993 until 2003. During the follow-up period, there were 1,458 newly diagnosed cases of invasive breast cancer.

Among the study cohort, 16,118 women (15 percent) had a history of induced abortion, and 21,753 (21 percent) had a history of miscarriage. There was no association between single or multiple abortions and the likelihood of developing breast cancer.

"We observed associations in two subgroups, an association between induced abortion and progesterone receptor-negative breast cancer and an inverse association between spontaneous abortion before the age of 20 years and breast cancer incidence," the authors write. They caution that "subgroup analyses have to be interpreted cautiously, especially if the strata are small. No obvious mechanisms can be provided for these subgroup findings; thus, chance has to be considered as a possible explanation."

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Migraine in Men Linked to Cardiovascular Disease Risk

Risk is particularly high for myocardial infarction

Men who experience migraine headaches are at higher risk of developing cardiovascular disease, particularly myocardial infarction, researchers report in the April 23 issue of the Archives of Internal Medicine.

Tobias Kurth, M.D., of Harvard School of Public Health and Brigham and Women's Hospital in Boston, conducted a study of 20,084 men aged 40 to 84, all of whom were free of cardiovascular disease at the start of the study. The men completed a yearly health questionnaire, including questions on migraine and risk factors for cardiovascular disease. Men who reported incidence of migraine in the first five years of the study were followed up.

In all, 1,449 men (7.2 percent) reported migraine and there were 2,236 major cardiovascular disease events in subsequent follow-up. Men who had reported migraine had a multivariable-adjusted hazard ratio of 1.24 for major cardiovascular disease, 1.12 for ischemic stroke, 1.42 for myocardial infarction, 1.15 for angina, 1.05 for coronary revascularization and 1.07 for ischemic cardiovascular death, compared with men who had not experienced migraine. Overall, the major cardiovascular disease incidence was 10.4 per 10,000 men per year for men with migraine and 8.5 for those without.

"Several mechanisms have been proposed supporting a biological link between migraine and vascular events. However, the precise mechanisms are currently unknown and are likely to be complex," the authors write.

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Depressed Elderly More Likely to Develop Diabetes

Association cannot be explained solely by normal risk factors for diabetes

Older adults are more likely to develop diabetes if they are depressed, and the association cannot be explained by diabetes risk factors alone, according to study findings published in the April 23 issue of the Archives of Internal Medicine.

Mercedes R. Carnethon, Ph.D., of Northwestern University in Chicago, and colleagues conducted a study among 4,681 adults aged 65 or older who enrolled in a cardiovascular health study in 1989 and who did not have diabetes at that time. They completed annual mental health questionnaires for the following 10 years.

Three measures of depression were considered in relation to incidence of diabetes: a single report of depressive symptoms; worsening symptoms; and persistently high symptoms. In all three groups, the odds of developing diabetes were significantly higher than for those who did not report feeling depressed. The association persisted after adjusting for confounding factors such as physical activity, smoking, alcohol intake, body mass index and C-reactive protein.

"Our findings in this population of older adults are of particular public health importance because there are 35 million U.S. adults older than 65 years. An estimated 2 million older adults may have a depressive illness, which is the second highest prevalence of depression across the age range," the authors write.

The study was supported by a grant from Amgen Inc.

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Cost-Sharing Not Likely to Reduce Health Care Costs

Physicians don't always consider out-of-pocket costs when making treatment decisions

Efforts to reduce health care spending by involving the patient in cost-sharing will probably have a limited effect because many physicians don't consider patient out-of-pocket costs when making clinical decisions, researchers report in the April 9 issue of the Archives of Internal Medicine.

Hoangmai H. Pham, M.D., from the Center for Studying Health System Change in Washington, D.C., and colleagues analyzed data from 6,628 respondents to the Community Tracking Study Physician Survey. The phone survey included physicians from 60 metropolitan areas. Primary care physicians were oversampled, and radiologists, anesthesiologists and other specialists were excluded.

The investigators found that 78 percent of physicians considered out-of-pocket costs when prescribing drugs, 51.2 percent did so when selecting care settings and 40.2 percent considered costs when choosing diagnostic tests. Primary care physicians were more likely to consider out-of-pocket costs for all three decisions while physicians in large practices or HMOs considered costs when prescribing generic drugs.

"More aggressive interventions such as accessible, detailed, and user-friendly information on costs of specific services might broadly change physicians' clinical decision making, but only if they result in a significant improvement in how often and how well patients and physicians communicate with one another about cost burdens," the authors write.

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Older HIV Patients More Likely to Adhere to HAART

Adherence may compensate for early blunted T-cell response in older patients

HIV-infected patients over age 50 tend to adhere more closely to highly active antiretroviral therapy (HAART) than younger patients, and subsequently show good early responses to treatment, according to the results of a study published in the April 9 issue of the Archives of Internal Medicine. However, they are also at greater risk of adverse events than younger patients.

Michael J. Silverberg, Ph.D., M.P.H., of Kaiser Permanente in Oakland, Calif., and colleagues monitored changes in HIV clinical markers in patients in three different age groups after they initiated HAART. Patients aged 40 to 49 years or 50 years and older were compared to a reference group of 18 to 39 years.

Initially, the investigators found that the 50 year and older group achieved the best response rate to HAART, measured by HIV RNA levels. However, response rates were similar after adjusting for adherence. Older patients had blunted T-cell responses early in treatment compared with younger patients but rebounded in later years. Adverse events including metabolic, hematologic and renal abnormalities were more likely in older patients.

"The added importance of high adherence in older patients with regard to HAART response, coupled with a high first-year incidence of metabolic, hematologic and renal abnormalities, indicates that close monitoring and potential treatment modifications may be needed in patients 50 years or older," the authors write.

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Nursing Home Environment Related to Antipsychotic Therapy

Despite known dangers, some nursing homes more liberally dispense antipsychotics

Residents who live in nursing homes that tend to be high prescribers of antipsychotic drugs are three times more likely to receive such a drug than are their counterparts in nursing homes with low prescribing rates, regardless of whether or not they actually need antipsychotics, according to a report in the April 9 issue of the Archives of Internal Medicine.

Paula A. Rochon, M.D., of Kunin-Lunenfeld Applied Research Unit in Toronto, Ontario, Canada, and colleagues looked at prescribing patterns by clinical indication at 485 nursing homes in December of 2003. Researchers classified the homes into quintiles based on their prescribing patterns.

Of 47,322 nursing home residents, 15,317 (or 32.4 percent) received an antipsychotic drug, suggesting that the magnitude of antipsychotic prescribing in nursing homes is even greater than previously thought, the researchers note. Regardless of clinical indication, residents in high-prescribing nursing homes were three times more likely to receive antipsychotics than their counterparts in homes with lower prescribing rates, the report indicates.

The risks of prescribing antipsychotics to nursing home residents are well-known and there has been concern about inappropriate and widespread prescribing in nursing homes for decades. Still the "results suggest that antipsychotic therapy is not being prescribed based on their clinical indication. Rather, the decision to prescribe an antipsychotic therapy appears to be related to the nursing home environment, with some environments being more permissive about antipsychotic use," the authors conclude.

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Cognitive Therapy Helps Relatives of Suicide Cases

But complicated grief, depression and suicidal thoughts remain

Relatives and spouses bereaved by suicide who undergo cognitive behavior therapy are less likely to blame themselves for the death, but they still endure complicated feelings of grief and depression and may contemplate their own suicide, according to a study published online April 20 in the BMJ.

Marieke de Groot, a psychiatric nurse at the University of Groningen in the Netherlands, and colleagues conducted a study of 122 first-degree relatives and spouses of 70 people who committed suicide. While 68 participants from 39 families underwent four sessions of family-based cognitive behavior therapy with a trained psychiatric nurse counselor, the remaining 54 participants from 31 families were assigned to a control group with no intervention.

When the two groups reported on their feelings, there was no difference in terms of complicated grief, thoughts of suicide or depression, but those in the intervention group were less likely to blame themselves for the suicide and were less likely to report maladaptive grief reactions.

"Having a chance in counseling to reflect on and acknowledge their loved one's difficulties before the suicide may have helped relatives to realize that they did nothing wrong. Informing relatives of the psychiatric context of suicidal behavior might have challenged their perceptions of guilt and self-blame," the authors concluded.

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Salt Restriction May Reduce Cardiovascular Disease

Long-term risk found to be 25 percent lower in patients who decreased salt intake by one-third

Patients who reduce their dietary sodium intake by about one-third could significantly reduce their chances of developing cardiovascular disease, according to a study published online April 20 in the BMJ.

Nancy R. Cook, Sc.D., of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues studied 744 prehypertensive enrollees from the first Trial of Hypertension Prevention, which was completed in 1990, and 2,382 prehypertensive enrollees from the second Trial of Hypertension Prevention, which ended in 1995. The intervention participants decreased their sodium intake by 44 mmol/24 hours and 33 mmol/24 hours, respectively.

After 10 to 15 years, the researchers found that 200 of the 2,415 subjects available for follow-up had developed a cardiovascular condition. They found that the intervention groups were 25 percent less likely to develop cardiovascular conditions and had a 20 percent lower mortality rate than the control groups who did not restrict salt intake.

"The observed reduction in cardiovascular risk associated with this sodium decrease was substantial and provides strong support for population-wide reduction in dietary sodium intake to prevent cardiovascular disease," the authors concluded.

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Telemonitoring Improves Heart Failure Patient Outcome

Remote monitoring programs reduce heart failure admissions and mortality rates

Remote monitoring that includes structured telephone support or telemonitoring helps improve clinical outcomes in community-dwelling patients with heart failure, researchers report in the April 10 online edition of BMJ. Remote monitoring may help those with poor access to health care due to geography, transport or infirmity.

Simon Stewart, Ph.D., from the Baker Heart Research Institute in Melbourne, Australia, and colleagues reviewed data from 15 electronic databases and previous randomized studies comparing remote monitoring with standard care to determine whether telephone monitoring can improve outcomes in patients with heart failure. Overall, 14 trials with a total of 4,264 patients were included.

Remote monitoring was found to reduce rates of admission for chronic heart failure by 21 percent and reduce all-cause mortality by 20 percent. Some of the studies showed improvements in quality of life and others showed that remote monitoring either has a positive effect or no additive effect on health care costs.

The authors caution that "monitoring is not a treatment but rather a different way of systematically organizing effective care. Thus, programs that include remote monitoring should not be seen as a replacement for specialist care or multidisciplinary chronic heart failure clinics."

The study was partly supported by Phillips Healthcare.

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Coronary Sinus Reducer Helps Reperfuse Ischemic Heart

Chronic angina patients untreatable by revascularization may benefit from new device

A Coronary Sinus Reducer device may help to reperfuse ischemic heart muscle in patients with chronic refractory angina pectoris who are not candidates for revascularization, according to the results of an open-label non-randomized trial published in the May 1 issue of the Journal of the American College of Cardiology.

Shmuel Banai, M.D., of Tel Aviv Medical Center in Tel Aviv, Israel, and colleagues electively treated 15 patients with coronary artery disease and severe angina, including reversible ischemia, with a Coronary Sinus Reducer device, which is an hourglass-shaped stainless steel stent. Clinical outcomes were measured before and up to six months after implantation. Narrowing the coronary sinus helps to redistribute blood from non-ischemic to ischemic tissue.

All procedures were successful and occurred without adverse events. Angina score and average Canadian Cardiovascular Society scores improved in most patients and stress-induced ST-segment depression was reduced or eliminated in six of nine patients studied. Computed tomography showed that the extent and severity of ischemia was also reduced.

"The use of percutaneous transvenous implantation of the Coronary Sinus Reducer in patients with refractory angina was found to be safe and feasible," the authors write. "These findings…support further evaluation of the Coronary Sinus Reducer in a randomized placebo-controlled trial, as an alternative tool for treating patients with refractory angina who are not candidates for or are at high risk for revascularization."

Some of the authors are consultants or employees of Neovasc Medical, Inc., the manufacturer of the Coronary Sinus Reducer.

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Rosiglitazone May Worsen Edema in Heart Failure Patients

Drug helps glycemic control and does not affect ejection fraction

Rosiglitazone improves glycemic control but does not affect left ventricular ejection fraction in patients with type 2 diabetes and chronic heart failure, according to a report in the April 24 issue of the Journal of the American College of Cardiology. Rosiglitazone-treated patients also tend to have more problems with edema.

Henry J. Dargie, M.B., Ch.B., from Western Infirmary in Glasgow, Scotland, and colleagues randomized 224 patients with type 2 diabetes and New York Heart Association functional class I and II chronic heart failure to 4 to 8 mg daily rosiglitazone or placebo, in addition to their background antidiabetes therapy, to study the effects on left ventricular ejection fraction.

Left ventricular ejection fraction at baseline and after 52 weeks was similar in both treatment groups. However, glycemic control was better in the rosiglitazone group as measured by a 0.65 percent reduction in hemoglobin A1c. Rosiglitazone treatment was associated with more edema events compared with placebo (25.5 percent vs. 8.8 percent, respectively) and increased congestive heart failure medication (32.7 percent vs. 17.5 percent) but was not associated with higher dropout.

The results provide "important information about the lack of a significant effect of [thiazolidinediones] on left ventricular systolic function in subjects with heart failure," wrote JoAnn Lindenfeld, M.D., and a colleague from the University of Colorado in an editorial. "Their data also confirm that worsening edema with the [thiazolidinediones] in such patients remains an important clinical problem."

Some of the authors were employed by GlaxoSmithKline or received support from the company.

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Autoantibody Response Linked to Dilated Cardiomyopathy

Study links Fc portion of autoantibodies to negative inotropic effects on cardiomyocytes

The Fcγ receptors IIa on cardiomyocytes may be the reason why autoantibodies generated in patients with dilated cardiomyopathy can trigger negative inotropic effects, according to a report in the April 24 issue of the Journal of the American College of Cardiology.

Dilated cardiomyopathy (DCM) is associated with autoantibodies that target cardiomyocytes, but how these antibodies impair cardiac function is unknown. Alexander Staudt, M.D., of the Ernst-Moritz-Arndt-Universitat in Greifswald, Germany, and colleagues isolated these antibodies from 11 DCM patients to determine which fragments of the antibodies triggered a response in cardiomyocytes.

The patients' antibodies reduced calcium transients and cell shortening of rat cardiomyocytes, while healthy patients' antibodies did not. However, the same effect was not seen using the isolated Fab portion of the antibody. Reconstituting the Fc portion of the antibody resulted in a regain of the effects on calcium transients and shortening of cardiomyocytes. These cells were found to express the corresponding Fcγ receptor IIa.

These results "should encourage investigators to explore this novel pathway to understand the pathogenesis of DCM and other autoimmune cardiac diseases," wrote Sudhir Gupta, M.D., Ph.D., from the University of California, Irvine, in an accompanying editorial. The antibodies should be used to subclassify patients with DCM and for development of immunoadsorption columns, Gupta added.

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BNP-Guided Treatment Helps Heart Failure Outcome

Lowering BNP levels reduces CHF-related deaths, hospital stays

A strategy of reducing plasma brain natriuretic peptide (BNP) levels in patients with chronic heart failure lowers the risk of death and hospital stays compared to standard care, according to results from the STARS-BNP multicenter study published in the April 24 issue of Journal of the American College of Cardiology.

Patrick Jourdain, M.D., of Rene Descartes University, Paris, France, and colleagues randomized 220 heart failure patients with New York Heart Association functional class II and III to either standard care or care with the goal of decreasing BNP levels. All patients were optimally treated with angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics.

After a mean follow-up of 15 months, 24 percent of patients in the BNP-guided strategy group reached the combined end-point of heart failure-related death or hospital stay compared with 52 percent of the standard-care group. This was accomplished largely through adjustments in ACE inhibitors and beta-blockers, which were used more frequently at three months in the BNP group.

"This study has shown that chronic heart failure treatment optimization based on plasma BNP levels is associated with a lower risk of death related to heart failure or hospital stay related to heart failure than the usual strategy based on clinical expertise," the authors wrote. "The benefit was observed despite optimization of therapy in both groups by cardiologists specialized in congestive heart failure before entry into the study."

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AHA Says Most Don't Need Antibiotics Before Dentist Visit

Updated AHA guidelines suggest that the benefits outweigh the risks only for certain patients

Only patients at the highest risk of infective endocarditis should have prophylactic antibiotic treatment before routine dental procedures, according to updated guidelines from the American Heart Association published in the April 19 issue of Circulation: Journal of the American Heart Association. High-risk patients would include those with a history of endocarditis, a heart transplant or an artificial valve transplant.

Walter Wilson, M.D., of the Mayo Clinic in Rochester, Minn., and a scientific panel updated the 1997 guidelines on the prevention of infective endocarditis by examining the data on the risk and benefits of prophylactic antibiotics.

The researchers found that despite decades of antibiotic treatment before routine dental procedures, the risks -- including allergic reactions and antibiotic resistance -- outweighed the benefits for most patients. Therefore, only those at highest risk from endocarditis should be given antibiotics before dental interventions, the panel recommended. High-risk patients include former endocarditis patients, heart transplant and artificial heart valve recipients, and patients with some congenital heart conditions.

"The Committee concluded that only an extremely small number of cases of infective endocarditis might be prevented by antibiotic prophylaxis for dental procedures," the authors wrote. In addition, "administration of antibiotics solely to prevent endocarditis is not recommended for patients who undergo a genitourinary tract procedure."

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Young Smokers Have Impaired Left Ventricular Function

Pulmonary venous flow parameters are sensitive markers of early subclinical diastolic dysfunction

In otherwise healthy young adults, smoking has chronic and acute adverse effects on left ventricular diastolic function, according to the results of a study published in the April issue of Chest.

Barbara Lichodziejewska, M.D., Ph.D., of Warsaw Medical University in Poland, and colleagues studied 66 healthy volunteers (33 smokers and 33 non-smokers) under age 40 with a normal body mass index. In the smoking group, the researchers assessed heart function before and after the volunteers smoked one cigarette.

The investigators found a significantly lower mitral valve flow early to late phase ratio in the smoking group before and after smoking a cigarette than in the control group. They also found a significantly higher pulmonary venous flow systolic to diastolic phase ratio in smokers than in controls.

"The results of the present study suggest that the pulmonary venous flow parameters are especially sensitive markers in detection of early subclinical left ventricular diastolic dysfunction, even when mitral valve flow parameters remain normal," the authors write. "It was not a major dysfunction but a bend from a normal state that did not cause any clinical symptoms of heart failure. Therefore, none of the studied smokers met the criteria of a major diastolic dysfunction presented in the report of the European Study Group on Diastolic Heart Failure."

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Lung Adenocarcinoma Declining in U.S. Men, Women

Although the reasons for the trend are unclear, analysis suggests that it will continue

Since 1999, the incidence of adenocarcinoma of the lung has declined in both men and women in the United States, but the reasons for this trend remain unclear, according to a study published in the April issue of Chest.

Philip Cole, M.D., of the University of Alabama at Birmingham, and colleagues used data from the Surveillance Epidemiology and End Results Program to assess 1973-2003 incidence rates of adenocarcinoma of the lung. They also assessed trends in low-tar cigarette consumption during that period.

Between 1973 and 1998, the researchers found that incidence rates increased by 83 percent in men and by more than 200 percent in women. Between 1999 and 2003, however, incidence rates declined by 14 percent in men and by 8 percent in women. The researchers suggest the driving forces behind this trend may be declining levels of air pollution and, to a lesser extent, increasing use of low-tar cigarettes and lower exposure to environmental tobacco smoke.

"The recent five-year decline in the age-adjusted incidence rate of adenocarcinoma of the lung, especially in men, is further explained by birth cohort patterns," the authors write. "Both genders show the same pattern, with persons born after 1930 having progressive declines in age-specific incidence rate of adenocarcinoma of the lung. This suggests that incidence rates in both genders will continue to decrease in coming years."

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Statins May Reduce Influenza and COPD Death Risk

But it's still unclear whether or not statins could prevent or delay death from avian flu

Patients who take statins in moderate doses have a reduced risk of death from chronic obstructive pulmonary disease (COPD) and influenza compared to those who do not, according to the results of a study published in the April issue of Chest.

Floyd J. Frost, Ph.D., of the University of New Mexico School of Medicine in Albuquerque, N.M., and colleagues conducted a matched cohort study of 76,232 patients and two separate case-control studies of 207 COPD and 397 influenza deaths.

In the cohort study, the researchers found that patients who took at least 4 milligrams of statins per day had a reduced risk of death from COPD (odds ratio, 0.17) and from influenza/pneumonia (OR, 0.60). The case-control studies confirmed these findings, according to the researchers.

"There remain, unfortunately, many uncertainties about the effectiveness of statins as an approach to preventing or delaying death from avian influenza," the authors conclude. "However, given the lack of effective alternatives, resolving these uncertainties should be a high priority."

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