Latest Research

Statistical Method Affects Observational Study Results

Investigators should 'be cautious' when choosing statistical methods to adjust for bias

The statistical methods that are used to analyze data from observational studies can have a large impact on the results derived from that data, researchers report in the Jan. 17 issue of the Journal of the American Medical Association.

Therese Stukel, Ph.D., from the Institute for Clinical Evaluative Sciences in Toronto, Canada, and colleagues used four analytic methods to remove the effects of selection bias in an observational study that assessed survival in 122,124 elderly patients with acute myocardial infarction who underwent cardiac catheterization.

After adjusting for overt or measured bias using either multivariable model risk adjustment, propensity score risk adjustment or propensity-based matching, the investigators found a 50 percent reduction in death rate from catheterization. However, adjusting for hidden or unmeasured bias using instrumental variable analysis, and using regional catheterization rate as an instrument, the drop in death rate from catheterization was only 16 percent.

The article "is an important reminder of the need for careful and rigorous approaches to observational data analyses," write Ralph B. D'Agostino, Jr., Ph.D., of Wake Forest University School of Medicine in Winston Salem, N.C., and Ralph B. D'Agostino, Sr., Ph.D., of Boston University, in an accompanying editorial. The investigators "must ensure that they have available what they consider to be the most important patient characteristics measured before treatment assignment."

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Virtual Reality 'Practice Run' May Help in Carotid Stenting

Using images of patient's own vascular anatomy during simulation is good practice for live procedure

A virtual reality "practice run" that is performed immediately prior to carotid artery stenting may save time and allow operators to learn the patient's anatomy without risk, according to a research letter in the Jan. 17 issue of the Journal of the American Medical Association. The patient's magnetic resonance images are converted to digital images that are used in a vascular training simulator program.

Christopher U. Cates, M.D., of Emory University School of Medicine in Atlanta, and colleagues performed such a simulation in a 64-year-old man with severe chronic obstructive pulmonary disease, whose right internal carotid artery had an ulcerated lesion and was 80 percent stenosed.

The simulation and live procedure were similar in angiography, as well as catheter handling, interactions, wire movements and embolic protection device use and retrieval. The simulation allowed the operator to anticipate the proper approach to the aortic arch and select devices without using online quantitative angiography analysis. The patient had no in-hospital complications and was asymptomatic at one year.

"This case shows that mission rehearsal in humans can be performed with currently available virtual reality-simulation technology, that decisions made during the rehearsal may directly translate to the actual patient, and that operators can practice with the patient's own anatomy without risk. By identifying optimal patient-specific techniques prior to the actual procedure and promoting proficiency, virtual reality simulation has the potential for improved patient safety," the authors conclude.

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South Asians at Risk for Early MI Due to Smoking, Diabetes

Average age of myocardial infarction nearly six years earlier in South Asia than in other countries

South Asians tend to have myocardial infarctions at a younger age than individuals in other countries largely because of lifestyle factors such as smoking and diabetes, researchers report in the Jan. 17 issue of the Journal of the American Medical Association.

Prashant Joshi, M.D., of the Government Medical College in Nagpur, India, and colleagues sought the reasons for early presentation of coronary heart disease shown previously in residents of the South Asian countries of India, Pakistan, Bangladesh, Sri Lanka and Nepal. The risk factor profiles of 1,732 myocardial infarction patients and 2,204 controls from South Asian countries were compared to 10,728 myocardial infarctions cases and 12,431 controls from other countries.

The researchers found that the average age of myocardial infarction patients from South Asian countries was 53 years compared with 58.8 years for residents of other countries. South Asians had both a higher prevalence of coronary heart disease risk factors -- such as a history of smoking, hypertension and diabetes -- and a lower prevalence of protective factors including physical activity and intake of alcohol, fruits and vegetables.

"The younger age of first acute myocardial infarction among the South Asian cases in our study appears to be largely explained by the higher prevalence of risk factors in native South Asians," the authors write. "These data suggest that lifestyle changes implemented early in life have the potential to substantially reduce the risk of acute myocardial infarctions in South Asians."

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Post-Op Chemo Delays Pancreatic Cancer Recurrence

Mean disease-free survival increased by six months, but no effect on overall survival

Postoperative gemcitabine therapy significantly delays the recurrence of pancreatic cancer compared to observation only, although it does not increase survival, according to a report in the Jan. 17 Journal of the American Medical Association.

Helmut Oettle, M.D., Ph.D., of Charite School of Medicine in Berlin, Germany, and colleagues conducted a multicenter, randomized, controlled trial to determine if adjuvant chemotherapy with gemcitabine after resection of pancreatic cancer improves disease-free survival by at least six months compared with standard treatment.

In the study, 179 patients were randomized to gemcitabine while 175 patients were designated to observation only, the current standard of care. During a median follow-up of 4.5 years, recurrent cancer developed in 74.3 percent of the gemcitabine group and 92 percent of the control group. Estimated mean disease-free survival increased from 6.9 months for observation only to 13.4 months for the gemcitabine group.

No difference in overall survival was found, however, prompting Al Benson III, M.D., of Northwestern University in Chicago, to write in an accompanying editorial: "Worldwide, there is a need to move away from the question of current chemotherapy agents versus chemoradiation to a research focus based on enhancing understanding of biologic principles."

Some of the authors of the original report have received compensation or funding from various pharmaceutical companies.

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Nine Percent of High School Football Linemen Obese

Iowa study suggests that almost half of all players overweight

Nearly one in 10 Iowa high school football linemen is severely obese, while almost half are overweight, according to a Research Letter in the Jan. 24/31 issue of the Journal of the American Medical Association.

Joey C. Eisenmann, Ph.D., of Iowa State University in Ames, Iowa, and a colleague analyzed the body mass index of 3,683 linemen on 251 of the 364 Iowa high school football teams in the fall of 2005.

The researchers found the players' mean body mass index was over the 85th percentile in all grades. Forty-five percent of players were overweight, far exceeding the 18.3 percent of boys aged 12 to 19 who were overweight in a national 2003-2004 survey. Meanwhile, 28 percent of the players ran the risk of being overweight.

Players' mean body mass index increased from 26.1 for freshmen to 28.5 for seniors. The researchers report that 7 percent of the players were adult class II obese, with a body mass index of 35-39, and 2 percent were class III obese, with a 40 or higher body mass index.

"The prevalence of overweight in this group of high school linemen was 45 percent," the authors write. "Of these students, 9 percent would be classified with adult severe obesity."

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Tuberculosis Intervention Boosts Adherence in Senegal

Intervention may benefit tuberculosis patients in other resource-poor countries

A tuberculosis intervention program of counseling and community involvement may boost treatment adherence in resource-poor countries, according to a report in the Jan. 24/31 issue of the Journal of the American Medical Association.

Sylla Thiam, M.D., of the Institut de Recherche pour le Developpement in Dakar, Senegal, and colleagues conducted a randomized controlled trial of 1,522 patients older than 15 years of age, who were newly diagnosed with pulmonary tuberculosis, to determine if a contextualized intervention program improved adherence to therapy among Senegal residents. The intervention arm involved improved communication between patients and their health care providers, decentralizing treatment, choice of directly observed therapy supporter by the patient and reinforcement of supervision activities.

Eighty-eight percent of patients in the intervention group were successfully treated for their tuberculosis, compared with 76 percent in the control group who received usual tuberculosis care. Moreover, the risk of defaulting from treatment was about 60 percent lower among individuals in the intervention arm compared with their counterparts who received usual tuberculosis care.

"This intervention could now be implemented in a stepwise manner throughout Senegal, and we believe that this approach may be generalized within the context of tuberculosis control programs in other resource-poor countries," the researchers conclude.

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Older Men and Women Have Similar Risk for Refracture

After first low-trauma break, older men have similar absolute risk for subsequent fracture as women

After an initial low-trauma fracture, men 60 and older have a similar absolute risk for subsequent fractures as women. The increased incidence persisted for 10 years and occurred for most clinical fractures, according to a 16-year follow-up study in the Jan. 24/31 issue of the Journal of the American Medical Association.

Jacqueline R. Center, Ph.D., of the University of New South Wales in Sydney, Australia, and colleagues analyzed data from a prospective cohort study of 2,245 women and 1,760 men aged 60 or older.

Of the 905 women and 337 men with an initial fracture, 253 women and 71 men had another fracture. Women's relative risk for refracture was 1.95 and men's was 3.47. The absolute risk for refracture was similar for both. Women and men 60 to 69 years had absolute refracture rates of 36/1,000 person-years and 37/1000 person years, respectively.

The increase in absolute fracture risk persisted for 10 years, with 40 percent to 60 percent having another fracture. Except for rib (men) and ankle (women), all fracture sites carried more refracture risk. Femoral neck bone mineral density, smoking and age predicted future fracture in women and femoral neck bone mineral density, calcium intake and physical activity were predictors in men.

The study was funded by grants from Merck Sharp and Dohme, Eli Lilly and GE Lunar Corp.

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SSRI Relieves Depression in Heart Disease Patients

Citalopram and clinical management reduces symptoms in depressed coronary artery disease patients

In depressed coronary artery disease (CAD) patients, citalopram coupled with clinical management relieves depression better than placebo alone, while interpersonal psychotherapy provides no additional benefit over clinical management, according to study findings published in the Jan. 24/31 Journal of the American Medical Association.

Francois Lesperance, M.D., of the Centre Hospitalier de l'Universite de Montreal in Quebec, Canada, and colleagues evaluated data from the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy study to determine the short-term efficacy of citalopram and interpersonal psychotherapy in reducing major depression in 284 CAD patients.

Patients were randomized to receive either: interpersonal psychotherapy plus clinical management and 20 to 40 mg/day of citalopram; therapy plus clinical management and placebo; clinical management only and citalopram; or clinical management only and placebo. In clinical management, patients received encouragement and information about depression, but did not discuss grief, life transitions or other emotional issues discussed in psychotherapy.

At 12 weeks, citalopram had a small to medium effect over placebo in reducing Hamilton Depression scores. Mean Hamilton Depression response and remission rates and the reduction in Beck Depression Inventory II scores favored citalopram. The authors noted no benefit of interpersonal therapy over clinical management, with the mean Hamilton Depression difference favoring clinical management.

"Citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression," write the authors, some of whom consult for or receive funding from various drug companies.

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Breast Density Linked to Greater Cancer Risk

High density also decreases detection by mammography

Women who have dense breast tissue are less likely to have cancer detected during mammography and have an increased risk of breast cancer compared to women with tissue that is less dense, according to a report in the Jan. 18 issue of the New England Journal of Medicine.

Norman F. Boyd, M.D., from the Ontario Cancer Institute in Toronto, Canada, and colleagues examined the association between mammographic breast density and risk of breast cancer in 1,112 matched case-control pairs based on age, method of cancer detection and time since initiating screening.

The researchers found that a higher breast density was associated with a greater risk of breast cancer (odds ratio, 4.7 for density of 75 percent or greater versus density less than 10 percent). For women with a 75 percent or greater mammographic density, the odds ratio was 3.5 for breast cancer that was detected by screening and 17.8 for cancer detected within a year after a negative screening test. The increased risk was higher in younger women and continued for at least eight years after entering the study.

A substantial percentage of breast cancers can be attributed to high mammographic density, the report indicates.

"The time has come to acknowledge breast density as a major risk factor for breast cancer and to determine, develop and test the best ways to measure breast density in clinical practice, and use this measurement to maximize primary and secondary prevention of breast cancer," Karla Kerlikowske, M.D., of the University of California San Francisco, writes in an accompanying editorial.

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'Gene Signature' Predicts Survival in Four Cancer Types

Survival predicted for breast cancer, medulloblastoma, lung cancer, prostate cancer

A "gene signature" is effective at predicting overall and metastasis-free survival in patients with breast cancer, medulloblastoma, lung cancer and prostate cancer, researchers report in the Jan. 18 issue of the New England Journal of Medicine.

Michael F. Clarke, M.D., of the University of Michigan in Ann Arbor, and colleagues developed an "invasiveness gene signature" consisting of 186 genes that were differentially expressed in normal breast epithelium and a subset of breast cancer cells that were CD44-positive and low-to-negative for CD24. The gene signature's ability to predict survival was assessed in 581 patients with high-risk early breast cancer or other types of cancer.

There was an association between the gene signature and overall and metastasis-free survival for breast cancer, independent of clinical and pathological factors, as well as medulloblastoma, lung cancer and prostate cancer. Combining the gene signature with National Institutes of Health prognostic criteria showed that breast cancer patients with a good prognosis had an 81 percent chance of 10-year metastasis-free survival compared with only 57 percent for those with a poor prognosis. The predictive value increased when combined with the wound-response signature.

"These are exciting results, but the disconcerting reality is that gene sets in the various studies are largely non-overlapping, raising questions about their biologic significance and clinical implications," Joan Massague, Ph.D., of the Memorial Sloan-Kettering Cancer Center in New York City, writes in an accompanying editorial.

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Congenital Leptin Receptor Deficiency Causes Child Obesity

Deficiency of receptor differs from deficiency in hormone itself

Congenital deficiency of the leptin receptor differs from a deficiency of leptin itself and is marked by excessive appetite in childhood and severe obesity without signs of developmental delay or dysmorphism, according to study findings published in the Jan. 18 issue of the New England Journal of Medicine.

I. Sadaf Farooqi, M.B., B.S., Ph.D., of Addenbrooke's Hospital in Cambridge, U.K., and colleagues sequenced the leptin-receptor gene in 300 subjects with hyperphagia and severe early-onset obesity. The cohort included 90 index patients from blood-related families.

Three percent of the 300 subjects had nonsense or missense leptin receptor mutations. The missense mutations resulted in impaired receptor signaling. Blood levels of leptin were not elevated among people with leptin-receptor deficiency. Less severe than leptin deficiency, leptin-receptor deficiency is characterized by hyperphagia, severe obesity, changes in immune function and delayed puberty, the researchers found.

"This diagnosis has implications for the care of these patients, both in terms of genetic counseling of the affected families and in terms of future prospects for treatment, since these patients would be predicted to have favorable response to drugs targeted at pathways downstream of the leptin receptor," the researchers conclude.

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Child Development Unaffected by Ear Tube Insertion

Development similar in children with middle-ear effusion regardless of when tube is inserted

Children with persistent middle-ear effusion have similar developmental outcomes regardless of whether they receive prompt or delayed insertion of tympanostomy tubes, according to the results of a study published in the Jan. 18 issue of the New England Journal of Medicine.

Jack L. Paradise, M.D., of the Children's Hospital of Pittsburgh, and colleagues compared developmental outcomes in 391 children with persistent middle-ear effusion who were less than 3 years old when they were randomized to either prompt insertion of tympanostomy tubes or insertion up to nine months later if the effusion persisted.

When the children were 9 to 11 years old, the researchers found that both groups were similar on 48 measures of literacy, attention, social skills and academic achievement.

The study "provides convincing evidence that persistent middle-ear effusion in otherwise normal children does not cause developmental impairments," Stephen Berman, M.D., from the University of Colorado School of Medicine in Denver, writes in an accompanying editorial. "These new findings are important because they provide reassurance that developmental impairments that are not identified at an earlier age do not come into play later in the setting of greater academic challenges."

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Antibodies Not Associated with Multiple Sclerosis

Presence of antimyelin antibodies not associated with progression to clinical disease

The presence of antimyelin antibodies in patients who have symptoms suggestive of multiple sclerosis is not associated with progression to clinical disease, researchers report in the Jan. 25 issue of the New England Journal of Medicine.

Ludwig Kappos, M.D., from University Hospital in Basel, Switzerland, and colleagues measured serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein in 462 patients who had had a clinical event suggestive of multiple sclerosis and lesions on a magnetic resonance imaging scan.

During the 24 months of follow-up, 32 percent of patients were diagnosed with clinically definite multiple sclerosis and 72 percent were diagnosed with multiple sclerosis based on the McDonald criteria. There was no association between the presence of either antibody and a diagnosis of multiple sclerosis, either in the whole group or in any subgroups, the researchers report.

"Our results strongly suggest that antimyelin antibodies have no role in the diagnosis of multiple sclerosis or in the identification of patients at high risk for the development of clinically definite disease," Kappos and colleagues conclude.

The study was supported in part by Schering.

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Posaconazole More Effective in Preventing Fungal Infections

Drug compared to fluconazole in immunosuppressed patients

Posaconazole may be more effective than fluconazole at preventing fungal infections in patients with graft-versus-host disease or prolonged neutropenia, and may prolong survival in the case of neutropenia, according to two studies in the Jan. 25 issue of the New England Journal of Medicine.

Andrew J. Ullmann, M.D., from Johannes Gutenberg University in Mainz, Germany, and colleagues randomized 600 patients with graft-versus-host disease being treated with immunosuppressive drugs to posaconazole or fluconazole as prophylaxis against invasive fungal infection.

The researchers found that posaconazole was as effective as fluconazole in preventing fungal infection (5.3 versus 9 percent, odds ratio 0.56), although this bordered on statistical significance, while posaconazole was more effective in preventing aspergillosis infection (2.3 versus 7 percent, odds ratio 0.31). Both groups had similar overall mortality, but there were fewer deaths from fungal infections in the posaconazole group (1 versus 4 percent).

Oliver A. Cornely, M.D., from the University of Cologne in Germany, and colleagues randomized 602 patients with prolonged neutropenia due to chemotherapy to posaconazole, fluconazole or itraconazole. They found fewer fungal infections in the posaconazole group compared with the other two groups (2 versus 8 percent), and fewer cases of invasive aspergillosis (1 versus 7 percent). Overall survival was longer in the posaconazole group.

Both studies were supported by the Schering-Plough Research Institute.

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Uterine Fibroid Recovery Faster After Embolization

But about 20 percent of embolization patients require further treatment

Women with uterine fibroids recover faster if treated by uterine artery embolization rather than surgery, but about 20 percent of embolization patients require further invasive treatment, according to a report in the Jan. 25 issue of the New England Journal of Medicine.

Jonathan G. Moss, M.B. Ch.B., from the University of Glasgow in Scotland, and colleagues randomly assigned 106 patients with symptomatic uterine fibroids to uterine artery embolization and 51 to surgery (hysterectomy or myomectomy).

The researchers found that the embolization group had significantly shorter median hospital stays than the surgical group (one day versus five days) and returned to work significantly earlier. After one year, quality of life was similar in both groups, but the surgical group had significantly better symptom scores. Twenty percent of patients in the embolization group required further invasive treatment, the report indicates.

The decision to treat with surgery or embolization "varies with the clinical situation, including a patient's age, her treatment preference, her wish to conceive and the type of surgery planned," Togas Tulandi, M.D., from McGill University in Montreal, Canada, writes in an accompanying editorial.

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Folic Acid May Slow Cognitive Decline of Aging

Age-related cognitive function decline reduced by three years of supplements

A three-year course of folic acid supplements may reduce age-related cognitive function declines in middle-aged and older adults, according to the results of a randomized, placebo-controlled trial published in the Jan. 20 issue of The Lancet.

Jane Durga, Ph.D., of Wageningen University in Wageningen, the Netherlands, and colleagues conducted, as part of the Folic Acid and Carotid Intima-media Thickness (FACIT) trial, a study of 818 patients in the Netherlands aged 50 to 70 years. Subjects were randomized to receive a daily oral dose of 800 μg folic acid or placebo for three years. At the end of the study, the researchers measured participants' memory, sensorimotor speed, complex speed, information processing speed and word fluency.

In the folic acid group, serum folate concentrations rose 576 percent and plasma total homocysteine concentrations declined by 26 percent. Memory, information processing speed and sensorimotor speed were better in the folic acid group compared to the placebo group.

In an accompanying editorial, Martha Clare Morris, Sc.D., and Christine Tangney, Ph.D., of Rush University Medical Center in Chicago, point out that the study participants' dietary intake of folate levels fell well below recommended levels. "Many individuals within populations have folate intakes that might be suboptimum for physiological function," they write. "To make more informed dietary recommendations for optimum folate intake, we need randomized trials that take the approach of the FACIT trial."

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Antihypertensive Drugs Ranked According to Diabetes Risk

Lowest odds from angiotensin-receptor blockers and angiotensin-converting-enzyme inhibitors

Patients with hypertension who are treated with angiotensin-receptor blockers or angiotensin-converting-enzyme (ACE) inhibitors may have a lower risk of developing diabetes than those treated with other drugs, according to a meta-analysis published in the Jan. 20 issue of The Lancet.

William J. Elliot, M.D., and Peter M. Meyer, Ph.D., of Rush University Medical Center in Chicago, conducted a meta-analysis of 22 clinical trials comprising 48 groups and 143,153 patients. Seventeen trials focused on hypertension patients, three on high-risk patients and one on heart failure patients.

Compared to diuretics, the odds ratio for incident diabetes was 0.57 for angiotensin-receptor blockers, 0.67 for ACE inhibitors, 0.75 for calcium-channel blockers, 0.77 for placebo and 0.90 for beta-blockers.

The authors note that a number of trials are currently under way that will provide important data on the association between antihypertensive drugs and diabetes risk.

"Until these trials are reported, however, our network meta-analysis provides a useful and complete picture of the propensity of antihypertensive drugs to be associated with incident diabetes," the authors conclude, adding that the method's ability to make indirect comparisons is particularly useful given that no trials have directly compared ACE and angiotensin-receptor blockers.

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Nitric Oxide Synthase Inhibitor Blocks Tumor Blood Supply

Phase I study shows for the first time drug has effect in vivo

The nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA) inhibits the blood supply to tumors and has been shown for the first time to be effective in vivo, according to the results of a study published online Jan. 15 in The Lancet Oncology.

Quan-Sing Ng, M.R.C.P., of Mount Vernon Cancer Centre in Middlesex, U.K., and colleagues conducted a study of 18 cancer patients, (11 men and seven women) including 12 with non-small-cell lung cancer, five with prostate cancer and one with cervical cancer, who were given escalating doses of L-NNA.

Eight of the patients underwent computed tomography scanning, which revealed that an hour after treatment with the drug, tumor blood volume decreased and stayed suppressed for up to 24 hours. However, several patients experienced toxic cardiovascular side effects from the drug, including hypertension, sinus bradycardia and palpitation.

"The sustained reductions in tumor blood volume after a single dose of L-NNA seem promising for use as a novel vascular targeting agent. However, the biological role of nitric oxide in cancer remains unclear," the authors write. "Although this study describes the tumor vascular effects of inhibition of nitric oxide synthesis, further studies will be necessary to relate these vascular findings to clinical outcome," they conclude.

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Shorter Telomeres Increase Risk of Cardiovascular Events

Risk can be reversed by statin treatment

Middle-aged men who have leukocytes with shorter telomeres, the repetitive DNA that caps the ends of chromosomes, are at higher risk of developing coronary heart disease events than men with longer telomeres, researchers report in the Jan. 13 issue of The Lancet. However, the elevated risk can be reversed by statin treatment in those who are telomere-deficient.

Nilesh J. Samani, F.R.C.P., from the University of Leicester in the United Kingdom, and colleagues compared mean leukocyte telomere lengths in 484 middle-aged men who had a coronary heart disease event and 1,058 matched controls. They also examined the association between telomere length and efficacy of statin treatment.

Although telomere length decreased with age in both groups, patients in the middle and bottom third of telomere length were at higher risk of a coronary heart disease event compared with those in the top third (odds ratios 1.51 and 1.44, respectively). Treatment with pravastatin reduced the risk of coronary heart disease associated with shorter telomeres (odds ratios 1.12 and 1.02, respectively).

"These findings should provide further motivation to identify a marker for individual telomere shortening, a marker for which absolute numbers predict absolute risk," Ioakim Spyridopoulos, M.D., and Stefanie Dimmeler, Ph.D., from the University of Frankfurt in Germany, write in an accompanying editorial.

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No Link Seen Between Benzodiazepines, Hip Fracture

Researchers suggest that federal and state restrictions on use may be unwarranted

Contrary to previous research, benzodiazepines may not increase the risk of hip fracture, and lawmakers should reconsider federal and state restrictions that limit the use of benzodiazepines in elderly patients as a way to reduce fractures, according to a report published in the Jan. 16 issue of the Annals of Internal Medicine.

Anita Wagner, Pharm.D., M.P.H., Dr.PH., of Harvard Medical School and Harvard Pilgrim Health Care in Boston, and colleagues studied benzodiazepine prescriptions and hip fractures in 51,529 New York Medicaid enrollees during the 12 months before and 21 months after New York adopted a triplicate-form prescription policy in 1989. As a control, they also studied 42,029 Medicaid enrollees in New Jersey, which has a less restrictive policy.

The researchers found that New York's triplicate prescription policy immediately resulted in decreases in benzodiazepine use in women (60.3 percent) and men (58.5 percent), while use in New Jersey remained stable. But the investigators found that age- and eligibility category-adjusted hazard ratios for hip fracture did not change in either state. The hazard ratio changed from 1.2 to 1.1 among female benzodiazepine users and from 1.3 to 1.1 among female non-users, and from 0.8 to 1.1 among male users and from 1.1 to 1.3 among male non-users.

"Policies that lead to substantial reductions in the use of benzodiazepines among elderly persons do not necessarily lead to decreased incidence of hip fracture," the authors conclude. "Limitations on coverage of benzodiazepines under Medicare Part D may not achieve this widely assumed clinical benefit."

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Growth Hormone Not Beneficial As Anti-Aging Therapy

Review finds little evidence for clinical efficacy in healthy elderly

Current data suggests that growth hormone should not be used as an anti-aging therapy in healthy elderly people because the risks far outweigh the benefits, which are minimal, according to a review of the literature published in the Jan. 16 issue of the Annals of Internal Medicine.

Hau Liu, M.D., of Stanford University in Stanford, Calif., and colleagues searched MEDLINE and EMBASE databases for studies related to the use of growth hormone as an anti-aging therapy in elderly patients. The final analysis included 18 unique studies with a total of 220 overweight elderly participants receiving growth hormone.

After treatment, body mass shifted to lower fat mass and higher lean muscle mass, but overall weight did not change nor did serum lipid levels. Soft tissue edema, arthralgias, carpal tunnel syndrome and gynecomastia were more likely to occur in growth hormone-treated individuals.

"Although growth hormone has been widely publicized as an anti-aging therapy and initial studies suggested that it might be clinically beneficial and safe in the healthy elderly, we find little evidence to support these claims," the authors write.

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HAART Improves Life Expectancy for HIV-Positive

Young persons on therapy live an average of more than 35 years after HIV diagnosis

With the advent of highly active antiretroviral therapy, or HAART, the median survival time for a young person with HIV is more than 35 years, according to a report in the Jan. 16 issue of the Annals of Internal Medicine. However, their life expectancy is still far from normal.

In the study, Nicolai Lohse, M.D., Ph.D., from Odense University Hospital in Odense, Denmark, and colleagues estimated the survival time and age-specific mortality in a population of 3,990 HIV-infected patients in the Danish HIV Cohort Study and nearly 380,000 persons from the general population in Denmark.

Overall, survival rate measured from the time of diagnosis until May 2005 for persons with HIV aged 25 years was 19.9 years but increased to 32.5 years during the 2000 to 2005 period. When persons with hepatitis C were excluded, survival further increased to 38.9 years. These rates are still different than the general population, however, which was found to be 51.1 years.

"The survival projections in our study depend on continuous treatment success beyond the 10 years of current experience with HAART," the authors write. "An ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population."

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Opioid Use for Back Pain Linked to Substance Abuse

Meta-analyses show little change in back pain compared with control

While short-term use of opioids may be effective for chronic back pain, the benefit of long-term use remains unclear and is associated with substance abuse disorders, according to a report in the Jan. 16 issue of the Annals of Internal Medicine.

David Fiellin, M.D., of Yale University School of Medicine in New Haven, Conn., and colleagues scanned multiple medical databases for studies testing opioid use for back pain in non-obstetric, adult subjects to determine the prevalence of use, efficacy and risk for addiction.

Two meta-analyses, including a total of nine studies that compared opioids to either placebo or to other opioids, failed to show a significant reduction in pain. Lifetime substance abuse in these studies ranged from 36 percent to 56 percent. However, none of the trials lasted longer than 16 weeks.

"Clinicians should reconsider treating chronic back pain with opioid medications, and consider other treatments with similar benefit yet fewer long-term adverse effects," the authors write. "Future research is needed to guide this common and often vexing management issue."

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Rapid Flu Diagnosis Reduces Antibiotic Use

Majority of flu patients with low-risk for bacterial infection still get antibiotics

Among adults hospitalized for influenza, the use of rapid influenza testing reduces the use of antibiotics, according to study findings published online Jan. 22 in the Archives of Internal Medicine.

Ann R. Falsey, M.D., of Rochester General Hospital in Rochester, N.Y., and colleagues analyzed medical records of 166 patients who were hospitalized for flu over four consecutive winters from 1999 through 2003, and compared the clinical date of patients whose antigen test was positive (Ag+) with those whose antigen test was negative or not performed (Ag0).

In all, there were 86 Ag+ and 80 Ag0 patients. All but one of the Ag0 patients were prescribed antibiotics, versus 74 of the 86 Ag+ patients. Only 2 percent of the Ag0 patients discontinued antibiotics, compared with 14 percent of the Ag+ patients. However, even among patients who tested positive for flu, 61 percent of those who had low-risk status for bacterial infection were still given antibiotics.

"Patients who continued to receive antibiotics were more often older, were smokers with higher rates of underlying chronic obstructive pulmonary disease, and had abnormal lung examination results. These trends suggest that physicians were not indiscriminate with their therapy but rather responding to a perceived increased risk of bacterial infection in an older and frailer group," the authors write.

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Antidepressants Linked to Fracture Risk in Elderly

Among those over 50, daily use doubles risk of fragility fracture

Older adults who take a daily dose of selective serotonin reuptake inhibitors (SSRIs) are twice as prone to clinical fragility fractures as their counterparts not taking an antidepressant, according to the results of a study published in the Jan. 22 issue of the Archives of Internal Medicine.

J. Brent Richards, M.D., of McGill University in Montreal, Canada, and colleagues conducted a study of 5,008 adults aged 50 and older who were followed up for five years to ascertain the incidence of clinical fragility fractures.

Of the sample, 137 subjects reported daily use of SSRIs, and when other potential covariates were taken into account, use of the drug more than doubled the risk of fracture and the odds of falling. Other dose-dependent associations included spine and lower hip bone mineral density.

"Our results suggest that bone mineral density and falls may be affected adversely by daily SSRI use but that fracture rates remain elevated despite adjustment for these two risk factors, indicating that other pathways, such as impaired bone quality leading to reduced bone strength, may be of particular relevance," the authors conclude. "In light of the high rate of SSRI use among the general population, and among elderly persons in particular, further studies that include controlled prospective trials are needed to confirm our findings."

Several drug companies contributed to the funding of this study.

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Little Benefit to Repeat Bone Density Scans in Older Women

Even after eight years, second scan reveals little useful information

Repeating bone mineral density (BMD) scans among postmenopausal women reveals little new information that is helpful in predicting fractures, according to a report in the Jan. 22 issue of the Archives of Internal Medicine.

Teresa A. Hillier, M.D., of Kaiser Permanente Northwest/Hawaii in Portland, Ore., and colleagues measured the total hip BMD of 4,124 women, average age 72, on two occasions eight years apart and predicted the risk of fracture. Between the two tests, women lost an average of 0.59 percent of BMD a year.

Of the sample, 877 women had an incident non-traumatic non-spine fracture, including 275 hip fractures, and 340 women had a spine fracture. There was no difference between risk of fracture and the BMD measurements taken on the first or the second occasion.

Although repeat testing may be of some value in some sub-groups, such as those with other risk factors for rapid bone loss and younger women who have gone into premature menopause, one test is adequate for most postmenopausal women, the authors conclude.

"For the average healthy older woman 65 years or older, a repeat BMD measurement has little or no value in classifying risk for future fracture -- even for the average older woman who has osteoporosis by initial BMD measure or high BMD loss," they write.

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Inflammatory Markers Linked to Psychosocial Factors

Elevated levels are observed in people with cynical distrust, chronic stress and depression

High levels of cynical distrust, chronic stress and depression may be associated with increased blood levels of three inflammatory markers of cardiovascular disease: fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6), according to a study in the Jan. 22 issue of the Archives of Internal Medicine.

Nalini Ranjit, Ph.D., of the University of Michigan in Ann Arbor, and colleagues analyzed data on 6,814 healthy adults aged 45 to 84.

The researchers found that cynical distrust was strongly associated with elevated blood levels of all three inflammatory markers. They also found that chronic stress was associated with elevated IL-6 and moderately associated with elevated CRP, and that depression was only associated with elevated IL-6.

"Associations of psychosocial factors with inflammatory markers were reduced by 20 percent to 55 percent after adjustment for behavioral factors and by 45 percent to 100 percent after adjustment for body mass index (BMI) and diabetes, mostly owing to the effect of BMI," the authors write. "No associations remained after controlling for socioeconomic position, behaviors, BMI and diabetes."

The authors suggest that low socioeconomic status, unhealthy behaviors such as smoking and increased rates of obesity -- all of which are associated with increased levels of inflammatory markers -- could be mediating factors. They conclude that longitudinal studies are needed to clarify the relationship between inflammation and these mediating factors.

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Selenium Supplementation May Benefit HIV Patients

Nine-month study shows the antioxidant mineral can suppress viral load and improve CD4 counts

In patients with HIV, a daily selenium supplement may be a safe and inexpensive strategy to suppress viral load and indirectly improve CD4 counts, according to a study in the Jan. 22 issue of the Archives of Internal Medicine.

Barry E. Hurwitz, Ph.D., of the University of Miami, and colleagues randomly assigned 262 HIV patients to receive either a capsule with 200 micrograms of selenium or a placebo capsule for nine months.

The researchers found that the selenium group had significantly elevated mean blood levels of selenium compared to the placebo group (32 μg/L versus 0.5 μg/L). They also found that higher selenium levels were associated with decreased HIV-1 viral load, which predicted an increased CD4 count. Subjects with high treatment adherence were most likely to see these benefits, according to the authors.

"The exact mechanism by which selenium exerts its effect on HIV-1 viral replication is not known, although the literature suggests several possibilities," the authors write. Among them: selenium's antioxidant activity may prevent free radicals, which are produced in high levels by HIV patients, from damaging immune cells. "Future research is necessary to confirm the directional relationships observed," the authors write. "An investigation of the mechanisms driving the effects of selenium on HIV-1 replication and other potential aspects of immunocellular expression and function is also indicated."

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U.S. Blood Pressure Control Better Than in Europe

Researchers attribute benefit to lower treatment threshold and more intensive treatment

American patients are more likely to receive aggressive treatment for hypertension and achieve better control than their European counterparts, possibly because the United States has a lower treatment threshold for high blood pressure than western European countries, researchers report in the Jan. 22 issue of the Archives of Internal Medicine.

Y. Richard Wang, M.D., Ph.D., of Temple University Hospital and the University of Pennsylvania in Philadelphia, and colleagues analyzed data on 21,053 hypertensive patients in the United States, France, Germany, Italy, Spain and the United Kingdom.

The researchers found that American patients had a significantly lower average blood pressure before treatment than European patients (161/94 mm Hg versus 167-173/96-99 mm Hg). They also found that Americans had a lower most recent average blood pressure reading (134/79 mm Hg versus 139-144/80-84 mm Hg). Americans were more likely to receive combination treatment (64 percent versus 44 to 59 percent in Europe).

"In our study, even in the United States, nearly half of the hypertensive patients did not achieve their goal blood pressure level set by the JNC 7 guidelines," the authors conclude. "Thus, better blood pressure control in the United States should not be too quickly praised. Substantial potential for better hypertension control and future cost saving exists in both Europe and the United States."

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Lifestyle Changes Comparable to Meds for Diabetes Delay

Both life changes and drugs can slow or prevent type 2 diabetes in those with impaired glucose

Lifestyle changes work at least as well as medication to delay or prevent the onset of type 2 diabetes in patients with glucose tolerance impairments, according to study findings published Jan. 19 in the Online First edition of BMJ.

Clare L. Gillies, a medical statistician from the University of Leicester in the U.K., and colleagues conducted a meta-analysis of 17 clinical studies involving 8,084 participants with impaired glucose tolerance.

The researchers calculated pooled hazard ratios of 0.32 for the herbal remedy jiangtang bushen as opposed to conventional diabetes advice, 0.44 for orlistat versus control, 0.51 for lifestyle changes versus conventional advice, and 0.70 for oral diabetes medications versus control.

"Lifestyle and pharmacological interventions reduce the rate of progression to type 2 diabetes in people with impaired glucose tolerance," the authors write. "Lifestyle interventions seem to be at least as effective as drug treatment."

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Informing Partners About STDs Helps Diminish Infections

Recurrence risk of some infections lower when patients are given drugs for partners

Encouraging patients to tell sex partners about sexually transmitted diseases shortens infections and improves outcomes, according to a report published Jan. 19 in the Online First edition of BMJ.

Nicola Low, M.D., of the University of Bern in Switzerland, and colleagues analyzed 14 studies involving 12,389 men and women diagnosed with a sexually transmitted infection syndrome, chlamydia, gonorrhea, trichomoniasis or non-gonococcal urethritis.

Five of six studies of patient-delivered partner therapy showed that lasting or recurrent infection risk was lower when gonorrhea or chlamydia patients were given drugs for partners. Giving partners extra information plus patient referrals (urging patients to tell partners to seek treatment) worked as well as giving patients drugs for their partners, the researchers report. Neither approach worked against trichomoniasis.

Two studies demonstrated that giving index chlamydia patients home testing kits for partners resulted in more treated partners, the report indicates.

"Involving index patients in shared responsibility for the management of sexual partners improves outcomes," the authors write. "Health professionals should consider the following strategies for the management of individual patients: patient delivered partner therapy, home sampling for partners, and providing additional information for partners."

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Oral Chemotherapy Lacks Safeguards

No consensus on safety measures

There is a lack of consensus and lax safeguards governing the use of oral chemotherapy drugs, according to research published online Jan. 12 in BMJ.

Saul N. Weingart, M.D., Ph.D., of the Dana-Farber Cancer Institute in Boston, and colleagues surveyed pharmacy directors from 54 U.S. cancer centers using a written questionnaire to assess whether the safeguards used in infusion chemotherapy are practiced in the administration of oral chemotherapy.

Most centers (29) relied on paper prescriptions for oral chemotherapy, while two used a preprinted version and six used electronic prescriptions. When asked about prescribing practices for six widely used oral chemotherapy drugs, respondents from 10 centers reported requiring the prescription to state a diagnosis, 11 required a protocol number and only nine double-checked the prescription.

Other routine safeguards were not widely adhered to for oral chemotherapy: 10 of the centers lacked adherence monitoring and two-thirds did not require written patient consent for therapies used off protocol. These lax standards resulted in 10 centers reporting at least one serious adverse drug event and 13 centers reporting a near-miss.

"Despite clinicians' concerns about oral chemotherapies, there is no apparent consensus among oncology professionals about safe practices for these drugs," the authors conclude.

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Mentally Distressed Prisoners Reluctant to Seek Help

Distrust of medical profession a major barrier to treatment

Distrust of the medical profession means that mental distress among male prisoners often goes untreated, and health professionals need more awareness training to better serve this population group, according to a report published online Jan. 12 in BMJ.

John Campbell, M.D., of Peninsula Medical School in Exeter, U.K., and colleagues conducted a qualitative interview study of 35 males offenders aged 18 to 52, of whom 25 percent had inflicted self-harm. When asked if they would consult a medical professional for help to deal with mental distress, most respondents reported that they would not.

Fear of the stigma of a diagnosis of mental illness, or an unwillingness to confront mental illness, were the main reasons why they did not consult a doctor. Traumatic childhood experiences were associated with an overall distrust of authority, but medical professionals specifically were distrusted because they were perceived as uncaring and only interested in dispensing drugs.

"Like most people, the respondents in this study wanted to feel listened to, acknowledged and treated as individuals by health professionals. By ensuring that a positive precedent is set, particularly for skeptical groups such as ex-prisoners, general practitioners and prison doctors may be able to encourage future help-seeking," the authors conclude.

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Diastolic Dysfunction Boosts Sickle Cell Mortality Risk

Combination of diastolic dysfunction, hypertension increases mortality risk 12-fold

Both diastolic dysfunction and pulmonary hypertension independently increase the risk for death in patients with sickle cell disease, according to a report in the Jan. 30 issue of the Journal of the American College of Cardiology.

Mark T. Gladwin, M.D., of the National Heart, Lung and Blood Institute in Bethesda, Md., and colleagues performed tissue Doppler imaging in 141 sickle cell disease patients and conventional echocardiography in another 235 patients to assess diastolic function.

Patients with diastolic dysfunction, as reflected by a low Doppler E/A ratio, had a mortality risk ratio of 3.5. A combination of diastolic dysfunction and pulmonary hypertension increased the mortality risk ratio to 12.0. Overall, 18 percent of patients had diastolic dysfunction and 11 percent had both diastolic dysfunction and pulmonary hypertension.

"Diastolic dysfunction and pulmonary hypertension each contribute independently to prospective mortality in patients with sickle cell disease. Patients with both risk factors have an extremely poor prognosis," the authors conclude. "These data support the implementation of echocardiographic screening of adult patients with sickle cell disease to identify high-risk individuals for further evaluation."

Gladwin is partly supported by INO Therapeutics of Clinton, N.J., and is co-inventor on patent application for therapeutic use of nitrate.

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Repeat Fibrinolysis Does Not Benefit MI Patients

Rescue angioplasty can reduce the risk of heart failure or reinfarction, but doesn't cut mortality risk

Patients with ST-segment elevation myocardial infarction (MI) who have failed a round of fibrinolytic therapy appear to benefit more from rescue angioplasty rather than repeat fibrinolysis, according to a meta-analysis of randomized trials published in the Jan. 30 issue of the Journal of the American College of Cardiology.

Dennis Ko, M.D., M.Sc., of the Institute for Clinical Evaluative Sciences in Toronto, Ontario, and colleagues reviewed eight randomized trials enrolling a total of 1,177 patients to estimate the benefits of rescue percutaneous coronary intervention (PCI) and repeat fibrinolysis compared to conservative management for ST-segment elevation MI.

Rescue PCI reduced the risk of both heart failure (relative risk, 0.73) and reinfarction (RR, 0.58) but had no effect on all-cause mortality compared with conservative treatment. The risks for stroke and bleeding were higher for PCI, however. Repeat fibrinolysis had no apparent benefits on all-cause mortality or reinfarction and carried an elevated risk for minor bleeding.

"Repeat fibrinolysis cannot be recommended based on the available evidence," the authors write. "In order to further improve outcomes and minimize risks, randomized trials should be performed to determine the most appropriate adjunctive pharmacotherapy in patients undergoing rescue PCI."

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Metabolic Syndrome Linked to Cardiovascular Risk, Death

Association highest in women, studies with low-risk individuals

Patients with metabolic syndrome are indeed at increased risk for cardiovascular events and death, according to a systematic review and meta-analysis published in the Jan. 30 issue of the Journal of the American College of Cardiology.

Apoor Gami, M.D., and colleagues from the Mayo Clinic College of Medicine in Rochester, Minn., reviewed 37 studies comprising 43 cohorts -- including a total of 172,573 individuals -- to assess the association between metabolic syndrome and incident cardiovascular events and death.

Metabolic syndrome was associated with a 1.78 relative risk for these outcomes and further increased to 2.63 when considering only women. The association with cardiovascular events and death was also stronger in studies enrolling low-risk individuals and studies using the World Health Organization criteria for identifying metabolic syndrome.

"The best available evidence suggests that people with metabolic syndrome are at increased risk of cardiovascular events," the authors write. "These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions."

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Anterior Fat Pad Preserves Postop Parasympathetic Tone

Postoperative fibrillation, hospital costs unaffected

Preservation of the anterior fat pad found on the surface of the atria between the aorta and right pulmonary artery helps to maintain parasympathetic tone after coronary artery bypass graft surgery, according to results from AFIST-III (Atrial Fibrillation Suppression Trial-III), published in the Jan. 23 issue of the Journal of the American College of Cardiology.

In the study, Jeffrey Kluger, M.D., of the University of Connecticut School of Medicine in Farmington, and colleagues conducted a randomized, blinded, controlled trial to evaluate the impact of anterior fat pad maintenance on the incidence of postoperative atrial fibrillation (POAF) in 180 patients undergoing coronary artery bypass grafting.

The investigators found that fat pad maintenance did not reduce the incidence of POAF or total hospital costs, but was associated with higher heart rate variability, an established marker of parasympathetic tone.

"Maintaining the anterior fat pad does not alter the incidence of POAF after coronary artery bypass grafting or total hospital costs in any appreciable way, even though it preserves parasympathetic tone," the authors conclude.

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Actos Has Anti-Inflammatory Effect in Non-Diabetics

Pioglitazone plus statin has additive effect in non-diabetic patients with heart disease

A combination of simvastatin and pioglitazone (Actos) reduces low-level inflammation in non-diabetic patients with heart disease, at least in patients without metabolic syndrome, according to a study in the Jan. 23 issue of the Journal of the American College of Cardiology.

Markolf Hanefeld, M.D., Ph.D., from the GWT Center for Clinical Studies in Dresden, Germany, and colleagues randomly assigned 125 non-diabetic patients with cardiovascular disease and elevated high-sensitivity C-reactive protein (hs-CRP) levels to either simvastatin plus a placebo, pioglitazone plus a placebo, or simvastatin plus pioglitazone for 12 weeks.

The researchers found that simvastatin or pioglitazone alone reduced hs-CRP levels, with the combination treatment having an additive effect. The additive effect of pioglitazone in reducing hs-CRP was only significant in the subset of patients without metabolic syndrome. Pioglitazone-treated patients were at higher risk of peripheral edema and of moderate weight gain compared with those not taking the drug.

"We found that pioglitazone and simvastatin exerted anti-inflammatory effects in non-diabetic patients with cardiovascular disease and elevated hs-CRP," Hanefeld and colleagues conclude. "Our study is the first to show that combining pioglitazone with simvastatin in non-diabetic patients with increased cardiovascular risk resulted in an additive effect on low-grade inflammation, without a significant increase in adverse events."

The study was supported by Takeda Pharmaceuticals.

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IV Insulin May Help Diabetics with Acute Coronary Syndrome

Extending insulin treatment to patients with acute coronary syndromes suggested

Aggressive glycemic control may reverse the platelet dysfunction common in diabetic patients with acute coronary syndromes, researchers report in the Jan. 23 issue of the Journal of the American College of Cardiology.

Matthew Worthley, Ph.D., of the University of Adelaide in Australia, and colleagues assessed blood sugar levels at admission, superoxide generation and platelet aggregation inhibition by sodium nitroprusside in 76 diabetic patients with acute coronary syndrome. These included 60 hyperglycemic patients who were randomized to subcutaneous or intravenous insulin.

The researchers found superoxide generation positively associated with blood sugar levels on admission, but negatively associated with asymmetric dimethylarginine and platelet sodium nitroprusside levels. Intravenous insulin infusion caused the greatest drop in blood glucose, decreased superoxide levels, and resulted in better platelet responsiveness to sodium nitroprusside, the report indicates.

"A component of platelet dysfunction in diabetic patients with acute coronary syndromes is impaired responsiveness to the anti-aggregatory effects of nitric oxide, probably reflecting increased nitric oxide clearance by superoxide," the authors write. "This phenomenon is reversed by acute aggressive glycemic control. These findings provide a further rationale for use of insulin therapy in acute myocardial infarction and suggest its extension to acute coronary syndrome patients."

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AHA Issues Advisory on Drug-Eluting Stents

Dual antiplatelet therapy should last 12 months and elective surgery deferred for one year

Patients who have been treated with drug-eluting stents should continue treatment with dual antiplatelet therapy with aspirin and a thienopyridine for 12 months, according to an advisory published online Jan. 16 in Circulation: Journal of the American Heart Association. The American Heart Association (AHA) advisory also recommends that elective surgery be postponed for one year after placement of a drug-eluting stent, and that bare metal stents be used in patients who need to have additional surgery in that year.

Cindy L. Grines, M.D., and colleagues warn that patients and health care providers often fail to maintain therapy for a year, and may not understand the importance of maintenance. Physicians should avoid the use of drug-eluting stents in patients who show signs of not complying with a 12-month course of treatment, the advisory states.

"The health care industry, insurers, the U.S. Congress and the pharmaceutical industry should ensure that issues such as drug cost do not cause patients to prematurely discontinue thienopyridine therapy and to thus incur catastrophic cardiovascular complications," the report states.

If surgery cannot be deferred, physicians should consider "the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents," the authors write.

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Sleep Apnea Linked to Family History of Premature Death

Association persists whether or not patients have coronary artery disease risk factors

Patients with obstructive sleep apnea are more than twice as likely as patients without obstructive sleep apnea to have a family history of premature coronary artery disease mortality, according to study findings published in the January issue of Chest.

Between May 2000 and June 2004, Virend K. Somers, M.D., Ph.D., of the Mayo Clinic College of Medicine in Rochester, Minn., and colleagues studied 588 patients who underwent polysomnography, which confirmed obstructive sleep apnea in 316 patients and excluded it in 202 patients.

The researchers calculated an unadjusted odds ratio of 2.11 for obstructive sleep apnea and a family history of premature coronary artery disease mortality. After adjusting for each patient's sex, body mass index and history of coronary artery disease, they still found a significant and independent association between obstructive sleep apnea and a family history of premature coronary artery disease mortality (OR, 2.13).

"These findings suggest that individuals with obstructive sleep apnea, regardless of whether they are healthy or have coronary artery disease risk factors, have an increased risk of coronary artery disease that is partly due to presently unknown familial factors acting independently of traditional coronary artery disease risk factors," the authors conclude.

Dr. Somers is a consultant for Respironics and has received honorarium from ResMed.

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Hospital Transfers Affect Standardized Mortality Ratio

Transferring even a few critically ill patients out of a hospital can artificially improve these benchmarks

Transferring even a few critically ill patients out of a hospital can significantly improve an intensive care unit's standardized mortality ratio, or SMR, and lead to an incorrect assumption of ICU quality, according to a simulation study published in the January issue of Chest.

Jeremy M. Kahn, M.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues used 2002-2003 data to calculate the mean SMR for 85 ICUs. During the simulation, they randomly transferred a set number of patients and recalculated the mean SMR.

The researchers found that the mean baseline SMR was 1.06. During the simulation, they found that increasing the number of transfers by 2 percent and 6 percent over baseline decreased the mean SMR by 0.10 and 0.14, respectively. They also found that a 2 percent increase in transfers resulted in a SMR decrease of greater than 0.10 at 27 ICUs and a decrease of greater than 0.20 at two ICUs. According to their calculations, transferring just one additional patient per month was sufficient to create a bias of greater than 0.10 in 27 ICUs.

"Uncritical use of the SMR to benchmark ICU performance is likely to misinform rather than provide meaningful information about ICU quality," the authors conclude. "ICU directors and administrators can monitor the number of transfer patients as a potential explanation for a decreasing SMR."

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Beta-Blockers May Suppress Central Sleep Apnea

Small study suggests the drugs may improve apnea in patients with chronic heart failure

Beta-blocker therapy may have a dose-dependent effect in the suppression of central sleep apnea in patients with chronic heart failure, according to the results of a study published in the January issue of Chest.

Akira Tamura, M.D., of Oita University in Oita, Japan, and colleagues performed polysomnography on 45 patients with chronic heart failure.

The researchers found that the 27 patients who took beta-blockers had a significantly lower apnea-hypopnea index and central apnea index than the 18 patients who did not take beta-blockers, and saw the greatest benefits in patients who took the highest doses. After conducting serial sleep studies on five patients who initiated beta-blocker therapy, they found that the central apnea index significantly decreased after six months of treatment.

"Considering the results of the present study and beneficial effects of beta-blocker therapy on mortality in chronic heart failure, widespread use of beta-blockers may modify the prevalence and prognostic significance of central sleep apnea in patients with chronic heart failure," the authors write. "The impact of beta-blockers on central sleep apnea remains to be clarified in patients with chronic heart failure."

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Florida Red-Tide Aggravates Asthma Symptoms

Symptoms worse in subjects regularly taking asthma medications

Toxins from Florida red-tide microalgae aggravate respiratory symptoms in people with asthma, particularly those regularly taking asthma medications, according to a report in the January issue of Chest.

Lora E. Fleming, M.D., Ph.D., from the University of Miami School of Medicine in Florida, and colleagues examined whether red-tide (marine microalgae Karenia brevis) aggravates asthma. They assessed respiratory parameters in 97 individuals at least 12 years old with asthma one hour before and after aerosol exposure or no exposure to red tides.

The researchers found that red-tide exposure significantly increased the likelihood of subjects reporting respiratory symptoms. There were small but significant decreases in forced expiratory volume in one second and forced expiratory flow after exposure, particularly in subjects who regularly used asthma medications.

"This study demonstrated objectively measurable adverse changes in lung function from exposure to aerosolized Florida red-tide toxins in asthmatic subjects, particularly among those requiring regular therapy with asthma medications," Fleming and colleagues conclude.

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