Latest Research

Women Lag Men as First Authors in Top Journals

More women are lead authors of studies in top journals, but gender gapremains

The percentage of women who are leading authors of medical studies has greatly increased over the past four decades, but women still comprise a minority of such authors, according to a report in the July 20 issue of the New England Journal of Medicine.

Reshma Jagsi, M.D., of Massachusetts GeneralHospitalin Boston, andcolleagues reviewed original research from six prominent medical journals,including during five different years since 1970. Sex was also determined forthe authors of guest editorials in the New England Journal of Medicineand the Journal of the American Medical Association.

The researchers found that "the proportion of first authors of originalresearch who were women increased from 5.9 percent in 1970 to 29.3 percent in2004, and the proportion of senior authors who were women increased from 3.7percent to 19.3 percent during the same period." The sharpest increaseswere noted in Obstetrics & Gynecology and the Journal ofPediatrics, while percentages remained low in the Annals of Surgery.

"Our findings validate the perception that although women have madesubstantial strides in the past four decades, a gender gap remains among theauthors of original articles in prestigious academic medical journals. Furtherinvestigation is necessary to understand more fully the causes for this gap,including the possibility that certain barriers may impede women's participationas authors early in their careers and, in turn, may diminish the pool of femalesenior faculty members who may serve in the prominent authorshippositions," the authors conclude.

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Brain Natriuretic Peptide Signals Sickle CellDeath Risk

Data from two studies show BNP levels above 160 pg/mLcorrelate with pulmonary hypertension

Elevated levels of N-terminal pro-brain natriuretic peptide, or NT-proBNP, are associated with pulmonary hypertension and death in patients with sickle cell disease, according to a report in the July 19 issue of the Journal of the American Medical Association. The findings provide further support for a mechanistic link between hemolytic anemia and pulmonary hypertension.

Roberto F. Machado, M.D., and investigators from the MulticenterStudy of Hydroxyurea in Sickle Cell Anemia (MSH)study measured NT-proBNP in two different groups ofsickle cell disease patients: one from the MSH study (121 patients) and onefrom the NIH Sickle Cell Disease-Pulmonary Hypertension Screening Study (230participants).

The investigators found that NT-proBNP levels werehigher in sickle cell patients with hypertension and were linked to tricuspidregurgitation velocity. NT-proBNP levels of 160 picograms/mL or greater predicted hypertension correctly 78percent of the time and caused an 11.9 percent to 19.5 percent absoluteincrease in risk of death.

"This is the first readily available laboratory biomarker to provideprognostic information in this population since white blood cell counts andfetal hemoglobin levels were demonstrated to be independent predictors of deathin the Cooperative Study of Sickle Cell Disease," the authors write.

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Gene Associated with Higher Macular Degeneration Risk

Carriers of CFH Y402H polymorphism have a higher risk ofvision-threatening eye condition

Homozygous carriers of a polymorphism in the complement factor H (CFH) gene are at higher risk of age-related macular degeneration than heterozygotes or non-carriers, according to a report in the July 19 issue of the Journal of the American Medical Association.

Dominiek D.G. Despriet,M.D., of the ErasmusMedicalCenterin Rotterdam, the Netherlands,and colleagues studied the effects of smoking, the CFH gene polymorphismCFH Y402H and age-related macular degeneration in 5,681 people 55 orolder in Rotterdam, the Netherlands.

The researchers found that 36.2 percent had the CFH Y402Hpolymorphism and 36.3 percent had age-related macular degeneration. Homozygouspatients had a cumulative 48.3 percent risk of late disease by age 95, versus42.6 percent for heterozygotes, and 21.9 percent fornon-carriers, the report indicates. Homozygotes who smoked, had elevated C-reactive protein and elevatederythrocyte sedimentation rates had a risk 34-fold, 28-fold and 20-fold higher,respectively, than non-carriers.

"The CFH Y402H polymorphism may account for a substantialproportion of age-related macular degeneration in individuals similar to thosein the Rotterdamstudy and may confer particular risk in the presence of environmental andgenetic stimulators of the complement cascade," the authors write.

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Migraine Plus Aura Increases Cardiovascular Riskin Women

Women who have migraines with visual aura at greater risk for myocardialinfarction and ischemic stroke

Middle-aged women who experience migraine with visual aura have a higher risk of cardiovascular events, including myocardial infarction and ischemic strokes, than those without migraines, researchers report in the July 19 issue of the Journal of the American Medical Association.

Tobias Kurth, M.D., of Brigham and Women'sHospital in Boston, and colleaguesanalyzed data on 27,840 U.S.women aged 45 and older; 18.4 percent had experienced migraines within the pastyear and 39.7 percent of these reported aura symptoms with migraine.

During the next 10 years, 580 women had a major cardiovascular diseaseevent. Compared to other women, those with migraine plus aura were twice aslikely to experience a major cardiovascular event (hazard ratio, 2.15), ischemic stroke (1.91), myocardial infarction (2.08),undergo coronary revascularization (1.74) and to dieof an ischemic cardiovascular disease event (2.33).

"In this large, prospective cohort of women, active migraine with aurawas associated with increased risk of major cardiovascular disease, myocardialinfarction, ischemic stroke, and death due to ischemic cardiovascular disease," the authors write.

In an editorial, Richard B. Lipton, M.D., of the MontefioreHeadacheCenter in the Bronx, New York, and a colleague point out that"for patients with migraine with aura, clinicians should have heightenedvigilance for modifiable cardiovascular risk factors."

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New Drugs Cut Opportunistic Infections in HIV+ Children

But for many HIV-infected children worldwide, the problem is access totherapy

Opportunistic infections in HIV-infected children plummeted after the advent of highly active antiretroviral therapy (HAART), researchers report in the July 19 issue of the Journal of the American Medical Association.

Philimon Gona, Ph.D., ofthe Harvard School of Public Health in Boston,and colleagues compared the incidence of 29 opportunistic infections in 3,331HIV-infected children before the advent of HAART (1988-1998) and in 2,767children after the medications became available (2000-2004).

The researchers found opportunistic infections were much lower after theintroduction of HAART than before. The incidence ratio for bacterial pneumoniawas 11.1 per 100 person-years before HAART versus 2.15 afterwards; for herpes zoster it was 2.9 before and 1.11 per 100 person-yearsafter; and for oral candidiasis it was 1.2 before and0.93 per 100 person-years after.

"Opportunistic infections and other related infections are uncommon inchildren in the HAART era," the authors write.

In an accompanying editorial, Joseph I. Harwell, M.D., of Brown MedicalSchool in Providence, R.I., and a colleague write: "For 2.3 millionchildren living with HIV infection worldwide, the question is not whether orhow but when they will receive (and, like their counterparts in the study by Gona et al, benefit from) the therapy that will allow themto reach adulthood."

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Women More Likely Than Men to Develop Lung Cancer

Female smokers nearly twice as likely to have lung cancer as males

Asymptomatic women with a history of smoking are more likely than men to have screening-detected lung cancer, but they are less likely to die of the disease than men, researchers report in the July 12 issue of the Journal of the American Medical Association.

Claudia I. Henschke, Ph.D., of the Weill Medical College of Cornell University in New York City, andcolleagues analyzed lung cancer screening data on 7,498 women and 9,427 menover age 40 who were asymptomaticwith a history of cigarette smoking. Overall, 2.1 percent of women and 1.2percent of men had lung cancer. Women were 1.9 times as likely as men to havelung cancer, but they were less likely to die of it (hazard ratio, 0.48).

"Women appear to have increased susceptibility to tobacco carcinogensbut have a lower rate of fatal outcome of lung cancer compared with men,"the authors write.

"The once prevalent adage, 'You've come a long way, Baby!' geared tofemale smokers, unfortunately now applies to increased smoking prevalence andlung cancer risk among women," according to an editorial by Alfred I. Neugut, M.D., Ph.D., and Judith S. Jacobson, Dr.P.H. "To prevent gender equality in lung cancerfrom becoming a reality, it's now time for women to turn back."

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JAMA Revises Conflict-of-Interest Policy

Starting January 2007, all authors will be required to submit completedisclosures

In response to criticism that some of its articles do not fully disclose potential conflicts of interest, the Journal of the American Medical Association has announced an updated policy requiring all corresponding authors to submit complete disclosures -- including specific financial interests, relationships and affiliations relevant to the subject matter -- in the Acknowledgements section of their manuscripts, according to an editorial published in the July 12 issue of the Journal of the American Medical Association.

Effective January 2007, the journal's Web-based manuscript submission systemwill require authors to state that they have included completeconflict-of-interest information in the manuscript at the time of submission.Between now and the end of 2006, JAMA will continue to allow submissionsin which the information is not yet included, but with the proviso that theinformation will be provided before any revisions are considered.

Under the new policy, authors will be expected to provide all relevantinformation from the past five years and for the foreseeable future. Thisincludes employment and affiliations, grants or funding, consultancies,honoraria, stock ownership or options, expert testimony, royalties, and patentsfiled, received, pending or in preparation.

"All authors are encouraged to read these policies carefully and tofollow them completely," state the editorial's authors: Managing DeputyEditor, Annette Flanagin, R.N.; Executive DeputyEditor, Phil B. Fontanarosa, M.D.; and Editor inChief, Catherine D. DeAngelis, M.D. "By doingso, peer reviewers and editors can expect full disclosure of potentialconflicts of interest in manuscripts submitted to JAMA, and physicians,other health care professionals, and the public can expect complete reportingof conflict-of-interest information in articles published in JAMA."

Editorial

Test Can Identify Risk for Recurring Blood Clots

Patients with low peak thrombin generation won't benefit from indefiniteanticoagulant therapy, authors report

A test that measures thrombin generation can be used to determine whether patients are at risk of having recurrent blood clots, according to a report in the July 26 issue of the Journal of the American Medical Association.

Gregor Hron, M.D., ofthe Medical University of Vienna in Austria, and colleagues studied 914patients who experienced their first spontaneous venous thromboembolism(VTE) between 1992 and 2005, and were followed for an average of 47 monthsafter ending vitamin K antagonist therapy.

VTE recurred in 11 percent of the subjects, and those without recurrent VTEhad lower thrombin generation than those with recurrent VTE. According to theanalysis, the likelihood of recurrent VTE in patients with peak thrombingeneration of less than 400 nM after ending vitamin Ktherapy was as low as 6.5 percent after four years versus 20 percent amongpatients with peak thrombin generation of 400 nM orhigher.

"Patients with low peak thrombin generation (less than 400 nM) would almost certainly not benefit from indefiniteanticoagulant therapy," the authors conclude. "Consequently,extensive thrombophilia screening appears to beunnecessary in this large, low-risk patient group."

Some study equipment came from Technoclone ofVienna, and one author is chief scientific officer for TechnocloneGmbH.

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Cardiac CT Scan is Limited for Detecting Blockages

Too many nonevaluable segments, but may beuseful for excluding heart disease in select patients

Detection of coronary atherosclerosis with 16-row multi-detector computed tomography (MDCT) can result in a higher number of nonevaluable segments and false-positive results than traditional angiography, though it may be useful in ruling out heart disease in some patients with inconclusive stress test results, according to a report in the July 26 issue of the Journal of the American Medical Association.

Mario J. Garcia, M.D., of the Cleveland Clinic Foundation in Ohio, and colleaguescompared the results of 187 patients who underwent contrast-enhanced MDCTscans, as well as conventional angiographies performed within two weeks.

Of 1,629 non-stented coronary artery segments withdiameters more than 2 millimeters, 71 percent were able to be evaluated by MDCTscan. When nonevaluable segments were classified aspositive, the sensitivity for detecting more than 50 percent stenosis was 89 percent, the specificity was 65 percent,the positive predictive value was 13 percent and the negative predictive valuewas 99 percent.

"Routine implementation in clinical practice is not justified,"the authors write. "Nevertheless, given its high sensitivity and negativepredictive value, 16-row MDCT may be useful in excluding coronary disease inselected patients in whom a false-positive or inconclusive stress test resultis suspected."

The study was funded by Philips Medical Systems, which providesrecommendations on computed tomography X-ray dosing.

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Early Onset Type 2 Diabetes Linked to Higher Death Risk

Also linked to higher risk of kidney disease

The onset of type 2 diabetes in patients younger than age 20 is linked to a substantially increased risk of end-stage kidney disease, as well as death between 25 and 55 years of age, according to the results of a study of Native Americans reported in the July 26 issue of the Journal of the American Medical Association.

Meda Pavkov, M.D.,Ph.D., of the National Institutes of Health in Phoenix, and colleagues studied 1,856 membersof the Gila River Indian community between 1965 and 2002, and analyzed theincidence of type 2 diabetes in patients first diagnosed when younger than 20and in those diagnosed between ages 20 and 55.

The researchers found the rate of end-stage kidney disease in patients withyouth-onset type 2 diabetes was 8.4 times higher thanthose between ages 25 and 34 years old, five times higher than in those 35 to44 years of age, and four times higher than patients between ages 45 and 54years. Similarly, death rates were twice as high in those with youth-onset type2 diabetes than in those with older-onset diabetes.

"Because youth-onset diabetes mellitus leads to substantially increasedcomplication rates and mortality in middle age, efforts should focus onpreventing or delaying the onset of diabetes, delaying the onset of diabeticnephropathy, or both," the authors conclude.

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Two Common Polymorphisms Linked to Diabetes

Genotype boosts risk of progression in those with impaired glucosetolerance

Two common polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with an increased risk of developing type 2 diabetes, according to a report in the July 20 issue of the New England Journal of Medicine.

Jose Florez, M.D., Ph.D., of GeorgeWashingtonUniversityin Rockville, Md., and colleaguesgenotyped 3,548 patients with impaired glucose tolerance who participated in adiabetes prevention trial between 1996 and 2001. In the trial, patients wererandomized to lifestyle changes or treatment with metforminor placebo.

Over an average of three years, patients with the high-risk TT version ofthe rs7903146 polymorphism were more likely to develop diabetes (hazard ratio,1.55) than those with a CC genotype. Patients with the TT genotype who were inthe placebo group were more likely to progress (1.81) than those in the metformin (1.62) or lifestyle-intervention groups (1.15).Similar results were seen for the rs12255372 polymorphism.

"Further understanding of the mechanisms by which variation in thisgene affects glucose homeostasis may provide new insights into the molecularbasis of diabetes and opportunities for more targeted interventions forprevention and therapy," the authors conclude.

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Ejection Fractions Up, But Heart Failure Deaths the Same

Mortality rates in those with preserved ejection fraction similar tothose with lower ejection fraction

The prevalence of heart failure with an ejection fraction greater than 50 percent has increased over the past 15 years, but survival rates for patients with preserved ejection fractions are similar to those with lower ejection fractions, according to two studies in the July 20 issue of the New England Journal of Medicine.

Margaret M. Redfield, M.D., and colleagues from the Mayo Clinic in Rochester, Minn.,studied all patients hospitalized at their institution for decompensatedheart failure between 1987 and 2001. They found that 47 percent of the 4,596patients had a preserved ejection fraction and that their proportion hadincreased over time. However, mortality rates in this group were only slightlybetter than those with lower ejection fractions and did not improve over time.

Peter P. Liu, M.D., from the Universityof Toronto in Ontario, Canada,and colleagues found that 31 percent of 2,802 newly diagnosed heart failurepatients admitted to Toronto-area hospitals between 1999 and 2001 had ejectionfractions of more than 50 percent. However, the 30-day mortality in suchpatients, who tended to be women with a history of atrialfibrillation, was no different than those with less than 40 percent ejectionfraction.

"The two current studies remind us that ejection fraction is not a goodpredictor of clinical disability and suggest that congestive symptoms are moreclosely related to the filling (diastolic) properties of the ventricle than tothe ejection (systolic) properties," Gerard P. Aurigemma,M.D., writes in an accompanying editorial. He adds, "thedevelopment of specific, effective management approaches for diastolic heartfailure must also become a high priority."

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Gene Mutation Linked to Congenital Diarrhea

Mutation affects differentiation of enteroendocrinecells and intestine's ability to absorb nutrients

Mutations in the neurogenin-3 gene required for the development of endocrine cells in the pancreas and intestine are associated with congenital malabsorptive diarrhea, and may be responsible for a newly discovered malabsorptive disease characterized by a lack of enteroendocrine cells, according to a report in the July 20 issue of the New England Journal of Medicine.

Martin G. Martin, M.D., of the University of California Los Angeles,and colleagues screened genomic DNA from three unrelated boys who lackedintestinal enteroendocrine cells and had similarclinical characteristics, including vomiting, dehydration and chronic,unremitting, malabsorptive diarrhea in the firstweeks of life.

The researchers found that the boys had two different mutations inneurogenin-3 (NEUROG3) that disrupted the protein's ability to activatethe promoter of NEUROD1, a similar gene. The mutation disrupted thedifferentiation of intestinal absorptive cells and secretorycells.

"The clinical findings highlight a critical role of enteroendocrinecells in augmenting nutrient absorption," the authors write. "Thesefindings may also help uncover the cause of several other associated forms ofdiarrhea, including diarrhea-predominant irritable bowel syndrome and variousinflammatory and other forms of congenital diarrhea," they conclude.

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Pay-for-Performance Plan Shows High Achievement

U.K. plan for primary care docs includes few who may underreport to skewrank, pay

Results from a British primary care pay-for-performance program show that most practices attain high levels of achievement, according to a report in the July 27 issue of the New England Journal of Medicine. However, a few practices may be skewing their performance by underreporting.

The program is part of a national initiative in which primary carephysicians can increase their pay up to 25 percent based on performance in thecare of 10 chronic diseases measured by 146 quality indicators. Tim Doran,M.P.H., from the University of Manchester in the U.K., and colleagues measured theperformance of 8,105 practices.

Overall achievement was found to be 83.4 percent and was determined, forexample, by how many asthma patients had a review within the past 15 months orhow many hypertensive patients' last blood pressuremeasurement was 150/90 mm Hg or less. Practices could exclude some patientsfrom their reporting, such as those allergic to a monitored drug, which usuallycorrelated with increased achievement. Most kept exclusion reporting low,although the few that excluded more than 15 percent of patients potentiallyincreased their performance and, ultimately, their pay.

"Perhaps the most important lesson we can take from the experience inthe United Kingdom would beto consider carefully the myriad potential consequences of pay for performanceand to monitor the implementation of such a program carefully," statesArnold M. Epstein, M.D., of HarvardMedicalSchoolin Boston, inan accompanying editorial.

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Nitric Oxide May Benefit Some Premature Infants

Less critically ill newborns may benefit from inhaled nitric oxide

Inhaled nitric oxide (NO) treatment may have some benefit for premature infants with respiratory failure, although benefits may be limited to those who are less critically ill, according to two reports in the July 27 issue of the New England Journal of Medicine.

John Kinsella, M.D., of Children's Hospital in Denver, and colleaguestested the safety and efficacy of NO therapy in premature newborns, weighingbetween 500 and 1,250 grams, randomized to 21 days of either 5 ppm inhaled NO or placebo. Overall, no differences in deathrates or bronchopulmonary dysplasiawere noted. However, newborns weighing at least 1,000 grams showed a lowerincidence of respiratory failure and brain injury with NO.

In the second study, Roberta Ballard, M.D., of the Children's Hospital of Philadelphia, and colleagues conducted asimilar placebo-controlled trial in premature infants requiring mechanicalventilation between seven and 21 days of age. Infants without bronchopulmonary dysplasia whoreceived decreasing amounts of NO (20 to 5 ppm) over24 days showed improved survival at 36 weeks, compared with controls (43.9percent versus 36.8 percent).

The authors have received grants, consulting fees and lecture fees from INOTherapeutics, Bunnell, Inhibitexand Viasys.

"In the most critically ill infants with extremely low birth weights,inhaled nitric oxide does not appear to improve survival or bronchopulmonarydysplasia and…cannot be recommended,"states an accompanying editorial.

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Adherence, Not Regimen, Key for OpioidAddiction

Patients who adhered to counseling and buprenorphine-naloxonehad lower opioid use

A variety of weekly regimens involving counseling and buprenorphine-naloxone appear to be equally effective in reducing opioid use among dependent patients, with patients who adhere to their medication more likely to remain drug-free regardless of treatment schedule, according to a report in the July 27 issue of the New England Journal of Medicine.

David A. Fiellin, M.D., and colleagues from YaleUniversity School of Medicine in New Haven, Conn.,conducted a 24-week controlled trial where 166 patients with opioid dependence were randomized to standard medicalmanagement with medication dispensing once a week, three times a week, orenhanced care with medication dispensed three times a week.

The three treatments were equally effective with respect to the number of opioid-free urine specimens collected and maximum number ofweeks abstained, and caused a similar reduction in opioiduse compared with baseline. Dropout rates for each were similar as well. Whileadherence to medication averaged at about 71 percent and also did not differsignificantly between the groups, a higher adherence rate correlated with more opioid-free weeks.

"The variability in buprenorphine-naloxoneadherence highlights the need both to measure adherence in future research andto monitor and encourage adherence in practice in order to reduce the potentialmisuse of the medication and to improve the treatment outcomes," theauthors write.

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International Youth Exercise Guidelines Need Updating

One hour a day may not be enough to stave off heart disease

Current international physical activity guidelines for youth that call for an hour a day of moderate intensity activity may be too low to stave off cardiovascular disease risk factors, according to results from the European Youth Heart Study published in the July 22 issue of The Lancet.

Lars Bo Andersen, Ph.D., of the NorwegianSchool of Sport Sciences in Oslo, and colleagues performed a cross-sectional study of1,732 randomly selected 9- and 15-year-old school children from Denmark, Estoniaand Portugal.They measured blood pressure, weight, waist circumference, insulin resistanceand cholesterol, and calculated a combined risk factor score for each child.Researchers monitored physical activity by strapping on an accelerometer tostudy participants for four consecutive days.

Youth in the three least active quintiles had higher risk factor scores whencompared with the most active quintiles. Youth in the fourth quintile hadvigorous activity (above 2,000 counts per minute) of 116 minutes per day for9-year-olds and 88 minutes per day for 15-year-olds, which is more than therecommended daily activity.

In light of these and other study findings, "the implementation of[daily physical activity] in schools should be a strong priority becausephysical activity represents a major disease-prevention measure and can promotefuture beneficial lifestyle practices," editorialists wrote in anaccompanying commentary.

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Unregulated Chinese Herbal Therapy Can Be Toxic

One 30-year-old man developed bladder cancer, kidney failure after takingLongdan Xieganwan

Unregulated Chinese herbal therapy can be toxic, according to a case study of a 30-year-old man who developed bladder tumors and kidney failure after taking the Chinese herb Longdan Xieganwan for five years in an effort to enhance his liver. The report is published in the July 22 issue of The Lancet.

Longdan Xieganwancontains Caulis aristolochia manshuriensis,and aristolochic acid is an active ingredient. Onestudy has linked cumulative doses of aristolochicacid exceeding 200 grams with bladder cancer, and the U.S. Food andAdministration issued a warning about its nephrotoxicityin May 2000.

Chris Liang, M.R.C.P., of WhittingtonHospital in London, and colleagues reported that thepatient presented to a kidney clinic in July 2003, after passing blood in hisurine. Cystoscopy revealed a bladder tumor that wassuccessfully resected. He developed recurrent bladdercancer despite the fact that he ceased taking the herbal remedy. A subsequentrenal biopsy showed interstitial fibrosis consistent with Chinese herbalnephropathy. As of June 2006, the patient was preparing for renal transplant,the researchers wrote.

In an accompanying editorial, Lancet editors wrote that complementarymedications "all need regulation as drugs. And practitioners in this fieldneed reminding, again, that they need to produce high-quality evidence ofefficacy: fully powered double-blind randomized trials with relevant endpointsand sufficient follow-up, and systematicreviews."

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Intervention Not Effective for Some SubfertileCouples

No effect seen from intrauterine insemination with controlled ovarian hyperstimulation

In couples with unexplained subfertility and an intermediate probability of a spontaneous ongoing pregnancy, the first-line treatment of intrauterine insemination with controlled ovarian hyperstimulation is no more effective than expectant management, according to a study in the July 15 issue of The Lancet.

Pieternel Steures, M.D.,of the Academic Medical Centre and Vrije Universiteit Medical Centre in Amsterdam, the Netherlands,and colleagues randomly assigned 253 couples with a 30 percent to 40 percentprobability of a spontaneous ongoing pregnancy within 12 months to eitherintrauterine insemination with controlled ovarian hyperstimulationor expectant management for six months.

The researchers found that 42 (33 percent) of women in the interventiongroup conceived and that 29 (23 percent) achieved ongoing pregnancies. Theyfound that 40 (32 percent) of women in the expectant management group conceivedand that 34 (27 percent) achieved ongoing pregnancies. They observed one twinpregnancy in each study group and one triplet pregnancy in the intervention group.

"Our study shows that identification of couples who will not benefitfrom intrauterine insemination is possible," the authors conclude."Through selection of these couples, the misuse of facilities and otherresources can be avoided. Our trial also emphasizes the importance of expectantmanagement, which is an efficient way to prevent multiple pregnancy."

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Case Report Details Risk of Rare ChikungunyaVirus

Researchers warn travelers to take precautions when visiting the Indian Ocean islands

Travelers who visit the Indian Ocean islands are at risk of contracting the rare Chikungunya virus, which caused 77 deaths in the islands between Jan. 1, 2006 and March 2, 2006, according to a case report published in the July 15 issue of The Lancet.

Patrick Bodenmann, M.D., and BlaiseGenton, M.D., of the Universityof Lausannein Switzerlanddescribed the case of a 28-year-old woman who presented at their clinic withfever, headache and photophobia that had lasted for three days and a rash thatlasted one day. Two days earlier, she had returned from a two-week trip to Mauritius,where she said she experienced frequent mosquito bites.

The patient received symptomatic treatment for suspected Chikungunya,was discharged the same day and followed up as an outpatient. Serology resultsconfirmed that she had Chikungunya fever.

"We strongly discouraged pregnant women, families with young children,people older than 70 years, and those with significant comorbidityfrom traveling to the Indian Oceanislands," the authors conclude. "We informed other patients about themagnitude of the risk of contracting the disease and let them decide accordingto their own judgment. We reinforced the message on protective measures againstmosquito bites. This case emphasizes the importance of disease-surveillancecommunication networks, which allow the constant modification of preventive andtherapeutic measures."

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Smoking Responsible for Social Inequality in Male Mortality

Smoking blamed for more than half of the difference in mortality acrosssocial strata

Smoking accounts for more than half of the difference in adult male mortality across socioeconomic classes, according to the results of a new study published online July 14 in The Lancet.

Prabhat Jha, M.D., ofthe University of Toronto in Canada,and colleagues examined smoking's contribution toadult male mortality among men aged 35 to 69 from three different social stratain four countries (England/Wales, Canada,United States and Poland). Theresearchers used the 1996 absolute lung cancer rates to estimate theproportions of deaths due to smoking. There were a total of 564,626 deathsduring the study period.

Men in the lowest strata were twice as likely to die during the study periodas those in the highest social strata and more than half of this difference wasattributed to smoking, the investigators found. For example, in England and Wales, 4 percent of deaths wereattributed to smoking among men in the highest social strata, compared with 19percent among men in the lowest strata. In the United States, these percentageswere 4 percent and 15 percent, respectively, the report indicates.

"Widespread cessation of smoking could eventually halve the absolutedifferences between these social strata in the risk of premature death,"the study authors conclude.

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Autism May Be Increasing in the United Kingdom

Researchers find that autistic spectrum disorders affect 1 percent of U.K. children

Autistic spectrum disorders (ASDs) are more prevalent than previously thought in the United Kingdom and may affect 1 percent of the child population, according to a study published in the July 15 issue of The Lancet.

Gillian Baird, M.D., of Guy's and St. Thomas' Hospital in London, U.K., andcolleagues studied a cohort of 56,946 children aged 9 and 10 years, andscreened 255 children with a clinical diagnosis of ASD and another 1,515children from a special-needs resister who were considered to be possibleundetected cases.

The researchers found that the prevalence of childhood autism and other ASDs was 38.9 per 10,000 and 77.2 per 10,000, respectively,for a total prevalence of 116.1 per 10,000 for all ASDs.If they had based their estimates on previously identified children with ASD,the total prevalence would have been 44 per 10,000.

"Whether the increase is due to better ascertainment, broadeningdiagnostic criteria, or increased incidence is unclear," the authors state. "Services in health, education andsocial care will need to recognize the needs of children with some form of ASD.This study emphasizes the need for agreed and shared tools and definitions inprevalence and incidence studies and for designs that are not reliant on localsystems of case identification that may exhibit educational and otherbiases."

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Obese Girls at Higher Risk of Premature Death Later On

Sibutramine helps overweight adolescentsslim down

Adolescent girls who are obese run a higher risk of premature death later in life, and sibutramine along with behavior therapy can help reduce body weight in teens, according to two reports published in the July 18 issue of the Annals of Internal Medicine.

Rob M. van Dam, Ph.D., of the Harvard School of Public Health in Boston, and colleaguesfollowed 102,400 cancer-free women, aged 24 to 44 years, assessing theircurrent weight and body mass index (BMI), as well as their recalled weight whenthey were 18.

After 12 years, 710 of the women had died. The researchers found that,compared with a BMI of 18.5 to 21.9 kg/m2 at age 18, the risk of prematuredeath increased progressively with a higher BMI, with a nearly threefold riskof premature death (hazard ratio, 2.79) for women who had a BMI of 30 kg/m2 orgreater.

"Moderately higher adiposity at age 18 years is associated withincreased premature death in younger and middle-aged U.S. women," van Dam andcolleagues write.

In another study supported by Knoll Pharmaceuticals, Robert I. Berkowitz,M.D., of The Children's Hospital of Philadelphia, andcolleagues compared the effects of sibutramine versusplacebo on 498 obese adolescents in weight-loss behavior therapy. They foundthat adolescents on sibutramine each lost a mean of8.4 kilograms of body weight more than those on placebo.

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Telephone Training Can Relieve Pain Symptoms

Coaching by a nurse-educator helps patients with psychosocial problems

Telephone pain management training by a nurse-educator can help relieve symptoms in pain patients with psychosocial problems, researchers report in the July/August issue of the Annals of Family Medicine.

Tim A. Ahles, Ph.D., of the Dartmouth-HitchcockMedicalCenterin Lebanon, N.H., and colleagues compared the effect ofpain management strategies versus no intervention in 644 patients withpsychosocial problems and 693 patients without psychosocial problems visiting14 rural practices.

Intervention involved giving patients exact data about their condition,telephone coaching by a nurse-educator in problem-solving and pain management,and updating physicians about patients' conditions and concerns.

The researchers found that after six months, intervention patients with painand psychosocial problems experienced significantly less pain and greaterphysical and emotional well-being than patients who got no such help. Thebenefits of even modest telephone intervention -- an average of three calls --lasted at least a year. But patients who received intervention without trainingcalls from the nurse-educator did not improve much by six months compared tountreated patients.

"For patients with pain and psychosocial problems, telephone-basedassistance resulted in significant, sustained benefit in pain and psychosocialproblems," the authors conclude.

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Estrogen, Testosterone May Up Breast Cancer Risk

Women who take estrogen and testosterone for menopause at higher risk ofbreast cancer

Women who take estrogen plus testosterone to combat the symptoms of menopause are at increased risk for developing invasive breast cancer, according to new results from the Nurse's Health Study published in the July 24 issue of the Archives of Internal Medicine.

Rulla M. Tamimi, Sc.D., of Brigham and Women's Hospital and HarvardMedicalSchool in Boston, and colleagues identified 4,610 casesof breast cancer among postmenopausal women during 24 years of follow-up, andascertained through questionnaires their use of hormone therapies.

The researchers found that women who had gone through menopause naturallyand were currently taking estrogen plus testosterone were almost 2.5 times morelikely to develop breast cancer than those who had never used hormone therapy. Those taking estrogen alone had a 15 percent increased risk ofbreast cancer and women currently using estrogen plus progestinhad a 58 percent increased risk of developing breast cancer.

While the precise reason for the increased risk is not fully understood,researchers suspect that enzymes in the breast tissue may convert testosteroneto estradiol. Hormone replacement therapies may helpalleviate symptoms of menopause, but "the increased risk of breast cancermay outweigh these benefits," the authors conclude.

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Longer Life for Light to Moderate Drinkers

Benefits of moderate alcohol consumption may include fewer cardiac events

Older adults who consume one to seven alcoholic beverages per week may live longer and have a reduced risk for cardiac events than their teetotaling counterparts, according to a study published in the July 24 issue of the Archives of Internal Medicine that suggests these associations are independent of alcohol's anti-inflammatory effects.

Cinzia Maraldi, M.D., ofthe University of Florida in Gainesville,and colleagues investigated the relationship between alcohol, death and cardiacevents among 2,487 adults without heart disease aged 70 to 79. Researchersassessed alcohol consumption and levels of several inflammatory markers atbaseline. During an average 5.6 years of follow-up, 397 participants died and383 experienced a cardiac event.

Compared with never or occasional drinkers (less than one drink per week),those who drank lightly to moderately (one to seven drinks per week) had a 26percent lower risk of death overall and an almost 30 percent lower risk ofcardiac events. Heavy drinkers (more than seven drinks per week) were morelikely to die or experience a cardiac event than never or occasional drinkers.The results held after researchers adjusted for inflammatory markers.

"The net benefit of light to moderate alcohol consumption may vary as afunction of sex, race and background cardiovascular risk," the studyauthors caution.

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Results Mixed on Alternative Menopause Therapies

Insufficient data to support use of complementary therapies formenopausal symptoms

Insufficient data exists to support the use of complementary and alternative therapies for the symptoms of menopause, according to a systematic evidence review of 70 studies published in the July 24 issue of the Archives of Internal Medicine.

Anne Nedrow, M.D., of the Oregon Health and ScienceUniversityin Portland,and colleagues reported mixed results for 48 studies that looked at vitamins,proteins, complete diets or other biologically based treatments. Of 15 fair- orgood-quality studies of phytoestrogens, only foursuggested the supplements provided a benefit in relieving symptoms ofmenopause. In four studies of black cohosh, just onelarge study showed an overall improvement in several symptoms, while threeshowed no benefit. Studies of energy, mind-body and other types of therapiessuggested few benefits for menopause-related symptoms.

"Individual trials suggest a benefit for certain therapies, yet dataare insufficient to recommend any complementary and alternative therapy aseffective for the management of menopausal symptoms," the study authorsconclude. They add that randomized, controlled trials of alternative therapiesare needed to better determine their benefits and safety as growing numbers ofwomen turn to these treatments to combat the symptoms of menopause.

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High Carb, Low GlycemicIndex Diet May Cut Heart Risk

In high-carb diet, lowering glycemicindex nearly doubles fat loss

High-carbohydrate diets low in glycemic index may help reduce the risk of cardiovascular disease, according to a study in the July 24 issue of the Archives of Internal Medicine.

Joanna McMillan-Price, of the Universityof Sydney in Australia, andcolleagues randomly assigned 129 obese or overweight young adults aged 18 to 40to one of four reduced-calorie, reduced-fat diets fora 12-week period. Two diets were high-carbohydrate diets and two werehigh-protein. One of each had a high glycemic loadand the others had low glycemic loads.

Between the two high-carbohydrate diets, lowering the glycemicindex nearly doubled fat loss. The effect was stronger in women and did notoccur among those on high-protein diets. Participants on the high-protein,high-glycemic index diet had increased levels oftotal and low-density lipoprotein (LDL) cholesterol, while those on thehigh-protein, low-glycemic index diet and highcarbohydrate, low-glycemic index diet showedreductions in total and LDL cholesterol. All other cardiovascular risk factorswere similar among the four groups.

Given the popularity of low-glycemic index andlow-carb diets, future studies "will continue toprovide welcome insights in a field that is often shrouded withconfusion," states the author of an accompanying editorial.

McMillan-Price is coauthor of The Low GI Diet Revolution, and thestudy was supported by Meat and Livestock Australia.

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Antibiotic Risk May Outweigh Benefit for Purulent Rhinitis

New meta-analysis in support of current guidelines

The risks of antibiotics, including gastrointestinal side effects and rashes, outweigh the benefits for treatment of acute purulent rhinitis, according to a meta-analysis published online July 20 in the BMJ.

Bruce Arroll, M.D., of the Universityof Auckland in New Zealand,and a colleague identified seven trials that compared antibiotics with placebofor acute purulent rhinitis lasting less than 10days. They found that while antibiotics are effective, they can cause harmincluding gastrointestinal effects and rashes. Moreover, most patients getbetter without antibiotics. The findings support current guidelines that statethat antibiotics should not be used as a first-line therapy for acute purulent rhinitis.

In the study, the number needed to treat ranged from 7 to 15, which meansthat, at best, six patients receive no benefit for every one patient with acutepurulent rhinitis who is helped by the antibiotics.Further, the number needed to treat overlaps with the number needed to harm,which ranged from 12 to 78, the study showed.

"Our summation would be to suggest initial management by non-antibiotictreatments or 'watchful waiting,' and that antibiotics should be used only whensymptoms have persisted for long enough to concern parents or patients,"the study authors concluded.

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High-Dose Statin Therapy May Lower Heart Risks

More effective than standard regimen

A high-dose statin regimen is more likely than standard treatment to prevent non-fatal cardiovascular problems, according to a report in the Aug. 1 issue of the Journal of the American College of Cardiology.

Christopher Cannon, M.D., of HarvardMedicalSchoolin Boston, andcolleagues reviewed the literature on four clinical trials that comparedintensive statin therapy with standard-dose therapyamong patients with either stable coronary heart disease or acute coronarysyndromes. The researchers performed a statistical analysis to determine thelikelihood of a patient experiencing a coronary death or any cardiovascularevent.

The investigators found a 16 percent reduction in coronary deaths or heartattacks among patients given high-dose statins. Thepredominant benefit was prevention of non-fatal heart attacks, strokes andunstable angina. By extrapolating the data, the authors suggest that for everymillion patients with chronic or acute coronary artery disease treated for fiveyears, intensive statin therapy would prevent morethan 35,000 cardiovascular events, including more than 14,000 coronary deathsor heart attacks.

"These data support a broader use of intensive statintherapy for patients with stable coronary heart disease, as well as those witha recent acute coronary syndrome," the authors conclude.

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Moderate Fish Intake May Aid Heart's Electrical Function

Tuna, other broiled or baked fish, once or twice weekly may reduce heartrisks in elderly

MONDAY, July 24 (HealthDay News) -- Eating fishwith a high content of omega-3 fatty acids may have a direct effect on theelectrical function of the heart in older people, according to a report in theAug. 1 issue of the Journal of the American College of Cardiology.

Dariush Mozaffarian,M.D., of HarvardMedicalSchool in Boston, and colleagues analyzed the diets of5,096 men and women, aged 65 or older, who participated in a cardiovascularhealth study started in 1989. The investigators also reviewed electrocardiographic results for heart rate, atrioventricular conduction, ventricular repolarization and ventricular conduction.

The researchers found that consuming tuna or other broiled or baked fish wasassociated with a lower heart rate, slower atrioventricularconduction and substantially lower likelihood of a prolonged adjustment periodof the heart's electrical system. The report indicates that most of the benefitwas achieved by eating fish once or twice a week.

"Additional studies are warranted to confirm these findings, andcellular mechanisms and implications for arrhythmic risk deserve furtherinvestigation," the authors conclude.

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Post-MI Outcome No Better with Remodeling Inhibitor

Patients were randomized to matrix metalloproteinaseinhibitor PG-116800

The matrix metalloproteinase (MMP) inhibitor PG-116800 does not prevent left ventricular remodeling after myocardial infarction, according to results from the Prevention of Myocardial Infarction Early Remodeling, or PREMIER trial, published in the July 4 issue of the Journal of the American College of Cardiology. PG-116800 has shown significant antiremodeling effects in animal models of myocardial infarction and ischemic heart failure.

W. Douglas Weaver, M.D., from Henry Ford Hospital in Detroit, and PREMIERtrial members conducted a double-blind, placebo-controlled study to testwhether PG-116800 could prevent left ventricular remodeling in 253 patientswith a recent ST-segment elevation myocardial infarction and low (15 percent to40 percent) ejection fraction.

Patients randomized to either PG-116800 or placebo for 90 days showed nodifference in left ventricular end-diastolic volume index measured byechocardiography (5.09 versus 5.48 mL permeter-squared, respectively). There were also no differences in the rates ofdeath or reinfarction.

"Contrary to animal and preclinical data, ourdisappointing results cast doubt on whether MMP inhibition might amelioratepost-myocardial infarction remodeling," the authors write. "SelectiveMMP inhibition with PG-116800 is ineffective for treating this condition, yetour current understanding of which MMP(s) contribute most to ventricularremodeling is rudimentary."

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Mitral Valve Surgery Outcomes Improvefor Elderly Patients

Study shows restoration of life expectancy now similar to youngerpatients

While mitral valve surgery is riskier for elderly patients, significant improvements have been made in the procedure so that the restoration of life expectancy is similar to that of younger patients who have the surgery, according to a report in the July 25 issue of Circulation: Journal of the American Heart Association.

Maurice Enriquez-Sarano, M.D., from the MayoClinic in Rochester, Minn., and colleagues examined the baselinecharacteristics of 1,344 patients who underwent surgery for mitralvalve regurgitation between 1980 and 1995, their outcomes, and trends insurgical improvement.

The investigators found that while patients aged 75 years and older hadshorter survival after surgery, they had a similar restoration of lifeexpectancy as younger patients. The improvements in outcome were likely due tolower operative mortality, lower declines in cardiac output and shorterhospital stay. Over time, operative mortality declined from 27 percent to 5percent in those 75 years and older, from 21 percent to 4 percent in those aged65 to 74 and from 7 percent to 2 percent in those under 65 years of age.

"Restoration of life expectancy after surgery is similar in elderly andyounger patients, and outstanding recent surgical improvements particularlybenefited elderly patients," the authors write. "Thus, elderly patientswith mitral regurgitation can now carefully beconsidered for surgery before refractory heart failure is present."

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Diabetes Quality Improvement Strategies of Limited Value

Team changes and case management have greater effect on glycemic control than other interventions

Most quality improvement strategies, such as case management or patient reminder systems, result in only small to modest improvements in glycemic control in patients with type 2 diabetes, according to a study published in the July 26 issue of the Journal of the American Medical Association.

Kaveh G. Shojania, M.D.,of the Ottawa Health Research Institute and Department of Medicine in Ottawa, Ontario,and colleagues used a meta-regression model with 66 trials to assess theeffectiveness of 11 quality improvement strategies. The studies includedpatients with a mean hemoglobin A1c value of 8 percentor greater at baseline.

The researchers found two strategies resulted in a mean reduction of HbA1cby 0.50 percent or greater, and they were team changes (0.67 percent) and casemanagement (0.52 percent). Overall, interventions reduced HbA1c values by amean of 0.42 percent during a median 13 months of follow-up.

"Team changes and case management showed more robust improvements,especially for interventions in which case managers could adjust medicationswithout awaiting physician approval," the authors conclude."Estimates of the effectiveness of other specific quality improvementstrategies may have been limited by difficulty in classifying complexinterventions, insufficient numbers of studies, and publication bias."

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Decision Model May Guide Pacemaker Replacement

Model is aimed at improving management of patients with recalledpacemakers and ICDs

A new decision model may help physicians decide whether or not to replace a pacemaker or an implantable cardioverter defibrillator (ICD) when a device advisory is issued, according to an article published in the July 26 issue of the Journal of the American Medical Association.

Mitesh S. Amin, M.D., ofthe VirginiaCommonwealthUniversityMedicalCenter in Richmond, and colleagues constructed adecision model to evaluate the risks and benefits associated with immediatedevice replacement versus continued monitoring.

The researchers found that device replacement is usually warranted inpacemaker-dependent patients when a device failure rate exceeds 0.3 percent andin patients with ICDs for primary or secondaryprevention when the rate exceeds 3 percent.

"As the number of implantable devicesincrease, device failures and advisories will remain a part of routinepractice," the authors conclude. "Having a rational mechanism toapproach these patients is critical to patient care. The risks of replacingdevices are not insignificant and outweigh all but very high risks of death dueto device malfunction."

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