Latest Research #12

AIDS: Simpler HIV Maintenance Therapy Promising

Preliminary outcomes good in patients switched to a single, boostedprotease inhibitor

In select patients with HIV, maintenance treatment with a single, boosted protease inhibitor instead of the standard three-drug regimen may be an effective strategy that results in less complexity, pill burden, long-term complications and cost, according to preliminary research presented this week at the 16th International AIDS Conference in Toronto, Canada. The study results are also published in a special HIV/AIDS-themed issue of the Journal of the American Medical Association.

Susan Swindells, M.B.B.S., of the University of Nebraska Medical Center in Omaha, and colleagues studied 36 HIV-infectedadults who achieved virologic suppression for 48weeks or longer after receiving their first protease inhibitor-based regimenand were switched to a simplified maintenance therapy with ritonavir-boostedatazanavir alone. The final analysis included 34patients.

During the 24-week study, the researchers found that 31 (91 percent) ofpatients achieved virologic success and that threepatients experienced virologic failure at 12, 14, and20 weeks after simplification. Plasma HIV-1 RNA levels were 4730, 1285, and28,397 copies/mL, respectively, in the patients. Theinvestigators also observed no treatment discontinuations for adverse eventsafter simplification, and no significant changes in CD4 cell counts or plasmalipid levels.

"These characteristics make boosted atazanavira promising candidate for maintenance therapy," the authors conclude."Larger, randomized trials comparing this approach with standardantiretroviral therapy are warranted."

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AIDS: Good Outcomes Seen in Zambian HIV Program

Massive expansion of free antiretroviral therapy services significantlyreduces mortality rates

A massive scale-up of free antiretroviral therapy services in Zambia shows that good outcomes are possible in sub-Saharan Africa, according to research presented this week at the 16th International AIDS Conference in Toronto, Canada. The findings are also published Aug. 16 in a special HIV/AIDS-themed issue of the Journal of the American Medical Association.

Jeffrey S.A. Stringer, M.D., of the Centre forInfectious Disease Research in Zambiaand the University of Alabama at Birmingham,and colleagues studied 16,198 Zambian adults who received free antiretroviraltherapy at 18 new primary care facilities between April 26, 2004 and Nov. 5,2005.

The researchers found that 1,142 patients died, including 1,120 who had areliable date of death. Of these, 792 died within the first 90 days ofbeginning therapy (early mortality rate: 26 per 100 patient-years) and 328 diedafter 90 days (post-90-day mortality rate: 5.0 per 100 patient-years, which iscomparable to rates in the developed world). The investigators also found amean CD4 cell count increase of 174/μL in 1,361 of 1,519 (90 percent)patients who received treatment long enough to have a 12-month repeat.

The authors of a related editorial comment on the success of a voluntary HIVcounseling and testing program in Kenya. "Experience fromincreasing voluntary counseling and testing also provides lessons applicablefor the expansion of antiretroviral therapy-related care," they conclude.

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AIDS: Panel Updates HIV Treatment Recommendations

Recent therapeutic advances have prompted refinements and changes toprevious guidelines

The 16-member International AIDS Society-U.S.A. panel has issued updated HIV treatment recommendations based on recent advances in potent combination antiretroviral therapies, according to research presented this week at the 16th International AIDS Conference in Toronto, Canada. The guidelines are also published in the Aug. 16 special HIV/AIDS-themed issue of the Journal of the American Medical Association.

Scott M. Hammer, M.D., of the Columbia University College of Physicians andSurgeons in New York, and other panel members identified and reviewed 181citations published between mid-2004 and May 2006, and issued updatedguidelines in four key areas: when to start antiretroviral therapy, what tostart, when to change and what to change.

Among their recommendations: changing therapy as mandated by toxicity,intolerance or treatment failure; recognizing a plasma HIV-1 RNA level below 50copies/mL as the virologictarget for patients with treatment failure; measuring plasma HIV-1 after initiationof antiretroviral therapy every four-to-eight weeks until it reaches anundetectable level; and thereafter measuring it three or four times per year.

"Given the rapid evolution of knowledge, clinicians are challenged tostay abreast of new information that can affect practice," the authorsconclude. "Therapeutic choices rooted in the pathogenesis of HIV diseaseand individualization of therapy to maximize benefit arethe principles that remain constant in a rapidly changing environment."

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AIDS: Formula As Risky As Breast Milk for HIV in Africa

Breast-feeding plus prophylaxis improves early survival compared toformula plus prophylaxis

Breast-feeding plus six months of infant zidovudine prophylaxis is not as effective as formula-feeding plus one month of infant zidovudine prophylaxis at preventing postnatal HIV transmission, but is associated with a significantly lower seven-month infant mortality rate, according to research presented this week at the 16th International AIDS Conference in Toronto, Canada. The study is also in a Aug. 16 special HIV/AIDS-themed issue of the Journal of the American Medical Association.

Ibou Thior, M.D., of theBotswana-Harvard School of Public Health AIDS Initiative Partnership for HIVResearch and Education in Bontleng and Gaborone, Botswana, and colleagues studied1,200 HIV-positive pregnant women, all of whom received zidovudinetwice daily after 34 weeks' gestation and during labor. They randomized infantsto receive one of the two feeding strategies.

At seven months, the researchers found a higher HIV infection rate inbreast-fed compared to formula-fed infants (9 percent versus 5.6 percent), butalso found a significantly lower mortality rate for breast-fed infants (4.9percent versus 9.3 percent). At 18 months, the cumulative mortality or HIVinfection rates were similar (15.1 percent in the breast-fed group versus 13.9percent in the formula-fed group).

"These results demonstrate the risk of formula feeding to infants insub-Saharan Africa, and the need for studiesof alternative strategies," the authors conclude.

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Hib Vaccine Cuts Childhood Disease in Kenya

Incidence of H. influenzae type bdisease down dramatically three years after vaccination program

Introductionof the Haemophilus influenzaetype b conjugate vaccine into the routine infant immunization program in Kenyahas dramatically reduced disease incidence in young children, according to areport in the Aug. 9 Journal of the American Medical Association.

J. Anthony G. Scott, F.R.C.P., from the Universityof Oxford in the U.K., and colleagues measured Haemophilus influenzaetype b (Hib) disease incidence in Kenya and theeffectiveness of a Hib vaccination program started in2001 with support from the Global Alliance for Vaccination and Immunization.

Culture-based surveillance showed that the annual incidence of Hib disease in children younger than age 5 dropped from 66per 100,000 one year before vaccination introduction to 7.6 per 100,000 atthree years after vaccine introduction, and from 119 per 100,000 to 16 per100,000 in children younger than age 2. From 2004 to 2005, the vaccine was 88percent effective for children younger than 5 years and 87 percent effectivefor children younger than age 2.

"In countries that have not yet introduced Hibvaccine, it would be highly desirable to establish surveillance beforeintroduction and vaccinate a sufficiently high proportion of young children toprovide evidence of effectiveness within the period of programevaluation," the authors write.

Some authors coordinate an African program that has been funded by GlaxoSmithKline.

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Two Anti-Clotting Regimens Have Similar Effectiveness

But low-molecular-weight heparin is nearly 20 times more expensive than unfractionated heparin

In patients with acute venous thromboembolism, fixed-dosesubcutaneous unfractionated heparin is as effectiveand safe as subcutaneous low-molecular-weight heparin, but is far less costly,according to a study in the Aug. 23/30 issue of the Journal of the AmericanMedical Association.

Clive Kearon, M.B.,Ph.D., of McMasterUniversity and the Henderson Research Centre in Hamilton, Ontario, and colleagues randomlyassigned 697 patients to receive either unfractionatedheparin or low-molecular-weight heparin (dalteparinor enoxaparin).

When comparing the unfractionated heparin andlow-molecular-weight heparin groups, the researchers found comparable rates ofboth recurrent venous thromboembolism within threemonths (3.8 percent and 3.4 percent, respectively) and major bleeding withinthe first 10 days of treatment (1.1 percent and 1.4 percent, respectively).

"Unfractionated and low-molecular-weightheparin were administered in the identical way; subcutaneous injection givenevery 12 hours without activated partial thromboplastintime monitoring," states the author of an accompanying editorial."Thus, the only variable that factored into a cost analysis was the priceof the two drugs. Kearon et al. estimate that drugcosts for a six-day course of low-molecular-weight heparin is $712 and for unfractionated heparin is $37, assuming the drug is administeredtwice daily using a multiple-dose vial in an 80-kg patient."

Some of the study authors have received support and honoraria from, or beenadvisers for, various drug companies.

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U.S.Prevalence of Herpes Simplex Virus Type 2 Decreasing

Researchers suggest that safer sex practices may account for lower seroprevalence of HSV-2

The seroprevalence of herpes simplex virus type 2 (HSV-2), theprimary cause of genital herpes, has significantly declined since the late1980s and early 1990s in the United States, especially among teenagers,according to a study in the Aug. 23/30 issue of the Journal of the AmericanMedical Association.

Fujie Xu, M.D., Ph.D.,of the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues compared data on9,165 people aged 14 to 49 from the 1988-1994 National Health and NutritionExamination Surveys with data on 11,508 people from the 1999-2004 survey.

The researchers found that overall age-adjusted HSV-2 seroprevalencedecreased from 21 percent in 1988-1994 to 17 percent in 1999-2004, withespecially significant decreases seen in those aged 14 to 19. The investigatorsalso found that the seroprevalence of HSV-1 decreasedfrom 62 percent in 1988-1994 to 57.7 percent in 1999-2004.

"The reasons that HSV-2 seroprevalencesignificantly decreased even after accounting for changes in measured sexualbehaviors may include a combination of unmeasured factors, such as carefulpartner selection, condom use, and/or choosing oral sex over vaginal sex,"the authors write. "Recent research into the structure of sexual networksindicates that in adolescents, relative low levels of behavioral change canradically limit the spread of sexually transmitted infections."

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Metabolic Disorder More Common Than Thought

But short-chain acyl-coenzyme A dehydrogenase deficiency isunsuitable for newborn screening

Short-chain acyl-coenzyme A dehydrogenasedeficiency (SCADD) is a more common metabolic disorder than previouslyrecognized, but is not currently suitable for inclusion in newborn screeningprograms, according to a study in the Aug. 23/30 issue of the Journal of theAmerican Medical Association.

Bianca T. van Maldegem,M.D., of the University of Amsterdam in the Netherlands, and colleagues studied31 Dutch SCADD patients and eight of their relatives to identify the disorder'sgenetic, biochemical and clinical characteristics.

The researchers calculated a SCADD birth-prevalence of at least one in50,000. They found that most patients presented before age 3 with symptoms suchas developmental delay, epilepsy, behavioral disturbances and hypoglycemia.They also found that seven of the eight SCADD relatives were symptom-free.

The study "deserves serious consideration," states the author ofan accompanying editorial. "Long-term studies comparing childrenidentified by newborn screening with clinically identified children are needed.In addition to laboratory and genetic tests, long-term follow-up studies shouldinclude objective measures of outcome, such as growth, nutritional status,physical well-being, number of hospitalizations, number of emergency departmentvisits, intelligence quotient levels, academic achievement, behavioral characteristics,language development and motor skills," the editorialist writes."Only through comprehensive, long-term research will a rational, fair anduniversal newborn screening policy become reality."

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Support Surfaces, Supplements May Prevent Bed Sores

Overall methodological quality of trials is poor

Use of support surfaces, repositioning patients, optimizing nutritional status andmoisturizing sacral skin may be appropriate strategies to prevent pressureulcers, according to the results of a systematic review published in the Aug.23/30 issue of the Journal of the American Medical Association.

Madhuri Reddy, M.D., M.Sc.,of the HebrewRehabilitationCenter in Boston, and colleagues conducted a systematicreview of 59 randomized controlled trials that assessed interventions toprevent pressure ulcers, including those that address impairments in mobility,nutritional status and skin health.

Overall, the methodological quality of these trials was poor, butresearchers did identify certain promising interventions, including the use ofsupport surfaces such as mattress overlays on operating tables, specializedfoam overlays and sheepskin overlays. One trial showed that nutritionalsupplements may help prevent pressure ulcers, but little specific informationis available. Moisturizing dry sacral skin seems to be a reasonable strategy,the report indicates. While repositioning patients is considered a mainstay forpreventing pressure ulcers, insufficient evidence exists on how to best turnpatients.

Going forward, "there is a need for well-designed randomized controlledtrials that follow standard criteria for reporting non-pharmacologicalinterventions that provide data on cost-effectiveness for theseinterventions," the authors conclude.

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At-Home Contamination May Be Cause of FusariumKeratitis

ReNu with MoistureLocused by 69 percent of recent cases of infection

The outbreak of the corneal infection Fusarium keratitis linked to the ReNu withMoistureLoc brand of contact lens solution was mostlikely due to contamination outside the manufacturing or storage processes,possibly in the patients' homes, according to a study in the Aug. 23/30 issueof the Journal of the American Medical Association. However, it isunlikely that poor contact lens hygiene practices were the major cause of theoutbreak.

To examine the cause of the outbreak of Fusariumkeratitis, which occurred from March 2006 across 33states and one U.S.territory and affected 164 confirmed cases as of June 30, Douglas C. Chang,M.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, and colleaguesconducted a case-control study of 45 confirmed case patients and 78 controls.

Sixty-nine percent of case patients reported using ReNuwith MoistureLoc, compared with 15 percent ofcontrols. Use of another ReNu product, ReNu MultiPlus solution, wassimilar between the two groups, at 18 percent for the cases and 20 percent forthe controls.

The authors tested 39 different isolates and found at least 10 different Fusarium species that comprised 19 unique multilocus genotypes. Samples gathered at themanufacturer's factory and warehouse yielded no Fusariumspecies, and none were recovered from solution filtrate or unopened solutionbottles.

"On-going studies may help to determine if the infections were causedby an interaction of its ingredients with Fusariumthat might have permitted growth of the organism," the authors write.

Some authors received research support from, or consulted for, companiesthat make contact lens solution.

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Daptomycin a Safe Alternative for S. Aureus Bacteremia

Similar outcome from treatment compared with standard therapy

The cyclic lipopeptide antibiotic daptomycinappears to be as effective as standard therapy for Staphylococcus aureus bacteremia complicatedby right-sided endocarditis, according to a report inthe Aug. 17 New England Journal of Medicine.

Vance G. Fowler, Jr., M.D., of Duke University Medical Center in Durham,N.C., and members of the S. aureus Endocarditis and Bacteremia StudyGroup randomly assigned 246 patients with S. aureusbacteremia with or without endocarditisto 6 mg/kg intravenous daptomycin daily, or low-dose gentamicin plus either an anti-staphylococcal penicillin orvancomycin.

The outcome of daptomycin treatment 42 days aftertherapy ended was similar to standard treatment, with 44.2 and 41.7 percent ofpatients having a successful outcome, respectively. Daptomycinwas associated with a higher rate of microbiologic failure, many withdrug-resistant clones, while standard treatment was associated with moreadverse events, but both differences were non-significant.

The authors did find a significant reduction in clinical renal dysfunctioncompared with standard therapy (11 percent for daptomycin;26.3 percent for standard therapy). "Daptomycin(6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia andright-sided endocarditis," they conclude.

The study was supported by Cubist Pharmaceuticals, which produces daptomycin. Many of the authors are consultants oremployees of the company.

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Alendronate Effective forSteroid-Induced Osteoporosis

Alendronate was more effective than alfacalcidol at preserving bone mineral density

Alendronate (Fosamax) may be moreeffective than alfacalcidol at staving offsteroid-induced bone loss among patients with rheumatic diseases, according tothe results of a double-blind study published in the Aug. 17 issue of the NewEngland Journal of Medicine.

Ron N.J. de Nijs, M.D., Ph.D., of the UniversityMedical Center Utrecht in the Netherlands,and colleagues followed patients who began taking glucocorticoidsat a daily dose equivalent to at least 7.5 milligrams of prednisonefor 18 months. Patients were randomized to receive 10 mg of alendronateand a placebo capsule of alfacalcidol daily or 1microgram of alfacalcidol and a placebo tablet of alendronate daily.

Patients taking alendronate showed a 2.1 percentincrease in spinal bone mineral density (BMD). By contrast, spine BMD decreasedby 1.9 percent in the alfacalcidol group. Between thegroups, there was a 4 percent difference in BMD of the lumbar spine at 18months, which favored those patients taking alendronate.Similar results were seen in the femoral neck and total hip, the report indicates.

"Alendronate may inhibit bone loss in glucocorticoid-induced osteoporosis more effectively thandoes alfacalcidol," the study authors conclude.

Merck provided the alendronate and placebo tabletsand Teva Pharmaceuticals provided alfacalcidoland placebo capsules, but the study was funded by the Dutch Health CareInsurance Board.

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Socioeconomic Status Linked to Late-Life Disability

Older poor six times more likely to have physical limitations than thosewith more money

While the link between extreme poverty and poor health has long been recognized, a newreport in the Aug. 17 New EnglandJournal of Medicine extends the socioeconomic disparity to functionallimitation and disability later in life.

In the study, Meredith Minkler, Dr.P.H., from the University of California-Berkeley, andcolleagues used questionnaire data from more than 890,000 households in thenationally representative Census 2000 Supplementary Survey to determine whether"a gradient in functional limitation exists across the full spectrum ofincome among persons 55 years of age or older."

The researchers found that functional limitation in older persons wasinversely proportional to income level up to age 85. The gradient was most pronouncedin those between the ages of 55 and 64 years, where those living below thepoverty level were six times more likely to report functional limitation thanpersons of the same age living well above this level -- at 700 percent of thepoverty line or above.

Since 85 percent of Americans aged 55 years or older live under 700 percentof the poverty line, the authors state that this work "suggests theimportance of paying greater attention to the 'ignored determinant' of health-- social class, which is strongly related to functional health across the fullrange of family income until very late in life."

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Most ED Patients with S. AureusInfection Have MRSA

Study of 11 U.S.emergency departments shows most infections due to community-associated USA300strain

Methicillin-resistant Staphylococcus aureus,or MRSA, is the most common cause of skin and soft-tissue infections inpatients presenting to emergency departments in 11 U.S. cities, according to astudy conducted in August 2004 and reported in the Aug. 17 issue of the NewEngland Journal of Medicine.

Gregory J. Moran, M.D., from the Universityof California Los Angeles, andcolleagues from the U.S. Centers for Disease Control and Prevention and the EMERGEncy ID Net Study Group, which is a network ofuniversity-affiliated emergency departments in 11 U.S. cities, obtained cultures fromadult patients presenting with acute, purulent skin and soft-tissue infections.They examined and genotyped the isolates.

Seventy-six percent of 422 patients presenting with infections had S. aureus-positive cultures, with MRSA having an overallprevalence of 59 percent. Most of the isolates were of community-associatedUSA300 MRSA, and 74 percent were of a single strain (USA300-0114) previouslyreported in community outbreaks. The isolates showed variable susceptibility toantimicrobial agents and many contained the Panton-Valentine leukocidin toxingene associated with necrotizing pneumonia.

The article "describes a landmark study that defines the amazing extentto which community-associated MRSA, particularly the USA300 clone, has spreadthrough the U.S.population," according to an editorial by M. Lindsay Grayson, M.D. The"optimal treatment approach is likely to depend on the principles of thetreatment triangle [surgical drainage, wound culture, antibiotics] forstaphylococcal infections for some time to come."

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Neonatal MRI May Predict Outcomes in PretermInfants

Moderate-to-severe white matter abnormalities suggest neurodevelopmentaloutcomes

Neonatal magnetic resonance imaging (MRI) may help predict adverse neurodevelopmentaloutcomes in very preterm infants, according to astudy in the Aug. 17 issue of the New England Journal of Medicine.

Lianne J. Woodward, Ph.D., of the University of Canterburyin Christchurch, New Zealand, and colleaguesassessed 167 infants born at or before 30 weeks' gestation using MRI at four tosix weeks after birth. They compared white-matter and gray-matter abnormalitiesamong the very preterm infants to those of infantsborn at term.

About two-thirds of the preterm infants showedwhite-matter abnormalities and one-half showed abnormalities in gray-matter.Moderate-to-severe white matter abnormalities predicted cognitive delay, motordelay, cerebral palsy and neurosensory impairment at2 years of age, while gray-matter abnormalities predicted cognitive delay,motor delay and cerebral palsy, but to a lesser extent, the report indicates.

While the new results are "intriguing," editorialists Olaf Dammann, M.D., of HannoverMedicalSchoolin Germany, and Alan Leviton, N.D., of Children's Hospital in Boston, write that they "consider itpremature to use the results of Woodward et al. to provide support for the moreroutine use of MRI in risk stratification."

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U.K.Drug Trial Disaster Sheds New Light on Cytokine Storm

Survival of all six trial volunteers testament to developments incritical care

The severe adverse reaction of six healthy volunteers in the United Kingdom during a phase1 drug trial of TGN1412 sheds new light on the natural course of the cytokinestorm and the systemic inflammatory response syndrome (SIRS), and must notprevent future research, according to a paper and editorial published onlineAug. 14 in the New England Journal of Medicine.

Ganesh Suntharalingam,F.R.C.A., of NorthwickPark and St. Mark's Hospital in London, U.K.,and colleagues describe the events of a phase 1 clinical trial of TGN1412, anovel superagonist anti-CD28 monoclonal antibody thatdirectly stimulates T cells, conducted on behalf of German firm TeGenero. All six of the eight trial participants given thedrug suddenly and rapidly released proinflammatorycytokines and developed clinical signs consistent with a diagnosis of SIRS.

Under intensive care from the researchers, all six survived. In anaccompanying editorial, Jeffrey M. Drazen, M.D.,editor-in-chief of the NEJM, writes that developments in critical caremedicine have emerged because of "countless patients who had previouslyput themselves at risk as each piece of the critical-illness puzzle wasdissected."

Drazen adds, "The troubling fact of thematter is that without people who are willing to place themselves at risk toadvance our knowledge, we will be frozen in our current state ofunderstanding."

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Mortality Linked to BMI in Two National Cohort Studies

Excess weight in midlife associated with greater mortality risk

Two trials, one involving more than 500,000 Americans and the other over one millionKoreans, suggest that even modest amounts of excess weight in middle age isassociated with a higher risk of mortality. Results of both studies arepublished in the Aug. 24 issue of the New England Journal of Medicine.

Kenneth F. Adams, Ph.D., from the National Cancer Institute in Rockville,Md., and colleagues prospectively examined 527,265 U.S. men and women, aged 50to 71 years, in the National Institutes of Health-AARP cohort for an average of10 years and found that those with the highest and lowest body mass index wereat greatest risk for all causes of death, while among those in midlife who hadnever smoked, obesity increased mortality risk by two to three times and beingoverweight increased the risk 20 to 40 percent.

In the second study, Sun Ha Jee, Ph.D., of YonseiUniversity in Seoul, Korea, andcolleagues followed over 1.2 million Koreans between the ages of 30 and 95 fora 12-year period and found that risk of death from any cause was lowest innon-smokers with a BMI of 23.0 to 24.9. Mortality from lower body mass indexwas driven by respiratory causes while risk from higher body mass index (eitheroverweight or obesity) was linked to cardiovascular disease or cancer andfollowed a J-shaped curve.

The Korean study is a "sobering reminder that because obesity is now aworldwide problem, the phenomenon of 'global fattening' will contribute to apandemic of chronic diseases for many years to come," according to aneditorial by Tim Byers, M.D., M.P.H., from the University of Colorado School ofMedicine in Denver.

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TGFBR1 and 2 Mutations Cause Aggressive Vascular Disease

Mutations linked to Loeys-Dietz syndrome causeaortic aneurysms and pregnancy complications

Mutations in the transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2),associated with the recently described autosomaldominant disease Loeys-Dietz syndrome, can causeaggressive and widespread vascular disease, according to a report in the Aug.24 issue of the New England Journal of Medicine.

A group led by Bart Loeys, M.D., and Harry Dietz,M.D., who described the disease in 2005 and are both affiliated with JohnsHopkins University in Baltimore, performed a clinical and molecularcharacterization of 52 Loeys-Dietz affected familiesand an additional 40 patients with the closely-related Ehlers-Danlos syndrome (also called Loeys-Dietzsyndrome type II).

The investigators found that all probands of Loeys-Dietz syndrome and 12 probandsof Ehlers-Danlos syndrome had mutations in either TGFBR1or TGFBR2. Six of 12 women had aggressive arterial aneurysms andpregnancy-related complications. Loeys-Dietz patientsunderwent cardiovascular surgery earlier than those with type II syndrome (age16.9 versus 26.9) and died earlier (age 22.6 versus 31.8).

"Aside from reinforcing the role of TGF-beta in aortic disease, thesecorrelations between genotype and phenotype provide a powerful clinicalrationale for the proper diagnosis," writes Bruce Gelb,M.D., of the Mount Sinai School of Medicine in New York, in an accompanying editorial.

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Researchers Create Risk Model for ChagasDisease Deaths

High score indicates 84 percent risk of death within 10 years

Investigators have developed and tested a simple model to predict the risk ofdeath from Chagas heart disease, which currently affectsmore than one million Latin Americans, according to a report in the Aug. 24issue of the New England Journal of Medicine.

Anis Rassi, Jr., M.D., Ph.D., from AnisRassiHospital in Goiania, Brazil, and colleaguesretrospectively analyzed 424 patients in a Brazilian cohort to develop ascoring system based on potential risk factors for death from Chagas disease, caused by the protozoan parasite Trypanosoma cruzi.The model was tested in a second group of 153 patients.

During a mean follow-up of 7.9 years where 130 patients died, theinvestigators identified six prognostic factors and weighted each according totheir regression coefficients. A value of 5 points was assigned for New YorkHeart Association class III or IV, 5 points for evidence of cardiomegaly,3 points for left ventricular systolic dysfunction, 3 points for non-sustainedventricular tachycardia, 2points for low QRS voltage and 2 points for being male.

A score of 12 or higher indicated the highest risk of death -- an 84 percent likelihood within 10 years. "At least onemillion of [currently infected individuals] will die unless scientific andpolitical breakthroughs lead to new strategies and tools for diagnosis,treatment and increased access to medical care," states the author of anaccompanying editorial.

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BMI Does Not Accurately Forecast Heart Disease Death

Body mass index cannot tell lean muscle mass from body fat

Body mass index does not dependably forecast heart disease mortality, most likely becauseit cannot differentiate between muscle mass and fat, researchers report in theAug. 19 issue of The Lancet.

Francisco Lopez-Jimenez, M.D., of the Mayo Clinic College of Medicine in Rochester, Minn.,and colleagues reviewed 40 studies involving 250,152 coronary artery diseasepatients.

The researchers found that patients with a body mass index under 20 had ahigher total mortality risk (relative risk, 1.37) and a higher heart diseasedeath risk (RR, 1.45) than patients with a normal body mass index. Overweightpatients with a body mass index of 25 to 29.9 had a lower total death risk (RR,0.87) and heart disease death risk (RR, 0.88) than those with a normal bodymass index (20-24.9).

"These findings could be explained by the lack of discriminatory powerof body mass index to differentiate between body fat and lean mass," theauthors write.

In an editorial, Maria Grazia Franzosi,Ph.D., of the Istituto Mario Negriin Milano, Italy, cautionsthat "uncertainty about the best index of obesity should not translateinto uncertainty about the need for a prevention policy against excessbodyweight."

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All Forms of Tobacco Raise Myocardial Infarction Risk

Regardless of method, tobacco exposure triples risk of heart attack

All forms of tobacco consumption, not just smoking, substantially raise the risk ofmyocardial infarction, according to the results of a global study published inthe Aug. 19 issue of The Lancet.

Koon K. Teo, M.B., of McMaster University-Hamilton Health Sciences in Hamilton, Ontario, Canada, andcolleagues conducted a study across 52 countries comprising 27,098participants, of whom 12,461 were myocardial infarction cases and 14,637 werecontrols.

The study included data on smoking history, including the type of tobacco,amount smoked, exposure to secondhand smoke and effect of smokeless tobacco.

Smoking was associated with an almost threefold higher risk of myocardialinfarction compared with never smoking. However, within three years of quittingsmoking, the odds ratio fell from 2.95 to 1.87, although there was a residualexcess (1.22) 20 years after quitting. Smoking beedies,a type of cigarette popular in South Asia, wasassociated with an odds ratio of 2.89, while chewing tobacco was associatedwith an odds ratio of 2.23. Exposure to secondhand smoke also raised the riskof myocardial infarction, with the level of risk dependent on the extent ofexposure.

"Tobacco use is one of the most important causes of acute myocardialinfarction globally, especially in men. All forms of tobacco use, includingdifferent types of smoking and chewing tobacco and inhalation of secondhandsmoke, should be discouraged to prevent cardiovascular disease," the authorsconclude.

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SAFE Strategy Effective in Trachoma-Endemic Areas

Surgery, antibiotics, facial cleanliness and environmental change achievegood results

The combination of surgery, antibiotics, facial cleanliness and environmentalchange, collectively known as SAFE, is effective in tackling trachoma in areaswhere it is endemic, according to a study in the Aug. 12 issue of The Lancet.

Jeremiah Ngondi, M.D., of the University of Cambridgein the U.K., and colleaguesconducted surveys in four areas in Sudan three years after SAFEinterventions had been implemented. The surveys assessed children aged 1 to 9years using clinical assessments and structured questionnaires.

In all areas surveyed, surgical coverage was low, ranging from 0.5 percentof individuals to 6 percent. Antibiotic uptake ranged from 14 percent to 75percent, and the rate of health education also varied widely from 49 percent to90 percent of households. Latrine coverage varied from 3 percent of householdsto 16 percent.

In two areas where there was high uptake of antibiotics and high levels ofhealth education, there were decreases of over 90 percent in the prevalence of trachomatous inflammation-follicular (TF) and a decrease inunclean faces of 87 percent in one area and 38 percent in the other. In thearea with the lowest uptake of antibiotics and health education, there was onlya 2 percent decrease in TF.

"Our results show that substantial falls in active trachoma can occurwhere SAFE is implemented," the authors conclude.

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ACE Inhibitors May Help AtherosclerosisPatients

Drug reduces serious vascular events in intermediate-risk patients

Angiotensin-converting enzyme (ACE) inhibitors, used totreat patients with heart failure or left ventricular systolic dysfunction(LVSD), may benefit patients with atherosclerosis,according to a study published in the Aug. 12 issue of The Lancet.

Gilles R. Dagenais, M.D., of the LavalHospitalin Quebec, Canada, and colleagues analyzed datafrom 29,805 participants in three large trials of patients with atherosclerosis and no symptoms of heart failure or LVSD.Patients were randomized to receive an ACE inhibitor or placebo, then followed up for a mean of 4.5 years.

When the results of all three trials were combined, patients assigned to theACE inhibitor group had lower all-cause mortality: 7.8 percent compared with8.9 percent of those in the placebo group. Cardiovascular mortality was lower,at 4.3 percent versus 5.2 percent; non-fatal myocardial infarction (MI) rateswere 5.3 percent versus 6.4 percent; stroke incidence was 2.2 percent versus2.8 percent; heart failure rates were 2.1 percent versus 2.7 percent,and 6 percent underwent coronary-artery bypass surgery versus 6.9 percent ofthe control group.

"Results showing these benefits in intermediate-risk patientscomplement existing evidence of similar benefit in higher-risk patients withLVSD or heart failure. Therefore, use of ACE inhibitors should be considered inall patients with atherosclerosis," the authorswrite.

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Woman Damages Vision After PrednisoloneSelf-Treatment

After self-diagnosing myalgicencephalomyelitis, patient bought the drug online for four years

A 64-year-old woman who self-diagnosed myalgic encephalomyelitispermanently damaged her eyesight as a result of four years of therapy with oralprednisolone, purchased from an online pharmacy basedin Thailand, according to a report published in the Aug. 12 issue of TheLancet.

Philip S. Severn, M.R.C.P., and Scott G. Fraser, F.R.C.Ophth.,of Sunderland Eye Infirmary in Sunderland, U.K., reportthat the woman presented with a six-month history of bilateral decreased visionand was diagnosed with steroid-induced glaucoma and cataract.

The patient disclosed that four years earlier she began to take between 10mg and 40 mg of prednisolone a day, and purchased thedrug from an online pharmacy. She had self-diagnosed myalgicencephalomyelitis and had not had any input from a health care professional inrelation to her diagnosis or treatment.

The authors conducted a Google search and found that 1,000 tablets of 5 mgof prednisolone was easily available for purchaseonline, and note the dangers of purchasing counterfeit drugs and takingmedication bought online without any guidance as to usage, side effects,interactions and monitoring.

"The online availability of controlled and uncontrolled drug therapiesneeds to be carefully monitored," the authors write. "As the Internetevolves so should our method of taking medical history." They suggestasking patients whether or not they are taking medications purchased online.

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Drug Promotion for Off-Label GabapentinExamined

Promotion involved influential physicians, sponsorship of research andpublications

Advisory boards, continuing medical education, influential physicians, and sponsorship of research and publications were used in the marketing and promotion of gabapentin (Neurontin), particularly to encourage off-label prescribing, according to a report in the Aug. 15 issue of the Annals of Internal Medicine.

Michael A. Steinman, M.D., and colleagues from theSan FranciscoVeteransAffairsMedicalCenter and the Universityof California, San Francisco, examined approximately 8,000pages of publicly available court documents to study how gabapentinwas promoted by Parke-Davis, a division ofWarner-Lambert, in terms of medical education, research, and publication.Warner-Lambert was acquired by Pfizer in June of 2000.

Gabapentin was initially approved in 1993 to treatpartial complex seizures, but was often prescribed for off-label uses such aspain and psychiatric conditions, leading to litigation that was settled in2004, according to the authors.

The researchers found that Parke-Davis deliveredpromotional messages through advisory boards, consultants meetings, andcontinuing medical education. Local champions and thought leaders (influentialphysicians affiliated with major academic medical centers) were used to promotegabapentin to their physician colleagues. The companyalso sponsored trials to encourage off-label prescribing, with plans tosuppress unfavorable results, and paid medical communication companies topublish articles about gabapentin.

The study "points out in stark detail that no patient is well-servedwhen a manufacturer engages in practices, whether inside or outside the law,that involve physicians in activities in which conflicts are present,"Jane E. Henney, M.D., of the Universityof Cincinnati in Ohio wrote in an accompanying editorial."But physicians are not passive participants: They can say 'No'."

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Cystatin C Predicts Adverse Outcomes inElderly

Marker of kidney function better predictor than creatinine

A marker of kidney function, cystatin C, predicts the risk ofdeath, cardiovascular disease and chronic kidney disease better than creatinine in the elderly, according to a report in theAug. 15 issue of the Annals of Internal Medicine.

Michael G. Shlipak, M.D., M.P.H., from the University of California San Francisco, and colleaguesexamined the ability of cystatin C to predict death,cardiovascular disease and incident chronic kidney disease in 3,659 elderlyadults without chronic kidney disease.

Over a median follow-up of 9.3 years, the researchers found that high levelsof cystatin C were associated with an increased riskof death (hazard ratio 1.33), heart failure (hazard ratio 1.28), stroke (hazardratio 1.22) and myocardial infarction (hazard ratio 1.20). Levels of serum creatinine were only predictive of cardiovascular death,according to the study. The authors found that patients with cystatin C levels of at least 1.0 mg/L had a fourfoldhigher risk of developing kidney disease after four years.

The study "strongly suggests that unlike standard cardiovascular riskfactors, which become less predictive in older adults, markers of kidneyfunction are strong risk factors for a wide range of adverse outcomes,"Josef Coresh, M.D., Ph.D., and Brad Astor, Ph.D.,from Johns Hopkins University in Baltimore, write in an accompanying editorial."Among older adults, cystatin C provides betterprediction than serum creatinine."

One of the study authors is an employee of Amgen.

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Nurse-Led Counseling Cuts Heart Failure Hospitalizations

Hospitalizations down, functioning improves after one year of nursecounseling by phone

TUESDAY, Aug. 15 (HealthDay News) -- A nurse-leddisease management program for patients with ambulatory congestive heartfailure may improve functioning and decrease hospitalizations, according to astudy conducted in an ethnically diverse community and reported in the Aug. 15 Annalsof Internal Medicine.

Jane E. Sisk, Ph.D., from the U.S. Centers for Disease Control andPrevention in Hyattsville, Md., and colleagues conducted a randomizedeffectiveness trial based at four hospitals in Harlem, N.Y.,between 2000 and 2002, to measure the effects of nurse-led intervention forambulatory care practice patients with systolic disease compared to usual care.

After 12 months of telephone-based counseling on diet, medication andself-management of symptoms, nurse-managed patients had 143 hospitalizationsper person-year compared with 180 hospitalizations per person-year for usualcare patients. However, the number of hospitalizations and deaths did notdiffer between the two groups. Nurse-managed patients also scored better on twofunctioning tests.

The authors conclude the program can "improve functioning and modestlyreduce hospitalizations among predominantly minority, low-educated ambulatorycare patients who have systolic dysfunction. Continued contact with a nurseseemed to be needed to maintain the intervention's effect."

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Effect of Financial Incentives on Quality of Care Unclear

Ongoing monitoring of programs essential to determine effectiveness

Studies examining the effect of financial incentives on quality of health care haveshown mixed results, and ongoing monitoring of these programs is essential todetermine their effectiveness, according to a report in the Aug. 15 issue ofthe Annals of Internal Medicine.

Laura A. Petersen, M.D., M.P.H., from Baylor College of Medicine in Houston,and colleagues reviewed the medical literature from 1980 to 2005 for studiesexamining the relationship between explicit financial incentives to improvehealth care quality and quantitative measures of health care quality.

The researchers identified 17 studies, of which 13 examined process-of-caremeasures, mostly focusing on preventive care. Only one study addressedcost-effectiveness. Five of six studies examining financial incentives forphysicians and seven of nine studies examining incentives for provider groupsshowed partial to positive effects on quality. The two studies examiningincentives at the payment-system level showed mixed results in terms of accessto care, according to the report. Overall, the authors found four studiessuggesting that incentives may have unintended effects, such as avoiding themost seriously ill patients.

Noting that "generalization from the existing studies is limited,"Petersen and colleagues suggest that "ongoing monitoring of incentive programsis critical to determine the effectiveness of financial incentives and theirpossible unintended effects on quality of care" and that "incentivesrequire very careful design."

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Smoking Cessation Drug Has Gone Unnoticed in West

Cytisine, long used in Eastern Europe,hardly mentioned in literature

Nicotine receptor agonist cytisine, a drug that has been usedfor the past 40 years in Eastern Europe as an aid to smoking cessation, hasbeen largely ignored by the English-language journals, according to a reviewand meta-analysis in the Aug. 14/28 issue of the Archives of InternalMedicine.

Jean-Francois Etter, Ph.D., M.P.H., of the University of Genevain Switzerland, conducted aliterature review of 10 studies published in Bulgaria,Germany, Poland and Russia, covering 4,404 smokerstreated with cytisine and 3,518 controls. Three ofthe studies were placebo-controlled, two of which were double-blind and onerandomized. The former two studies yielded a pooled odds ratio of smokingcessation after three to six months of 1.83, and one of the placebo-controlleddouble-blind trials had a 1.77 odds ratio of cessation at the two-year mark.

However, the quality of the research trials was poor and the author notesdiscrepancies between the adverse effects reported by the manufacturer andthose that emerged in the studies. Most of the studies have never been cited inEnglish-language literature.

While the available data is not of a high standard, the drug has been widelyused and is apparently safe and effective, the author writes. "How manyother effective drugs are there for which efficacy remained unnoticed becauseexisting trials were not published in English in Western countries?" heasks.

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Varenicline TartrateHelps Smokers Kick the Habit

Two new studies suggest novel agent is efficacious for smoking cessation

Varenicline tartrate (Chantix) can help smokers kick the habit, according to twostudies in the Aug. 14/28 issue of the Archives of Internal Medicine. TheU.S. Food and Drug Administration approved vareniclinein May 2006.

Mitchell Nides, Ph.D., of Los Angeles ClinicalTrials in California, and colleagues conducted a seven-week, randomized trialin otherwise healthy smokers aged 18 to 65. Four-week continuous quit rateswere 48 percent for smokers who took 1 milligram twice daily of varenicline; 37.3 percent for 1 mg daily of varenicline; 33.3 percent for bupropionhydrochloride; and 17.1 percent for placebo. Long-term quit rates from fourweeks to one year were 14.4 percent for the group that received 1 mg twicedaily of varenicline versus 4.9 percent for placebo.

In a second study by the same researchers, continuous quit rates were higherin smokers who took 1.0 mg or 0.5 mg of vareniclinetwice daily compared with those who took a placebo for weeks nine through 12.Quit rates remained significantly higher for the vareniclinegroup than placebo at one year. Nausea was the main side effect, but it wasreduced when doses were titrated.

"Varenicline is a novel medication to aid insmoking cessation," Bankole A. Johnson, D.Sc.,M.D., Ph.D., of the University of Virginia in Charlottesville, writes in anaccompanying editorial.

Pfizer sponsored and funded both studies.

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Doctors' Views on Disclosure of Errors Varies Widely

Culture of medical world, medical specialty play role in attitudes ontransparency

There is a wide variation across the medical profession when it comes to disclosingmedical errors to patients, with the visibility of the error and medicalspecialty both playing a role, according to two studies in the August 14/28issue of the Archives of Internal Medicine.

Thomas H. Gallagher, M.D., of the University of WashingtonSchool of Medicine in Seattle, and colleagues conducted two studiesusing a postal survey of 2,637 physicians in the United States and Canada to assess their attitudes onthe disclosure of medical errors.

The first study posed four scenarios with different serious errors, usingscripted statements to gauge the physician's reaction. Overall, 56 percent ofrespondents said they would describe an adverse event without using the word"error," but only 19 percent of surgical specialists would explicitlymention an error, compared to 58 percent of medical specialists.

In the second study, the authors write that the malpractice environment doesnot seem to play a pivotal role in physicians' attitudes toward disclosure oferrors. While 98 percent supported the idea of disclosure of serious errors, 74percent thought this would be very difficult. Two-thirds said that disclosureof errors reduced the risk of malpractice suits.

"The medical profession should consider whether the culture of medicineitself represents a more important barrier than the malpractice environment tothe disclosure of harmful medical errors to patients," the authorsconclude.

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Low Testosterone Level Raises Mortality Risk for Men

Suboptimal levels of the hormone raiseodds by 68 percent

Men with low levels of testosterone after the age of 40 are at higher risk of death thantheir counterparts with normal levels of the hormone, according to a studypublished in the August 14/28 issue of the Archives of Internal Medicine.

MollyM.Shores,M.D., of the VA Puget Sound Health Care System in Seattle, and colleagues analyzeddata from 858 male veterans who were age 40 or older and free of prostatecancer. The men had been repeatedly tested for testosterone levels. There were166 men (19.3 percent) with a low testosterone level, defined as less than 250 ng/dL; 240 (28 percent) with an equivocal testosteronelevel; and 452 (52.7 percent) with a normal testosterone level.

Over a four-year period, 20.1 percent of the men with normal testosteronedied, compared with 24.6 percent of those with equivocal testosterone levelsand 34.9 percent of those with low testosterone.

Even after adjustment for age, medical morbidity and other clinicalcovariates, as well as excluding those who died within the first year tominimize the impact of acute illness, low testosterone was still associatedwith 68 percent greater risk of mortality.

"The persistence of elevated mortality risk after excluding earlydeaths suggests that the association between low testosterone and mortality isnot simply due to acute illness," the authors conclude.

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Chinese Women At Risk from Husbands' Smoking

Over 80 percent of women in China exposed to secondhand smoke,survey finds

Chinese women are often exposed to secondhand smoke, primarily from their husbands, whichincreases their risk of death from lung cancer and cardiovascular disease,according to the results of a study published in the Aug. 19 issue of BMJ.

Wanqing Wen, M.D., M.S.,of Vanderbilt University School of Medicine in Nashville,Tenn., and colleagues conducted a study in Shanghai, China,of 72,829 women who had never smoked. Of these, 65,180 gave information ontheir husbands' smoking habits, and 66,520 gave information on tobacco smokeexposure in the workplace and in early life within the family.

Of the women surveyed, 83.1 percent were exposed to tobacco smoke from theirhusbands, the workplace or family members in early life, or due to acombination of factors. Exposure to tobacco smoke from husbands was associatedwith a hazard ratio of 1.15 for all-cause mortality and 1.37 for cardiovasculardisease.

Workplace exposure was associated with a hazard ratio of 1.19 for mortalitydue to cancer, and of 1.79 for lung cancer. Early life exposure also raised therisk of mortality due to cardiovascular disease, with a hazard ratio of 1.26.

"Given the high prevalence of exposure to environmental tobacco smokein this population, a moderate association with a hazard ratio of 1.15 wouldyield an attributable risk in the population of 11.1percent," the authors conclude.

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China'sOne-Child Policy Has Led to Gender Imbalance

Some studies suggest relaxing policy could correct gender imbalancewithout baby boom

China's one-child family policy has resulted in a reduction in the country's totalbirth rate and in family size, but the country is also experiencing a hugeimbalance in the ratio of male to female births, according to researchpublished in the Aug. 19 issue of BMJ.

Qu Jian Ding, M.D., of ZhejiangUniversity in Hangzhou,China, and Therese Hesketh, Ph.D., of the Instituteof Child Health in London, U.K.,analyzed data from a cross-sectional national family planning and reproductivehealth survey conducted in 2001. The survey included data from 39,585 women, ofwhom 17,078 were over 35 years of age. The data included 73,202 pregnancies and56,830 live births.

The average fertility rate for women aged under 35was 1.73, while the rate for women over 35 was 1.94. Aside from younger age,higher education level and urban residence were also associated with smallerfamilies. Most of the women surveyed said they wanted either one child (35percent) or two (57 percent). The ratio of males to females rose from 1.11 in1980-1999 to 1.23 for 1996-2001.

The authors note that previous studies have recommended a relaxation of thepolicy to allow two children per family. "It is unlikely that a baby boomwould result, and such a change in policy might help to correct the abnormalsex ratio," they write.

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High-Fat Meals Cut Protective Effects of HDL Cholesterol

A single high-saturated fat meal can reduce endothelial and vascularfunction

Just one meal high in saturated fat can reduce the protective anti-inflammatory effects ofhigh-density lipoprotein and impair endothelial function, according to a reportpublished online Aug. 7 in the Journal of the American College of Cardiology.This single meal could possibly influence the atherogenicprocess, the authors report.

A group led by David Celermajer, Ph.D., of Royal PrinceAlfredHospital in Camperdown, Australia, measured vascular andendothelial function shortly after 14 adults consumed an isocaloricmeal on two separate occasions, one of which was high in saturated fat and theother high in polyunsaturated fat.

The investigators found that high-density lipoprotein collected from plasmaof patients who consumed a saturated-fat meal was poorer at suppressinginflammation in cultured endothelial cells, measured by expression of ICAM-1and VCAM-1. Post-hyperemic microvascular flowincreased by an average of 21 percent three hours after the saturated fat meal,compared with an average 45 percent after the polyunsaturated meal, whileflow-mediated dilation decreased by an average 2.2 percent after the saturatedmeal and by an average 0.9 percent after the polyunsaturated meal.

"The present study raises the possibility that the differential effectsof dietary fats on the anti-inflammatory potential of high-density lipoproteinand endothelial function may contribute to the apparent benefits ofpolyunsaturated over saturated diets observed in the epidemiologicliterature," the authors conclude.

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Angina Care Can Top $1 Million During a Woman'sLifetime

Cost of care high even among women with non-obstructive coronary arterydisease

Angina may be the greatest driver of women's cardiovascular health care costs, andnon-obstructive coronary artery disease is no exception, according to resultsfrom the National Institutes of Health-National Heart, Lung, and BloodInstitute-sponsored Women's Ischemia SyndromeEvaluation, published online Aug. 21 in Circulation: Journal of the AmericanHeart Association.

Leslee J. Shaw, Ph.D., of Cedars-SinaiMedicalCenterin Los Angeles,and colleagues reviewed data on 883 women referred for coronary angiography and compared the data with their direct andindirect health care costs through five years of follow-up.

While researchers anticipated that women with non-obstructive coronaryartery disease (CAD) would have fewer health care needs, after a year offollow-up, repeat catheterizations and angina hospitalizations were 1.8-foldhigher in women with non-obstructive CAD compared with women with one-vesselCAD. Drug treatment was higher for women with non-obstructive or one-vesselCAD, while costs for anti-ischemic therapy werehigher for women with non-obstructive CAD.

Women with non-obstructive CAD had average lifetime health-care costs of$767,288, while costs ranged from $1,001,493 to $1,051,302 for women withone-vessel to three-vessel CAD. Five year costs ranged from $32,239 for womenwith non-obstructive CAD to $53,398 for women with three-vessel CAD.

"Enumerating the expected costs of care for women with non-obstructiveand obstructive CAD is an important step toward identifying vulnerable subsetsof women who require more resource-intensive cardiovascular care," the authorsconclude.

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AHA Issues Statement on Physical Activity in Schools

Not enough physical education programs are offered to children, accordingto American Heart Association

Schools must take the lead in promoting adequate physical activity for children during theschool day, according to a scientific statement published online Aug. 14 in Circulation:Journal of the American Heart Association.

Russell Pate, Ph.D., of the Universityof South Carolina in Columbia,and colleagues cited statistics for obesity rates among children in the United States overthe past 20 years, as well as the amount of time that states require studentsto spend each day in physical education between 1991 and 2003.

The report noted that 15.8 percent of children between the ages of 6 and 11years are overweight and 16.1 percent of adolescents between 12 and 19 yearsold are considered overweight. At the same time, the authors noted that thepercentage of high school students enrolled in daily physical education fell to28.4 percent in 2003 from 41.6 percent in 1991. They also noted that onlyone-third of students who live within one mile of school walk or ride a bicyclethere. And only 8 percent of elementary schools, 6.4 percent of middle orjunior high schools, and 5.8 percent of high schools provided daily physicaleducation programs or allocated a recommended amount of time each week.

"Although schools are under increasing pressure to increase studentscores on standardized tests, the recent dramatic rise in the prevalence ofobesity in children and adolescents in the United States suggests that there isa pressing need for the nation's schools to systematically and effectivelypromote behaviors that will prevent the development of overweight,"according to the statement.

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Guidelines on Sudden Cardiac Death Prevention Released

U.S.and European cardiologists reach consensus on treatment for ventriculararrhythmias

The American College of Cardiology, the American Heart Association, and the European Societyof Cardiology, in collaboration with the European Heart Rhythm Association andthe Heart Rhythm Society have released the 2006 Guidelines on Management ofPatients with Ventricular Arrhythmias and the Prevention of Sudden CardiacDeath.

Important updates are included, such as the range of ejection fractions andtheir relationship to implantable cardioverterdefibrillators (ICD). "Prior to this document, practitioners facedinconsistent recommendations for prophylactic ICD implantation based onejection fractions," said Douglas P. Zipes,M.D., M.A.C.C., co-chair of the Guideline Writing Committee, in a statement.

The guidelines also give recommendations on how to evaluate and treatpatients with ventricular arrhythmia or who are at risk of developing thecondition. They outline the various noninvasive and invasive evaluationtechniques as well as the range of therapies including drugs, devices,ablation, surgery and revascularization. Theguidelines also cover acute and chronic therapies and management of patientsbased on the burden of their symptoms and severity of underlying heart disease.

The guidelines were released on Aug. 21 and were expected to be publishedonline in the Sept. 5 issue of the Journal of the American College ofCardiology and Circulation: Journal of the American Heart Association,as well as in the first September issue of the European Heart Journal,while the print versions of these publications will carry an executive summaryof the guidelines.

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Lifestyle Benefits Seen From Sinus Rhythm Restoration

Exercise performance and quality of life improves in patients withpersistent atrial fibrillation

While restoration and maintenance of sinus rhythm may not confer survival benefits inpatients with persistent atrial fibrillation, it doesimprove exercise performance and quality of life, according to a studypublished in the Aug. 15 issue of the Journal of the American College ofCardiology.

Steven N. Singh, M.D., of the Department of Veterans Affairs Medical Centerin Washington, D.C., and colleagues conducted a sub-studyof atrial fibrillation patients who were randomizedto receive amiodarone, sotalol,or placebo. They classified the subjects by rhythm status as either sinusrhythm or atrial fibrillation and assessed 624 ofthem at eight weeks and 556 of them at one year.

The researchers found that the sinus rhythm group showed a modestimprovement in treadmill exercise tolerance. At eight weeks, the researchersobserved favorable changes in the sinus rhythm group in physical functioning,physical role limitations, general health and vitality compared to patients whoremained in atrial fibrillation. At one year, alsothey saw favorable changes in the sinus rhythm group in general health andsocial functioning.

"This is particularly intriguing in light of recent studies showingthat restoration of sinus rhythm in atrialfibrillation patients has no effect on mortality or on major physical endpoints, which therefore implies no benefit in attempted restoration of sinusrhythm if survival or complications alone is the reason for such therapy,"wrote the author of an accompanying editorial.

The study was supported by the Department of Veterans Affairs, Berlex Laboratories and Wyeth-Ayerst.

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