Latest Research

Hospital Ratings Do Not Always Indicate Patient Outcomes

Quality measures do not reflect myocardial infarction mortality rates

Hospitals' reported quality process measures for acute myocardial infarction are not always indicative of patient outcomes, according to a study published in the July 5 issue of the Journal of the American Medical Association.

Harlan M. Krumholz, M.D., S.M., of Yale UniversitySchool of Medicine in New Haven, Conn., and colleagues assessedthe performance of 962 hospitals that were participants in the NationalRegistry of Myocardial Infarction, and used Medicare claims data to calculateeach hospital's 30-day mortality rates.

Process measures such as β-blocker and aspirin use at admission anddischarge, and use of angiotensin-converting enzymeinhibitors were strongly correlated with each other, and these medicationmeasures were weakly associated with measures of smoking cessation counselingand time to reperfusion. Although some measures were strongly correlated withmortality rates, in sum they accounted for only 6 percent of hospital-levelvariations in mortality rates among acute myocardial infarction patients.

"The publicly reported acute myocardial infarction process measurescapture a small proportion of the variation in hospitals' risk-standardizedshort-term mortality rates. Multiple measures that reflect a variety ofprocesses and also outcomes, such as risk-standardized mortality rates, areneeded to more fully characterize hospital performance," the authorsconclude.

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Health Risks for Extremely Obese Women Underestimated

Homogenous interpretations of obesity data downplay risk

The escalating rate of extreme obesity is worsening the health effects and costs of the U.S. obesity epidemic, according to a study published in the July 5 issue of the Journal of the American Medical Association. The mortality and cardiac risks of extreme obesity (body mass index of 40 or higher) are greater than those seen in patients who are obese but have a lower body mass index.

Kathleen McTigue, M.D., M.S., M.P.H., of the University of Pittsburgh,and colleagues analyzed data from 90,185 women from 40centers across the United States who were recruited to the Women'sHealth Initiative Observational Study, and examined incident mortality andcardiovascular outcomes in relation to the women's body mass index, or BMI.

Among women with a normal BMI (below 25) the all-cause mortality rate was68.39 per 10,000 person-years, versus 84.47 for women in the obesity 1 category(BMI of 30 to 34.9), 102.85 for obesity 2 category women (BMI of 35 to 39.9)and 116.85 for extremely obese women (BMI of 40 or above). Diabetes,hypertension and hyperlipidemia mediated most of theobesity-related mortality and coronary heart disease risk. Among white women,older women were at less risk of weight-related all-cause mortality.

"Considering obesity as a homogenous condition with fixed risk isinappropriate. Weight-related health risk clearly varies with degree of excessweight," the authors conclude. "More accurately assessingweight-related health risk may both improve policy decisions about obesity andassist women in making informed decisions about their health."

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Max Acetominophen Dose Linked to Liver EnzymeRise

Healthy subjects in controlled trial taking 4 grams for four or more daysshow serum aminotransferase elevations

Patients taking acetaminophen dosages in the upper range of the recommended daily intake can have an increase in liver enzymes, according to a report in the July 5 issue of the Journal of the American Medical Association.

To determine the cause of serum alanine aminotransferase (ALT) elevations observed in a clinicaltrial of an acetaminophen combination product, Paul B. Watkins, M.D., from theUniversity of North Carolina in Chapel Hill, and colleagues conducted asingle-blind, placebo-controlled study in 145 healthy adults randomized to 4grams daily of acetaminophen alone, or in combination with selected opioids.

While only one of the placebo group participants had an ALT level two timesabove the upper limit of normal, 31 percent to 44 percent of all groups takingacetaminophen had ALT levels at three times normal or above, irrespective ofconcomitant opioid treatment. Acetaminophen levelsnever exceeded therapeutic limits and decreased to undetectable levels evenwhen ALT elevations were still present.

"A history of recurrent acetaminophen ingestion should therefore besought when evaluating otherwise unexplained elevations in serum aminotransferase observed in clinical practice or duringclinical trials," the authors conclude.

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Varenicline Helps Prevent Smoker Relapse

Medication may have lower relapse rate than bupropion,but more likely to cause nausea

Varenicline, the newly approved smoking-cessation drug, may have a lower relapse rate than sustained-release bupropion, but can cause side effects, such as nausea, according to three studies from the Varenicline Phase 3 Study Group published in the July 5 issue of the Journal of the American Medical Association.

In one study, 1,927 smokers were treated with vareniclinefor 12 weeks and 1,236 (64.1 percent) were abstinent from nicotine use in thelast week of treatment. Of these, 1,210 were then randomized to receiveadditional treatment or placebo. The abstinence maintenance rate over thefollowing 12 weeks was 70.5 percent for the vareniclinegroup versus 49.6 percent for the placebo group.

Two related studies compared the efficacy of varenicline,sustained-release bupropion (bupropionSR) and placebo. One included 1,027 adult smokers, of whom 43.9 percent whowere randomized to receive varenicline remainedabstinent by weeks nine to 12 of the study, comparedwith 29.8 percent in the bupropion SR group and 17.6percent in the placebo group.

In the other study, 1,025 smokers were randomized to receive varenicline, bupropion SR orplacebo for 12 weeks, followed by 40 weeks of non-drug follow-up. Rates ofabstinence were higher among the varenicline group inthe last four weeks of the study, and maintenance was better sustained duringthe nearly one-year follow-up period.

An accompanying editorial cautions, however, that the drug is not a panaceafor smoking as it produced a higher rate of side effects, notably nausea (30percent of participants).

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Elderly with High Activity Levels Live Longer

Climbing stairs, working for pay common among those with high levels offree-living activity

Older adults with higher levels of free-living activity live longer than their less active counterparts, according to a study in the July 12 issue of the Journal of the American Medical Association.

Todd M. Manini, Ph.D., of the National Instituteon Aging in Bethesda, Md., and colleagues measured total energyexpenditure with doubly labeled water for two weeks among 302 high-functioning,community-dwelling adults aged 70 to 82. They also measured participants'resting metabolic rate. Participants were followed an average of 6.15 years,and 55 people died during the study period.

Individuals with the highest expenditure of energy had a significantly lowerrisk of death compared to their less active counterparts, the study showed,with the absolute risk of death at 12.1 percent in the highest tertile of activity energy expenditure, 17.6 percent amongparticipants in the middle tertile and 24.7 in thelowest tertile. Participants who expended higheramounts of free-living activity energy were more likely to work for pay and toclimb stairs, but self-reports of high-intensityexercise, walking, volunteering and caregiving didnot differ across the tertiles.

An accompanying editorial calls the study results "striking" andnotes that "public health experts should consider how these results can betranslated into recommendations for individuals."

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Preventive Oophorectomy May Cut Risk of SomeCancers

Oophorectomy in high-risk women mayreduce risk of ovarian, fallopian tube cancers; hikerisk of peritoneal cancer

Women with a mutation in the BRCA1 or BRCA2 gene who undergo preventive bilateral salpingo-oophorectomy can reduce their risk of ovarian and fallopian tube cancer, according to a paper in the July 12 issue of the Journal of the American Medical Association. However, they do have a residual risk of developing peritoneal cancer following the preventive surgery.

Researchers led by Steven A. Narod, M.D., of the Toronto-SunnybrookRegionalCancerCenter in Ontario, Canada,compared cancer rates among 1,828 women with mutations of the BRCA1 and BRCA2genes. Of these, 555 underwent preventive oophorectomybefore entering the study, 490 underwent the procedure after entering the studyand 783 women had no surgery.

During a mean follow-up of 3.5 years, 50 new ovarian, fallopian tube andperitoneal cancer cases were diagnosed. There were 32 incident cancersdiagnosed among women with intact ovaries. Eleven cancer cases were diagnosedat the time of surgery and seven were found following surgery.

The magnitude of risk reduction is approximately 80 percent and there is a4.3 percent residual risk of peritoneal cancer among BRCA1 and BRCA2mutation carriers 20 years after oophorectomy, theauthors conclude, adding that the latter risk "is not sufficiently high torecommend against the procedure."

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Biofilm Bacteria Linked to ChronicMiddle Ear Infections

Findings support avoidance of antibiotics to treat otitismedia in children

Recurrent otitis media infections and otitis media with effusion in children are associated with the presence of biofilm bacteria, according to a study in the July 12 issue of the Journal of the American Medical Association.

Garth D. Ehrlich, Ph.D., of the Allegheny-Singer Research Institute in Pittsburgh, andcolleagues analyzed middle-ear mucosa specimens from26 children aged 6 months to 14 years who underwent tympanostomytube placement to treat otitis media with effusionand otitis media. Confocallaser scanning microscopic images were analyzed for the presence of H. influenzae, Streptococcus pneumoniaeand Moraxella catarrhalis.

In all, 13 of the 26 children (50 percent) undergoing tympanostomytube placement had otitis media with effusion, and 20(77 percent) had recurrent otitis media. Of the 52ears, 27 (52 percent) had effusions, of which 24 of 24 effusions testedpositive using polymerase chain reaction-baseddiagnostics for one or more otitis media pathogens.

Using generic and pathogen-specific probes, the researchers identified mucosal biofilms on 46 (92percent) of 50 middle-ear mucosa specimens fromchildren with otitis media with effusion andrecurrent otitis media.

"Given that bacteria living in biofilms aremetabolically resistant to antibiotics, this studymakes a definitive, scientifically based statement against the use of thesedrugs to treat children with chronic ear infections. It simply does not helpthe child and increases the risk of breeding more resistant strains ofbacteria, " Ehrlich said in a statement.

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Postmenopausal Weight Linked to Breast Cancer Risk

Gaining weight ups the odds; losing weight reduces them

Postmenopausal weight gain is associated with a higher risk of breast cancer, and weight loss at the same time of life is associated with a reduced risk, according to a study in the July 12 issue of the Journal of the American Medical Association.

A. Heather Eliassen, Sc.D.,of Brigham and Women's Hospital and Harvard Medical School in Boston, andcolleagues conducted a prospective cohort study of 87,143 postmenopausal womenaged 30 to 55 years who did not have cancer, and followed them for up to 26years from 1976 to 2002, assessing weight change since age 18. Of the sample,49,514 women had their postmenopause weight changeassessed for up to 24 years.

During the study, 4,393 cases of invasive breast cancer were detected. Womenwho gained 25 kg or more from their weight at age 18 increased their odds ofbreast cancer 1.45 times, compared with those who maintained a stable weight.

Among women who had never taken postmenopausal hormones, those who lost 10kg or more after menopause and maintained their new weight had a lower risk(relative risk, 0.43) of developing breast cancer compared to those who onlymaintained their weight.

"Our results provide another reason for women approaching menopause tomaintain or lose weight, as appropriate," the authors conclude.

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High-Volume Hospitals Have Better Ventilation Outcomes

Lower mortality rates independent of academic status of facility

Hospitals with a high volume of patients have lower mortality rates among critically ill patients who receive mechanical ventilation compared with low-volume hospitals, according to a study published in the July 6 issue of the New England Journal of Medicine.

Jeremy M. Kahn, M.D., of the University of Washington in Seattle,and colleagues analyzed data on 20,241 non-surgical patients who receivedmechanical ventilation at 37 acute care hospitals.

Among mechanical ventilation patients in both the hospitals and in thehospitals' intensive care units, higher patient volumes were associated withimproved survival. Patients at hospitals with 400 or more patients requiringmechanical ventilation each year (the top quartile by volume) had 37 percentlower adjusted odds of death compared to their counterparts in hospitals in thelowest quartile, which received 150 or fewer mechanical ventilation patients ayear.

The in-hospital mortality rate for patients in the lowest quartile volumehospitals was 34.2 percent versus 25.5 percent for those in the highestquartile hospitals.

The authors cite a range of possible reasons why high-volume hospitalsgenerate better outcomes. They may have better practices such as lowernurse-to-patient ratios and multidisciplinary care teams, for example."More-experienced as opposed to less-experienced clinicians may be betterat recognizing and treating the complications of critical illness," theywrite.

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Perioperative

Chemotherapy Boosts Gastric Cancer Survival

Researchers find it improves survival in patients with resectable gastric cancer

In patients with operable gastroesophageal cancer, perioperative chemotherapy decreases tumor size and stage, and significantly improves overall and progression-free survival, according to a study published in the July 6 issue of the New England Journal of Medicine.

David Cunningham, M.D., of RoyalMarsdenHospital in Surrey, U.K., andcolleagues studied 503 randomly assigned patients with resectableadenocarcinoma of the stomach, esophagogastricjunction or lower esophagus to receive either a perioperativeregimen of epirubicin, cisplatinand infused fluorouracil (ECF) and surgery, orsurgery alone.

The researchers found that the perioperative-chemotherapygroup had significantly smaller and less advanced tumors than the surgery-onlygroup, and had improved rates of overall survival (hazard ratio for death,0.75), five-year survival (36 percent versus 23 percent) and progression-freesurvival (hazard ratio for progression, 0.66).

"The most important question for physicians who treat patients withgastric cancer is whether the report by Cunningham et al. should influencetheir management of the disease. Is perioperativechemotherapy an advance in the treatment of gastric cancer?" states theauthor of an accompanying editorial. "The trial conducted by Cunninghamand colleagues was well designed and well executed, and clinicians can haveconfidence in the solid evidence that perioperativetherapy with a regimen of ECF improves the outcome for patients with resectable gastric cancer identified before gastrectomy."

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Influenza Under-Recognized in Young Children

Because few laboratory-confirmed cases are diagnosed, few children arereceiving therapy

Influenza infections cause a substantial disease burden in children under age 5, yet few such infections are clinically recognized and treated with specific therapy, according to a study published in the July 6 issue of the New England Journal of Medicine.

Katherine A. Poehling, M.D., of VanderbiltUniversityMedicalCenterin Nashville, Tenn., and colleagues conducted apopulation-based surveillance of medical visits associated withlaboratory-confirmed influenza during the 2002-2003 and 2003-2004 influenzaseasons.

The researchers found that the average annual rate of influenza-associatedhospitalization was 0.9 per 1,000 children. The average annual rates ofinfluenza-associated outpatient visits were 50 clinic visits and six emergencydepartment visits per 1,000 children during the 2002-2003 seasonand 95 clinic visits and 27 emergency department visits per 1,000 childrenduring the 2003-2004 season. Among children with laboratory-confirmedinfluenza, only 28 percent of inpatients and 17 percent of outpatients receiveda diagnosis of influenza by the treating physician.

"As a consequence, few patients were offered specific therapy forinfection with the influenza virus," states the author of an accompanyingeditorial. "This lack of recognition represents a missed opportunity tointervene to reduce both the risk of complications and the spread of the virusto contacts."

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Carbon Particles Affect Children's Lung Function

Carbon content of airway macrophages correlates with reductions in forcedexpiratory volume

Inhaling carbon particles, a common component of air pollution, may cause impaired lung function in children, according to a study published in the July 6 issue of the New England Journal of Medicine.

Neeta Kulkarni, M.D., ofthe University of Leicester in Leicester, U.K., and colleagues measuredconcentrations of particulate matter 10 (PM10) microns or smaller in theneighborhoods of 114 healthy children, assessed the carbon content of thechildren's airway macrophages and used spirometry toevaluate their lung function.

The researchers were able to assess the carbon content of airway macrophagesin 64 (56 percent) of the children. They found that each increase in primaryPM10 of 1.0 μg per cubic meter was associatedwith an increase of 0.10 μm2 in the carbon content of airway macrophages,and that each increase of 1.0 μm2 in carbon content was associated with a17 percent reduction in forced expiratory volume in one second (FEV1).

"Findings from [such] studies will provide necessary support foractions by policymakers and will guide the choice of specific controlstrategies," states the author of an accompanying editorial. "The bestcontrol strategy from the standpoint of human health, supported by thescientific evidence to date, is to reduce the levels of all types of airpollutants. Our children's health depends on it."

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Doppler Ultrasound Better Than Amnio For Rh+ Pregnancy

Researchers suggest it may replace amniocentesis in management of Rh-alloimmunized pregnancies

In the management of Rh-alloimmunized pregnancies, Doppler ultrasonography of the middle cerebral artery is superior to amniocentesis in predicting fetal anemia and is a safe alternative for monitoring such pregnancies, according to a study in the July 13 issue of the New England Journal of Medicine.

Dick Oepkes, M.D., of LeidenUniversityMedicalCenterin Leiden, the Netherlands,and colleagues compared the accuracy of Doppler ultrasonographyand amniocentesis in assessing 165 fetuses, 74 of which had severe anemia.

The researchers found that Doppler ultrasonographyhad superior sensitivity (88 percent versus 76 percent), specificity (82percent versus 77 percent) and accuracy (85 percent versus 76 percent) comparedto amniocentesis.

"The current results support the hypothesis that Doppler values in themiddle cerebral artery may largely replace amniocentesis in the management ofred-cell alloimmunization in pregnancy, but there aresome exceptions," states Kenneth Moise, Jr.,M.D., of the University of North Carolina School of Medicine in Chapel Hill, inan accompanying editorial. The findings "suggest that the time has come toput our needles aside when evaluating affected fetuses," Moise writes.

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Heart Failure More Likely If a Parent Had the Condition

Study shows significant increase in chances of heart failure over 10years if parents had the disease

Patients who have a parent with heart failure are more likely to have left ventricular dysfunction and eventually develop the condition themselves compared with those whose parents do not have heart failure, according to a report in the July 13 issue of the New England Journal of Medicine.

Ramachandran S. Vasan,M.D., of the Boston University School of Medicine and the Framingham HeartStudy in Boston,and colleagues examined the cross-sectional association of heart failure inparents in the Framingham Offspring Study cohort. The study included 1,497offspring with an average age of 57, including 1,039 offspring whose parentsdid not have heart failure.

The 458 participants who had parents with heart failure were more likelythan those who did not to have increased left ventricular mass (26.9 versus 17percent), left ventricular internal dimensions (23.4 versus 18.6 percent), andleft ventricular systolic dysfunction (5.7 versus 3.1 percent). The adjusted10-year incidence of heart failure was 2.72 percent in subjects who had parentswith heart failure compared to 1.62 percent in those whose parents did not.

"Our data emphasize the contribution of familial factors to theheart-failure burden in the community," the authors write. "Providedthat parental occurrence of heart failure can be ascertained reliably by athorough history taking, this information may facilitate early identificationof persons at risk for heart failure."

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No Benefit from Raloxifene for CHD, FatalStroke Risk Up

Study shows breast cancer down, but fatal stroke and venous thromboembolism up

The selective estrogen-receptor modulator raloxifene reduces the risk of invasive breast cancer but does not prevent coronary heart disease (CHD) and increases the risk of venous thromboembolism and fatal stroke, according to the Raloxifene Use for The Heart (RUTH) trial results published in the July 13 issue of the New England Journal of Medicine.

Elizabeth Barrett-Connor, M.D., of the Universityof California San Diego in La Jolla, Calif.,and RUTH trial members randomized 10,101 postmenopausal women with CHD, or withrisk factors for CHD, to either 60 milligrams of raloxifenedaily or a placebo, then measured the incidence ofcoronary events and invasive breast cancer. Average follow-up was 5.6 years.

While raloxifene reduced the risk of invasivebreast cancer by 44 percent and helped prevent vertebral fractures, it showedno effect on CHD incidence in women with or at-risk for CHD. In addition, therisks for venous thromboembolism and fatal strokewere up by 44 percent and 49 percent, respectively.

The results suggest considering a careful risk-benefit analysis beforerecommending raloxifene or another selectiveestrogen-receptor modulator, like tamoxifen, forindividual women, according to Marcia L. Stefanick,Ph.D., of the Stanford School of Medicine in Stanford, Calif. "For now,there is no magic bullet that can reduce the risks of major health problemsrelated to estrogens and aging without introducing other potentially serioushealth concerns," she writes in an accompanying editorial.

The study was supported by Eli Lilly.

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Doxycycline Effective in PreventingTick-Borne Fever

Small placebo-controlled study found all subjects with fever were inplacebo group

Doxycycline was 100 percent effective in preventing tick-borne relapsing fever in a small, placebo-controlled trial of subjects suspected of having a recent tick exposure, according to a report in the July 13 issue of the New England Journal of Medicine.

Tal Hasin, M.D., fromthe Medical Corps of the Israel Defense Force in Jerusalem, Israel, andcolleagues conducted a randomized, double-blind trial of a five-day course of doxycycline to prevent tick-borne relapsing fever (TBRF)caused by Borrelia persicain 93 subjects with suspected tick exposure. The 47 subjects randomized to doxycycline were given a 200 milligram dose the first dayand 100 mg per day for the next four days.

There were 26 subjects in both the doxycycline andplacebo groups with signs of tick bites, with the remainder in each grouphaving had close contact. All 10 subjects identified by blood smears as havingTBRF were part of the placebo group, suggesting the doxycyclinetreatment was 100 percent effective.

"Treatment with doxycycline is safe andefficacious in preventing TBRF after suspected exposure to ticks in a high-riskenvironment," the authors conclude. In areas where tick exposure is lessfrequent, thorough physical examinations for tick bites will help limit the useof doxycycline to those with the greatest likelihoodof infection and reduce medication-associated adverse events, they note.

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Poor Children at Higher Risk of Death from Injury

In England and Wales,inequalities persist despite overall decline in death rate

Despite the fact that overall rates of death from injury have declined over the past 20 years in England and Wales, rates for children from the poorest families have not changed and are 13-fold greater than those in the highest socioeconomic class, according to a study published online July 7 in BMJ.

Phil Edwards, of the London School of Hygiene and Tropical Medicine in London, and colleaguesanalyzed the death rates from injury in children from birth up to 15 years ofage divided according to the eight social classifications of the NationalStatistics Socio-Economic Classification (NS-SEC).

Overall, the death rate from injury among children fell from 11.1 deaths per100,000 children per year as measured by the 1981 census, to 4.0 deaths per100,000 children around the time of the 2001 census. However, for children ofthe long-term unemployed, the death rate from injury was 13.1 times higher thanthe rate for children in the NS-SEC 1 group (higher managerial and professionaloccupations). The biggest inequalities were found among deaths that occurredamong pedestrians and cyclists, deaths due to house fires and deaths that didnot have a determined cause.

"If all children in Englandand Waleshad experienced the relatively low mortality seen among children in the mostadvantaged families, there would have been 600 fewer deaths from injury andpoisoning in 2001-2003," the authors conclude.

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Whooping Cough Endemic Among U.K.Schoolchildren

Despite immunization, 40 percent of children with persistent cough testedpositive for pertussis

Nearly 40 percent of U.K. children with persistent cough show signs of infection with Bordatella pertussis, despite being vaccinated, according to a study published online July 7 in BMJ. Pertussis appears to be endemic in the United Kingdom and whooping cough should be considered in children with cough lasting two weeks or more, the report indicates.

Anthony Harnden, M.B., Ch.B., M.Sc.,of the University of Oxford in Oxford, U.K., andcolleagues conducted a study among 172 children aged 5 to 16 years who visitedtheir general practitioner with a cough of 14 days duration or more. In all, 64of the children (37.2 percent) had serological evidence of recent infectionwith Bordatella pertussis,even though 55 (85.9 percent) had been fully immunized.

Children who tested positive for whooping cough were more likely to whoop,vomit and produce sputum, have a cough that persisted for two months or morecomprising five or more coughing episodes a day, andcause disturbed sleep for their parents.

"For school-age children presenting to primary care with a coughlasting two weeks or more, a diagnosis of whooping cough should be consideredeven if the child has been immunized. Making a secure diagnosis of whoopingcough may prevent inappropriate investigations and treatment, " the authors conclude.

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Adherence to Therapy Lowers Mortality, Even with Placebo

Review of studies shows good adherence is marker for overall healthybehavior

Subjects in clinical trials who adhere to their drug therapy regimen have a lower mortality rate, even when they are part of the placebo group, according to a report in the July 1 issue of BMJ. The results support the existence of a "healthy adherer" effect in which adherence is a surrogate marker for overall healthy behavior.

Scot H. Simpson, Pharm.D., from the Universityof Alberta in Edmonton, Canada,and colleagues conducted a meta-analysis of 21 studies reporting mortality dataand level of adherence to drug therapy regimens.

Overall, good adherence to drug therapy was associated with a lower risk formortality than poor adherence (odds ratio, 0.56). And mortality risk wassimilar when considering good adherence to placebo or to beneficial drugtherapy (odds ratio, 0.56 versus 0.55, respectively).

The lower mortality seen in healthy adherers may be linked withplacebo-related effects seen in other studies, according to a commentary byBetty Chewning, Ph.D., from the University ofWisconsin-Madison. She suggests that patient-centered approaches to treatmentand motivational interviewing could yield extra value in treatment regimensthat patients agree to and believe in.

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Boost Radiotherapy Effective for Early Breast Cancer

Researchers find that extra dose nearly doubles local relapse-freesurvival at 10 years

In younger women with ductal carcinoma in situ (DCIS), a boost radiotherapy dose to the tumor site after whole breast irradiation may reduce the risk of relapse after breast-conserving surgery, according to a study published online July 6 in The Lancet Oncology.

Guenther Gruber, M.D., of the Instituteof Radiation Oncology, Kantonsspital in Aarau, Switzerland,and colleagues studied 373 DCIS patients aged 45 or younger who had undergonebreast-conserving surgery. Fifty-seven (15 percent) of the patients had noradiotherapy after surgery, 166 (45 percent) had radiotherapy without boost(median dose 50 Gy; range 40-60) and 150 (40 percent)had radiotherapy with a boost (median dose 60 Gy;range 53-76).

After a median follow-up of 72 months, the researchers found that localrelapse-free survival at 10 years was 46 percent for those who had no radiotherapy,72 percent for those given radiotherapy without boost and 86 percent for thosegiven radiotherapy and boost.

"According to guidelines and recent overviews, new studies to answerthe boost question also in DCIS are encouraged," the authors conclude."Our findings clearly suggest that the radiation dose is very importantfor local tumor control for patients with DCIS aged 45 years or younger.However, because of our study's limitations, our results can only generatehypotheses, and data from large randomized trials should answer the boostquestion, especially in patients with DCIS who are at high risk for localrelapse."

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Noma Infections in Young Children Can BePrevented

Researchers urge control plans in regions where the disfiguring infectionis prevalent

Noma, the disfiguring facial infection that primarily affects young children in sub-Saharan Africa and occasionally those in Europe and the United States, can be prevented, according to a seminar published in the July 8 issue of The Lancet.

Cyril O. Enwonwu, Ph.D., of the University of Marylandin Baltimore, and colleagues describe noma as anopportunistic infection associated with extreme poverty, poor sanitation andunsafe drinking water. According to the authors, it results from complexinteractions between malnutrition, infections and compromised immunity andoften is preceded by measles, malaria, severe diarrhea and necrotizingulcerative gingivitis. In severe cases, it rapidly progresses from gingivalinflammation to orofacial gangrene.

Although noma responds well in the acute phase toantibiotic treatment, it often causes functional and aesthetic impairments thatrequire reconstructive surgery. To increase awareness of the disease, thereshould be information campaigns at the national, regional and village levels,the authors state.

"Noma robs many children of theirfuture," the authors state. "There is urgent need for countries wherenoma is still prevalent to set up control plans thatemphasize prevention and early detection of the disease, while addressingpoverty, environmental hygiene, perinatal healthcare, maternal and infant nutrition, and timely immunization of children againstendemic diseases, particularly measles."

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Face Transplant Surgeons Describe Pioneering Procedure

Operation declared a success four-months on

The team of French researchers who successfully performed a face transplant in November 2005 provide a detailed description of the technique in a paper published online on July 4 in The Lancet.

Bernard Devauchelle, M.D., of the Centre Hospitalier Universitaire Amiens in Amiens, France,and colleagues performed the transplant of the central and lower face of abrain-dead woman onto a 38-year-old woman. The recipient had lost the distalnose, both lips, chin and parts of the cheeks as aresult of a severe dog bite.

The surgery comprised revascularization of thefacial arteries and veins, nerve and muscular repair and skin closure. Thepatient received two infusions of donor bone-marrow cells and was givenimmunosuppressive treatment with thymoglobulin, tacrolimus, mycophenolate mofetil and prednisone.

Apart from mild signs of rejection at the 20-day mark, which subsided afterthree boluses of prednisone, there were nocomplications, and the recovery process was smooth. A week after surgery, thepatient was able to eat and there was a rapid improvement in speech, althoughshe required physiotherapy to improve lip movement.

"The four-month outcome demonstrates the feasibility of this procedure.The functional result will be assessed in the future, but this graft canalready be deemed successful with respect to appearance, sensitivity, and acceptanceby the patient," the authors conclude.

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Having Diabetes Equivalent to Aging 15 Years

Diabetic patients over 40 have cardiovascular disease risk four timeshigher than peers

Diabetics fall into the high-risk category for cardiovascular disease (CVD) risk 15 years earlier than their non-diabetic counterparts, according to a study published in the July 1 issue of The Lancet.

Gillian L. Booth, M.D., of the Universityof Toronto, and colleagues conducted apopulation-based study of 379,003 diabetics and 9,018,082 non-diabetics whowere resident in Ontario, Canada in April 1994 and followedup on them to ascertain CVD events that occurred through March 2000.

Compared with non-diabetics, the transition to the CVD high-risk categoryoccurred on average 14.6 years earlier in diabetics. Men and women became highrisk for stroke, acute myocardial infarction and death from any cause at ages47.9 and 54.3 years, respectively. When the data were analyzed using a broaderdefinition of CVD that included coronary or carotid revascularization,entry into the high-risk category occurred at 41.3 and 47.7 years for diabeticmen and women, respectively.

Given that diabetics who were aged 40 years or younger did not usually fallinto the high-risk category, the authors recommend that age should be taken intoaccount when devising targeted risk-reduction strategies.

"However, further work to develop appropriate algorithms for CVD riskin young adults with type 1 and type 2 diabetes is crucially important to guidetherapeutic decisions in these individuals," they conclude.

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Marker Predicts Renal Cancer Metastasis and Survival

Testing at diagnosis could identify patients who need early systemictreatment

Researchers have identified a marker in renal cell carcinomas that can predict tumor metastasis and patient outcome, according to a study published in the July issue of The Lancet Oncology.

Zhong Jiang, M.D., ofthe University of Massachusetts Medical Center in Worcester, Mass.,and colleagues examined the expression of IMP3, an oncofetalRNA-binding protein, in 501 primary and metastaticrenal-cell tumors by western blot, immunohistochemistryand quantitative real-time polymerase chain reaction,and studied survival in 371 patients with primary tumors.

The researchers found that IMP3 expression was much higher both in metastatic tumors and primary tumors that had a highlikelihood of becoming metastatic. When they comparedIMP3-positive patients with IMP3-negative patients, they found that positivestatus was associated with significantly lower five-year metastasis-freesurvival (44 percent versus 98 percent) and a significantly lower five-yearsurvival (32 percent versus 89 percent for those with stage I tumors; 41percent versus 88 percent for those with stage II tumors, and 14 percent versus58 percent for those with stage III tumors).

"IMP3 is an independent prognostic marker that can be used at initialdiagnosis of renal-cell carcinoma to identify patients who have a highpotential to develop metastasis and who might benefit from early systemictreatment," the authors conclude.

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New Chemical Markers May Not Help Predict Heart Disease

Routine testing for C-reactive protein and 18 other risk factors may notimprove risk forecasting

Testing for novel chemical markers such as C-reactive protein levels may not help predict heart disease risk any better than traditional methods, according to a report in the July 10 issue of the Archives of Internal Medicine.

Aaron R. Folsom, M.D., of the Universityof Minnesota in Minneapolis, and colleagues analyzedfollow-up data on 15,792 adults involved in the AtherosclerosisRisk in Communities Study. The study explored the link between heart diseaseand 19 novel risk markers in adults followed up between 1987 and 1989.

The researchers found that traditional risk factors, such as cholesterollevels, blood pressure, smoking and antihypertensivedrug use, were reliable heart disease predictors. But they concluded thattesting for C-reactive protein levels and most other novel chemical markers wasunwarranted.

"Our findings suggest that routine measurement of these novel markersis not warranted for risk assessment," the authors write. "On theother hand, our findings reinforce the utility of major, modifiable risk factorassessment to identify individuals at risk for coronary heart disease forpreventive action."

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Most Clinicians Don't Follow PharyngitisGuidelines

Antibiotics over-prescribed to low-risk patients

In almost two-thirds of primary care office visits for pharyngitis, health care practitioners sidestep established guidelines, usually by testing or prescribing antibiotics to patients at low risk of streptococcal pharyngitis, according to a report in the July 10 issue of the Archives of Internal Medicine.

Jeffrey A. Linder, M.D., of Brigham and Women's Hospital in Boston, and colleagues investigated treatmentstrategies used during 2,097 visits by adults with pharyngitisto Boston-area clinics.

The researchers found that clinicians followed AmericanCollege of Physicians' strategyguidelines in 12 percent of visits, and AmericanCollegeof Physicians' and Infectious Diseases Society of America's testing guidelinesin 30 percent of visits. But clinicians followed no strategy in 66 percent ofvisits, the researchers report.

"The major problem in the testing and treatment of adults with pharyngitis is not which guideline to follow, but thatclinicians usually fail to follow any guideline," the authors write.

In an editorial, Robert M. Centor, M.D., of theUniversity of Alabama School of Medicine in Birmingham, and acolleague write that "adult pharyngitis deservesa coordinated approach. We can greatly decrease antibiotic use if we wouldfocus on withholding both testing and antibiotic treatment from those patientswho have no clinical indication for these strategies."

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Low Testosterone Linked to Anemia Risk in Elderly

Non-anemic older adults with low testosterone levels run risk of beinganemic three years later

Older adults with low testosterone levels may run a higher risk of developing anemia, according to a report in the July 10 issue of the Archives of Internal Medicine.

Luigi Ferrucci, M.D., Ph.D., of the NationalInstitute on Aging in Baltimore, and colleagues evaluated testosterone andhemoglobin levels in 905 people aged 65 or older who did not have cancer orkidney problems, and who were not undergoing antiandrogenictreatment.

The researchers found that among the 31 men and 57 women who had anemia, hemogloblin levels were linked to testosterone levels.

Men in the lowest quartile of total and bioavailabletestosterone were 5.4 times more likely than men in the highest quartile to beanemic, while women in the lowest testosterone quartile were 2.1 times morelikely to be anemic than women in the highest quartile.

Further, men and women who were not anemic but who had low levels of totaland bioavailable testosterone were significantly morelikely than those with normal testosterone levels to be anemic at a three-yearfollow up.

"Older men and women with low testosterone levels have a higher risk ofanemia," the authors conclude.

The study was funded in part by a grant from Ortho Biotech Clinical Affairs,for which two of the researchers served as consultants.

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Healthy Habits May Help Prevent Some Types of Stroke

Study of women finds that not smoking, moderate drinking, high-fiber dietcould lower risk

Women who avoid smoking, drink moderately, eat a healthy diet and exercise regularly may lower their risk of ischemic stroke, but not hemorrhagic stroke, according to a report in the July 10 issue of the Archives of Internal Medicine.

Tobias Kurth, M.D., of Brigham and Women'sHospital in Boston,and colleagues studied lifestyle and stroke data on 37,636 women aged 45 orolder involved in the Women's Health Study. The researchers found that therewere 450 strokes among the women over the next 10 years.

Women leading a healthier lifestyle (17-20 health index points) had a lowerrisk of total stroke (multivariable-adjusted hazard ratio, 0.45), and ischemic stroke (HR, 0.29) compared with women who did nothave a healthy lifestyle (0-4 health index points). However, there was noassociation between a healthy lifestyle and hemorrhagic stroke (HR, 1.27). Theresearchers defined healthy living as having never smoked, consuming four to10.5 alcoholic drinks weekly, exercising at least four times weekly, low bodymass index and a high-fiber diet rich in omega-3 fatty acids andpolyunsaturated fats.

"In this large prospective cohort of apparently healthy women, ahealthy lifestyle consisting of abstinence from smoking, low body mass index,moderate alcohol consumption, regular exercise and healthy diet was associatedwith a significantly reduced risk of total and ischemicstroke but not of hemorrhagic stroke," the authors write.

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Exercise Benefits Patients with Peripheral Arterial Disease

Study finds that high physical activity levels are associated with lowermortality

Physically active people with peripheral arterial disease (PAD) have lower rates of mortality and cardiovascular events than their sedentary counterparts, according to a study published online July 3 in Circulation: Journal of the American Heart Association.

Mary M. McDermott, M.D., of NorthwesternUniversity's Feinberg School of Medicine in Chicago, and colleaguesstudied 460 men and women with PAD and followed them for a mean of 57 months.The researchers assessed levels of physical activity of all patients atbaseline and used vertical accelerometers to measure physical activity in 225patients during a seven-day period.

The investigators found that higher physical activity levels measured byvertical accelerometer were associated with lower all-cause mortality. Comparedto patients in the highest quartile of accelerometer-measured physicalactivity, they found that those in the lowest quartile had significantlyincreased total mortality (hazard ratio 3.48). They observed similar resultsfor the combined outcome of cardiovascular events or cardiovascular mortality.

"Future study with a clinical trial is necessary to determine whetherinterventions that increase physical activity levels during daily life reducemortality in patients with PAD," the authors conclude. "In themeantime, the present findings suggest that clinicians should encouragepatients with PAD to increase their physical activity during daily life."

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Healthy Habits Could Prevent Most Coronary Events

Researchers identify five healthy choices that reduce risk in middle-agedand older men

In middle-aged and older men, a combination of five healthy lifestyle practices -- healthy diet, moderate-to-vigorous activity for at least 30 minutes a day, maintenance of a body mass index (BMI) of less than 25 kg/m2, not smoking and drinking alcohol only in moderation -- may prevent a majority of coronary heart disease (CHD) events, according to a study published online July 3 in Circulation: Journal of the American Heart Association.

Stephanie E. Chiuve, Sc.D.,of the Harvard School of Public Health in Boston,and colleagues studied 42,847 male health professionals aged 40 to 75 who weredisease-free in 1986 and followed them for 16 years.

The researchers found that men who were at low risk for all five lifestylefactors had a lower risk of CHD (relative risk: 0.13) compared with men whowere not low risk in any lifestyle variable. Among the entire cohort, theydetermined that 62 percent of coronary events may have been prevented with alow-risk lifestyle. Among men taking medication for hypertension or hypercholesterolemia, they determined that such a lifestylemay have prevented 57 percent of all coronary events.

"This study underscores the extent to which healthy lifestyle changescan lower the risk of CHD, even during middle age or later in life," theauthors state.

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Researchers Forecast Epidemic of AtrialFibrillation

If incidence continues rising, nearly 16 million Americans could beaffected by 2050

The incidence of atrial fibrillation has increased significantly since 1980. If the rate of increase continues, atrial fibrillation could become an epidemic affecting 15.9 million Americans by 2050, according to a study published online July 3 in Circulation: Journal of the American Heart Association.

Teresa S.M. Tsang, M.D., of the Mayo Clinic in Rochester,Minn., and colleagues studied 4,618 Olmsted County, Minn.,adults who were diagnosed with atrial fibrillationbetween 1980 and 2000.

In 1980, the researchers found that the age-adjusted incidence of atrial fibrillation in OlmstedCountywas 3.04 per 1,000 person-years. By 2000, they found that the incidence hadincreased to 3.68, a relative increase of 12.6 percent over 21 years. Theyfound no difference in incidence rates between men and women.

"Such an increase in age-adjusted incidence suggests a relativelyconservative projection of a threefold increase in the number of persons with atrial fibrillation over the next 50 years," theauthors conclude. "Aggressive intervention and primary prevention ofreversible risk factors of atrial fibrillation arepivotal to contain this epidemic."

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Chinese Acupuncture May Improve Knee Osteoarthritis

But researchers say more research needed to determine if effects are dueto psychology of needling

Traditional Chinese acupuncture may be more effective than medical management alone in the treatment of patients with osteoarthritis of the knee, according to a study in the July issue of the Annals of Internal Medicine.

Hanns-Peter Scharf,M.D., of the University Hospital Mannheim in Germany, and colleagues conducted a26-week study of 1,007 osteoarthritis patients whoreceived up to six physiotherapy sessions and as-needed anti-inflammatory drugs.The subjects were randomly assigned to receive an additional 10 sessions oftraditional Chinese acupuncture, 10 sessions of sham acupuncture orconservative therapy.

The researchers defined success as at least a 36 percent improvement inscores on the Western Ontario and McMaster Universities OsteoarthritisIndex (WOMAC) score. They found success rates of 53.1 percent for traditionalChinese acupuncture, 51 percent for sham acupuncture and 29.1 percent forconservative therapy.

"We believe that our findings support the role of acupuncture in the multimodal treatment of patients with pain and functionallimitations due to osteoarthritis of the knee, evenif the mechanisms of its effects remain unclear," the authors conclude."Acupuncture could improve conservative therapy and reduce the use ofanalgesics. Further investigation is necessary to determine whether themechanism of the observed effect of acupuncture is due to physiologic effectsof needling, intensity of provider contact, or placebo effects."

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Mediterranean Diets Linked to Heart-Healthy Effects

Such diets may have a greater effect than a low-fat diet oncardiovascular risk factors

Mediterranean diets including nuts or olive oil may have more beneficial cardiovascular effects than a standard low-fat diet, according to a study published in the July issue of the Annals of Internal Medicine.

Ramon Estruch, M.D., of the University ofBarcelona in Spain, and colleagues randomly assigned 772 healthy Spanishvolunteers aged 55 to 80 with high cardiovascular risk to either a standardlow-fat diet, a Mediterranean diet including one liter per week of virgin oliveoil or a Mediterranean diet including 30 grams per day of walnuts, hazelnutsand almonds.

After three months, the researchers found that subjects on the Mediterraneandiets had lower levels of blood pressure, cholesterol and blood sugar than thesubjects on the standard low-fat diet and were better able to maintain theirdiets. They also found that the Mediterranean diet with olive oil reducedC-reactive protein levels by a mean of 0.54 mg/L compared with the low-fatdiet.

"Our results suggest that the healthy effects of the Mediterranean dietobserved in epidemiologic studies are exerted partlythrough plausible mechanisms: improved lipid profiles and reductions in bloodpressure, insulin resistance, and systemic markers of inflammation," theauthors conclude. "An increasing body of knowledge supports theMediterranean diet as a useful tool in managing individuals who are at highrisk for coronary heart disease."

Several businesses donated olive oil and nuts for the study.

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