Latest Research

March 2, 2007

A summary of the "must-read" articles from the journals in that pile on your desk.

Intranasal Influenza Vaccine Benefits Most Young Children

Fewer cases of influenza, but more cases of wheezing and hospitalizations in infants aged 6 to 11 months given nasal spray

In young children who do not have a history of asthma or wheezing, live attenuated influenza vaccine delivered in a nasal spray is more effective than inactivated vaccine delivered intramuscularly, according to the results of a study in the Feb. 15 issue of the New England Journal of Medicine.

Robert B. Belshe, M.D., of Saint Louis University Health Sciences Center in St. Louis, and colleagues studied children aged 6 months to 59 months who were randomized to receive either cold-adapted trivalent live attenuated vaccine or trivalent inactivated vaccine and followed through the 2004-2005 flu season. Patients treated with nasal spray were given a placebo injection, and those who received the vaccine injection received a placebo nasal spray.

Of the 7,852 children who completed the study, the researchers found that the live attenuated vaccine group developed 54.9 percent fewer cases of culture-confirmed influenza than the other group. The live attenuated vaccine was also more effective against both antigenically well-matched and drifted viruses. But a higher percentage of infants aged 6 to 11 months in the live vaccine group experienced wheezing episodes (3.8 percent versus 2.1 percent) or were hospitalized for any cause within 180 days postvaccination (6.1 percent versus 2.6 percent).

The intranasal spray should be a "highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing," the authors conclude.

"Further discussion and careful review of the safety data for cold-adapted trivalent live attenuated vaccine by the U.S. Food and Drug Administration and others are needed before developing guidance on the use of this vaccine versus trivalent inactivated vaccine in young children," state the authors of an accompanying editorial.

The study was supported by MedImmune.

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Methylprednisolone May Not Help Treat Kawasaki Disease

Study shows no difference in clinical outcome, hospital stay compared to placebo

Methylprednisolone should not be added to conventional immunoglobulin therapy for routine primary treatment of children with Kawasaki disease, according to results from a randomized, double-blind, placebo-controlled trial published in the Feb. 15 issue of the New England Journal of Medicine.

Jane Newburger, M.D., M.P.H., of Children's Hospital in Boston, and colleagues conducted the study to determine whether a single pulsed dose of intravenous methylprednisolone at 30 mg per kilogram of body weight, in addition to standard therapy, would reduce the risk of coronary artery abnormalities in 199 pediatric patients with fewer than 10 days of fever compared with placebo.

Patients in both study groups had similar coronary dimensions at one and five weeks after randomization, had similar number of days in the hospital and days with fever, the same retreatment rates of intravenous immune globulin and had similar numbers of adverse events. The methylprednisolone group did have a significantly shorter initial hospital stay and lower sedimentation rate at one week, however.

"Since post hoc subgroup analysis suggested that primary therapy with intravenous methylprednisolone might benefit children with persistent fever after treatment with intravenous immune globulin, future prospective studies should explore the usefulness of corticosteroid or other immunomodulatory therapies in children at highest risk for resistance to intravenous immune globulin," the authors write.

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Surgery Bests Endoscopic Drainage for Pancreatitis Pain

Randomized study shows 75 percent reduction in pain with surgery compared with 32 percent for endoscopy

Surgery is more effective than endoscopic treatment for relief of pain in patients with chronic pancreatitis, according to a report in the Feb. 15 issue of the New England Journal of Medicine.

Djuna L. Cahen, M.D., from the Academic Medical Center in Amsterdam, the Netherlands, and colleagues randomly assigned 39 symptomatic patients with chronic pancreatitis to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. Patients were followed-up for two years to assess pain relief, physical and mental health, and morbidity and mortality among other measures.

The 20 patients randomized to surgery reported lower Izbicki pain scores and better scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire than the 19 who underwent endoscopy. Overall, 75 percent of patients assigned to surgery reported complete or partial pain relief compared to 32 percent of patients assigned to endoscopic drainage. Rates of complications and length of hospital stay were similar, but those receiving endoscopic procedures required more procedures (eight versus three) than those receiving surgery.

"Although surgical drainage in patients with dilated pancreatic ducts and intraductal stones gives better pain relief than does endoscopic therapy and requires fewer procedures, endoscopic therapy remains a reasonable treatment option, depending on patient preferences," according to Grace H. Elta, M.D., of the University of Michigan in Ann Arbor, in an accompanying editorial.

The study was supported by an unrestricted grant from AstraZeneca. Some of the authors have received compensation from Boston Scientific. Elta reports receiving a consulting fee from Ethicon Endo-Surgery and grant support from Boston Scientific.

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Colorectal Cancer Has Epigenetic Inheritance Pattern

Epigenetic MLH1 mutation passed from mother to son, but erased in his spermatozoa

A mutant colorectal cancer susceptibility gene has an epigenetic pattern of inheritance in some families, and can be expressed in offspring or revert to normal, according to a report in the Feb. 15 issue of the New England Journal of Medicine.

Robyn Ward, Ph.D., of St. Vincent's Hospital in Sydney, Australia, and colleagues obtained tissue samples from patients who developed colorectal cancer at an early age, and their family members, to determine the status of the MLH1 DNA mismatch repair gene. Mutation in MLH1 is linked to hereditary nonpolyposis colorectal cancer and can occur sporadically in tumors through promoter DNA hypermethylation.

The investigators found two families with an epigenetic mutation in MLH1, one of which showed transmission from mother to son despite being erased in his spermatozoa. Three other siblings from these two families inherited the maternal allele but showed reversion to normal expression.

Acquired epigenetic changes can be erased during early embryogenesis and in the germ line during development, according to an accompanying editorial by Roger G. Gosden, Ph.D., and Andrew P. Feinberg, M.D. However, results from this study show that "this eraser may leave smudges, potentially allowing disease to be transmitted epigenetically as well as genetically."

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Studies Suggest Drug-Eluting Stents As Safe As Bare Metal

In clinical trials both types have similar rates of death and myocardial infarction

Drug-eluting stents are as safe as bare-metal stents when used on the basis for which they were granted approval, but their widespread off-label use has made it difficult to assess safety in a real-world setting, according to five studies and three editorials published online Monday, ahead of print publication in the March 8 issue of the New England Journal of Medicine.

The articles represent presentations and discussions during a meeting of the U.S. Food and Drug Administration's Circulatory System Devices Advisory Panel held on Dec. 7-8, 2006.

Three studies, led by Patrick W. Serruys, M.D., Ph.D., Adnan Kastrati, M.D., and Donald E. Cutlip, M.D., pooled data from clinical trials and concluded that rates of death, myocardial infarction and stent thrombosis were similar in sirolimus-eluting stents and bare-metal stents.

However, Bo Lagerqvist, M.D., Ph.D., and colleagues conclude that drug-eluting stents were associated with an increased rate of death, as compared with bare-metal stents, a trend that did not emerge until after six months of use. A study by Gregg W. Stone, M.D., and colleagues found that while there was a higher incidence of stent thrombosis after one year with sirolimus-eluting stents and paclitaxel-eluting stents compared with bare-metal stents, there was a significant reduction in target-lesion revascularization with both drug-eluting stents.

"Off-label use has made assessments of stent safety beyond the setting of clinical trials considerably more challenging. There is also the important matter of adjunctive antiplatelet therapy," write the Journal's editors in an editorial. "The optimal duration of therapy has not yet been precisely determined."

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Low Fish Intake in Pregnancy May Reduce IQ in Offspring

Recommendations to limit seafood consumption during pregnancy could do more harm than good

Women who consume less than 340 grams of seafood (three portions) per week during pregnancy may have offspring at elevated risk for suboptimal IQ, fine motor skill development, communication, and other social and developmental outcomes compared to women who consume more fish, according to a report published Feb. 17 in The Lancet. U.S. government agencies recommend that pregnant women limit seafood consumption to 340 g per week.

Joseph Hibbeln, M.D., of the U.S. National Institute on Alcohol Abuse and Alcoholism, and colleagues analyzed data from 11,875 pregnant women in Bristol, U.K., who gave birth in 1991 and 1992. Women were surveyed during pregnancy and then at various times after birth as part of the Avon Longitudinal Study of Parents and Children (ALSPAC). Child IQ was assessed at age 8 and 28 potential confounders were considered in multivariate logistical analyses.

Even considering social and other confounders, children whose mothers consumed less than 340 g of seafood per week during pregnancy were at elevated risk for being in the lowest quartile of verbal IQ (odds ratio for no seafood intake, 1.48) compared to those who consumed more. Fine motor skill development, communication, and other social and developmental outcomes were also lower.

"The information obtained in ALSPAC shows no evidence that consumption of more than three portions of seafood a week during pregnancy has an adverse effect on the behavior or development of the child," the authors write. "By contrast, maternal consumption of more than 340 g seafood a week was beneficial for the child's neurodevelopment."

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Single Antibiotic Course Can Lead to Long-Term Resistance

Resistance to macrolide antibiotics lasts as long as six months

A single course of macrolide antibiotics can lead to macrolide-resistance in oral streptococci that lasts as long as six months, according to study findings published in the Feb. 10 issue of The Lancet.

Herman Goossens, M.D., of University Hospital Antwerp in Belgium, and colleagues randomized 224 healthy adults to placebo or the macrolide antibiotics clarithromycin (500 mg twice a day for seven days) or azithromycin (500 mg once a day for three days). Pharyngeal swabs were taken for six months to assess the resistance of streptococci to macrolides.

The researchers found that both antibiotics significantly increased the proportion of resistant streptococci. The proportion was higher after azithromycin treatment, with a peak difference of 17.4 percent at day 28. Resistance increased by a mean of 50 percent in the clarithromycin group, peaking at day eight, while resistance increased by a mean of 53.4 percent in the azithromycin group, peaking at day four. Clarithromycin selected for the erm(B) gene, conferring high-level macrolide resistance, while azithromycin selected for resistance in the early post-therapy phase.

"The key message is that antibiotic prescribing affects the patient, their environment and all the people that come into contact with that patient or with their environment," Stephanie J. Dancer, M.D., from Southern General Hospital in Glasgow, Scotland, writes in an accompanying editorial. "Doctors who understand this point can influence the risk of antimicrobial resistance, not only for our current patients but also for patients in the future."

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Benefits of Annual Checkups Seem to Outweigh Risks

Patients who undergo well exams more likely to be up-to-date with preventive services

One or more well visits per year may benefit patients by encouraging them to undergo routine screening tests and by reducing their health worries in general, according to a review in the Feb. 20 issue of the Annals of Internal Medicine.

L. Ebony Boulware, M.D., of Johns Hopkins School of Medicine in Baltimore, and colleagues reviewed 21 studies that assessed the benefits and harms of periodic health exams.

Patients who underwent periodic health examinations were more likely to have gynecological examinations, PAP tests, cholesterol screening and fecal occult blood tests than their counterparts who did not. One study showed that patients who underwent periodic exams tended to worry less about their health. What's more, there did not appear to be any harm associated with period health exams, such as undergoing unnecessary or inappropriate tests.

"Although additional research is needed to clarify the long-term benefits, harms and costs of receiving the periodic health exam, evidence of benefits in this study justifies implementation of the periodic health exam in clinical practice," the researchers conclude.

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Gap Between Specialist, Primary Care Incomes Grows

The expanding divide between primary care and specialist incomes undermines U.S. health care

The income disparity between primary care physicians and specialists continues to grow and needs urgent attention in order to keep attracting medical school graduates into primary care, according to a Perspective in the Feb. 20 issue of the Annals of Internal Medicine.

Thomas Bodenheimer, M.D., of the University of California San Francisco, and colleagues analyzed the results of the Resource-Based Relative Value Scale, a tool meant to decrease the disparity between office visit charges and fees for procedures.

The researchers found that the system did not succeed in closing the gap between specialist and primary care physicians' incomes. This is because private insurance companies often pay more than Medicare for procedures but not for office visits; Medicare efforts to limit physician costs targets primary care physicians; the Relative Value Scale Update Committee, a specialist-dominated body, strongly influences the five-year fee updating system; and the number of procedures has grown faster than the number of office visits, benefiting specialists.

"Payment reform is essential to guarantee a healthy primary care base to the U.S. health care system," the authors write.

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Immunochemical FOBT May Be More Sensitive, Specific

Three-sample tests detect neoplasms in above-average risk people

Three-sample quantitative immunochemical fecal occult blood tests (FOBTs) have high sensitivity and specificity for detecting colorectal cancer and neoplasias in above-average risk people, according to the results of a study published in the Feb. 20 Annals of Internal Medicine.

Zohar Levi, M.D., of the Rabin Medical Center in Petach Tikva, Israel, and colleagues conducted a prospective, cross-sectional study of 1,000 patients, some of whom were asymptomatic but at increased risk for colorectal neoplasia, to measure the sensitivity and specificity of quantitative immunochemical FOBTs.

Ninety-one patients had clinically significant neoplasms identified by colonoscopy: cancer in 17 and advanced adenomas in 74. Using three immunochemical FOBTs and a specificity threshold of 75 ng/mL of buffer, sensitivity was 94.1 percent and specificity was 87.5 percent for cancer, and 67 percent and 91.4 percent for neoplasia. The authors caution that these results may not apply to those at average risk.

"The ability to choose different positivity thresholds makes quantitative immunochemical FOBT a potentially important test for colorectal cancer screening. It is a better test than guaiac-based FOBT for detecting occult bleeding and should be preferred to guaiac-based FOBT wherever FOBT is a component of a recommended screening strategy," writes Thomas Imperiale, M.D., of Indiana University Medical Center in Indianapolis, in an accompanying editorial.

One of the authors has received grants from the Eiken Chemical Company.

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Siestas Linked to Lower Heart Disease Mortality

Association strongest in working men

Taking siestas of any frequency or duration is associated with about a one-third reduction in mortality from coronary heart disease, particularly in working men, according to study findings published in the Feb. 12 issue of the Archives of Internal Medicine.

Androniki Naska, Ph.D., of the University of Athens Medical School in Greece, and colleagues examined the association between taking midday naps and mortality from coronary heart disease in 23,681 healthy Greek men and women.

After a mean follow-up of 6.32 years, the researchers found that subjects who took siestas had a lower mortality from heart disease (mortality ratio 0.66). The magnitude of the reduction varied depending on whether the napping was occasional or regular. The association was strongest among working men, according to the study.

"After controlling for potential confounders, siesta in apparently healthy individuals is inversely associated with coronary mortality, and the association was particularly evident among working men," Naska and colleagues conclude.

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Medicare Covers Colonoscopies, But Screening Gap Persists

Age, race/ethnicity, gender, income affect likelihood of screening since expanded Medicare coverage

Although Medicare coverage of colonoscopy started in 2001 for those at average risk, there are still disparities in colon cancer screening among Medicare beneficiaries based on age, race/ethnicity, gender and income, according to the results of a study published in the Feb. 12 issue of the Archives of Internal Medicine.

Joan M. Neuner, M.D., M.P.H., and colleagues from the Medical College of Wisconsin in Milwaukee, examined the rates of colorectal cancer screening in 596,470 Medicare recipients at average risk in New York, Florida and Illinois in 2002 and 2003.

The researchers found that 18.3 percent of beneficiaries had undergone a screening test. Non-whites were less likely to be screened than whites (relative risk, 0.52). Whites living in higher income areas were more likely to be screened (RR 1.19 for men, 1.09 for women), which was not the case for non-whites. Screening colonoscopy decreased with age, with a relative risk of 0.41 for men and 0.32 for women for the oldest recipients (at least 80 years old).

"Despite the expansion of Medicare coverage for colorectal cancer screening, there still remain significant disparities between sex and racial/ethnic groups in screening practices," Neuner and colleagues conclude.

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Breast Cancer Patients Benefit From Exercise Program

Improvements seen in various aspects of physical and psychological quality of life

A supervised group exercise program can have beneficial effects on breast cancer patients' physical and psychological function, according to a report in the Feb. 16 issue of BMJ.

Nanette Mutrie, Ph.D., of Strathclyde University in Glasgow, Scotland, and colleagues randomized 203 early-stage breast cancer patients, aged 29 to 76, to a 12-week group exercise program or conventional care. The patients were treated in three oncology clinics in Scotland, and followed for over six months.

At three months, the beneficial effects of the exercise program in terms of intervention minus control included an extra 129 meters walked in 12 minutes, 182 minutes of moderately intense activity per week, 2.6 points on the shoulder mobility score, 2.5 for breast cancer quality of life, and 4.0 for mood improvement in the exercise group. There was no significant difference in terms of general quality of life. Most of these benefits were maintained at the six-month follow-up.

"Supervised group exercise provided functional and psychological benefit after a 12-week intervention and six months later," the authors write. "Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services."

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Anemia Drug Boosts Exercise Capacity in HF Patients

Darbepoetin alfa treatment improves hemoglobin, exercise time and quality of life in study of anemic heart failure patients

Darbepoetin alfa can help maintain hemoglobin concentrations and improve the health-related quality of life of patients with symptomatic chronic heart failure and anemia, according to a report in the Feb. 20 issue of the Journal of the American College of Cardiology.

Ken McDonald, M.D., of St. Vincent's University Hospital in Dublin, Ireland, and colleagues conducted a multicenter, randomized, double-blind trial of 0.75 microgram/kg darbepoetin alfa or placebo every two weeks for 26 weeks to determine if the treatment improves exercise capacity in these patients.

The treatment group showed a 1.5 gram per deciliter improvement in hemoglobin levels, improved peak VO2, and performed an average of 108 seconds longer in exercise tests. Patients receiving darbepoetin also had improved Patient's Global Assessment of Change scores although they did not show improvement in other health questionnaires.

"We need to learn more on erythropoietin dose regimens; definition of patients likely to benefit from erythropoietin, including functional severity, hemoglobin threshold for intervention, and target values; and on the long-term safety," writes Michel Komajda, M.D., of University Pierre Marie Curie in Paris, France, in an accompanying editorial. "Until this information is available, we cannot make any recommendation on the potential benefit of erythropoietin in the management of chronic heart failure."

The study was funded by Amgen and some of the authors have received compensation from Amgen or Hoffmann-La Roche.

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Tiny Sensor Can Remotely Monitor Pulmonary Artery

Acoustic wireless communication technology provides repeated pulmonary artery measurement

A miniature sensor can be implanted in the pulmonary artery of heart failure patients to transmit pressure measurements remotely using acoustic wireless communication, according to a pilot study published in the Feb. 20 issue of the Journal of the American College of Cardiology. The findings suggest that such deeply implanted sensors could be used for a variety of conditions.

Yoseph Rozenman, M.D., of The E. Wolfson Medical Center in Holon, Israel, and colleagues implanted a sensor using right heart catheterization into eight pigs and 10 patients with congestive heart failure. Six months later they conducted macroscopic and histopathological examination. The accuracy of the measurements taken using the sensor and remote wireless technology was compared with simultaneous pressures from a Millar catheter.

Implantation was achieved successfully; the implants provided repeated pulmonary artery pressure tracings and there were no complications. There was a standard deviation between the implant and the Millar readings of 1.45 mm Hg in animals and 1.2 mm Hg in humans, and the data generated by the implants was useful for the management of patients.

"This study demonstrated that wireless communication with a miniature pulmonary artery pressure sensor is feasible," the authors conclude. "Repeated, high-quality pulmonary artery tracings were easily obtained. Acoustic telemetry makes possible multiple novel monitoring and therapeutic interventions based on communication with deeply implanted devices in the heart and elsewhere."

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Imaging May Help in Diagnosis of Chest Pain

Multi-slice computed tomography is faster, cheaper than standard care

Multi-slice computed tomography (MSCT) can determine whether coronary disease is the source of chest pain in 75 percent of patients and is significantly faster and cheaper than standard care, researchers report in the Feb. 27 issue of the Journal of the American College of Cardiology.

Gilbert L. Raff, M.D., and colleagues from William Beaumont Hospital in Royal Oak, Mich., randomized 197 patients with low-risk acute chest pain to MSCT or standard of care diagnostic work-ups. Patients with normal MSCT scans were eligible for immediate discharge, those whose scan showed severe stenosis (over 70 percent) underwent invasive angiography, and those whose scan showed intermediate lesions or an unclear diagnosis underwent nuclear stress scans. Patients receiving standard of care underwent nuclear stress scans.

The researchers found that MSCT was able to determine whether coronary disease was the source of chest pain in 75 percent of patients. MSCT diagnosis was also significantly faster (3.4 hours versus 15 hours) and significantly cheaper ($1,586 versus $1,872), and fewer patients undergoing MCST required further evaluations for recurrent chest pain (2 percent versus 7 percent).

"Multi-slice computed tomographic coronary angiography can definitely establish or exclude coronary disease as the cause of chest pain," Raff and colleagues conclude. "However, inability to determine the physiological significance of intermediate severity coronary lesions and cases with inadequate image quality are present limitations."

This work was supported in part by a grant from Minestrelli Advanced Cardiac Research Imaging.

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Post-Defibrillator Implant Driving Restrictions Clarified

Patients who receive ICD for primary prevention can drive one week later

Patients who receive an implantable cardioverter-defibrillator (ICD) for primary prevention can resume driving one week after implantation, according to a scientific statement from the American Heart Association and the Heart Rhythm Society. The statement is published in the March issue of Heart Rhythm and Circulation: Journal of the American Heart Association.

"This updated joint AHA/HRS scientific statement will remove impediments to accessing this life-saving therapy for patients and families contemplating ICD therapy for primary prevention," Dwight W. Reynolds, M.D., president of the Heart Rhythm Society, said in a statement.

Andrew E. Epstein, M.D., and committee members concluded that patients with ICDs for primary prevention who have no arrhythmia symptoms can resume driving a private automobile one week after implantation. The guidelines do not apply to commercial drivers. If a patient is being treated for ventricular tachycardia or ventricular fibrillation, particularly if they have cerebral hypoperfusion symptoms, then they would fall under the same driving guidelines for patients with ICDs for secondary prevention.

"Patients with ICDs for primary prevention must be instructed that impairment of consciousness is a possible future event," according to the guidelines.

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Secondhand Smoke Boosts Fibrinogen, Homocysteine

Effect on cardiovascular biomarkers is one-third to one-half that seen in active smokers

Even a low level of exposure to secondhand smoke increases cardiovascular disease biomarkers, such as fibrinogen and homocysteine, according to a report in the Feb. 12 issue of Circulation: Journal of the American Heart Association.

Andrea Venn, Ph.D., of the University of Nottingham in the U.K., and a colleague conducted a cross-sectional study of blood cotinine levels and cardiovascular biomarkers among 7,599 non-smoking adults from the Third National Health and Nutrition Examination Survey. Eighteen percent had no detectable cotinine and the remaining participants had either low or high levels. Of these, 18 percent with low levels and 56 with high levels of cotinine reported living with a smoker or occupational exposure to tobacco smoke.

Participants with high or low cotinine had fibrinogen levels that were 9 to 10 milligrams per deciliter of blood higher than those with no detectable cotinine and homocysteine levels that were 0.8 micromoles per liter of blood higher than their counterparts without detectable cotinine. No effect was seen on C-reactive protein and white blood cell count. Overall, the cotinine levels seen in the new study were about 0.1 percent of those in active smokers, but the effects on biomarkers were about one-third to one-half of those for active smoking.

"These findings lend support to existing evidence that secondhand smoke has a clinically important effect on susceptibility to cardiovascular disease," the researchers conclude.

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Estrogen Receptor Gene Has No Effect on Heart, Stroke Risk

Modest increase in breast cancer risk, but no link to cardiovascular disease, hip fracture and lipoprotein response to HRT

The estrogen receptor α (ESR1) IVS1-397T/C polymorphism has no impact on the risk of cardiovascular disease, hip fracture, most reproductive cancers or lipoprotein response to hormone replacement therapy, according to a study published online Feb. 19 in Circulation: Journal of the American Heart Association. However, there is a modest increase in breast cancer risk associated with the TT genotype.

Alisa D. Kjaergaard, M.D., of Herlev University Hospital in Herlev, Denmark, and colleagues conducted a study of 9,244 people in the Danish general population who were followed up for 23 to 25 years. Among the sample, the frequency of the CC, CT and TT genotypes was 21 percent, 50 percent and 29 percent, respectively.

Rates of cardiovascular disease, reproductive organ cancers and hip fracture were observed. The authors also compared 2,495 patients with ischemic heart disease, 856 with ischemic cardiovascular disease and 1,256 with breast cancer to population-based controls.

The only difference in odds ratio across the three genotypes was a 40 percent higher risk of breast cancer in those with the TT genotype compared with the CC genotype. For all other risk factors there was no difference.

"Important new findings include that our study rebuts the current hypothesis that the ESR1 IVS1-397T/C polymorphism is associated with risk of myocardial infarction and other cardiovascular diseases in both men and women but that this polymorphism possibly is associated with a modest increase in risk of breast cancer," the authors conclude.

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Women Less Likely to Have Post-MI Angioplasty

Age-adjusted data shows lower rates of percutaneous coronary intervention, higher mortality compared to men

Although the higher myocardial infarction mortality rates in women are partially attributable to age, a new study suggests that even after age-adjustment, women with acute myocardial infarction have higher in-hospital mortality rates than men, which is due in part to a lower likelihood of percutaneous coronary intervention. The findings were published online Feb. 19 in Circulation: Journal of the American Heart Association.

Carine Milcent, Ph.D., of the PSE Paris-Jourdan Sciences Economiques, in Paris, France, and colleagues analyzed French hospital admission data for 74,389 patients who were hospitalized with acute myocardial infarction, of whom 30 percent were women.

The average age of female patients was 75 and male patients was 63, and the mortality rate was 14.8 percent in women and 6.1 percent in men. Overall, 7.4 percent of men and 4.8 percent of women underwent percutaneous coronary intervention. Of these, 24.4 percent of men and 14.2 percent of women received a stent. The absolute mortality rate adjusted for age and co-morbidities was 1.95 percent higher in women, 0.46 percent of which was attributed to reduced use of procedures.

"Simulations suggest that women would derive benefit from more frequent use of percutaneous coronary intervention, although these procedures appear less protective in women than in men," the authors conclude.

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Heart Disease Prevention Guidelines Updated for Women

American Heart Association recommendations based on most recent research

The American Heart Association has updated guidelines for the prevention of cardiovascular disease in women, which will be published in a report in the Mar. 13 issue of Circulation: Journal of the American Heart Association.

Lori Mosca, M.D., M.P.H., Ph.D., of the American Heart Association, chaired a panel of experts that reviewed the guidelines released in 2004 and updated them with results of evidence-based research on the prevention of cardiovascular disease. They looked at research published between January 2003 and June 2006. Out of an initial 5,774 articles identified, 828 were selected for full-text screening and 246 met the panel's criteria for inclusion in the updated recommendations.

The updated recommendations cover a range of factors associated with cardiovascular risk and include intervention recommendations for lifestyle factors, risk factors and preventive drugs. They also outline interventions that are not useful or may be harmful and suggest future directions in research, including more rigorous testing, communicating risks and the role of genetics.

"Population-wide strategies are necessary to combat the pandemic of cardiovascular disease in women, because individually tailored interventions alone are likely insufficient to maximally prevent and control cardiovascular disease," the authors write. "Public policy as an intervention to reduce gender-based disparities in cardiovascular disease preventive care and improve cardiovascular outcomes among women must become an integral strategy to reduce the global burden of cardiovascular disease."

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Oral Estrogen, But Not Patch, Boosts Clot Risk with HRT

Progestogen derivative also influences venous thromboembolism risk

Oral, but not transdermal, estrogen is associated with a fourfold increase in the risk of venous thromboembolism (VTE) in postmenopausal women taking hormone therapy, and VTE risk is also influenced by the progestogen derivative used, according to the results of a study published in the Feb. 20 issue of Circulation: Journal of the American Heart Association.

Pierre-Yves Scarabin, M.D., of Inserm Unit 780 in Villejuif, France, and colleagues examined 271 postmenopausal women with idiopathic VTE and 610 matched controls.

Compared with non-users of estrogen, the risk of VTE was higher for users of oral rather than transdermal estrogen (odds ratio, 4.2 and 0.9, respectively). Micronized progesterone and pregnane derivatives were not associated with VTE (OR, 0.7 and 0.9, respectively), while norpregnane derivatives increased the risk of VTE (OR, 3.9).

"At present, the totality of evidence appears compelling enough to suggest that transdermal preparations be considered, among other factors relevant to decision making, when choosing a hormone therapy regimen," Kathryn M. Rexrode, M.D., and JoAnn E. Manson, M.D., of Brigham and Women's Hospital in Boston, write in an accompanying editorial. "The findings?remind us that hormone therapy is not a singular entity; we need to consider route, type and dose of these complex agents in practice and in future research."

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Prehypertension Risky for Postmenopausal Women

Borderline hypertension associated with risk of stroke, myocardial infarction

Prehypertension is common in postmenopausal women and is associated with an increased risk of cardiovascular events such as stroke and myocardial infarction, researchers report in the Feb. 20 issue of Circulation: Journal of the American Heart Association.

Judith Hsia, M.D., of George Washington University in Washington, D.C., and colleagues examined the association between prehypertension and cardiovascular disease in 60,785 postmenopausal women. Prehypertension was defined as having a systolic blood pressure of 120-139 mm Hg or a diastolic pressure of 80-89 mm Hg.

There was significant variation in the prevalence of prehypertension based on ethnic group, ranging from 32.1 percent of black women to 42.6 percent for Hispanic women. Compared with normotensive women, prehypertensive women had an increased risk of cardiovascular death during 7.7 years of follow-up (adjusted hazard ratio, 1.58), myocardial infarction (HR, 1.76), stroke (HR, 1.93), hospitalization for heart failure (HR, 1.36) and any cardiovascular event (HR, 1.66).

"Prehypertension is common and was associated with increased risk of myocardial infarction, stroke, heart failure and cardiovascular death in white and non-white postmenopausal women," Hsia and colleagues conclude.

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Supplements Do Not Increase Female Cardiovascular Risk

Calcium, vitamin D supplements do not affect risk of events such as heart attack and stroke

Calcium and vitamin D supplements do not increase the risk of cardiovascular events such as myocardial infarction or stroke in postmenopausal women, according to a report in the Feb. 20 issue of Circulation: Journal of the American Heart Association.

Judith Hsia, M.D., of George Washington University in Washington, D.C., and colleagues randomized 36,282 postmenopausal women to placebo or calcium carbonate (500 mg) plus vitamin D (200 IU) twice a day.

After seven years of follow-up, the researchers found that the calcium/vitamin D group had a similar risk as the placebo group in terms of myocardial infarction or coronary heart disease death (hazard ratio, 1.04), stroke (HR, 0.95), coronary artery bypass grafting or percutaneous coronary intervention (HR, 1.09), confirmed angina (HR, 1.08), hospitalized heart failure (HR, 0.95), or transient ischemic attack (HR, 1.16).

"Calcium and vitamin D supplementation did not increase the risk for myocardial infarction, coronary heart disease death, stroke, coronary revascularization, hospitalized angina, heart failure, or transient ischemic attack," Hsia and colleagues conclude. "Thus, women taking these supplements need not fear adverse cardiovascular consequences while protecting their bone health."

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Heartburn Patients' Reflux Patterns Vary During Sleep

Small study finds that proton-pump inhibitor suppresses overall but not non-acidic episodes

A proton-pump inhibitor, or PPI, reduces overall and acid-reflux episodes during sleep in patients with gastroesophageal reflux disease, but may not reduce non-acidic reflux events, according to research published in the February issue of Chest. The findings could explain why some patients still have symptoms when taking a PPI.

William C. Orr, Ph.D., of the Lynn Health Science Institute in Oklahoma City, and colleagues treated 15 patients with esomeprazole or placebo, in random order, for one week each. Patients were monitored during sleep after consuming a meal designed to trigger reflux events.

The researchers found that total reflux events and acid reflux events were significantly lower in the PPI-treated patients compared with those taking a placebo. They also found that non-acid reflux events were more common, but not statistically more significant, in the PPI group. The ratio of non-acidic to acidic events was significantly greater with PPI treatment.

"The esophagus was equally responsive to acidic and non-acidic reflux events in terms of both eliciting arousal responses, and preventing significant proximal migration," the authors conclude. "Although the esophagus does appear to recognize and respond to non-acid reflux events, the relative increase in non-acidic reflux events may explain the persistence of symptoms in some patients treated with PPIs."

This study was supported by a research grant from Astra Zeneca.

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Rapid Recovery with Outpatient Pneumonia Treatment

Low-risk cases can return to work or usual activities more quickly than if treated as inpatients

Low-risk pneumonia patients return to work or their usual activities more quickly if they are treated on an outpatient basis rather than as an inpatient, according to study findings published in the February issue of Chest. There is no greater risk of mortality in patients treated outside the hospital.

Jose Labarere, M.D., of the Veterans Affairs Pittsburgh Healthcare System in Pittsburgh, and colleagues compared outcomes in 944 outpatients and 549 inpatients with pneumonia severity index risk classes I-III.

After adjusting for other factors, the researchers found that outpatients were more likely to return to work (odds ratio, 2.0) or usual activities (OR, 1.4) than were inpatients. They also found that the overall mortality rate was lower for outpatients than inpatients (0.1 percent versus 2.6 percent) although there was no difference in mortality rates between the 242 outpatients and 242 inpatients who were matched by their propensity score (0.4 percent versus 0.8 percent, respectively).

"The higher observed mortality rate among all low-risk inpatients suggests that physician judgment is an important complement to objective risk stratification in the site-of-treatment decision for patients with pneumonia," the authors conclude.

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Waist-to-Hip Ratio Linked to Breathing Issues in the Obese

Poor gas exchange seen in obese individuals with large waist-to-hip ratios

Morbidly obese patients with large waist-to-hip ratios are more likely to have breathing problems than their counterparts with smaller waist-to-hip ratios, according to a report in the February issue of the journal Chest.

Gerald S. Zavorsky, Ph.D., of McGill University Health Center in Montreal, Quebec, Canada, and colleagues examined the effects of waist-to-hip ratio on pulmonary gas exchange among 25 morbidly obese individuals who were scheduled to undergo bariatric surgery. Researchers measured arterial blood gases after the patient had rested for five minutes while seated upright in a chair.

At rest, the mean PaO2 was 88 mm Hg. The alveolar-arterial oxygen pressure difference ranged from 1 to 37 mm Hg and the PaCO2 ranged from 32 to 44 mm Hg. The waist-to-hip ratio explained 32 percent of the variance in alveolar-arterial oxygen pressure difference and 36 percent of the variance in PaO2. Moreover, 20 percent of the variance in PaCO2 was explained by the waist-to-hip ratio. Men had larger waist-to-hip ratios and poorer gas exchange than their female counterparts.

"There was both an oxygenation problem, as reflected by alveolar-arterial oxygen pressure difference and PaO2 values, and a minor ventilatory constraint, as reflected by the PaCO2 values, which was related, in part, to the waist/hip ratio," the researchers conclude.

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Intensive Program Helps Hospitalized Smokers Quit

Three months of therapy helps those with cardiovascular disease stay smoke-free

Intensive, three-month-long smoking cessation programs can help hospitalized smokers with cardiovascular disease to stay smoke-free after discharge, according to the results of a study published in the February issue of Chest.

Syed M. Mohiuddin, M.D., of the Creighton University Cardiac Center in Omaha, Neb., and colleagues randomized 209 hospitalized smokers into two groups: a control group of patients given counseling and printed material prior to discharge, and a group that received free-of-charge behavior modification counseling for 12 weeks, in addition to pharmacotherapy. Expired carbon monoxide measurements were taken to confirm smoking status at three, six, 12 and 24 months.

The intensive therapy group had better abstinence rates than the control group at all points of follow-up, and by the two-year mark, abstinence rates for the intervention group were 33 percent compared with 9 percent of controls. Hospitalization rates for the intervention group were lower, too: 25 patients over 24 months compared with 41 in the control group.

"Smoking is the greatest risk factor for patients with heart disease and our study showed that intense treatment intervention not only succeeded in getting patients to quit smoking, but it reduced hospitalizations and mortality, as well," said Mohiuddin, in a statement.

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Study Examines Timing of Glycoprotein IIb/IIIa Therapy

Deferred selective treatment for glycoprotein IIb/IIIa affects bleeding rates

Patients with acute coronary syndrome seem to have similar rates of ischemia at 30 days if glycoprotein IIb/IIIa inhibitor treatment is initiated prior to angiography or deferred until angioplasty, and lower rates of major bleeding at 30 days if therapy is deferred, according to a report in the Feb. 14 issue of the Journal of the American Medical Association.

Gregg W. Stone, M.D., of Columbia University Medical Center in New York City, and colleagues randomized 9,207 patients with moderate- and high-risk acute coronary syndrome to receive glycoprotein IIb/IIIa inhibitor therapy before angiography (routine upstream) or to defer treatment until angioplasty in patients undergoing the procedure (deferred selective).

Deferred selective treatment resulted in a non-significant increase in composite ischemia at 30 days (7.9 versus 7.1 percent), but the finding did not meet the criterion for non-inferiority either. There was a significant reduction in major bleeding events within 30 days in the deferred selective group (4.9 versus 6.1 percent).

In the study, angioplasty was performed about five hours after randomization, according to an editorial. "This narrow window of treatment difference makes it difficult to conclude that the two strategies of drug use have been adequately tested," writes Kenneth Mahaffey, M.D., and a colleague from Duke Clinical Research Institute in Durham, N.C.

The study was funded by the Medicines Company of Parsippany, N.J. and Nycomed of Denmark.

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Cardiovascular Risk Algorithms Developed for Women

Tests reclassify half of intermediate-risk women in lower and higher categories

Researchers have developed and validated two global cardiovascular risk assessment algorithms for women that reclassify around half of women currently at intermediate risk into lower or higher risk categories, according to study findings published in the Feb. 14 issue of the Journal of the American Medical Association.

Paul M. Ridker, M.D., M.P.H., of Brigham and Women's Hospital in Boston, and colleagues assessed 35 factors in 24,558 initially healthy women, aged 45 years or older, and followed-up for an average of 10.2 years for cardiovascular events, to develop and validate risk algorithms based on both traditional and novel risk factors.

The new tests, one of which is called the Reynolds Risk Score, had lower Bayes Information Criterion scores and improved fit, discrimination and calibration compared with an older model used in the Adult Treatment Panel III study. Both newer models reclassified about half of women in the Adult Treatment Panel III with estimated 10-year risks for cardiovascular events of 5 percent to 20 percent into lower or higher categories that more accurately reflected real event rates.

"The Reynolds Risk Score is an important contribution to preventive cardiology and provides the framework for evaluating future emerging risk factors," Roger Blumenthal, M.D., from the Johns Hopkins University School of Medicine in Baltimore, and colleagues write in an accompanying editorial.

Authors of both the original report and the editorial have received compensation in some form from various pharmaceutical or biotechnology companies.

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Blood Draw Ineffective for Peripheral Arterial Disease

All-cause mortality, non-fatal MI and stroke similar after blood drawing every six months

Reducing the body's iron stores through phlebotomy does not decrease all-cause mortality, non-fatal myocardial infarction or stroke in patients with peripheral arterial disease, researchers report in the Feb. 14 issue of the Journal of the American Medical Association.

Leo R. Zacharski, M.D., of White River Junction VA Medical Center in White River Junction, Vt., and colleagues conducted a randomized controlled study of 1,277 patients with symptomatic but stable peripheral arterial disease to test the hypothesis that reducing iron through blood drawing will influence clinical outcome in these patients.

The investigators found no significant decrease in all-cause mortality for the 636 patients assigned to phlebotomy at six-month intervals compared to the control group, even after adjusting for multiple factors. All-cause death or death plus myocardial infarction and stroke were 23 and 32 percent in the control group, and 20 and 28 percent in the treatment group, respectively.

"It is not necessary to wait for additional data to implement effective strategies that can prevent coronary arteries from getting 'rusty,'" Frank B. Hu, M.D., Ph.D., of Harvard Medical School, writes in an accompanying editorial. "Even though the question of whether reduced iron stores and coronary heart disease risk are causally linked remains unanswered, there is solid evidence that regular exercise and maintaining a healthy weight can reduce both iron stores and risk of coronary heart disease."

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Off-Pump Surgery Does Not Prevent Cognitive Decline

More demanding procedure but same degree of cognitive decline as on-pump surgery

Patients who undergo off-pump coronary artery bypass graft surgery have similar cognitive function and cardiovascular outcomes five years later as patients who undergo on-pump surgery, according to a study in the Feb. 21 issue of the Journal of the American Medical Association.

Diederik van Dijk, M.D., Ph.D., of the University Medical Center in Utrecht, the Netherlands, and colleagues randomly assigned 281 low-risk coronary artery bypass graft patients to two groups: 139 patients underwent on-pump surgery and 142 underwent off-pump surgery.

Five years after surgery, a psychologist who was blinded to the patients' type of procedure conducted 10 neuropsychological tests on the 130 patients in each group who were still alive. About half of the patients in each group had cognitive decline, using a standard definition of the condition. The results showed that 41 patients in each group (33.3 percent of the off-pump group and 35 percent of the on-pump group) had cognitive decline when stricter criteria were used.

Cardiovascular event outcomes were also similar; 30 patients (21.1 percent) in the off-pump group and 25 (18 percent) in the on-pump group had a cardiovascular event. Angina status and quality-of-life measures were similar for both groups.

"The present results suggest that factors other than cardiopulmonary bypass may be responsible for cognitive decline, such as anesthesia and the generalized inflammatory response that is associated with major surgical procedures. It is also possible that the cognitive decline observed at five-year follow-up is not caused by the operation but reflects natural aging," the authors conclude.

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Pulse Pressure a Risk Factor for Atrial Fibrillation

Findings may identify another modifiable risk factor in aging patients

Pulse pressure is a risk factor for new-onset atrial fibrillation in patients as they age, according to the results of a study published in the Feb. 21 issue of the Journal of the American Medical Association.

Gary F. Mitchell, M.D., of Cardiovascular Engineering, Inc. in Waltham, Mass., and colleagues conducted a community-based study of 5,331 participants in the Framingham Heart Study cohort. Subjects had a median age of 57 years, and 55 percent were female. None of the participants had atrial fibrillation at the start of the study.

Overall, 698 patients (363 men and 335 women) developed atrial fibrillation, with a median time to diagnosis of 12 years from baseline. This gave a cumulative 20-year incidence rate of 5.6 percent for pulse pressure of 40 mm Hg or less and 23.3 percent for pulse pressure of more than 61 mm Hg, representing the cohort's 25th and 75th percentiles, respectively.

As a measure of arterial stiffness, pulse pressure is indirect but easy to assess, the authors note, adding that although arterial stiffness is associated with increasing age, it need not necessarily increase if other cardiovascular risk factors are reduced.

"Given the aging of the population, further research is needed to determine whether interventions aimed at reducing pulse pressure or preventing the increase in pulse pressure with advancing age effectively reduce the incidence of atrial fibrillation," the authors write.

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Grief Typically Peaks in First Six Months After Loss

Negative grief signs that continue for longer may merit further evaluation

After the loss of a family member from natural causes, grief indicators typically peak in the first six months, and contrary to the stage theory of grief, disbelief is not the dominant emotion, according to a report in the Feb. 21 issue of the Journal of the American Medical Association. Family members who continue to score high on grief indicators after this time may need further evaluation.

Paul K. Maciejewski, Ph.D., of Yale University School of Medicine in New Haven, Conn., and colleagues conducted a longitudinal study of 233 bereaved individuals who were assessed for indications of the five conventionally accepted stages of grief (disbelief, yearning, anger, depression and acceptance) in the two years after a loss.

The study found that the initial, dominant grief item was not disbelief, but yearning, which peaked at four months after the loss, compared to one month after the loss for disbelief. Anger and depression peaked at five and six months post-loss, respectively. The final stage, acceptance, increased steadily over the 24-month follow-up period.

"Regardless of how the data are analyzed, all of the negative grief indicators are in decline by approximately six months post-loss. The persistence of these negative emotions beyond six months is therefore likely to reflect a more difficult than average adjustment and suggests the need for further evaluation of the bereaved survivor and potential referral for treatment," the authors conclude.

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