Latest Research

April 20, 2007

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

Timing of Hormone Therapy May Affect Heart Risk

Non-significant reduced risk seen in women who start therapy soon after menopause

A secondary analysis of data from the Women's Health Initiative suggests that the timing of hormone therapy may play a role in its cardiac risk. When started soon after menopause, hormone therapy appears to be associated with a non-significant reduction in coronary heart disease risk, according to a study in the April 4 issue of the Journal of the American Medical Association.

Jacques E. Rossouw, M.D., of the National Heart, Lung, and Blood Institute in Bethesda, Md., and colleagues analyzed data from 10,739 postmenopausal women who had undergone a hysterectomy and 16,608 postmenopausal women who had not. Women with a uterus were randomized to placebo or conjugated equine estrogens (CEE) plus medroxyprogesterone acetate, and women without a uterus were randomized to placebo or CEE alone.

The researchers found that the therapy-associated hazard ratio for coronary heart disease was lower among women within 10 years of menopause (0.76) than for those within 10 to 19 years (1.10) or 20 or more years (1.28). They also found a non-significant tendency toward reduced total mortality among women aged 50-59 (HR, 0.70) compared to women aged 60-69 and 70-79 (HR, 1.05 and 1.14, respectively). However, stroke risk was elevated regardless of timing of hormone therapy (HR, 1.32).

"The absence of excess absolute risk of coronary heart disease and the suggestion of reduced total mortality in younger women offers some reassurance that hormones remain a reasonable option for the short-term treatment of menopausal symptoms, but does not necessarily imply an absence of harm over prolonged periods of hormone use," the authors conclude. "In contrast, risk of stroke did not depend on years since menopause or the presence of vasomotor symptoms."

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Combination Therapy Found Effective in Migraine

Sumatriptan-naproxen sodium combination produces more sustained pain-free response than either alone

Combination treatment with sumatriptan and naproxen sodium is more effective for migraine than treatment with either agent alone, according to a report in the April 4 issue of the Journal of the American Medical Association.

Jan Lewis Brandes, M.D., of the Nashville Neuroscience Group in Nashville, Tenn., and colleagues conducted two identical studies in which 1,461 (study 1) and 1,495 (study 2) acute migraine patients were randomized to take a single tablet containing 85 milligrams of sumatriptan and 500 milligrams of naproxen sodium; sumatriptan alone; naproxen sodium alone; or placebo.

In study 1 and study 2, the sustained pain-free response at two to 24 hours was higher for the combination-therapy groups (25 percent and 23 percent, respectively) than for the sumatriptan-only groups (16 percent and 14 percent, respectively), the naproxen sodium-only groups (10 percent for both) and the placebo groups (8 percent and 7 percent, respectively). They also found that the combination-therapy groups experienced significantly more headache relief and less photophobia and phonophobia two hours after dosing than the placebo groups.

"The superior efficacy of sumatriptan-naproxen sodium compared with sumatriptan monotherapy might be explained by its targeting of multiple pathogenic mechanisms in migraine," the authors state.

GlaxoSmithKline and Pozen Inc. funded the study, and played a role in monitoring, data collection and data analysis.

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Statins May Reduce Sepsis Risk in Dialysis Patients

Hospitalization rate for statin users is 41 per 1,000 patient-years, versus 110 per 1,000 patient-years for non-users

Fewer kidney dialysis patients who are treated with statins are hospitalized for sepsis than those not on statins, researchers report in the April 4 issue of the Journal of the American Medical Association.

Neil Powe, M.D., of the Johns Hopkins Medical Institutions in Baltimore, Md., and colleagues analyzed sepsis hospitalization records for 1,041 dialysis patients treated at 81 non-profit clinics between 1995 and 1998 and followed-up in 2005.

Of 303 sepsis hospitalizations, the researchers found that the patients treated with statins had a crude incidence rate of hospitalization for sepsis of 41 per 1,000 patient-years, versus 110 per 1,000 patient-years for those not taking statins. The trend held true after adjusting for demographics, comorbidities and other variables.

"Use of statins was strongly and independently associated with a reduction in the risk of hospitalization for sepsis in patients who had chronic kidney disease and were receiving dialysis," the authors write. "Randomized trials of statins in patients with chronic kidney disease should examine the prevention of sepsis as a potentially important benefit."

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Influenza B Viruses Showing Some Drug Resistance

Small number of patients have strains resistant to zanamivir and oseltamivir

Influenza B viruses may be developing resistance against zanamivir and oseltamivir, according to a study published in the April 4 issue of the Journal of the American Medical Association.

Shuji Hatakeyama, M.D., Ph.D., of the University of Tokyo in Japan, and colleagues studied 74 children before and after oseltamivir therapy and 348 untreated flu patients. They collected and analyzed 74 influenza B isolates from the treated patients and 422 isolates from the untreated patients.

The researchers identified a variant with reduced drug sensitivity to zanamivir, oseltamivir or both in one (1.4 percent) of the 74 children who had received oseltamivir, and in seven (1.7 percent) of the 422 influenza B viruses isolated from untreated patients.

"The emergence of drug-resistant influenza B should draw attention to the importance of continual monitoring of strains over time and to the need for frequent rethinking of policies for use of antiviral drugs," states the author of an accompanying editorial. "While the news about resistance is not good and certainly calls into question some of the current assumptions about drug-resistant viruses, an effective response to this news can help contend with the new challenges of influenza."

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Genetic Links to Acute Coronary Syndromes Debunked

Only one of 85 proposed genetic variations found to have an even nominal association with acute coronary syndromes

Gene variations may not be risk factors for acute coronary syndromes, according to the results of a study published in the April 11 issue of the Journal of the American Medical Association.

Thomas M. Morgan M.D., of Washington University School of Medicine in St. Louis, and colleagues genotyped 811 acute coronary syndrome patients and 650 age- and sex-matched controls for 85 variants in 70 genes previously reported in smaller studies to be associated with acute coronary syndromes.

The researchers found a nominally significant association with only one genotype: −455 promoter variant in beta-fibrinogen. They also found that only 41 of 84 of the predefined risk variants were even marginally more frequent in cases than in controls (with one tie).

"Our findings come at a critical juncture in complex disease genetics," the authors write. "Some cardiovascular gene variants included in our study can already be ordered clinically, for indications that explicitly include possible acute coronary syndrome risk. However, our findings suggest that such clinical genetic testing is premature and underscore the importance of robust replication studies of reported associations prior to their application to clinical care."

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Experimental Flu Vaccine Created in Insect Cells

Expressing recombinant hemagglutinin in insect cells avoids using embryonated eggs

An experimental influenza vaccine produced in insect cells appears to be safe and effective in early testing, making it a possible alternative to vaccines made using embryonated hen's eggs, researchers report in the April 11 issue of the Journal of the American Medical Association.

John Treanor, M.D., of the University of Rochester in Rochester, N.Y., and colleagues tested an experimental trivalent influenza virus hemagglutinin (rHAO) vaccine created with recombinant baculoviruses in insect cells on 460 healthy adults during the 2004-2005 flu season.

Participants were randomly injected with placebo, 75 μg of vaccine including various amounts of hemagglutinin from influenza A/New Caledonia/20/99 (H1N1), influenza B/Jiangsu/10/03, and influenza A/Wyoming/3/03 (H3N2); or 135 μg with equal amounts of each.

The researchers found similar adverse effect rates for placebo and the vaccines. Sixty-seven percent of those given 135 μg vaccine, 51 percent given 75 μg, and 3 percent on placebo responded to H1N1; 92 percent given 135 μg, 65 percent given 75 μg, 4 percent given placebo responded to influenza B/Jiangsu/10/03; 77 percent given 135 μg, 81 percent on 75 μg, 11 percent given placebo responded to H3N2.

"In this study, a trivalent rHAO vaccine was safe and immunogenic in a healthy adult population," the authors write.

Financial support and study design support provided by Protein Sciences Corp., the manufacturers of the vaccine.

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Postoperative Corticosteroids May Benefit Heart Patients

Administration of hydrocortisone reduces the incidence of atrial fibrillation

In patients who undergo cardiac surgery, postoperative corticosteroid therapy may reduce the risk of atrial fibrillation, according to study findings published in the April 11 issue of the Journal of the American Medical Association.

Jari Halonen, M.D., of Kuopio University Hospital in Kuopio, Finland, and colleagues studied 241 patients without a history of atrial fibrillation who underwent coronary artery bypass grafting (CABG) surgery, aortic valve replacement, or combined CABG surgery and aortic valve replacement. They randomized the patients to receive either 100 milligrams of hydrocortisone or placebo for three days after the operations.

The researchers found that the hydrocortisone group experienced a significantly lower incidence of atrial fibrillation than the placebo group (30 percent versus 48 percent). They also found no significant group differences in the rates of superficial or deep wound infections, or other major complications.

"Larger trials will be needed to confirm our findings and determine short- and long-term safety of corticosteroids to prevent postoperative atrial fibrillation and other arrhythmias," the authors conclude.

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Stem Cell Transplants Benefit Type 1 Diabetics

Small study demonstrates that the treatment can lead to prolonged insulin independence

High-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation may be an effective treatment for type 1 diabetes mellitus, according to the results of a small study published in the April 11 issue of the Journal of the American Medical Association.

Julio C. Voltarelli, M.D., Ph.D., of the University of Sao Paulo in Ribeirao Preto, Brazil, and colleagues studied 15 patients aged 14 to 31 who underwent the treatment and followed them for seven to 36 months.

The researchers found that 14 patients became insulin-free. The duration ranged from 35 months (one patient) to at least 21 months (four patients) and to at least six months (seven patients). The other two late-responding patients were insulin free for one and five months, respectively.

"This study by Voltarelli et al. is the first of what likely will be many attempts at cellular therapy to interdict the type 1 diabetes mellitus disease process," states the author of an accompanying editorial. "Research in this field is likely to explode in the next few years and should include randomized controlled trials as well as mechanistic studies. As these further studies confirm and build on the results of Voltarelli et al. -- the time may indeed be coming for starting to reverse and prevent type 1 diabetes mellitus."

Funding provided in part by Genzyme Corporation and Johnson & Johnson-LifeScan-Brazil.

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Inactivated Poliovirus Vaccine Immunogenic in Cuba

Reduces shedding of oral poliovirus vaccine after challenge

Using inactivated poliovirus vaccine in Cuban infants leads to seroconversion rates of at least 90 percent for most virus subtypes and reduces shedding of oral poliovirus vaccine after challenge, according to the results of a study published in the April 12 issue of the New England Journal of Medicine.

Victor Caceres, M.D., M.P.H., from the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues randomized 166 Cuban infants to three doses of a combined vaccine (group A, diphtheria-pertussis-tetanus vaccine, Haemophilus influenzae type b vaccine and inactivated poliovirus vaccine) or three doses of the vaccine minus the poliovirus vaccine (group B). A separate group of 100 Cuban infants received two doses of the combined vaccine (group C).

The seroconversion rates for types 1, 2 and 3 poliovirus were 94, 83 and 100 percent, respectively, in group A, and 90, 89 and 90 percent, respectively, in group C. There were no seroconversions in group B. After challenge with oral poliovirus vaccine, the virus isolation rates in stool in groups A, B and C were 94, 91 and 97 percent, respectively, and the mean log10 viral titers for any serotype were 3.46, 3.89 and 3.37, respectively.

"The viral titer of oral poliovirus vaccine shed in the stool after oral poliovirus vaccine challenge was reduced in both groups receiving inactivated poliovirus vaccine," the authors conclude.

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Radiotherapy Benefits Elderly Glioblastoma Patients

Improves survival without harming quality of life

Radiotherapy can improve survival in glioblastoma patients who are 70 years or older without compromising their quality of life or cognition, according to a study in the April 12 issue of the New England Journal of Medicine.

Jean-Yves Delattre, M.D., from Hopital de la Salpetriere in Paris, France, and colleagues randomized 85 patients with glioblastoma (aged 70 years or older) to supportive therapy alone or supportive care plus focal radiotherapy (1.8 Gy daily five days a week, for a total of 50 Gy).

The trial was terminated early due to a clear benefit of added radiotherapy. After a median follow-up of 21 weeks, the researchers found that patients receiving radiotherapy had a significantly higher median survival (29.1 versus 16.9 weeks) and a significantly lower risk of death (hazard ratio 0.47). There were no serious adverse effects associated with radiotherapy, and the two groups had similar quality-of-life and cognitive function over time.

Radiotherapy "may provide a standard of care for glioblastoma in the elderly," according to an editorial. However, the "results are applicable only to older patients with sufficient performance status (that is, those who are at least capable of self-care), since it is unrealistic to expect any meaningful gain in quantity or quality of life in patients with rapidly declining functional status."

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Anakinra Improves Glycemia, Beta-Cell Function in Diabetes

Interleukin-1-receptor antagonist also reduces inflammation

A drug that blocks the interleukin-1 receptor improves glycemia and beta-cell secretory function and reduces inflammation in patients with type 2 diabetes, researchers report in the April 12 issue of the New England Journal of Medicine.

Marc Y. Donath, M.D., from University Hospital Zurich in Switzerland, and colleagues randomly assigned 70 patients with type 2 diabetes to 100 mg subcutaneous anakinra (a recombinant human interleukin-1-receptor antagonist) once daily, or placebo for 13 weeks.

The researchers found that the anakinra group had significantly lower glycated hemoglobin levels, enhanced C-peptide secretion, a reduced ratio of proinsulin to insulin and lower levels of interleukin-6 and C-reactive protein. There were no serious drug-related adverse events nor symptomatic hypoglycemia. The two groups were similar in terms of insulin resistance, body mass index, serum adipokine levels and insulin-regulated gene expression in skeletal muscle.

The study "provides insight into a shared mechanism of beta-cell dysfunction in type 1 diabetes and type 2 diabetes and suggests a new therapeutic approach to type 2 diabetes," Kristina I. Rother, M.D., from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., writes in an accompanying editorial.

The study was partially supported by Novo Nordisk, and study drugs were provided by Amgen.

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Vitamins Reduce Low Birth Weight in Developing Nations

Daily multivitamin supplements reduce low birth weight and small-for-gestational-age births

Pregnant women in Tanzania who take multivitamin supplements are less likely to have low birth weight and small-for-gestational-age infants, suggesting multivitamins should be considered for all pregnant women in developing countries, researchers report in the April 5 issue of the New England Journal of Medicine.

Wafaie W. Fawzi, M.B., B.S., Dr.Ph., of Harvard School of Public Health in Boston, and colleagues randomly assigned 8,468 HIV-negative Tanzanian women to either a daily multivitamin supplement or placebo starting at 12 to 27 weeks of gestation. The multivitamin included 20 mg of vitamin B1, 20 mg of vitamin B2, 25 mg of vitamin B6, 100 mg of niacin, 50 μg of vitamin B12, 500 mg of vitamin C, 30 mg of vitamin E, and 0.8 mg of folic acid.

The investigators found the incidence of low birth weight was 7.8 percent in the multivitamin group compared with 9.4 percent in the placebo group, with a mean difference in birth weight of 67 grams. Vitamin supplementation also reduced the incidence of small-for-gestational-age birth size in some groups by 23 percent and cut the risk of maternal anemia by 12 percent. There were no significant differences in premature births or fetal deaths.

"The increase in cost of incorporating the recommended dietary allowance of additional nutrients is conservatively estimated to be about 20 percent, and scaling up prenatal multiple micronutrient supplementation could be a highly cost-effective approach to improving birth outcome among pregnant women in developing countries," the authors write.

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Normal Natural Killer Cell Level Found in COPD Patients

Results suggest the cells not as abundant in obstructive diseases as previously thought

Natural killer T cells represent a minority of the CD4+ bronchoalveolar cells in patients with asthma and chronic obstructive pulmonary disease (COPD), and are present at levels seen in healthy subjects, according to study findings published in the April 5 issue of the New England Journal of Medicine.

To address conflicting reports regarding the abundance of invariant natural killer T cells in patients with pulmonary diseases, Pandurangan Vijayanand, M.D., of Southampton General Hospital in Southampton, U.K., and colleagues used flow cytometry and real-time polymerase chain reaction (RT-PCR) to measure the levels of these cells in patients with mild or moderately severe asthma, COPD, and in healthy control subjects.

Invariant natural killer T cells were found to represent 2 percent of the total population of CD4+ T cells in bronchoalveolar lavage, sputum and airway biopsy samples taken from all subjects. The investigators found no significant differences between patient and healthy control samples and RT-PCR analyses for invariant natural killer T-cell-receptor genes were negative.

"Whether or not natural killer T cells expand in numbers to the extent reported?[previously], studies in animals suggest that these cells are likely to have a role in the pathogenesis of asthma," according to Ling-Pei Ho, M.D., Ph.D., of Oxford, U.K., in an accompanying editorial. "Further work on the precise role of this potent group of immunoregulatory cells in airway inflammation is overdue."

The study authors report multiple affiliations with various pharmaceutical companies.

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Computer-Aided Detection Reduces Mammogram Accuracy

Implementation of computer-aided detection decreases diagnostic specificity, increases biopsy rates

The use of computer-aided detection systems for screening mammography has reduced the accuracy of mammogram interpretation, researchers report in the April 5 issue of the New England Journal of Medicine.

Joshua Fenton, M.D., from the University of California Davis in Sacramento, and colleagues examined data from 222,135 women (429,345 mammograms), including 2,351 women diagnosed with breast cancer within one year of the screening. The researchers measured the sensitivity, specificity and positive predictive value of computer-aided detection. The screening mammograms were conducted between 1998 and 2002 at 43 facilities, including seven that used computer-aided detection.

Use of computer-aided detection resulted in a drop in diagnostic specificity from 90.2 to 87.2 percent, a decrease in positive predictive value from 4.1 to 3.2 percent, and an increase in the rate of biopsy by 19.7 percent. The rate of cancer detection was unchanged and, overall, the accuracy was lower for computer-aided detection than for non-use.

Screening mammography is fraught with a number of difficulties including a lack of interpretive expertise, long training time and low sensitivity for certain breast and tumor types, according to an editorial by Ferris M. Hall, M.D., of Beth Israel Deaconess Medical Center in Boston. He suggests that genetic testing in combination with magnetic resonance imaging may provide more sensitive screening results.

The study authors report affiliations with R2 Technologies, Koning, Biolucent and GE Medical Systems.

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Three Gene Mutations Linked to Neural-Tube Defects

Mutated copies of the VANGL1 gene may increase risk of neural-tube defects

Mutations in the VANGL1 gene, which is expressed in the developing neural tube, are associated with both familial and sporadic cases of spina bifida, anencephaly and other neural-tube defects, according to a report in the April 5 issue of the New England Journal of Medicine.

Zoha Kibar, Ph.D., of McGill University in Montreal, Quebec, Canada, and colleagues compared genes associated with the VANGL1 gene among 144 patients with neural-tube defects (including 137 Italian patients with non-syndromic spinal dysraphisms and seven fetuses with craniorachischisis) with those of 106 healthy controls who did not have a first-degree relative with a neutral-tube defect.

The researchers identified three VANGL1 mutations in patients with sporadic (M328T) and familial (V239I, R274Q) neural-tube defects. A spontaneous mutation (V239I) can appear in the familial setting. The investigators showed that these mutations affected amino acid residues conserved in Vangl proteins across species.

Further testing is needed to confirm and clarify the association, the authors note. Going forward, "studying the effect of periconceptional supplementation with folic acid, inositol, and methionone on the emergence of neural-tube defects in these mutants may shed further light on the preventive mechanism associated with these nutrients," they conclude.

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Pergolide Products Recalled Due to Heart Valve Damage

Parkinson disease drugs carry risk of heart damage

The U.S. Food and Drug Administration and manufacturers have voluntarily recalled pergolide drug products used to treat Parkinson disease because they can cause serious damage to patients' heart valves. The affected drugs include Permax, marketed by Valeant Pharmaceuticals, Aliso Viejo, Calif., and generic versions produced by Par and Teva.

Pergolide was the subject of two recent studies published in the New England Journal of Medicine that reiterated previous findings on the drug's association with valve regurgitation. The drug was prescribed to an estimated 12,000 patients in the United States in 2006.

"If treatment with a dopamine agonist is to be discontinued, pergolide should not be stopped abruptly, because rapid discontinuation of all dopamine agonist therapies can be dangerous," according to an FDA statement. "Instead, gradually decrease the dose of pergolide. Patients who will be taken off pergolide should be told that other effective options for treatment exist, including three other dopamine agonists that are not associated with damage to heart valves."

Another dopamine agonist associated with heart valve problems is Dostinex (cabergoline). However, the drug is not approved to treat Parkinson disease and is approved for use in hyperprolactinemic disorders, which require much lower doses of the drug. Because lower doses don't appear to pose a major risk to the heart, the drug will remain on the market, according to the FDA.

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CFC-Containing Inhalers Banned in 2008

Hydrofluoroalkane just as effective but more expensive alternative

After 2008, chlorofluorocarbon-containing metered-dose inhalers will no longer be available in the United States and will be replaced by equally effective but costlier hydrofluoroalkane inhalers, according to a report in the March 29 issue of the New England Journal of Medicine.

Leslie Hendeles, Pharm.D., from the University of Florida in Gainesville, and colleagues explain the rationale for the change and how hydrofluoroalkane, or HFA, inhalers compare with chlorofluorocarbon, or CFC, albuterol inhalers. CFCs have been found to accumulate in the atmosphere and affect the stratospheric ozone layer important for absorbing UVB radiation.

HFA-based albuterol inhalers have similar efficacy and safety characteristics as the CFC-based inhalers, but may have a slightly different taste, different spray characteristics, and may result in increased tachycardia at higher doses. The transition may cost up to $1.2 billion annually.

"Clinical trials in children and adults with asthma have demonstrated that when these HFA albuterol products are administered at the FDA-approved dose, their efficacy and safety profiles are similar to those of the CFC albuterol products they are intended to replace," the authors write. "However, there are differences between HFA and CFC albuterol products and among the various HFA albuterol products."

The study authors have received fees and funding from pharmaceutical firms including GlaxoSmithKline, IVAX/Teva, Schering-Plough and AstraZeneca.

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Bronchial Thermoplasty Cuts Asthma Exacerbations

Industry-funded study finds technique reduces incidence of mild exacerbation events

Heat-controlled reduction of smooth muscle mass in the airways via bronchial thermoplasty can improve quality of life and reduce mild exacerbations for at least one year in patients with asthma, according to the results of a study published in the March 29 issue of the New England Journal of Medicine.

Gerard Cox, M.B., of McMaster University in Ontario, Canada, and colleagues from the Asthma Intervention Research Trial Study Group randomized 112 adult patients with moderate to severe persistent asthma into two groups: one group received bronchial thermoplasty with an Asthmatx Alair system and the other did not. Patients were assessed at three, six and 12 months post-therapy to see if removal of long-acting beta-2-adrenergic agonists resulted in asthmatic exacerbation.

At 12 months, the mean number of mild (but not severe) exacerbation events in the bronchial thermoplasty group had decreased by half, amounting to some 10 fewer mild exacerbations per patient per year. In the control group the number remained essentially unchanged. Patients in the bronchial thermoplasty group saw improvements in morning peak expiratory flow, symptom-free days and symptom score, but also were at higher risk for adverse respiratory events immediately following treatment. The number of adverse events between six weeks and 12 months post-therapy was the same between groups.

"The results reported by Cox and colleagues suggest that we should now contemplate other approaches to targeting airway smooth muscle that might prove to be less invasive, more practical, and more amenable to application throughout the airways [than bronchial thermoplasty]," the authors of an accompanying editorial suggest.

This study was supported by Asthmatx.

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Newborn Screening for Cystic Fibrosis Saves Money

Study suggests screening makes economic, clinical and social sense

Newborn screening for cystic fibrosis saves money in treatment costs in the long run and such programs should be adopted internationally, according to the results of a study published in the April 7 issue of The Lancet.

Erika J. Sims, Ph.D., of the University of East Anglia in Norwich, U.K., and colleagues compared treatment costs of 184 children, aged 1 to 9, with cystic fibrosis that was identified by newborn screening, with 950 children the same age who were diagnosed after clinical presentation of the disease.

Treatment costs for children diagnosed clinically were from 60 to 400 percent more than those of children identified via newborn screening. In some cases, drug cost savings alone for children identified via newborn screening would often be enough to offset the cost of a national screening program, the study authors conclude.

The new study provides "more evidence in favor of newborn screening for cystic fibrosis," write Bridget Wilcken and Kevin Gaskin, M.D., of Children's Hospital at Westmead in Sydney, Australia, in an accompanying editorial. "It remains an enigma that newborn screening for cystic fibrosis has until now been so controversial, when there is so much evidence in favor."

AbstractFull Text (subscription or payment may be required)Editorial

Pneumococcal Vaccine Cuts Hospitalizations in Children

Pneumonia-related hospital admissions down 40 percent since program inception

Routine vaccination with the seven-valent pneumococcal conjugate vaccine resulted in a 40 percent drop in pneumonia-related hospital admissions in children under age 2 in the United States, according to a new analysis published in the April 7 issue of The Lancet.

Carlos G. Grijalva, M.D., of Vanderbilt University School of Medicine in Nashville, Tenn., and colleagues assessed the effect of routine infant immunizations on rates of all-cause and pneumococcal pneumonia hospital admissions. They compared estimated monthly admission rates for 2001-2004 (after the vaccination program began) with estimated rates calculated from 1997-1999. They excluded 2000 (the year the vaccine was introduced).

There was a reduction in all-cause pneumonia admissions of 506 per 100,000 children under age 2 per year, which represents about 41,000 pneumonia hospitalizations. Two percent of children younger than 2 years of age admitted with pneumonia were coded as having pneumococcal disease during the eight-year study period. These rates dropped by 65 percent since the vaccine program began, representing about 17 fewer admissions per 100,000 children in 2004. Owing to herd immunity, pneumonia rates also declined by 30 percent in adults aged 18 to 39 during the study period.

"Our results contribute to the growing body of evidence supporting the beneficial effects of the pneumococcal conjugate vaccines in children," the study authors write.

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New Protease Inhibitor Shows Promise in HIV+ Patients

Darunavir expands options for treatment-experienced patients

A new antiretroviral drug, darunavir, has shown promising results in treatment-experienced HIV-1 infected patients, according to a report published online April 5 in The Lancet.

Bonaventura Clotet, M.D., of the Hospital Universitari Germans Trias i Pujol in Barcelona, Spain, and colleagues conducted a trial of 230 HIV-1 infected patients, all of whom remained on an optimized background regimen. While 110 were randomized to receive 600 mg of darunavir in combination with 100 mg of ritonavir twice daily, 120 controls received other protease inhibitors.

After 48 weeks of treatment, 67 (61 percent) of the darunavir-ritonavir patients achieved a 10-fold drop in viral load, compared with only 18 (15 percent) of the control group patients. Both groups had similar rates of adverse events.

"This treatment is expected to fulfil the clinical need for a new protease inhibitor capable of expanding the treatment options available for a treatment-experienced, drug-resistant population of patients," the authors conclude. "Darunavir-ritonavir is now being assessed in patients with less or no treatment experience in phase III trials."

Those in the field of HIV/AIDS "will probably rejoice in the availability of darunavir," said Rodger MacArthur, M.D., of Wayne State University in Detroit, in an editorial. However, the full efficacy of the drug will only be established in two to three years after clinical endpoint studies have been conducted.

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If HIV+ Women Breast-Feed, Best Not to Add Formula

HIV transmission 10-fold higher with mixed nutrition of breast-milk and solids compared to breast-feeding alone

HIV-infected women who choose to breast-feed are less likely to transmit the virus to their infant if they avoid mixed feedings with formula and solids and exclusively breast-feed instead. The study of South African women is published in the March 31 issue of The Lancet.

Nigel C. Rollins, M.D., of the University of KwaZulu-Natal in Congella, South Africa, and colleagues conducted a study of 2,722 HIV-infected and uninfected pregnant women from nine antenatal clinics. The mothers supplied data on infant feeding every week and the babies underwent monthly blood tests for HIV.

There were 1,372 infants born to HIV-infected mothers, of whom 1,132 (83 percent) were exclusively breast-fed from birth and for a median 159 days. By the age of 6 weeks, 14.1 percent of the infants were infected with HIV-1, and 19.5 percent were infected by age 6 months. However, breast-fed babies who received solids and who were given mixed feeding with formula and breast-milk were at significantly higher risk of infection (adjusted hazard ratios, 10.87 and 1.82, respectively). At three months, the cumulative mortality rate for exclusively breast-fed infants was 6.1 percent, versus 15.1 percent for those given mixed nutrition.

"The association between mixed breast-feeding and increased HIV transmission risk, together with evidence that exclusive breast-feeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO and UNAIDS infant feeding guidelines," the authors conclude.

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New Drug May Improve Therapy for Type 2 Diabetes

Exenatide shown to improve suboptimal thiazolidinedione therapy

Patients with type 2 diabetes who show suboptimal disease control with thiazolidinediones may benefit from added exenatide therapy, researchers report in the April 3 issue of the Annals of Internal Medicine.

Bernard Zinman, M.D., from Mount Sinai Hospital in Toronto, Ontario, Canada, and colleagues conducted a randomized, double-blind, controlled trial including 233 patients with type 2 diabetes suboptimally controlled with thiazolidinediones to compare the effects of added exenatide therapy (10 micrograms twice daily for 16 weeks) versus placebo on glycemic control. Exenatide is the first in a new class of incretin mimetic therapies that show glucoregulatory effects.

The investigators found that exenatide reduced hemoglobin A1C levels by almost one percentage point, and reduced both fasting glucose levels and body weight compared with placebo. Gastrointestinal symptoms including nausea and vomiting occurred in up to 40 percent of patients in the exenatide group.

Saul Malozowski, M.D., Ph.D., from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., cautions in an accompanying editorial that the study was relatively small and short, and that patients were not provided lifestyle and diet advice.

The study was supported by Eli Lilly and Company in Indianapolis and Amylin Pharmaceuticals in San Diego.

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Kidney Disease Management Poor in Black Neighborhoods

Time to transplantation, dialysis facility performance lower in areas with predominately black residents

The racial composition of a community is associated with time to kidney transplantation for those with end-stage renal disease and to the performance of the kidney dialysis facility that serves the community, according to a report in the April 3 issue of the Annals of Internal Medicine.

Rudolph Rodriguez, M.D., from the University of California San Francisco, and colleagues conducted a retrospective cohort study of nearly 400,000 black and non-Hispanic white patients who initiated long-term dialysis treatment to determine how the racial composition of their residence ZIP code affects time to kidney transplantation and performance of their local dialysis facility.

The investigators found that time to transplantation was higher in regions with at least 75 percent black residents, no matter if the patient was black or white. Facilities in predominately black regions had higher than expected mortality for whites but not blacks and were less likely to meet performance targets on anemia management and dialysis adequacy.

"Closer scrutiny of care provided to patients receiving dialysis who live in predominately black residential areas and to dialysis facilities operating in these areas may be warranted," the authors write.

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Guidelines Say Not All Women in 40s Need Mammogram

Recommendations for screening in this age group issued by the American College of Physicians

The risk of breast cancer can vary significantly in women in their 40s, and not all women in that age group may need annual mammograms, according to new guidelines from the American College of Physicians. Women and physicians should weigh the risks and benefits of mammography screening before age 50, researchers report in the April 3 issue of the Annals of Internal Medicine.

Katrina Armstrong, M.D., from the University of Pennsylvania in Philadelphia, and colleagues conducted a systematic review of the literature and found that screening mammography reduces breast cancer mortality from 7 percent to 23 percent in the 40 to 49 age group. The rate of false-positive results from mammography screening ranged from 20 to 56 percent after 10 mammograms.

Amir Qaseem, M.D., Ph.D., of the American College of Physicians in Philadelphia, and colleagues issued recommendations for mammography screening for this age group, which included periodic individual assessments of risk, informing women of the risks and benefits of screening, and including patients in the decision-making process.

"Clinicians and patients must try to untangle the complex knot of social, political and economic forces that influence decisions in breast cancer screening," Joann Elmore, M.D., from the University of Washington in Seattle, and a colleague write in an accompanying editorial. "No simple recommendation applies to all women in their 40s."

Some of the authors have affiliations with Johnson & Johnson. Elmore has served as an expert witness on the topic of risk communication.

Abstract - ArmstrongFull TextAbstract - QaseemFull TextEditorial

False-Positive Mammograms May Affect Feelings, Actions

Women who receive false-positive results more anxious and focused on breast cancer

False-positive results on screening mammography may have long-term effects on women's feelings and health behaviors, according to a review of 23 studies published in the April 3 issue of the Annals of Internal Medicine.

Noel T. Brewer, Ph.D., of the University of North Carolina in Chapel Hill, and colleagues found that women in the United States who received false-positive results on mammograms were slightly more likely to return for routine screening (risk ratio, 1.07); women in Canada were less likely to return (risk ratio, 0.63); and European women were unaffected by false-positive results in terms of returning for routine mammograms.

Overall, women who received false-positive results were more likely to do breast self-exams, had somewhat higher levels of distress or anxiety and thought about breast cancer more than their counterparts who had received normal results when they underwent screening mammography.

Breast cancer screening may be just be the tip of the iceberg. "Given our findings that false-positive mammograms have long-term effects on the behavior and well-being of the women who receive them, these effects may also be results of testing for other types of cancer, diseases and health threats," the researchers conclude.

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Most Doctors Say Religion Plays Role in Patient Health

Religion and spirituality provide positive state of mind, coping skills, support

More than half of physicians believe that religion and spirituality affect patient health in some way, according to the results of a survey published in the April 9 issue of the Archives of Internal Medicine.

In 2003, Farr A. Curlin, M.D., and colleagues from the University of Chicago, sent surveys to a random sample of 2,000 physicians aged 65 and younger to examine the association between physicians' religious beliefs and their view of the influence of religion and spirituality on health.

The investigators found that 56 percent of responding physicians felt that religion and spirituality had "much" or "very much" influence on health, not by changing "hard" medical outcomes but by helping patients cope, giving them a positive state of mind and providing emotional and practical support through the religious community. Around 54 percent of physicians felt that God or some other supernatural being sometimes intervenes in patient health. Physicians with high religiosity were more likely to report that religion and spirituality strongly affect patient health, compared to those with low religiosity.

"These findings might rather lend support to the Association of American Medical Colleges' recommendation that physicians 'recognize that their own spirituality?might affect the ways they relate to, and provide care to, patients,'" the authors write.

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Smoking Status Could Indicate Alcohol Misuse

Occasional smokers are more than five times as likely to be hazardous drinkers than non-smokers

Daily, occasional and ex-smokers are more likely to be hazardous drinkers than never-smokers, suggesting that smoking status could be used as a clinical indicator of alcohol misuse, according to a report in the April 9 issue of the Archives of Internal Medicine.

Sherry A. McKee, Ph.D., from Yale University School of Medicine in New Haven, Conn., and colleagues used data from 42,374 U.S. adults enrolled in the National Epidemiological Survey on Alcohol and Related Conditions to assess smoking as a clinical indicator of alcohol misuse.

Daily, occasional and ex-smokers were up to 5.33 times more likely to be hazardous drinkers and up to 5.39 times more likely to meet the criteria for alcohol diagnoses, as assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. The tests were found to be 42 to 51 percent sensitive and have a specificity around 80 percent.

"Smoking status can be used to help identify primary care patients at higher risk for alcohol misuse (i.e., current smokers) and as a helpful mnemonic for alcohol screening in general," the authors write. "Better screening of alcohol use problems could lead to better assessment and intervention related to alcohol misuse."

One of the authors is affiliated with several drug companies and is an inventor on patents held by Yale University for naltrexone and smoking cessation.

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Polyphenol-Rich Cocoa May Help Lower Blood Pressure

But meta-analysis of studies shows tea has no effect on systolic and diastolic pressures

Foods rich in cocoa, a common source of heart-healthy polyphenols, may help reduce blood pressure, while tea, another major source of polyphenols, has no effect, researchers report in the April 9 issue of the Archives of Internal Medicine.

Dirk Taubert, M.D., Ph.D., from the University Hospital of Cologne, Germany, and colleagues conducted a meta-analysis of five studies measuring the effects of cocoa consumption on blood pressure and another five studies measuring the same effects from drinking tea.

Results from the randomized, controlled trials of cocoa consumption, which included 173 subjects and lasted two weeks, found that mean systolic and diastolic blood pressure dropped by 4.7 mm Hg and 2.8 mm Hg, respectively. While the five studies of tea consumption had a median duration of four weeks, no significant changes in blood pressure were found.

The authors suggest that the different types of plant phenols found in the two foods may be responsible for the different effects of cocoa and tea. They also suggest that cocoa products should be considered as part of dietary approaches to lower hypertension risk, but they caution that the sugar, fat and caloric value of these products should be considered as well.

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Atrial Fibrillation Diagnoses on the Rise in U.S.

Some patients are not receiving treatment and others are being over-treated

Atrial fibrillation and the use of anticoagulation therapies to treat it have increased in the United States over the last decade, although some patients are still not receiving treatment and others who are low risk are being over-treated, according to a study published online March 26 in the Journal of the American College of Cardiology.

Robert J. Anderson, M.D., and colleagues from the University of Colorado at Denver examined trends in the use of anticoagulation for atrial fibrillation using data on 40.5 million visits from the 1994-2003 National Ambulatory Medical Care Survey.

The researchers found that the prevalence of atrial fibrillation diagnoses increased and that anticoagulation treatment increased as well, from 40.3 to 49.1 percent (odds ratio 1.07). Anticoagulation treatment was more common in older patients and those taking rate control agents (beta-blockers, calcium channel blockers, digoxin). Anticoagulation treatment was used less in patients taking rhythm control rather than rate control agents. The data also suggest that anticoagulation might be overused in some low-risk patients, the report indicates.

"From 1995 through 2002, an increase has occurred in anticoagulation for atrial fibrillation, especially in those at highest risk for thromboembolic phenomena," Anderson and colleagues conclude. "A substantial number of patients at risk for thromboembolic events are not anticoagulated, and further studies are needed to determine how many of these patients are candidates for anticoagulation. Anticoagulation use has increased in non-targeted, low-risk groups in whom antiplatelet agents are appropriate."

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Mortality After CABG Drops, But Still Higher in Women

Thirty-day mortality declined in both genders over 14-year period

Thirty-day mortality after coronary artery bypass graft (CABG) surgery dropped in both men and women over a 14-year period, but the risk of death was still 42 percent higher in women, according to a study published online March 26 in the Journal of the American College of Cardiology.

Karin H. Humphries, M.B.A., D.Sc., from the University of British Columbia in Vancouver, Canada, and colleagues examined 30-day mortality after CABG surgery in 20,229 men and 4,983 women treated in Canada between 1991 and 2004.

The researchers found that although women were older and had more comorbid conditions, they had better ejection fractions and less extensive coronary disease than men. Thirty-day mortality dropped significantly in both men (2.4 to 1.9 percent) and women (5.6 to 1.9 percent) over the study period. However, 30-day mortality was still significantly higher in women (3.6 versus 2.0 percent), even after adjusting for baseline differences (odds ratio 1.42), although the risk was attenuated after adjusting for body surface area (OR, 1.26).

"The 30-day mortality after CABG decreased significantly between 1991 and 2004, especially in women, suggesting that the gender difference in short-term outcomes is diminishing," Humphries and colleagues conclude. "The overall 42 percent higher mortality risk in women seems to be partially mediated through body surface area, a surrogate for vessel size."

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Less Plaque in Women with Coronary Artery Disease

Women respond as well as men to treatment and risk factor modification

Although women have more risk factors for coronary artery disease than men, they have less plaque and respond as well as men to established treatments and intensive risk factor modification, according to the results of a study published online March 26 in the Journal of the American College of Cardiology.

Stephen J. Nicholls, Ph.D., and colleagues from the Cleveland Clinic Foundation in Ohio examined the extent and progression of coronary artery disease as assessed by intravascular ultrasound in 978 subjects (251 women).

The researchers found that although women were more likely to have risk factors such as hypertension, a high body mass index and high cholesterol, they had significantly less plaque as a percentage of atheroma volume and total atheroma volume. After treatment with established medical therapies, the rate of change of both parameters was similar in both men and women. After intensive risk factor modification, both groups had a similar rate of plaque progression or regression, according to the study.

"Despite the presence of more risk factors, the extent of atheroma in women with angiographic coronary artery disease is less than in men in subjects participating in clinical trials that employed serial assessments with intravascular ultrasound," Nicholls and colleagues conclude. "The finding that the rate of plaque progression or regression does not differ between genders in the setting of intensive risk factor modification supports the use of established medical therapies in women with coronary artery disease."

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Statin Usage Affected by Insurance Coverage

Usage falls after switch from full coverage to copayment and coinsurance

Elderly patients reduce their usage of statins after switching from full insurance coverage to copayment and coinsurance, according to a report in the April 9 issue of Circulation: Journal of the American Heart Association.

Sebastian Schneeweiss, M.D., from Harvard Medical School in Boston, and colleagues examined statin usage in 51,561 Canadian adults aged 66 and older, based on when there was full coverage (2001), coverage with a CAN$10-25 copay (2002), and coverage with a 25 percent coinsurance benefit (2003-2004).

The researchers found that adherence to statin therapy dropped by 5.4 percent after the switch from full coverage to a fixed copayment plan, and dropped 5.4 percent after the switch from a copayment to a coinsurance plan. However, there was a steady 1.7 percent increase per quarter in the number of patients starting statin treatment after an acute myocardial infarction. Patients were more likely to stop taking statins after a sudden switch to full out-of-pocket spending (adjusted odds ratio 1.94), "similar to Medicare's Part D 'doughnut hole,'" the report indicates.

"Fixed patient copayment and coinsurance policies have negative effects on adherence to statin lipid-lowering drug therapy but not on their initiation after myocardial infarction," Schneeweiss and colleagues conclude.

Schneeweiss has received grant support from Pfizer. Another author has received grant support from Pfizer, AstraZeneca and Bristol-Myers Squibb.

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Questionnaire Predicts Mortality After Heart Failure

Simple questionnaire also predicts risk of hospitalization

A simple health assessment questionnaire given regularly can help predict the risk of mortality and hospitalization in patients with heart failure, according to a report in the April 9 issue of Circulation: Journal of the American Heart Association.

John A. Spertus, M.D., from the University of Missouri-Kansas City, and colleagues examined whether regular health assessments using the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) could identify patients at higher risk of death or hospitalization. The questionnaire, which took an average of four to six minutes to complete, was completed by 1,358 patients who had experienced heart failure due to acute myocardial infarction at four time-points up to one year after heart failure.

The researchers found that after multivariable adjustment, decreases in KCCQ values were associated with a higher risk of all-cause mortality (hazard ratio 1.09 for each 5-point drop in KCCQ) and combined cardiovascular mortality or hospitalization (HR 1.11 for each 5-point drop in KCCQ).

"In heart failure outpatients, serial health status assessments with the KCCQ can identify high-risk patients and may prove useful in directing the frequency of follow-up and the intensity of treatment," Spertus and colleagues conclude.

The study was funded by Pfizer.

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