Latest Research

Doctors Too Pessimistic About Pulmonary Disease Prognosis

Patients could be unfairly denied life-saving intubation

Clinicians have an overly pessimistic view of the prognosis for patients with chronic obstructive pulmonary disease or asthma that could adversely affect their treatment options and ultimately their survival, according to research published online Nov. 1 in BMJ.

Martin J. Wildman, of Northern General Hospital in Sheffield, United Kingdom, and colleagues conducted a study of 832 patients admitted to 95 intensive care and respiratory high dependency units in the United Kingdom to see how the clinical prognosis of survival at 180 days compared with actual events.

Although 62 percent (517 patients) survived to 180 days, the clinical prognosis was for a mean 49 percent survival at 180 days. The mismatch between expectations and reality was worst among those in the lowest 20 percent in terms of prognosis, who had a 10 percent predicted survival rate and a 40 percent actual survival rate.

"Because decisions on whether to admit patients with chronic obstructive pulmonary disease or asthma to intensive care for intubation depend on clinicians' prognoses, some patients who might otherwise survive are probably being denied admission because of unwarranted prognostic pessimism," the authors conclude.

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Cause of Sudden Infant Death Syndrome Eludes Scientists

Immature cardiorespiratory autonomic control may play a role

While public health initiatives have made strides in reducing the incidence of sudden infant death syndrome (SIDS), it is unlikely to be eliminated until the cause of SIDS is understood, posits a review article published in the Nov. 3 issue of The Lancet.

Rachel Y. Moon, M.D., of George Washington University School of Medicine and Health Sciences in Washington, D.C., and colleagues reviewed the epidemiological trends, known risk factors, and pathophysiology and genetic factors surrounding SIDS.

The report indicates that the incidence of SIDS has declined by 50 to 90 percent in the last few decades due to public-health campaigns discouraging the prone sleeping position for infants, however, rates of SIDS among minority and indigenous groups continue to be disproportionately high. Behavioral risk factors for SIDS include prone and side infant sleep position, smoke exposure, soft bedding and overheating. Though the cause of SIDS is unknown, it is believed to be multifactorial, including abnormalities in sleep arousal and underdeveloped cardiorespiratory autonomic control. Polymorphisms in genes regulating autonomic nervous system development may predispose to SIDS.

While efforts should be focused on measures to reduce risk, such as supine sleep position for infants and avoidance of prenatal smoke exposure, "the disorder is unlikely to be completely eliminated or reduced to the lowest possible rates until the specific causative mechanisms are understood more fully," the authors write.

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Obesity, Alcohol Primary Dietary Risk Factors for Cancer

Preventive role of fruits and vegetables still unclear

The World Cancer Research Fund's second report on diet and cancer confirms the consensus view of alcohol and obesity as primary risk factors, and highlights red and processed meats as a significant dietary risk factor, according to an editorial published in the Nov. 3 issue of BMJ.

The report, "Food, Nutrition, Physical Activity and the Prevention of Cancer," is based on the work of scientists from nine universities in four countries conducted over a period of five years. Tim Key, Ph.D., of Oxford University in the United Kingdom, writes that the report's conclusions on the adverse impact of alcohol and obesity on cancer risk are in line with other expert thinking.

However, the report states that there is not yet convincing evidence on the benefits of eating fruits, vegetables and other fibrous foods, yet recommends people should eat five portions of fruits and vegetables a day. The evidence in support of increased risk of colorectal cancer from consumption of red and processed meats is more convincing, the report states.

"Many challenges remain," Key writes. "Obesity and excessive alcohol intake definitely increase the risk of cancer but are hard to control, while our understanding of whether and how particular foods affect risk is still rudimentary."

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No Cost-Benefit with Routine Use of Drug-Eluting Stents

Bare-metal stents better use of money in low-risk patients

An economic analysis shows that drug-eluting stents are only cost-effective in patients at high-risk for cardiac events, such as those needing small vessel or bypass graft stenting, according to a report in the Nov. 3 issue of The Lancet.

Hans Peter Brunner-La Rocca, M.D., of University Hospital in Basel in Switzerland, and colleagues examined data from a trial of 826 patients undergoing percutaneous coronary intervention who were randomized to either drug-eluting stents (545 patients) or bare-metal stents (281 patients). The researchers followed patients for 18 months, and compared the incremental cost-effectiveness ratios of drug-eluting and bare-metal stents in patients deemed to be low risk (stents greater than or equal to 3 mm in native vessels) versus those at high risk (stents less than 3 mm in bypass grafts) for cardiac events.

The mean cost per patient was higher with drug-eluting than bare-metal stents (11,808 Euros versus 10,450 Euros, respectively), primarily due to higher stent costs. In low-risk patients, the probability that a drug-eluting stent would have an incremental cost-effectiveness ratio of less than 10,000 Euros to prevent one major cardiac event was 0.016, whereas in high-risk patients the probability was 0.874.

These results "show that drug-eluting stents are not cost effective if used in all patients, compared with other accepted medical procedures. However, in a subset of high-risk patients with small vessel or bypass-graft stenting, which represented about a third of the study sample, drug-eluting stents were truly cost effective or even cost saving," the authors conclude.

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Heart Disease Risk Assessment Should Look at Pre-Eclampsia

Association might point to common cause or effect on disease risk profile

When assessing women for risk of cardiovascular disease, history of pre-eclampsia should be taken into account, and women with cardiovascular disease may be more prone to pre-eclampsia, according to two studies published online Nov. 1 in BMJ.

In one study, Elisabeth Balstad Magnussen, of the Norwegian University of Science and Technology in Trondheim, Norway, and colleagues studied 3,494 women, of whom 133 had a pre-eclamptic pregnancy, and found a positive association between pre-pregnancy triglyceride levels, cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and blood pressure, and pre-eclampsia. Use of oral contraceptives at baseline reduced the risk of pre-eclampsia by half compared to those who had never or no longer used them.

In a second study, Leanne Bellamy, a medical student at Imperial College School of Medicine in London, U.K., and colleagues reviewed studies with a combined dataset of 3,488,160 women, of whom 198,252 were affected by pre-eclampsia. The data also comprised 29,495 episodes of cardiovascular disease and cancer. The data showed no association between history of pre-eclampsia and cancer risk, but pointed to increased risk of various types of cardiovascular disease including hypertension, ischemic heart disease, stroke and venous thromboembolism. Overall mortality was also increased after pre-eclampsia with a relative risk of 1.49 after 14.5 years.

"This association might reflect a common cause for pre-eclampsia and cardiovascular disease, or an effect of pre-eclampsia on disease development, or both," the authors conclude.

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Broad Coalition Needed to Address Obesity Epidemic

Finland cited as an example of a nation that reversed its obesity trend through targeted efforts

A broad approach uniting government, private industry and other societal groups is needed to address the obesity epidemic in the United Kingdom, and enacting the necessary cultural change to combat obesity is indeed feasible, according to an editorial published in the Nov. 3 issue of The Lancet.

The editorial summarizes the problem of obesity in the United Kingdom and discusses recent government reports such as the Health Profile of England 2007 and the Oct. 17 report Tackling Obesities: Future Choices.

The author takes issue with the Tackling Obesities standpoint on obesity: though it avoids excessive blame-placing on an individual for becoming obese, the report depicts societal factors predisposing one to obesity as being beyond an individual's control, which is, according to the editorial, a "defeatist" point of view. Rather, "obesity ought to be a preventable -- and reversible -- condition, to which an educated population, motivated government, and conscientious food industry can respond."

The author gives the example of Finland, a nation which, through well-planned interventions that included the food industry, was able to enact broad cultural change and reverse its obesity trend.

The editorial calls for national efforts uniting public and private sectors to address the obesity epidemic. "To facilitate such changes, an apolitical, cross-departmental approach is required…so that henceforth prevention and treatment of obesity are interwoven synergistically with other initiatives," the author concludes.

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Statewide Reperfusion Program Improves Care

Regional treatment for myocardial infarction overcomes systemic problems

Coronary reperfusion to treat ST-segment elevation myocardial infarction has better outcomes if performed under a statewide program with regional systems, according to a report published online Nov. 4 in the Journal of the American Medical Association.

James G. Jollis, M.D., of Duke University in Durham N.C., and colleagues conducted a study of 1,164 patients with ST-segment elevation myocardial infarction, of whom 579 were treated before a statewide system was implemented and 585 who were treated post-implementation. The setting was five regions comprising 65 hospitals in North Carolina.

After the implementation of a statewide system, door-to-device times dropped from 85 to 74 minutes, transfer to percutaneous coronary intervention hospital times went from 165 to 128 minutes, and door-to-needle times in non-percutaneous coronary intervention hospitals went from 35 to 29 minutes. At non-percutaneous coronary intervention hospitals, non-perfusion rates remained at 15 percent after system implementation, but in hospitals that did perform the procedure it went from 23 percent to 11 percent.

"We have demonstrated that a statewide program on the development of regional systems for ST-elevation segment myocardial infarction reperfusion can significantly improve quality of care," the authors conclude. "Further research is needed to ensure that this and other programs lead to reduced mortality and morbidity from acute myocardial infarction."

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New HDL-Raising Drug May Increase Mortality Risk

Clinical trial of torcetrapib halted early due to increased risk of death

The new cholesterol drug torcetrapib, despite being able to raise serum high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein (LDL) cholesterol levels, leads to an increased risk of mortality and cardiovascular events, according to the results of a randomized controlled trial published online Nov. 5 in the New England Journal of Medicine.

Philip J. Barter, M.D., Ph.D., of St. Bartholomew's Hospital in London, U.K., and colleagues reported data from the ILLUMINATE trial, in which 15,067 patients at high cardiovascular risk were randomized in a double-blind fashion to receive either torcetrapib plus atorvastatin or atorvastatin alone. Torcetrapib is an inhibitor of cholesteryl ester transfer protein (CETP), an enzyme involved in cholesterol transport.

After 12 months, patients in the torcetrapib group had a mean increase in serum HDL cholesterol of 72.1 percent and a decrease in LDL cholesterol of 24.9 percent compared to baseline. However, the torcetrapib group had an increased risk of cardiovascular events (hazard ratio, 1.25) and death from any cause (hazard ratio, 1.58). Due to these findings the trial was halted early.

"There are at least two possible explanations for the observation of increased mortality and morbidity associated with the use of torcetrapib in our study: an off-target effect of torcetrapib, unrelated to CETP inhibition, and an adverse effect of CETP inhibition per se, with the possible generation of dysfunctional or even proatherogenic HDL cholesterol," the authors write.

This study was funded by Pfizer.

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New Antiplatelet Agent Tested in Acute Coronary Syndrome

Reduced ischemic events better than clopidogrel, but also increased likelihood of major bleeding

In patients undergoing percutaneous coronary intervention following acute coronary syndrome, long-term treatment with prasugrel, a new thienopyridine, prevents more cardiovascular events than clopidogrel, though this stronger antiplatelet effect carries an increased risk of bleeding, according to research published online Nov. 4 in the New England Journal of Medicine.

Stephen D. Wiviott, M.D., of Harvard Medical School in Boston, and colleagues randomized 13,608 patients with acute coronary syndromes scheduled for percutaneous coronary intervention to receive prasugrel or clopidrogrel for six to 15 months. The primary endpoint was death from cardiovascular causes or non-fatal myocardial infarction or stroke.

Rates of myocardial infarction, urgent target-vessel revascularization, stent thrombosis and death from cardiovascular cause were reduced in patients receiving prasugrel compared to clopidogrel (primary efficacy endpoint 9.9 percent versus 12.1 percent, respectively). The number of patients needed to treat with prasugrel compared to clopidogrel in order to prevent one efficacy end point during a 15-month period was 46. However, prasugrel was associated with an increased rate of major bleeding compared to clopidogrel (2.4 percent of patients versus 1.8 percent).

"Prasugrel would probably benefit patients with acute coronary syndromes who are undergoing PCI and who are at high risk for ischemic events and at low risk for bleeding, though those with a lower risk for ischemic events and a high risk of bleeding may be better served with clopidogrel," writes the author of an accompanying editorial.

This study was sponsored by Daiichi Sankyo and Eli Lilly.

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Hyperkalemia Risk Higher in Elderly with Heart Failure

Candesartan increases hyperkalemia risk but also reduces risk of death and hospitalization

Heart failure patients are at higher risk of hyperkalemia if they are older and male, and the risk of hyperkalemia increases in patients treated with candesartan even though the drug also reduces the risk of death and hospitalization, according to a report published in the Nov. 13 issue of the Journal of the American College of Cardiology.

Akshay S. Desai, M.D., from Brigham and Women's Hospital in Boston, and colleagues examined the incidence of hyperkalemia in 7,599 patients with heart failure randomly assigned to standard heart failure therapy plus either placebo or the renin-angiotensin-aldosterone inhibitor candesartan.

The researchers found that the candesartan group had a significantly higher rate of aggregate hyperkalemia (1.8 to 5.2 percent) and serious hyperkalemia associated with death or hospitalization (1.1 to 1.8 percent). Candesartan reduced the risk of cardiovascular death or heart failure hospitalization by 16 percent. Regardless of treatment, the risk of hyperkalemia was higher in older patients, males, diabetics, those with high creatinine or potassium, and those taking angiotensin-converting enzyme inhibitors or spironolactone.

"The risk of hyperkalemia is increased in symptomatic heart failure patients with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, or combined renin-angiotensin-aldosterone system blockade," Desai and colleagues conclude. "Although these groups derive incremental clinical benefit from candesartan, careful surveillance of serum potassium and creatinine is particularly important."

The study was funded by AstraZeneca.

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C-Reactive Protein Does Not Predict Aortic Valve Disease

Clinical factors such as age and gender related to risk

Clinical factors such as increasing age and male gender, but not C-reactive protein levels, predict the risk of calcific aortic-valve disease in the elderly, according to a report published in the Nov. 13 issue of the Journal of the American College of Cardiology.

Gian M. Novaro, M.D., from the Cleveland Clinic Florida in Weston, Fla., and colleagues measured calcific aortic stenosis by echocardiography and C-reactive protein in 5,621 elderly adults.

After a mean of five years, the researchers found that 9 percent of adults with aortic sclerosis progressed to aortic stenosis. The risk of aortic stenosis was significantly higher with increasing age (odds ratio 1.13) and in males (OR, 3.05) and was significantly lower with increasing height (OR, 0.96) and in those with African-American ethnicity (OR, 0.49). C-reactive protein levels did not significantly affect the risk of aortic sclerosis or stenosis.

"In this large population-based cohort, approximately 9 percent of subjects with aortic sclerosis progressed to aortic stenosis over a five-year follow-up period," Novaro and colleagues conclude. "C-reactive protein appears to be a poor predictor of subclinical calcific aortic-valve disease."

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High Protein Activity in Younger Heart Attack Victims

Attack occurs earlier in patients with high cholesteryl ester transfer protein activity

Patients who have high cholesteryl ester transfer protein activity soon after their first myocardial infarction are younger and have their attack at a younger age, according to study findings published in the Nov. 13 issue of the Journal of the American College of Cardiology.

Marianne Zeller, Ph.D., from IFR Sante STIC in Dijon, France, and colleagues measured cholesteryl ester transfer protein activity within 24 hours of symptom onset in 347 patients with a first myocardial infarction.

The researchers found that compared with the lowest tertile of cholesteryl ester transfer activity, patients in the highest tertile had their first myocardial infarction a mean of 8.5 years earlier. Further stratification based on non-high-density lipoprotein (HDL) cholesterol and HDL2b tertiles showed that patients in the highest tertile of cholesteryl ester transfer activity were 18 years younger than patients in the lowest tertile.

"The association of high cholesteryl ester transfer rates with young age at first myocardial infarction lends support to a significant contribution of cholesteryl ester transfer protein to the accelerated progression of disease among asymptomatic patients," Zeller and colleagues conclude.

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Fenofibrate May Lower Retinopathy Risk in Diabetics

Mechanism appears to be unrelated to lipid-lowering effects

Treating individuals with type 2 diabetes with fenofibrate may reduce the progression of diabetic retinopathy, though this effect does not appear to be related to fenofibrate's lipid-lowering effects, according to study findings published online Nov. 6 in the The Lancet.

A.C. Keech, of the University of Sydney in Australia, and colleagues followed participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial for a mean of five years to assess whether fenofibrate treatment was associated with lower rates of laser surgery for diabetic retinopathy. The trial randomized 9,795 patients with type 2 diabetes to receive either daily fenofibrate or placebo. Standardized retinal photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions was done in a substudy of 1,012 patients.

Treatment with fenofibrate was associated with a reduction in the need for first laser treatment for diabetic retinopathy (hazard ratio 0.69). In the substudy group, reduction in two-step progression grade was largely seen in patients with pre-existing retinopathy. The need for laser treatment was not found to be affected by plasma lipid concentrations.

"These findings suggest that the mechanism of benefit of fenofibrate in diabetic retinopathy must go beyond the effects of this drug on lipid concentrations or to lower blood pressure, and might be conferred mainly by other means," the authors write.

Several authors report financial relationships with the pharmaceutical industry.

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Cardiac Resynchronization Benefit Questioned

Peak oxygen consumption doesn't improve in patients with a narrow QRS interval

In patients with moderate-to-severe heart failure, cardiac-resynchronization therapy (CRT) does not improve peak oxygen consumption, suggesting that those with a narrow QRS interval may not benefit from implantable cardioverter-defibrillators, according to a report published online Nov. 6 in the New England Journal of Medicine.

John F. Beshai, M.D., of the University of Chicago, and colleagues randomly assigned 172 patients with a standard indication for an implantable cardioverter-defibrillator to receive either CRT or no CRT for six months.

The researchers found no significant group differences in the primary end point: an increase in peak oxygen consumption of at least 1.0 milliliter per kilogram of body weight per minute during cardiopulmonary exercise testing. Forty-six percent of the CRT group achieved that goal compared to 41 percent of the control group. Although CRT improved oxygen consumption in a subgroup of patients with a prolonged QRS interval of at least 120 milliseconds, it had no effect on patients with an interval of less than 120 milliseconds.

"CRT did not improve peak oxygen consumption in patients with moderate-to-severe heart failure, providing evidence that patients with heart failure and narrow QRS intervals may not benefit from CRT," the authors conclude.

This study was supported by St. Jude Medical.

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Higher Level of Obesity Means More Disability

Effect of body mass index on mortality risk varies by cause of death

The effect of body mass index on mortality rates varies with the cause of death, while the burden of disability among older obese adults is growing, despite improvements in cardiovascular factors, according to two studies published in the Nov. 7 issue of the Journal of the American Medical Association.

Katherine M. Flegal, Ph.D., of the National Center for Health Statistics at the Centers for Disease Control and Prevention in Hyattsville, Md., and colleagues analyzed national health survey data to look at the relationship between body mass index and mortality.

Underweight was associated with increased mortality due to non-cancer, non-cardiovascular disease causes but was not associated with increased mortality due to cancer and cardiovascular disease. There was an association between obesity and mortality due to cardiovascular disease but not due to cancer, except those cancers considered to be obesity-related, nor to non-cancer, non-cardiovascular disease mortality.

Dawn E. Alley, Ph.D., and Virginia W. Chang, M.D., Ph.D., of the University of Pennsylvania in Philadelphia, analyzed two sets of data from 1988-1994 and 1999-2004 on 9,928 adults aged 60 years and older, and found that the burden of disability due to obesity is increasing.

"Over time, declines in obesity-related mortality, along with younger age at onset of obesity, could lead to an increased burden or disability within the obese older population," Alley and Chang conclude.

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Kidney Disease on the Rise in United States

More diabetes, hypertension, more complications to come

The incidence of chronic kidney disease in the United States is on the rise, especially among those with diabetes and hypertension, researchers report in the Nov. 7 issue of the Journal of the American Medical Association.

Josef Coresh, M.D., Ph.D., of Johns Hopkins University in Baltimore, and colleagues analyzed data from the 1988-1994 and 1999-2004 National Health and Nutrition Examination Surveys and found rising incidence of increased albuminuria and decreased glomerular filtration rate between the two periods.

In the earlier period, the prevalence of stage 1 to 4 chronic kidney disease was 10 percent, but rose to 13.1 percent in the later period. While the rising prevalence of increased albuminuria could be explained by greater prevalence of diabetes and hypertension, this only went some way toward explaining the greater incidence of decreased glomerular filtration rate.

"Because individuals with early stages of chronic kidney disease have a higher risk of cardiovascular disease morbidity and mortality than their risk of progression to kidney failure, cardiovascular risk factor management in this group is critical," the authors write. "The high prevalence of chronic kidney disease overall, and particularly among older individuals and persons with hypertension and diabetes, suggests that chronic kidney disease needs to be a central part of future public health planning."

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Tezosentan No Help in Acute Heart Failure

Endothelin receptor antagonist did not improve clinical outcomes or symptoms

The endothelin receptor antagonist tezosentan does not improve either the symptoms or the clinical outcome for patients with acute heart failure, according to study findings published in the Nov. 7 issue of the Journal of the American Medical Association.

John J.V. McMurray, M.D., of Western Infirmary in Glasgow, U.K., and colleagues conducted two independent, identical studies, which ran concurrently and comprised patients enrolled in Australia, Europe, Israel and North America. To be admitted to the trial, patients fulfilled two of four criteria: left ventricular systolic dysfunction; radiologic pulmonary congestion or edema; clinical pulmonary edema; and elevated plasma concentrations of B-type or N-terminal pro-B-type natriuretic peptide.

While 730 patients were given 5 mg/hour of tezosentan for 30 minutes and then 1 mg/hour for 24 to 72 hours, 718 patients were given placebo. In both treatment groups the baseline dyspnea scores were similar and treatment did not result in any more improvement than placebo. The seven-day incidence of death or worsening heart failure was identical at 26 percent in both groups.

"So far, it has proved impossible to identify a therapeutic role for endothelin antagonists in patients with acute or chronic heart failure," the authors conclude.

The trials were funded by Actelion Ltd., of Allschwil, Switzerland.

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PET Revascularization Beneficial in Heart Patients

PET imaging beneficial in certain subgroups of patients

F-18-fluorodeoxyglucose positron emission tomography (PET) leads to beneficial outcomes in patients with ventricular dysfunction and suspected coronary disease if its recommendations on revascularization are followed and in patients who have not had recent angiography, according to research published in the Nov. 13 issue of the Journal of the American College of Cardiology.

Rob S.B. Beanlands, M.D., from the University of Ottawa Heart Institute in Ontario, Canada, and colleagues randomly assigned 430 patients with severe left ventricular dysfunction and suspected coronary disease to standard care or F-18-fluorodeoxyglucose PET.

After one year, the researchers found that 30 percent of patients in the PET group and 36 percent of the standard care group experienced cardiac death, myocardial infarction or recurrent hospitalization for cardiac causes. The difference was not statistically significant. Significant benefits for all three outcomes were observed in patients who followed PET recommendations on revascularization (hazard ratio 0.62) and for cardiac death in patients without recent angiography (hazard ratio 0.40).

"The study adheres to every detail of a randomized trial except for one weakness -- 25 percent of the patients with PET-indicated revascularization did not have it done," K. Lance Gould, M.D., from the University of Texas Medical School at Houston, writes in an accompanying editorial. He adds that "the study is substantially a trial of whether the deciding physician chose to adhere to treatment indicated by PET F-18-fluorodeoxyglucose on the basis of 'clinical judgment' and/or bias against revascularization."

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Atherectomy Allows Simple Drug-Eluting Stenting

Avoids need for complex stenting in patients with coronary lesions

Performing directional coronary atherectomy before implanting drug-eluting stents may avoid the need for complex stenting in patients with bifurcated coronary lesions, according to the results of a study published Nov. 13 in the Journal of the American College of Cardiology.

Etsuo Tsuchikane, M.D., Ph.D., from Toyohashi Heart Center in Aichi, Japan, and colleagues performed directional coronary atherectomy in 99 patients with bifurcated coronary lesions before implanting drug-eluting stents by simple stenting in all but two patients.

The researchers found that the nine-month binary restenosis rates were 1.1 percent in the main branch and 3.4 percent in the side branch. Two patients underwent target lesion revascularization. There were no in-hospital major adverse cardiac events, and there were no deaths, coronary artery bypass grafting, or myocardial infarctions in the first year.

"Directional coronary atherectomy before drug-eluting stent implantation can possibly avoid complex stenting," Tsuchikane and colleagues conclude. "This strategy may provide a good long-term outcome in patients with bifurcated lesions."

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Prenatal Drug Therapy Reduces HIV Drug Resistance

Tenofovir and emtricitabine at delivery reduce resistance six weeks later

In pregnant women infected with HIV, a single dose of tenofovir and emtricitabine administered at delivery as an adjunct to nevirapine results in reduced resistance to non-nucleoside reverse transcriptase inhibitors six weeks after delivery, according to study findings published online Nov. 7 in The Lancet.

Benjamin H. Chi, M.D., of the Centre for Infectious Disease Research in Zambia in Lusaka, Zambia, and colleagues conducted a study of 400 HIV-infected pregnant women of whom 200 were randomized to receive a single oral dose of 300-mg tenofovir disoproxil fumarate with 200-mg emtricitabine, while 199 received no drug.

Six weeks after delivery, women in the intervention group were 53 percent less likely to have resistance to non-nucleoside reverse transcriptase inhibitors. In both groups there were four cases of anemia. Serious adverse events among infants occurred in 10 percent of the intervention group and 12 percent of the control group, none of which were attributed to the intervention.

"Despite its effectiveness, this intervention might need modification to achieve the optimum protective effect," the authors write. "Nevertheless, it is an important adjunct to regimens that incorporate intrapartum nevirapine and should be considered in settings where drug combinations to be taken over several days might be impractical for patients or for the local health infrastructure," they conclude.

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Cancer Risk Related to Body Mass Index

Study of postmenopausal U.K. women finds 6,000 cases a year attributable to overweight or obesity

The risk of 10 different cancers increases as body mass index rises, according to research published online Nov. 6 in BMJ Online First.

Gillian K. Reeves, Ph.D., of the University of Oxford in Oxford, United Kingdom, and colleagues analyzed data from the Million Women Study cohort, comprising 1.2 million U.K. women aged 50 to 64 during 1996 to 2001.

During the average follow-up of 5.4 years for cancer incidence and 7.0 years for cancer mortality, there were 45,037 cases of cancer and 17,203 cancer-related deaths. With every 10-unit increase in body mass index the risk of incidence increased for endometrial, kidney, ovarian and pancreatic cancers, adenocarcinoma of the esophagus, leukemia, multiple myeloma, non-Hodgkin's lymphoma, colorectal cancer in premenopausal women and breast cancer in postmenopausal women.

"Among postmenopausal women in the U.K., 5 percent of all cancers (about 6,000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the esophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity," the authors conclude.

"The strongest empirical support for mechanisms to link obesity and cancer risk involves the metabolic and endocrine effects of obesity," Eugenia E. Calle, Ph.D., of the American Cancer Society, writes in an accompanying editorial.

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Peptide Levels Predict Mortality in Heart Failure

Midregional pro-ANP adds prognostic value to NT-proBNP

Midregional pro-atrial natriuretic peptide (proANP) levels predict mortality in patients with chronic heart failure and adds prognostic value to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, researchers report in the Nov. 13 issue of the Journal of the American College of Cardiology.

To assess its prognostic value, Stephan von Haehling, M.D., from Charite Medical School in Berlin, Germany, and colleagues measured midregional proANP in 525 patients with chronic heart failure (mean NT-proBNP 3,637 pg/mL) and validated the results in an independent group of 249 heart failure patients (mean NT-proBNP 1,116 pg/mL).

The researchers found that 33 percent of patients in the first group died and that increasing midregional proANP predicted poor survival (adjusted risk ratio 1.35 per increase in standard deviation). Midregional proANP added prognostic value to NT-proBNP and had higher prognostic value in obese patients.

"Midregional proANP is an independent predictor of mortality in patients with chronic heart failure," von Haehling and colleagues conclude. "Midregional proANP adds prognostic information to NT-proBNP."

B.R.A.H.M.S., a company that developed midregional proANP, employs several of the physicians participating in the study.

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Caffeine Therapy Beneficial in Apnea of Prematurity

At 18 to 21 months, caffeine-treated infants more likely to survive without neurodevelopmental disabilities

In very low birth weight infants with apnea of prematurity, caffeine therapy increases the odds of survival without neurodevelopmental disability at 18 to 21 months, according to a report published in the Nov. 8 issue of the New England Journal of Medicine.

Barbara Schmidt, M.D., of McMaster University in Hamilton, Ontario, Canada, and colleagues randomly assigned 2,006 infants with birth weights of 500 to 1,250 grams to receive either caffeine or placebo.

Of the infants for whom adequate data were available on the primary outcome (death, cerebral palsy and cognitive delay), the researchers found that the caffeine group was less likely to die or survive with a neurodevelopmental disability (40.2 percent versus 46.2 percent). They also found that the caffeine group was significantly less likely to develop cerebral palsy (4.4 percent versus 7.3 percent). At follow-up, however, they observed no significant group differences in the rates of death, deafness and blindness, and the mean percentiles for height, weight and head circumference.

"In the aggregate, the data from the current report of Schmidt et al., combined with the data from their earlier report, suggest that the temporary adverse effect of diminished weight gain for three weeks in infants treated with caffeine for apnea of prematurity is outweighed by the long-term benefit of improved survival without neurodevelopmental disability at 18 to 21 months," states the author of an accompanying editorial. "Nevertheless, longer follow-up is warranted, since the neurodevelopmental outcome at 18 to 21 months is not wholly predictive of later neurodevelopmental outcome and school performance."

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Humoral Immunity Has Long Duration to Viral Antigens

But peripheral memory B-cell numbers may not correlate with antigen-specific antibody levels

The duration of humoral immunity to common viral antigens is remarkably long, but its duration to common vaccine antigens is somewhat shorter, according to a report published in the Nov. 8 issue of the New England Journal of Medicine.

Ian J. Amanna, Ph.D., of the Oregon Health & Science University in Beaverton, Ore., and colleagues followed 45 subjects for up to 26 years, measuring antibody titers specific for six viral antigens (vaccinia, measles, mumps, rubella, varicella-zoster, and Epstein-Barr) and two non-replicating antigens (tetanus and diphtheria). They also measured antigen-specific memory B cells and compared memory B-cell frequencies to their corresponding serum antibody levels.

The researchers estimated that the half-lives of antiviral antibody responses ranged from about 50 years for varicella-zoster virus to more than 200 years for other viruses such as measles and mumps, and that the half-lives of antibody responses against tetanus and diphtheria were 11 years and 19 years, respectively. Although the investigators found that B-cell memory was long-lived, they could find no significant association between peripheral memory B-cell numbers and antibody levels for five of the eight antigens.

"In cases in which multiple exposures or repeated vaccinations were common, memory B-cell numbers did not correlate with antibody titers," the authors conclude. "This finding suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity."

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Congenital Heart Disease Linked to Brain Abnormalities

Pre-surgical imaging studies suggest that affected infants develop abnormalities in utero

Term infants with severe congenital heart disease requiring surgery often have widespread brain abnormalities similar to those seen in premature infants, which may reflect abnormal brain development in utero, according to the results of a study published in the Nov. 8 issue of the New England Journal of Medicine.

Steven P. Miller, M.D., of the University of California San Francisco, and colleagues studied 41 term newborns with congenital heart disease, including 29 with transposition of the great arteries and 12 with single-ventricle physiology, and compared their pre-surgical imaging studies, ratio of N-acetylaspartate to choline, ratio of lactate to choline, average diffusivity, and fractional anisotropy of white-matter tracts with 16 control newborns of a similar gestational age.

The researchers found that infants with congenital heart disease had a decrease of 10 percent in the ratio of N-acetylaspartate to choline, an increase of 28 percent in the ratio of lactate to choline, an increase of 4 percent in average diffusivity, and a decrease of 12 percent in white-matter fractional anisotropy compared to control infants. They also found white-matter injury in 13 (32 percent) of infants with congenital heart disease but in none of the controls.

"The new information provided by advanced brain imaging and spectroscopy makes it essential to learn more about fetal brain development in children with congenital heart disease to develop better neuroprotective strategies and improve outcome," states the author of an accompanying editorial.

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Chemotherapy Plus Radiation Best for Early Hodgkin's

Most effective regimens identified for patients with favorable and unfavorable prognoses

In early-stage Hodgkin's disease, patients with favorable prognostic features should receive chemotherapy plus involved-field radiotherapy while those with unfavorable prognostic features should receive four courses of chemotherapy plus involved-field radiotherapy, researchers report in the Nov. 8 issue of the New England Journal of Medicine.

Christophe Ferme, M.D., of the Institut de Cancerologie Gustave Roussy in Villejuif, France, and colleagues studied 1,538 patients with favorable or unfavorable prognostic features. In a first trial, they compared two regimens: three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone. In a second trial, they compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy, four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy.

After a median follow-up of 92 months, the researchers found that estimated five-year event-free survival in the first trial was significantly higher in patients who received the first regimen (98 percent versus 74 percent). They found that estimated five-year event-free survival in the second trial was similar for all three regimens (84 percent, 88 percent and 87 percent, respectively).

"As a result of the long second phase -- up to 10 years in some instances -- it is possible that results reported by Ferme et al. are already outdated," states the author of an accompanying editorial.

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