A summary of the "must-read" articles from the journals in that pile on your desk.
Hepatitis A Vaccine Good for Postexposure Prophylaxis
Immune globulin and vaccine confer similar level of protection
After exposure to hepatitis A, both immune globulin and vaccination confer good levels of protection against infection, but vaccination also offers long-term protection, according to the results of a study published in the Oct. 25 issue of the New England Journal of Medicine.
John C. Victor, Ph.D., of the University of Michigan in Ann Arbor, and colleagues conducted a study of 1,090 people (average age 12 years) who were susceptible to hepatitis A and had been exposed to infected patients within the previous two weeks. The participants were randomized to receive one dose of immune globulin (522 subjects) or one dose of hepatitis A vaccine (568 subjects).
Among the vaccinated group, 25 (4.4 percent) became infected with hepatitis A, versus 17 (3.3 percent) of those who had received immune globulin. Although there was better protection from immune globulin, the differential was never greater than 1.5 percent, the authors write.
"By providing a scientific context in which to re-evaluate the relative benefits of immune globulin and vaccine, our study informed policy decisions regarding hepatitis A vaccine," the authors conclude.
Merck donated the hepatitis vaccine, VAQTA, and provided funds for purchase of immune globulin.
ACP Endorses CDC's Adult Immunization Schedule
Publication of updated recommendations will help physicians meet adult patients' vaccination needs
The American College of Physicians (ACP) has endorsed the U.S. Centers for Disease Control and Prevention's adult immunization schedule for 2007-2008, according to an article published online Oct. 18 in the Annals of Internal Medicine, which is publishing the recommendations for the first time.
Sandra Fryhofer, M.D., an Atlanta-based member of the ACP Adult Immunization Advisory Board, said in a statement that physicians should know of these updated provisions so they can better meet patient needs.
New recommendations include varicella vaccinations for all adults with no evidence of immunity to varicella, and zoster vaccinations for all adults aged 60 and over, including those who have had prior episodes of shingles.
Nearly 50,000 Americans -- 99 percent of them adults -- die each year from vaccine-preventable diseases, note the authors of an accompanying editorial. Although they caution that it will take time for adult immunization to achieve the same level of success as the U.S. childhood immunization program, they call the ACP's endorsement of the CDC guidelines "an important step."
Antibiotics Reduce Pneumonia Risk After Chest Infection
No reason for routine use in common respiratory tract infections
Although there is no justification for using antibiotics to prevent serious complications as a result of upper respiratory tract infections, they are useful in protecting against pneumonia in elderly patients with chest infection, according to a report published online Oct. 18 in BMJ.
Irene Petersen, of University College London in the United Kingdom, and colleagues analyzed data on 3.36 million cases of respiratory tract infection from the U.K.'s general practice research database. They looked at the risk of a number of serious complications, such as pneumonia after upper respiratory tract infection, quinsy after sore throat and mastoiditis after otitis media.
To prevent one complication it was necessary to treat over 4,000 patients with antibiotics. However, among elderly patients with chest infection, treating 39 patients prevented one case of pneumonia, and among younger age groups the number needed to treat ranged from 96 to 119 people.
"For chest infection, research should focus on developing clinical algorithms and diagnostic technology that can be easily applied in primary care to enable confident distinction between acute bronchitis and early pneumonia and to identify those who are most likely to develop pneumonia," the authors conclude.
Better Nutrition, Sanitation Would Reduce Child Mortality
Priority should be given to the poor in order to achieve greatest impact
Nutritional and environmental interventions aimed at poor people can help achieve United Nations Millennium Development Goals (MDG) targets for reducing child mortality, according to a report published in the Oct. 24/31 issue of the Journal of the American Medical Association.
To assess whether improved child nutrition, and provision of clean water, sanitation and fuels had an impact on child mortality rates, Emmanuela Gakidou, Ph.D., of Harvard University in Cambridge, Mass., and colleagues analyzed data from 42 countries in Latin America and the Caribbean, South Asia, and sub-Saharan Africa.
If clean household fuels and water, sanitation and improved child nutrition were implemented in families with children under 5 years of age, child deaths would be reduced in each area, the investigators found. It would result in 49,700 fewer deaths (14 percent) in Latin America and the Caribbean, 800,000 (24 percent) in South Asia, and 1.47 million (31 percent) in sub-Saharan Africa.
Such benefits would enable the three regions to bridge between 30 percent and 48 percent of the gap between the current situation and the MDG target on reducing child mortality.
"Fifty percent coverage of the same environmental and nutritional interventions, as envisioned by the MDGs, would reduce child mortality by 26,900, 510,000 and 1.02 million in the three regions, respectively, if the interventions are implemented among the poor first," the authors write.
Whole Grain Cereals Protect Men Against Heart Failure
Effect does not extend to cereals made with refined grains
Eating whole grain breakfast cereals is associated with a lower risk of heart failure among men, researchers report in the Oct. 22 issue of the Archives of Internal Medicine.
Luc Djousse, M.D., of Harvard Medical School in Boston, and a colleague followed 21,376 men, median age 53.7 years, who were participants in the Physicians' Health Study. Cereal consumption and health habits were ascertained at baseline, and medical histories were followed up with annual questionnaires.
After an average follow-up of 19.6 years, there were 1,018 new cases of heart failure. Hazard ratios for those who consumed one or fewer servings of cereal a week were 0.92, versus 0.79 for those who consumed between two and six servings per week and 0.71 for those consuming seven or more servings per week. These associations held after adjustments for age, smoking, alcohol consumption and other potential confounders, but only for whole grain cereals, not refined cereals.
"If confirmed in other studies, a higher intake of whole grains along with other preventive measures could help lower the risk of heart failure," the authors conclude.
Study Finds Opportunities for More HIV Testing in U.S.
Less than 25 percent of individuals at medium or high risk reported an HIV test within the last year
Low rates of HIV testing are likely contributing to a "substantial" number of undiagnosed cases in the United States, according to research presented in the Oct. 22 issue of the Archives of Internal Medicine.
Jan Ostermann, Ph.D., of Duke University in Durham, N.C., and colleagues analyzed data from six consecutive annual National Health Interview Surveys, which asked 146,868 participants, aged 18 to 64 years, about past HIV testing, planned future testing, and risk exposure and perceptions.
Testing rates over the 2000-2005 survey period remained low and relatively steady, with lifetime and past year rates of 37 percent and 10 percent, respectively. Females and non-white minorities were most likely to report testing. People reporting medium and high self-perceived risk were more likely to plan to get tested than actually do so. Also, the investigators found, almost half of HIV tests were done during medical check-ups or prenatal care.
"Increased integration of HIV testing into routine medical care, as currently recommended by the Centers for Disease Control and Prevention, is likely to increase overall testing rates in the United States," the authors write. "Although groups at higher risk of HIV (including those with heavier alcohol use and depressive symptoms) have higher rates of both planned and actual testing, it is precisely these groups who exhibit the greatest gaps between testing intention and action. These findings suggest that considerable potential exists to increase testing in higher-risk groups if individual and structural barriers can be identified and addressed."
Apolipoprotein B Testing Recommended for Heart Patients
Low-density lipoprotein and non-high-density lipoprotein cholesterol tests less predictive of cardiovascular events, according to review
Apolipoprotein B is an effective indicator of low-density lipoprotein (LDL) particle numbers and should be tested in heart patients, along with the ratio of apolipoprotein B to apolipoprotein A-1, after other tests, researchers report in the Oct. 30 issue of the Journal of the American College of Cardiology.
James Mudd, M.D., of Johns Hopkins University in Baltimore, and colleagues reviewed studies of LDL and coronary artery disease that showed that curbing LDL in heart patients helps prevent new events. But most heart attacks occur despite aggressive treatment, possibly due to late treatment or other reasons.
The current standard involves curbing LDL levels by targeting LDL cholesterol. Measuring non-high-density lipoprotein (HDL) cholesterol is advised when triglyceride levels drop below 200 mg/dL. Most studies show that measuring apolipoprotein B is a better heart attack risk predictor than LDL cholesterol and non-HDL cholesterol. Other tests for LDL particles are not routinely advised.
"Because apolipoprotein B is a superior predictor of LDL particles, we recommend that apolipoprotein B and the apolipoprotein B/apolipoprotein A-1 ratio be determined after measurement of LDL cholesterol, non-HDL cholesterol, and the ratio of total cholesterol/HDL cholesterol to better predict coronary artery disease and assess efficacy of treatment," the authors write.
Studies' Funding Linked to Reporting of Adverse Effects
Pharmaceutical-funded studies less likely to find statistically significant adverse effects
Studies of inhaled corticosteroids that are funded by the pharmaceutical manufacturer of the drug are less likely to find statistically significant adverse effects than studies that derive their funding elsewhere, according to a report published in the Oct. 22 Archives of Internal Medicine.
Antonio Nieto, M.D., of the Children's Hospital La Fe in Valencia, Spain, analyzed data from 275 pharmaceutically funded (PF) studies and 229 other studies (NoPF) that reported on the presence or absence of adverse effects of inhaled corticosteroids, which have become widely used even for mild and moderate asthma.
The investigators found that the PF studies were significantly less likely to report statistically significant differences in adverse effects than NoPF studies (prevalence ratio 0.53), though this finding became non-significant after controlling for certain design features more common in PF studies. However, authors of PF articles were more likely to call a drug "safe" (prevalence ratio 3.68) when the study found a statistically significant increase in adverse effects than authors of NoPF studies.
"Funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings," the authors write. "Disclosure and conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs."
Lifestyle Key to Preventing Most Heart Attacks in Women
Swedish study shows strong benefits of diet, exercise, weight control and avoiding smoking
Most heart attacks in women can be prevented with a combination of healthy diet and other heart-healthy lifestyle behaviors, researchers report in the Oct. 22 issue of the Archives of Internal Medicine.
Agneta Akesson, Ph.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues studied 24,444 postmenopausal women who were free of cancer, cardiovascular disease and diabetes at baseline in late 1997 and followed them for an average of 6.2 years, during which there were 308 cases of primary myocardial infarction.
The researchers found that women who ate a diet rich in vegetables, fruit, whole grains, fish, legumes, and had a moderate alcohol intake of 5 grams or less per day -- in combination with not smoking, regular exercise and maintaining a lean body mass -- had a 92 percent decreased risk of heart attack compared to women who had no low-risk diet and lifestyle factors.
"Our results suggest that important steps can be taken to significantly reduce the risk of primary non-fatal coronary heart disease, although precaution is needed when deriving more stringent recommendations based on the results," the authors write. "Randomized trials are clearly preeminent to establish causality between both diet and lifestyle and coronary heart disease risk, but because long-term randomized trials are difficult to perform for multiple risk factors, the combined low-risk behavior may never be able to be tested in primary prevention trials."
Weight Gain Through Life Linked to Breast Cancer Risk
Risk higher among women who don't use menopausal hormone therapy
Women whose body mass index increases as they get older and who don't use menopausal hormone therapy may have an increased risk of developing breast cancer, according to a report in the Oct. 22 Archives of Internal Medicine.
Jiyoung Ahn, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues followed 99,039 postmenopausal women, aged 57 years and older, who were participants in the National Institutes of Health-AARP Diet and Health Study. Weight, height, and waist and hip circumferences at ages 18, 35, 50 years, and as of 1996, was determined by questionnaire. Breast cancer incidence through 2000 was determined by follow-up mailings and public database searches.
Among women who had never used menopausal hormone therapy or who had stopped using it, weight gains at ages 18-35 years, 35-50 years and 50 years and older were each consistently associated with an increased risk of breast cancer. Women who had been obese throughout their lives had no increased risk of breast cancer relative to women who had consistently maintained a normal weight. No relationship was observed between those who maintained or lost weight as adults and breast cancer.
"Because weight gain during adulthood mainly reflects the deposition of fat mass rather than lean body mass, weight gain potentially represents age-related metabolic change that may be important in breast cancer development," the authors conclude.
Annual Death Rates Analyzed in Cardiogenic Shock Patients
Long-term risk largely due to cardiovascular risk factors
For patients with myocardial infarction who experience cardiogenic shock and survive the first year, annual mortality rates are similar to those without shock and are largely determined by cardiovascular risk factors, according to research published in the Oct. 30 issue of the Journal of the American College of Cardiology.
Mandeep Singh, M.D., from the Mayo Clinic in Rochester, Minn., and colleagues assessed predictors of long-term outcome in 22,883 patients with ST-segment elevation myocardial infarction, of whom 1,891 experienced cardiogenic shock.
The researchers found that 96.9 percent of patients without shock survived 30 days and 67.3 percent survived 11 years, compared with 50.4 percent and 27.8 percent, respectively, for patients with shock. After the first year, regardless of whether they had experienced shock, 2 percent to 4 percent of patients died each year. Long-term outcomes were largely determined by risk factors such as age, diabetes and hypertension.
The results "suggest that the cup can be viewed as half full -- approximately one-half of patients with shock complicating myocardial infarction will be alive at one year, with a long-term prognosis determined largely by typical cardiovascular risk factors," Judith S. Hochman, M.D., and Renato Apolito, M.D., from New York University School of Medicine in New York City, write in an accompanying editorial.
Motivated Hospital Staff Improves Malaria Survival
African study shows significantly lower mortality rates in children who receive more attentive care
More children with malaria who are admitted to hospitals in developing countries will survive if hospital staff are given a financial incentive to follow guidelines for care, according to a report published online Oct. 22 in BMJ.
Sidu Biai, M.D., of the INDEPTH Network in Guinea-Bissau, Africa, and colleagues randomized 951 children with malaria (aged 3 months to 5 years) to either an intervention ward or a control ward in the national hospital of Guinea-Bissau in northwest Africa. All the children received a free drug kit for malaria and staff members assigned to both wards were trained in a standardized protocol for management of malaria. Nurses and doctors on the intervention ward were rigorously supervised to ensure they followed the protocol and received an extra stipend as an incentive to do so.
In the intervention group, 5 percent of patients died in the hospital, compared to 10 percent of patients in the control group. The length of stay was shorter in the intervention group than in the control group (seven versus eight days) and the rate of discharge from the hospital was 35 percent shorter in the intervention group. At follow-up visits 28 days after discharge, mortality was 7 percent in the intervention group and 11 percent in the control group.
"Our results imply that consideration should be given to supporting health staff salaries, possibly on the basis of performance targets," the authors conclude.
Exercise Cuts Known Risk Factors for Heart Disease
Blood pressure, hemostatic and inflammatory factors most affected risk factors
Exercise leads to a decline in heart disease risk due to its effect on well-known risk factors such as inflammation and blood pressure, researchers report in the Nov. 6 issue of Circulation: Journal of the American Heart Association.
Samia Mora, M.D., of Brigham and Women's Hospital in Boston, and colleagues analyzed baseline blood levels of inflammatory and hemostatic biomarkers, novel lipids, traditional lipids, low-density lipoprotein, total cholesterol and hemoglobin A1c in 27,055 apparently healthy female study subjects, and data the women volunteered on diabetes, hypertension, height, weight and exercise.
After a mean follow-up of 10.9 years, there were 979 cardiovascular disease episodes reported. Physical exercise was linked to significantly decreased cardiovascular disease risk. The researchers found an exercise-related cardiovascular disease reduction from effects on hemoglobin A1c and diabetes (8.9 percent), body mass index (10.1 percent), novel lipids (15.5 percent), traditional lipids (19.1 percent), blood pressure (27.1 percent), inflammatory and hemostatic biomarkers (32.6 percent).
"The inverse association between physical activity and cardiovascular disease risk is mediated in substantial part by known risk factors, particularly inflammatory/hemostatic factors and blood pressure," the authors write.
Good Results for Primary Care HIV Treatment in Zambia
But early mortality rate remains high
In sub-Saharan Africa, pediatric antiretroviral therapy delivered in a primary health care setting by nurses and physician assistants can achieve good results, but earlier intervention is needed to reduce the high levels of mortality in the first 90 days of therapy, researchers report in the Oct. 24/31 issue of the Journal of the American Medical Association.
Carolyn Bolton-Moore, of the Centre for Infectious Disease Research in Zambia, and colleagues analyzed data on 4,975 children enrolled into HIV care in 18 government primary health care facilities in Lusaka, Zambia. Of these, 2,938 (59.1 percent) started antiretroviral therapy, including 2,087 who were in stage III or IV of infection.
When the data was analyzed, among the children who started antiretroviral therapy, 158 (5.4 percent) had withdrawn from treatment, and 382 (13 percent) were 30 days or more late for follow-up. Of those who continued on antiretroviral therapy, 198 (8.3 percent) died over 3,018 child-years of follow-up, with 112 deaths (56.6 percent) occurring within the first 90 days of onset of treatment.
"Care provided by clinicians such as nurses and clinical officers can result in good outcomes for HIV-infected children in primary health care settings in sub-Saharan Africa. Mortality during the first 90 days of therapy is high, pointing to a need for earlier intervention," the authors conclude.
Growing Waist Circumferences Are a Worldwide Problem
Overweight widespread; bigger bodily measurements linked with more health risks
A major endeavor to take a snapshot of the state of obesity around the globe found that excess weight was pandemic in most areas and that abdominal obesity had a graded relationship with cardiovascular disease and diabetes. The study was published in the Oct. 23 issue of Circulation: Journal of the American Heart Association.
Beverley Balkau, Ph.D., of Inserm in Villejuif, France, and colleagues analyzed data from 182,970 patients screened in 63 countries as part of the International Day for the Evaluation of Abdominal Obesity (IDEA) study.
Based on body mass index, 24 percent of men and 27 percent of women were obese, and another 40 percent of men and 30 percent of women were overweight. Obesity differed more between regions than the relatively similar overweight rates, with lows near 7 percent in men and women in eastern Asia and highs at roughly 39 percent in women in the Middle East and northern and southern Africa. The frequency of diabetes and cardiovascular disease rose with waist circumference and body mass index, even in normal-weight patients.
"Routine measurement of waist circumference -- a convenient and inexpensive measure in primary care -- provides a clinical marker for risk of cardiovascular disease and diabetes mellitus in all regions of the world, even in patients with normal weight. The rise in adiposity worldwide is likely to contribute to major increases in morbidity and mortality from diabetes mellitus and cardiovascular disease unless it can be adequately addressed by public health programs," the authors write.
Drug Improves Outcomes After Coronary Intervention
Fondaparinux reduces risk of bleeding and adverse events better than enoxaparin
Fondaparinux reduces the risk of bleeding and adverse outcomes in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) better than enoxaparin, according to the results of a study published in the Oct. 30 issue of the Journal of the American College of Cardiology.
Shamir R. Mehta, M.D., from McMaster University in Hamilton, Ontario, Canada, and colleagues studied 12,715 patients with acute coronary syndrome who underwent heart catheterization during the initial hospitalization, of whom 6,238 underwent PCI. Patients were randomized to intravenous fondaparinux or enoxaparin to compare the drugs' efficacy and safety.
The researchers found that fondaparinux significantly reduced the risk of major bleeding (hazard ratio 0.46) at day 9, significantly reducing the risk of death, myocardial infarction, stroke and major bleeding (hazard ratio 0.78). Although catheter thrombus occurred more often in patients receiving fondaparinux, this could be prevented by giving intravenous unfractionated heparin at the time of PCI, which did not increase bleeding.
"Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit," Mehta and colleagues conclude.
Mehta and several colleagues have received honoraria and consulting fees from GlaxoSmith Kline, Sanofi-Aventis, and Bristol-Myers Squibb.
Glycemic Control Suboptimal with a Single Insulin Type
Trial compares short-acting and basal insulins added to oral therapy in individuals with type 2 diabetes
Adding a single analogue-insulin formulation to the treatment of individuals with diabetes who are failing oral therapy leads to target glycemic control in a minority of individuals, according to a report published in the Oct. 25 issue of the New England Journal of Medicine.
As part of the Treating to Target in Type 2 Diabetes (4-T) study, Rury R. Holman, of the University of Oxford in the United Kingdom, and colleagues randomized 708 patients with suboptimally controlled type 2 diabetes on maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, insulin aspart three times daily with meals, or basal insulin detemir once daily (or twice daily if needed).
After one year, the biphasic and prandial aspart insulin groups achieved similar glycated hemoglobin levels (7.3 percent and 7.2 percent, respectively), but individuals in the basal insulin group had significantly higher values (7.6 percent). The proportion of patients achieving glycated hemoglobin levels of 6.5 percent or less in the biphasic, prandial and basal insulin groups were 17 percent, 23.9 percent and 8.1 percent, respectively.
"The first phase of the 4-T study, which compared three alternative analogue-insulin initiation therapies, suggests that most patients are likely to need more than one type of insulin to achieve target glucose levels. The final two years of the trial will examine specifically the use of complex insulin regimens in these patients," the authors write.
This research was partially funded by Novo Nordisk.
Docetaxel Improves Survival in Head and Neck Cancer
Two studies compare standard induction chemotherapy with and without docetaxel
The addition of docetaxel to standard cisplatin and fluorouracil induction chemotherapy regimens leads to improved disease-free and overall survival, according to two phase 3 randomized trials published in the Oct. 25 issue of the New England Journal of Medicine.
In the first study, Marshall R. Posner, M.D., of the Dana-Farber Cancer Institute in Boston, and colleagues randomized 501 patients with locally advanced squamous-cell head and neck cancer to receive docetaxel plus cisplatin and fluorouracil induction chemotherapy or cisplatin and fluorouracil induction chemotherapy, followed by chemoradiotherapy. Patients receiving docetaxel had improved survival over those not receiving docetaxel (median survival 71 months versus 30 months).
In the second study, Jan B. Vermorken, M.D., Ph.D., of the Universitair Ziekenhuis Antwerpen in Edegem, Belgium, and colleagues randomized 358 patients with unresectable head and neck cancer but no distant metastases to receive docetaxel plus cisplatin and fluorouracil induction chemotherapy or standard cisplatin and fluorouracil induction chemotherapy. Those receiving docetaxel had improved progression-free survival compared to those receiving standard induction chemotherapy (11 months versus 8.2 months). Overall survival was also improved in the docetaxel group (18.8 months versus 14.5 months).
"The results of both phase 3 induction trials support the conclusion that docetaxel plus cisplatin and fluorouracil combinations are appropriate for induction chemotherapy," write the authors of the first study.
Both studies were supported by grants from Sanofi-Aventis.
Medical Errors Trigger Variety of Powerful Emotions
Communication problems may be compounded by feelings of guilt, fear and isolation
Following a medical error, clinicians and patients are often left with a range of strong emotions that could be resolved in a more satisfying manner with better communication, according to the authors of a commentary published in the Oct. 25 New England Journal of Medicine.
Tom Delbanco, M.D., and Sigall K. Bell, M.D., of Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston, offer perspective gleaned from a documentary on the aftermath of medical error, to which Delbanco contributed.
Following an error, patients and families often have three emotions that are under-recognized, the authors write. Families feel guilty that they didn't watch their loved ones closely enough to prevent an error such as the administration of a drug that they knew would cause a serious reaction, or that they didn't press clinicians hard enough to properly diagnose and treat a problem. Patients also fear retribution from staff or poor treatment in the future if they confront a health care provider, and they feel isolated when clinicians back away and fall silent following an error.
Clinicians' cautious communications with patients and their families may be due to feelings of guilt, shame, legal concerns, or fear about their job security. To address these situations, they write, "First steps might include creating structured curricula for professionals addressing both error prevention and response, removing stigma from transparent reporting systems, and deploying a system of expert first responders who guide patients and clinicians when an error occurs."
Prepared jointly by the editors of Medical Economics and HealthDay's Physicians' Briefing (www.physicianbriefing.com)