The Skinny on Four Popular Diets

In overweight, nondiabetic, premenopausal women, the diets had only modest effects on body weight and cardiovascular risk factors, with a slight advantage for the Atkins diet over the others.

Current national guidelines recommend a reduced-calorie, low-fat, high-carbohydrate diet for weight loss. Comparisons with low-carbohydrate diets have had limitations, prompting these researchers to conduct a randomized trial of four popular diets: Atkins (very low-carb), Zone (low-carb), LEARN (guideline-recommended), and Ornish (very high-carb, very low-fat). Participants were 311 overweight, nondiabetic, premenopausal women (age range, 25–50; 71% white; mean body-mass index, 32).

The 1-year retention rate was similar among the groups (range, 76%–88%). By 1 year, mean weight loss was greatest in the Atkins group (–4.7 kg), followed by the Ornish (–2.6 kg), LEARN (–2.2 kg), and Zone (–1.6 kg) groups. Only the difference between Atkins and Zone was significant.

At 1 year, Atkins dieters had the greatest, though still modest, improvements in HDL cholesterol (mean increase, 5 mg/dL vs. <3 mg/dL with the other diets), triglycerides (mean decrease, 29 mg/dL vs. <15 mg/dL), and blood pressure (mean decrease, 7.6/4.4 mm Hg vs. <4/<3 mm Hg). Ornish dieters had the greatest, though also a modest, mean decline in LDL cholesterol (4 mg/dL vs. <1 mg/dL with the other diets). Changes in fasting insulin and glucose levels were similar among the four groups.

Comment: In this rigorous assessment of the effects of four popular diets on weight loss and cardiovascular risk factors in overweight, nondiabetic, premenopausal women, the Atkins diet had a slight overall advantage, but changes were modest and relatively similar with all the diets. Consistent with evidence from previous studies, a very low-carbohydrate diet was associated with increased HDL levels, reduced triglyceride levels, and little effect on LDL levels. To determine whether particular diets offer advantages in other subgroups, future studies must include men, older women, people with diabetes, and more nonwhite participants.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology March 14, 2007

High Prevalence of HPV in U.S. Females

But the prevalence of dangerous types is low.

Genital human papillomavirus (HPV) types are categorized as low risk (e.g., types 6 and 11) or high risk (e.g., types 16 and 18) for causing cervical, anal, and other genital cancers. A new highly publicized quadrivalent vaccine, licensed in June 2006, is nearly 100% effective for preventing infection and related diseases caused by these HPV types. To determine the prevalence of HPV in the U.S. before availability of the vaccine, researchers analyzed data from the National Health and Nutrition Examination Survey 2003–2004 for 1921 female participants aged 14 to 59 years. They obtained data on demographics, sexual behavior, and HPV analysis (by polymerase chain reaction) of self-collected vaginal swab specimens.

HPV prevalence was 26.8% overall. Prevalence was highest in participants aged 20 to 24 (25%), lowest in those aged 50 to 59 (20%), and intermediate in those aged 14 to 19 and 25 to 49 (approximately 25%). Overall, prevalence of HPV types 6, 11, 16, and 18 was 1.3%, 0.1%, 1.5%, and 0.8%, respectively. Being unmarried, having more than two recent or lifetime sexual partners, and being younger than 25 were independent risk factors for HPV.

Comment: The manufacturer of the recently licensed vaccine created a furor when it initially recommended vaccination of all girls aged 11 to 12 years. On the one hand, HPV is the most prevalent sexually transmitted infection in the U.S., and these data suggest that the prevalence is 60% higher than the previous estimate. On the other hand, the prevalence of the more dangerous types was quite low. These data will aid in development of more cost-effective strategies for vaccine use.

— John A. Marx, MD, FAAEM, FACEP

Published in Journal Watch Emergency Medicine March 16, 2007

Quantitative Fecal Occult Blood Testing Promising

A noninvasive screening test for colorectal cancer would be useful.

Guaiac-based fecal occult blood tests (FOBTs) are nonspecific and insensitive. Researchers with support from the maker of a quantitative immunochemical FOBT specific for human hemoglobin tested its performance in 1000 ambulatory adults undergoing elective colonoscopy. Some patients were asymptomatic, some were at high risk for cancer, and some were symptomatic.

At colonoscopy, cancer was detected in 17 patients, and advanced polyps in 74. Fecal hemoglobin concentrations were significantly higher in these patients than in others. A fecal hemoglobin threshold of 75 ng/dL (as measured in 3 samples) was used to define an abnormal result; at this level, the immunochemical FOBT had a sensitivity of 67% and specificity of 91% for advanced neoplasia. For cancer, sensitivity and specificity were 94% and 88%.

Comment: Because the quantitative immunochemical FOBT appears to have reasonable sensitivity and specificity for a screening test, some people might use it to select patients for colonoscopy. But people who desire greater certainty will likely forgo this test, as they forgo the guaiac-based tests. An editorialist recommends that quantitative FOBTs be preferred to guaiac-based tests whenever an FOBT is a component of a screening strategy. In the U.S., some currently available immunochemical FOBTs can be reported quantitatively, but they are not generally used that way yet.

— Richard Saitz, MD, MPH, FACP, FASAM

Published in Journal Watch General Medicine March 22, 2007

Long-Distance Treatment for Panic Disorder: Does It Work?

Treatment administered via the internet and telephone was beneficial to individuals with PD.

Panic disorder (PD) affects twice as many women as men and may lead to severe functional impairment. Despite highly effective therapies, people with PD (particularly those with agoraphobia) often find it prohibitively difficult to seek treatment. To assess the benefit of remote cognitive behavior therapy, investigators randomized 60 adults (60% women) with PD to 10 weeks of treatment via the internet, e-mail, and telephone or a waiting list (control).

The treatment consisted of 10 modules of cognitive therapy techniques distributed via e-mail, plus brief (about 10 minutes/week) therapist contact by telephone to motivate treatment adherence. The modules covered psycho-education, socialization, breathing retraining, relapse prevention, and assertiveness training. Each module included information, exercises, and homework; feedback was provided within 24 hours of homework completion. At the end of the study, treatment and control groups were reassessed; the control group was offered a different treatment format, and the treatment group was followed up again 9 months later.

At the end of the therapy period, the treatment group showed significant improvement compared with controls, as assessed with standardized instruments (e.g., the Body Sensations Questionnaire, Mobility Inventory, and Beck Anxiety Inventory). Moreover, clinical telephone interviews conducted 1 month after completion of treatment revealed that 77% of treated patients no longer suffered from PD, whereas all untreated patients still met the criteria for this disorder. Nine-month follow-up showed sustained clinical improvement in the treatment group.

Comment: This small study included highly motivated, relatively well-educated adults, half of whom were receiving concomitant medications. Although the results might not be applicable to the general population of patients with PD, they are provocative and should stimulate further research. During certain periods in life, such as the postpartum period, regular attendance at treatment sessions might be particularly problematic. Internet-based self-help therapies are an excellent treatment alternative for women who have new or recurrent symptoms of PD and who would not otherwise seek treatment. If this type of therapy proves to be cost-effective on a larger scale, clinicians might face the challenge of convincing insurance plans to cover it.

— Claudio N. Soares MD, PhD

Published in Journal Watch Women's Health February 8, 2007

FDA Approves OTC Orlistat

The FDA approved an over-the-counter version of the weight loss drug Xenical (orlistat) on Wednesday. The lipase inhibitor will be sold under the name Alli as a 60 mg capsule -- a lower dose than the prescription version of the drug.

Alli is meant to be used by adults with a BMI of 27 or more, in conjunction with a reduced-calorie diet and exercise plan. Users can take up to three capsules a day, one with each fat-containing meal, and should take a multivitamin at bedtime, as the drug can block the absorption of some vitamins.

The most common side effects are diarrhea and other changes in bowel habits, which can be reduced by eating a low-fat diet. The drug is contraindicated in transplant recipients. Patients on anticoagulants or who are being treated for diabetes or thyroid disease should only use the product under physician supervision.

Clomiphene More Effective Than Metformin for Infertility in Polycystic Ovary Syndrome

Clomiphene outperforms metformin at increasing fertility in women with polycystic ovary syndrome (PCOS), a randomized trial in the New England Journal of Medicine concludes.

Researchers randomized some 600 infertile women with PCOS to up to 6 months of treatment with either clomiphene plus placebo, extended-release metformin plus placebo, or clomiphene plus metformin. Conception rates were higher with clomiphene than with metformin (30% versus 12%), as were rates of live births (23% versus 7%). Combination therapy did not increase conception or birth rates over clomiphene alone. Multiple pregnancy was more common with clomiphene than with the other treatments.

Metformin "may well be important" for treating metabolic disturbances in women with PCOS, concludes the author of an accompanying editorial, but this study "provides strong evidence that the metabolic benefits of metformin do not translate into live-birth rates that are as high as those with the old-fashioned standard, clomiphene citrate."

NEJM article (Free abstract; full text requires subscription)

NEJM editorial (Subscription required)

Screening for Elevated Lead Levels in Children

The evidence is insufficient to recommend for or against routine screening.

The U.S. Preventive Services Task Force (USPSTF) periodically releases new and updated guidelines (guidelines homepage).

The USPSTF concludes each of its guidelines with a recommendation, graded as follows:

A — The intervention is strongly recommended.

B — The intervention is recommended.

C — The USPSTF makes no recommendation for or against the intervention.

D — The intervention is not routinely recommended.

I — Evidence is insufficient to recommend for or against the intervention.

The prevalence of blood lead levels >10 µg/dL among U.S. children aged 1 to 5 years dropped dramatically from 9.0% in 1990 to 1.6% in 2000. Risk factors for elevated blood lead levels include minority race or ethnicity, low income, and residing in a house built before 1950. Research in the last decade indicates that lead levels as low as 10 µg/dL in children might affect neurocognitive development. In addition, the effects of chelation, nutritional, and environmental interventions in asymptomatic children with relatively low (10 µg/dL) blood lead levels have been assessed in clinical trials. This new information led the USPSTF to reconsider their 1996 recommendations regarding screening for elevated blood lead levels in children and pregnant women. The revised recommendations are:

·         The task force states that the evidence is insufficient to recommend for or against routine screening for elevated blood lead levels in asymptomatic children aged 1 to 5 who are at high risk for exposure to harmful levels of lead. Recommendation: I

·         The task force recommends against routine screening of blood lead levels in children aged 1 to 5 who are at average risk for exposure to harmful lead levels. Recommendation: D

·         The task force recommends against routine screening in asymptomatic pregnant women. Recommendation: D

Comment: A superb review of the effects of chelation, nutritional, and environmental interventions accompanies the USPSTF statement. The decline in lead levels in U.S. children is largely attributable to the reduction of lead in air, paint, and gasoline. The effects of chelation and residential lead-hazard control (including dust and paint removal and soil abatement) are uncertain. What do these recommendations mean for clinicians who care for high-risk children? Should we continue to screen for elevated lead levels? Until the recommendations of the AAP or the Early Periodic Screening, Diagnosis, and Treatment (EPSDT) Program (child health component of Medicaid with regulations that vary from state to state) change, we will likely continue to screen for elevated lead levels in high-risk children. However, I am concerned that many of the same children are affected by other conditions associated with developmental delay (e.g., iron deficiency anemia) for which the USPSTF has determined that the evidence is insufficient to recommend for or against interventions aimed at detection and treatment. To prove that screening, case-finding, and interventions aimed at any one of these conditions individually improves cognitive outcome has been virtually impossible, but I believe that the cumulative effects of multiple conditions reduce the likelihood that these children will reach their full cognitive potential.

— Howard Bauchner, MD

Published in Journal Watch Pediatrics and Adolescent Medicine February 7, 2007

The Problem with Being Second

Second-born full-term twins have greater risk for mortality from anoxia than first-born twins.

Some data suggest that second-born twins have an increased risk for perinatal anoxic events, sometimes even leading to death. Researchers analyzed 1377 twin pregnancies that involved an intrapartum stillbirth or neonatal death in England, Northern Ireland, and Wales from 1994 to 2003. Twins who died from other causes, such as congenital anomalies, were excluded.

Birth order was not associated with risk for death overall or among preterm twins (before 36 weeks’ gestation). However, among term twins (at or after 36 weeks), second-born twins had increased risk for death overall and for death related to anoxia compared with first-born twins (odds ratios, 2.3 and 3.4, respectively). In an analysis of term births by mode of delivery, compared with first-born twins, second-born twins delivered vaginally had twofold greater risk for death caused by anoxia than those delivered by cesarean section (OR, 4.1 and 1.8). The increase in risk among second-born twins delivered by cesarean section was of borderline significance.

Comment: That twins are at increased risk for prematurity and that prematurity is associated with a variety of problems probably explain why birth order had no significant effect on mortality risk in premature twins. Among the relatively small number of term twin deliveries (177 of 1377), second-born twins delivered vaginally had four times the risk for death from anoxia than first-born twins. The authors did not separate the findings for monozygotic and dizygotic twins or for infant sex (although 57% of infants who died were male). Despite these limitations, consideration of cesarean section for term twin deliveries might be appropriate to give the second twin a better chance.

— Judith G. Hall, OC, MD

Published in Journal Watch Pediatrics and Adolescent Medicine May 30, 2007

Study Finds Soy Nuts Lower Blood Pressure

Soy nuts may reduce blood pressure in postmenopausal women, a small study published in the Archives of Internal Medicine concludes.

The randomized crossover study included 60 women. It investigated the effects of including unsalted soy nuts containing 25 g of soy protein in the National Cholesterol Education Program's Therapeutic Lifestyle Changes diet.

Compared with a diet without the nuts, adding soy nuts lowered systolic BP 9.9% and diastolic BP 6.8% in hypertensive women. The decline was a more modest 5.2% systolic and 2.9% diastolic in normotensive women.

The diet with nuts also lowered LDL 11% and apolipoprotein B 8% in hypertensive women but had no effect on these measures in normotensive women.

The authors said dietary soy "may be a practical, safe and inexpensive modality to reduce BP." They characterize the effects as being "comparable with those seen with antihypertensive drugs."

Calcium and Vitamin D Associated with Reduced Breast Cancer Risk

A study in the Archives of Internal Medicine suggests that high consumption of calcium and vitamin D is associated with a modestly reduced risk for breast cancer in premenopausal women.

The findings were based on a prospective investigation of nutrient intake in about 10,000 premenopausal and about 20,000 postmenopausal participants of the Women's Health Study. Over a 10-year follow-up, some 1000 women were diagnosed with invasive breast cancer. The hazard ratio for breast cancer development was 0.61 for premenopausal women in the highest versus the lowest quintile of calcium intake and 0.65 for the highest versus the lowest quintile of vitamin D consumption. However, these nutrients were not associated with lower breast cancer risk in postmenopausal women.

In explaining the effect, the authors note that in vitro, calcium and vitamin D appear to inhibit breast cancer cells that express high levels of IGF-I and IGF binding protein 3, both of which decline with age.

Can NSAIDs Prevent Alzheimer Disease?

Neither celecoxib nor naproxen prevented AD or mild cognitive impairment.

Although inflammation plays a role in the pathogenesis of Alzheimer disease (AD), nonsteroidal anti-inflammatory drugs (NSAIDs) have not slowed the progression of early AD in several clinical trials (Journal Watch Feb 6 2004 and Journal Watch Jun 27 2003). But can NSAIDs prevent or delay the development of AD?

The ADAPT trial included people aged 70 or older who had no evidence of dementia or cognitive impairment, but had at least one first-degree relative with Alzheimer-like dementia. Participants were randomized to receive celecoxib (200 mg twice daily), naproxen (220 mg twice daily), or placebo. The trial was terminated in December 2004 when another study reported increased cardiovascular risk with celecoxib. At that point, 2528 people had been enrolled in ADAPT, and median follow-up was about 2 years (the original intent was 7 years of follow-up).

According to standardized cognitive testing and further evaluation of subjects with abnormal test results, neither celecoxib nor naproxen prevented AD or mild cognitive impairment. In fact, the annual risk for AD was higher in the celecoxib and naproxen groups (about 1%) than in the placebo group (about 0.5%), a difference that approached statistical significance.

Comment: In this halted study, neither celecoxib nor naproxen prevented Alzheimer disease, and there was a hint of harm. It remains possible that NSAIDs could prevent some cases of AD if started many years before disease onset, but a trial would have to be very large and protracted to address this possibility.

— Allan S. Brett, MD

Published in Journal Watch General Medicine May 29, 2007

The Effects of Soft Drink Consumption

A meta-analysis confirms the negative effects of soft drinks on health-related measures.

The obesity epidemic has fueled concerns that the consumption of soft drinks might adversely affect nutritional health. In a meta-analysis of 88 studies (many involving children), investigators assessed the effects of consumption of sugar-sweetened soft drinks on energy intake, weight, consumption of milk and calcium, nutrient intake, and overall health. Cross-sectional, longitudinal, and randomized trials were included.

Soft drink intake was associated with increased energy intake in 24 of 33 relevant studies (overall effect size, 0.16), including 4 randomized controlled trials that examined consumption for 3 to 10 weeks (average effect size, 0.30). Results of 32 studies that evaluated the relation between soft drink consumption and weight were variable, but 5 of 7 randomized trials showed an association with weight gain (average effect size, 0.24). Soft drink consumption also had negative effects on milk and calcium consumption, micronutrient intake, and overall health.

Comment: I struggle with meta-analyses. Although the increased sample size adds statistical power, interventions vary from study to study. In addition, dozens of comparisons were made in this meta-analysis, increasing the likelihood of a "positive" finding. With those caveats in mind, the data are remarkably consistent. Soft drink consumption appears to increase caloric intake and weight and to reduce calcium, milk, and valuable micronutrient intake.

— Howard Bauchner, MD

Do PPIs Increase Risk for CAP?

In a large population-based case-control study, the use of proton-pump inhibitors was associated with increased risk for community-acquired pneumonia.

Proton-pump inhibitors (PPIs) have been associated with increased risk for gastrointestinal infections such as salmonellosis and Clostridium difficile colitis. In addition, one study (Journal Watch Infectious Diseases Nov 22 2004) has shown PPI use to be associated with community-acquired pneumonia (CAP). Now, investigators have conducted a large population-based case-control study to evaluate the relation between PPI use and CAP.

Through use of patient registries, the researchers obtained data on 7642 individuals hospitalized with CAP in the county of Funen, Denmark, at any time from 2001 through 2004. These case patients were matched by sex and age with 34,176 controls drawn from the same population. PPI and other drug exposures were obtained from a complete database of all reimbursed prescriptions in the county.

Eleven percent of case patients were current PPI users, versus 5% of controls (adjusted odds ratio, 1.5; 95% confidence interval, 1.3–1.7). No association was found with past use of PPIs or with current or past use of histamine₂-receptor antagonists. The PPI-CAP association was similar across all sex, age, and underlying illness strata (adjusted ORs, 1.2). A temporal relationship was noted, with the strongest association seen among those in the first week of PPI therapy (OR, 5.0; 95% CI, 2.1–11.7).

Comment: Although case-control studies can be limited by bias and confounding, this investigation was population-based and had essentially complete acquisition of CAP admissions and PPI use; furthermore, the PPI-CAP association remained significant after adjustment for age and comorbidity. If confirmed, the present findings further support the importance of an acidic gastric environment as a host defense against pulmonary infections.

— Daniel J. Diekema, MD, MS

An Aspirin Every Other Day Won’t Keep Cognitive Decline Away

Long-term low-dose aspirin use did not protect against cognitive decline among healthy nonsmoking women 65 or older.

Studies of cognitive benefit from aspirin and other anti-inflammatory agents have yielded mixed results. The Women’s Health Study was a large, randomized, placebo-controlled study of vitamin E (600 IU on alternate days) and low-dose aspirin (100 mg on alternate days) for the prevention of cardiovascular disease and cancer. In this 4-year subgroup analysis of approximately 6400 women 65 or older, investigators administered tests of general cognition and verbal memory by telephone interview at 2-year intervals to women who had already received aspirin or placebo for an average of 5.6 years.

Global scores for cognitive function and scores for verbal memory did not differ between the two groups at initial testing, and the mean decline in overall cognitive performance was also similar between groups at each of the two follow-up assessments. The aspirin group performed better than the placebo group in category fluency (a test of executive brain function) at all three assessments. In the subsets of women who were current smokers or who had hyperlipidemia, the aspirin group experienced significantly less cognitive decline than did the placebo group.

Comment: In terms of category fluency, the effects of aspirin appeared to offset age-related decline by the equivalent of about 2.6 years; however, because only one test was used to assess executive brain function, the results should be interpreted with caution. In general, low-dose aspirin did not prevent cognitive decline during a 4-year period in nonsmoking, nonhyperlipidemic women. In women with known cardiovascular risk factors, aspirin might prevent some cognitive decline, but additional long-term studies are needed.

— Wendy S. Biggs, MD

Published in Journal Watch Women's Health May 24, 2007

nfectious Diseases May 23, 2007

Pneumococcal Vaccine: The Good, the Bad, and the Uncertain

Conjugated pneumococcal vaccine works, but pockets of disease remain.

The introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) in the U.S. in 2000 was a welcome addition to our preventive armamentarium; however, questions remain regarding the degree of protection in immunized children with fever or pneumonia. Two studies examined recent trends in invasive pneumococcal infection.

In the first study, researchers used data from the Nationwide Inpatient Sample to evaluate discharge diagnoses in more than 35 million hospital admissions before (1997–1999) and after (2001–2004) routine immunization with PCV7 in the U.S. Among children younger than 2 years, admissions for pneumonia decreased by 39% overall and by 65% for pneumonia attributed to Streptococcus pneumoniae.

In the second study, investigators analyzed serotypes of colonization and invasive pneumococcal disease (IPD) from 1995 through 2006 in highly immunized children younger than 2 years in Alaska. During the first years after introduction of routine PCV7 (2001–2003), Native Alaska children had a dramatic (67%) decrease in IPD, but the decrease was followed by an 82% increase from 2003 through 2006. The increase was due to non-PCV7 serotypes, most commonly 19A. Non–Native Alaska children had a sustained decrease in IPD.

Comment: Although PCV7 clearly has had an effect on invasive pneumococcal infections in the pediatric population, pockets of at-risk children exist, such as the Native Alaska children in this study and, as previously reported, some children in Salt Lake City. In addition, anecdotal reports have been circulating about an increased incidence of infections with non-vaccine S. pneumoniae strains 1, 3, and 19A in other parts of the country. We must continue to be vigilant in the evaluation of all febrile children and children with pneumonia, regardless of immunization status. When invasive pneumococcal disease is identified, isolates should be typed and sent to public health laboratories so we may better understand the evolving epidemiology.

— Peggy Sue Weintrub, MD

Published in Journal Watch Pediatrics and Adolescent Medicine May 23, 2007

Apolipoprotein Ratio Does Not Improve Prediction of Cardiac Risk

The ratio of apolipoprotein B to apolipoprotein A-I was associated with coronary artery disease but added little to existing measures of risk assessment.

Many new risk factors have been found to be associated with coronary artery disease (CAD), but whether they improve risk prediction over established measures is the key question. U.K. researchers evaluated whether the ratio of apolipoprotein B to apolipoprotein A-I was associated with CAD among 869 adults with CAD and 1511 controls matched for age, sex, and time of enrollment.

The highest quartile of the apolipoprotein ratio was significantly associated with fatal and nonfatal CAD (odds ratio, 1.85) in analyses adjusted for cardiovascular risk factors (sex, diabetes, body mass index, smoking, systolic blood pressure, C-reactive protein levels, and LDL and HDL cholesterol levels). The ratio also was associated with CAD (OR, 1.77) in analyses adjusted for the Framingham risk score (a well-established algorithm for combining risk factors to predict CAD). However, the total/HDL cholesterol ratio and the apolipoprotein ratio categorized cases and controls similarly. In addition, the proportion of people with CAD who were predicted to have higher risk for CAD was similar when both ratios were used and when the apolipoprotein ratio was added to the Framingham risk score.

Comment: The researchers should be commended not only for studying whether the apolipoprotein ratio was associated with CAD (it was), but also for testing whether it added anything to conventional risk factor assessments (it didn’t). An editorialist sums it up well, concluding that "risk factor proliferation puts patients and clinicians at risk for confusion."

— Richard Saitz, MD, MPH, FACP, FASAM

Published in Journal Watch General Medicine May 17, 2007

First Continuous-Use Birth Control Pill Approved

The FDA has approved the first continuous-use birth control pill for women.

The contraceptive, Lybrel, has a 28-day pill pack with tablets that contain 90 micrograms of levonorgestrel and 20 micrograms of ethinyl estradiol. Women who use the pill do not have regular monthly menstrual periods, however, they can have breakthrough bleeding. The agency said that "unscheduled bleeding decreases over time in most women who continue to take Lybrel for a full year." It occurred in about 40% of women in the last month they participated in a 1-year clinical trial.

The FDA cautioned that because they do not have regular periods, women may not recognize if they become pregnant. The manufacturer says it plans to introduce Lybrel in July. Observation vs. Surgery for Asymptomatic Primary Hyperparathyroidism

No significant differences in quality of life were noted between the surgery group and the observation group.

Many patients are diagnosed with primary hyperparathyroidism when mild hypercalcemia is discovered incidentally. Observation is considered acceptable for such patients if they are asymptomatic and serum calcium is only mildly elevated. However, some clinicians believe that many "asymptomatic" patients actually have subtle symptoms and would benefit from surgery.

In this Scandinavian trial, 191 patients with mild, presumably asymptomatic, hyperparathyroidism (mean serum calcium, 10.8 mg/dL) were randomized to observation or to parathyroidectomy. The authors provide data for the first 99 patients to have completed 1- and 2-year follow-up visits, at which quality of life was monitored using standardized surveys. Although a few minor differences between the surgical and medical groups were noted at 2 years, no significant differences emerged in most quality-of-life and psychological domains. Statistically borderline improvements in bone density were noted at the lumbar spine and femoral neck (but not at the radius) in the surgical group compared with the observation group at 2 years. Mean serum calcium remained stable during follow-up in the observation group.

Comment: In this randomized trial, surgery did not appear to improve quality of life in patients with mild asymptomatic primary hyperparathyroidism, but trends toward improved bone density were noted. The results support the view that observation without surgery is acceptable for selected patients. Participants in an NIH-sponsored workshop have published widely referenced criteria for surgery in patients with asymptomatic primary hyperparathyroidism (J Clin Endocrinol Metab 2002;87:5353).

— Allan S. Brett, MD

Published in Journal Watch General Medicine May 22, 2007

Aspirin Associated with Reduced Risk for Preeclampsia

Antiplatelet therapy was associated with a small but consistent reduction in the rates of preeclampsia and preterm birth among high-risk women, according to a meta-analysis published early online by the Lancet.

Researchers analyzed data from 31 studies that randomized some 32,000 women at risk for preeclampsia to receive antiplatelet therapy (mostly aspirin). The risks for preeclampsia and for preterm birth before 34 weeks' gestation were both reduced by 10% with antiplatelet use. The number needed to treat to prevent one case of preeclampsia was 114 women. Overall, the association was not significantly stronger or weaker in particular subgroups.

Editorialists conclude that aspirin is justified in "... settings in which pre-eclampsia is almost a certainty, including women with pre-eclampsia in more than one pregnancy or women with chronic hypertension and pre-eclampsia in a previous pregnancy."

Lancet meta-analysis (Free abstract with one-time registration; full text requires subscription)

Lancet comment (Subscription required)

Related Journal Watch link(s):

Journal Watch General Medicine summary of 2001 BMJ meta-analysis of aspirin and preeclampsia (Your Physician's First Watch registration required)

Choosing to Avoid Diabetes

Adherence to 2005 dietary guidelines reduced insulin resistance in women.

The USDA 2005 Dietary Guidelines for Americans (DGA) provide recommendations about calorie and nutrient intake (Table 1) to maintain ideal body weight and to reduce risk for chronic disease. When followed, are these guidelines actually effective at reducing risk? Approximately 1600 women and 1400 men in the Framingham Offspring Cohort completed a food frequency questionnaire during the preceding year. Researchers assessed whether diets were consistent with the 2005 DGA using a standardized tool, the 2005 Dietary Guidelines Adherence Index (DGAI). The index includes items such as food-intake patterns, calorie intake, and calorie expenditure. Higher DGAI scores reflect stricter adherence to the guidelines. Height, weight, waist circumference, and fasting plasma glucose and insulin were measured for calculations of BMI and insulin resistance. Participants also provided information about age, smoking, multivitamin use, physical activity, and sleep habits. Mean age and BMI were 54.2 years and 26.5 for women and 54.0 years and 27.3 for men. Participants in the highest DGAI quintile were about three times more likely to be women than men. A higher DGAI score was significantly inversely related to insulin resistance in women; no association was noted for men. Adjustment for BMI, smoking, multivitamin use, waist circumference, physical activity, and energy intake did not affect the results.

Comment: Although these study results are limited by their basis in retrospective dietary recall, they show that women with the healthiest eating patterns had reduced insulin resistance, and thus lower diabetes risk, compared with those making less-healthy food choices. Women frequently ask their clinicians to recommend "a diet"; the 2005 DGA (http://www.mypyramid.gov/guidelines/ or http://www.mypyramid.gov/sp-index.html [Spanish]) provide basic information about nutrition and physical activity that women can tailor to their individual needs.

— Diane E. Judge, APN/CNP

Published in Journal Watch Women's Health May 17, 2007

Low-Glycemic-Load Diets May Work Better for People with High Insulin Secretion

Individuals with high insulin secretion may lose more weight on low-glycemic-load than on low-fat diets, according to a study published today in JAMA.

Researchers tested the glucose tolerance of 73 obese 18- to 35-year-olds, randomized them to either a low-fat (55% carbohydrate, 20% fat) or low-glycemic-load diet (40% carbohydrate, 35% fat), and provided 6 months of intensive nutritional education and dietary counseling to both groups.

After 18 months, they found no significant differences in body-fat or body-weight percentage change between groups overall, or between groups among people with normal insulin secretion. In individuals with high insulin secretion, however, the low-glycemic-load diet resulted in a greater decrease in weight (–5.8 kg vs. –1.2 kg) and body-fat percentage (–2.6% vs. –0.9%). Additionally, regardless of insulin status, the low-glycemic-load diet improved triglyceride and HDL profiles; conversely, the low-fat diet improved LDL but not HDL or triglyceride levels.

JAMA article (Free abstract; full text requires subscription)

Gender and Racial Disparities Found in Screening for and Management of CVD

Cardiovascular disease management, especially cholesterol control, is poorer in women and African Americans that in white men, according to four papers in Women's Health Issues.

The studies analyze national data collected both by commercial and Medicare managed care plans and focus on screening for cardiovascular disease and control and treatment of risk factors such as diabetes and LDL levels.

All studies find gender disparities in LDL control. In one, female Medicare enrollees with diabetes had a relative risk for LDL control of 0.81; the odds ratio in another study among women with a history of CVD was 0.72.

A separate study reports that, among diabetics, African American men had the highest likelihood of poor HbA1c control (30%, vs. 21% in white men) and African American women fared worse (28%) than white women (21%).

Editorialists comment: "The finding that large disparities were most often observed for intermediate control outcomes, such as control of hyperlipidemia, while gender differences on process measures, such as [ordering] lipid profiles in diabetics, tended to be small, is particularly concerning."

Women's Health Issues articles (Free PDFs of all articles)

Does CPAP Lower Blood Pressure in Patients with Sleep Apnea?

In this meta-analysis, CPAP had a modest effect on blood pressure.

The association between cardiovascular morbidity and obstructive sleep apnea syndrome (OSAS) is widely recognized. The effect of treatment with continuous positive airway pressure (CPAP) on blood pressure, a potential mediator of cardiovascular events, has not been fully delineated. In a meta-analysis of 12 placebo-controlled randomized trials involving 572 patients, researchers assessed whether CPAP treatment reduces 24-hour ambulatory mean blood pressure (MBP). The proportion of patients who were hypertensive ranged from 0% to 100%. Study duration ranged from 1 to 12 weeks.

In all studies, 24-hour MBP decreased in the CPAP groups compared with the placebo groups, with relative decreases ranging from 0.30 to 10.50 mm Hg. Pooled results showed a net decrease of 1.69 mm Hg among patients treated with CPAP. The largest decreases in blood pressure were obtained in two small trials that enrolled a substantially higher proportion of patients with severe OSAS.

Comment: This meta-analysis found a statistically significant reduction in 24-hour MBP among patients with OSAS who were treated with CPAP, but reductions were quite modest on average. The extent of blood pressure reduction may depend on the severity of OSAS.

— Jamaluddin Moloo, MD, MPH

Published in Journal Watch General Medicine May 8, 2007

Polio: Sustaining the Struggle

Efficacy of monovalent type 1 poliovirus vaccine was 30% per dose; a dynamic model shows the high cost of failing to eradicate wild polioviruses.

The WHO initiated the Global Polio Eradication Initiative in 1988. Despite impressive progress, transmission of wild poliovirus continues in four regions of the world. Two new studies address key challenges.

A high-potency monovalent oral type 1 poliovirus vaccine (mOPV1), aimed at preventing paralytic disease, was introduced in India in 2005. This preparation was developed for use in environments with high population density, poor sanitation, and frequent diarrheal and other infections that reduce the effectiveness of trivalent live poliovirus vaccine and favor wild-poliovirus transmission. Working in areas of India with persistent wild poliovirus transmission, Grassly and colleagues conducted a case-control study to assess the efficacy of mOPV1. In Uttar Pradesh, they matched 388 cases of acute flaccid paralysis caused by type 1 poliomyelitis in 2006 (children for whom complete vaccination records were available; 86% of all such cases in the area) with controls. The investigators estimated that mOPV1’s protective efficacy against ty pe 1 paralytic polio was 30% per dose, assuming no routine coverage with trivalent vaccine. In contrast, trivalent vaccine was estimated to have a per-dose efficacy of 11% in that setting, regardless of whether coverage was routine.

Thompson and Tebbens developed a dynamic model to show the long-term health and economic implications of different strategies to control or eradicate polio. They assessed various levels of control and modeled outcomes in number of paralytic poliomyelitis cases per year, over a 20-year period, based on data from endemic areas of India. They also considered possible policy options regarding vaccination after eradication (necessary to prevent reintroduction of virus from persistently infected immunodeficient persons or virus derived from live oral vaccine). Their model projects that reducing vaccine coverage in endemic areas would lead to a rapid accumulation of susceptible persons and outbreaks of paralytic disease. Eradication would cost billions of dollars, but over 20 years the cumulative expense would be far less than with any of the various control strategies.

Comment: The effectiveness of poliovirus vaccine varies by population. In Grassly and colleagues’ study, a monovalent vaccine showed promise in a particularly difficult population. Thompson and Tebbens’s findings strongly support a continued push to eradicate wild polioviruses. As editorialists note, the decision involving when to stop using live oral poliovirus vaccine in developing countries remains difficult.

— Mary E. Wilson, MD

Published in Journal Watch Infectious Diseases May 9, 2007

HPV Linked to Oropharyngeal Cancer, Study Finds

Human papillomavirus is strongly associated with oropharyngeal cancer, independent of smoking history or alcohol use, according to a case-control study in the current New England Journal of Medicine.

Researchers compared 100 patients with newly diagnosed cancers with 200 control patients without cancer. Factors strongly associated with cancer included seropositivity for HPV-16 (odds ratio, 32.2), oral infection with HPV-16 (14.6), a high lifetime number of vaginal-sex partners (3.1), and having had six or more oral-sex partners (3.4).

An editorialist wonders "whether there is any need for screening for persistent oral or oropharyngeal HPV infection in high-risk groups (smokers and drinkers)," and further writes that "it is worth considering the possibility that some oral, oropharyngeal, and laryngeal cancers might be prevented by HPV vaccination."

Statins Associated with Reduced Risk for Lung Cancer

Statins are associated with a reduced risk for lung cancer, even among smokers, according to a large retrospective case-control study of U.S. veterans published in Chest.

Researchers examined data from a cohort of over 480,000 patients, 7280 of whom had lung cancer and one-third of whom were on statins. Users of statins for more than 6 months had a risk reduction for lung cancer of 55%. After 6 months' use, longer usage was associated with progressively smaller odds ratios for lung cancer. (Those who used statins for less than 6 months, however, had an increased odds ratio — 2.32.)

Editorialists note previous studies showing statins to increase apoptosis, suppress angiogenesis, and alter metastatic potential. The current results, they write, "are encouraging and strengthen the hypothesis that statins may be useful for lung cancer chemoprevention." They point to weaknesses in the study's design, however, and say that until further studies are done statins should be used "based on the strict guidelines of the Adult Treatment Panel III."

More on Antidepressants in Children and Adolescents: Analysis of Benefits and Risks

Treatment benefits outweigh the risk for suicide ideation.

Antidepressant use in children and adolescents has been associated with a twofold increase in risk for suicidal behavior. To further assess both efficacy and risk for suicidal thoughts and behaviors in the pediatric population, researchers conducted a meta-analysis of data from 27 randomized, placebo-controlled clinical trials of antidepressant treatment (mostly selective serotonin reuptake inhibitors [SSRIs]) for major depressive disorder (MDD, 15 trials), obsessive-compulsive disorder (OCD, 6 trials), and other anxiety disorders (6 trials) in pediatric patients.

The pooled differences in response for antidepressant groups compared with placebo groups were 11% for treatment of pediatric MDD, 20% for OCD, and 37% for other anxiety disorders. The differences in risks for suicidal behavior were 1.0%, 0.5%, and 0.7%, respectively. Overall, the authors calculated that a clinician would have to treat 143 patients to see suicidal behavior in a single patient. No completed suicides were reported.

Comment: This meta-analysis is the largest to date to examine efficacy and risk of antidepressant use in children and adolescents. Its importance for pediatricians is twofold: First, pediatricians may be surprised at the modest improvement in patients with depression and OCD. This finding serves as a reminder that cognitive behavioral therapy should be a part of treatment with or without medication and that SSRI medications are most effective in patients with non-OCD anxiety disorders. Second, in contrast with previous meta-analyses, this study assessed risks associated with the three disorders separately; these results point out that the risk association is with suicidal thoughts and behaviors, not completed suicides. Pediatricians can feel confident in prescribing SSRI medications for children and adolescents with specific men tal health disorders as long as side effects are monitored appropriately (in particular, agitation and increasing sadness and isolation during the first month after starting or increasing the medication).

— Martin T. Stein, MD

Published in Journal Watch Pediatrics and Adolescent Medicine May 2, 2007

Ovarian Cancer Treatment: Predictors of Comprehensive Surgery

Patient, surgeon, and hospital characteristics were associated with receiving comprehensive surgery.

Ovarian cancer is rare, but it is more deadly than other gynecologic malignancies because most ovarian tumors are already advanced at diagnosis. Optimal initial surgical treatment is a key factor in improving ovarian cancer outcomes. In this federally funded U.S. cohort study, investigators evaluated the surgical treatment of more than 10,000 women (mean age, 60; 84% white) who received primary surgical treatment for ovarian cancer from 1999 to 2002 in one of nine states.

Forty-two percent of the patients underwent surgery in teaching hospitals. One third of the patients had surgery in low-volume hospitals (<10 ovarian cancer surgeries annually). Nearly half the patients (48%) were operated on by surgeons who performed fewer than 10 ovarian cancer surgeries each year, with 25% of patients undergoing surgery by very-low-volume surgeons ( 1 ovarian cancer surgery annually). In South Carolina (the only state in which surgeon subspecialist status was available), gynecologic oncologists (GOs) performed 70% of ovarian cancer operations. Patients with primary ovarian cancer who underwent both a lymph node dissection and omentectomy/cytoreduction were considered to have received comprehensive surgery.

Overall, 67% of patients received comprehensive surgery. Factors significantly associated with being less likely to receive comprehensive surgery included age 71 and older, black or Hispanic race, Medicaid funding, surgery performed by a very-low-volume surgeon, and surgery not performed by a GO. Among nonteaching hospitals, operations performed at low-volume facilities were less likely to be comprehensive. Among teaching hospitals, surgery volume was not associated with likelihood of receiving comprehensive surgery.

Comment: That so many U.S. women with ovarian cancer do not receive appropriate primary surgery may come as a surprise. These data underscore the importance of referring women with suspected ovarian cancer to GOs who operate at hospitals prepared to meet the surgical needs of women with this lethal malignancy.

— Andrew M. Kaunitz MD

Published in Journal Watch Women's Health May 3, 2007

Homocysteine-Lowering Therapy After Venous Thromboembolism

A randomized trial found that homocysteine lowering with B vitamins did not reduce the risk for recurrence.

Elevated homocysteine levels are associated with both arterial and venous thrombotic events. However, in recent trials, homocysteine-lowering B-vitamin therapy did not prevent arterial events such as myocardial infarction or stroke (Journal Watch Mar 28 2006 and Feb 17 2004). But what about secondary prevention of venous thromboembolism?

European researchers enrolled 701 patients with recent venous thromboembolism (VTE; either proximal deep-vein thrombosis or pulmonary embolism), but without major predisposing risk factors such as recent surgery or immobilization. At baseline, half the patients had hyperhomocysteinemia (mean, 15.5 µmol/L), and half had normal levels (mean, 9.0 µmol/L). Patients were randomized to receive a B-vitamin supplement (5 mg folic acid, 0.4 mg B₁₂, and 50 mg B₆) or placebo, in addition to standard anticoagulation.

During 2.5 years of follow-up, the overall incidence of recurrent VTE was not significantly different in the B-vitamin and placebo groups (5.4% vs. 6.4%). In hyperhomocysteinemic patients, the incidence of recurrent VTE was nonsignificantly higher in B-vitamin recipients than in placebo recipients (6.7% vs. 6.0%); in those with normal homocysteine, the incidence of recurrent VTE was nonsignificantly lower in B-vitamin recipients (4.1% vs. 7.0%).

Comment: In this, the first randomized trial of homocysteine-lowering therapy to prevent recurrent venous thromboembolism, B vitamins did not reduce the risk for recurrence. The authors note that their study might have been underpowered to detect a small beneficial effect. However, they also speculate that homocysteine's observed epidemiologic association with VTE might in fact be mediated by some other thrombophilic factor that is correlated with homocysteine.

— Allan S. Brett, MD

Published in Journal Watch General Medicine February 6, 2007

Diabetes Risk with Antihypertensive Meds

A meta-analysis yields a ranking of antihypertensive drug classes according to their association with incident diabetes.

Concerns that some antihypertensive medications, particularly thiazide diuretics and beta-blockers, can increase the risk for new-onset diabetes have been difficult to validate. Now, researchers have conducted a "network meta-analysis" to study new-onset diabetes in 22 long-term, randomized antihypertensive-drug trials (involving 143,158 subjects). This type of analysis enables comparison of different treatments across similar trials even when specific strategies have not been compared within trials.

When diuretics were used as the referent, the risk for incident diabetes was significantly lower with angiotensin-receptor blockers (ARBs; odds ratio, 0.57), ACE inhibitors (OR, 0.67), calcium-channel blockers (OR, 0.75), and placebo (OR, 0.77) — and nonsignificantly lower with beta-blockers (OR, 0.90). Compared with placebo, only ARBs were associated with significantly reduced risk for incident diabetes (OR, 0.75) and only diuretics with significantly increased risk (OR, 1.30). Excluding trials in which some subjects did not have hypertension did not change the findings substantially.

Comment: Among the limitations of this meta-analysis are that the definition of diabetes changed over time, diabetes was not a prespecified endpoint in many of the trials, and antihypertensive strategies often involved adding second or third drugs. In addition, the trials didn’t have many new diabetes cases during their roughly 3 to 5 years of follow-up, so the absolute differences in incidence between antihypertensive agents never exceeded 3.6%. However, even this risk increase might matter in high-risk populations (e.g., obese people), particularly in the longer term. Therefore, it’s reasonable to use this study’s diabetes-risk hierarchy of antihypertensive drug classes to inform medication selection in such populations.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology February 7, 2007

Beyond Skin and Joints: Psoriasis and the Metabolic Syndrome

Researchers identified the metabolic syndrome in 30% of psoriasis patients seen at tertiary skin centers.

Recent studies have linked psoriasis and psoriatic arthritis to health impairment beyond joints and skin. Compared with the general population, patients with psoriasis are more likely to smoke and to be overweight, and cardiovascular disease and mortality have been associated with psoriatic diseases. The metabolic syndrome is a significant predictor of cardiovascular risk.

To determine the prevalence of the metabolic syndrome in patients with psoriasis, the authors evaluated 338 patients with psoriasis and 334 patients with other skin diseases. Although the article’s title suggests that the study was hospital-based, it was conducted in outpatient clinics at three Italian university hospitals. Patients were at least 18, had had psoriasis for at least 6 months, and had not received systemic therapies for psoriasis for at least 1 month. The researchers measured weight, body-mass index, blood pressure, and fasting glucose and cholesterol levels. The metabolic syndrome was defined by the presence of at least three of the following criteria: waist circumference >102 cm in men or >88 cm in women; hypertriglyceridemia >1.7 mmol/L; high-density lipoprotein (HDL) cholesterol <1.0 mmol/L in men or <1.3 mmol/L in women; blood pressure >135/85 mm Hg; and fasting plasma glucose >6.1 mmol/L. The authors do not report whether patie nts were receiving treatment for elevated blood pressure, hyperglycemia, or lipid abnormalities or how they evaluated the presence of the metabolic syndrome in patients receiving such treatment.

They found that 102 psoriasis patients and 69 control patients had the metabolic syndrome (30.1% vs. 20.6%; P<0.0001). In addition, psoriasis patients had significantly greater mean BMI and waist circumference and higher prevalence of hypertriglyceridemia and were more likely to smoke than control patients. The differences were evident at all decades of age.

Comment: The metabolic syndrome has been linked to excess cardiovascular risk, excess all-cause and colon cancer mortality, and insulin resistance. The authors note that the TNF antagonist treatment improves insulin resistance and may, therefore, decrease risk for morbidity and mortality. They acknowledge that because the study population comprised patients referred to tertiary centers, their data may not be generalizable. Nevertheless, these observations replicate findings from multiple studies in the general population. Whether treatments that address the metabolic syndrome improve psoriasis control is unknown. Still, those of us who treat psoriatic patients should not give up our role as physicians and should look for these abnormalities in our patients.

— Jeffrey P. Callen, MD

Published in Journal Watch Dermatology July 13, 2007

WHO Report: Risk for Thromboembolism on Long Plane Rides Is 1 in 6000

The risk for venous thromboembolism approximately doubles after a plane flight lasting at least 4 hours but is still low, about 1 in 6000, according to WHO researchers.

Their report, released online, is based largely on three epidemiologic studies and two pathophysiologic studies.

Among the findings:

• The risk also increases with other forms of travel — such as by car, bus, or train — where riders sit immobile for long periods.

• The risk remains elevated for 2 months after the trip.

• The risk is also increased by obesity, use of oral contraceptives, presence of the factor V Leiden mutation, and extremes of height (above 6.2 or below 5.2 feet).

Middle Age Not Too Late to Lower Cardiac Risk

Adopting a healthy lifestyle after age 45 may confer cardiovascular and mortality benefits even just 4 years later, according to a study in the July edition of the American Journal of Medicine.

To study the origin and progression of atherosclerosis, researchers prospectively followed roughly 16,000 adults aged 45 to 64 at baseline. After 6 years, about 1000 had newly adopted an overall healthy lifestyle, defined as four behaviors: eating at least five fruits and vegetables daily, exercising at least 2.5 hours weekly, maintaining a BMI between 18.5 and 30, and not smoking. Some 11,000 were following three or fewer of these behaviors.

During the next 4 years, those who had newly adopted all four behaviors had a 40% reduction in all-cause mortality and a 35% reduction in cardiovascular events, compared with those who were following three or fewer healthy behaviors.

The authors conclude that adhering to a healthy lifestyle is "extremely worthwhile, and that middle-age is not too late to act."

Routine Meningitis Vaccine Recommended for All Adolescents

All adolescents between ages 11 and 18 should now routinely receive a dose of meningococcal conjugate vaccine (MCV4), the CDC's Advisory Committee on Immunization Practices recommends.

Because of short supply, priority was previously given to college freshmen, high school freshmen, and 11- and 12-year-olds.

However, when meeting in Atlanta last week, the committee sought to simplify its current recommendations by extending the coverage to a much wider group of adolescents now that adequate supplies of MCV4 are anticipated, according to a CDC spokesperson. As before, unvaccinated college freshmen and those at increased risk for meningococcal disease should also receive the vaccine.

Advisory Committee Updates Flu Vaccination Recommendations

The Advisory Committee on Immunization Practices has issued 2007 influenza vaccination guidelines in an MMWR early release that make few changes to previous recommendations.

In one of the few modifications from last year, the agency recommends that children aged 6 months to 8 years who have received only a single dose of flu vaccine in their first vaccination year get two doses — rather than the previously recommended single dose — the following year. The guidelines also recommend that healthcare administrators consider the level of vaccination coverage among healthcare workers to be a measure within a patient safety quality program

Pneumonia and Heart Disease Go Together

New research confirms the old association.

The association between pneumonia and acute cardiac events was of considerable clinical interest in the early 20th century (when pneumonia was routinely treated with digitalis). Houston researchers have reassessed the association using today’s more precise diagnostic tools.

Of 170 patients with culture-confirmed pneumococcal pneumonia treated from 2001 through 2005 at a single Veterans Affairs hospital, 33 (19%) presented with 46 acute cardiac problems on admission: MI was diagnosed in 12 (7%), a new arrhythmia (most commonly atrial fibrillation) in 10 (6%), and new or worsening congestive heart failure in 24 (14%). Thirty-one of the 33 patients had severe pneumonia. Mortality rates varied from 40% in MI patients to 0% in those with new arrhythmias; the overall mortality rate of 27% in pneumonia patients with cardiac complications contrasted with the 9% mortality rate in those without.

Interestingly, all 12 patients with acute MI had at least two cardiac risks, but in 8 patients, these risks had not been identified before admission.

Comment: Acute bacterial pneumonia might be considered nature’s little stress test. Although this study doesn’t prove a causal relation, it makes sense that pneumonia might worsen preexisting cardiac problems and bring new ones to light. Here’s yet another reason to endorse the pneumococcal vaccine: It also may reduce the likelihood of cardiac decompensation.

— Abigail Zuger, MD

Does Age of Onset Predict Outcomes in Bipolar Disease?

Childhood onset of illness was associated with long treatment delay and more severe disease than adult onset.

Bipolar disorder affects about 1% to 3% of adults; in many cases, the illness starts in childhood or adolescence. Investigators examined whether age of onset predicted the severity of bipolar disorder in 480 carefully diagnosed adult outpatients (mean age, 42) who had been ill for an average of more than 20 years.

Data on self-reported age of onset of manic or depressive symptoms and age of first pharmacologic treatment were available for 420 patients. Overall, 14% of patients experienced onset of illness before age 13 (childhood onset), and 36% experienced onset between ages 13 and 18 (adolescent onset). Among the childhood-onset group, the average time before first treatment was more than 16 years. Compared with adult-onset patients, those who had onset in childhood and adolescence reported more affective episodes, comorbidities, and rapid ultradian cycling (days during which both mania and depression occurred).

Comment: Early onset of bipolar disorder is associated with treatment delay that might contribute to more affective episodes and treatment-resistant illness, as well as comorbidities such as substance use and anxiety. The diagnosis of bipolar disorder is difficult and often is complicated by episodic, fragmented care and physicians’ reluctance to label a child or adolescent with the disorder. Coordination of care for affected youth remains a challenge. The lack of available mental health care often results in visits to primary-care providers who tend to view symptoms in isolation. As a result, some bipolar children are treated with stimulants for ADHD or antidepressants for depression, which can prolong the time to diagnosis of bipolar disorder and to treatment with mood stabilizers or antipsychotics, as recommended in treatment guidelines (see J Am Acad Child Adolesc Psychiatry 2005; 44:213). Early detection, diagnosis, and treatment remain key to improved quality of life for those affected with bipolar disorder.

— M. Susan Jay, MD

 Transdermal Delivery May Cut Clot Risk of Estrogen

Transdermal estrogen therapy may not pose the same risk for venous thromboembolism as oral estrogen therapy does, according to a study in Circulation.

The French case-control study compared 271 postmenopausal women 45 to 70 years old who had a first episode of idiopathic venous thromboembolism with 610 controls. After adjustment for potential confounders, women who took oral estrogen were four times as likely to have had a venous thromboembolism as those who did not take hormones. But women who used transdermal estrogen had about the same risk as nonusers. The study also suggests that norpregnane derivatives are thrombogenic, while micronized progesterone and pregnane derivatives appear not to be.

Editorialists write that the study "suggests that, at least for risk of VTE, both the route of estrogen administration and the choice of progestogen make a difference."

High Pulse Pressure Identified as an Important Risk Factor for Atrial Fibrillation

High pulse pressure indicates heightened risk for new-onset atrial fibrillation, according to an observational study in today's JAMA.

Researchers measured baseline pulse pressures in some 5300 men and women aged 35 or older participating in the Framingham Heart Study. Subjects were monitored for incident atrial fibrillation over about two decades. Roughly 13% of subjects developed atrial fibrillation during follow-up, which averaged 16 years. After adjusting for age, sex, and clinical risk factors, each 20-mm-Hg increment in pulse pressure above 40 was associated with a 24% increase in risk.

The authors conclude that high pulse pressure "is the single blood pressure component most predictive of future development" of atrial fibrillation and speculate that therapy aimed at reducing pulse pressure, such as renin-angiotensin system blockade, may markedly reduce its incidence.

Benefit of Prophylactic Tamoxifen Persists After Treatment Stops

Women taking tamoxifen to prevent breast cancer have a reduced risk for at least several years after their treatment ends, according to two studies in the Journal of the National Cancer Institute.

In one study, over 7000 women were randomized to tamoxifen or placebo for 5 years and followed a median of 8 years from randomization. Tamoxifen was associated with a 26% reduction in the incidence of ER-positive invasive breast cancers during treatment and a 44% reduction during the subsequent years.

In the other, about 2500 women were randomized to tamoxifen or placebo for 8 years and followed a median of 13 years. The risk for ER-positive breast cancer was not significantly lower during the treatment period but was significantly reduced afterward (hazard ratio, 0.48).

An editorial said these and other data "convincingly move tamoxifen beyond the proof-of-principle stage and underscore its worth as a viable standard option for preventing ER-positive breast cancer in high-risk women."