IMWR Newswatch %u2013 March 2005

IMWR Newswatch — March 2005

Circumcision Reduces HIV Risk

Male circumcision decreases the risk of acquiring HIV infection but not the risk of other sexually transmitted infections. In a study of >5000 men in Uganda, the prevalence of HIV infection was 15% in uncircumcised men and 9.5% in circumcised men. The incidence of HIV infection was 1.1 per 100 person-years in the circumcised group and 1.8 per 100 person-years in the uncircumcised group among those who were followed at 10-month intervals (P = .03). Circumcision had no effect on the prevalence of genital ulcer disease, genital discharge and dysuria, or the incidence of gonorrhea, Chlamydia, syphilis, or herpes simplex virus 2 (AIDS. 2004;18:2428-2430).

Consider DHEA for Midlife Depression

Dehydroepiandrosterone (DHEA) is an effective treatment for midlife-onset major and minor depression. In a randomized, double-blind, placebo-controlled, crossover study, 46 men and women aged 45 to 65 years with midlife-onset major or minor depression received 6 weeks of DHEA therapy (90 mg/d for 3 weeks and 450 mg/d for 3 weeks) or placebo. Treatment with DHEA was associated with significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P <.01) and 6 weeks of placebo treatment (P <.01). A ³50% reduction in baseline Hamilton Depression Rating Scale scores was observed in 23 patients after DHEA and in 13 patients after placebo (Arch Gen Psychiatry. 2005;62:154-162).

Low BMD Linked to Alzheimer’s Risk

Low femoral neck bone mineral density (BMD) is associated with an increased risk of Alzheimer’s disease (AD) and all-cause dementia in women but not men. BMD was measured at the femoral neck, the trochanter, and the radial shaft in 987 cognitively intact elderly persons who were followed for 8 years. Women in the lowest quartile of femoral neck BMD had more than twice the incidence of AD (hazard ratio, 2.04) and all-cause dementia (hazard ratio, 2.01) compared with those in higher quartiles after adjusting for age, sex, estrogen use, smoking, and other variables. There was a trend toward an inverse relationship between BMD and the risk of AD in men, but the relationship was not statistically significant at any of the 3 sites (Arch Neurol. 2005;62:107-111).

CRP Levels Predict Cardiomyopathy Mortality

C-reactive protein (CRP) levels independently predict mortality in patients with ischemic cardiomyopathy. CRP levels were measured in 123 men who underwent cardiac catheterization and were found to have a left ventricular ejection fraction (LVEF) of £45% and significant angiographic coronary artery disease. CRP levels predicted the risk of death during follow-up of 3 years. Each mg/dL increment of CRP was associated with a 26% increase in mortality risk. The correlation was independent of other prognostic factors, including age, LVEF, symptoms of severe congestive heart failure, and use of beta blockers or angiotensin-converting enzyme inhibitors (Am J Cardiol. 2005;95:88-90).

CHF Risk Doubles in Patients with Arthritis

Rheumatoid arthritis (RA) is associated with a 2-fold increase in the risk of congestive heart failure (CHF). A group of 575 patients with RA and 583 controls without RA were followed-up until death, incident CHF, or the study cut-off point. The CHF incidence rates were 1.99 and 1.16 cases per 100 person-years in the RA patients and controls, respectively (rate ratio, 1.7). After 30 years of follow-up, the cumulative incidence of CHF was 34.0% in the patients with RA and 25.2% in the controls (P <.001). After adjusting for demographics and cardiovascular risk factors, RA was associated with a 1.87-fold increase in the risk of CHF. The risk hazard ratio was 2.59 among patients with RA who were rheumatoid factor (RF)-positive compared with 1.28 in those who were RF-negative (Arthritis Rheum. 2005;52:412-420).

Protease Inhibitors Increase Metabolic Syndrome Risk

Patients with HIV infection treated with protease inhibitors (PI) are at increased risk of metabolic syndrome, according to a study of 710 patients with HIV infection who underwent a medical examination and laboratory studies following an overnight fast. Metabolic syndrome was defined as ³3 of the following components: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, or fasting hyperglycemia. The prevalence of metabolic syndrome was 17% and ranged from 5.1% in persons aged <30 years to 27% in those aged 50 to 59 years. Past and present PI use was independently associated with increased risk for metabolic syndrome (odds ratio, 2.96 and 4.18, respectively). Only stavudine (odds ratio, 1.74) and lopinavir/ritonavir(odds ratio, 2.46) were associated with the metabolic syndrome after adjusting for age and body mass index (Diabetes Care. 2005;28:132-137).

Statins Increase Osteoarthritis Risk in Elderly Women

Treatment with statins is associated with an increased risk of developing incident radiographic hip osteoarthritis (RHOA) in elderly women, according to a study of 5674 women aged ³65 years who underwent anteroposterior pelvic radiography at baseline and after a mean of 8 years. Overall, 7% of the participants were statin users. Statin use was associated with an increased risk of developing incident RHOA (odds ratio, 1.92) but was not significantly related to other measures of new RHOA. There was a nonsignificant trend toward decreased progression of RHOA in statin users with RHOA at baseline (J Rheumatol. 2005;32:106-110).

Statins Enhance Survival of Hemodialysis Patients

Statin therapy significantly reduces mortality in hemodialysis patients, according to a study of 7365 patients enrolled in the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients in Europe, Japan, and the United States. Statins were prescribed for 11.8% of the patients overall. Most facilities (81%) prescribed statins to <20% of their patients. Patients treated with statins had a 31% lower relative risk for death compared with those not receiving statins (P <.001). Statin treatment was associated with a 23% decrease in cardiac mortality risk (P = .03) and a 44% decrease in noncardiac mortality risk (P <.001). At the facility level, the overall mortality rate decreased 5% for every 10% increase in the number of patients prescribed statins within the facility (P = .02) (Am J Kidney Dis. 2005;45:119-126).

Biotic Therapy Decreases Inflammation in Colitis

Synbiotic treatment with prebiotic and probiotic agents decreases inflammation in patients with ulcerative colitis (UC). A group of 18 patients with active UC were randomized to receive placebo or synbiotic treatment including a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic, a preferential inulin/oligofructose growth substrate for the probiotic strain. After 1 month, sigmoidoscopy scores on a 7-point scale decreased from 4.5 to 3.1 in the synbiotic group and increased from 2.6 to 3.2 in the placebo group (P = .06). Levels of human beta-defensins 2, 3, and 4 in mRNA, which are strongly upregulated in active UC, decreased significantly in the synbiotic group (P = .016, .038, and .008, respectively). Tumor necrosis factor and interleukin 1 were also significantly decreased in the synbiotic group (P = .018 and .023, respectively). Biopsies in the synbiotic group revealed decreased inflammation and regeneration of epithelial tissue (Gut. 2005;54:242-249).

Type 2 Diabetes Adversely Affects Pregnancy Outcomes

The pregnancy outcomes of women with type 2 diabetes have worsened during the past 10 years, according to a study comparing the pregnancy outcomes of 61 women with type 2 diabetes from 1996 to 2001 with that of type 1 diabetics, the general population during the same period, and that of women with type 2 diabetes between 1980 and 1992. As compared with women with type 1 diabetes and the general population, women with type 2 diabetes were 4 and 9 times more likely to experience perinatal mortality, respectively. The risk of congenital malformations was twice as high in the women with type 2 diabetes as in the other 2 groups. Comparison of the 2 groups with type 2 diabetes revealed that perinatal mortality and the rate of major congenital malformations among such patients increased during the last decade (Diabetes Care. 2005;28:323-328).

FDA Rounds

Nasal Spray for Vitamin B Deficiency

A nasal spray formulation of cyanocobalamin (Nascobal; Questcor) has been approved for the treatment of vitamin B₁₂ deficiency associated with pernicious anemia and other malabsorptive conditions, such as gastric bypass surgery, Crohn’s disease, multiple sclerosis, or HIV/AIDS. The 500-mg spray is administered once/week (www.nascobal.com).

Low-Dose Norethindrone/Estradiol Formulation

A low-dose formulation of norethindrone acetate plus ethinyl estradiol (femhrt 0.5 mg/2.5 mg; Warner Chilcott) has been approved for the treatment of moderate-to-severe vasomotor symptoms associated with menopause and for the prevention of osteoporosis in women with an intact uterus. The new formulation provides half the dose of the previously approved 1-mg/5 mg norethindrone acetate/ethinyl estradiol product. The FDA guidelines recommend using the lowest effective dose of hormone therapy for the shortest duration of time based on individual risks and therapeutic goals (www.warnerchilcott.com).

Extended-Release Carbamazepine Capsules

Carbamazepine extended-release capsules (Equetro; Shire) have been approved for the treatment of acute manic and mixed episodes associated with bipolar disorder. The most commonly reported adverse effects included dizziness, drowsiness, nausea, and vomiting. Carbamazepine extended-release capsules will be available in 100-, 200-, and 300-mg strengths (www.equetro.com).

Disintegrating Tablet of Alprazolam

An orally disintegrating tablet formulation of alprazolam (Niravam; Schwarz) has been approved for the management of generalized anxiety disorder, the short-term relief of anxiety symptoms, and the treatment of panic disorder with or without agoraphobia (www.schwarzpharma.com).

Transurethral Injection for Incontinence

A urethral bulking agent for transurethral injection (Uryx; Genyx Medical) has been approved for the treatment of adult women with stress urinary incontinence due to intrinsic sphincter deficiency. The biocompatible polymer implant is injected into urethral tissues as a liquid that separates and solidifies into a spongy material to bulk the urethral wall. Adverse effects included urinary tract infection, urinary hesitancy, dysuria, and hematuria (www.genyx.com).

New Indication for Dialysis Solution

A new indication has been approved for icodextrin 7.5% peritoneal dialysis solution (Extraneal; Baxter), allowing its use for improved (compared with 4.25% dextrose) long-dwell ultrafiltration and clearance of creatinine and urea nitrogen in patients with high average or greater transport characteristics as defined using the peritoneal equilibration test (www.baxter.com).

Imaging System for CABG Surgery

An intraoperative imaging system (Spy; Novadaq) has been approved for use in confirming the proper placement of grafts and assessing their functionality during coronary artery bypass graft surgery. The system uses an injection of indocyanine green to visualize flow restrictions before surgery and validate graft patency during surgery. The hardware includes an imaging head with an automatic range detector and a laser light source activated by a computerized system. The resulting digital images are displayed in real time on a high-resolution monitor (www.novadaq.com).

FDA Reforms Aims at Improving Oversight, Openness

In response to recent criticisms that the FDA has been too slow to remove unsafe drugs from the market the agency will create a new independent Drug Safety Oversight Board to oversee the management of drug safety issues and to provide emerging information to physicians and patients about the risks and benefits of medications. Specifically, the new board will oversee the management of important safety issues, such as recommending information and updates for placement on the Drug Watch, resolving disagreements over approaches to drug safety issues, assessing the need for MedGuides, and overseeing development and implementation of center-wide drug safety policies. Despite claims that this new oversight board will be independent, the FDA announced that the panel would be comprised of FDA officials and medical experts from other Health and Human Services agencies, which some critics have complained is not independent at all (www.fda.gov).

Medication Errors Alert

Eli Lilly has revealed it has received reports of medication dispensing or prescribing errors involving 2 of its drugs—the atypical antipsychotic olanzapine (Zyprexa) and the antihistamine cetirizine (Zyrtec). These reports include instances where olanzapine was incorrectly dispensed for cetirizine and vice versa, which has led to several adverse events in some cases. Physicians are advised to watch for such errors, which could result in unnecessary adverse events and/or potential relapse in patients with schizophrenia or bipolar disorder (www.fda.gov).