Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients

STUDY OBJECTIVES: To assess the effect of megestrol acetate (MA), a progestational appetite stimulant commonly used in patients with AIDS and cancer, on body weight and composition, respiratory muscle strength, arterial blood gas levels, and subjective perceptions in COPD patients. DESIGN AND SETTING: Prospective, double-blind, randomized, placebo-controlled trial conducted on an outpatient basis at 18 sites. PATIENTS: Underweight (< 95% ideal body weight) COPD patients > or = 40 years old. INTERVENTIONS: Either MA, 800 mg/d oral suspension, or placebo at a 1:1 ratio for 8 weeks. RESULTS: Of 145 randomized patients (63% men), 128 patients completed the trial. Body weight increased by 3.2 kg in the MA group and 0.7 kg in the placebo group (p < 0.001). Anthropometric and dual-energy radiograph absorptiometry assessments confirmed that weight gain was mainly fat. Spirometry and maximal voluntary ventilation showed no significant changes from baseline in either group, and the difference in the change in maximum inspiratory pressure between groups was not significant. The 6-min walk distances did not differ statistically between groups at week 2 and week 4, but were greater in the placebo group at week 8 (p = 0.012). Consistent with the known ability of MA to stimulate ventilation, PaCO(2) decreased (4.6 mm Hg, p < 0.001) and PaO(2) increased (2.8 mm Hg, p < 0.04) in the MA group. Questionnaires revealed that body image and appetite improved in the MA group but not the placebo group. Adverse event frequency and type were similar in both groups, but cortisol and testosterone (in men) levels decreased substantially in the MA group. CONCLUSIONS: We conclude that MA safely increased appetite and body weight, stimulated ventilation, and improved body image in underweight COPD patients, but did not improve respiratory muscle function or exercise tolerance.     

Universal nevirapine upon presentation in labor to prevent mother-to-child HIV transmission in high prevalence settings

OBJECTIVE: To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary efficacy of the approach. DESIGN: Women of unknown HIV serostatus presenting in labor were offered single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison populations were also studied. METHODS: We measured uptake by counting the number of women that accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of life. RESULTS: Of 1591 women approached in labor, 634 (40%) took up the intervention and received nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%) adherence rate observed in a comparison cohort in which women self-administered nevirapine before presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). CONCLUSIONS: Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of mother-to-child transmission of HIV.     

The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial

OBJECTIVE: Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS: A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS: The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION: At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.     

High‐frequency vibration for the recanalization of guidewire refractory chronic total coronary occlusions

Background: Recanalization of coronary chronic total occlusions (CTOs) remains a clinical challenge, particularly when standard guidewire attempts fail. Objectives: We sought to determine the safety and efficacy of a novel method that used high‐frequency (20 kHz) vibration to fragment occlusive fibrous tissue and facilitate guidewire crossing into the distal vessel. Methods: A total of 125 patients with CTO, who failed at attempts of conventional guidewire recanalization after more than 5 min of fluoroscopy time, were enrolled in the study. The primary efficacy endpoint was the advancement of the CROSSER? catheter through the occlusion and attainment of coronary guidewire positioning in the distal coronary lumen. The primary safety endpoint was the occurrence of death, myocardial infarction, clinical perforation, or target vessel revascularization within the first 30 days. Results: The average fluoroscopy time while delivering the CROSSER catheter was 12.4 min. CROSSER‐assisted guidewire recanalization was achieved in 76 (60.8%) procedures and a final diameter stenosis <50% was obtained in 68 (54.4%) of cases. Major adverse events occurred in 11 (8.8%) patients, lower than the predefined objective performance criteria. Angina frequency and quality of life were improved in patients with successful guidewire recanalization. Conclusions: We conclude that high‐frequency vibration using the CROSSER catheter is a safe and effective therapy for patients with CTO, which are refractory to standard guidewire recanalization. © 2008 Wiley‐Liss, Inc.     

Offering patients the opportunity to choose their hospital for total knee replacement: impact on satisfaction with the surgery

OBJECTIVE: To describe the extent to which patients were offered a choice between 2 or more hospitals for total knee replacement (TKR); to examine the association between having a choice of hospital for TKR and satisfaction with the surgery; and to identify population groups less likely to be offered a choice. METHODS: We studied a population-based sample of 932 Medicare beneficiaries who underwent elective TKR in 2000. We surveyed patients about their participation in choosing a hospital and their satisfaction with surgery. We examined whether lack of hospital choice influenced satisfaction with surgery after adjusting for age, sex, preoperative function, and socioeconomic status. RESULTS: Among 932 TKR recipients (mean age 74 years, 67% women), more than half (53%) reported having a lack of hospital choice. After adjusting for socioeconomic status, patients reporting lack of choice were approximately twice as likely to be dissatisfied with the results of surgery as patients who reported choosing among 2 or more hospitals for TKR (odds ratio [OR] 2.09, 95% confidence interval [95% CI] 1.13-3.87). Results of logistic regression revealed that patients reporting lack of choice were more likely to be women (OR 1.52, 95% CI 1.14-2.04), >80 years of age (as compared with 65-70 years; OR 1.63, 95% CI 1.03-2.57), living in suburban areas (OR 1.68, 95% CI 1.23-2.30), nonwhite (OR 1.57, 95% CI 0.86-2.87), and were less likely to have TKR performed by a high-volume surgeon (OR 0.71, 95% CI 0.53-0.96). CONCLUSION: More than half of the patients did not have a choice in selecting the hospital where they had TKR. Patients reporting lack of choice were more likely to be dissatisfied with surgery. Interventions to address preferences for hospital may improve satisfaction with care for patients with advanced knee arthritis.     

Managing abnormal blood lipids: a collaborative approach

Current data and guidelines recommend treating abnormal blood lipids (ABL) to goal. This is a complex process and requires involvement from various healthcare professionals with a wide range of expertise. The model of a multidisciplinary case management approach for patients with ABL is well documented and described. This collaborative approach encompasses primary and secondary prevention across the lifespan, incorporates nutritional and exercise management as a significant component, defines the importance and indications for pharmacological therapy, and emphasizes the importance of adherence. Use of this collaborative approach for the treatment of ABL ultimately will improve cardiovascular and cerebrovascular morbidity and mortality.     

Concordance of Collagen-Based Radiocarbon and Aspartic-Acid Racemization Ages

By determining the extent of racemization of aspartic acid in a well-dated bone, it is possible to calculate the in situ first-order rate constant for the interconversion of the L and D enantiomers of aspartic acid. Collagen-based radiocarbon-dated bones are shown to be suitable samples for use in "calibrating" the racemization reaction. Once the aspartic-acid racemization reaction has been "calibrated" for a site, the reaction can be used to date other bones from the deposit. Ages deduced by this method are in good agreement with radiocarbon ages. These results provide evidence that the aspartic-acid racemization reaction is an important chronological tool for dating bones either too old or too small for radiocarbon dating. As an example of the potential application of the technique for dating fossil man, a piece of Rhodesian Man from Broken Hill, Zambia, was analyzed and tentatively assigned an age of about 110,000 years.