Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 +/- 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 +/- 0.4% in the placebo group (P = 0. 005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P = 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy.

The cognitive performance of a group of 82 newly diagnosed patients with Parkinson's disease who had never been treated was reassessed approximately 4 mths after randomization to one of three monotherapies (levodopa, bromocriptine or anticholinergic drugs). Dopaminergic and anticholinergic treatments both led to improvement in motor control but their effects upon cognitive performance dissociated. Anticholinergic drugs produced impairment in processes underlying the immediate registration of information whilst dopaminergic therapy produced improvement on a task dependent on working memory and cognitive sequencing. Other cognitive measures showed no change on treatment. The deficits that were affected by cholinergic and dopaminergic modulation are those that were most compromised in the early, untreated state in Parkinson's disease. The data support the notion that cognitive impairment in Parkinson's disease is multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcortico-frontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex.

Objective. To compare work disability and job loss in early rheumatoid arthritis (RA) patients receiving adalimumab plus methotrexate (adalimumab ؉ MTX) versus MTX alone. Methods. In this multicenter, randomized, controlled trial, patients with RA for <2 years who had never taken MTX and who self-reported work impairment were randomized to adalimumab ؉ MTX or placebo ؉ MTX for 56 weeks. Primary outcome was job loss of any cause and/or imminent job loss at or after week 16. Secondary outcomes included disease activity, function (Health Assessment Questionnaire [HAQ] score), and RA quality of life (RAQoL) questionnaire score. Work was evaluated with work diaries and the RA Work Instability Scale. Results. Although job loss during the 56-week study was significantly lower with adalimumab ؉ MTX (14 of 75 patients) compared with MTX alone (29 of 73 patients; P ‫؍‬ 0.005), the primary end point was not met (12 of 75 versus 20 of 73 patients; P ‫؍‬ 0.092), likely owing to early drop out in the MTX group. There were significant improvements in American College of Rheumatology 20% response criteria, 28-joint Disease Activity Score, ⌬HAQ, ⌬RAQoL, and working time lost in the adalimumab ؉ MTX group. Twenty-four serious adverse events were reported in 17 participants, with no differences between groups. Conclusion. Adalimumab ؉ MTX reduced job loss and improved productivity in early RA when compared with MTX alone, which supports the early use of anti-tumor necrosis factor therapy and suggests its cost efficacy.

Osteopenia and osteoporosis have recently been described as complications of antiretroviral therapy in HIV-infected patients. The advent of highly active antiretroviral therapy in conjunction with improved standard antiviral and antibiotic regimens has dramatically changed the clinical course of HIV infection, resulting in prolonged survival. The pathogenesis and role of each individual medication are poorly understood. Avascular necrosis has also been described in AIDS patients receiving or not receiving antiretroviral therapy. This article is a clinically focused review of the literature on osteopenia, osteoporosis, and mineral metabolism related to HIV infection. In patients with HIV infection, the risks of osteopenia and osteoporosis are not very clear. The suggested risk factors for the development of osteopenia are use of protease inhibitors, longer duration of HIV infection, high viral load, high lactate levels, low bicarbonate levels, raised alkaline phosphatase level, and lower body weight before antiretroviral therapy. There have also been a few case reports of pathologic fractures in AIDS patients with antiretroviral therapy-induced osteopenia and osteoporosis. The underlying mechanism triggering bone loss in HIV-infected patients is unknown. The proinflammatory cytokines tumor necrosis factor and interleukin-6 have been found to be constitutionally produced in increased amounts in HIV-positive individuals, and they may have a role in osteoclast activation and resorption. Serum markers of bone formation are decreased and resorption is increased in patients with advanced clinical disease. Hypocalcemia, hypercalcemia, and abnormalities of the parathyroid hormone axis have been described in HIV infection. Histomorphometric analyses have shown altered bone remodeling in HIV-infected patients when compared with controls. Patients with known risk factors for osteoporosis-advancing age, low body weight, and prolonged duration of HIV infection-and those receiving protease inhibitor treatment should be considered for dual x-ray absorptiometry imaging. If bone mineral density is osteopenic or osteoporotic, then the patient should also be screened for other known medical causes of osteoporosis and consider treatment with a bisphosphonate or, if hypogonadal, testosterone replacement under close monitoring.

The associations between sociodemographic variables, psychological factors, and changes in dietary fat consumption over 4 months were assessed in a randomized controlled trial of behavioral counseling versus standard advice. Patients were 141 men and 150 women, with an average age of 52.1 years and total cholesterol level of 7.27 mmol/l (278 mg/dl). Smokers, younger patients, and those with greater body mass index had higher fat intake at baseline. Behavioral counseling led to greater reductions in fat intake than did standard advice. Self-efficacy and ratings of benefits of low-fat diets were related to fat consumption at baseline, and changes in these measures were correlated with changes in fat intake. Family support, baseline anticipated regret, and (for the behavioral counseling group only) baseline behavioral intentions predicted reductions in fat intake. The results indicated that psychosocial variables associated cross-sectionally with fat consumption do not necessarily predict change and that factors involved in the process of change and the prediction of change need to be differentiated.