Rational design of a combination medication for the treatment of obesity.

Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice. Finally, a randomized, blinded, placebo-controlled trial in obese adult subjects was conducted. Randomization included: BUP (300 mg) + NAL (50 mg), BUP (300 mg) + placebo (P), NAL (50 mg) + P or P+P for up to 24 weeks. BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy, an effect consistent with synergism. Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment. BUP+NAL completers diverged from NAL+P (P < 0.01) and P+P (P < 0.001) at week 16 and from BUP+P by week 24 (P < 0.05). The combination was also well tolerated. Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone. These results supported the hypothesis that NAL, through blockade of beta-endorphin mediated POMC autoinhibition, prevents the classic weight loss plateau observed with monotherapies such as BUP. This novel treatment approach (BUP+NAL) holds promise for the treatment of obesity.\

A review of barriers to utilization of the medicare hospice benefits in urban populations and strategies for enhanced access.

Disparities in access to health care extend to end-of-life care. Lack of access to hospice mirrors lack of access to health maintenance and primary care. Patients who are served by hospice nationally are disproportionately white and likely to reside in economically stable communities. In many urban low-income communities, less than 5% of decedents receive hospice care in the last 6 months of life. This review focuses on barriers to palliative care and hospice in urban, predominantly low-income communities, including cultural and reimbursement factors and the paucity of hospice providers, outreach projects, and in-patient hospice beds in urban communities. This review will also address some strategies that are being implemented by hospices locally and nationally to overcome demographic barriers to hospice care.