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 β‐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.

Our data indicate that use of dexfenfluramine and phentermine/fenfluramine is associated with an increase in the prevalence of AR using FDA echocardiographic criteria, but was not associated with an increase in the prevalence of MR using FDA criteria or with serious cardiac events.

Objective: To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss. Design: Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. Patients: A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30-65 kg/m 2 ) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38711 year), weight (110.7723 kg), and BMI (39.876.5 kg/m 2 ) were similar across the four treatment groups. Measurements: Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis -3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Litet); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events. Results: After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of À1.98 and À1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m 2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during the 6-month treatment in the two higher dose groups. The lowest dose to reach statistical significance in weight loss after 6 months' treatment was 40 mg. Post hoc analysis revealed a 3.5-3.8% weight loss at month 6 in the two higher dose groups among Caucasian patients having insulin secretion greater than the median of the cohort, defined as CIR gp (corrected insulin response at the glucose peak) X1.43. There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake. Mean changes of blood glucose AUC 0-180 min during an oral glucose tolerance test in patients taking octreotide LAR were 39-40 mg/dl h higher than those on placebo. A total of 7-21% of the patients taking octreotide LAR reached a 5% or greater decrease in body weight from Baseline, compared to 11% for the placebo group. This was not statistically significant. The most common adverse events included diarrhea, headache, cholelithiasis, nausea, and abdominal pain. Conclusion: Octreotide LAR given at 40 or 60 mg r...

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.

LUTES. Combined drug treatmet of obesity. Obes Res.Pharmacologicaltreatment of obesity has beenneglected as aviable therapeuticoption formany years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs stillin development include alipaseinhibitorthat produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modestweight loss,and formost,weight loss continuesfor as long as medication is given. The most successful drug regimens to date are combinations of phentermineandfenfluramineorof ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesityfor2 to almost4 yearsinclinicaltrials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.1995;3(S~ppl4):497S-5OOS.