Health benefits of gastric bypass surgery after 6 years.

CONTEXT: Extreme obesity is associated with health and cardiovascular disease risks. Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term, long-term outcomes are uncertain. OBJECTIVE: To examine the association of Roux-en-Y gastric bypass (RYGB) surgery with weight loss, diabetes mellitus, and other health risks 6 years after surgery. DESIGN, SETTING, AND PARTICIPANTS: A prospective Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese (body mass index [BMI] ≥ 35) participants aged 18 to 72 years (82% women; mean BMI, 45.9; 95% CI, 31.2-60.6) who sought and received RYGB surgery (n = 418), sought but did not have surgery (n = 417; control group 1), or who were randomly selected from a population-based sample not seeking weight loss surgery (n = 321; control group 2). MAIN OUTCOME MEASURES: Weight loss, diabetes, hypertension, dyslipidemia, and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment. RESULTS: Six years after surgery, patients who received RYGB surgery (with 92.6% follow-up) lost 27.7% (95% CI, 26.6%-28.9%) of their initial body weight compared with 0.2% (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, -1.2% to 1.2%) in control group 2. Weight loss maintenance was superior in patients who received RYGB surgery, with 94% (95% CI, 92%-96%) and 76% (95% CI, 72%-81%) of patients receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after surgery, respectively. Diabetes remission rates 6 years after surgery were 62% (95% CI, 49%-75%) in the RYGB surgery group, 8% (95% CI, 0%-16%) in control group 1, and 6% (95% CI, 0%-13%) in control group 2, with remission odds ratios (ORs) of 16.5 (95% CI, 4.7-57.6; P < .001) vs control group 1 and 21.5 (95% CI, 5.4-85.6; P < .001) vs control group 2. The incidence of diabetes throughout the course of the study was reduced after RYGB surgery (2%; 95% CI, 0%-4%; vs 17%; 95% CI, 10%-24%; OR, 0.11; 95% CI, 0.04-0.34 compared with control group 1 and 15%; 95% CI, 9%-21%; OR, 0.21; 95% CI, 0.06-0.67 compared with control group 2; both P < .001). The numbers of participants with bariatric surgery-related hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for the RYGB surgery group and 2 control groups, respectively. CONCLUSION: Among severely obese patients, compared with nonsurgical control patients, the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years.

Gene-based warfarin dosing compared with standard of care practices in an orthopedic surgery population: a prospective, parallel cohort study.

Warfarin remains a difficult drug to manage due to a narrow therapeutic range and wide interindividual variability in dose requirements. The relationship between warfarin sensitivity and CYP2C9 and VKORC1 variants is strong, and is the basis for several proposed dosing algorithms. Here a gene-based dosing algorithm was compared with standard of care dosing in patients receiving warfarin to prevent venous thromboembolism after joint replacement surgery. Participants (n = 229) were adults (> or =18 years) undergoing elective total hip or knee arthroplasty and receiving warfarin under the direction of a dedicated anticoagulation services team. Patients were assigned to genotype-based or standard of care dosing arms in an alternating fashion. Initial dose for patients was determined by validated algorithms from Sconce 2005 and Pendleton 2008. Management was based on INR, but dose was adjusted less aggressively for patients with CYP2C9 variants. The primary endpoint was reduction in the incidence of adverse events; additional endpoints included time to first therapeutic INR (1.8-2.9), time to first supratherapeutic INR, and percent of INR determinations that fell below, within, and above the therapeutic range. Endpoints did not achieve statistical significance, possibly due to the management of this study by a dedicated and experienced anticoagulation services team. Trends in the data suggest that patients with genetic variants progressed to a therapeutic INR faster than patients in whom genetic variants were not detected, and there were fewer adverse events in the genotype-based dosing arm. In addition, the results of this study confirm those of others demonstrating clear relationship of genotype for CYP2C9 and VKORC1 with warfarin dose requirements; as the number of variants in these genes increases, the dose requirement decreases. Of note, the gene-based algorithm utilized here significantly underpredicted the dose requirement for participants with no variants, indicating that patients with no variants should be managed with a different algorithm than patients who inherit genetic variants in CYP2C9 and/or VKORC1. In conclusion, gene-based dosing did not improve warfarin management as defined by INR dose response, using the described protocols for implementation. Findings suggest alternative strategies for dosing based on the presence or absence of genetic variants is needed.