Association of Obesity Subtypes in the Longitudinal Assessment of Bariatric Surgery Study and 3-Year Postoperative Weight Change.

OBJECTIVE: The study objective was to empirically identify subgroups of patients with obesity and investigate their association with postoperative weight change. METHODS: A longitudinal analysis of 2,458 adults in the Longitudinal Assessment of Bariatric Surgery (LABS) study was used. Baseline data were used to identify subgroups. The outcome was 3-year weight change after bariatric surgery. RESULTS: We identified four classes (subtypes) of obesity, which could be characterized as diabetes with low rates of high-density lipoprotein (Class 1), disordered eating (Class 2), mixed (Class 3), and extreme obesity with early onset (Class 4). Approximately 98% of participants in Class 1 had diabetes compared with < 40% in the other classes. There were high rates of binge eating in Class 2, and more than 92% of those in this class reported eating when not hungry. Class 4 was characterized by a higher BMI at baseline. Adults in Class 4 lost an average of 25.0% (males) and 30.3% (females) of their baseline weight over 3 years. In contrast with participants in Class 1, those in Classes 2 and 3 had significantly larger 3-year weight losses than their peers in Class 4. CONCLUSIONS: Obesity is a heterogeneous disease. Bariatric surgery may be most beneficial for adults with disordered eating.

Type 2 Diabetes Remission Rates After Laparoscopic Gastric Bypass and Gastric Banding: Results of the Longitudinal Assessment of Bariatric Surgery Study.

OBJECTIVE: The goals of this study were to determine baseline and postbariatric surgical characteristics associated with type 2 diabetes remission and if, after controlling for differences in weight loss, diabetes remission was greater after Roux-en-Y gastric bypass (RYGBP) than laparoscopic gastric banding (LAGB). RESEARCH DESIGN AND METHODS: An observational cohort of obese participants was studied using generalized linear mixed models to examine the associations of bariatric surgery type and diabetes remission rates for up to 3 years. Of 2,458 obese participants enrolled, 1,868 (76%) had complete data to assess diabetes status at both baseline and at least one follow-up visit. Of these, 627 participants (34%) were classified with diabetes: 466 underwent RYGBP and 140 underwent LAGB. RESULTS: After 3 years, 68.7% of RYGBP and 30.2% of LAGB participants were in diabetes remission. Baseline factors associated with diabetes remission included a lower weight for LAGB, greater fasting C-peptide, lower leptin-to-fat mass ratio for RYGBP, and a lower hemoglobin A1c without need for insulin for both procedures. After both procedures, greater postsurgical weight loss was associated with remission. However, even after controlling for differences in amount of weight lost, relative diabetes remission rates remained nearly twofold higher after RYGBP than LAGB. CONCLUSIONS: Diabetes remission up to 3 years after RYGBP and LAGB was proportionally higher with increasing postsurgical weight loss. However, the nearly twofold greater weight loss-adjusted likelihood of diabetes remission in subjects undergoing RYGBP than LAGB suggests unique mechanisms contributing to improved glucose metabolism beyond weight loss after RYGBP.

Weighted log-rank statistic to compare shared-path adaptive treatment strategies.

Adaptive treatment strategies (ATSs) more closely mimic the reality of a physician's prescription process where the physician prescribes a medication to his/her patient, and based on that patient's response to the medication, modifies the treatment. Two-stage randomization designs, more generally, sequential multiple assignment randomization trial designs, are useful to assess ATSs where the interest is in comparing the entire sequence of treatments, including the patient's intermediate response. In this paper, we introduce the notion of shared-path and separate-path ATSs and propose a weighted log-rank statistic to compare overall survival distributions of multiple two-stage ATSs, some of which may be shared-path. Large sample properties of the statistic are derived and the type I error rate and power of the test are compared with the standard log-rank test through simulation.

Up-front versus sequential randomizations for inference on adaptive treatment strategies.

Adaptive treatment strategies are useful in the treatment of chronic diseases such as AIDS and cancer because they allow tailoring the treatment to a patient's need and disease status. We consider two randomization schemes for clinical trials that are commonly used to design studies comparing adaptive treatment strategies, namely, up-front randomization and sequential randomization. Up-front randomization is the classical method of randomization where patients are randomized at the beginning of the study to pre-specified treatment strategies. In sequentially randomized trials, patients are randomized sequentially to available treatment options over the duration of the therapy as they become eligible to receive subsequent treatments. We compare the efficiency and the power of the traditional up-front randomized trials with that of sequentially randomized trials designed for comparing adaptive treatment strategies based on a continuous outcome. The analytical and simulation results indicate that, when properly analyzed, sequentially randomized trials are more efficient and powerful than up-front randomized trials.

Thirty-day mortality after bariatric surgery: independently adjudicated causes of death in the longitudinal assessment of bariatric surgery.

BACKGROUND: Mortality following bariatric surgery is a rare event in contemporary series, making it difficult for any single center to draw meaningful conclusions as to cause of death. Nevertheless, much of the published mortality data come from single-center case series and reviews of administrative databases. These sources tend to produce lower mortality estimates than those obtained from controlled clinical trials. Furthermore, information about the causes of death and how they were determined is not always available. The aim of the present report is to describe in detail all deaths occurring within 30 days of surgery in the Longitudinal Assessment of Bariatric Surgery (LABS). METHODS: LABS is a ten-center observational cohort study of bariatric surgical outcomes. Data were collected prospectively for bariatric surgeries performed between March 2005 and April 2009. All deaths occurring within 30-days of surgery were identified, and cause of death assigned by an independent Adjudication Subcommittee, blinded to operating surgeon and site. RESULTS: Six thousand one hundred eighteen patients underwent primary bariatric surgery. Eighteen deaths (0.3%) occurred within 30-days of surgery. The most common cause of death was sepsis (33% of deaths), followed by cardiac causes (28%), and pulmonary embolism (17%). For one patient cause of death could not be determined despite examination of all available information. CONCLUSIONS: This study confirms the low 30-day mortality rate following bariatric surgery. The recognized complications of anastomotic leak, cardiac events, and pulmonary emboli accounted for the majority of 30-day deaths.

Relationship between surgeon volume and adverse outcomes after RYGB in Longitudinal Assessment of Bariatric Surgery (LABS) study.

BACKGROUND: Bariatric surgery is technically demanding surgery performed on high-risk patients. Previous studies using administrative databases have shown a relationship between surgeon volume and patient outcome after Roux-en-Y gastric bypass (RYGB). We examined the relationship between surgeons' annual RYGB volumes and 30-day patient outcomes at 10 centers within the United States. METHODS: The Longitudinal Assessment of Bariatric Surgery (LABS)-1 is a prospective study examining the 30-day adverse outcomes after bariatric surgery. The outcomes after RYGB were adjusted by procedure type (open versus laparoscopic), functional status, body mass index, history of deep vein thrombosis, pulmonary embolism, and obstructive sleep apnea. The data were examined to determine the nature and strength of the association between surgeon volume and patients' short-term (30-day) adverse outcomes after RYGB. RESULTS: The analysis included 3410 initial RYGB operations performed by 31 surgeons, 15 of whom averaged <50 cases annually. The crude composite adverse outcome (i.e., death, deep vein thrombosis, pulmonary embolism, reintervention or nondischarge at day 30) incidence was 5.2%. After risk adjustment, a greater surgeon RYGB volume was associated with lower composite event rates, with a continuous relationship (i.e., varying cutpoints differentiated the composite event rates), such that for each 10-case/yr increase in volume, the risk of a composite event decreased by 10%. CONCLUSION: In the LABS, the patient's risk of an adverse outcome after RYGB decreased significantly with the increase in surgeon RYGB volume (cases performed annually).

Perioperative safety in the longitudinal assessment of bariatric surgery.

BACKGROUND: To improve decision making in the treatment of extreme obesity, the risks of bariatric surgical procedures require further characterization. METHODS: We performed a prospective, multicenter, observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007. A composite end point of 30-day major adverse outcomes (including death; venous thromboembolism; percutaneous, endoscopic, or operative reintervention; and failure to be discharged from the hospital) was evaluated among patients undergoing first-time bariatric surgery. RESULTS: There were 4776 patients who had a first-time bariatric procedure (mean age, 44.5 years; 21.1% men; 10.9% nonwhite; median body-mass index [the weight in kilograms divided by the square of the height in meters], 46.5). More than half had at least two coexisting conditions. A Roux-en-Y gastric bypass was performed in 3412 patients (with 87.2% of the procedures performed laparoscopically), and laparoscopic adjustable gastric banding was performed in 1198 patients; 166 patients underwent other procedures and were not included in the analysis. The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric banding was 0.3%; a total of 4.3% of patients had at least one major adverse outcome. A history of deep-vein thrombosis or pulmonary embolus, a diagnosis of obstructive sleep apnea, and impaired functional status were each independently associated with an increased risk of the composite end point. Extreme values of body-mass index were significantly associated with an increased risk of the composite end point, whereas age, sex, race, ethnic group, and other coexisting conditions were not. CONCLUSIONS: The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics. In helping patients make appropriate choices, short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese. (ClinicalTrials.gov number, NCT00433810.)

Physicians encouraging colorectal screening: a randomized controlled trial of enhanced office and patient management on compliance with colorectal cancer screening.

BACKGROUND: Colorectal cancer screening is underused. Our objective was to evaluate methods for promoting colorectal cancer screening in primary care practice. METHODS: A 2 x 2 factorial randomized clinical trial measured the effects of a tailored vs nontailored physician recommendation letter and an enhanced vs nonenhanced physician office and patient management intervention on colorectal cancer screening adherence. The enhanced and nonenhanced physician office and patient management interventions varied the amount of external support to help physician offices develop and implement colorectal cancer screening programs. The study included 10 primary care physician office practices and 599 screen-eligible patients aged 50 to 79 years. The primary end point was medical-record-verified flexible sigmoidoscopy or colonoscopy. Statistical end-point analysis (according to randomization intent) used generalized estimating equations to account for correlated outcomes according to physician group. RESULTS: During a 1-year period, endoscopy in the lower gastrointestinal tract (lower endoscopy) occurred in 289 of 599 patients (48.2%). This finding included the following rates of lower endoscopy: 81 of 152 patients (53.3%) in the group that received the tailored letter and enhanced management; 103 of 190 (54.2%) in the group that received the nontailored letter and enhanced management; 58 of 133 (43.6%) in the group that received the tailored letter and nonenhanced management; and 47 of 124 (37.9%) in the group that received the nontailored letter and nonenhanced management. Enhanced office and patient management increased the odds of completing a colonoscopy or flexible sigmoidoscopy by 1.63-fold (95% confidence interval, 1.11-2.41; P = .01). However, the tailored letter increased the odds of completion by only 1.08-fold (95% confidence interval, 0.72-1.62; P = .71). CONCLUSIONS: Approximately one-half of the screen-eligible primary medical care patients aged 50 to 79 years obtained lower endoscopic colorectal cancer screening within 1 year of recommendation. An enhanced office and patient management system significantly improved colorectal cancer screening adherence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00327457.