Wendy C. King

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.)

Myoblast Transfer in the Treatment of Duchenne's Muscular Dystrophy

BACKGROUND Myoblast transfer has been proposed as a technique to replace dystrophin, the skeletal-muscle protein that is deficient in Duchennes muscular dystrophy. Donor myoblasts injected into muscles of affected patients can fuse with host muscle fibers, thus contributing their nuclei, which are potentially capable of replacing deficient gene products. Previous controlled trials involving a single transfer of myoblasts have been unsuccessful. METHODS We injected donor muscle cells once a month for six months to the biceps brachii muscles of one arm of each of 12 boys with Duchennes muscular dystrophy. The opposite arms served as sham-injected controls. In each procedure 110 million cells donated by fathers or brothers were transferred. The patients were randomly assigned to receive either cyclosporine or placebo. Strength was measured by quantitative isometric muscle testing. Six months after the final myoblast transfer, the presence of dystrophin was assessed with the use of peptide antibodies specific to the deleted exons of the dystrophin gene. RESULTS There was no significant difference in muscle strength between arms injected with myoblasts and sham-injected arms. In one patient, 10.3 percent of muscle fibers expressed donor-derived dystrophin after myoblast transfer. Three other patients also had a low level of donor dystrophin (< 1 percent); eight had none. CONCLUSIONS Myoblasts transferred once a month for six months failed to improve strength in patients with Duchennes muscular dystrophy. The value of exon-specific peptide antibodies in the interpretation of myoblast-transfer results was demonstrated in a patient with Duchennes muscular dystrophy who had a high percentage of donor-derived dystrophin. Specific variables affecting the efficiency of myoblast transfer need to be identified in order to improve upon this technique.

Weight Change and Health Outcomes at 3 Years After Bariatric Surgery Among Individuals With Severe Obesity

IMPORTANCE Severe obesity (body mass index [BMI] ≥35) is associated with a broad range of health risks. Bariatric surgery induces weight loss and short-term health improvements, but little is known about long-term outcomes of these operations. OBJECTIVE To report 3-year change in weight and select health parameters after common bariatric surgical procedures. DESIGN AND SETTING The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. PARTICIPANTS AND EXPOSURE: Adults undergoing first-time bariatric surgical procedures as part of routine clinical care by participating surgeons were recruited between 2006 and 2009 and followed up until September 2012. Participants completed research assessments prior to surgery and 6 months, 12 months, and then annually after surgery. MAIN OUTCOMES AND MEASURES Three years after Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), we assessed percent weight change from baseline and the percentage of participants with diabetes achieving hemoglobin A1c levels less than 6.5% or fasting plasma glucose values less than 126 mg/dL without pharmacologic therapy. Dyslipidemia and hypertension resolution at 3 years was also assessed. RESULTS At baseline, participants (N = 2458) were 18 to 78 years old, 79% were women, median BMI was 45.9 (IQR, 41.7-51.5), and median weight was 129 kg (IQR, 115-147). For their first bariatric surgical procedure, 1738 participants underwent RYGB, 610 LAGB, and 110 other procedures. At baseline, 774 (33%) had diabetes, 1252 (63%) dyslipidemia, and 1601 (68%) hypertension. Three years after surgery, median actual weight loss for RYGB participants was 41 kg (IQR, 31-52), corresponding to a percentage of baseline weight lost of 31.5% (IQR, 24.6%-38.4%). For LAGB participants, actual weight loss was 20 kg (IQR, 10-29), corresponding to 15.9% (IQR, 7.9%-23.0%). The majority of weight loss was evident 1 year after surgery for both procedures. Five distinct weight change trajectory groups were identified for each procedure. Among participants who had diabetes at baseline, 216 RYGB participants (67.5%) and 28 LAGB participants (28.6%) experienced partial remission at 3 years. The incidence of diabetes was 0.9% after RYGB and 3.2% after LAGB. Dyslipidemia resolved in 237 RYGB participants (61.9%) and 39 LAGB participants (27.1%); remission of hypertension occurred in 269 RYGB participants (38.2%) and 43 LAGB participants (17.4%). CONCLUSIONS AND RELEVANCE Among participants with severe obesity, there was substantial weight loss 3 years after bariatric surgery, with the majority experiencing maximum weight change during the first year. However, there was variability in the amount and trajectories of weight loss and in diabetes, blood pressure, and lipid outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00465829.

Prevalence of Alcohol Use Disorders Before and After Bariatric Surgery

CONTEXT Anecdotal reports suggest bariatric surgery may increase the risk of alcohol use disorder (AUD), but prospective data are lacking. OBJECTIVE To determine the prevalence of preoperative and postoperative AUD, and independent predictors of postoperative AUD. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study (Longitudinal Assessment of Bariatric Surgery-2) of adults who underwent bariatric surgery at 10 US hospitals. Of 2458 participants, 1945 (78.8% female; 87.0% white; median age, 47 years; median body mass index, 45.8) completed preoperative and postoperative (at 1 year and/or 2 years) assessments between 2006 and 2011. MAIN OUTCOME MEASURE Past year AUD symptoms determined with the Alcohol Use Disorders Identification Test (indication of alcohol-related harm, alcohol dependence symptoms, or score ≥8). RESULTS The prevalence of AUD symptoms did not significantly differ from 1 year before to 1 year after bariatric surgery (7.6% vs 7.3%; P = .98), but was significantly higher in the second postoperative year (9.6%; P = .01). The following preoperative variables were independently related to an increased odds of AUD after bariatric surgery: male sex (adjusted odds ratio [AOR], 2.14 [95% CI, 1.51-3.01]; P < .001), younger age (age per 10 years younger with preoperative AUD: AOR, 1.31 [95% CI, 1.03-1.68], P = .03; age per 10 years younger without preoperative AUD: AOR, 1.95 [95% CI, 1.65-2.30], P < .001), smoking (AOR, 2.58 [95% CI, 1.19-5.58]; P = .02), regular alcohol consumption (≥ 2 drinks/week: AOR, 6.37 [95% CI, 4.17-9.72]; P < .001), AUD (eg, at age 45, AOR, 11.14 [95% CI, 7.71-16.10]; P < .001), recreational drug use (AOR, 2.38 [95% CI, 1.37-4.14]; P = .01), lower sense of belonging (12-item Interpersonal Support Evaluation List score per 1 point lower: AOR, 1.09 [95% CI, 1.04-1.15]; P = .01), and undergoing a Roux-en-Y gastric bypass procedure (AOR, 2.07 [95% CI, 1.40-3.08]; P < .001; reference category: laparoscopic adjustable gastric band procedure). CONCLUSION In this cohort, the prevalence of AUD was greater in the second postoperative year than the year prior to surgery or in the first postoperative year and was associated with male sex and younger age, numerous preoperative variables (smoking, regular alcohol consumption, AUD, recreational drug use, and lower interpersonal support) and undergoing a Roux-en-Y gastric bypass procedure.

Long‐term benefit from prednisone therapy in Duchenne muscular dystrophy

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 ing/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months)

Prednisone has been shown to improve strength in Duchenne dystrophy. Azathioprine often benefits corticosteroid-responsive diseases and can reduce the dose of prednisone needed. The present study reports a randomized, controlled trial of prednisone and azathioprine designed to assess the longer-term effects of prednisone and to determine whether azathioprine alone, or in combination with prednisone, improves strength. Ninety-nine boys (aged five to 15 years) with Duchenne dystrophy were randomized to one of three groups: (I) placebo; (II) prednisone 0.3 mg/kg/d; or (III) prednisone 0.75 mg/kg/d. After 6 months, azathioprine 2 to 2.5 mg/kg/d was added in groups I and II and placebo added in group III. The study showed that the beneficial effect of prednisone (0.75 mg/kg/d) is maintained for at least 18 months and is associated with a 36% increase in muscle mass. There was weight gain, growth retardation, and other side effects. Azathioprine did not have a beneficial effect. This study suggests that prednisones beneficial effect is not due to immunosuppression.

Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss: The IDEA Randomized Clinical Trial

Importance Effective long-term treatments are needed to address the obesity epidemic. Numerous wearable technologies specific to physical activity and diet are available, but it is unclear if these are effective at improving weight loss. Objective To test the hypothesis that, compared with a standard behavioral weight loss intervention (standard intervention), a technology-enhanced weight loss intervention (enhanced intervention) would result in greater weight loss. Design, Setting, Participants Randomized clinical trial conducted at the University of Pittsburgh and enrolling 471 adult participants between October 2010 and October 2012, with data collection completed by December 2014. Interventions Participants were placed on a low-calorie diet, prescribed increases in physical activity, and had group counseling sessions. At 6 months, the interventions added telephone counseling sessions, text message prompts, and access to study materials on a website. At 6 months, participants randomized to the standard intervention group initiated self-monitoring of diet and physical activity using a website, and those randomized to the enhanced intervention group were provided with a wearable device and accompanying web interface to monitor diet and physical activity. Main Outcomes and Measures The primary outcome of weight was measured over 24 months at 6-month intervals, and the primary hypothesis tested the change in weight between 2 groups at 24 months. Secondary outcomes included body composition, fitness, physical activity, and dietary intake. Results Among the 471 participants randomized (body mass index [BMI], 25 to <40; age range, 18-35 years; 28.9% nonwhite, 77.2% women), 470 (233 in the standard intervention group, 237 in the enhanced intervention group) initiated the interventions as randomized, and 74.5% completed the study. For the enhanced intervention group, mean base line weight was 96.3 kg (95% CI, 94.2-98.5) and 24-month weight 92.8 kg (95% CI, 90.6- 95.0) [corrected]. For the standard intervention group, mean baseline weight was 95.2kg (95%CI,93.0-97.3)and24-month weight was 89.3 kg (95%CI, 87.1-91.5) [corrected]. Weight change at 24 months differed significantly by intervention group (estimated mean weight loss, 3.5 kg [95% CI, 2.6-4.5} in the enhanced intervention group and 5.9 kg [95% CI, 5.0-6.8] in the standard intervention group; difference, 2.4 kg [95% CI, 1.0-3.7]; P = .002). Both groups had significant improvements in body composition, fitness, physical activity, and diet, with no significant difference between groups. Conclusions and Relevance Among young adults with a BMI between 25 and less than 40, the addition of a wearable technology device to a standard behavioral intervention resulted in less weight loss over 24 months. Devices that monitor and provide feedback on physical activity may not offer an advantage over standard behavioral weight loss approaches. Trial Registration clinicaltrials.gov Identifier: NCT01131871.

Objectively measured physical activity of USA adults by sex, age, and racial/ethnic groups: a cross-sectional study.

BackgroundAccelerometers were incorporated in the 2003–2004 National Health and Nutritional Examination Survey (NHANES) study cycle for objective assessment of physical activity. This is the first time that objective physical activity data are available on a nationally representative sample of U.S. residents. The use of accelerometers allows researchers to measure total physical activity, including light intensity and unstructured activities, which may be a better predictor of health outcomes than structured activity alone. The aim of this study was to examine objectively determined physical activity levels by sex, age and racial/ethnic groups in a national sample of U.S. adults.MethodsData were obtained from the 2003–2004 NHANES, a cross-sectional study of a complex, multistage probability sample of the U.S. population. Physical activity was assessed with the Actigraph AM-7164 accelerometer for seven days following an examination. 2,688 U.S. adults with valid accelerometer data (i.e. at least four days with at least 10 hours of wear-time) were included in the analysis. Mean daily total physical activity counts, as well as counts accumulated in minutes of light, and moderate-vigorous intensity physical activity are presented by sex across age and racial/ethnic groups. Generalized linear modeling using the log link function was performed to compare physical activity in sex and racial/ethnic groups adjusting for age.ResultsPhysical activity decreases with age for both men and women across all racial/ethnic groups with men being more active than women, with the exception of Hispanic women. Hispanic women are more active at middle age (40–59 years) compared to younger or older age and not significantly less active than men in middle or older age groups (i.e. age 40–59 or age 60 and older). Hispanic men accumulate more total and light intensity physical activity counts than their white and black counterparts for all age groups.ConclusionPhysical activity levels measured objectively by accelerometer demonstrated that Hispanic men are, in general, more active than their white and black counterparts. This appears to be in contrast to self-reported physical activity previously reported in the literature and identifies the need to use objective measures in situations where the contribution of light intensity and/or unstructured physical activity cannot be assumed homogenous across the populations of interest.

Pilot trial of etanercept in the treatment of inclusion-body myositis.

Inclusion-body myositis (IBM) is an inflammatory muscle disease that has proven resistant to treatment. Tumor necrosis factor molecules have been detected in muscle biopsies from patients with IBM. Etanercept is a TNFα receptor fusion protein that binds and inactivates tumor necrosis factor. Nine patients were treated with etanercept at a dose of 25 mg, two times a week for an average of 17 ± 6.1 months. Each patient was evaluated using quantitative strength testing. Their data were compared to two different control groups. The first control group consisted of patients who participated in trials of beta-interferon-1A and had received placebo. There was no significant difference. The second control group was a natural history cohort of IBM patients. There was no statistically significant difference between the treated group and the natural history group at 6 and 12 months when looking at elbow flexors, or 6 months when looking at hand grip. In the treated patients there was a small but significant improvement (p = 0.002) in handgrip at 12 months.

Pre- to postoperative changes in physical activity: report from the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2)

BACKGROUND Numerous studies have reported that bariatric surgery patients report more physical activity (PA) after surgery than before; however, the quality of the PA assessment has been questionable. METHODS The longitudinal assessment of bariatric surgery-2 is a 10-center longitudinal study of adults undergoing bariatric surgery. Of 2458 participants, 455 were given an activity monitor, which records the steps per minute, and an exercise diary before and 1 year after surgery. The mean number of steps/d, active min/d, and high-cadence min/wk were calculated for 310 participants who wore the monitor ≥10 hr/d for ≥3 days at both evaluations. Pre- and postoperative PA were compared for differences using the Wilcoxon signed-rank test. Generalized estimating equations were used to identify independent preoperative predictors of postoperative PA. RESULTS PA increased significantly (P < .0001) from before to after surgery for all PA measures. The median values before and after surgery were 7563 and 8788 steps/d, 309 and 340 active min/d, and 72 and 112 high-cadence min/wk, respectively. However, depending on the PA measure, 24-29% of participants were ≥5% less active postoperatively than preoperatively. Controlling for surgical procedure, gender, age, and body mass index, more PA preoperatively independently predicted for more PA postoperatively (P < .0001, for all PA measures). Less pain, not having asthma, and the self-report of increasing PA as a weight loss strategy preoperatively also independently predicted for more high-cadence min/wk postoperatively (P < .05). CONCLUSIONS The majority of adults increase their PA level after bariatric surgery. However, most remain insufficiently active, and some become less active. Increasing PA, addressing pain, and treating asthma before surgery might have a positive effect on postoperative PA.