Singh, Sneha

ObjectiveLittle is known about the predictors of response to obesity interventions.MethodsIn 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12‐month, pragmatic, real‐world trial performed in a weight management center, 312 patients were randomly assigned to phenotype‐guided treatment or non‐phenotype‐guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months.ResultsFour phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype‐guided approach was associated with 1.75‐fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non‐phenotype‐guided group (difference −6.9% [95% CI −9.4% to −4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype‐guided group compared with 34% with non‐phenotype‐guided treatment group.ConclusionsBiological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.

Obesity is a chronic, multifactorial disease associated with a large number of comorbidities. The clinical management of obesity involves a stepwise integrated approach, beginning with behavioral and lifestyle modification, followed by antiobesity medications, endobariatric procedures, and bariatric surgery. Weight gain and subsequent obesity are common side effects of medications, such as prednisone or antipsychotics. In this era of precision medicine, it is essential to identify patients at the highest risk of weight gain as a result of medication use. Pharmacogenomics could play an important role in obesity management by optimizing use of antiobesity medications as well as minimizing adverse weight gain. This review aims to provide a comprehensive analysis of the current literature on the role of pharmacogenomics in obesity and medication‐induced weight gain. In summary, there are more robust studies of medication associated with weight gain and pharmacogenomics, and more studies are needed to understand the role of pharmacogenomics in antiobesity medications.

INTRODUCTION: Over-the-scope clips (OTSC) are used for closure of fistulas, leaks, and acute perforations, and for GI bleeding. Adverse events include perforation, migration, and ulceration. Little is know about the natural history of OTSCs and no data addressing the longevity of clips is available. We present an interim analysis of our center’s experience with OTSC focusing on natural history. METHODS: OTSCs used from 1/1/2011 to 1/1/2019 were compiled and retrospective chart review undertaken. Primary endpoint was clip retention time (time when the clip was placed to time the clip was last seen or was physically removed). Secondary endpoints were rate of complications and factors that influence clip retention time and clinical success. Cox proportional hazards were used to evaluate variables impacting clip retention. Univariate regression was used to assess potential risk factors for adverse events. RESULTS: A total of 358 OTSC were placed in 299 patients (55.8% male, n = 184) with mean age 64 + 15.3 years. Procedures and indications presented in Table 1. Clip placement was clinically successful in 81% of cases (N = 265). Median time to clip loss as assessed by Kaplan-Meier curve was 267 days (95% CI 196-406) (Figure 1). Adverse events occurred in 34 clip placements (10.7%) and included bleeding (n = 8, 24.2%), perforation (n = 5, 15.2%), ulceration (n = 3, 9.1%), migration (n = 15, 45.5%), and infection (n = 1, 3.0%). Univariate analysis (Table 2) revealed that age, gender, type of clip used (there are 3 types of OTSC), and performing endoscopist did not impact clip retention rate. A size 14 clip had marginally higher rates of retention compared to others. Clips placed in the rectum or esophagus were lost earlier compared to those in the small/large intestine and stomach. Clips placed for fistulas and those associated with adverse event were associated with earlier clip loss. In evaluation of clinical success, clips placed for fistulas had a relative risk of clinical failure of 2.08 (95% CI 1.29-3.36) compared to all other indications. CONCLUSION: OTSCs are retained for a median of 8.9 months with clip location and indication for placement being key factors in time to clip loss. Clips used for fistula closure were more likely to be lost compared to those placed for other indications, less likely to be clinically successful, and more likely to cause a complication. These data help guide decision-making when considering OTSC use across clinical indications.