A method for comparing multiple imputation techniques: A case study on the U.S. national COVID cohort collaborative.

Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients' predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases, whose removal may introduce severe bias. Several multiple imputation algorithms have been proposed to attempt to recover the missing information under an assumed missingness mechanism. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithm works best in a given scenario. Furthermore, the selection of each algorithm's parameters and data-related modeling choices are also both crucial and challenging. In this paper we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. Extensive experiments show that our approach can effectively highlight the most promising and performant missing-data handling strategy for our case study. Moreover, our methodology allowed a better understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.

Binge size and loss of control as correlates of eating behavior and psychopathology among individuals with binge eating disorder and higher weight.

Studies comparing individuals with loss of control (LOC) eating who do and do not have objectively large binge episodes have found that degree of LOC is more important than binge size to psychological and behavioral outcomes. However, the relative importance of these characteristics has not been investigated in a population with binge eating disorder (BED), who by definition all have objectively large binge episodes. Persons with BED and higher weight (N = 34) were enrolled in a BED treatment trial and completed the Loss of Control Over Eating Scale, the Eating Disorder Examination, and measures of eating behavior, mood, and quality of life. Body mass index (BMI) was calculated from measured height and weight. The size of the largest binge episode (measured in kilocalories) and degree of LOC were entered into multiple regression equations to determine their relationships with disordered eating symptoms, depression, quality of life, and BMI in this pilot study. Greater LOC had a stronger independent association than binge size with higher total eating psychopathology, shape dissatisfaction, hunger, food cravings and food addiction symptoms. Larger binge size had a stronger independent association than LOC with higher weight concern and lower general and social quality of life. Both characteristics were associated with higher eating concern and neither were associated with depression or BMI. Both binge size and degree of LOC are associated with important psychosocial treatment targets in patients with BED. Future research should validate the largest binge episode measurement method and replicate the present findings in a larger sample.

Semaglutide for the treatment of obesity.

Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning. The approval of this medication provides patients with greater options for weight management.

The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities.

PURPOSE OF REVIEW: This review examines lifestyle modification for obesity management with the goal of identifying treatment components that could support the use of a new generation of anti-obesity medications (AOMs). RECENT FINDINGS: Semaglutide reliably reduces baseline body weight by approximately 15% at 68 weeks, in contrast to 5-10% for lifestyle modification. Tirzepatide induces mean losses as great as 20.9%. Both medications reduce energy intake by markedly enhancing satiation and decreasing hunger, and they appear to lessen the need for traditional cognitive and behavioral strategies (e.g., monitoring food intake) to achieve calorie restriction. Little, however, is known about whether patients who lose weight with these AOMs adopt healthy diet and activity patterns needed to optimize body composition, cardiometabolic health, and quality of life. When used with the new AOMs, the focus of lifestyle modification is likely to change from inducing weight loss (through calorie restriction) to facilitating patients' adoption of dietary and activity patterns that will promote optimal changes in body composition and overall health.

Are fewer cases of diabetes mellitus diagnosed in the months after SARS-CoV-2 infection? A population-level view in the EHR-based RECOVER program.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.

A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder.

Objective: To assess the efficacy of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist, for binge eating disorder (BED). Methods: Adults with a body mass index (BMI) ≥ 27 kg/m2 enrolled in a pilot, 17-week double-blind, randomized controlled trial of liraglutide 3.0 mg/day for BED. The primary outcome was number of objective binge episodes (OBEs)/week. Binge remission, weight change, and psychosocial variables were secondary outcomes. Mixed effect models were used for continuous variables, and generalized estimating equations were used for remission rates. Results: Participants (n = 27) were 44.2 ± 10.6 years; BMI = 37.9 ± 11.8 kg/m2; 63% women; and 59% White and 41% Black. At baseline, the liraglutide group (n = 13) reported 4.7 ± 0.7 OBEs/week, compared with 3.0 ± 0.7 OBEs/week for the placebo group, p = 0.07. At week 17, OBEs/week decreased by 4.0 ± 0.6 in liraglutide participants and by 2.5 ± 0.5 in placebo participants (p = 0.37, mean difference = 1.2, 95% confidence interval 1.3, 2.0). BED remission rates of 44% and 36%, respectively, did not differ. Percent weight loss was significantly greater in the liraglutide versus the placebo group (5.2 ± 1.0% vs. 0.9 ± 0.7%, p = 0.005). Conclusion: Participants in both groups reported reductions in OBEs, with the liraglutide group showing clinically meaningful weight loss. A pharmacy medication dispensing error was a significant limitation of this study. Further research on liraglutide and other GLP-1 agonists for BED is warranted.

Binge eating disorder and eating self-efficacy in adults seeking bariatric surgery.

This study assessed the relationships between binge eating disorder (BED) and eating self-efficacy in a sample of patients prior to bariatric surgery. The study also examined the extent that BED status accounted for variance in self-efficacy after controlling for demographic factors (age, sex and race), physical variables (comorbidities and body mass index [BMI]) and depressive symptoms. This was a cross-sectional study of pre-surgical data from patients seeking bariatric surgery at a university-based healthcare system (N = 98; mean ± SD age of 46.2 ± 12.5 years; BMI of 45.4 ± 7.2 kg/m2 ; 86.7% female; and 60.2% of patients self-identified as White). Patients completed the Weight and Lifestyle Inventory (WALI), Beck Depression Inventory-II (BDI-II) and Weight Efficacy Lifestyle Questionnaire. Of the total sample, 15.3% met criteria for BED, 33.7% had subthreshold BED and 51.0% were free of this disorder. In adjusted analyses, total self-efficacy was significantly lower in patients with subthreshold BED (B ± SE = -15.88 ± 7.23, p = .03) and individuals with BED (B ± SE = -35.07 ± 10.23, p = .001) than in those without BED. Patients with BED, compared to those without, had significantly worse scores (in adjusted analyses) on the self-efficacy subscales of negative emotions (p = .003), availability of food (p < .001), social pressure (p = .004) and positive activities (p = .03). In patients seeking bariatric surgery, total self-efficacy scores were significantly lower in patients with BED and subthreshold BED than those without BED. The results suggest that eating self-efficacy may be an important factor to target in patients with BED who seek bariatric surgery.

Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database.

OBJECTIVE: The purpose of the study is to evaluate the relationship between HbA1c and severity of coronavirus disease 2019 (COVID-19) outcomes in patients with type 2 diabetes (T2D) with acute COVID-19 infection. RESEARCH DESIGN AND METHODS: We conducted a retrospective study using observational data from the National COVID Cohort Collaborative (N3C), a longitudinal, multicenter U.S. cohort of patients with COVID-19 infection. Patients were ≥18 years old with T2D and confirmed COVID-19 infection by laboratory testing or diagnosis code. The primary outcome was 30-day mortality following the date of COVID-19 diagnosis. Secondary outcomes included need for invasive ventilation or extracorporeal membrane oxygenation (ECMO), hospitalization within 7 days before or 30 days after COVID-19 diagnosis, and length of stay (LOS) for patients who were hospitalized. RESULTS: The study included 39,616 patients (50.9% female, 55.4% White, 26.4% Black or African American, and 16.1% Hispanic or Latino, with mean ± SD age 62.1 ± 13.9 years and mean ± SD HbA1c 7.6% ± 2.0). There was an increasing risk of hospitalization with incrementally higher HbA1c levels, but risk of death plateaued at HbA1c >8%, and risk of invasive ventilation or ECMO plateaued >9%. There was no significant difference in LOS across HbA1c levels. CONCLUSIONS: In a large, multicenter cohort of patients in the U.S. with T2D and COVID-19 infection, risk of hospitalization increased with incrementally higher HbA1c levels. Risk of death and invasive ventilation also increased but plateaued at different levels of glycemic control.

Are fewer cases of diabetes mellitus diagnosed in the months after SARS-CoV-2 infection?

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include an increased incidence of diabetes. Our objective was to describe the temporal relationship between new diagnoses of diabetes mellitus and SARS-CoV-2 infection in a nationally representative database. There appears to be a sharp increase in diabetes diagnoses in the 30 days surrounding SARS-CoV-2 infection, followed by a decrease in new diagnoses in the post-acute period, up to 360 days after infection. These results underscore the need for further investigation, as understanding the timing of new diabetes onset after COVID-19 has implications regarding potential etiology and screening and treatment strategies.

Effect of SARS-CoV-2 Infection and Infection Severity on Longer-Term Glycemic Control and Weight in People With Type 2 Diabetes.

OBJECTIVE: To evaluate the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severity of infection with longer-term glycemic control and weight in people with type 2 diabetes (T2D) in the U.S. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using longitudinal electronic health record data of patients with SARS-CoV-2 infection from the National COVID Cohort Collaborative (N3C). Patients were ≥18 years old with an ICD-10 diagnosis of T2D and at least one HbA1c and weight measurement prior to and after an index date of their first coronavirus disease 2019 (COVID-19) diagnosis or negative SARS-CoV-2 test. We used propensity scores to identify a matched cohort balanced on demographic characteristics, comorbidities, and medications used to treat diabetes. The primary outcome was the postindex average HbA1c and postindex average weight over a 1 year time period beginning 90 days after the index date among patients who did and did not have SARS-CoV-2 infection. Secondary outcomes were postindex average HbA1c and weight in patients who required hospitalization or mechanical ventilation. RESULTS: There was no significant difference in the postindex average HbA1c or weight in patients who had SARS-CoV-2 infection compared with control subjects. Mechanical ventilation was associated with a decrease in average HbA1c after COVID-19. CONCLUSIONS: In a multicenter cohort of patients in the U.S. with preexisting T2D, there was no significant change in longer-term average HbA1c or weight among patients who had COVID-19. Mechanical ventilation was associated with a decrease in HbA1c after COVID-19.

Lifestyle modification approaches for the treatment of obesity in adults.

The U.S. Preventive Services Task Force has recommended that primary care clinicians screen all adults for obesity and provide those affected intensive multicomponent behavioral interventions. Approximately 95 million U.S. adults qualify for such care, also referred to as lifestyle modification. Using the Guidelines (2013) for Managing Overweight and Obesity in Adults (hereafter, Obesity Guidelines) as a framework, this article reviews the principal components of comprehensive lifestyle modification, which include diet, physical activity, and behavior therapy. To lose weight, the Obesity Guidelines recommend participation for 6 months in high-intensity programs that provide 14 or more counseling sessions with a trained interventionist. When provided face-to-face individual or group treatment, participants lose up to 8 kg (8% of weight) in 6 months and experience improvements in cardiovascular disease risk factors and quality of life. To prevent weight regain, the Obesity Guidelines recommend participation for 1 year in weight-loss-maintenance programs that provide at least monthly counseling. High levels of physical activity, frequent monitoring of body weight, and consumption of a reduced-calorie diet are associated with long-term weight loss. Investigators currently are seeking to increase the availability of lifestyle modification by delivering it in community-based programs, as well as on digital platforms (e.g., Internet and Smartphone). Digitally delivered programs lower costs and expand treatment reach; their efficacy is likely to improve further with the addition of new technologies for monitoring food intake, activity, and weight. Ultimately, to improve long-term weight management, individual lifestyle counseling must be joined with collective and institutional efforts to improve the nation's eating and activity environments. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Six-Month Follow-up from a Randomized Controlled Trial of the Weight BIAS Program.

OBJECTIVE: The aim of this study was to investigate the 6-month nonintervention follow-up effects of a cognitive behavioral intervention for weight bias internalization (WBI; i.e., self-stigma) combined with behavioral weight loss (BWL). METHODS: Adults with obesity and elevated WBI were previously randomized to receive BWL alone or in combination with the Weight Bias Internalization and Stigma program (BWL + BIAS). Participants attended weekly group meetings for 12 weeks, followed by two biweekly and two monthly meetings (26 weeks total). Follow-up assessments were conducted at week 52. Changes on the Weight Bias Internalization Scale and Weight Self-Stigma Questionnaire at week 52 were the principal outcomes. Other outcomes included changes in eating, coping, and weight. RESULTS: Of 72 randomized participants, 54 (75%) completed week 52 assessments. Linear mixed models showed improvements across groups, but no significant differences between groups, in week 52 change on the Weight Bias Internalization Scale (P = 0.25) or Weight Self-Stigma Questionnaire (P = 0.27). BWL + BIAS participants reported significantly greater benefits than BWL participants on measures of eating and affective coping with weight stigma. Percent weight loss at week 52 did not differ significantly between groups (BWL + BIAS = -3.1% [SE 1.0%], BWL = -4.0% [SE 1.0%], P = 0.53). CONCLUSIONS: Reductions in WBI did not differ between groups at 6-month follow-up. Further research is needed to determine the potential benefits of a stigma-reduction intervention beyond BWL.

Mindful Eating, General Mindful Awareness, and Acceptance as Predictors of Weight Loss.

OBJECTIVES: The goal of the present study was to determine whether baseline mindful eating, general mindful awareness, or acceptance was most strongly associated with short- and long-term weight loss in a lifestyle modification program. METHODS: Data were from 178 participants (baseline BMI=40.9±5.9 kg/m2, age=44.2±11.2 years; 87.6% female; 71.3% black) who enrolled in a two-phase trial. All participants attended an initial 14-week lifestyle modification program that included a meal replacement diet. Participants who had lost ≥5% of initial weight (N=137) were then randomized to 52 weeks of lifestyle modification with lorcaserin or placebo. Linear mixed models examined whether mindful eating (Mindful Eating Questionnaire) and general mindful awareness and acceptance (Philadelphia Mindfulness Scale) predicted short-term weight loss at week 14 in the full sample and long-term weight loss at the end of the trial in the subsample of randomized participants. RESULTS: In the full sample, higher baseline acceptance predicted greater short-term weight losses (p=.004). At week 14, individuals low in acceptance (-1SD) lost an average of 8.7 kg (SE=0.6) compared to 11.2 kg (SE=0.6) among those high in acceptance (+1SD). In the subsample of participants who successfully lost weight in phase 1, the independent effect of acceptance on total losses at the end of the trial did not reach statistical significance (p=.058). Neither mindful eating nor general mindful awareness independently predicted weight loss at either time point. CONCLUSIONS: Acceptance was a stronger predictor than either general or eating-specific awareness of weight loss with lifestyle modification.

Effects of Dietary Self-Monitoring, Physical Activity, Liraglutide 3.0 mg, and Placebo on Weight Loss in the SCALE IBT Trial.

INTRODUCTION: Individuals who enroll in intensive behavioral therapy (IBT) programs are asked to make several lifestyle changes simultaneously. However, few studies have examined the relative effects of adherence to different treatment components on weight loss. OBJECTIVE: This secondary analysis of the SCALE IBT trial assessed adherence to the medication regimen, dietary self-monitoring, and physical activity recommendations and their relative contributions to weight change in individuals with obesity who were provided with IBT combined with either liraglutide 3.0 mg or placebo. METHODS: SCALE IBT was a double-blinded, multicenter, randomized controlled trial comparing 56-week weight losses in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140), as an adjunct to IBT. Adherence to dietary self-monitoring, physical activity, and medication usage (liraglutide or placebo) were measured during the 56-week treatment period. A regression model was used to estimate the relative contribution of adherence to each treatment component to weight loss at week 56. RESULTS: The proportion of individuals who adhered to each intervention component decreased over time. Compared with non-adherence, complete adherence to dietary self-monitoring and physical activity recommendations were associated with estimated weight changes of -7.2% (95% CI -10.4 to -4.0; p < 0.0001) and -2.0% (95% CI -3.2 to -0.8; p = 0.0009), respectively. Complete adherence to liraglutide predicted an additional weight loss of -6.5% (95% CI -10.2 to -2.9; p = 0.0005) relative to individuals who did not adhere to the medication regimen, while adherence to placebo did not have a statistically significant effect on weight loss (p = 0.33). CONCLUSIONS: High adherence to dietary self-monitoring and use of liraglutide 3.0 mg was associated with clinically relevant weight loss with IBT and adjunctive pharmacotherapy. The effect of adherence to physical activity was significant but smaller.

Measures of adherence as predictors of early and total weight loss with intensive behavioral therapy for obesity combined with liraglutide 3.0 mg.

Individual weight loss outcomes with intensive behavioral therapy (IBT) for obesity are variable. The present study assessed whether visit attendance, dietary self-monitoring, medication, and meal-replacement adherence were associated with 52-week weight loss with IBT and tested whether these relationships were independent of associations with early weight loss. This was a secondary analysis of a randomized trial in which 150 participants (76.1% female, 55.8% white, BMI = 38.8 ±â€¯4.8 kg/m2) received either IBT alone, IBT with liraglutide 3.0 mg/d, or IBT-liraglutide combined with a 12-week meal replacement diet (Multi-component). In the full sample, visit attendance accounted for 14.8% of the variance in 52-week weight loss and dietary self-monitoring added 14.9%. Only self-monitoring was independently associated with weight loss. In the 100 liraglutide-treated participants, medication adherence accounted for an additional 9.9% of the variance in 52-week weight loss, and both self-monitoring and medication adherence were independent correlates. For the 50 Multi-component participants, meal replacement adherence did not predict weight loss. Early weight loss was associated with higher early and subsequent session attendance and dietary self-monitoring. However, self-monitoring and medication adherence remained important correlates of total weight loss when controlling for this variable. Strategies that help improve self-monitoring consistency and medication usage could improve weight loss with IBT.

Effects of a cognitive-behavioral intervention targeting weight stigma: A randomized controlled trial.

OBJECTIVE: To test the effects of a cognitive-behavioral intervention for weight bias internalization (WBI; i.e., self-stigma) combined with behavioral weight loss (BWL). METHOD: Adults with obesity and elevated WBI were randomly assigned to BWL alone or combined with the Weight Bias Internalization and Stigma Program (BWL + BIAS). Participants attended weekly group meetings for 12 weeks, followed by 2 biweekly and 2 monthly meetings (26 weeks total). Changes at Week 12 on the Weight Bias Internalization Scale (WBIS) and Weight Self-Stigma Questionnaire (WSSQ) were the principal outcomes, with changes at Week 26 assessed as secondary outcomes. Other outcomes included changes in mood, body image, eating behaviors, self-monitoring, and weight. RESULTS: Seventy-two participants were randomized (84.7% female, 66.7% Black, mean age = 47.1 ± 11.5 years) Linear mixed models showed no significant differences between the BWL + BIAS and BWL groups in WBIS changes at Week 12 (-1.3 ± 0.2 vs. -1.0 ± 0.2) or week 26 (-1.5 ± 0.2 vs. -1.3 ± 0.2). BWL + BIAS participants had greater reductions in WSSQ total scores at Week 12 (p = .03), with greater changes on the self-devaluation subscale at Weeks 12 and 26 (p ≤ .03). BWL + BIAS participants reported significantly greater benefits on measures of eating and self-monitoring. Percent weight loss at Week 26 did not differ significantly between groups (BWL + BIAS = -4.5 ± 1.0%, BWL = -5.9 ± 1.0%, p = .28). CONCLUSION: A psychological intervention for WBI produced short-term reductions in some aspects of weight self-stigma in persons with obesity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effects of Liraglutide and Behavioral Weight Loss on Food Cravings, Eating Behaviors, and Eating Disorder Psychopathology.

OBJECTIVE: This exploratory analysis examined the effects of intensive behavioral therapy (IBT) for obesity ("IBT-alone"), IBT plus liraglutide 3.0 mg/d ("IBT-liraglutide"), and IBT plus liraglutide 3.0 mg/d plus 12 weeks of a portion-controlled diet that provided 1,000 to 1,200 kcal/d ("Multicomponent") on changes in food cravings, eating behaviors, and eating disorder psychopathology at 24 and 52 weeks post randomization. METHODS: Adults with obesity (mean age = 47.6 ± 11.8 years and BMI = 38.4 ± 4.9 kg/m2 ; 79.3% female; 54.0% non-Hispanic white; 44.7% black) were randomized to IBT-alone (n = 50), IBT-liraglutide (n = 50), or Multicomponent (n = 50). RESULTS: At weeks 24 and 52, liraglutide-treated groups reported significantly larger declines in weight concern relative to the IBT-alone group. At week 24, compared with IBT-alone, liraglutide-treated groups reported significantly greater reductions in dietary disinhibition, global eating disorder psychopathology, and shape concern. The Multicomponent group had significantly greater reductions in binge eating at week 24 relative to the IBT-alone group. However, differences among groups were no longer significant at week 52. Groups did not differ in total food cravings at week 24 or 52. CONCLUSIONS: The combination of liraglutide and IBT was associated with greater short-term improvements in dietary disinhibition, global eating disorder psychopathology, and shape concern than IBT alone.

Changes in health-related quality of life with intensive behavioural therapy combined with liraglutide 3.0 mg per day.

This study examined the effects of intensive behavioural therapy (IBT) for obesity (IBT-alone), IBT plus liraglutide 3.0 mg/day (IBT-liraglutide), and IBT-liraglutide combined with 12 weeks of a portion-controlled diet (Multicomponent) on changes in general health-related (HR) quality of life (QoL) and weight-related QoL. Adults with obesity (79.3% female; 54.0% white; 44.7% black; mean age = 47.6 ± 11.8 years and body mass index = 38.4 ± 4.9 kg/m2 ) were randomized to IBT-alone (n = 50), IBT-liraglutide (n = 50) or Multicomponent (n = 50). General HRQoL was measured with the Short Form-36 (SF-36), and weight-related QoL was assessed with the Impact of Weight on Quality of Life-Lite scale. At week 52, participants in the three groups lost 6.1 ± 1.3%, 11.5 ± 1.3% and 11.8 ± 1.3% of initial body weight, respectively. Both liraglutide-treated groups were significantly more likely than IBT-alone to achieve clinically meaningful improvements in total weight-related QoL. They also both achieved greater improvements than IBT-alone in weight-related public distress and in general mental health, as measured by the SF-36 mental component summary score. Independent of treatment group, greater categorical weight loss was associated with greater improvements in several domains of both general and weight-related QoL. The addition of liraglutide to IBT appeared to improve aspects of both general HRQoL and weight-related QoL.