Evaluating appetite/satiety hormones and eating behaviours as predictors of weight loss maintenance with GLP-1RA therapy in adolescents with severe obesity.

INTRODUCTION: Whilst glucagon-like peptide-1 receptor agonists (GLP1-RAs) are effective for treating adolescent obesity, weight loss maintenance (WLM; preventing weight regain) remains a challenge. Our goal was to investigate appetite/satiety hormones and eating behaviours that may predict WLM with exenatide (a GLP1-RA) versus placebo in adolescents with severe obesity. METHODS: Adolescents who had ≥5% body mass index (BMI) reduction with meal replacement therapy were randomized to 52 weeks of once-weekly exenatide extended release or placebo. In this secondary analysis, eating behaviours and appetite/satiety regulation hormones post-meal replacement therapy (pre-randomization to exenatide or placebo) were evaluated as possible predictors of WLM. Percent change in BMI from randomization to 52 weeks served as the primary measure of WLM. RESULTS: The analysis included 66 adolescents (mean age 16.0 years; 47% female). Lower leptin response to meal testing was associated with greater WLM in terms of BMI percent change in those receiving exenatide compared to placebo (p = 0.007) after adjusting for sex, age and BMI. There were no other significant predictors of WLM. CONCLUSIONS: Prior to exenatide, lower leptin response to meals was associated with improved WLM with exenatide compared to placebo. The mostly null findings of this study suggest that GLP1-RA treatment may produce similar WLM for adolescents with obesity regardless of age, BMI, sex and eating behaviours.

Successful use of split-dose intravenous daratumumab in a multiple myeloma patient after a first-dose life-threatening infusion-related reaction.

INTRODUCTION: Daratumumab is a humanized IgG1 kappa monoclonal antibody directed against CD38 used to treat myeloma. The recommended dose of daratumumab is 16 mg/kg, with no lower or upper threshold. Here, we present the first split-dose daratumumab infusion experience in a myeloma patient with morbid obesity in whom daratumumab was interrupted because of grade 3 infusion-related reaction. CASE REPORT: A female myeloma patient with morbid obesity received a combination of chemotherapy with daratumumab because of disease relapse. The calculated dose for the first intravenous daratumumab infusion was 1840 mg/day based on the weight of the patient, which was measured as 115 kilograms. Daratumumab infusion was initiated as appropriate but needed to be stopped because of a severe sudden presentation of shortness of breath and hypoxemia. MANAGEMENT AND OUTCOME: After daratumumab was stopped, premedication was repeated, and oxygen, intravenous and inhaler steroids, inhaler ß2 agonists and intravenous diphenhydramine were given in repeated doses. She was monitored and followed up in the emergency critical care unit. Daratumumab treatment with a split-dose schedule was planned after she fully recovered from all signs and symptoms. The total dose was divided into two doses and was given without any complications on two consecutive days. After that, she was also able to tolerate once a week 1840 mg of daratumumab in a single day. DISCUSSION: There is a paucity of data regarding the best practice for instituting intravenous daratumumab in patients with morbid obesity regarding the infusion rate and duration, optimal dosing, and ideal way to cope with infusion-related reactions. Our case suggests a potential role for a split-dose schedule for patients with obesity and potential dose reductions and infusion-related reactions.

Effect of Swallow Balloon Therapy with the Combination of Semaglutide Oral Formulation: a Randomised Double-Blind Single-Centre Study.

BACKGROUND: Obesity is a significant public health issue; new therapies and pharmaceutical approaches to weight management are needed. OBJECTIVE: This study assesses weight reduction efficacy in the novel swallow balloon procedure and semaglutide, both promising non-surgical and pharmaceutical options, addressing obesity's critical public health challenge. METHODS: This was a computer-generated, blocked randomisation, double-blind, single-centre study. Fifty-seven participants were assigned to swallow balloon therapy group I (with semaglutide), and 58 were assigned to swallow balloon therapy group II (without semaglutide). All treatment doses were orally administered once daily (3 mg for the 1st month, 7 mg for the 2nd month, and 14 mg for the 3rd and 4th months after the placement of the swallow balloon). All the data were statistically analysed. RESULTS: The groups were highly well-matched. The %TWL in group I was 7.9%, 12.5%, 15.2%, and 17.6% and in group II was 6.1%, 10.5%, 12.8%, and 13.7% at 1, 2, 3, and 4 months, respectively. The most common adverse events (AEs) were nausea and vomiting, observed within the week. The resolution of T2DM, HTN, and OSA was 64.7% vs 55.5%, 64.3% vs 58.8%, and 72.0 vs 57.8% in groups I vs II, respectively. QoL significantly improved 4 months postoperatively in both groups. No major late complications occurred in either of the groups. CONCLUSION: The study supports the efficacy of swallow balloon therapy combined with semaglutide oral formulation in promoting weight loss and improving comorbid conditions. The findings highlight the potential of this combined approach in managing obesity and its associated health issues.

Antiretroviral Drug Exposure and Response in Obese and Morbidly Obese People With Human Immunodeficiency Virus (HIV): A Study Combining Modelling and Swiss HIV Cohort Data.

BACKGROUND: Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals. METHODS: Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, the model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and nonobese individuals. RESULTS: The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with nonobese (BMI: 18.5-25 kg/m2) individuals, consistent with observed clinical data. Etravirine and rilpivirine were the most impacted, especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load than nonobese PWH. CONCLUSIONS: The concentrations of ARVs are modestly reduced in obese individuals, with no negative impact on the virological response. Our data provide reassurance that standard doses of ARVs are suitable in obese PWH, including those who gained substantial weight with some of the first-line ARVs.

Direct oral anticoagulants and the risk of adverse clinical outcomes among patients with different body weight categories: a large hospital-based study.

OBJECTIVE: Through predictable pharmacokinetics-including a convenient fixed-dose regimen, direct oral anticoagulants (DOACs) are preferred over previous treatments in anticoagulation for various indications. However, the association between higher body weight and the risk of adverse consequences is not well studied among DOAC users. We aim to explore the association of body weight and adverse clinical outcomes in DOAC users. METHODS: A total of 97,413 anonymised DOAC users in a tertiary care setting were identified following structured queries on the electronic health records (EHRs) to extract the feature-rich anonymised dataset. The prepared dataset was analysed, and the features identified with machine learning (ML) informed the adjustments of covariates in the multivariate regression analysis to examine the association. Kaplan-Meier analysis was performed to evaluate the mortality benefits of DOACs. RESULTS: Among DOAC users, the odds of adverse clinical outcomes, such as clinically relevant non-major bleeding (CRNMB), ischaemic stroke, all-cause mortality, and prolonged hospital stay, were lower in patients with overweight, obesity, or morbid obesity than in patients with normal body weight. The odds of ischaemic stroke (OR 0.42, 95% CI: 0.36-0.88, p = 0.001) and all-cause mortality (OR 0.87, 95% CI: 0.81-0.95, p = 0.001) were lower in patients with morbid obesity than in patients with normal body weight. In the Kaplan-Meier analysis, apixaban was associated with a significantly lower rate of mortality overall and in obesity and overweight subgroups than other DOACs (p < 0.001). However, rivaroxaban performed better than apixaban in the morbid obesity subgroup (p < 0.001). CONCLUSION: This study shows the positive effects of DOAC therapy on clinical outcomes, particularly in patients with high body weight. However, this still needs validation by further studies particularly among patients with morbid obesity.

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery.

OBJECTIVE: This retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m2 ) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI. METHODS: The authors analyzed data from 129 patients with a BMI ≥ 40 kg/m2 , including 39 with (BS+) and 90 without (BS-) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference. RESULTS: Semaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS- groups. CONCLUSIONS: This study is the first, to the authors' knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m2 and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.

Trends in prescribing and outcomes in obese versus non-obese patients receiving rivaroxaban therapy: an observational study using real-world data.

PURPOSE: To investigate real-world prescribing trends and clinical outcomes based on body mass index (BMI) categorization in patients who received rivaroxaban therapy. METHODS: This was a retrospective cohort study involving all patients who received rivaroxaban therapy across all Hamad Medical Corporation (HMC) hospitals from 2015 to 2020. RESULTS: The number of patients initiated on rivaroxaban therapy significantly increased from 152 (3.3%) in 2015 to 1342 (28.9%) in 2020 (p <0.001). Within BMI categories, a similar increasing trend was observed in underweight, normal, and overweight patients, while from 2018 to 2020, there was a decreasing trend in rivaroxaban prescribing in all obese classes. The prevalence rate of all-cause mortality differed significantly between the BMI groups, with the highest mortality being among morbidly obese patients (BMI ≥ 40 kg/m2) (p< 0.001). On the other hand, no significant differences were found between the BMI groups in terms of bleeding, pulmonary embolism, deep vein thrombosis and stroke incidences. Multivariate logistic regression analyses showed that the likelihood of all-cause mortality was significantly higher in overweight and all categories of obese patients compared to underweight patients: overweight (OR: 5.3, 95% CI: 2.3-11.9, p< 0.001); obese class 1 (OR: 5.4, 95% CI: 2.3 - 12.2, p< 0.001); obese class 2 (OR: 6.5, 95% CI: 2.7 - 15.6, p< 0.001); and obese class 3 (OR: 3.7, 95% CI: 1.6 - 8.7, p = 0.003). CONCLUSIONS: Rivaroxaban prescribing has significantly increased over the years across general population, with a noticeable decline in obese population during the last few years (from 2018 onwards). Furthermore, an appreciable association was evident between all-cause mortality and BMI of these patients.

Postoperative Remission of Diabetes Mellitus After Gastrectomy in Patients With Diabetes Mellitus and Gastric Cancer.

BACKGROUND/AIM: We investigated the postoperative treatment status for diabetes mellitus and perioperative HbA1c levels in patients with diabetes mellitus and examined the effects of clinical factors on the remission of diabetes mellitus. PATIENTS AND METHODS: In this study, 126 patients with gastric cancer were considered to have diabetes mellitus preoperatively, of whom 79 were treated with oral antidiabetic drugs and/or insulin treatment. We compared diabetic treatment status and HbA1c values between the preoperative and postoperative periods in patients who underwent gastrectomy and examined the effects of clinical factors on improving diabetes mellitus. RESULTS: Of the 79 patients treated preoperatively for diabetes mellitus, 34 (43%) discontinued all medications for diabetes mellitus and for 37 (47%) the therapeutic dose was reduced or switched from insulin to oral antidiabetic drugs. Total gastrectomy was an independent factor for remission of antidiabetic treatments after gastrectomy. Concerning HbA1c levels, only the absence of preoperative insulin use was an independent factor for improvement. However, reconstruction was not a significantly correlated factor for the improvement of postoperative HbA1c levels and reduction of antidiabetic medications after distal gastrectomy. CONCLUSION: Almost all patients discontinued or had their dose of antidiabetic medications reduced after gastrectomy in clinical practice, and special attention should be paid in the management methods for diabetes mellitus in patients who underwent total gastrectomy for gastric cancer.

Cost-Effectiveness of Antiobesity Drugs for Adolescents With Severe Obesity.

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Bronchodilator reversibility testing in morbidly obese non-smokers: fluticasone/salmeterol efficacy versus salbutamol bronchodilator.

A positive response in reversibility testing is widely used to diagnose patients with airway limitations. However, despite its simple procedure, it doesn't accurately reflect the exact airway irreversibility. This study aimed to investigate the efficacy of a bronchodilation reversibility test using salbutamol and fluticasone/salmeterol combination in obese non-smoker subjects.The study included patients without a history of obstructive lung disease or bronchodilators. A sub-classification of patients based on body mass index (BMI) was carried out into normal (< 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI ≥ 30). Spirometry measurements were performed before and after salbutamol or fluticasone/salmeterol administration.The study included 415 (49.9% male) patients with a mean age of 40.92 ± 10.86 years. Obese subjects showed a high prevalence of restrictive patterns (23.4%), with non-significantly lower spirometric values compared to normal and overweight subjects (p > 0.05). The magnitude of bronchodilation, as identified by spirometry, following fluticasone/salmeterol was higher in all participants, with a significant increase in obese subjects with a p-value of 0.013, 0.002, and 0.035 for FEV1, FEV1% predicted, and FEV1/FVC, respectively.Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio than the conventional test using salbutamol inhaler, and it can be a potential candidate for assessment of airway obstruction using reversibility test, especially among the obese population.

Impact of body mass index and its change on survival outcomes in patients with early breast cancer: A pooled analysis of individual-level data from BCIRG-001 and BCIRG-005 trials.

INTRODUCTION: The relationships between body mass index (BMI) and survival rates are complex, and have not been thoroughly investigated in breast cancer patients who received adjuvant chemotherapy. METHODS: We collected data on 2394 patients from two randomized, phase III clinical trials that investigated adjuvant chemotherapy in breast cancer identified in Project Data Sphere. The objective was to examine the effect of baseline BMI, BMI after adjuvant chemotherapy, and BMI change from baseline to post-adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS). Restricted cubic splines were used to examine potential non-linear associations between continuous BMI value and survival. Stratified analyses involved chemotherapy regimens. RESULTS: Severe obesity (BMI≥40.0 kg/m2) at baseline was independently associated with worse DFS (hazard ration [HR] = 1.48, 95% confidence interval [CI] 1.02-2.16, P = 0.04) and OS (HR = 1.79, 95%CI 1.17-2.74, P = 0.007) compared with underweight/normal weight (BMI≤24.9 kg/m2). A BMI loss >10% was also an independent prognostic factor for adverse OS (HR = 2.14, 95%CI 1.17-3.93, P = 0.014). Stratified analyses revealed that severe obesity adversely affected DFS (HR = 2.38, 95%CI 1.26-4.34, P = 0.007) and OS (HR = 2.90, 95%CI 1.46-5.76, P = 0.002) in the docetaxel-based group, but not in the non-docetaxel-based group. Restricted cubic splines revealed a "J-shaped" association of baseline BMI with risk of recurrence or all-cause death, and this relationship was more pronounced in the docetaxel-based group. CONCLUSIONS: In early breast cancer patients treated with adjuvant chemotherapy, baseline severe obesity was significantly linked to worse DFS and OS, and a BMI loss over 10% from baseline to post-adjuvant chemotherapy also negatively affected OS. Moreover, the prognostic role of BMI might differ between docetaxel-based and non-docetaxel-based groups.

The effect of bariatric surgery on opioid consumption in patients with obesity: a registry-based cohort study.

BACKGROUND: Misuse of opioid medication has become a major health crisis in several countries. A significant number of patients with obesity use opioid medications, mostly to alleviate symptoms due to obesity-related co-morbidities. OBJECTIVE: To compare patterns of opioid drug usage before and after bariatric surgery in this population, hypothesizing that weight loss and improvement of obesity-related co-morbidities could reduce opioid consumption. SETTING: The Ontario Bariatric Registry (Ontario, Canada). METHODS: In this retrospective cohort study, the Ontario Bariatric Registry was used to compare opioid consumption in adult patients undergoing bariatric surgery between 2010 and 2021. The primary outcome was the number of patients using opioid medication at 1 year after surgery. Multiple logistic regression analyses were performed to identify potential predictors of opioid consumption. RESULTS: Data of 11,179 patients were analyzed. Mean age was 45.7 ± 10.2 years, mean baseline body mass index was 48.9 ± 8 kg/m2, and 83.6% of patients were female. Roux-en-Y gastric bypass was performed in the majority of patients (85.6%), followed by sleeve gastrectomy (14.2%). At baseline, opioids were used by 7.7% and nonopioid pain medications by 42.3% of patients. At 1 year after surgery, these numbers significantly decreased (Δ-1.9% and Δ-18.0%, respectively). The decrease in the consumption of nonopioid pain medication needs to be interpreted in the context of the contraindication to nonsteroidal anti-inflammatory drugs after Roux-en-Y gastric bypass, which was the most commonly performed procedure. Presence of musculoskeletal pain and use of nonopioid pain medication at baseline were identified as independent predictors of opioid consumption at 1 year after surgery. CONCLUSIONS: At 1 year after bariatric surgery, a significant decrease in opioid and nonopioid pain medication consumption was seen among patients with obesity. Aggressive management of excess weight, especially with bariatric surgery, can potentially reduce the impact of the opioid crisis in this population.

A Real-World Exploration into Clinical Outcomes of Direct Oral Anticoagulant Dosing Regimens in Morbidly Obese Patients Using Data-Driven Approaches.

INTRODUCTION: The clinical outcomes of direct oral anticoagulant (DOAC) dosage regimens in morbid obesity are uncertain due to limited clinical evidence. This study seeks to bridge this evidence gap by identifying the factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. METHOD: A data-driven observational study was carried out using supervised machine learning (ML) models with a dataset extracted from electronic health records and preprocessed. Following 70%:30% partitioning of the overall dataset via stratified sampling, the selected ML classifiers (e.g., random forest, decision trees, bootstrap aggregation) were applied to the training dataset (70%). The outcomes of the models were evaluated against the test dataset (30%). Multivariate regression analysis explored the association between DOAC regimens and clinical outcomes. RESULTS: A sample of 4,275 morbidly obese patients was extracted and analysed. The decision trees, random forest, and bootstrap aggregation classifiers achieved acceptable (excellent) values of precision, recall, and F1 scores in terms of their contribution to clinical outcomes. The length of stay, treatment days, and age were ranked highest for relevance to mortality and stroke. Among DOAC regimens, apixaban 2.5 mg twice daily ranked highest for its association with mortality, increasing the mortality risk by 43% (odds ratio [OR] 1.430, 95% confidence interval [CI] 1.181-1.732, p = 0.001). On the other hand, apixaban 5 mg twice daily reduced the odds of mortality by 25% (OR 0.751, 95% CI 0.632-0.905, p = 0.003) but increased the odds of stroke events. No clinically relevant non-major bleeding events occurred in this group. CONCLUSION: Data-driven approaches can identify key factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. This will help design further studies to explore well tolerated and effective DOAC doses for morbidly obese patients.

Effectiveness of semaglutide versus liraglutide for treating post-metabolic and bariatric surgery weight recurrence.

OBJECTIVE: The aim of this study was to compare the effectiveness of semaglutide versus liraglutide for treating post-metabolic and bariatric surgery (MBS) weight recurrence. METHODS: A retrospective analysis of 207 adults with post-MBS weight recurrence treated with semaglutide 1.0 mg weekly (n = 115) or liraglutide 3.0 mg daily (n = 92) at an academic center from January 1, 2015, through April 1, 2021, was conducted. The primary end point was percentage body weight change at 12 months of treatment with regimens containing semaglutide or liraglutide. RESULTS: The mean sample age was 55.2 years; mean BMI was 40.4 kg/m2 ; 89.9% were female; and 50% completed sleeve gastrectomy, 29% completed Roux-en-Y gastric bypass, and 21% completed adjustable gastric banding. Least-squares mean weight change at 12 months was -12.92% versus -8.77% in the semaglutide and liraglutide groups, respectively (p < 0.001). The adjusted odds ratios were 2.34 (95% CI: 1.28-4.29) for ≥10% weight loss and 2.55 (95% CI: 1.22-5.36) for ≥15% weight loss over 12 months in the semaglutide group versus liraglutide group, respectively. Weight-loss efficacy of semaglutide (vs. liraglutide) did not differ by subgroups explored, including age, sex, and MBS procedure. CONCLUSIONS: These results show that treatment regimens including semaglutide 1.0 mg weekly lead to superior weight loss compared with liraglutide 3.0 mg daily for treating post-MBS weight recurrence, regardless of procedure type or the magnitude of weight recurrence.

Pharmacokinetics and Dosing Regimens of Direct Oral Anticoagulants in Morbidly Obese Patients: An Updated Literature Review.

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m2) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients.To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations.A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers.A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m2), and standard dosing of edoxaban may be effective and safe for AF patients.Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.

Safety and efficacy of apixaban, dabigatran and rivaroxaban in obese and morbidly obese patients with heart failure and atrial fibrillation: A real-world analysis.

BACKGROUND: Atrial fibrillation and heart failure are combined risk factors for thromboembolic events. Obese and morbidly obese individuals have been underrepresented in clinical trials studying safety and efficacy of direct oral anticoagulants (DOACs). OBJECTIVES: Study the comparative safety and efficacy of DOACs in obese and morbidly obese patients with atrial fibrillation or flutter, and concomitant congestive heart failure. METHODS: In the present single-center retrospective observational study, patients with an ICD-9 code of atrial fibrillation or atrial flutter, and congestive heart failure on a DOAC (apixaban[n = 155], rivaroxaban[n = 335], dabigatran[n = 393]) were followed for a median 12.5 months (IQR: 22.1 months). Obesity was defined as a body mass index, BMI ≥ 30 and < 40 kg/m2 [n = 614], and morbid obesity as BMI ≥ 40 kg/m2 [n = 269]. Clinical endpoints were grouped into safety (composite of intracranial-hemorrhage, gastrointestinal-bleeds, hemorrhagic-stroke, and other bleeds), and efficacy (composite of ischemic-stroke and systemic-embolism) endpoints. Cox proportional hazard models were used to compare safety, efficacy, and all-cause mortality outcomes. RESULTS: In obese patients, no statistical difference was observed in efficacy of DOACs. A statistical difference was observed in the safety of DOACs in obese patients. Apixaban was found to be safer than dabigatran [hazard ratio [HR] 0.37 (0.16-0.87), p = .02] and rivaroxaban [HR 0.29 (0.12-0.67), p = .004]. In morbidly obese patients, there was no overall statistical difference in the efficacy or safety of DOACs. CONCLUSION: In obese patients with congestive heart failure and atrial fibrillation or atrial flutter on DOACs, apixaban has the most favorable safety profile compared to rivaroxaban and dabigatran.

Proton pump inhibitor prophylaxis after Roux-en-Y gastric bypass: A national survey of surgeon practices.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently used after Roux-en-Y gastric bypass (RYGB) to prevent marginal ulceration. The optimal duration of PPI treatment after surgery to minimize ulcer development is unclear. OBJECTIVES: Assess bariatric surgeon practice variability regarding postoperative PPI prophylaxis. SETTING: Survey of medical directors of Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited centers. METHODS: Members of the American Society for Metabolic and Bariatric Surgery research committee developed and administered a web-based anonymous survey in November 2021 to bariatric surgeons of Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited programs detailing questions related to surgeons' use of PPI after RYGB including patient selection, medication, dosage, and treatment duration. RESULTS: The survey was completed by 112 surgeons (response rate: 52.6%). PPIs were prescribed by 85.4% of surgeons for all patients during their hospitalization, 3.9% for selective patients, and 10.7% not at all. After discharge, 90.3% prescribed PPIs. Pantoprazole was most often used during hospitalization (38.5%), while omeprazole was most prescribed (61.7%) after discharge. The duration of postoperative PPI administration varied; it was 3 months in 43.6%, 1 month in 20.2%, and 6 months in 18.6% of patients. Finally, surgeons' practice setting and case volume were not associated with the duration of prophylactic PPI administration after RYGB. CONCLUSIONS: PPI administration practices vary widely among surgeons after RYGB, which may be related to the limited comparative evidence and guidelines on best duration of PPI administration. Large prospective clinical trials with objective outcome measures are needed to define optimal practices for PPI prophylaxis after RYGB to maximize clinical benefit.

Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and bariatric surgery have proven to be effective treatments for obesity and cardiometabolic conditions. We aimed to explore the early metabolomic changes in response to GLP-1RA (liraglutide) therapy vs. placebo and in comparison to bariatric surgery. METHODS: Three clinical studies were conducted: a bariatric surgery cohort study of participants with morbid obesity who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) studied over four and twelve weeks, and two randomized placebo-controlled, crossover double blind studies of liraglutide vs. placebo administration in participants with type 2 diabetes (T2D) and participants with obesity studied for three and five weeks, respectively. Nuclear magnetic resonance spectroscopy-derived metabolomic data were assessed in all eligible participants who completed all the scheduled in-clinic visits. The primary outcome of the study was to explore the changes of the metabolome among participants with obesity with and without T2D receiving the GLP-1RA liraglutide vs. placebo and participants with obesity undergoing bariatric surgery during the three to five-week study period. In addition, we assessed the bariatric surgery effects longitudinally over the twelve weeks of the study and the differences between the bariatric surgery subgroups on the metabolome. The trials are registered with ClinicalTrials.gov, numbers NCT03851874, NCT01562678 and NCT02944500. RESULTS: Bariatric surgery had a more pronounced effect on weight and body mass index reduction (-14.19 ± 5.27 kg and - 5.19 ± 5.27, respectively, p < 0.001 for both) and resulted in more pronounced metabolomic and lipidomic changes compared to liraglutide therapy at four weeks postoperatively. Significant changes were observed in lipoprotein parameters, inflammatory markers, ketone bodies, citrate, and branched-chain amino acids after the first three to five weeks of intervention. After adjusting for the amount of weight loss, a significant difference among the study groups remained only for acetoacetate, ß-hydroxybutyrate, and citrate (p < 0.05 after FDR correction). Glucose levels were significantly reduced in all intervention groups but mainly in the T2D group receiving GLP-1RA treatment. After adjusting for weight loss, only glucose levels remained significant (p = 0.001 after FDR correction), mainly due to the glucose change in the T2D group receiving GLP-1RA. Similar results with those observed at four weeks were observed in the surgical group when delta changes at twelve weeks were assessed. Comparing the two types of bariatric surgery, an intervention effect was more pronounced in the RYGB subgroup regarding total triglycerides, triglyceride-rich lipoprotein size, and trimethylamine-N-oxide (p for intervention: 0.031, 0.028, 0.036, respectively). However, after applying FDR correction, these changes deemed to be only suggestive; only time effects remained significant with no significant changes persisting in relation to the types of bariatric surgery. CONCLUSIONS: The results of this study suggest that the early metabolomic, lipid and lipoprotein changes observed between liraglutide treatment and bariatric surgery are similar and result largely from the changes in patients' body weight. Specific changes observed in the short-term post-surgical period between bariatric vs. nonsurgical treated participants, i.e., acetoacetate, ß-hydroxybutyrate, and citrate changes, may reflect changes in patient diets and calorie intake indicating potential calorie and diet-driven metabolomics/lipidomic effects in the short-term postoperatively. Significant differences observed between SG and RYGB need to be confirmed and extended by future studies.

Topiramate for Weight Management in Children With Severe Obesity.

Background: Topiramate has been shown to result in significant weight loss compared to placebo in adults with obesity. However, there are no consensus guidelines on the acceptability, safety, and efficacy of topiramate for weight loss in children. We present a literature review and case series on topiramate use in young children with severe obesity. Methods: We performed a PubMed search from January 2000 to February 2022 utilizing keywords, "topiramate" and "obesity" and "children" and "adolescent." For our case series, children were identified through retrospective chart review from a multidisciplinary weight management program. Eligibility criteria: age ≤12 years, class II or III obesity, completed 16 weeks of topiramate therapy as adjunct to lifestyle modifications. Semistructured interviews were conducted with one parent to review side effects. Results: Literature search yielded nine articles. All studies reported trends toward BMI reduction and weight loss with topiramate monotherapy. Five children met case series eligibility (mean age 10 years 3 months ±1.5 years, 60% female). After 16 weeks of topiramate, all children had a decrease in BMI as a percentage of the 95th percentile (mean -12% [-5% to -18%]). Parents reported improvement in impulsive eating and decreased desire to overeat compared to baseline. Four out of five reported no side effects, one reported drowsiness which resolved by dosing at nighttime. Conclusions: Results suggest that topiramate is well tolerated and may be utilized for weight management in younger children. A randomized controlled trial investigating the impact of topiramate for weight management in this age group is warranted.