Gastric Bypass vs Diet and Cardiovascular Risk Factors: A Nonrandomized Controlled Trial.

Importance: Roux-en-Y gastric bypass (RYGB) is associated with reduced cardiovascular (CV) risk factors, morbidity, and mortality. Whether these effects are specifically induced by the surgical procedure or the weight loss is unclear. Objective: To compare 6-week changes in CV risk factors in patients with obesity undergoing matching caloric restriction and weight loss by RYGB or a very low-energy diet (VLED). Design, Setting, and Participants: This nonrandomized controlled study (Impact of Body Weight, Low Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers [COCKTAIL]) was conducted at a tertiary care obesity center in Norway. Participants were individuals with severe obesity preparing for RYGB or a VLED. Recruitment began February 26, 2015; the first patient visit was on March 18, 2015, and the last patient visit (9-week follow-up) was on August 9, 2017. Data were analyzed from April 30, 2021, through June 29, 2023. Interventions: VLED alone for 6 weeks or VLED for 6 weeks after RYGB; both interventions were preceded by 3-week LED. Main Outcomes and Measures: Between-group comparisons of 6-week changes in CV risk factors. Results: Among 78 patients included in the analyses, the mean (SD) age was 47.5 (9.7) years; 51 (65%) were women, and 27 (35%) were men. Except for a slightly higher mean (SD) body mass index of 44.5 (6.2) in the RYGB group (n = 41) vs 41.9 (5.4) in the VLED group (n = 37), baseline demographic and clinical characteristics were similar between groups. Major atherogenic blood lipids (low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein[a]) were reduced after RYGB in comparison with VLED despite a similar fat mass loss. Mean between-group differences were -17.7 mg/dL (95% CI, -27.9 to -7.5), -17.4 mg/dL (95% CI, -29.8 to -5.0) mg/dL, -9.94 mg/dL (95% CI, -15.75 to -4.14), and geometric mean ratio was 0.55 U/L (95% CI, 0.42 to 0.72), respectively. Changes in glycemic control and blood pressure were similar between groups. Conclusions and Relevance: This study found that clinically meaningful reductions in major atherogenic blood lipids were demonstrated after RYGB, indicating that RYGB may reduce CV risk independent of weight loss. Trial Registration: ClinicalTrials.gov Identifier: NCT02386917.

Analysis of Use and Outcomes of the Balance Digital Disease Management Tool for Patients with Type 2 Diabetes.

Management of type 2 diabetes mellitus (T2DM) is a serious medical need for millions of patients and clinicians worldwide. Numerous smartphone apps for T2DM management are available. Due to their global accessibility, computing power and cellular connectivity, the pervasiveness of mobile phones now provide an opportunity for non-invasive Digital Therapeutics that have the potential to manage disease by modifying patient behavior as new modality for disease management and intervention. However, this novel approach has yet to be tested in large clinical studies. The BALANCE clinical study was designed to evaluate mobile phone App usage in a large multi-center clinical trial and its impact on T2DM outcomes. It included a digital aid for the management of, blood glucose, diet, physical activity, and medication adherence. Overall, patient use of the BALANCE-App was low (21% of significant patients users), and it diminished over time. BALANCE showed no effect on HbA1c or weight, what is consistent with other smartphone apps for T2DM which were tested on large clinical trials. Nevertheless, post-hoc subgroup analysis showed women using the App significantly achieved a significant reduction in HbA1c and weight.Clinical relevance Suitability of Digital Therapeutics, at least in the form of smartphone apps, for T2DM is under question. The low use indicates need for a strong focus in patient acceptability and patient engagement in the design process.

Home-based Digital Assessments with Applied Sentiment & Emotion AI Capture Improved Quality-of-life in Asthma Patients.

With the rise of digital transformation in the pharmaceutical industry, digital therapeutics are being integrated in drug development clinical trials. In the TWINKLE study, information about asthmatic patients' disease control and quality-of-life (QoL) was measured by daily video recording, in conjunction with daily electronic questionnaires and home-based spirometry. From the video messages, sentiment and emotion AI was applied to detect subtle QoL changes in asthmatic patients after receiving treatments. Sentiment scores, derived from patients' daily messages via natural language processing, correlated strongly with metrics of lung functions and outcomes of electronic questionnaires. However, video-derived emotional analysis exhibited strong interpersonal variations and systematic biases, yet still showed utility in detecting QoL changes after personalized calibration and signal aggregation. Compared to traditional patient-reported outcomes, all three categories of digital measurements were able to detect significantly improved asthma control from patients who responded to treatments. The result provides insights into developing novel digital outcomes through the application of connected digital devices and advanced AI tailored to clinical settings.Clinical relevance- Digital outcomes involving connected digital devices and AI for sentiment/emotion analysis could capture subtle QoL changes reliably and earlier than hospital visits, reducing burden and improving disease management. Integrating digital therapeutics in asthma drug development trials may prove to be feasible and valuable.

Assessment of Objectively Measured Physical Activity as an Independent Estimator of Functional Status in Clinical Trials.

Functional status of patients is an important concept in clinical trials. It subsumes functional capacity, which is traditionally estimated by exercise tests, and functional performance, which is often estimated by questionnaires. Objectively measured physical activity by means of wearables devices containing accelerometers (PA) have recently been proposed as a novel and advantageous way to estimate physical status including capacity and performance. There is nonetheless insufficient evidence of the association between PA and traditional ways to estimate functional status. In the ACTIVATE clinical trial, cycle ergometry tests were performed multiple times in all 267 patients, PA was measured for a week prior to each cycle ergometry test, and questionnaires were answered daily during the same week. Pearson's correlation tests and clustering analysis revealed that PA, physical activity experience as assessed by questionnaires, and exercise endurance time as measured by the cycle ergometry test, are largely independent. Therefore, all three approaches together might achieve a complete assessment of the functional status of patients in clinical trials, as they each independently correlate with health-related quality of life and important clinical outcomes such as hospitalizations but are weakly associated among themselves.