A model-based approach to predict individual weight loss with semaglutide in people with overweight or obesity.

AIMS: To determine the relationship between exposure and weight-loss trajectories for the glucagon-like peptide-1 analogue semaglutide for weight management. MATERIALS AND METHODS: Data from one 52-week, phase 2, dose-ranging trial (once-daily subcutaneous semaglutide 0.05-0.4 mg) and two 68-week phase 3 trials (once-weekly subcutaneous semaglutide 2.4 mg) for weight management in people with overweight or obesity with or without type 2 diabetes were used to develop a population pharmacokinetic (PK) model describing semaglutide exposure. An exposure-response model describing weight change was then developed using baseline demographics, glycated haemoglobin and PK data during treatment. The ability of the exposure-response model to predict 1-year weight loss based on weight data collected at baseline and after up to 28 weeks of treatment, was assessed using three independent phase 3 trials. RESULTS: Based on population PK, exposure levels over time consistently explained the weight-loss trajectories across trials and dosing regimens. The exposure-response model had high precision and limited bias for predicting body weight loss at 1 year in independent datasets, with increased precision when data from later time points were included in the prediction. CONCLUSION: An exposure-response model has been established that quantitatively describes the relationship between systemic semaglutide exposure and weight loss and predicts weight-loss trajectories for people with overweight or obesity who are receiving semaglutide doses up to 2.4 mg once weekly.

Urinary Lithiasis Risk Assessment after Bariatric Surgery.

Malabsorption is a consequence of gastric bypass (GB). GB increases the risk of kidney stone formation. This study aimed to evaluate the accuracy of a screening questionnaire for assessing the risk of lithiasis in this population. We performed a monocentric retrospective study to evaluate a screening questionnaire administered to patients who underwent gastric bypass surgery between 2014 and 2015. Patients were asked to answer a questionnaire that included 22 questions divided into four parts: medical history, episodes of renal colic before and after bypass surgery, and eating habits. A total of 143 patients were included in the study, and the mean age of the patients was 49.1 ± 10.8 years. The time between gastric bypass surgery and the completion of the questionnaire was 50.75 ± 4.95 months. The prevalence of kidney stones in the study population was 19.6%. We found that with a score of ≥6, the sensitivity and specificity were 92.9% and 76.5%, respectively. Positive and negative predictive values were 49.1% and 97.8%, respectively. The ROC curve showed an Area Under the Curve (AUC) of 0.932 ± 0.029 (p < 0.001). We developed a reliable and short questionnaire to identify patients at a high risk of kidney stones after gastric bypass. When the results of the questionnaire were equal to or greater than six, the patient was at a high risk of kidney stone formation. With a good predictive negative value, it could be used in daily practice to screen patients who have undergone gastric bypass and are at a high risk of renal lithiasis.

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

Association between higher ambient temperature and orthopaedic infection rates: a systematic review and meta-analysis.

INTRODUCTION: Many infectious diseases display seasonal variation corresponding with particular conditions. In orthopaedics a growing body of evidence has identified surges in post-operative infection rates during higher temperature periods. The aim of this research was to collate and synthesize the current literature on this topic. METHODS: A systematic review and meta-analysis was performed using five databases (PubMed, Embase, CINAHL, Web of Science and Central (Cochrane)). Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. Odds ratios (ORs) were calculated from monthly infection rates and a pooled OR was generated using the DerSimonian and Lairds method. A protocol for this review was registered with the National Institute for Health Research International Prospective Register of Systematic Reviews (CRD42017081871). RESULTS: Eighteen studies analysing over 19 000 cases of orthopaedic related infection met inclusion criteria. Data on 6620 cases and 9035 controls from 12 studies were included for meta-analysis. The pooled OR indicated an overall increased odds of post-operative infection for patients undergoing orthopaedic procedures during warmer periods of the year (pooled OR 1.16, 95% confidence interval 1.04-1.30). CONCLUSION: A small but significantly increased odds of post-operative infection may exist for orthopaedic patients who undergo procedures during higher temperature periods. It is hypothesized that this effect is geographically dependent and confounded by meteorological factors, local cultural variables and hospital staffing cycles.

A randomised, placebo-controlled trial of transcranial pulsed electromagnetic fields in patients with multiple chemical sensitivity.

OBJECTIVE: To evaluate the efficacy of transcranially applied pulsed electromagnetic fields (PEMF) on functional impairments and symptom severity in multiple chemical sensitivity (MCS) patients. METHODS: The study was conducted as a nationwide trial in Denmark using a randomised, parallel-group, double-blind and placebo-controlled design. Sample size was estimated at 40 participants. Eligibility criteria were age 18-75 years and fulfilment of the MCS case criteria. Participants received either PEMF or placebo PEMF (no stimulation) applied transcranially for 6 weeks. The primary outcome was the Life Impact Scale (LIS) of the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Secondary outcomes were the Symptom Severity Scale (SSS) and the Chemical Intolerance Scale of QEESI. RESULTS: A total of 39 participants were randomised to PEMF or placebo treatment. No significant difference was observed on QEESI LIS between groups with a mean change score of -5.9 in the PEMF group compared with -1.5 in the placebo group (p=0.35, effect size=-0.31). However, a significant decrease was detected on QEESI SSS within and between groups with a mean change score of -11.3 in the PEMF group compared with -3.2 in the placebo group (p=0.03, effect size=-0.60). CONCLUSION: PEMF treatment of 6 weeks showed no effect on functional impairments in MCS. However, a significant decrease in symptom severity was observed.

Motivating underserved Vietnamese Americans to obtain colorectal cancer screening: evaluation of a culturally tailored DVD intervention.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death among Vietnamese Americans, yet screening remains underutilized. We investigated the effectiveness of a culturally tailored DVD intervention in promoting CRC screening among unscreened Vietnamese Americans age 50 and over. MATERIALS AND METHODS: Using a community-based participatory research approach, we conducted a trial comparing twenty-eight subjects who received a mailed DVD in Vietnamese, with twenty-eight subjects who received a mailed brochure in Vietnamese. Subjects completed telephone surveys at baseline, One-month, and one-year. The primary outcome was receipt of screening. Secondary measures were participants' knowledge, attitudes, and beliefs about CRC screening. Two focus groups explored the intervention's acceptability and effectiveness. RESULTS: At one year, CRC screening rates of 57.1% and 42.9% were observed in experimental and control group respectively (p=0.42), Subjects in both groups showed increased knowledge about CRC after one month. Focus group findings revealed that the DVD was an effective method of communicating information and would help promote screening. CONCLUSIONS: The findings suggest that culturally tailored, linguistically appropriate content is more important than the type of media used. This relatively low intensity, low cost intervention utilizing a DVD can be another useful method for outreach to the often hard-to-reach unscreened population.

Two of three patients with multiple chemical sensitivity had less symptoms and secondary hyperalgesia after transcranially applied pulsed electromagnetic fields.

Background Multiple chemical sensitivity (MCS) is a chronic, disabling condition characterized by recurrent multisystem symptoms triggered by common airborne chemicals. Evidence points towards abnormal sensory processing in the central nervous system (CNS) as a likely pathophysiological mechanism. No effective treatment has yet been reported, but clinical observations suggest that as pulsed electromagnetic fields (PEMF) is a treatment for some CNS disorders (depression and chronic pain), it may also be a treatment modality for MCS. Methods In an open case study, the effects of PEMF were assessed in three MCS patients. All cases received 30 min daily treatment 5 days a week for 8 consecutive weeks. Symptoms and functional impairments related to MCS, depressive symptoms, and capsaicin-induced secondary punctate hyperalgesia were assessed at baseline and weekly until an 18-week follow-up. Results Two of the three cases showed considerable improvement on all measures of symptoms and functional impairments related to MCS in response to PEMF therapy. One case showed no improvement and during the treatment period was unexpectedly diagnosed with depression. Conclusion Our findings indicate potential benefits of PEMF therapy in MCS. Implication The therapeutic effect of PEMF in MCS needs to be investigated by a randomized placebo-controlled trial.

Transcranial pulsed electromagnetic fields for multiple chemical sensitivity: study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology. MCS is characterized by recurrent nonspecific symptoms from multiple organ systems in response to chemical exposures in concentrations that are normally tolerated by the majority of the population. The symptoms may have severe impact on patients' lives, but an evidence-based treatment for the condition is nonexisting. The pathophysiology is unclarified, but several indicators point towards abnormal processing of sensory signals in the central nervous system. Pulsed electromagnetic fields (PEMF) offer a promising new treatment for refractory depression and can be targeted at the brain, thereby activating biochemical cell processes. METHODS/DESIGN: In a parallel, randomized, double-blind, placebo-controlled trial conducted at the Danish Research Centre for Chemical Sensitivities, the effects of PEMF in MCS patients will be assessed using the Re5 Independent System. Based on sample size estimation, 40 participants will be randomized to either PEMF therapy or placebo. The allocation sequence will be generated by computer. All involved parties (that is, participants, investigators, the research nurse, and the statistician) will be blinded to group allocation. The participants will receive PEMF therapy or placebo applied transcranially 30 minutes twice a day for 7 days a week over 6 consecutive weeks. Outcomes will be measured at baseline, once weekly during treatment, post treatment, and at 2.5-month and 4.5-month follow-up according to a predefined timetable. The primary outcome will be a measurement of the impact of MCS on everyday life. The secondary outcomes will be measurements of MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia, immunological markers in serum, and quality of life. DISCUSSION: This trial will assess the effects of PEMF therapy for MCS. Currently, there is no treatment with a documented effect on MCS, and in terms of healthcare there is very little to offer these patients. There is thus a great need for well-conducted randomized trials aimed at assessing possible treatment effects. A positive outcome will pave the way for improved healthcare and understanding of this very disabling and overlooked condition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01834781.