Achieving consensus on the language of obesity: a modified Delphi study.

Background: Obesity is recognized by the World Health Organization as a chronic disease. As such, it should be referred to using the language of chronic diseases, with correct and established terminology and definitions. This study was designed to map the current language used to discuss obesity and to compare this with the standard language used for chronic disease. Methods: We performed a modified Delphi study to identify the language of chronic disease that is being used in the context of obesity, and to identify discrepancies and potential use of inadequate language with respect to the standard language used for chronic diseases. Participants (n = 24) were identified from relevant stakeholder groups and desk research, and included patients, healthcare professionals, policymakers, researchers, industry, and payers (social insurers) of 18 nationalities/regions in Europe, North/South America, and South Africa. Participants were enrolled between 20.10.2020 and 30.10.2020. The study comprised two rounds of qualitative surveys. In Round 1, participants responded to six open-ended questions. Round 2 comprised 38 statements based on key terms/themes identified in Round 1 and covered the definition, causes, progression, treatment, management, and complications of obesity. Consensus was defined as ≥70% participant agreement on a statement. Findings: All participants completed Round 1 and 23 participants completed Round 2. In Round 2, consensus was reached for 28 of the 38 statements. Participants reached a consensus regarding the use of statements that acknowledge the heterogeneous nature of obesity, but not on the use of statements that: defined obesity based on body mass index; regarded psychological, physical, or physiological factors among the main causes of obesity; or implied that weight loss should be the aim of obesity treatment. Interpretation: This study uses expert consensus to provide insight into the language used to describe obesity as a chronic disease, and forms the basis for a unified language of obesity. Funding: Innovative Medicines Initiative, Novo Nordisk A/S.

Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.

BACKGROUND: Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. METHODS: We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m2 or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711. FINDINGS: Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102-103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m2. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was -2·3% for the placebo group versus -6·0% (0·05 mg), -8·6% (0·1 mg), -11·6% (0·2 mg), -11·2% (0·3 mg), and -13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (-13·8% to -11·2% vs -7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37-65% receiving 0·1 mg or more of semaglutide (p<0·0001 vs placebo). All semaglutide doses were generally well tolerated, with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, as seen previously with GLP-1 receptor agonists. INTERPRETATION: In combination with dietary and physical activity counselling, semaglutide was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses. FUNDING: Novo Nordisk A/S.

The use of ultrasound to identify veins for peripheral venous access in morbidly obese patients.

INTRODUCTION: Peripheral intravenous access (PIA) is a necessity in the treatment and monitoring of the majority of hospitalised patients. Patients with an increased body mass index (BMI) more often than normal-weight patients have a difficult PIA. Identifying veins with ultrasonography has proven helpful when facing a difficult intravenous (IV) access. We hypothesise that, with the help of ultrasonography (US), it is possible to identify at least one vein suitable for IV access in morbidly obese patients (BMI > 40 kg/m(2)). METHODS: We included 55 morbidly obese patients with a BMI > 40 kg/m(2). We performed a detailed US of seven anatomic areas routinely used for PIA. We present a description of parameters that are relevant when attempting PIA. RESULTS: In our study group, all patients had a minimum of one peripheral vein that was suitable for peripheral venous access, including seven patients (12.7%) who did not have clinically detectable veins. CONCLUSIONS: With the aid of US it is possible to identify a minimum of one peripheral vein suitable for IV access in morbidly obese patients. FUNDING: none. TRIAL REGISTRATION: not relevant.

Effect of valproic acid and injury on lesion size and endothelial glycocalyx shedding in a rodent model of isolated traumatic brain injury.

BACKGROUND: In isolated traumatic brain injury (TBI), little is known about the endothelial response and the effects of endothelial glycocalyx shedding. We have previously shown that treatment with valproic acid (VPA) improves outcomes following TBI and hemorrhagic shock.In this model, we hypothesized that severe isolated TBI would cause shedding of the endothelial glycocalyx, as measured by serum syndecan-1 (sSDC-1) levels. We further hypothesized that VPA treatment would reduce this response and reduce lesion size volume. METHODS: Forty Sprague-Dawley rats were allocated to TBI + VPA (n = 8), TBI + saline vehicle control infusion (n = 8), sham + saline vehicle control infusion (n = 6), or sham + VPA (n = 8). TBI animals were subjected to severe controlled cortical impact and killed 6 hours after injury. VPA 300 mg/kg was given as an intravenous bolus 30 minutes after injury. Serum samples were analyzed for sSDC-1, and lesion size was determined on Nissl-stained cryosections. RESULTS: sSDC-1 was significantly elevated in injured compared with uninjured animals at 3 hours (p = 0.0009) and 6 hours (p = 0.0007) after injury. This effect was significantly more pronounced in the animals treated with VPA (p = 0.019) 3 hours after injury, in which sSDC-1 levels were also significantly inversely correlated with lesion size (ρ = -0.55, p = 0.038).Lesion size was significantly smaller in TBI + VPA (40.45 mm ± 13.83 mm) as compared with vehicle control (59.57 mm ± 16.83 mm) (p = 0.023). CONCLUSION: Severe isolated TBI caused shedding of the endothelial glycocalyx. Treatment with VPA was associated with increased glycocalyx shedding and reduced lesion size volume in injured animal.