PARIS: Protocol for a prospective single arm, theory-based, group-based feasibility intervention study to increase Physical Activity and reduce sedentary behaviouR after barIatric Surgery

Introduction Increased physical activity and reduced sedentary behaviour can encourage favourable outcomes after bariatric surgery. However, there is a lack of evidence as to how to support patients with behaviour change. The aim of this study is to assess the feasibility of a physiotherapist led, online group-based behaviour change intervention to increase physical activity and reduce sedentary behaviour following bariatric surgery. Methods and analysis Single arm feasibility study of a theory and evidence-based group behaviour change intervention based on the Behaviour Change Wheel and Theoretical Domains Framework using behaviour change techniques from the Behaviour Change Technique Taxonomy v1. The intervention has eight objectives and specifies behaviour change techniques that will be used to address each of these. Groups of up to eight participants who have had surgery within the previous 5 years will meet weekly over 6 weeks for up to 1½ hours. Groups will be held online led by a physiotherapist and supported by an intervention handbook. Feasibility study outcomes include: rate of recruitment, retention, intervention fidelity, participant engagement and acceptability. Secondary outcomes include: physical activity, sedentary behaviour, body composition, self-reported health status and will be analysed descriptively. Change in these outcomes will be used to calculate the sample size for a future evaluation study. Qualitative interviews will explore participants' views of the intervention including its acceptability. Data will be analysed according to the constant comparative approach of grounded theory. Ethics and dissemination This study has National Health Service Research Ethics Committee approval; Haydock 20/NW/0472. All participants will provide informed consent and can withdraw at any point. Findings will be disseminated through peer-reviewed journals, conference and clinical service presentations. Trial registration number ISRCTN31524689

Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes

De manera general, la apendicitis aguda es la causa de abdomen agudo más frecuente en la edad pediátrica, representa el 10% de todas las admisiones a los diferentes servicios de urgencias; sin embargo, en los niños menores de dos años su presentación es infrecuente, alrededor del 2% de todos los casos de abdomen agudo. Se presenta un caso clínico que corresponde a una paciente de 13 días de vida que fue llevada al servicio de emergencia por presentar vómitos de tipo bilioso. Fue intervenida quirúrgicamente con diagnóstico preoperatorio de atresia intestinal, posterior a la cirugía el diagnóstico definitivo correspondió a apendicitis y peritonitis por perforación apendicular. Se explora y se encuentra como hallazgo quirúrgico: obstrucción íleon terminal con una banda adherida al ciego, apéndice cecal perforada, peritonitis localizada. La apendicitis neonatal puede presentarse en otras patologías como la enfermedad de Hirschsprung, la enterocolitis necrosante, el íleo o el tapón meconial, entre otras. La apendicitis se presenta como un cuadro clínico inespecífico, su diagnóstico se lo realiza como un hallazgo transoperatorio lo que eleva la mortalidad.

Long-Term Weight Loss Effects of Semaglutide in Obesity Without Diabetes in the Select Trial

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P \u3c 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes A Prespecified Secondary Analysis of a Randomized Clinical Trial

ImportanceSodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown.ObjectiveTo assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).Design, setting, and participantsThis secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (InterventionsDapagliflozin vs placebo.Main outcomes and measuresThe dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF.ResultsAt baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher.Conclusions and relevanceThe effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria.Trial registrationClinicalTrials.gov Identifier: NCT01730534

The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58

OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk. RESEARCH DESIGN AND METHODS DECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance >60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (15 to = 30 to 300 mg/g) by treatment arm. The composite cardiorenal outcome was a >= 40% sustained decline in the estimated glomerular filtration rate (eGFR) to 15 to 300 mg/g. Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories (all P = 1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 1.45 [95% CI 1.35-1.56], P = 30 mg/g (P < 0.0125, P-interaction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P < 0.05, P-interaction = 0.480). CONCLUSIONS In DECLARE-TIMI 58, dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m 2, or at least 27 kg/m 2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P -2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597

Comparative Genomics of the Anopheline Glutathione S-Transferase Epsilon Cluster

Enzymes of the glutathione S-transferase (GST) family play critical roles in detoxification of xenobiotics across many taxa. While GSTs are ubiquitous both in animals and plants, the GST epsilon class (GSTE) is insect-specific and has been associated with resistance to chemical insecticides. While both Aedes aegypti and Anopheles gambiae GSTE clusters consist of eight members, only four putative orthologs are identifiable between the species, suggesting independent expansions of the class in each lineage. We used a primer walking approach, sequencing almost the entire cluster from three Anopheles species (An. stephensi, An. funestus (both Cellia subgenus) and An. plumbeus (Anopheles subgenus)) and compared the sequences to putative orthologs in An. gambiae (Cellia) in an attempt to trace the evolution of the cluster within the subfamily Anophelinae. Furthermore, we measured transcript levels from the identified GSTE loci by real time reverse transcription PCR to determine if all genes were similarly transcribed at different life stages. Among the species investigated, gene order and orientation were similar with three exceptions: (i) GSTE1 was absent in An. plumbeus; (ii) GSTE2 is duplicated in An. plumbeus and (iii) an additional transcriptionally active pseudogene (ψAsGSTE2) was found in An. stephensi. Further statistical analysis and protein modelling gave evidence for positive selection on codons of the catalytic site in GSTE5 albeit its origin seems to predate the introduction of chemical insecticides. Gene expression profiles revealed differences in expression pattern among genes at different life stages. With the exception of GSTE1, ψAsGSTE2 and GSTE2b, all Anopheles species studied share orthologs and hence we assume that GSTE expansion generally predates radiation into subgenera, though the presence of GSTE1 may also suggest a recent duplication event in the Old World Cellia subgenus, instead of a secondary loss. The modifications of the catalytic site within GSTE5 may represent adaptations to new habitats

Public health campaigns and obesity - a critique

<p>Abstract</p> <p>Background</p> <p>Controlling obesity has become one of the highest priorities for public health practitioners in developed countries. In the absence of safe, effective and widely accessible high-risk approaches (e.g. drugs and surgery) attention has focussed on community-based approaches and social marketing campaigns as the most appropriate form of intervention. However there is limited evidence in support of substantial effectiveness of such interventions.</p> <p>Discussion</p> <p>To date there is little evidence that community-based interventions and social marketing campaigns specifically targeting obesity provide substantial or lasting benefit. Concerns have been raised about potential negative effects created by a focus of these interventions on body shape and size, and of the associated media targeting of obesity.</p> <p>Summary</p> <p>A more appropriate strategy would be to enact high-level policy and legislative changes to alter the obesogenic environments in which we live by providing incentives for healthy eating and increased levels of physical activity. Research is also needed to improve treatments available for individuals already obese.</p