Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Improving the assessment and management of obesity in UK children and adolescents: the PROMISE research programme including a RCT

BackgroundFive linked studies were undertaken to inform identified evidence gaps in the childhood obesity pathway.Objectives(1) To scope the impact of the National Child Measurement Programme (NCMP) (study A). (2) To develop a brief evidence-based electronic assessment and management tool (study B). (3) To develop evidence-based algorithms for identifying the risk of obesity comorbidities (study B). (4) To conduct an efficacy trial of the Healthy Eating and Lifestyle Programme (HELP) (study C). (5) To improve the prescribing of anti-obesity drugs in UK adolescents (study D). (6) To investigate the safety, outcomes and predictors of outcome of adolescent bariatric surgery in the UK (study E).MethodsFive substudies – (1) a parental survey before and after feedback from the National Childhood Measurement Programme, (2) risk algorithm development and piloting of a new primary care management tool, (3) a randomised controlled trial of the Healthy Eating and Lifestyle Programme, (4) quantitative and qualitative studies of anti-obesity drug treatment in adolescents and (5) a prospective clinical audit and cost-effectiveness evaluation of adolescent bariatric surgery in one centre.ResultsStudy A – before the National Childhood Measurement Programme feedback, three-quarters of parents of overweight and obese children did not recognise their child to be overweight. Eighty-seven per cent of parents found the National Childhood Measurement Programme feedback to be helpful. Feedback had positive effects on parental knowledge, perceptions and intentions. Study B – risk estimation models for cardiovascular and psychosocial comorbidities of obesity require further development. An online consultation tool for primary care practitioners is acceptable and feasible. Study C – the Healthy Eating and Lifestyle Programme, when delivered in the community by graduate mental health workers, showed no significant effect on body mass index at 6 months (primary outcome) when compared with enhanced usual care. Study D – anti-obesity drugs appear efficacious in meta-analysis, and their use has expanded rapidly in the last decade. However, the majority of prescriptions are rapidly discontinued after 1–3 months of treatment. Few young people described positive experiences of anti-obesity drugs. Prescribing was rarely compliant with the National Institute for Health and Care Excellence guidance. Study E – bariatric surgery appears safe, effective and highly cost-effective in adolescents in the NHS.Future work and limitationsWork is needed to evaluate behaviour and body mass index change in the National Childhood Measurement Programme more accurately and improve primary care professionals’ understanding of the National Childhood Measurement Programme feedback, update and further evaluate the Computer-Assisted Treatment of CHildren (CATCH) tool, investigate delivery of weight management interventions to young people from deprived backgrounds and those with significant psychological distress and obtain longer-term data on anti-obesity drug use and bariatric surgery outcomes in adolescence.Trial registrationCurrent Controlled Trials ISRCTN99840111.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 8, No. 3. See the NIHR Journals Library website for further project information.</jats:sec

Accommodation to Simulations of Defocus and Chromatic Aberration in the Presence of Chromatic Misalignment

AbstractPrevious studies have demonstrated that accommodation will respond to sine gratings in which the relative modulations of red, green and blue image components have been altered to simulate the effects of defocus and longitudinal chromatic aberration. The present study aimed to determine the tolerance of the accommodative system to relative phase shifts in those components induced by chromatic misalignment. It was found that accommodation can tolerate moderate amounts of chromatic misalignment (6′), but responds adversely when misalignments are large. Applications to visual display terminals and spectacle lens and instrument design are discussed

Interferometric Observations of the Quiet Sun at 20 and 25 MHz in May 2014

© 2018, Springer Nature B.V. We present the results of solar observations at 20 and 25 MHz with the Ukrainian T-shaped Radio telescope of the second modification (UTR-2) in the interferometric session from 27 May to 2 June 2014. In this case, the different baselines 225, 450, and 675 m between the sections of the east–west and north–south arms of UTR-2 were used. On 29 May 2014, strong sporadic radio emission consisting of Type III, Type II, and Type IV bursts was observed. On other days, there was no solar radio activity in the decameter range. We discuss the observation results of the quiet Sun. Fluxes and sizes of the Sun in east–west and north–south directions were measured. The average fluxes were 1050 – 1100 Jy and 1480 – 1570 Jy at 20 and 25 MHz, respectively. The angular sizes of the quiet Sun in equatorial and polar directions were 55 ′ and 49 ′ at 20 MHz and 50 ′ and 42 ′ at 25 MHz. The brightness temperatures of the radio emission were Tb=5.1×105K and Tb=5.7×105K at 20 and 25 MHz, respectively.status: publishe

Relationship Between Food Insecurity and Neighborhood Child Opportunity Index

OBJECTIVES: To evaluate the association between the Child Opportunity Index (COI) and food insecurity. STUDY DESIGN: This was a secondary analysis of a comprehensive screening instrument for social determinants of health and behavioral health risks. It was administered in two urban pediatric emergency departments to adolescents aged 13-21 years and caregivers of children 0-17 years. FI was assessed using the two-item Hunger Vital Sign. Residential addresses were geocoded and linked with COI data. Bivariable and multivariable logistic regression models were developed to measure the relationship between COI and FI. RESULTS: Of the 954 participants (384 adolescents, 570 caregivers) who underwent screening, 15.7% identified food insecurity (14.3% of adolescent and 16.7% of caregiver participants). The majority of participants were non-Hispanic Black (overall: 62.3%; food secure: 60.9%; food insecure: 72.0%), publicly insured (overall: 56.6%; food secure: 53.1%; food insecure: 73.3%) and lived in neighborhoods of low/very low opportunity (overall: 76.9%; food secure: 74.7%; food insecure: 88.3%). In adjusted analyses, participants living in neighborhoods of low/very low child opportunity had three times greater odds of being food insecure compared with children living in neighborhoods of high child opportunity (aOR: 3.0; 95% CI: 1.4, 6.3). CONCLUSION: We demonstrate that FI is associated with lower neighborhood opportunity. Our results could inform future screening initiatives and support the development of novel, place-based interventions to tackle the complex issue of food insecurity