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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Defining human-centricity in Industry 5.0 and assessing the readiness of Ergonomics/Human Factors communities in UK

There is a lack of a clear and consistent definition of human-centricity in Industry 5.0. This study identified the definition of human-centricity in Industry 5.0 through a systematic literature review and used it to assess the readiness of Ergonomics/Human Factors communities in the UK. The assessment of the communities readiness was conducted by reviewing UK accredited courses and events of three professional bodies; and interviewing practitioners (n=8). Eleven themes were identified as elements of human-centricity from the thematic analysis of 30 publications. Gaps that had to be addressed to better equip UK practitioners to support the realisation of human-centricity in Industry 5.0 were also identified

Assessing Livestock Production Practices on Small-Scale Multi-Species Farms Located on Floreana Island, Galápagos Islands

Globally to date, established international standards for animal welfare, a priority of sustainable agriculture, have primarily focused on large-scale producers. However, across Latin America, including in Ecuador’s Galápagos Islands, smallholder farms play a critical role in food safety and security. We assessed five basic animal welfare measures (feed and water access, shelter availability and housing systems, animal health management, animal behavior, and timely euthanasia) for poultry, pigs, and cattle on Floreana Island, Galápagos. Utilizing assessment standards from multiple US sources and international standards, we developed a questionnaire and used it to conduct in-depth interviews during 4–5 July 2022 with eight participating producers, representing 75% of animal agriculture on Floreana. While we identified opportunities to enhance competencies in animal health management and timely euthanasia, farms performed well in the other assessed measures. Future work should promote knowledge transfer and in-country capacity building in farm biosecurity, access to veterinary care, antimicrobial resistance surveillance, and euthanasia methods. Efforts to positively impact smallholder farm livelihoods in Galápagos—one of the most biodiverse and protected ecosystems on the planet—will sustainably support human health through the interconnected realms of animal health and welfare, wildlife and environmental health, and food safety and security

Effects of resistance training, detraining, and retraining on strength and functional capacity in elderly

Background: The interruption of training (detraining) results in loss of the gains acquired. Partial retention could occur after detraining, and variation in training stimuli may optimize retraining adaptations. Aim: To evaluate the effect of a resistance-retraining program on strength and functional capacity performance after a detraining period. Methods: Ten elderly men and women (63–68 years) completed 12 weeks of training, 16 weeks of detraining, and 8 weeks of retraining. One-repetition maximum (1-RM) at 45° leg press, maximum isometric knee extension torque, rate of torque development (RTD), 30-s sit-to-stand, timed up and go, and stair ascent and descent tests were assessed. Results: The 1-RM increased after training (p 0.05). For RTD and 30-s sit-to-stand, there was an increase after retraining when compared to pre-training values (p < 0.05). For timed up and go and stair ascent and descent, reductions were observed between pre-training and post-training periods (p < 0.05), only timed up and go increased after the detraining period (p < 0.01). Discussion: After 16 weeks of detraining, the maximum strength did not return to baseline levels, and a retraining with explosive strength exercise sessions can recover maximum strength gains, RTD, and functional capacity at the same level obtained after a detraining period. Conclusions: The inclusion of an explosive strength session in retraining period improves RTD and 30-s sit-to-stand performance and can accelerate the recovery of strength after a detraining period.</p

Clinical characteristics of 153 brazilian patients with neuromyelitis optica spectrum disorder (NMOSD)

The 2015 criteria for diagnosing neuromyelitis optica spectrum disorder (NMOSD) have encouraged several groups across the world to report on their patients using these criteria. The disease typically manifests with severe relapses of optic neuritis, longitudinally extensive myelitis and/or brainstem syndromes, often leading to severe disability. Some patients are seropositive for antibodies against aquaporin-4 (AQP4), others are positive for anti-myelin oligodendrocyte glycoprotein (MOG), while a few are negative for both biomarkers. The disease is complex, and only now are specific therapeutic clinical trials being carried out The present study adds to the literature through detailed clinical data from 153 medical records of Brazilian patients. Methods: Retrospective assessment of medical records from nine specialized units in Brazil. NMOSD was more prevalent in females (4.1:1), who had significantly fewer relapses than males (p = 0.007) but presented similar levels of disability over time. African ancestry was associated with higher levels of disability throughout the disease course (p < 0.001), although the number of relapses was similar to that observed in white patients. Concomitant autoimmune diseases were relatively rare in this population (6.5%). Positivity for anti-AQP4 antibodies was identified in 62% of the patients tested, while 3% presented anti-MOG antibodies. Anti-AQP4 antibodies were not associated to worse disease course. The last medical record showed that six patients had died and 13 were wheelchair-bound. Seventy percent of the patients did not respond to first-line therapy (azathioprine and/or corticosteroids), and five patients continued to relapse even after four different courses of treatment. The present study adds to the reports from other countries presenting original data on Brazilian patients diagnosed with NMOSD according to the 2015 criteria2739239