Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The bone response in endurance long distance horse

The aim of this study was to understand the bone against the exercise adaptations to reduce the occurrence of orthopedic injuries in endurance horses. To this end, the objective of the present work was to investigate how the bone adaptation on adult equines that was trained for 4 to 5 years to endurance races respond to long-term exercise of moderate intensity by comparing to non-athlete horses. For this purpose, 14 Arabian horses were selected and divided equally in two groups, a control group (CG) formed by animals that had never practised physical activity nor been tamed and an exercise group (EG) formed by athlete animals. Radiographs were obtained using a digital radiography system and penetrometer. The radiographs were stored and later processed to determine cortical bone thickness using the ProgRes® Capture Pro 2.5 (Jenoptik, Germany), cortical bone density using Adobe Photoshop CS6 (version 6.0, Adobe Systems Inc., San Jose, CA, USA), and trabecular bone density using the Image-Pro Plus 4.1 (Media Cybernetics Inc. Silver Springs, MD). The EG presented an increase in cortical bone density and thickness compared to the control. This adaptation of the cortical bone in the exercised horses is an important factor increasing bone resistance to exercise. These structural changes are related to a morphofunctional response by the bone tissue as a whole

The bone response in endurance long distance horse

The aim of this study was to understand the bone response against the exercise adaptations to reduce the occurrence of orthopedic injuries in endurance horses. To this end, the objective of the present work was to investigate how the bone adaptation on adult equines that were trained for 4-5 yr to endurance races responds to the long-term exercise of moderate intensity by comparing to non-athlete horses. For this purpose, 14 Arabian horses were selected and divided equally into two groups; a control group formed by animals that had never practiced physical activity nor been tamed and an exercise group formed by athlete animals. Radiographs were obtained using a digital radiography system and penetrometer. The radiographs were stored and later processed to determine cortical bone thickness using the ProgRes® Capture Pro 2.5 (Jenoptik, Germany), cortical bone density using Adobe Photoshop CS6 (version 6.0, Adobe Systems Inc., San Jose, CA), and trabecular bone density using the Image-Pro Plus 4.1 (Media Cybernetics Inc. Silver Springs, MD). The EG presented an increase in cortical bone density and thickness compared to the control. This adaptation of the cortical bone in the exercised horses is an important factor in increasing bone resistance to exercise. These structural changes are related to a morphofunctional response by the bone tissue as a whole

Impact of social isolation during COVID-19 on anthropometric data, quality of life, baseline physical activity and aortic pulse wave parameters in children and adolescents in two independent samples

Abstract Background The social restrictions resulting from the COVID-19 pandemic had a great impact on the routine of children and adolescents, with important consequences such as sleep, eating, and psychological/psychiatric disorders. Even though there are no studies on the subject, it is possible that these changes in habit and routine have also affected arterial stiffness (AS) in this population, which is an important predictor of cardiovascular risk. This study aimed to assess possible changes in AS, anthropometry, and quality of life (QoL) resulting from the COVID-19 pandemic in children and adolescents. Methods A controlled observational cross-sectional study was performed with 193 children and adolescents aged 9 to 19 years, allocated into two groups: before the pandemic (BPG) and one year after the pandemic (APG), matched by age and sex. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main AS indices evaluated were the augmentation index (AIx) and pulse wave velocity (PWV) derived from the aortic pulse wave. QoL was assessed using the Paediatric Quality of Life Inventory version 4.0 (PedsQL 4.0). Results Regarding QoL, the APG showed a worsening in emotional (p = 0.002) and school-related (p = 0.010) aspects. There was no statistically significant difference for most anthropometric parameters, except for the hip circumference, which was higher in the APG group (p < 0.001). The main predictor of AS in the paediatric population, AIx@75, was shown to be increased in the APG group (p < 0.001). Other cardiovascular parameters were also different, such as peripheral (p = 0.002) and central (p = 0.003) diastolic blood pressure, stroke volume (p = 0.010), and total vascular resistance (p = 0.002), which were shown to be decreased in the APG group, while the heart rate was increased (p < 0.001). Conclusions Our results show that routine changes resulting from the period of social isolation increased cardiovascular risk in children and adolescents, evident by the increase in AIx@75, which is considered to be an important marker of cardiovascular risk in the paediatric population

Gravimetric composition of municipal solid waste disposed in a large-scale experimental cell in Southeastern Brazil

The increasing consumption in emerging countries like Brazil has caused the increased generation of municipal solid waste (MSW) and hence the demand for environmentally friendly and relatively inexpensive disposal of the waste, such as sanitary landfills. In this research, it is presented the gravimetric composition of MSW disposed in a large-scale experimental cell, built on a sanitary landfill, Campinas, state of São Paulo, Brazil. For such, it was adopted the hypothesis that the characteristics of MSW vary with the income level of the population and the type of activity that generates it (domestic or commercial). Twenty-two tests were performed for gravimetric characterisation. Statistical analyses considering the results of this characterisation showed that the adopted hypothesis was correct. The MSW composition was preponderant by organic matter (52.7%), paper (17.5%) and plastic (13.0%). The methodology used was considered feasible to achieve the proposed objective of the characterisation17212814

Núcleos de Ensino da Unesp: artigos 2012: volume 6: formação de professores e trabalho docente

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES