Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Cost-effectiveness analysis of newborn screening for congenital adrenal hyperplasia: comparison of two populations diagnosed with and without newborn screening

Introdução: A hiperplasia adrenal congênita por deficiência da 21-hidroxilase (HAC) é uma doença de eleição para um programa de triagem neonatal. Entretanto, a implementação triagem para essa doença ainda não é um consenso mundial, devido a escassez de informação sobre a sua custo-efetividade. Objetivo: Determinar o custo-efetividade do programa de triagem neonatal (TN) para HAC no Brasil, avaliando seu benefício no incremento do diagnóstico precoce da doença, na diminuição da taxa de mortalidade e no impacto na redução dos custos em saúde pública em relação à diminuição de sua morbidade em longo prazo. Metodologia: Foi construído um modelo de decisão para comparar as duas estratégias, testado por análise de sensibilidade. Os dados dos pacientes não triados foram extraídos dos prontuários médicos do Hospital das Clínicas-São Paulo e os dados da triagem do Centro de referência de triagem de São Paulo, Instituto Jô Clemente. A perspectiva do custo é a do Sistema Único de Saúde. Os desfechos relacionados ao diagnóstico tardio foram medidos em ambas as coortes e a razão incremental de custo-efetividade (RICE) foi calculada. Pacientes: 195 pacientes clássicos, diagnosticados clinicamente e confirmados por análise hormonal/molecular, e 378.790 recém-nascidos submetidos à TN em 2017. Resultados: Na análise de custo da coorte não triada, na forma perdedora de sal a hospitalização ocorreu em 76% dos pacientes, comprometimento mental em 8,6% e 3% das mulheres foram criadas no sexo masculino. O custo total desses desfechos foi de US$86.230/paciente com perda de sal. A leuprorelina foi utilizada em 28$ 4.232,74/paciente com virilização simples. Entre os 378,790 recém-nascidos (RN) triados, 25 eram afetados pela doença (incidência de 1:15.135). A taxa de falso-positivo da triagem foi de 0,22%. A taxa de mortalidade foi calculada em 11% nos não triados, enquanto não foram relatadas mortes pela doença na coorte triada. Comparando a coorte não triada versus a triada, o nível médio de sódio sérico foi de 121,2 mEq/L (118,3 to 124,1) x 131,8 mEq/L (129,3 to 134,5), a idade média no diagnóstico foi de 38,8 x 17 dias e a hospitalização ocorreu em 76% x 58% dos pacientes com a forma perdedora de sal, respectivamente. O custo incremental da triagem neonatal foi de US$771.185,82 por morte evitada, o que gera uma RICE de US$ 25.535,95 por anos de vida salvo, considerada custo-efetiva. Conclusão: A realidade brasileira em relação a HAC é de diagnóstico clínico ainda é deficiente e por tanto atrasado, levando a ocorrência de diversos desfechos adversos, que tem impacto econômico para o estado e psicossocial para os pacientes. Considerando esse contexto, a triagem neonatal para HAC é uma estratégia custo-efetiva e através do presente estudo tem respaldo científico para ser implementada em todo território nacionalIntroduction: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a eligible disease for a newborn screening program (NBS). However, the implementation of NBS for this disease is not yet a worldwide consensus, due to the lack of information about its cost- effectiveness. Objective: To determine the cost-effectiveness of the NBS for CAH in Brazil, assessing its benefit in increasing the early diagnosis of the disease, in decreasing the mortality rate and in the impact on reducing public health costs in relation to decreased long-term morbidity. Methodology: A decision model was developed to compare the two strategies, tested by a sensitivity analysis. The data of the unscreened patients were extracted from the medical records of the Hospital das Clínicas-São Paulo and the NBS data from the São Paulo Reference Screening Center, Instituto Jô Clemente. The cost perspective is from the Public Health System. The outcomes related to late diagnosis were measured in both cohorts and the incremental cost-effectiveness ratio (ICER) was calculated. Patients: 195 classical patients, clinically diagnosed and confirmed by hormonal / molecular analysis, and 378,790 newborns screened in 2017. Results: The cost of illness analysis of the unscreened cohort revealed that in salt wasting form hospitalization occurred in 76% of patients, mental impairment in 8.6% and 3% of females were raised as males. These outcomes\' total cost was US$86,230/salt wasting patient. Leuprorelin was used in 28$4,232.74/simple-virilizing patient. Among the 378,790 newborns screened, 25 were affected by the disease (incidence of 1: 15,135). The false-positive rate of the screening was 0.22%. The mortality rate was estimated at 11% in the unscreened, while no deaths from the disease were reported in the screened cohort. Comparing the unscreened versus screened cohort, the mean serum sodium level was 121.2 mEq/L (118.3 to 124.1) x 131.8 mEq/L (129.3 to 134.5), the mean age at diagnosis was 38.8 x 17 days and hospitalization occurred at 76% x 58 % of patients with the salt-wasting form, respectively. The incremental cost of neonatal screening was US$771,185.82 for avoided death, which generates an ICER of US$ 25,535.95 for years of life saved, considered cost-effective. Conclusion: The Brazilian reality in relation to CAH is that the clinical diagnosis is still deficient and therefore delayed, leading to the occurrence of several adverse outcomes, which have an economic impact for the state and psychosocial for the patients. Considering this context, NBS for CAH is a cost-effective strategy and through this study has scientific support to be implemented throughout the national territor

International practice of corticosteroid replacement therapy in congenital adrenal hyperplasia: data from the I-CAH registry.

Objective: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH

Strategies and performance of the CMS silicon tracker alignment during LHC Run 2

The strategies for and the performance of the CMS silicon tracking system alignment during the 2015–2018 data-taking period of the LHC are described. The alignment procedures during and after data taking are explained. Alignment scenarios are also derived for use in the simulation of the detector response. Systematic effects, related to intrinsic symmetries of the alignment task or to external constraints, are discussed and illustrated for different scenarios

Critical care admission following elective surgery was not associated with survival benefit:prospective analysis of data from 27 countries

Purpose: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. Methods: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. Results: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10–5.21]; p &lt; 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. Conclusions: We did not identify any survival benefit from critical care admission following surgery

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine