Glycated hemoglobin as a surrogate for evaluating the effectiveness of drugs in diabetes mellitus trials: a systematic review and trial-level meta-analysis.

OBJECTIVE: The objective of this study was to investigate whether glycated hemoglobin (HbA1c) is a valid surrogate for evaluating the effectiveness of antihyperglycemic drugs in diabetes mellitus (DM) trials. METHODS: We conducted a systematic review of placebo-controlled randomized clinical trials (RCTs) evaluating the effect of a treatment on HbA1c (mean difference between groups) and clinical outcomes (relative risk of mortality, myocardial infarction, stroke, heart failure, and/or kidney injury) in patients with DM. Then, we investigated the association between treatment effects on HbA1c and clinical outcomes using regression analysis at the trial level. Lastly, we interpreted the correlation coefficients (R) using the cut-off points suggested by the Institute for Quality and Efficiency in Healthcare (IQWiG). HbA1c was considered a valid surrogate if it demonstrated a strong association: lower limit of the 95 percent confidence interval (95 percent CI) of R greater than or equal to .85. RESULTS: Nineteen RCTs were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate for any clinical outcome: mortality (R = .34; 95 percent CI -.14 to .69), myocardial infarction (R = .20; -.30 to .61), heart failure (R = .08; -.40 to .53), kidney injury (R = -.04; -.52 to .47), and stroke (R = .81; .54 to .93). CONCLUSIONS: The evidence from multiple placebo-controlled RCTs does not support the use of HbA1c as a surrogate to measure the effectiveness of antihyperglycemic drugs in DM studies.

Factores de riesgo asociados a mortalidad en pacientes adultos con neumonía por SARS- CoV-2 en un hospital público de Lima, Perú / Risk factors for in-hospital mortality in SARS-CoV-2 pneumonia adult patients from Lima, Peru

RESUMEN Objetivo: describir los principales factores asociados a la mortalidad en una cohorte de pacientes hospitalizados por neumonía por SARS-CoV-2 en un hospital público de Lima, Perú. Materiales y métodos: estudio de cohorte retrospectivo con muestreo no aleatorio por conveniencia. Se incluyó pacientes adultos con sospecha clínica o confirmados para SARS-CoV-2 con pruebas rápidas y/o moleculares. Se identificaron variables demográficas, clínicas, de laboratorio, tomográficas y de tratamiento. Se emplearon técnicas de estadística descriptiva, análisis bivariado y de regresión de Poisson para determinar el riesgo relativo (RR) ajustado. Resultados: se incluyó 122 pacientes, 70,5% del sexo masculino, edad promedio de 55,8 años, con antecedentes de obesidad (25,4%) e hipertensión arterial (HTA 13,1%). El análisis multivariado de los factores clínicos identificó que la edad (RR ajustado [RRa] 1,03; IC 95%: 1,00-1,06, p=0,021), el índice de masa corporal (IMC, RRa 1,03; IC 95%: 1,01-1,05; p=0,006), la HTA (RRa 1,68; IC 95%: 1,09-2,56; p=0,017), el índice de PaO2/FiO2 (RRa 0,99; IC 95%: 0,99-1,00; p<0,001), la exposición a lopinavir/ritonavir (RRa 0,83; IC 95%: 0,76-0,91; p<0,001), y corticoides sistémicos (RRa 1,18; IC 95%: 1,09-1,27; p<0,001) estuvieron asociados a la mortalidad de manera significativa. Conclusiones: la edad, IMC, HTA, índice PaO2/FiO2, y la exposición a corticoides y LPV/r estuvieron asociadas a la mortalidad en pacientes hospitalizados por neumonía por SARS-CoV-2.

ABSTRACT Objective: this study aimed to describe the main factors associated to mortality in a cohort of patients hospitalized with SARS-CoV-2 pneumonia in a public hospital in Lima, Peru. Materials and methods: this was a retrospective cohort study, with a non-random convenience sampling. Adult patients with confirmed/suspicious SARS-CoV-2 pneumonia with rapid and/ or molecular tests were included. Demographic, clinical, laboratory, tomographic and treatment variables were identified. Descriptive statistics, bivariate analysis, and Poisson regression techniques were used to determine the adjusted relative risk (aRR). Results: 122 patients were included, 70.5% were male, with a mean age of 55.8 years, with a history of obesity (25.4%) and high blood pressure (HBP, 13.1%). The multivariate analysis of clinical factors identified that age (aRR 1.03; 95% CI: 1,00- 1.06; p=0.021), body mass index (BMI; aRR 1.03; 95% CI: 1.01-1.05; p=0.006), HBP (aRR 1.68; 95% CI: 1.09-2.56; p=0.017), PaO2/FiO2 index (aRR 0.99; 95% CI: 0.99-1.00; p<0.001), exposure to lopinavir/ritonavir (LPV/r; aRR 0.83; 95% CI: 0.76-0.91; p <0.001), and systemic corticosteroids (aRR 1.18; 95% CI: 1.09-1.27; p<0.001) were significantly associated with mortality. Conclusions : Age, BMI, HBP, PaO2/FiO2 index, and exposure to corticosteroids and LPV/r were associated with mortality in our cohort of patients hospitalized with SARS-CoV-2 pneumonia.