Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting.

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study.

The aim of our study was to evaluate all-cause mortality risk in patients with laboratory-confirmed COVID-19 in Mexico City treated with repurposed antivirals and antibiotics. This real-world retrospective cohort study contemplated 395,343 patients evaluated for suspected COVID-19 between February 24 and September 14, 2020 in 688 primary-to-tertiary medical units in Mexico City. Patients were included with a positive RT-PCR for SARS-CoV-2; those receiving unspecified antivirals, excluded; and groups of antivirals prescribed in < 30 patients, eliminated. Survival and mortality risks were determined for patients receiving antivirals, antibiotics, both, or none. We assessed the effect of early (<2 days) versus late (>2 days) use of antivirals on mortality in a sub-cohort of patients. Multivariable adjustment, propensity score matching, generalized estimating equations, and calculation of E-values were performed to limit confounding. 136,855 patients were analyzed; mean age 44.2 (SD:16.8) years; 51.3 % were men. 16.6 % received antivirals (3 %), antibiotics (10 %), or both (3.6 %). Antivirals studied were Oseltamivir (n=8414), Amantadine (n=319), Lopinavir-Ritonavir (n=100), Rimantadine (n=61), Zanamivir (n=39), and Acyclovir (n=36). Survival with antivirals (73.7 %, p<0.0001) and antibiotics (85.8 %, p<0.0001) was lower than no antiviral/antibiotic (93.6 %). After multivariable adjustment, increased risk of death occurred with antivirals (HR=1.72, 95 % CI: 1.61-1.84) in ambulatory (HR=4.7, 95 % CI: 3.94-5.62) and non-critical (HR=2.03, 95 % CI: 1.86-2.21) patients. Oseltamivir increased mortality risk in the general population (HR=1.72, 95 % CI: 1.61-1.84), ambulatory (HR=4.79, 95 % CI: 4.01-5.75), non-critical (HR=2.05, 95 % CI: 1.88-2.23), and pregnancy (HR=8.35, 95 % CI: 1.77-39.30); as well as hospitalized (HR=1.13, 95 % CI: 1.01-1.26) and critical patients (HR=1.22, 95 % CI: 1.05-1.43) after propensity score-matching. Early versus late oseltamivir did not modify the risk. Antibiotics were a risk factor in general population (HR=1.13, 95 % CI: 1.08-1.19) and pediatrics (HR=4.22, 95 % CI: 2.01-8.86), but a protective factor in hospitalized (HR=0.81, 95 % CI: 0.77-0.86) and critical patients (HR=0.67, 95 % CI: 0.63-0.72). No significant benefit for repurposed antivirals was observed; oseltamivir was associated with increased mortality. Antibiotics increased mortality risk in the general population but may increase survival in hospitalized and critical patients.

Recomendaciones latinoamericanas para el manejo de la hipertensión arterial en adultos (RELAHTA 2)

RESUMEN Se presenta la segunda parte de las recomendaciones latinoamericanas para el manejo de la Hipertensión Arterial (HTA) en adultos. En una primera fase se han descripto los aspectos más relevantes de la epidemiología, aspectos fisiopatológicos, cómo hacer diagnóstico, pautas terapéuticas, urgencias y emergencias hipertensivas, poblaciones especiales, hipertensión refractaria y la aplicación de las guías en la vida real. En esta segunda parte, se emiten recomendaciones respondiendo a preguntas específicas para prevención primaria, secundaria, terciaria y cuaternaria. En general pocas recomendaciones al respecto del manejo de la hipertensión arterial surgen desde la clínica médica/ medicina interna, a pesar de dos situaciones: la mayoría de los pacientes con hipertensión arterial son evaluados y manejados por los clínicos, y la clínica médica es la especialidad que permite la mirada holística e integrada de los problemas de salud del adulto, permitiendo agregar el enfoque biográfico al biológico, comprender e interpretar no solo el problema de salud sino sus causas y consecuencias (que muchas veces suelen corresponder a diferentes parénquimas, lo cual en el modelo fragmentado haría transitar al paciente por distintas especialidades). El bajo porcentaje de pacientes hipertensos controlados obliga a todos los profesionales involucrados en el manejo de los mismos a optimizar recursos y detectar problemas que se asocien a un control deficitario como la sub utilización del tratamiento farmacológico, baja tasa de pacientes tratados con estrategia combinada (la mayoría de los pacientes actualmente recibe monoterapia), falta de prescripción adecuada de los cambios en el estilo de vida, baja adherencia terapéutica e inercia clínica. En la presente publicación se presentan recomendaciones efectuadas por especialistas en clínica médica / medicina interna para el manejo de la hipertensión arterial en adultos, respondiendo preguntas de prevención primaria, secundaria, terciaria, y cuaternaria.

ABSTRACT The second part of the Latin American recommendations for the management of Arterial Hypertension (HTA) in adults is presented. In a first phase, the most relevant aspects of epidemiology, physiopathological aspects, how to diagnose, therapeutic guidelines, hypertension emergencies, special populations, refractory hypertension and the application of guides in real life have been described. In this second part, recommendations are issued answering specific questions for primary, secondary, tertiary and quaternary prevention. In general, few recommendations regarding the management of arterial hypertension arise from the medical clinic / internal medicine, despite two situations: the majority of patients with hypertension are evaluated and managed by the clinicians, and the medical clinic is the specialty that allows the holistic and integrated look of the health problems in adults, allowing to add the biographical approach to the biological, to understand and interpret not only the health problem but its causes and consequences (which often correspond to different parenchyma, which in the fragmented model would make the patient move through different specialties). The low percentage of controlled hypertensive patients forces all the professionals involved in the management of them to optimize resources and detect problems that are associated with a deficit control such as the under utilization of pharmacological treatment, low rate of patients treated with combined strategy (the most patients currently receive monotherapy), lack of adequate prescription of changes in lifestyle, low therapeutic adherence and clinical inertia. This publication presents recommendations made by specialists in medical clinic/internal medicine for the management of hypertension in adults, answering primary, secondary, tertiary and quaternary prevention questions.