Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.

Background: Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease. Methods: We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome. Participants: Patients admitted due to COVID-19 infection with mild disease. Results: Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy. Conclusions: Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration. Trial registration: https://clinicaltrials.gov/, identifier NCT04348695.

Interactions of Comorbidity and Five Simple Environmental Unhealthy Habits Concerning Physical and Mental Quality of Life in the Clinical Setting.

The objective of this study was to examine the interactions between comorbidity and five lifestyle single habits concerning different subscales of quality of life (QoL). For the study, 302 patients were consecutively recruited at the internal medicine department of a tertiary teaching hospital. Lifestyle habits, comorbidities and QoL were recorded according to validated questionnaires. Five single unhealthy habits, such as tobacco consumption, dietary intake of ultra-processed pastries, raw nuts or carbonated drinks, sleep time and physical activity patterns were selected according to previously published data. The main outcomes of the study were the scores of the eight subscales of the SF-36 QoL survey. The aggregate of unhealthy habits showed statistically significant association to every category in the SF-36 questionnaire, both in the univariate and the multivariate analysis when adjusting by age, sex and comorbidity. An interaction was found between comorbidity and unhealthy habits in both physical and mental summaries of SF-36. In conclusion, the lifestyle assessment according to five unhealthy habits is associated with a worse QoL. The interaction between comorbidity and unhealthy habits is especially clear in diseased patients due to the interplay between illness and lifestyle in the prediction of QoL.

Risk Score for Predicting In-Hospital Mortality in COVID-19 (RIM Score).

Infection by SARS-CoV2 has devastating consequences on health care systems. It is a global health priority to identify patients at risk of fatal outcomes. 1955 patients admitted to HM-Hospitales from 1 March to 10 June 2020 due to COVID-19, were were divided into two groups, 1310 belonged to the training cohort and 645 to validation cohort. Four different models were generated to predict in-hospital mortality. Following variables were included: age, sex, oxygen saturation, level of C-reactive-protein, neutrophil-to-platelet-ratio (NPR), neutrophil-to-lymphocyte-ratio (NLR) and the rate of changes of both hemogram ratios (VNLR and VNPR) during the first week after admission. The accuracy of the models in predicting in-hospital mortality were evaluated using the area under the receiver-operator-characteristic curve (AUC). AUC for models including NLR and NPR performed similarly in both cohorts: NLR 0.873 (95% CI: 0.849-0.898), NPR 0.875 (95% CI: 0.851-0.899) in training cohort and NLR 0.856 (95% CI: 0.818-0.895), NPR 0.863 (95% CI: 0.826-0.901) in validation cohort. AUC was 0.885 (95% CI: 0.885-0.919) for VNLR and 0.891 (95% CI: 0.861-0.922) for VNPR in the validation cohort. According to our results, models are useful in predicting in-hospital mortality risk due to COVID-19. The RIM Score proposed is a simple, widely available tool that can help identify patients at risk of fatal outcomes.

Empiric antibiotics for community-acquired pneumonia in adult patients: a systematic review and a network meta-analysis.

OBJECTIVE: The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) . METHOD: Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. EXCLUSION CRITERIA: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. DATA SOURCES: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. STATISTICAL ANALYSES: frequentist method performed with the 'netmeta' library, R package. RESULTS: 27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate. CONCLUSION: For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).

Antioxidant Lifestyle, Co-Morbidities and Quality of Life Empowerment Concerning Liver Fibrosis.

The assessment of liver fibrosis has gained importance since the progression of non-alcoholic fatty liver disease (NAFLD). Indeed, the description of the association between undetected liver fibrosis and lifestyle in terms of antioxidant habits, comorbidity and quality of life (QoL) domains may help in the characterization of subjects with NAFLD. A cross-sectional evaluation of (n = 116) consecutive patients from an Internal Medicine ambulatory evaluation was performed. Demographic data, lifestyle, co-morbidity, QoL (according to the SF-36 index) and analytical values to calculate the oxidative related Fibrosis-4 (FIB-4) index were recorded. The association between FIB-4 and co-morbidity, antioxidant habits in QoL was assessed in univariate analysis (p < 0.05) and confirmed in multivariable analysis for 4 of the 8 SF-36 categories: Physical QoL, Physical role, Social QoL and General QoL, as well as in the Physical summary of SF-36 (p < 0.05). Finally, interactions were assessed between co-morbidity, FIB-4 and antioxidant habits showed in the prediction of mean SF-36 (p < 0.01). Liver fibrosis assessed by the oxidative surrogate index FIB-4 is associated with the interaction between antioxidant lifestyle, co-morbidity and physical, social and general aspects of QoL in apparent liver disease-free individuals, generating a proof of concept for health empowerment and personalized medicine.