Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.

An evidence-based systematic review of the off-label uses of lisinopril.

AIMS: Lisinopril is an angiotensin-converting-enzyme inhibitor that is largely administered for off-label uses. This study aims to provide a comprehensive review of off-label uses of lisinopril to aid physicians to make evidence-based decisions. METHODS: The following bibliographic databases were searched from inception up to 30 March 2017: PubMed, EMBASE, the Cochrane Library, Cochrane Central Register of Controlled Trials, Scopus, Ovid and Proquest. This systematic review sought all randomized trials conducted on adult individuals comparing lisinopril on its off-label uses with alternative drugs or placebos and reported direct or alternative clinical outcomes. Risk of bias assessment by using the Cochrane Collaboration risk-of-bias tool and quality evaluation took place. RESULTS: Included studies demonstrated significant positive effects of lisinopril on proteinuric kidney disease; however, lisinopril caused a slight reduction of glomerular filtration rate (GFR) especially for patients with GFR < 90 ml min-1 . Lisinopril offered better outcomes in comparison to other standard treatments of diabetic nephropathy. Other studies showed positive effects of lisinopril for migraine, prevention of diabetes, myocardial fibrosis, mitral valve regurgitation, cardiomyopathy in patients with Duchenne muscular dystrophy, oligospermia and infertility, and diabetic retinopathy. Conversely, the studies reported that lisinopril was ineffective for five other off-label uses. CONCLUSIONS: The identified studies showed that lisinopril was highly effective for proteinuric kidney disease with a minor but inconsiderable decrease in GFR. Positive effects of lisinopril were demonstrated in seven other off-label uses; however, lisinopril cannot be recommended as the first choice for these until further clinical trials confirm these positive effects.

Prenatal Administration of Betamethasone and Neonatal Respiratory Distress Syndrome in Multifetal Pregnancies: A Randomized Controlled Trial.

BACKGROUND: Neonatal Respiratory Distress Syndrome (NRDS) is one of the most frequent causes of neonatal mortality especially in premature infants. Although it has been well established that maternal antenatal corticosteroid therapy has a positive effect on NRDS reduction, yet the effectiveness of this treatment in multifetal pregnancies is dubious. OBJECTIVE: We aimed to investigate the effect of betamethasone therapy on the incidence of NRDS in multifetal pregnancies through a randomized controlled trial. METHODS: 140 women with a multifetal pregnancy at less than 28 weeks' gestational age were randomly allocated into intervention and control groups. Women at the intervention group received intramuscularly betamethasone (12 mg/kg/BW twice). Neonatal outcomes were evaluated between two groups of intervention and control, and two subgroups of preterm and term births. This study is registered with the Iranian Clinical Trials Registry, number IRCT20180227038879N1. RESULTS: The incidence of NRDS was significantly lower in infants of betamethasone group than the ones in the control group (4.9% vs 18.1%, P=0.034) while it did not show a significant reduction in preterm infants compared to mature ones. Also, the intervention group presented a significant lower neonatal ventilation than the control group (47.2% vs 63.2%, P=0.041). Other neonatal outcomes, including age at birth, birth weight, Apgar score, NICU admission, and the number of mortalities were not significantly different between study groups. CONCLUSION: Betamethasone therapy during 28-32 weeks of gestation in multifetal pregnancies was associated with better neonatal outcomes through significant reductions in NRDS incidence and requiring ventilator treatment. However, betamethasone administration did not reduce the chance of NRDS in premature infants.

Comparison of global strain values of myocardium in beta-thalassemia major patients with iron load using specific feature tracking in cardiac magnetic resonance imaging.

Thalassemia defined a spectrum of diseases characterized by reduced or absent production of one of the globin chains of hemoglobin. High iron deposition in the myocardium may cause functional impairment even before any changes in left ventricular (LV) ejection fraction. These impairments may appear as changes in strain values. Early detection of myocardial dysfunction is essential for improving survival and preventing further complications. Therefore, this study aims to evaluate the cardiac strain patterns by Feature Tracking -Cardiac Magnetic Resonance Imaging (FT-CMR) method and their correlation with T2* values as a new parameter in determining myocardial iron overload (MIO). In this retrospective investigation, ninety-one patients with B-thalassemia major included from May 2016 to July 2019. Twenty-three healthy subjects, also incorporated as a control group. CMR used to evaluate ventricular volumes, LVEF, and the amount of myocardial T2*. Moreover, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS), and Global Radial Strain (GRS) were measured and analyzed in both rights and left ventricles. Correlations of cardiac T2* with GLS, GCS, and GRS were evaluated. The optimal cutoff value of GLS for prediction of cardiac T2* < 20 ms (as an indicator of inadequate chelation) calculated as well. There were significant correlations between cardiac T2* with LV GLS, LV GCS, and right ventricular GLS (p < 0.05 for each one). Moreover, a significant difference detected between the group of TM - MIO and TM + MIO and control group in terms of GLS (p < 0.001). The optimal cutoff value of GLS for prediction of cardiac T2* < 20 ms was at - 16.5% with sensitivity and specificity of 73% and 63%, respectively. Our study demonstrates that strain values measured by FT and myocardial T2* values are correlated. FT-CMR can be considered as an efficient tool for early detection of iron deposition and its effects on cardiac tissue so that proper and timely modification could have applied to chelation therapy.

Severe complications of tramadol overdose in Iran.

OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran. METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose. RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score <15, having taken a tramadol dose of >1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose. CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.