Iridium-catalysed hydroamination of internal homoallylic amines.

An Ir-catalysed regioselective hydroamination of internal homoallylic amines is reported. Both cyclic and acyclic internal olefins undergo directed hydroamination reactions with both aromatic and cyclic aliphatic amines to afford a variety of 1,4-diamines in fair to excellent yields. Diastereoselectivity and mechanistic investigations support that for cyclic substrates the reactions are proceeding via trans-aminoiridation to form a 5-membered metalacyclic intermediate.

Management of Persistent, Post-adenotonsillectomy Obstructive Sleep Apnea in Children: An Official American Thoracic Society Clinical Practice Guideline.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Although adenotonsillectomy is first-line management for pediatric OSA, up to 40% of children may have persistent OSA. This document provides an evidence-based clinical practice guideline on the management of children with persistent OSA. The target audience is clinicians, including physicians, dentists, and allied health professionals, caring for children with OSA. Methods: A multidisciplinary international panel of experts was convened to determine key unanswered questions regarding the management of persistent pediatric OSA. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Results: Recommendations were developed for six management options for persistent OSA. Conclusions: The panel developed recommendations for the management of persistent pediatric OSA based on limited evidence and expert opinion. Important areas for future research were identified for each recommendation.

The Rising Tide of Point-of-Care Ultrasound (POCUS) in Medical Education: An Essential Skillset for Undergraduate and Graduate Medical Education.

As point-of-care ultrasound (POCUS) becomes an integral component of healthcare, both undergraduate and graduate medical POCUS education is urgently necessary in curricula. Despite the apparent need of POCUS curricula, there remains a lingering question: Are there evidence-based benefits to POCUS training in undergraduate and/or graduate medical education settings? Qualitative review of research was conducted to identify common themes for benefits of POCUS and the requirements and/or characteristics for effective POCUS educational curricula. Results for undergraduate medical education were separated into preclinical and clinical education. In preclinical POCUS education, POCUS education improves anatomy education and physical examination skills for sonographic assessment of abdominal, reproductive, cardiovascular, and renal structures. Further enhancement can be achieved via simulation devices that are generalized ultrasound simulation mannequins, one defined body region such as the abdomen, or local regions of interest such as the femoral triangle. In clinical undergraduate POCUS education, benefits involved greater performance on knowledge tests and general ultrasound competency in emergency medicine, surgical, family medicine, and physical medicine and rehabilitation clerkships. These studies also found improved comprehension of specific POCUS examinations such as those for ultrasound-guided injections, FAST, eFAST, and RUSH. Further integration of POCUS education into graduate medical education was found to successfully improve ultrasound knowledge and competency in both academic and military internal medicine residencies. One limitation of this study is that this article is a review resulting in no specific intervention being introduced. The resultant hypothesis of this systematic review cannot be tested; rather evidence-based recommendations are restricted to the currently available literature within the searched databases. From this review, it was found that the inclusion of a properly integrated POCUS curriculum can result in greater confidence in ultrasound use, increased knowledge of anatomy and basic sciences for various organ systems, improved ultrasound knowledge and performance in clinical clerkships, and offers improved confidence and knowledge in ultrasound during residency.

Review of the clinical outcomes of therapeutic bronchoscopy for central airway obstruction.

Central airway obstruction (CAO) is a debilitating condition with a significant impact on patient's quality of life and risk of hospitalization from respiratory failure. The causes of CAO can be both benign and malignant. Benign CAO may be idiopathic or secondary to other disease processes (infection, intubation, tracheostomy, etc.). Malignant central airway obstruction (MCAO) may occur in patients with primary lung malignancy as well as metastasis from other malignancies including renal cell, colon, and breast. In a cohort review, MCAO was found in up to 13% of patients with newly diagnosed lung cancer. The obstruction may occur either due to endoluminal disease, extrinsic compression, or a combination of both. Several bronchoscopic tools are available to manage such obstruction. Practice patterns and tools used to relieve CAO vary between institutions and may depend on physician preference, patient characteristics, emergency nature of the procedure, and nature of the obstruction. To quantify the effect and added value of such interventions, it is crucial to understand the clinical impact these interventions have on patients. The clinical impact of therapeutic bronchoscopy (TB) must then be weighed against the potential complications to justify its value. Early studies of TB for CAO included patients with both malignant and benign etiologies. The study population's heterogeneity makes it difficult to determine how TB affects clinical outcomes, as clinical outcomes are disease specific. The impact of TB for a MCAO may be different when compared to a benign CAO. Similarly, the clinical outcome of treating an idiopathic benign CAO may be different than that of a post tracheostomy airway obstruction. In this article, we will focus on the clinical outcomes of TB in MCAO. TB has been shown to have a clear impact on weaning from mechanical ventilation, dyspnea, health-related quality of life, survival and quality adjusted survival. The potential impact of TB on these outcomes should be weighed against the potential risk of complications. Understanding the factors associated with improved clinical outcomes will help physicians decide when and if TB is helpful. Future studies should focus on creating a decision analysis tool to further define decision thresholds.

Colorectal Arteriovenous Malformations causing Prolonged Bleeding were Managed Successfully by Laparoscopic Low Anterior Resection with Sphincter Preservation: A Case Report.

Gastrointestinal arteriovenous malformations (AVMs) are a rare disease. Sigmoid-anorectal AVM has only been reported in a few cases. The condition is usually detected when patients have gastrointestinal bleeding complications. The diagnosis and treatment of colorectal AVMs are still challenging. This paper presents a case of an Asian 32-year-old female patient admitted to hospital because of lower gastrointestinal bleeding lasting 17 years. The patient was diagnosed with sigmoid-rectal arteriovenous malformation and failed with other medical treatments. The damaged gastrointestinal tract was removed by a laparoscopic low anterior resection. The results were positive after a three-month follow-up; the bleeding was resolved, and the anal sphincter function was intact. Laparoscopic low anterior resection is a safe, less invasive, and effective approach for managing patients with digestive tract bleeding due to extensive colorectal AVM and preservation of the anal sphincter.

Solitary Lung Nodule: CT-Guided Transthoracic Biopsy vs Transbronchial Biopsy With Endobronchial Ultrasound and Flexible Bronchoscope, a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Transbronchial lung biopsy with radial endobronchial ultrasound (rEBUS-TBB) and Computed tomography (CT) scan-guided transthoracic biopsy (CT-TTB) are commonly used to investigate peripheral lung nodules but high-quality data are still not clear about the diagnostic and safety profile comparison of these two modalities. METHOD: We included all randomized controlled trials (RCT) comparing rEBUS-TBB with a flexible bronchoscope and CT-TTB for solitary lung nodules. Two reviewers extracted data independently on diagnostic performance and complication rates. RESULTS: 170 studies were screened, 4 RCT with a total of 325 patients were included. CT-TTB had a higher diagnostic yield than rEBUS-TBB (83.45% vs 68.82%, risk difference - 0.15, 95% CI, [- 0.24, - 0.05]), especially for lesion size 1-2 cm (83% vs 50%, risk difference - 0.33, 95% CI, [- 0.51, - 0.14]). For malignant diseases, rEBUS-TBB had a diagnostic yield of 75.75% vs 87.7% of CT-TTB. rEBUS-TBB had a significant better safety profile with lower risks of pneumothorax (2.87% vs 21.43%, OR = 0.12, 95% CI [0.05-0.32]) and combined outcomes of hospital admission, hemorrhage, and pneumothorax (8.62% vs 31.81%, OR 0.21, 95% CI, [0.11-0.40]). Factors increasing diagnostic yield of rEBUS were lesion size and localization of the probe but not the distance to the chest wall and hilum. CONCLUSION: CT-TTB had a higher diagnostic yield than rEBUS-TBB in diagnosing peripheral lung nodules, particularly for lesions from 1 to 2 cm. However, rEBUS-TBB was significantly safer with five to eight times less risk of pneumothorax and composite complications of hospital admission, hemorrhage, and pneumothorax. The results of this study only apply to flexible bronchoscopy with radial ebus without navigational technologies. More data are needed for a comparison between CT-TTB with rEBUS-TBB combined with advanced navigational modalities.

Intramuscular Neural Distribution of Adductor Pollicis Muscle Spasticity in Cadaver Model Regarding Botulinum Neurotoxin Treatment

Purpose@#The adductor pollicis muscle is frequently targeted for botulinum neurotoxin injective treatment for spasticity. However, there are no injective guidelines for delivering injection to the muscle. @*Materials and Methods@#A method known as the modified Sihler’s method was used to stain the adductor pollicis muscle in 16 specimens to reveal intramuscular neural distribution of the muscle. @*Results@#The most intramuscular neural distribution was located on 1/5 to 3/5 of the muscle regarding midline of 3rd metacarpal bone (0) to the base of the 1st proximal phalanx (5/5). The nerve entry point was mostly located on 0 to 1/5 of the muscle. @*Conclusion@#The result suggests that botulinum neurotoxin should be delivered at the middle of second metacarpal bone via deep injection.

Intramuscular Neural Distribution of the Gastrocnemius for Botulinum Neurotoxin Injection:Application to Cosmetic Calf Shaping

Purpose@#Anatomical landmarks can provide vital information on the distribution of nerves in the gastrocnemius muscle. We aimed to provide an anatomical perspective on appropriate locations for botulinum neurotoxin (BoNT) injections in the medial and lateral parts of the gastrocnemius for calf shaping. @*Materials and Methods@#A modified Sihler’s method was applied to both the medial and lateral parts of the gastrocnemius muscles (16 specimens). Intramuscular neural distributions were revealed by dissecting along a transverse line crossing the fibular head and superior margin of the calcaneal tuberosity. @*Results@#The intramuscular neural distribution for the medial and lateral parts of the gastrocnemius had the greatest arborized patterns in the 7/10–8/10 section of the medial head and 7.5/10–8.5/10 section of the lateral part of the gastrocnemius. @*Conclusion@#We propose that BoNT injections should be directed to the 7/10–8/10 section of the medial head and the 7.5/10– 8.5/10 section of the lateral part of the gastrocnemius. Following our guidelines, clinicians can ensure satisfactory results with the use of minimal doses to limit adverse effects, such as gait disturbance, antibody production, and bruising, due to multiple injections. The results can also be altered and applied to electromyography.

Optimizing Public Health Preparedness for Highly Infectious Diseases in Central Vietnam.

Our primary objectives were (a) to determine the need for and the availability of point-of-care testing (POCT) for infectious diseases and (b) to recommend point-of-care testing strategies and Spatial Care PathsTM (SCPs) that enhance public health preparedness in the regional districts of Thua Thien Hue Province (TTHP), Central Vietnam, where we conducted field surveys. Medical professionals in seven community health centers (CHCs), seven district hospitals (DHs) and one provincial hospital (PH) participated. Survey questions (English and Vietnamese) determined the status of diagnostic testing capabilities for infectious diseases and other acute medical challenges in TTHP. Infectious disease testing was limited: six of seven CHCs (86%) lacked infectious disease tests. One CHC (14%, 1/7) had two forms of diagnostic tests available for the detection of malaria. All CHCs lacked adequate microbiology laboratories. District hospitals had few diagnostic tests for infectious diseases (tuberculosis and syphilis), blood culture (29%, 2/7), and pathogen culture (57%, 4/7) available. The PH had broader diagnostic testing capabilities but lacked preparedness for highly infectious disease threats (e.g., Ebola, MERS-CoV, SARS, Zika, and monkeypox). All sites reported having COVID-19 rapid antigen tests; COVID-19 RT-PCR tests were limited to higher-tier hospitals. We conclude that infectious disease diagnostic testing should be improved and POC tests must be supplied near patients' homes and in primary care settings for the early detection of infected individuals and the mitigation of the spread of new COVID-19 variants and other highly infectious diseases.

Rhodium-/Iridium-Catalyzed Hydroamination for the Synthesis of 1,2-, 1,3-, or 1,4-Diamines.

An Ir-catalyzed regioselective hydroamination of allyl amines using aryl amines and catalyst-controlled regiodivergent hydroamination of allylic and homoallylic amines with aniline nucleophiles are reported. The directed hydroamination reactions afford a variety of 1,2-, 1,3-, and 1,4-diamines in good to excellent yields and high regio- and chemoselectivities. Mechanistic investigations suggests that the reactions are proceeding through an oxidative addition into the ArHN-H bond and that the observed regioselectivity is due to the selective formation of a 5- or 6-membered metalacyclic intermediate, depending on the catalyst employed.

Trends in Mortality of Acute Pulmonary Embolism.

Despite substantial advances in the diagnosis and management, pulmonary embolism (PE) continues to be a significant cause of mortality. In this article, we provide a concise overview of the evolution of worldwide mortality trends related to PE. Despite the data being derived mainly from observational studies, there is a clear trend toward decreasing mortality over time from PE. Whether this truly represents a treatment effect or is more related to increased diagnosis of small PEs is not fully clear. Modern approaches to PE management such as the PE response teams have the potential to further reduce the mortality from PE.

Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis.

BACKGROUND: Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion. This drug has also been granted breakthrough designation for NSCLCs with MET exon 14 alterations. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the efficacy and safety of crizotinib in patients with these diseases. METHODS: We searched PubMed and Web of Science for relevant studies. Meta-analysis of proportions was conducted to calculate the pooled rate of complete response, partial response, stable disease, progressive disease, disease control rate (DCR), objective response rate (ORR), and drug adverse effects (AEs) of crizotinib in NSCLCs with ROS1 rearrangement or MET alterations. RESULTS: A total of 20 studies were included for meta-analysis. Among patients with ROS1-positive NSCLC, crizotinib exhibited a pooled DCR of 93.2% (95% confidence interval [CI] 90.8-95.5) and a pooled ORR of 77.4% (95% CI 72.8-82.1). The median progression-free survival (PFS) and overall survival (OS) of patients in this group was 14.5 and 32.6 months, respectively. For NSCLC with MET alterations, crizotinib was associated with a lower efficacy (DCR 78.9% [95% CI 70.3-87.4] and ORR 40.6% [95% CI 28.3-53.0]). The median PFS was 5.2 months, and median OS was 12.7 months. The most common drug AEs were vision impairment (43.7%), edema (42.9%), and fatigue (40.1%). CONCLUSION: Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations. Crizotinib had remarkable effects on advanced NSCLC with ROS1 fusion, as previously reported. However, the role of this targeted therapy in MET-altered NSCLC remains investigational.

Poly(N-isopropylacrylamide)-b-Poly(L-lysine)-b-Poly(L-histidine) Triblock Amphiphilic Copolymer Nanomicelles for Dual-Responsive Anticancer Drug Delivery.

A series of ABC triblock poly(N-isopropylacrylamide)75-block-poly(L-lysine)35-block-poly(L-histidine)n (p(NIPAM)75-b-p(Lys)35-b-p(His)N) (N = 35,50,75,100) copolymer bio-conjugates were prepared by combining reversible addition-fragmentation chain transfer polymerization and fast ring-opening polymerization of N-carboxyanhydride a-amino acid using 1,3-dicyclohexylimidazolium hydrogen carbonate as a catalyst. All the resulting triblock copolymers self-assembled into spherical micellar aggregates in aqueous solution, irrespective of the chain length of the histidine block. The micellar aggregates encapsulated the anticancer drug doxorubicin (Dox) and exhibited high drug loading efficiency. Temperature and pH stimuli were applied to investigate the controlled release of Dox. The non-cytotoxic nature of the polymers was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake of the Dox-loaded micelles revealed that the micelles successfully release Dox in cancer cells in response to pH- and temperature-induced morphological change. In-vitro studies further confirmed that the Dox-loaded triblock copolymer micelle is an excellent platform for drug delivery.

Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea

ObjectivesTo assess the efficacy of hydroxychloroquine on mild-moderate COVID-19 patients in South Korea. MethodsA retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 226 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were utilized to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 31) or conservative treatment (n = 195). ResultsKaplan-Meier curves drawn using propensity score-matched data revealed no differences between the length of time to viral clearance and duration of hospital stay between the two treatment arms (p=0.18, p=0.088). Multivariable Cox regression analysis similarly showed that time to viral clearance(Hazard ratio (HR) 0.97, [95%-confidence interval (CI): 0.57-1.67]) and symptom duration(HR 1.05, [95%-CI: 0.62-1.78]) were not different between groups. No severe adverse event or death was observed in either group. ConclusionsHQ with antibiotics was not associated with better clinical outcomes in terms of time to viral clearance, length of hospital stay, and duration of symptoms compared to conservative treatment alone. Large prospective randomized trials are necessary for definitive conclusions.

Clinical spectrum of primary adrenal lymphoma: results of a multicenter cohort study.

Purpose: We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency. Methods: Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017. Results: Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63-613.7, P = 0.008) and 2.69 (95% CI: 0.61-11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004). Conclusion: We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.

Trends and seasonal variation of hospitalization and mortality of interstitial lung disease in the United States from 2006 to 2016.

BACKGROUND: In the recent years, the overall trends in hospital admission and mortality of interstitial lung disease (ILD) are unknown. In addition, there was some evidence that interstitial lung disease death rate highest in the winter but this finding was only available in one study. This study will investigate the trend and seasonal variations in hospital admission and mortality rates of ILD from 2006 to 2016. METHOD: From the Nationwide Inpatient Sample database, we collected all cases with the International Classification of Diseases (ICD)-9 or ICD-10 codes of ILD excluding identifiable external causes (drug, organic or inorganic dusts) from 2006 to 2016. Hospitalization rates of each year were calculated based on U.S Census population data. Monthly hospitalization and in-hospital mortality rates were analyzed by seasonal and trend decomposition. Subgroups of idiopathic interstitial fibrosis (IPF), acute respiratory failure (ARF), pneumonia were analyzed. RESULTS: From 2006 to 2016, all-cause hospital admission rate of patients with interstitial lung disease (ILD) and IPF-only subgroup declined but their overall mortality remained unchanged (except IPF subgroup and acute respiratory failure subgroup). Acute respiratory failure related admission account for 23% of all causes and pneumonia 17.6%. Mortality of ILD in general and subgroup of ILD with ARF was highest in winter, up to 8.13% ± 0.60 and 26.3% ± 10.2% respectively. The seasonal variations of hospital admission and mortality of ILD in general was not changed when infectious pneumonia cases were ruled out. All cause admission rates were highest in months from January to April. Subgroup analysis also showed seasonal variations with highest hospitalization rates for all subgroups (IPF, ARF, pneumonia) in the months from December to April (winter to early Spring). CONCLUSION: From 2006 to 2016, admission rates of ILD of all causes and IPF subgroup declined but in-hospital mortality of ILD of all causes remained unchanged. Mortality of IPF subgroup and acute respiratory failure subgroup trended down. All-cause hospital admissions and mortality of ILD have a strong seasonal variation. Hospitalization rates for all subgroups (IPF, ARF, pneumonia) were highest in the months from December to April.

Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients

ObjectiveTo evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. DesignSystematic review and network meta-analysis Data SourcesPubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study SelectionPublished and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome MeasuresThe outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). ConclusionAnti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty and can be considered in practice and policy; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review RegistrationPROSPERO 2020: CRD42020186527. Summary BoxO_ST_ABSSection 1: What is already known on this topicC_ST_ABS- Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for COVID-19. - Results from numerous studies are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. - Level of evidence behind each outcome from diverse studies remains unknown. Section 2: What this study adds- Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve clinical outcomes of COVID-19. - Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks. - Only 20% of current evidence on pharmacological management of COVID-19 is on moderate/high evidence certainty and can be considered in practice and policy; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions.

Seek COVER: Development and validation of a personalized risk calculator for COVID-19 outcomes in an international network

ObjectiveTo develop and externally validate COVID-19 Estimated Risk (COVER) scores that quantify a patients risk of hospital admission (COVER-H), requiring intensive services (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis. MethodsWe analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries. We developed and validated 3 scores using 6,869,127 patients with a general practice, emergency room, or outpatient visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The scores were validated on patients with confirmed or suspected COVID-19 diagnosis across five databases from South Korea, Spain and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death iii) death in the 30 days after index date. ResultsOverall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved high performance in influenza. When transported to COVID-19 cohorts, the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration was overall acceptable. ConclusionsA 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and fatality. The models could aid in providing reassurance for low risk patients and shield high risk patients from COVID-19 during de-confinement to reduce the virus impact on morbidity and mortality.

Comparative Efficacy and Safety of Pharmacological Managements for Hospitalized COVID-19 Patients: Protocol for Systematic Review and Trade-Off Network Meta-Analysis.

Coronavirus-Disease 2019 (COVID-19) is the clinical disease caused by the SARS-CoV-2 virus, the infectious agent causing the ongoing pandemic that has impacted the lives of hundreds of millions of people in almost every nation worldwide. It is a potentially fatal disease to many vulnerable patients including the elderly and those with chronic illnesses; but because this virus is a novel one, there are no firmly established treatment protocols. Many treatment methods are being investigated worldwide, and scientific conclusions drawn from these endeavors are crucial for healthcare professionals in combating this disease. In this network meta-analysis, we focus specifically on the pharmacologic agents that have been investigated for the treatment of COVID-19 and aim to produce a comprehensive picture of the evidence from current data in order to produce relevant insights on the comparative efficacy and safety profiles of various pharmacologic agents against COVID-19.