Citations

Often clinicians are interested in determining whether a subject's measurement falls within a normal range, defined as a range of values of a continuous outcome which contains some proportion (eg, 95%) of measurements from a healthy population. Several studies in the biomedical field have estimated reference ranges based on a meta‐analysis of multiple studies with healthy individuals. However, the literature currently gives no guidance about how to estimate the reference range of a new subject in such settings. Instead, meta‐analyses of such normative range studies typically report the pooled mean as a reference value, which does not incorporate natural variation across healthy individuals in different studies. We present three approaches to calculating the normal reference range of a subject from a meta‐analysis of normally or lognormally distributed outcomes: a frequentist random effects model, a Bayesian random effects model, and an empirical approach. We present the results of a simulation study demonstrating that the methods perform well under a variety of scenarios, though users should be cautious when the number of studies is small and between‐study heterogeneity is large. Finally, we apply these methods to two examples: pediatric time spent awake after sleep onset and frontal subjective postural vertical measurements.

SummaryBackgroundHyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients.AimTo evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients.MethodsWe enrolled UC patients hospitalised for acute flares (Mayo score 6‐12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen.ResultsWe treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second‐line therapy. Day 3 hyperbaric oxygen responders were less likely to require re‐hospitalisation or colectomy by 3 months vs non‐responders (0% vs 66%, P = 0.002). No treatment‐related adverse events were observed.ConclusionHyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re‐hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.

ObjectiveAntirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID‐19) and its complications. We conducted a systematic review and meta‐analysis to describe the current evidence.MethodsA search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta‐analysis of effect sizes using random‐effects models was performed when possible.ResultsThe search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer‐reviewed journal. In a meta‐analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta‐analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias.ConclusionIn this systematic review and meta‐analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID‐19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID‐19 is currently inconclusive.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that can infect healthcare personnel (HCP) and patients in healthcare settings. Specific care activities, in particular, aerosol-generating procedures, may have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 has created significant challenges in healthcare facilities, particularly with severe shortages of personal protective equipment (PPE) used to protect HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care are needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. Objective Our objective was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel that included front-line clinicians, infectious diseases specialists, experts in infection control, and guideline methodologists with representation from the disciplines of preventive care, public health, medical microbiology, pediatrics, critical care medicine, and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then, a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations and provided narrative summaries of other interventions undergoing evaluations. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE for HCP who provide care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. Significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 remain, and PPE recommendations may need to be modified in response to new evidence.

AbstractBackgroundDescriptions of coronavirus disease 2019 (COVID-19) have focused on the nonpregnant adult population. This study aims to describe the clinical characteristics and perinatal outcomes of COVID-19 in pregnancy.MethodsWe searched databases from December 2019 to 30 April 2020. Eligible studies reported clinical characteristics, radiological findings, and/or laboratory testing of pregnant women during infection. Data were pooled across studies using a random-effects model.ResultsTwenty-four studies (136 women) were included. The most common symptoms were fever (62.9%) and cough (36.8%). Laboratory findings included elevated C-reactive protein (57%) and lymphocytopenia (50%). Ground-glass opacity was the most common radiological finding (81.7%). Preterm birth rate was 37.7% and cesarean delivery rate was 76%. There was 1 maternal death. There were 2 fetal COVID-19 cases.ConclusionsThe clinical picture in pregnant women with COVID-19 did not differ from the nonpregnant population; however, the rate of preterm birth and cesarean delivery are considerably higher than international averages.

Abstract IDSA Disclaimer As of the time of this publication, updates have been made to IDSA’s Guidelines on the Diagnosis of COVID-19. For the most updated version of these guidelines, please go to https://www.idsociety.org/covid19guidelines. Background Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution, and public health–level decision-making. The number of available SARS-CoV-2 nucleic acid detection tests is rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. Objective The IDSA’s goal was to develop an evidence-based diagnostic guidelines to assist clinicians, clinical laboratorians, patients, and policy makers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, the society provides a conceptual framework for understanding molecular diagnostic test performance, discusses the nuance of test result interpretation in a variety of practice settings, and highlights important unmet research needs in the COVID-19 diagnostic testing arena. Methods IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 15 diagnostic recommendations. Conclusions Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals who have had a known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institution-specific resources and the needs of different patient populations.