The 50 most-cited articles in Annals of Internal Medicine, 2020

BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The…

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as…

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not…

BACKGROUND: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse transcriptase polymerase chain reaction (RT-PCR) are being used to rule out infection among high-risk persons, such as exposed inpatients and health care workers. It is critical to understand how the predictive value of the test varies with time from exposure and symptom onset to avoid being falsely reassured by negative test results. OBJECTIVE: To estimate the false-negative rate by day since infection. DESIGN: Literature review and pooled analysis. SETTING: = 1330). PATIENTS: A mix of inpatients and outpatients with SARS-CoV-2 infection. MEASUREMENTS: A Bayesian hierarchical model was fitted to estimate the false-negative rate by day since exposure and symptom onset. RESULTS: Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to…

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly instigated a global pandemic. Vaccine development is proceeding at an unprecedented pace. Once available, it will be important to maximize vaccine uptake and coverage. OBJECTIVE: To assess intent to be vaccinated against COVID-19 among a representative sample of adults in the United States and identify predictors of and reasons for vaccine hesitancy. DESIGN: Cross-sectional survey, fielded from 16 through 20 April 2020. SETTING: Representative sample of adults residing in the United States. PARTICIPANTS: Approximately 1000 adults drawn from the AmeriSpeak probability-based research panel, covering approximately 97% of the U.S. household population. MEASUREMENTS: Intent to be vaccinated against COVID-19 was measured with the question, "When a vaccine for the coronavirus becomes available, will you get vaccinated?" Response options were "yes," "no," and "not sure." Participants who responded "no" or "not sure" were asked to provide a reason. RESULTS: = 107) did not intend to be vaccinated. Factors independently associated…

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM…

Systemic lupus erythematosus (lupus) is characterized by aberrant activity of the immune system, leading to variable clinical symptoms. Lupus is more prevalent in African American women and women in other ethnic minority groups. Diagnosing, treating, and identifying novel therapies for lupus is challenging because of its genetic and phenotypic heterogeneity. Lupus nephritis is the most common target-organ manifestation and requires individualized care to minimize toxicity. A multidisciplinary approach to caring for pregnant patients with lupus is essential to optimize outcomes.

Letters29 June 2020Worldwide Effect of COVID-19 on Physical Activity: A Descriptive StudyFREEGeoffrey H. Tison, MD, MPH, Robert Avram, MD, MSc, Peter Kuhar, BS, Sean Abreau, MSc, Greg M. Marcus, MD, MAS, Mark J. Pletcher, MD, MPH, and Jeffrey E. Olgin, MDGeoffrey H. Tison, MD, MPHUniversity of California, San Francisco, and Bakar Computational Health Sciences Institute, San Francisco, California (G.H.T.)Search for more papers by this author, Robert Avram, MD, MScUniversity of California, San Francisco, San Francisco, California (R.A., S.A., G.M.M., M.J.P., J.E.O.)Search for more papers by this author, Peter Kuhar, BSAzumio, Redwood City, California (P.K.)Search for more papers by this author, Sean Abreau, MScUniversity of California, San Francisco, San Francisco, California (R.A., S.A., G.M.M., M.J.P., J.E.O.)Search for more papers by this author, Greg M. Marcus, MD, MASUniversity of California, San Francisco, San Francisco, California (R.A., S.A., G.M.M., M.J.P., J.E.O.)Search for more papers by this author, Mark J. Pletcher, MD, MPHUniversity of California, San Francisco, San…

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked…

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of…

Letters11 November 2020Sixty-Day Outcomes Among Patients Hospitalized With COVID-19FREEVineet Chopra, MD, MSc, Scott A. Flanders, MD, Megan O’Malley, PhD, Anurag N. Malani, MD, and Hallie C. Prescott, MD, MScVineet Chopra, MD, MScUniversity of Michigan Health System and The Michigan Hospital Medicine Safety Collaborative, Ann Arbor, MichiganSearch for more papers by this author, Scott A. Flanders, MDUniversity of Michigan Health System and The Michigan Hospital Medicine Safety Collaborative, Ann Arbor, MichiganSearch for more papers by this author, Megan O’Malley, PhDUniversity of Michigan Health System and The Michigan Hospital Medicine Safety Collaborative, Ann Arbor, MichiganSearch for more papers by this author, Anurag N. Malani, MDSt. Joseph Mercy Health System and The Michigan Hospital Medicine Safety Collaborative, Ann Arbor, MichiganSearch for more papers by this author, and Hallie C. Prescott, MD, MScUniversity of Michigan Health System and The Michigan Hospital Medicine Safety Collaborative, Ann Arbor, MichiganSearch for more papers by this authorAuthor, Article, and…

BACKGROUND: Primary aldosteronism is a nonsuppressible renin-independent aldosterone production that causes hypertension and cardiovascular disease. OBJECTIVE: To characterize the prevalence of nonsuppressible renin-independent aldosterone production, as well as biochemically overt primary aldosteronism, in relation to blood pressure. DESIGN: Cross-sectional study. SETTING: 4 U.S. academic medical centers. PARTICIPANTS: = 408). MEASUREMENTS: Participants completed an oral sodium suppression test, regardless of aldosterone or renin levels, as a confirmatory diagnostic for primary aldosteronism and to quantify the magnitude of renin-independent aldosterone production. Urinary aldosterone was measured in participants in high sodium balance with suppressed renin activity. Biochemically overt primary aldosteronism was diagnosed when urinary aldosterone levels were higher than 12 μg/24 h. RESULTS: Every blood pressure category had a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher blood pressure, kaliuresis, and lower…

BACKGROUND: Health care workers (HCWs) are at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PURPOSE: To examine the burden of SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome (MERS)-CoV on HCWs and risk factors for infection, using rapid and living review methods. DATA SOURCES: Multiple electronic databases, including the WHO database of publications on coronavirus disease and the medRxiv preprint server (2003 through 27 March 2020, with ongoing surveillance through 24 April 2020), and reference lists. STUDY SELECTION: Studies published in any language reporting incidence of or outcomes associated with coronavirus infections in HCWs and studies on the association between risk factors (demographic characteristics, role, exposures, environmental and administrative factors, and personal protective equipment [PPE] use) and HCW infections. New evidence will be incorporated on an ongoing basis by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; verification was done by a…

Letters15 December 2020Autopsy Findings and Venous Thromboembolism in Patients With COVID-19FREEDominic Wichmann, MDDominic Wichmann, MDUniversity Medical Center Hamburg-Eppendorf, Hamburg, Germany (D.W.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-1206 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Epelbaum raises concerns that focusing on VTE or PE in patients with COVID-19 may misdirect investigators' attention to an epiphenomenon. We strongly disagree, especially because we believe that the references he gives do not back up his statements.Dr. Epelbaum states that lack of VTE prophylaxis “remains a global deficiency,” citing a study by Kröger and colleagues (1). The main topic of this study was to investigate whether patients presenting with VTE/PE in Germany had a risk factor that could have been identified previously. Most of these patients had no medical condition and no identifiable risk factor. The algorithm consequently decided against…

Letters16 March 2020COVID-19 and the Risk to Health Care Workers: A Case ReportFREEKangqi Ng, MBBS, Beng Hoong Poon, MBBS, MPH, MMed (Family Med), Troy Hai Kiat Puar, MBBS, Jessica Li Shan Quah, MBBS, Wann Jia Loh, MBBS, Yu Jun Wong, MD, Thean Yen Tan, MBBCh, and Jagadesan Raghuram, MB BCh BAOKangqi Ng, MBBSChangi General Hospital, Singapore (K.N., B.H.P., T.H.K., J.L.S., W.J.L., Y.J.W., T.Y.T., J.R.), Beng Hoong Poon, MBBS, MPH, MMed (Family Med)Changi General Hospital, Singapore (K.N., B.H.P., T.H.K., J.L.S., W.J.L., Y.J.W., T.Y.T., J.R.), Troy Hai Kiat Puar, MBBSChangi General Hospital, Singapore (K.N., B.H.P., T.H.K., J.L.S., W.J.L., Y.J.W., T.Y.T., J.R.), Jessica Li Shan Quah, MBBSChangi General Hospital, Singapore (K.N., B.H.P., T.H.K., J.L.S., W.J.L., Y.J.W., T.Y.T., J.R.), Wann Jia Loh, MBBSChangi General Hospital, Singapore (K.N., B.H.P., T.H.K., J.L.S., W.J.L., Y.J.W., T.Y.T., J.R.), Yu Jun Wong, MDChangi General Hospital, Singapore (K.N., B.H.P., T.H.K., J.L.S., W.J.L., Y.J.W., T.Y.T., J.R.), Thean Yen Tan, MBBChChangi General Hospital, Singapore (K.N., B.H.P., T.H.K.,…

BACKGROUND: Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects. OBJECTIVE: To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PATIENTS: Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020. MEASUREMENTS: Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex. RESULTS: had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino…

Diagnostic testing to identify persons infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction-based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test…

BACKGROUND: The evolving outbreak of coronavirus disease 2019 (COVID-19) is requiring social distancing and other measures to protect public health. However, messaging has been inconsistent and unclear. OBJECTIVE: To determine COVID-19 awareness, knowledge, attitudes, and related behaviors among U.S. adults who are more vulnerable to complications of infection because of age and comorbid conditions. DESIGN: Cross-sectional survey linked to 3 active clinical trials and 1 cohort study. SETTING: 5 academic internal medicine practices and 2 federally qualified health centers. PATIENTS: 630 adults aged 23 to 88 years living with 1 or more chronic conditions. MEASUREMENTS: Self-reported knowledge, attitudes, and behaviors related to COVID-19. RESULTS: A fourth (24.6%) of participants were "very worried" about getting the coronavirus. Nearly a third could not correctly identify symptoms (28.3%) or ways to prevent infection (30.2%). One in 4 adults (24.6%) believed that they were "not at all likely" to get the virus, and 21.9% reported that COVID-19 had little or no effect on their daily…

DESCRIPTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done…

BACKGROUND: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). OBJECTIVE: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668). SETTING: Internet-based trial across the United States and Canada (40 states and 3 provinces). PARTICIPANTS: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset. INTERVENTION: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. MEASUREMENTS: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days. RESULTS: = 0.29). LIMITATION: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages. CONCLUSION: Hydroxychloroquine did not…

Letters20 March 2020Knowledge and Perceptions of COVID-19 Among the General Public in the United States and the United Kingdom: A Cross-sectional Online SurveyFREEPascal Geldsetzer, MBChB, ScD, MPHPascal Geldsetzer, MBChB, ScD, MPHStanford University, Stanford, California (P.G.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0912 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: The behavior of the general public will probably have an important bearing on the course of the coronavirus disease 2019 (COVID-19) epidemic. Human behavior is influenced by people's knowledge and perceptions (1).Objective: To assess knowledge and perceptions about COVID-19 among a convenience sample of the general public in the United States and United Kingdom.Methods and Findings: This study is a cross-sectional survey conducted on an online platform managed by Prolific Academic Ltd. The platform's pool of participants numbers approximately 80 000 individuals, of…

Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and progressive airflow obstruction. Tobacco smoking is the leading cause but not the only one. A postbronchodilator FEV1–FVC ratio less than 0.70 is required for a diagnosis of COPD. Inhaler therapy is the backbone of treatment and should be complemented by a multifaceted management strategy that includes counseling and pharmacotherapy for smoking cessation, pulmonary rehabilitation, treatment of comorbidities, administration of influenza and pneumococcal immunizations, and prescription of long-term oxygen therapy in hypoxemic patients.

BACKGROUND: The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. OBJECTIVE: To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. DESIGN: Cross-sectional analysis with separate pooled data sets for development and validation. SETTING: = 13) with measured GFR available. PATIENTS: 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). MEASUREMENTS: Clearance of an exogenous marker (reference…

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of…

BACKGROUND: Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. OBJECTIVE: To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. DESIGN: Prospective cohort study. SETTING: Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. PARTICIPANTS: 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. MEASUREMENT: Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. RESULTS: Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or…

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity…

Background: Several pharmacologic options for type 2 diabetes are available. Purpose: To compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes. Data Sources: Several databases from inception through 18 December 2019 and ClinicalTrials.gov on 10 April 2020. Study Selection: English-language randomized trials that had at least 24 weeks of intervention and assessed the effects of glucose-lowering drugs on mortality, glycemic, and vascular outcomes. Data Extraction: Pairs of reviewers extracted data and appraised risk of bias. Data Synthesis: 453 trials assessing 21 antidiabetic interventions from 9 drug classes were included. Interventions included monotherapies (134 trials), add-on to metformin-based therapies (296 trials), and monotherapies versus add-on to metformin therapies (23 trials). There were no differences between treatments in drug-naive patients at low cardiovascular risk. Insulin regimens and specific glucagon-like peptide-1 receptor agonists (GLP-1 RAs) added to metformin-based background therapy produced the greatest reductions in…

Background: Coronavirus disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in China in December 2019, was recently recognized as pandemic threat by the World Health Organization, with the potential of rapidly overloading health care systems and causing substantial mortality worldwide (www.who.int/dg/speeches/detail/who-director-general -s-opening-remarks-at-the-media-briefing-on-covid-19 —11-march -2020). Human-to-human transmission occurs mainly through respiratory droplets, but other routes are under investigation, because SARS-CoV-2 has been detected in several body fluids (1). So far, few data are available on ocular samples from patients with COVID-19, although conjunctivitis has been occasionally reported among COVID-19 symptoms, similar to infections caused by other human coronaviruses (2, 3). During the SARS epidemic, eye exposure to infectious fluids was associated with an increased risk for SARS-CoV transmission to health care workers (3, 4). Although SARS-CoV RNA was occasionally found in…

BACKGROUND: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. OBJECTIVE: To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART. DESIGN: Cohort study. SETTING: HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020. PARTICIPANTS: 77 590 HIV-positive persons receiving ART. MEASUREMENTS: Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models. RESULTS: Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were…

Fibromyalgia is characterized by chronic, widespread musculoskeletal pain and associated fatigue, sleep disturbances, and other cognitive and somatic symptoms. For many patients, these symptoms persist for years and lead to frequent health care use; for some, fibromyalgia and its symptoms can be debilitating. Although many treatments are available, management remains challenging. This article highlights the clinical features of fibromyalgia, discusses diagnostic criteria and their evolution, and reviews treatment options.

Delirium is an acute confusional state that is common and costly and is associated with significant functional decline and distress. It is the manifestation of acute encephalopathy and is variably called acute brain failure, acute brain dysfunction, or altered mental status. All patients are at risk for delirium, although those with more vulnerabilities (such as advanced age, exposures to other stressors like infection, and certain medications) are at higher risk. The pathophysiologic cause of delirium is not well understood. It is important to recognize patients at risk for and those with delirium and to immediately identify and treat factors contributing to it. There is no single intervention or medication to treat delirium, making it challenging to manage. Therefore, risk mitigation and prompt treatment rely on a sophisticated strategy to address the contributing factors. Delirium may be prevented or attenuated when multimodal strategies are used, thereby improving patient outcomes.

Background: Coronavirus disease 2019 (COVID-19) has spread, causing a worldwide pandemic, and prolonged effects are emerging (1, 2). The term “long COVID” describes illness in persons who continue to report lasting effects after infection (3, 4). To date, little information exists about outpatient settings in this novel disease where 81% of cases are reportedly on the mild end of the spectrum (5). Informing patients and physicians about COVID-19 symptom evolution may help them recognize the time course of the disease, legitimize patients' concerns, and reassure them when possible. Messages around potentially persisting symptoms could also assist in reinforcing public health measures to avoid the spread of infection. Objective: To describe COVID-19 symptom evolution and persistence in an outpatient setting in Geneva, Switzerland, from day 1 through day 30 to 45 after diagnosis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic challenges hospital leaders to make time-sensitive, critical decisions about clinical operations and resource allocations. OBJECTIVE: To estimate the timing of surges in clinical demand and the best- and worst-case scenarios of local COVID-19-induced strain on hospital capacity, and thus inform clinical operations and staffing demands and identify when hospital capacity would be saturated. DESIGN: Monte Carlo simulation instantiation of a susceptible, infected, removed (SIR) model with a 1-day cycle. SETTING: 3 hospitals in an academic health system. PATIENTS: All people living in the greater Philadelphia region. MEASUREMENTS: The COVID-19 Hospital Impact Model (CHIME) (http://penn-chime.phl.io) SIR model was used to estimate the time from 23 March 2020 until hospital capacity would probably be exceeded, and the intensity of the surge, including for intensive care unit (ICU) beds and ventilators. RESULTS: Using patients with COVID-19 alone, CHIME estimated that it would be 31 to 53 days before demand exceeds existing…

Background: Allogeneic hematopoietic cell transplantation is indicated for refractory hematologic cancer and some nonmalignant disorders. Survival is limited by recurrent cancer and organ toxicity. Objective: To determine whether survival has improved over the past decade and note impediments to better outcomes. Design: The authors compared cohorts that had transplants during 2003 to 2007 versus 2013 to 2017. Survival outcome measures were analyzed, along with transplant-related complications. Setting: A center performing allogeneic transplant procedures. Participants: All recipients of a first allogeneic transplant during 2003 to 2007 and 2013 to 2017. Intervention: Patients received a conditioning regimen, infusion of donor hematopoietic cells, then immunosuppressive drugs and antimicrobial approaches to infection control. Measurements: Day-200 nonrelapse mortality (NRM), recurrence or progression of cancer, relapse-related mortality, and overall mortality, adjusted for comorbidity scores, source of donor cells, donor type, patient age, disease severity, conditioning regimen,…

BACKGROUND: However, the clinical sequelae of PN have not been quantified in the general population. OBJECTIVE: To assess the associations of PN with all-cause and cardiovascular mortality in the general adult population of the United States. DESIGN: Prospective cohort study. SETTING: NHANES (National Health and Nutrition Examination Survey), 1999 to 2004. PARTICIPANTS: 7116 adults aged 40 years or older who had standardized monofilament testing for PN. MEASUREMENTS: Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality after adjustment for demographic and cardiovascular risk factors, overall and stratified by diabetes status. RESULTS: The overall prevalence of PN (±SE) was 13.5% ± 0.5% (27.0% ± 1.4% in adults with diabetes and 11.6% ± 0.5% in adults without diabetes). During a median follow-up of 13 years, 2128 participants died, including 488 of cardiovascular causes. Incidence rates (per 1000 person-years) of all-cause mortality were 57.6 (95% CI, 48.4 to 68.7) in adults with diabetes and PN, 34.3 (CI, 30.3 to 38.8) in adults with PN but no…

BACKGROUND: Financial payments from the drug industry to U.S. physicians are common. Payments may influence physicians' clinical decision making and drug prescribing. PURPOSE: To evaluate whether receipt of payments from the drug industry is associated with physician prescribing practices. DATA SOURCES: MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science, and EconLit were searched without language restrictions. The search had no limiting start date and concluded on 16 September 2020. STUDY SELECTION: Studies that estimated the association between receipt of industry payments (exposure) and prescribing (outcome). DATA EXTRACTION: Pairs of reviewers extracted the primary analysis or analyses from each study and evaluated risk of bias (ROB). DATA SYNTHESIS: = 6) had a mix of positive and null findings. No study had only null findings. Of 101 individual analyses, 89 identified a positive association. Payments were associated with increased prescribing of the paying company's drug, increased prescribing costs, and increased prescribing of branded drugs. Nine studies assessed and…

Letters10 August 2020Reduced In-Person and Increased Telehealth Outpatient Visits During the COVID-19 PandemicFREEAaron Baum, PhD, Peter J. Kaboli, MD, MS, and Mark D. Schwartz, MDAaron Baum, PhDIcahn School of Medicine at Mount Sinai and VA New York Harbor Healthcare System, New York, New York (A.B.)Search for more papers by this author, Peter J. Kaboli, MD, MSVeterans Rural Health Resource Center–Iowa City VA Office of Rural Health and Center for Access and Delivery Research and Evaluation, Iowa City VA Healthcare System, and University of Iowa Carver College of Medicine, Iowa City, Iowa (P.J.K.)Search for more papers by this author, and Mark D. Schwartz, MDVA New York Harbor Healthcare System and New York University School of Medicine, New York, New York (M.D.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-3026 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: During the coronavirus disease 2019 (COVID-19) pandemic,…

Background: The amount of time that providers spend using electronic health records (EHRs) to support the care delivery process is a concern for the U.S. health care system. Given the potential effect on patient care and the high costs related to this time, particularly for medical specialists whose work is largely cognitive, these findings warrant more precise documentation of the time physicians invest in these clinically focused EHR functions. Objective: To describe how much time ambulatory medical subspecialists and primary care physicians across several U.S. care delivery systems spend on various EHR functions. Design: Descriptive study. Setting: U.S.-based, adult, nonsurgical, ambulatory practices using the Cerner Millennium EHR. Participants: 155 000 U.S. physicians. Measurements: Data were extracted from software log files in the Lights On Network (Cerner) during 2018 that totaled the time spent on each of the 13 clinically focused EHR functions. Averages per encounter by specialty were computed. Results: This study included data from approximately 100 million patient…

BACKGROUND: Cost-effectiveness analysis is an important tool for informing treatment coverage and pricing decisions, yet no consensus exists about what threshold for the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life-year (QALY) gained indicates whether treatments are likely to be cost-effective in the United States. OBJECTIVE: To estimate a U.S. cost-effectiveness threshold based on health opportunity costs. DESIGN: Simulation of short-term mortality and morbidity attributable to persons dropping health insurance due to increased health care expenditures passed though as premium increases. Model inputs came from demographic data and the literature; 95% uncertainty intervals (UIs) were constructed. SETTING: Population-based. PARTICIPANTS: Simulated cohort of 100 000 individuals from the U.S. population with direct-purchase private health insurance. MEASUREMENTS: Number of persons dropping insurance coverage, number of additional deaths, and QALYs lost from increased mortality and morbidity, all per increase of $10 000 000 (2019 U.S. dollars) in…

BACKGROUND: The role of fecal aerosols in the transmission of severe acute respiratory syndrome coronavirus 2 has been suspected. OBJECTIVE: To investigate the temporal and spatial distributions of 3 infected families in a high-rise apartment building and examine the associated environmental variables to verify the role of fecal aerosols. DESIGN: Epidemiologic survey and quantitative reverse transcriptase polymerase chain reaction analyses on throat swabs from the participants; 237 surface and air samples from 11 of the 83 flats in the building, public areas, and building drainage systems; and tracer gas released into bathrooms as a surrogate for virus-laden aerosols in the drainage system. SETTING: A high-rise apartment building in Guangzhou, China. PARTICIPANTS: 9 infected patients, 193 other residents of the building, and 24 members of the building's management staff. MEASUREMENTS: Locations of infected flats and positive environmental samples, and spread of virus-laden aerosols. RESULTS: 9 infected patients in 3 families were identified. The first family had a history of travel…

Letters30 March 2020SARS-CoV-2–Positive Sputum and Feces After Conversion of Pharyngeal Samples in Patients With COVID-19FREEChen Chen, PhD, Guiju Gao, MD, Yanli Xu, MD, Lin Pu, MD, Qi Wang, MD, Liming Wang, PhD, Wenling Wang, PhD, Yangzi Song, MS, Meiling Chen, MS, Linghang Wang, MD, PhD, Fengting Yu, MS, Siyuan Yang, MS, Yunxia Tang, PhD, Li Zhao, PhD, Huijuan Wang, PhD, Yajie Wang, PhD, Hui Zeng, MD, PhD, and Fujie Zhang, MD, PhDChen Chen, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.), Guiju Gao, MDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.), Yanli Xu, MDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W.,…

Background: Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred. Objective: To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo. Design: Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333). Setting: North America. Participants: Adults with known cardiovascular disease and diabetes or metabolic syndrome. Intervention: Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week. Measurements: Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication. Results: After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a…

BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis.…

BACKGROUND: Risk factors for progression of coronavirus disease 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts. OBJECTIVE: To determine the factors on hospital admission that are predictive of severe disease or death from COVID-19. DESIGN: Retrospective cohort analysis. SETTING: Five hospitals in the Maryland and Washington, DC, area. PATIENTS: 832 consecutive COVID-19 admissions from 4 March to 24 April 2020, with follow-up through 27 June 2020. MEASUREMENTS: Patient trajectories and outcomes, categorized by using the World Health Organization COVID-19 disease severity scale. Primary outcomes were death and a composite of severe disease or death. RESULTS: Median patient age was 64 years (range, 1 to 108 years); 47% were women, 40% were Black, 16% were Latinx, and 21% were nursing home residents. Among all patients, 131 (16%) died and 694 (83%) were discharged (523 [63%] had mild to moderate disease and 171 [20%] had severe disease). Of deaths, 66 (50%) were nursing home residents. Of 787 patients admitted with mild to moderate disease, 302 (38%)…

BACKGROUND: Obesity is a risk factor for pneumonia and acute respiratory distress syndrome. OBJECTIVE: To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: A quaternary academic medical center and community hospital in New York City. PARTICIPANTS: 2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation. MEASUREMENTS: Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis. RESULTS: for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis. LIMITATIONS: Body mass index was missing for 28% of…

Ninety percent of health care systems now offer patient portals to access electronic health records (EHRs) in the United States, but only 15% to 30% of patients use these platforms. Using PubMed, the authors identified 53 studies published from September 2013 to June 2019 that informed best practices and priorities for future research on patient engagement with EHR data through patient portals, These studies mostly involved outpatient settings and fell into 3 major categories: interventions to increase use of patient portals, usability testing of portal interfaces, and documentation of patient and clinician barriers to portal use. Interventions that used one-on-one patient training were associated with the highest portal use. Patients with limited health or digital literacy faced challenges to portal use. Clinicians reported a lack of workflows to support patient use of portals in routine practice. These studies suggest that achieving higher rates of patient engagement through EHR portals will require paying more attention to the needs of diverse patients and systematically…

Abstract The blood pressure response of 48 hypertensive persons and 32 normotensive persons to elemental calcium (as the carbonate or citrate salt), 1000 mg/d for 8 weeks, was assessed in a randomi...

Background: Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain. Objective: To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy. Design: Retrospective cohort study. Setting: Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015. Patients: Adults with RA receiving a stable DMARD regimen for more than 6 months. Measurements: Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability–weighted analyses, with 1-year cumulative incidence predicted from weighted models. Results: 247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were…