The 50 most-cited articles in Annals of Internal Medicine, 2021

BACKGROUND: Asymptomatic infection seems to be a notable feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), but the prevalence is uncertain. PURPOSE: To estimate the proportion of persons infected with SARS-CoV-2 who never develop symptoms. DATA SOURCES: . STUDY SELECTION: Observational, descriptive studies and reports of mass screening for SARS-CoV-2 that were either cross-sectional or longitudinal in design; were published through 17 November 2020; and involved SARS-CoV-2 nucleic acid or antibody testing of a target population, regardless of current symptomatic status, over a defined period. DATA EXTRACTION: The authors collaboratively extracted data on the study design, type of testing performed, number of participants, criteria for determining symptomatic status, testing results, and setting. DATA SYNTHESIS: = 61 075), which suggest that at least one third of SARS-CoV-2 infections are asymptomatic. LIMITATION: For PCR-based studies, data are limited to distinguish presymptomatic from asymptomatic…

Most psychiatric care is delivered in primary care settings, where depression is the most common presenting psychiatric symptom. Given the high prevalence of depression worldwide and the well-established consequences of untreated depression, the ability of primary care clinicians to effectively diagnose and treat it is critically important. This article offers up-to-date guidance for the diagnosis and treatment of major depressive disorder, including practical considerations for delivering optimal and efficient care for these patients.

BACKGROUND: Individuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. METHODS: binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. RESULTS: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively…

Letters15 June 2021Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case SeriesFREEWilliam A. Werbel, MD, Brian J. Boyarsky, MD, PhD, Michael T. Ou, BS, Allan B. Massie, PhD, Aaron A.R. Tobian, MD, PhD, Jacqueline M. Garonzik-Wang, MD, PhD, and Dorry L. Segev, MD, PhDWilliam A. Werbel, MDJohns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this author, Brian J. Boyarsky, MD, PhDJohns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this author, Michael T. Ou, BSJohns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this author, Allan B. Massie, PhDJohns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this author, Aaron A.R. Tobian, MD, PhDJohns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this author, Jacqueline M. Garonzik-Wang, MD, PhDJohns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this author, and Dorry L.…

Comparative diagnostic test accuracy studies assess and compare the accuracy of 2 or more tests in the same study. Although these studies have the potential to yield reliable evidence regarding comparative accuracy, shortcomings in the design, conduct, and analysis may bias their results. The currently recommended quality assessment tool for diagnostic test accuracy studies, QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), is not designed for the assessment of test comparisons. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative) tool was developed as an extension of QUADAS-2 to assess the risk of bias in comparative diagnostic test accuracy studies. Through a 4-round Delphi study involving 24 international experts in test evaluation and a face-to-face consensus meeting, an initial version of the tool was developed that was revised and finalized following a pilot study among potential users. The QUADAS-C tool retains the same 4-domain structure of QUADAS-2 (Patient Selection, Index Test, Reference Standard, and Flow and Timing) and comprises…

Insomnia—the unwelcome experience of difficulty sleeping—is common and can be acute, intermittent, or chronic. Insomnia can be the presenting symptom for several common sleep disorders, but it also often occurs comorbidly with mental and physical health conditions. Evaluating the symptom of insomnia requires assessing—largely by history—whether an underlying condition explains it. Insomnia disorder is the diagnostic term for the symptom of insomnia that merits specific attention. Cognitive behavioral therapy for insomnia is the preferred treatment approach because of its efficacy, safety, and durability of benefit, but pharmaceutical treatments are widely used for insomnia symptoms.

BACKGROUND: The surge in background checks beginning in March 2020 suggested an acceleration in firearm purchases. Little was known about the people who bought these guns. OBJECTIVE: To estimate the number and describe characteristics of firearm purchasers over a period spanning prepandemic and pandemic time, characterize new gun owners, and estimate the number of persons newly exposed to household firearms. DESIGN: Probability-based online survey conducted in April 2021. Survey weights generated nationally representative estimates. SETTING: United States, 1 January 2019 to 26 April 2021. PARTICIPANTS: 19 049 of 29 985 (64%) English-speaking adults responded to the survey invitation; 5932 owned firearms, including 1933 who had purchased firearms since 2019, of whom 447 had become new gun owners. MEASUREMENTS: The estimated number and characteristics of adults who, since 2019, have purchased firearms, distinguishing those who became new gun owners from those who did not, and the estimated number of household members newly exposed to firearms. RESULTS: An estimated 2.9% of U.S. adults…

Abstract Importance Healthcare workers (HCW) are slated to be early recipients of SARS-CoV-2 vaccines due to increased risk of exposure to patients with COVID-19, and will be tasked with administering approved vaccines to the general population. As lynchpins of the vaccination effort, HCWs’ opinions of a vaccine’s safety and efficacy may affect both public perception and uptake of the vaccine. Therefore, it is crucial to understand and address potential hesitancy prior to vaccine administration. Objective To understand healthcare workers’ attitudes about vaccine safety, efficacy, and acceptability in the context of the COVID-19 pandemic, including acceptance of a novel coronavirus vaccine. Design, Setting, Participants A cross-sectional survey was distributed to participants enrolled in a longitudinal cohort study surveilling SARS-CoV-2 infection among 1,093 volunteer sampled University of California, Los Angeles (UCLA) Health System employees. Surveys were completed online between September 24 and October 16, 2020. In total, 609 participants completed this supplemental survey.…

LettersFebruary 2021Prevalence of Asymptomatic SARS-CoV-2 InfectionFREEDaniel P. Oran, AM, Eric J. Topol, MDDaniel P. Oran, AMScripps Research Translational Institute, Scripps Research La Jolla, CaliforniaSearch for more papers by this author, Eric J. Topol, MDScripps Research Translational Institute, Scripps Research La Jolla, CaliforniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-1285 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:In our view, Dr. Halperin does not fairly characterize the evidence of asymptomatic transmission presented by Lavezzo and colleagues (1) concerning their research in Vo’, Italy. Lavezzo and colleagues state, “The presence of a significant number of asymptomatic SARS-CoV-2 infections raises questions about their ability to transmit the virus. To address this issue, we conducted an extensive contact tracing analysis of the 8 new infections.” After describing the various contacts of the…

BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to…

Pulmonary hypertension is the term used to describe a group of disorders characterized by abnormally high pressures in the pulmonary arteries. Initial evaluation is focused on identifying the cause, which helps guide appropriate treatment. Pulmonary hypertension is often a feature of advanced common diseases, such as chronic obstructive pulmonary disease and left heart disease, and treatment is focused primarily on the underlying disease. More rarely, pulmonary hypertension results from chronic organized thromboemboli or a primary vasculopathy. The former requires evaluation for surgical intervention, and the latter is treated with advanced medical therapies.

BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups.…

Abstract Background Preliminary evidence has shown inequities in COVID-19 related cases and deaths in the US. Objective We explored the emergence of spatial inequities in COVID-19 testing, positivity, confirmed cases, and mortality in New York City, Philadelphia, and Chicago during the first six months of the pandemic. Design Ecological, observational study at the zip code tabulation area (ZCTA) level from March to September 2020. Setting Chicago, New York City and Philadelphia. Participants All populated ZCTAs in the three cities. Measures Outcomes were ZCTA-level COVID-19 testing, positivity, confirmed cases, and mortality cumulatively through the end of September. Predictors were the CDC social vulnerability index and its four domains, obtained from the 2014-2018 American Community Survey. We examined the spatial autocorrelation of COVID-19 outcomes using global and local Moran’s I and estimated associations using spatial conditional autoregressive negative binomial models. Results We found spatial clusters of high and low positivity, confirmed cases and mortality, co-located…

BACKGROUND: Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE: To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and outcomes. DESIGN: Retrospective cohort study (1 February 2020 to 31 May 2020). SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: Adult health plan members. MEASUREMENTS: Age, sex, neighborhood deprivation index, comorbid conditions, acute physiology indices, and race/ethnicity; SARS-CoV-2 testing and incidence of positive test results; and hospitalization, illness severity, and mortality. RESULTS: Among 3 481 716 eligible members, 42.0% were White, 6.4% African American, 19.9% Hispanic, and 18.6% Asian; 13.0% were of other or unknown race. Of eligible members, 91 212 (2.6%) were tested for SARS-CoV-2 infection and 3686 had positive results (overall incidence, 105.9 per 100 000 persons; by racial group, White, 55.1; African American, 123.1; Hispanic, 219.6; Asian, 111.7; other/unknown, 79.3). African American persons had the…

BACKGROUND: Nasopharyngeal swabs are the primary sampling method used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but they require a trained health care professional and extensive personal protective equipment. PURPOSE: To determine the difference in sensitivity for SARS-CoV-2 detection between nasopharyngeal swabs and saliva and estimate the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs. DATA SOURCES: Embase, Medline, medRxiv, and bioRxiv were searched from 1 January to 1 November 2020. Cost inputs were from nationally representative sources in Canada and were converted to 2020 U.S. dollars. STUDY SELECTION: Studies including at least 5 paired nasopharyngeal swab and saliva samples and reporting diagnostic accuracy for SARS-CoV-2 detection. DATA EXTRACTION: Data were independently extracted using standardized forms, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). DATA SYNTHESIS: Thirty-seven studies with 7332 paired samples were included. Against a…

Background: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness. Objective: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE. Design: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003) Setting: England. Participants: Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019. Intervention: Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks. Measurements: The prespecified primary end point was serum IgG anti–double-stranded DNA…

Low back pain is a common problem that is the leading cause of disability and is associated with high costs. Evaluation focuses on identification of risk factors indicating a serious underlying condition and increased risk for persistent disabling symptoms in order to guide selective use of diagnostic testing (including imaging) and treatments. Nonpharmacologic therapies, including exercise and psychosocial management, are preferred for most patients with low back pain and may be supplemented with adjunctive drug therapies. Surgery and interventional procedures are options in a minority of patients who do not respond to standard treatments.

BACKGROUND: With millions of SARS-CoV-2 infections worldwide, increasing numbers of patients are coming forward with long-term clinical effects of the disease lasting several weeks to months. OBJECTIVE: To characterize symptoms 7 to 9 months after diagnosis of COVID-19. DESIGN: Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis. SETTING: From 18 March to 15 May 2020, symptomatic persons who tested positive for SARS-CoV-2 at the Geneva University Hospitals were followed by CoviCare, a virtual, clinical, outpatient follow-up program. Persons were contacted again at 30 to 45 days and 7 to 9 months from diagnosis. PARTICIPANTS: Persons who were a part of the CoviCare program from 18 March to 15 May 2020. MEASUREMENTS: A standardized interview of symptoms consistent with COVID-19, with grading of intensity. RESULTS: Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the…

BACKGROUND: The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. PURPOSE: To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. STUDY SELECTION: Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. DATA EXTRACTION: Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. DATA SYNTHESIS: Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received…

Background: Recipients of solid organ transplant (SOT) are a high-risk group for severe SARS-CoV-2 infection. The mortality rate of patients with SOT during the COVID-19 pandemic has been reported to be approximately 20% (1). The anti–SARS-CoV-2 vaccines represent a hope to protect this population against this life-threatening infection.Objective: To assess the humoral response to messenger RNA (mRNA)–based vaccination in recipients of SOT.Methods: All patients with heart, kidney, liver, or pancreas transplants from the Midi-Pyrénées region (southwest France) are followed in our department. When the vaccination campaign started (7 January 2021), these patients were invited via text message, e-mail, or transplant patients' associations to be vaccinated. Patients were asked to register via a dedicated telephone number or website. They were vaccinated consecutively according to their registration date. According to the recommendations of the Francophone Society of Transplantation, anti–SARS-CoV-2 spike protein antibodies were monitored before and after vaccination. We used the…

Background: Delivering hospital-level care with comprehensive geriatric assessment (CGA) in the home is one approach to deal with the increased demand for bed-based hospital care, but clinical effectiveness is uncertain. Objective: To assess the clinical effectiveness of admission avoidance hospital at home (HAH) with CGA for older persons. Design: Multisite randomized trial. (ISRCTN registry number: ISRCTN60477865) Setting: 9 hospital and community sites in the United Kingdom. Patients: 1055 older persons who were medically unwell, were physiologically stable, and were referred for a hospital admission. Intervention: Admission avoidance HAH with CGA versus hospital admission with CGA when available using 2:1 randomization. Measurements: The primary outcome of living at home was measured at 6 months. Secondary outcomes were new admission to long-term residential care, death, health status, delirium, and patient satisfaction. Results: Participants had a mean age of 83.3 years (SD, 7.0). At 6-month follow-up, 528 of 672 (78.6%) participants in the CGA HAH group versus 247 of 328…

BACKGROUND: Although racial/ethnic disparities in U.S. COVID-19 death rates are striking, focusing on COVID-19 deaths alone may underestimate the true effect of the pandemic on disparities. Excess death estimates capture deaths both directly and indirectly caused by COVID-19. OBJECTIVE: To estimate U.S. excess deaths by racial/ethnic group. DESIGN: Surveillance study. SETTING: United States. PARTICIPANTS: All decedents. MEASUREMENTS: Excess deaths and excess deaths per 100 000 persons from March to December 2020 were estimated by race/ethnicity, sex, age group, and cause of death, using provisional death certificate data from the Centers for Disease Control and Prevention (CDC) and U.S. Census Bureau population estimates. RESULTS: An estimated 2.88 million deaths occurred between March and December 2020. Compared with the number of expected deaths based on 2019 data, 477 200 excess deaths occurred during this period, with 74% attributed to COVID-19. Age-standardized excess deaths per 100 000 persons among Black, American Indian/Alaska Native (AI/AN), and Latino males and females…

Many groundbreaking advances have occurred in the field of multiple sclerosis since this series last reviewed the disorder in 2014. The U.S. Food and Drug Administration has approved 7 new medications for relapsing-remitting multiple sclerosis and approved the first medication for primary progressive multiple sclerosis. The McDonald criteria for diagnosing multiple sclerosis were updated in 2017. New blood tests can now differentiate patients with multiple sclerosis from those with neuromyelitis optica spectrum disorder, and 3 new medications have been approved specifically for the latter disorder. Also, new medications for treating the symptoms of multiple sclerosis have been introduced.

BACKGROUND: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain. OBJECTIVE: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF. DESIGN: Cohort study. SETTING: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland. PARTICIPANTS: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer. MEASUREMENTS: tests. RESULTS: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7…

BACKGROUND: Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals. OBJECTIVE: To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Patients and staff with cluster-related SARS-CoV-2 infections. INTERVENTION: Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing. A case-control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2-positive versus negative staff. MEASUREMENTS: Description of the cluster, mitigation activities, and risk factor analysis. RESULTS: Fourteen patients and 38 staff members were…

Background: Lung cancer is the leading cause of cancer death worldwide, and about one half of patients with lung cancer are active smokers at diagnosis. Objective: To determine whether quitting smoking after diagnosis of lung cancer affects the risk for disease progression and mortality. Design: Prospective study of patients with non–small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020. Setting: N.N. Blokhin National Medical Research Center of Oncology and City Clinical Oncological Hospital No. 1, Moscow, Russia. Patients: 517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC. Measurements: Probabilities of overall survival, progression-free survival, and lung cancer–specific mortality and hazard ratios (HRs) for all-cause and cancer-specific mortality. Results: During an average of 7 years of follow-up, 327 (63.2%) deaths, 273 (52.8%) cancer-specific deaths, and 172 (33.7%) cases of tumor progression (local recurrence or metastasis) were recorded. The adjusted median overall survival time was 21.6 months higher…

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239…

Acute pancreatitis is one of the most common reasons for gastroenterology-related hospitalization in the United States. With significant morbidity and subsequent mortality related to both the acute presentation and subsequent sequelae, prompt diagnosis and appropriate management are critical, especially in the first 24 hours of illness. It is also important to accurately recognize complications, such as pancreatic fluid collections and vascular events, and identify a definitive cause so that a strategy to prevent future attacks can be implemented.

Background: The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. Objective: To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. Design: 1:1 propensity score–matched analysis of Medicare data, 2010 to 2017. Setting: Community. Patients: Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin. Measurements: Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index. Results: In the dabigatran–warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], −2.2 [CI, −6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban–warfarin cohort (n = 275 944; median…

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of point-of-care ultrasonography (POCUS) in patients with acute dyspnea in emergency department (ED) or inpatient settings to improve the diagnostic, treatment, and health outcomes of those with suspected congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax. METHODS: The ACP Clinical Guidelines Committee based this guideline on a systematic review on the benefits, harms, and diagnostic test accuracy of POCUS; patient values and preferences; and costs of POCUS. The systematic review evaluated health outcomes, diagnostic timeliness, treatment decisions, and test accuracy. The critical health, diagnostic, and treatment outcomes evaluated were in-hospital mortality, time to diagnosis, and time to treatment. The important outcomes evaluated were intensive care unit admissions, correctness of diagnosis, disease-specific outcomes, hospital readmissions, length of hospital stay, and quality of life. The critical test…

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during…

BACKGROUND: The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear. PURPOSE: To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity. DATA SOURCES: MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English. STUDY SELECTION: Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with…

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. OBJECTIVE: To describe the epidemiology of COVID-19-related critical illness, including trends in outcomes and care delivery. DESIGN: Single-health system, multihospital retrospective cohort study. SETTING: 5 hospitals within the University of Pennsylvania Health System. PATIENTS: Adults with COVID-19-related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. MEASUREMENTS: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. RESULTS: Among 468 patients with COVID-19-related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a…

SOURCE CITATION: N Engl J Med. 2020;383:2603-15. 33301246.

LettersOctober 2021Thrombosis With Thrombocytopenia After the Messenger RNA–1273 VaccineFREESwathi Sangli, MBBS, Ahmed Virani, MD, Nicholas Cheronis, MD, Brittany Vannatter, DO, Corbyn Minich, DO, Shaun Noronha, MBBS, Rama Bhagavatula, MD, Daniel Speredelozzi, MD, Meera Sareen, MD, and Robert B. Kaplan, MDSwathi Sangli, MBBSAllegheny Health Network, Pittsburgh, Pennsylvania, Ahmed Virani, MDAllegheny Health Network, Pittsburgh, Pennsylvania, Nicholas Cheronis, MDAllegheny Health Network, Pittsburgh, Pennsylvania, Brittany Vannatter, DOAllegheny Health Network, Pittsburgh, Pennsylvania, Corbyn Minich, DOAllegheny Health Network, Pittsburgh, Pennsylvania, Shaun Noronha, MBBSAllegheny Health Network, Pittsburgh, Pennsylvania, Rama Bhagavatula, MDAllegheny Health Network, Pittsburgh, Pennsylvania, Daniel Speredelozzi, MDAllegheny Health Network, Pittsburgh, Pennsylvania, Meera Sareen, MDAllegheny Health Network, Pittsburgh, Pennsylvania, and Robert B. Kaplan, MDAllegheny Health Network, Pittsburgh, PennsylvaniaAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0244…

BACKGROUND: With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting. OBJECTIVE: To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection. DESIGN: Test-negative case-control study using conditional logistic regression. SETTING: U.S. Department of Veterans Affairs health care system. PARTICIPANTS: All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020. INTERVENTION: SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care. MEASUREMENTS: Effectiveness of vaccination against confirmed SARS-CoV-2 infection. RESULTS: among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%).…

Background: Hospitalized patients with comorbid substance use disorders (SUDs) are at high risk for poor outcomes, including readmission and emergency department (ED) use. Objective: To determine whether patient navigation services reduce hospital readmissions. Design: Randomized controlled trial comparing Navigation Services to Avoid Rehospitalization (NavSTAR) versus treatment as usual (TAU). (ClinicalTrials.gov: NCT02599818) Setting: Urban academic hospital in Baltimore, Maryland, with an SUD consultation service. Participants: 400 hospitalized adults with comorbid SUD (opioid, cocaine, or alcohol). Intervention: NavSTAR used proactive case management, advocacy, service linkage, and motivational support to resolve internal and external barriers to care and address SUD, medical, and basic needs for 3 months after discharge. Measurements: Data on inpatient readmissions (primary outcome) and ED visits for 12 months were obtained for all participants via the regional health information exchange. Entry into SUD treatment, substance use, and related outcomes were assessed at 3-, 6-,…

Background: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. Objective: To assess the long-term efficacy of acupuncture for CP/CPPS. Design: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938) Setting: Ten tertiary hospitals in China. Participants: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. Intervention: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. Measurements: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. Results: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in…

Description: Antimicrobial overuse is a major health care issue that contributes to antibiotic resistance. Such overuse includes unnecessarily long durations of antibiotic therapy in patients with common bacterial infections, such as acute bronchitis with chronic obstructive pulmonary disease (COPD) exacerbation, community-acquired pneumonia (CAP), urinary tract infections (UTIs), and cellulitis. This article describes best practices for prescribing appropriate and short-duration antibiotic therapy for patients presenting with these infections. Methods: The authors conducted a narrative literature review of published clinical guidelines, systematic reviews, and individual studies that addressed bronchitis with COPD exacerbations, CAP, UTIs, and cellulitis. This article is based on the best available evidence but was not a formal systematic review. Guidance was prioritized to the highest available level of synthesized evidence. Best Practice Advice 1: Clinicians should limit antibiotic treatment duration to 5 days when managing patients with COPD exacerbations and acute uncomplicated…

BACKGROUND: Scalable knee osteoarthritis programs are needed to deliver recommended education, exercise, and weight loss interventions. OBJECTIVE: To evaluate two 6-month, telehealth-delivered exercise programs, 1 with and 1 without dietary intervention. DESIGN: 3-group, parallel randomized (5:5:2) trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000930280). SETTING: Australian private health insurance members. PARTICIPANTS: who were aged 45 to 80 years. INTERVENTION: All groups received access to electronic osteoarthritis information (control). The exercise program comprised 6 physiotherapist consultations via videoconference for exercise, self-management advice, and behavioral counseling, plus exercise equipment and resources. The diet and exercise program included an additional 6 dietitian consultations for a ketogenic very-low-calorie diet (2 formulated meal replacements and a low-carbohydrate meal daily) followed by a transition to healthy eating, as well as nutrition and behavioral resources. MEASUREMENTS: Primary outcomes were changes in knee pain (numerical…

BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). OBJECTIVE: To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD. DESIGN: Population-based cohort study. SETTING: Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017). PARTICIPANTS: 1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy. MEASUREMENTS: Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates. RESULTS: The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated…

Background: Autonomous cortisol secretion in patients with adrenal incidentalomas is associated with increased mortality, but detailed information about the risk associated with specific levels of autonomous cortisol secretion is not available. Objective: To measure the association between mortality and levels of autonomous cortisol secretion in patients with adrenal incidentalomas. Design: Retrospective cohort study. (ClinicalTrials.gov: NCT03919734) Setting: Two hospitals in southern Sweden. Patients: Consecutive patients who had adrenal incidentalomas identified between 2005 and 2015 and were followed for up to 14 years. Outcome data were collected from national registers. Measurements: Patients were grouped according to plasma cortisol level after a 1-mg dexamethasone suppression test (cortisolDST; <50, 50 to 82, 83 to 137, or ≥138 nmol/L). Results: During a median follow-up of 6.4 years, 170 of 1048 patients died. Compared with a cortisolDST less than 50 nmol/L, a cortisolDST of 50 to 82 nmol/L was not associated with increased mortality (hazard ratio [HR], 1.15 [95% CI, 0.78…

BACKGROUND: Identifying occupational risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs) can improve HCW and patient safety. OBJECTIVE: To quantify demographic, occupational, and community risk factors for SARS-CoV-2 seropositivity among HCWs in a large health care system. DESIGN: A logistic regression model was fitted to data from a cross-sectional survey conducted in April to June 2020, linking risk factors for occupational and community exposure to coronavirus disease 2019 (COVID-19) with SARS-CoV-2 seropositivity. SETTING: A large academic health care system in the Atlanta, Georgia, metropolitan area. PARTICIPANTS: Employees and medical staff members elected to participate in SARS-CoV-2 serology testing offered to all HCWs as part of a quality initiative and completed a survey on exposure to COVID-19 and use of personal protective equipment. MEASUREMENTS: Demographic risk factors for COVID-19, residential ZIP code incidence of COVID-19, occupational exposure to HCWs or patients who tested positive on polymerase…

Background: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials. Objective: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID. Design: Nationwide cohort study. Setting: The Netherlands. Patients: 4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019. Measurements: Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival. Results: A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or “other” (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti–cytotoxic T lymphocyte–associated protein 4 (CTLA-4), 187 with anti–programmed cell death 1 (PD-1), and 34 with the…

Letters12 January 2021Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort StudyFREEBjörn Pasternak, MD, PhD, Martin Neovius, PhD, Jonas Söderling, PhD, Mia Ahlberg, RNM, PhD, Mikael Norman, MD, PhD, Jonas F. Ludvigsson, MD, PhD, and Olof Stephansson, MD, PhDBjörn Pasternak, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Martin Neovius, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Jonas Söderling, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Mia Ahlberg, RNM, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Mikael Norman, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Jonas F. Ludvigsson, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, and Olof Stephansson, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-6367…

BACKGROUND: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited. OBJECTIVE: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban. DESIGN: Nationwide population-based cohort study. SETTING: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland. PATIENTS: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. MEASUREMENTS: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression. RESULTS: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had…

Sickle cell disease is an umbrella term for a group of hemoglobinopathies characterized by the presence of 2 β-globin gene mutations or deletions, at least 1 of which is the point mutation that leads to the production of hemoglobin S. Sickle cell disease is associated with hemolytic anemia, significant chronic end-organ damage, and early death. In high-income countries, at least 95% of children with the disease survive into adulthood, resulting in a growing population of affected adults with significant comorbidities, complex medical issues, and not enough specialists to provide care. Hydroxyurea is the primary therapy, and recent advances in understanding disease pathophysiology have led to new therapies; progress in bone marrow transplant and gene editing has resulted in cure in some patients. The purpose of this review is to provide an overview of the diagnosis, common acute and chronic clinical manifestations, and best practices for management of sickle cell disease.

BACKGROUND: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. PURPOSE: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. DATA SOURCES: MEDLINE from 1 January 1995 until 1 January 2021. STUDY SELECTION: 16 studies assessing at least 1 diagnostic strategy. DATA EXTRACTION: Individual-patient data from 20 553 patients. DATA SYNTHESIS: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However,…

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were…