Showing papers in "Annals of Internal Medicine in 2022"

Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments

Abstract: Background: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. Objective: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). Design: Retrospective chart reviews. Setting: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. Patients: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. Measurements: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. Results: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [−26.5 to −17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). Limitation: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. Conclusion: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. Primary Funding Source: None.

Detection of Monkeypox Virus in Anorectal Swabs From Asymptomatic Men Who Have Sex With Men in a Sexually Transmitted Infection Screening Program in Paris, France

Abstract: Letters16 August 2022Detection of Monkeypox Virus in Anorectal Swabs From Asymptomatic Men Who Have Sex With Men in a Sexually Transmitted Infection Screening Program in Paris, FranceFREEValentine Marie Ferré, PharmD, Antoine Bachelard, MD, Meryem Zaidi, BSc, Laurence Armand-Lefevre, PharmD, PhD, Diane Descamps, MD, PhD, Charlotte Charpentier, PharmD, PhD, and Jade Ghosn, MD, PhDValentine Marie Ferré, PharmDService de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (V.M.F., M.Z., D.D., C.C.)Search for more papers by this author, Antoine Bachelard, MDService de Maladies Infectieuses et Tropicales, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (A.B., J.G.)Search for more papers by this author, Meryem Zaidi, BScService de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (V.M.F., M.Z., D.D., C.C.)Search for more papers by this author, Laurence Armand-Lefevre, PharmD, PhDService de Bactériologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (L.A.)Search for more papers by this author, Diane Descamps, MD, PhDService de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (V.M.F., M.Z., D.D., C.C.)Search for more papers by this author, Charlotte Charpentier, PharmD, PhDService de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (V.M.F., M.Z., D.D., C.C.)Search for more papers by this author, and Jade Ghosn, MD, PhDService de Maladies Infectieuses et Tropicales, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (A.B., J.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-2183 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: A monkeypox virus (MPXV) outbreak emerged in May 2022, affecting mostly men who have sex with men (MSM). Although most infections were characterized by cutaneous lesions, a recent report described 3 asymptomatic men with no cutaneous lesions but with positive results on anorectal MPXV polymerase chain reaction (PCR) testing (1). Determining whether MPXV infection can be asymptomatic may better inform epidemic management.Objective: To assess the presence of MPXV in anorectal samples among asymptomatic MSM routinely tested for bacterial sexually transmitted infections (2).Methods and Findings: We retrospectively performed testing for MPXV on all anorectal swabs that were collected in our center as part of a screening program for Neisseria gonorrhoeae and Chlamydia trachomatis. Per French guidelines, this screening is performed every 3 months among MSM with multiple sexual partners who are either taking HIV preexposure prophylaxis (PrEP) or living with HIV and receiving antiretroviral treatment (2). Patients could have urine samples and anal swabs collected at our clinic or a private laboratory. After the first case of MPXV infection was identified in France on 19 May 2022, screening was halted in patients who had lesions suspicious for MPXV (3). We report on asymptomatic MSM who tested negative for N gonorrhoeae and C trachomatis on MPXV anal swabs collected at the Infectious Disease Department and the Sexual Health Clinic of Bichat-Claude Bernard Hospital in Paris, France, from 5 June to 11 July 2022. All participants attended a clinical visit on the day of sampling as part of routine PrEP or HIV treatment follow-up. Participants gave written informed consent to have their data recorded in Nadis (www.dataids.org; Fedialis Medica, CNIL number 1171457 [24 May 2006]), an electronic medical record designed for follow-up of persons living with HIV or receiving HIV PrEP and use of their data for research. The local review board did not require specific consent to use remnant routine biological samples in the setting of the MPXV epidemic.After heat inactivation (12 minutes at 70 °C), nucleic acids were extracted using a STARMag 96 X 4 Universal Cartridge Kit (Seegene) on the MICROLAB NIMBUS system (Seegene). MPXV-specific PCR was performed using a previously published protocol (4).During the study period, 706 MSM visited our clinic, 383 had symptoms suggestive of MPXV infection (40% had anal lesions), and MPXV infection was confirmed in 271 of those with symptoms (Table). Screening for C trachomatis and N gonorrhoeae infection was not performed when MPXV infection was suspected because of laboratory biosafety restrictions (5). Of the 706 MSM, 323 had no MPXV symptoms, and 213 had anal swabs collected and were negative for C trachomatis and N gonorrhoeae (Table). Among these 213 MSM, the median age was 38 years (IQR, 29 to 48 years), and 110 (52%) were living with HIV and receiving antiretroviral therapy, with a median of 9 years (IQR, 4 to 18 years) since diagnosis. Among those with HIV, 78% had undetectable viral load (median viral load was 74 copies/mL [IQR, 37 to 2270 copies/mL] in the others), and the median last CD4 T-cell count was 0.766 × 109 cells/L (IQR, 0.560 to 1.001 × 109 cells/L).Table. Screening for Sexually Transmitted Infections and MPXV Infection in 706 MSM Visiting the Sexual Health Clinic Between 5 June and 11 July 2022MPXV PCR was successfully performed on 200 of 213 anal swabs and was positive in 13 (6.5%). Of those testing positive, 8 were living with HIV; all had undetectable HIV-1 viral load, and all had a CD4 T-cell count above 0.500 × 109 cells/L, except 1 who had a CD4 T-cell count of 0.123 × 109 cells/L. We contacted all 13 MPXV-positive participants who were initially asymptomatic to assess symptom status and advised them to limit sexual activity for 21 days after the test date and to notify their recent sexual partners. None reported symptoms suggestive of MPXV infection, but 2 subsequently presented to our clinic with symptoms. One had a cycle threshold (Ct) value of 20.7 on PCR of the sample taken during the asymptomatic stage and a Ct value of 33.0 seven days later, when he presented with anal rash. The other presented with pharyngitis and fever but no anal symptoms; PCR on the anal swab taken during the asymptomatic phase showed a Ct value of 38.2, and PCR on a pharyngeal swab 9 days later showed a Ct value of 24.Of the 187 asymptomatic participants who tested negative for MPXV, 3 presented to our clinic more than 3 weeks after the initial MPXV-negative anal swab with symptoms suggestive of MPXV infection and tested positive.Discussion: This report documents positive MPXV PCR results from anal samples in asymptomatic MSM. Whether this indicates viral shedding that can lead to transmission is unknown. If so, the practice of ring postexposure vaccination around symptomatic persons with probable or confirmed MPXV infection may not be sufficient to contain spread. Recent French recommendations have advised vaccination for all MSM with multiple partners (5).References1. De Baetselier I, Van Dijck C, Kenyon C, et al. Asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium. Preprints with The Lancet. Preprint posted online 21 June 2022. doi:10.2139/ssrn.4142074 CrossrefGoogle Scholar2. Conseil National du Sida et des Hépatites Virales; Agence Autonome de l'Inserm. Medical Care for People Living with HIV: Recommendations from Expert Group. April 2018. Accessed at https://cns.sante.fr/wp-content/uploads/2018/05/experts-vih_suivi.pdf on 13 July 2022. Google Scholar3. Société Française de Microbiologie. Gestion des prélèvements biologiques d'un patient suspect ou confirmé d'infection par le Monkeypox virus (MPXV). Version 1_MAJ. 11 June 2022. Google Scholar4. Li Y, Zhao H, Wilkins K, et al. Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA. J Virol Methods. 2010;169:223-7. [PMID: 20643162] doi:10.1016/j.jviromet.2010.07.012 CrossrefMedlineGoogle Scholar5. General directorate of health. Monkeypox – evolution de la conduite a tenir, elargissement de la vaccination et mise a disposition du tecovirimat. 8 July 2022. Accessed at https://solidarites-sante.gouv.fr/IMG/pdf/_corruss_dgs-urgent_n2022_65_avis_has.pdf on 13 July 2022. Google Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Service de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (V.M.F., M.Z., D.D., C.C.)Service de Maladies Infectieuses et Tropicales, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (A.B., J.G.)Service de Bactériologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP.Nord, Hôpital Bichat-Claude Bernard, Paris, France (L.A.)* Professor Charpentier and Professor Ghosn contributed equally to this work.See Also: Editorial commentDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-2183.Reproducible Research Statement: Study protocol, statistical code, and data set: Not available.Corresponding Author: Charlotte Charpentier, PharmD, PhD, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, 46 Rue Henri Huchard, 75018 Paris, France; e-mail, charlotte.[email protected]fr.This article was published at Annals.org on 16 August 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals of Internal Medicine16 Aug 2022Asymptomatic Infection? Another Reason to Consider Monkeypox a Disease of Public Health Concern Stuart N. Isaacs Metrics Cited ByAsymptomatic Infection? Another Reason to Consider Monkeypox a Disease of Public Health ConcernStuart N. Isaacs, MD LatestKeywordsChlamydia trachomatisHIVLesionsMale male sexual contactMonkeypoxPreexposure prophylaxisSexually transmitted diseasesSkin infections CopyrightCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...

Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus Vaccine

Abstract: Case reports of carditis after BNT162b2 vaccination are accruing worldwide.To examine the association of BNT162b2 and CoronaVac (Sinovac) vaccination with carditis.Case-control study with hospital control participants.Territory-wide, public health care database with linkage to population-based vaccination records in Hong Kong.Inpatients aged 12 years or older first diagnosed with carditis were selected as case patients. All other hospitalized patients without carditis were treated as control participants. Ten control participants were randomly matched with each case patient by age, sex, and admission date.Vaccination with BNT162b2 or CoronaVac.Incident diagnosis of carditis based on the International Classification of Diseases, Ninth Revision, and elevated troponin levels.A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. Subanalysis showed an OR of 9.29 (CI, 3.94 to 21.91) for myocarditis and 1.06 (CI, 0.35 to 3.22) for pericarditis associated with BNT162b2. The risk was mainly seen after the second dose of BNT162b2 rather than the first. No association between CoronaVac and carditis with a magnitude similar to that for BNT162b2 was seen.Limited sample size, absence of electrocardiography and other clinical investigative data, and unrecorded overseas vaccination exposure.Despite a low absolute risk, there is an increased risk for carditis associated with BNT162b2 vaccination. This elevated risk should be weighed against the benefits of vaccination.Health and Medical Research Fund.

Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination—United States, December 2020 to August 2021

Abstract: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described.To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States.Case series.United States.Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required.Reporting rates (cases per million vaccine doses) and descriptive epidemiology.A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%).Underreporting and incomplete case follow-up.Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate.Centers for Disease Control and Prevention.

Firearm Purchasing During the COVID-19 Pandemic: Results From the 2021 National Firearms Survey

Abstract: 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.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.Probability-based online survey conducted in April 2021. Survey weights generated nationally representative estimates.United States, 1 January 2019 to 26 April 2021.19 049 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.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.An estimated 2.9% of U.S. adults (7.5 million) became new gun owners from 1 January 2019 to 26 April 2021. Most (5.4 million) had lived in homes without guns, collectively exposing, in addition to themselves, over 11 million persons to household firearms, including more than 5 million children. Approximately half of all new gun owners were female (50% in 2019 and 47% in 2020 to 2021), 20% were Black (21% in 2019 and in 2020-2021), and 20% were Hispanic (20% in 2019 and 19% in 2020-2021). By contrast, other recent purchasers who were not new gun owners were predominantly male (70%) and White (74%), as were gun owners overall (63% male, 73% White).Retrospective assessment of when respondents purchased firearms. National estimates about new gun owners were based on 447 respondents.Efforts to reduce firearm injury should consider the recent acceleration in firearm purchasing and the characteristics of new gun owners.The Joyce Foundation.

A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings

Abstract: Background: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). Objective: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. Design: Cohort study. (ClinicalTrials.gov: NCT04411147) Setting: National Institutes of Health Clinical Center, Bethesda, Maryland. Participants: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. Measurements: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. Results: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. Limitations: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. Conclusion: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. Primary Funding Source: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Effectiveness of Inactivated COVID-19 Vaccines Against Illness Caused by the B.1.617.2 (Delta) Variant During an Outbreak in Guangdong, China

Abstract: Real-world evidence on inactivated COVID-19 vaccines against the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2 is limited, leaving an important gap in the evidence base about inactivated COVID-19 vaccines for use by immunization programs.To estimate inactivated vaccine effectiveness (VE) against the B.1.617.2 variant.Retrospective cohort study.The study was based on the first outbreak of the B.1.617.2 variant in mainland China that was discovered and traced in Guangdong in May and June 2021.10 805 adult case patients with laboratory-confirmed infection and close contacts.Participants were categorized as unvaccinated, partially vaccinated (1 dose), and fully vaccinated (2 doses). We estimated VE against the primary outcome of pneumonia and the secondary outcomes of infections, symptomatic infections, and severe or critical illness associated with the B.1.617.2 variant.Results are reported in the order of outcome severity. Of 10 805 participants, 1.3% contracted infections, 1.2% developed symptomatic infections, 1.1% had pneumonia, and 0.2% had severe or critical illness. The adjusted VEs of full vaccination were 51.8% (95% CI, 20.3% to 83.2%) against infection, 60.4% (CI, 31.8% to 88.9%) against symptomatic infection, and 78.4% (CI, 56.9% to 99.9%) against pneumonia. Also, full vaccination was 100% (CI, 98.4% to 100.0%) effective against severe or critical illness. By contrast, the adjusted VEs of partial vaccination against infection, symptomatic infection, and pneumonia were 10.7% (CI, -41.2% to 62.6%), 6.8% (CI, -47.4% to 61.0%), and 11.6% (CI, -42.6% to 65.8%), respectively.Observational study with possible unmeasured confounders; insufficient data to do reliable subgroup analyses by age and vaccine brand.Full vaccination with inactivated vaccines is effective against the B.1.617.2 variant. Effort should be made to ensure full vaccination of target populations.National Natural Science Foundation of China and Key-Area Research and Development Program of Guangdong Province.

SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis

Abstract: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear.To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination.Prospective study.Nationwide sample from dialysis facilities.4791 patients receiving dialysis.Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence.Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively).Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records.The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection.Ascend Clinical Laboratory.

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels

Abstract: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment.To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high.Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978).Multicenter trial.Hospitalized patients with COVID-19 without end-organ failure.Bamlanivimab (7000 mg) or placebo.Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections).Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs.Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed.Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting.U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Comparison of SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction and BinaxNOW Rapid Antigen Tests at a Community Site During an Omicron Surge

Abstract: Background: SARS-CoV-2 rapid antigen tests are an important public health tool. Objective: To evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2. Design: Cross-sectional surveillance study. Setting: Free, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19. Participants: Persons seeking COVID-19 testing in January 2022. Measurements: Simultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus. Results: Among 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either. Limitation: Participants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics. Conclusion: BinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing. Primary Funding Source: University of California, San Francisco.

Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine

Abstract: COVID-19 is more severe in transplant recipients. Variants of concern have supplanted wild-type virus. In transplant recipients, data are limited on 2-dose or 3-dose vaccine immunogenicity against variant viruses.To assess neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses.Secondary analysis of a randomized, double-blind, controlled trial of a third dose of mRNA-1273 vaccine versus placebo. (ClinicalTrials.gov: NCT04885907).Single-center transplant program.Organ transplant recipients.Third dose of mRNA-1273 vaccine versus placebo.Sera were analyzed for neutralization against wild-type virus and the Alpha, Beta, and Delta variants using a surrogate virus neutralization assay and a spike-pseudotyped lentivirus assay.A total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). The differences were 36 (CI, 17 to 51) percentage points for the Alpha variant and 31 (CI, 15 to 46) percentage points for the Beta variant. In the mRNA-1273 group, lower neutralization values were observed for variants compared with wild-type virus, especially the Beta variant.There is no clear correlate of protection for neutralizing antibody. This was a secondary analysis.In organ transplant recipients, a third dose of mRNA vaccine increases neutralizing antibody response against SARS-CoV-2 variants compared with placebo.Ajmera Transplant Centre.

Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial

Abstract: Immunoassays for determining past SARS-CoV-2 infection have not been systematically evaluated in vaccinated persons in comparison with unvaccinated persons.To evaluate antinucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection.Nested substudy of a phase 3 randomized, double-blind, placebo-controlled vaccine efficacy trial. (ClinicalTrials.gov: NCT04470427).99 sites in the United States, July 2020 through March 2021.Participants were aged 18 years or older, had no known history of SARS-CoV-2 infection, and were at risk for SARS-CoV-2 infection or severe COVID-19. Substudy participants were diagnosed with SARS-CoV-2 infection during the trial's blinded phase.2 mRNA-1273 or placebo injections 28 days apart.Nasopharyngeal swabs from days 1 and 29 (vaccination days) and from symptom-prompted illness visits were tested for SARS-CoV-2 via polymerase chain reaction (PCR). Serum samples from days 1, 29, and 57 and the participant decision visit (PDV, when participants were informed of treatment assignment; median day 149) were tested for anti-N Abs by the Elecsys immunoassay.Among 812 participants with PCR-confirmed COVID-19 illness during the blinded phase of the trial (through March 2021), seroconversion to anti-N Abs (median of 53 days after diagnosis) occurred in 21 of 52 mRNA-1273 vaccinees (40% [95% CI, 27% to 54%]) versus 605 of 648 placebo recipients (93% [CI, 92% to 95%]). Each 1-log increase in SARS-CoV-2 viral copies at diagnosis was associated with 90% higher odds of anti-N Ab seroconversion (odds ratio, 1.90 [CI, 1.59 to 2.28]).The scope was restricted to mRNA-1273 vaccinees and the Elecsys assay, the sample size was small, data on Delta and Omicron infections were lacking, and the analysis did not address a prespecified objective of the trial.Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing.National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma

Abstract: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP.These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations.The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence).The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2.The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence).The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence).The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence).CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Type 1 Diabetes Mellitus

Abstract: Type 1 diabetes mellitus (T1DM) is an endocrine disorder in which pancreatic β cells stop producing insulin, typically due to autoimmune destruction. This results in hyperglycemia and ketosis; thus, insulin replacement is vital to management. Incidence peaks in puberty and early adulthood, but onset can occur at any age. However, prevalence is highest among adults because persons with T1DM live for many years. Symptoms include polyuria, polydipsia, and weight loss. Acute complications include diabetic ketoacidosis, which requires urgent management. Long-term complications include microvascular and macrovascular disease. Patients with T1DM are at higher risk for other autoimmune diseases and psychosocial issues. Management should focus on optimizing glucose control to reduce acute and long-term complications.

Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors

Abstract: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined.To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.Cross-sectional study.14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016).1305 prospectively recruited persons with benign adrenal tumors.Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry.Of the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased.Cross-sectional design; possible selection bias.A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes.Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19

Abstract: Background: In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease. Objective: To identify other potential clinical benefits of molnupiravir versus placebo. Design: Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597) Setting: 107 sites globally. Participants: 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19. Intervention: Molnupiravir, 800 mg, or placebo every 12 hours for 5 days. Measurements: Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo 2), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization. Results: Participants receiving molnupiravir showed faster normalization of CRP and Spo 2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19–related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants. Limitations: Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2. Conclusion: The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death. Primary Funding Source: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update

Abstract: These updated Good Publication Practice (GPP) guidelines include recommendations for publishing company-sponsored biomedical research. The GPP guidelines apply to peer-reviewed or peer-oriented biomedical publications, such as manuscripts, meeting presentations, posters, and abstracts, as well as enhanced content, such as plain-language summaries. The current GPP guidelines incorporate guidance on ethics and transparency as well as the planning, development, review, and approval of biomedical publications and policies and procedures that describe these practices. Supplemental materials lay out processes for steering committees, publication plans, publication working groups, determining authorship, and documentation. Information about new topics, such as alliances and working with patients, has been included where appropriate within these supplemental materials. Incorporating the principles and best practices presented in these GPP guidelines will result in increased transparency and a firm ethical footing. This guidance is also intended to enable the compliant incorporation of new and emerging publication tools for the ethical publication of company-sponsored research.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population

Abstract: Background: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. Purpose: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose–response relations with characteristics of the pandemic and its containment. Data Sources: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19–related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. Study Selection: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. Data Extraction: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. Data Synthesis: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, −0.39 [95% credible interval, −0.76 to −0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. Limitations: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. Conclusion: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. Primary Funding Source: Swiss National Science Foundation. (PROSPERO: CRD42020180049)

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort

Abstract: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.Breast Cancer Surveillance Consortium (BCSC) facilities.Women aged 50 to 74 years at first mammography screen between 2000 and 2018.Screening mammograms and screen-detected or interval breast cancer.The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.Exclusion of women with first mammography screen outside BCSC.On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.National Cancer Institute.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine

Abstract: There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity.To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine.A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials.Nationally centralized database of Maccabi Healthcare Services, Israel.Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection.Forty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial.SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021.A statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found.Hybrid protection against non-Delta variants could not be inferred.Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare.None.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction

Abstract: 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).To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms.PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479).Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI.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.A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays.Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies.The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI.National Taiwan University Hospital.

Risk for Reinfection After SARS-CoV-2: A Living, Rapid Review for American College of Physicians Practice Points on the Role of the Antibody Response in Conferring Immunity Following SARS-CoV-2 Infection

Abstract: The strength and duration of immunity from infection with SARS-CoV-2 are important for public health planning and clinical practice.To synthesize evidence on protection against reinfection after SARS-CoV-2 infection.MEDLINE (Ovid), the World Health Organization global literature database, ClinicalTrials.gov, COVID19reviews.org, and reference lists.Longitudinal studies that compared the risk for reinfection after SARS-CoV-2 infection versus infection risk in individuals with no prior infection.Two investigators sequentially extracted study data and rated quality.Across 18 eligible studies, reinfection risk ranged from 0% to 2.2%. In persons with recent SARS-CoV-2 infection compared with unvaccinated, previously uninfected individuals, 80% to 98% of symptomatic infections with wild-type or Alpha variants were prevented (high strength of evidence). In the meta-analysis, previous infection reduced risk for reinfection by 87% (95% CI, 84% to 90%), equaling 4.3 fewer infections per 100 persons in both the general population (risk difference, -0.043 [CI, -0.071 to -0.015]) and health care workers (risk difference, -0.043 [CI, -0.069 to -0.016]), and 26.6 fewer infections per 100 persons in care facilities (risk difference, -0.266 [CI, -0.449 to -0.083]). Protection remained above 80% for at least 7 months, but no study followed patients after the emergence of the Delta or Omicron variant. Results for the elderly were conflicting.Methods to ascertain and diagnose infections varied.Before the emergence of the Delta and Omicron variants, persons with recent infection had strong protection against symptomatic reinfections for 7 months compared with unvaccinated, previously uninfected individuals. Protection in immunocompromised persons, racial and ethnic subgroups, and asymptomatic index case patients is unclear. The durability of protection in the setting of the Delta and Omicron variants is unknown.Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality

Abstract: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without.To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality.Prospective cohort study.Data were extracted from the UK Biobank.A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018.Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated.During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee.Exposure assessed at baseline might not capture changes in intake over time.Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death.National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring

Abstract: Background: Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown. Objective: To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes. Design: Nationwide prospective registry-based cohort study. Setting: Denmark from 1997 to 2016. Participants: All liveborn singletons from mothers without histories of diabetes or essential hypertension. Measurements: Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings. Results: Of 1 116 779 offspring included, 3.3% had 1 or more major birth defects (reference). Insulin-exposed offspring (n = 5298) had the reference birth defect frequency (adjusted odds ratio [aOR], 0.98 [95% CI, 0.85 to 1.14]). Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92). Offspring whose fathers filled a metformin prescription in the year before (n = 1751) or after (n = 2484) sperm development had reference birth defect frequencies (aORs, 0.88 [CI, 0.59 to 1.31] and 0.92 [CI, 0.68 to 1.26], respectively), as did unexposed siblings of exposed offspring (3.2%; exposed vs. unexposed OR, 1.54 [CI, 0.94 to 2.53]). Among metformin-exposed offspring, genital birth defects, all in boys, were more common (aOR, 3.39 [CI, 1.82 to 6.30]), while the proportion of male offspring was lower (49.4% vs. 51.4%, P = 0.073). Limitation: Information on underlying disease status was limited. Conclusion: Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation. Primary Funding Source: National Institutes of Health.

COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System

Abstract: Background: Little is known about real-world COVID-19 vaccine effectiveness (VE) in racially and ethnically diverse, elderly populations with high comorbidity burden. Objective: To determine the effectiveness of messenger RNA COVID-19 vaccines. Design: Target trial emulation study comparing newly vaccinated persons with matched unvaccinated controls. Setting: U.S. Department of Veterans Affairs health care system. Participants: Among persons receiving care in the Veterans Affairs health care system (n = 5 766 638), those who received at least 1 dose of the Moderna or Pfizer–BioNTech COVID-19 vaccine from 11 December 2020 to 25 March 2021 (n = 2 099 871) were matched to unvaccinated controls in a 1:1 ratio according to demographic, clinical, and geographic characteristics. Intervention: Follow-up for SARS-CoV-2 infection or SARS-CoV-2–related death, defined as death within 30 days of infection, began after the vaccination date or an identical index date for the matched unvaccinated controls and continued until up to 30 June 2021. Measurements: Vaccine effectiveness against SARS-CoV-2 infection or SARS-CoV-2–related death. Results: Vaccinated and unvaccinated groups were well matched; both were predominantly male (92.9% vs. 93.4%), had advanced age (mean, 68.7 years in both groups), had diverse racial and ethnic distribution (for example, Black: 17.3% vs. 17.0%, Hispanic: 6.5% vs. 6.1%), and had substantial comorbidity burden. Vaccine effectiveness 7 or more days after the second vaccine dose was 69% (95% CI, 67% to 70%) against SARS-CoV-2 infection and 86% (CI, 82% to 89%) against SARS-CoV-2–related death and was similar when follow-up was extended to 31 March versus 30 June. Vaccine effectiveness against infection decreased with increasing age and comorbidity burden. Limitation: Predominantly male population and lack of data on SARS-CoV-2 variants. Conclusion: In an elderly, diverse, high-comorbidity population, COVID-19 VE against infection was substantially lower than previously reported, but VE against death was high. Complementary infection mitigation efforts remain important for pandemic control, even with vaccination. Primary Funding Source: U.S. Department of Veterans Affairs.

Comparing Video-Based, Telehealth-Delivered Exercise and Weight Loss Programs With Online Education on Outcomes of Knee Osteoarthritis

Abstract: Scalable knee osteoarthritis programs are needed to deliver recommended education, exercise, and weight loss interventions.To evaluate two 6-month, telehealth-delivered exercise programs, 1 with and 1 without dietary intervention.3-group, parallel randomized (5:5:2) trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000930280).Australian private health insurance members.415 persons with symptomatic knee osteoarthritis and a body mass index between 28 and 40 kg/m2 who were aged 45 to 80 years.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.Primary outcomes were changes in knee pain (numerical rating scale [NRS] of 0 to 10, higher indicating worse) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]; scale, 0 to 68, higher indicating worse) at 6 months (primary time point) and 12 months. Secondary outcomes were weight, physical activity, quality of life, mental health, global change, satisfaction, willingness to have surgery, orthopedic appointments, and knee surgery.A total of 379 participants (91%) provided 6-month primary outcomes, and 372 (90%) provided 12-month primary outcomes. At 6 months, both programs were superior to control for pain (between-group mean difference in change on NRS: diet and exercise, -1.5 [95% CI, -2.1 to -0.8]; exercise, -0.8 [CI, -1.5 to -0.2]) and function (between-group mean difference in change on WOMAC: diet and exercise, -9.8 [CI, -12.5 to -7.0]; exercise, -7.0 [CI, -9.7 to -4.2]). The diet and exercise program was superior to exercise (pain, -0.6 [CI, -1.1 to -0.2]; function, -2.8 [CI, -4.7 to -0.8]). Findings were similar at 12 months.Participants and clinicians were unblinded.Telehealth-delivered exercise and diet programs improved pain and function in people with knee osteoarthritis and overweight or obesity. A dietary intervention conferred modest additional pain and function benefits over exercise.Medibank, the Medibank Better Health Foundation Research Fund, and a National Health and Medical Research Council Centre of Research Excellence.

Major Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points

Abstract: Background: Remdesivir is approved for the treatment of adults hospitalized with COVID-19. Purpose: To update a living review of remdesivir for adults with COVID-19. Data Sources: Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021. Study Selection: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. Data Extraction: One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. Data Synthesis: Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms—remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event. Limitation: The RCTs differed in definitions of COVID-19 severity and outcomes reported. Conclusion: In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event. Primary Funding Source: U.S. Department of Veterans Affairs.

Cost-Effectiveness of Long-Acting Injectable HIV Preexposure Prophylaxis in the United States

Abstract: Background: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP). Objective: To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States. Design: Simulation, cost-effectiveness analysis. Data Sources: Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine–tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed. Target Population: 476 700 MSM/TGW at very high risk for HIV (VHR). Time Horizon: 10 years. Perspective: Health care system. Intervention: CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP. Outcome Measures: Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP. Results of Base-Case Analysis: Compared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year). Results of Sensitivity Analysis: In a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year). Limitation: Uncertain clinical and economic benefits of averting future transmissions. Conclusion: Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA. Primary Funding Source: FHI 360; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.