The 50 most-cited articles in Annals of Internal Medicine, 2022

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…

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.

BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave.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…

Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUSs). Only a minority of VUSs are likely to prove pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision making and can result in harms and costs to patients and the health care system, including the time-consuming analysis required to interpret a VUS and the potential for unnecessary treatment and adverse psychological effects. Current efforts to improve variant interpretation will help reduce the scope of the problem, but the high prevalence of rare and novel variants in the human genome points to VUSs as an ongoing challenge. Additional strategies can help mitigate the potential harms of VUSs, including testing protocols that limit identification or reporting of VUSs, subclassification of VUSs according to the likelihood of pathogenicity, routine family-based evaluation of variants, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance…

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…

BACKGROUND: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. OBJECTIVE: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. DESIGN: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. SETTING: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). PATIENTS: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. MEASUREMENTS: The primary outcome was a composite…

Risk prediction models need thorough validation to assess their performance. Validation of models for survival outcomes poses challenges due to the censoring of observations and the varying time horizon at which predictions can be made. This article describes measures to evaluate predictions and the potential improvement in decision making from survival models based on Cox proportional hazards regression. As a motivating case study, the authors consider the prediction of the composite outcome of recurrence or death (the "event") in patients with breast cancer after surgery. They developed a simple Cox regression model with 3 predictors, as in the Nottingham Prognostic Index, in 2982 women (1275 events over 5 years of follow-up) and externally validated this model in 686 women (285 events over 5 years). Improvement in performance was assessed after the addition of progesterone receptor as a prognostic biomarker. The model predictions can be evaluated across the full range of observed follow-up times or for the event occurring by the end of a fixed time horizon of interest. The…

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.), 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.), 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.), 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.),…

BACKGROUND: Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments. OBJECTIVE: To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure). DESIGN: Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124). SETTING: 410 sites in 20 countries. PATIENTS: Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide. INTERVENTION: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. MEASUREMENTS: The primary outcome was worsening HF or cardiovascular death. RESULTS: Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI ≤0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI ≥0.311;…

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…

BACKGROUND: 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. OBJECTIVE: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS. DESIGN: Cross-sectional study. SETTING: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016). PARTICIPANTS: 1305 prospectively recruited persons with benign adrenal tumors. MEASUREMENTS: 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. RESULTS: = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2…

BACKGROUND: 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. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: 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. MEASUREMENTS: Reporting rates (cases…

BACKGROUND: Contemporary data are needed about the utility of cannabinoids in chronic pain. PURPOSE: To evaluate the benefits and harms of cannabinoids for chronic pain. DATA SOURCES: Ovid MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and Scopus to January 2022. STUDY SELECTION: English-language, randomized, placebo-controlled trials and cohort studies (≥1 month duration) of cannabinoids for chronic pain. DATA EXTRACTION: Data abstraction, risk of bias, and strength of evidence assessments were dually reviewed. Cannabinoids were categorized by THC-to-CBD ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant). DATA SYNTHESIS: = 13 095) assessed cannabinoids. Studies were primarily short term (1 to 6 months); 56% enrolled patients with neuropathic pain, with 3% to 89% female patients. Synthetic products with high THC-to-CBD ratios (>98% THC) may be associated with moderate improvement in pain severity and response (≥30% improvement) and an increased risk for sedation and are probably associated with a large increased risk for dizziness.…

BACKGROUND: Case reports of carditis after BNT162b2 vaccination are accruing worldwide. OBJECTIVE: To examine the association of BNT162b2 and CoronaVac (Sinovac) vaccination with carditis. DESIGN: Case-control study with hospital control participants. SETTING: Territory-wide, public health care database with linkage to population-based vaccination records in Hong Kong. PATIENTS: 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. INTERVENTION: Vaccination with BNT162b2 or CoronaVac. MEASUREMENTS: Incident diagnosis of carditis based on the International Classification of Diseases, Ninth Revision, and elevated troponin levels. RESULTS: 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…

Venous thromboembolism (VTE) is the third most common cardiovascular disorder, affecting up to 5% of the population. VTE commonly manifests as lower-extremity deep venous thrombosis (DVT) or pulmonary embolism. Half of these events are associated with a transient risk factor and may be preventable with prophylaxis. Direct oral anticoagulants are effective and safe and carry a lower risk for bleeding than vitamin K antagonists. Many patients with VTE will have a chronic disease requiring long-term anticoagulation. Postthrombotic syndrome affects 25% to 40% of patients with DVT and significantly impacts function and quality of life.

Abstract Importance The performance of immunoassays for determining past SARS-CoV-2 infection, which were developed in unvaccinated individuals, has not been assessed in vaccinated individuals. Objective To evaluate anti-nucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 vaccine efficacy trial participants after SARS-CoV-2 infection during the trial’s blinded phase. Design Nested analysis in a Phase 3 randomized, placebo-controlled vaccine efficacy trial. Nasopharyngeal swabs for SARS-CoV-2 PCR testing were taken from all participants on Day 1 and Day 29 (vaccination days), and during symptom-prompted illness visits. Serum samples from Days 1, 29, 57, and the Participant Decision Visit (PDV, when participants were informed of treatment assignment, median day 149) were tested for anti-N Abs. Setting Multicenter, randomized, double-blind, placebo-controlled trial at 99 sites in the US. Participants Trial participants were ≥ 18 years old with no known history of SARS-CoV-2 infection and at appreciable risk of SARS-CoV-2 infection and/or high risk of severe Covid-19. Nested…

BACKGROUND: With the widespread use of advanced imaging technology, adrenal tumors are increasingly being identified. OBJECTIVE: To investigate the prevalence and characteristics of adrenal tumors in an unselected screening population in China. DESIGN: Cross-sectional study. (ClinicalTrials.gov: NCT04682938). SETTING: A health examination center in China. PATIENTS: Adults having an annual checkup were invited to be screened for adrenal tumors by adrenal computed tomography. MEASUREMENTS: The participants with adrenal tumors had further evaluation for malignancy risk and adrenal function. RESULTS: A total of 25 356 participants were screened, 351 of whom were found to have adrenal tumors, for a prevalence of 1.4%. The prevalence increased with age, from 0.2% in participants aged 18 to 25 years to 3.2% in those older than 65 years. Among 351 participants with adrenal tumors, 337 were diagnosed with an adrenocortical adenoma, 14 with another benign nodule, and none with a malignant mass. In 212 participants with an adenoma who completed endocrine testing, 69.3% were diagnosed with a…

Background: Low vitamin D status is associated with increased mortality, but randomized trials on severely deficient participants are lacking. Objective: To assess genetic evidence for the causal role of low vitamin D status in mortality. Design: Nonlinear Mendelian randomization analyses. Setting: UK Biobank, a large-scale, prospective cohort from England, Scotland, and Wales with participants recruited between March 2006 and July 2010. Participants: 307 601 unrelated UK Biobank participants of White European ancestry (aged 37 to 73 years at recruitment) with available measurements of 25-hydroxyvitamin D (25-(OH)D) and genetic data. Measurements: Genetically predicted 25-(OH)D was estimated using 35 confirmed variants of 25-(OH)D. All-cause and cause-specific mortality (cardiovascular disease [CVD], cancer, and respiratory) were recorded up to June 2020. Results: There were 18 700 deaths during the 14 years of follow-up. The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped (P for nonlinearity < 0.001), and risk for death decreased steeply with…

BACKGROUND: 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. OBJECTIVE: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Data were extracted from the UK Biobank. PARTICIPANTS: 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. MEASUREMENTS: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated. RESULTS: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD…

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive…

Abstract The US FDA has recently authorized immunocompromised people to receive a third dose of mRNA Covid-19 vaccine following the two-doses regimen to further boost protection. Unfortunately, a non-negligible proportion of people treated with immunosuppressive drugs either do not respond or show only a weak response after a third boost and should, therefore, still be considered at risk of severe Covid-19. As of June 2021, we were granted the opportunity to offer a fourth vaccine dose to French solid organ transplant recipients who still showed a weak antibody response after the third dose. In this multicenter study, we demonstrate that that the protection conferred by a fourth dose is adequate for the majority of kidney transplant recipients.

BACKGROUND: It remains unclear if a low-carbohydrate, high-fat (LCHF) diet is a possible treatment strategy for type 2 diabetes mellitus (T2DM), and the effect on nonalcoholic fatty liver disease (NAFLD) has not been investigated. OBJECTIVE: To investigate the effect of a calorie-unrestricted LCHF diet, with no intention of weight loss, on T2DM and NAFLD compared with a high-carbohydrate, low-fat (HCLF) diet. DESIGN: 6-month randomized controlled trial with a 3-month follow-up. (ClinicalTrials.gov: NCT03068078). SETTING: Odense University Hospital in Denmark from November 2016 until June 2020. PARTICIPANTS: 165 participants with T2DM. INTERVENTION: Two calorie-unrestricted diets: LCHF diet with 50 to 60 energy percent (E%) fat, less than 20E% carbohydrates, and 25E% to 30E% proteins and HCLF diet with 50E% to 60E% carbohydrates, 20E% to 30E% fats, and 20E% to 25E% proteins. MEASUREMENTS: Glycemic control, serum lipid levels, metabolic markers, and liver biopsies to assess NAFLD. RESULTS: (mean difference in change, -6.1 mmol/mol [95% CI, -9.2 to -3.0 mmol/mol] or -0.59% [CI, -0.87%…

BACKGROUND: 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. OBJECTIVE: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer. DESIGN: 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. SETTING: Breast Cancer Surveillance Consortium (BCSC) facilities. PARTICIPANTS: Women aged 50 to 74 years at first mammography screen between 2000 and 2018. MEASUREMENTS: Screening mammograms and screen-detected or interval breast cancer. RESULTS: The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5%…

BACKGROUND: Cannabis policy liberalization has increased cannabis availability for medical or recreational purposes. Up-to-date trends in medical cannabis licensure can inform clinical policy and care. OBJECTIVE: To describe recent trends in medical cannabis licensure in the United States. DESIGN: Ecological study with repeated measures. SETTING: State registry data via state reports and data requests on medical cannabis licensure from 2016 to 2020. PARTICIPANTS: Medical cannabis patients (persons with medical cannabis licenses) in the United States. MEASUREMENTS: Total patient volume, patients per 10 000 of total population, and patient-reported qualifying conditions (that is, symptoms or conditions qualifying patients for licensure)-including whether these symptoms align with current therapeutic evidence of cannabis-cannabinoid efficacy. RESULTS: In 2020, 26 states and Washington, DC reported patient numbers, and 19 states reported patient-reported qualifying conditions. Total enrolled patients increased approximately 4.5-fold from 678 408 in 2016 to 2 974 433 in 2020. Patients…

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the…

Opioid use disorder (OUD) is a treatable chronic disorder with episodes of remission and recurrence characterized by loss of control of opioid use, compulsive use, and continued use despite harms. If untreated, OUD is associated with significant morbidity and mortality. Buprenorphine and methadone reduce fatal and nonfatal opioid overdose and infectious complications of OUD and are the first-line treatment options. Physicians have an important role to play in diagnosing OUD and its comorbidities, offering evidence-based treatment, and delivering overdose prevention and other harm reduction services to people who continue to use opioids. Interdisciplinary office-based addiction treatment programs support high-quality OUD care.

BACKGROUND: Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC. OBJECTIVE: To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice. DESIGN: Multinational population-based cohort study. SETTING: Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States. PARTICIPANTS: Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription. MEASUREMENTS: Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model. RESULTS: = 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95%…

Whereas diagnostic tests help detect the cause of signs and symptoms, prognostic tests assist in evaluating the probable course of the disease and future outcome. Studies to evaluate prognostic tests are longitudinal, which introduces sources of bias different from those for diagnostic accuracy studies. At present, systematic reviews of prognostic tests often use the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess risk of bias and applicability of included studies because no equivalent instrument exists for prognostic accuracy studies. QUAPAS (Quality Assessment of Prognostic Accuracy Studies) is an adaptation of QUADAS-2 for prognostic accuracy studies. Questions likely to identify bias were evaluated in parallel and collated from QUIPS (Quality in Prognosis Studies) and PROBAST (Prediction Model Risk of Bias Assessment Tool) and paired to the corresponding question (or domain) in QUADAS-2. A steering group conducted and reviewed 3 rounds of modifications before arriving at the final set of domains and signaling questions. QUAPAS follows the same steps…

BACKGROUND: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF). OBJECTIVE: To determine which treatment is superior in terms of clinical scores and adverse events. DESIGN: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307). SETTING: 17 National Health Service trusts across the United Kingdom. PATIENTS: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure. INTERVENTION: Patients were randomly assigned to TAR or AF surgical treatment. MEASUREMENTS: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible. RESULTS: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52…

BACKGROUND: Older adults have many comorbidities contributing to mortality. OBJECTIVE: To develop a summary Elixhauser (S-Elixhauser) comorbidity score to predict 30-day, in-hospital, and 1-year mortality in older adults using the 38 comorbidities operationalized by the Agency for Healthcare Research and Quality (AHRQ). DESIGN: Retrospective cohort study. SETTING: Medicare beneficiaries from 2017 to 2019. PATIENTS: 899 844) and 3 disease-specific hospitalized cohorts. MEASUREMENTS: Weights were derived for 38 comorbidities to predict 30-day, in-hospital, and 1-year mortality. The S-Elixhauser score was internally validated and calibrated. Individual Elixhauser comorbidity indicators (38 comorbidities), the modified application of the AHRQ-derived Elixhauser summary score, the Charlson comorbidity indicators (17 comorbidities), and the Charlson summary score were externally validated. The c-statistic was used to evaluate discrimination of a comorbidity score model. RESULTS: The S-Elixhauser score was well calibrated and internally validated, with a c-statistic of 0.705 (95% CI, 0.703…

BACKGROUND: Tea is frequently consumed worldwide, but the association of tea drinking with mortality risk remains inconclusive in populations where black tea is the main type consumed. OBJECTIVE: To evaluate the associations of tea consumption with all-cause and cause-specific mortality and potential effect modification by genetic variation in caffeine metabolism. DESIGN: Prospective cohort study. SETTING: The UK Biobank. PARTICIPANTS: 498 043 men and women aged 40 to 69 years who completed the baseline touchscreen questionnaire from 2006 to 2010. MEASUREMENTS: Self-reported tea intake and mortality from all causes and leading causes of death, including cancer, all cardiovascular disease (CVD), ischemic heart disease, stroke, and respiratory disease. RESULTS: During a median follow-up of 11.2 years, higher tea intake was modestly associated with lower all-cause mortality risk among those who drank 2 or more cups per day. Relative to no tea drinking, the hazard ratios (95% CIs) for participants drinking 1 or fewer, 2 to 3, 4 to 5, 6 to 7, 8 to 9, and 10 or more cups per day were 0.95…

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart…

DESCRIPTION: In August 2021, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of substance use disorders (SUDs). This synopsis summarizes key recommendations. METHODS: In March 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2015 VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 35 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis presents the recommendations that were believed to be the most clinically impactful. RECOMMENDATIONS: The scope of the CPG is broad; however, this synopsis focuses on key recommendations for the management of alcohol use disorder, use of…

BACKGROUND: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators. OBJECTIVE: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care. DESIGN: Multicenter, randomized, noninferiority trial. (ClinicalTrials.gov: NCT04296643). SETTING: 29 health care facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022. PARTICIPANTS: 1009 health care workers who provided direct care to patients with suspected or confirmed COVID-19. INTERVENTION: Use of medical masks versus fit-tested N95 respirators for 10 weeks, plus universal masking, which was the policy implemented at each site. MEASUREMENTS: The primary outcome was confirmed COVID-19 on reverse transcriptase polymerase chain reaction (RT-PCR) test. RESULTS: In the intention-to-treat analysis, RT-PCR-confirmed COVID-19 occurred in 52 of 497 (10.46%) participants in the medical mask group versus 47 of 507 (9.27%) in the N95 respirator group (hazard ratio [HR], 1.14 [95% CI, 0.77 to 1.69]).…

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,…

Background: Implantable cardioverter defibrillators (ICDs) improve survival in patients at risk for cardiac arrest, but are associated with intravascular lead-related complications. The subcutaneous ICD (S-ICD), with no intravascular components, was developed to minimize lead-related complications. Objective: To assess key ICD performance measures related to delivery of ICD therapy, including inappropriate ICD shocks (delivered in absence of life-threatening arrhythmia) and failed ICD shocks (which did not terminate ventricular arrhythmia). Design: Randomized, multicenter trial. (ClinicalTrials.gov: NCT02881255) Setting: The ATLAS trial. Patients: 544 eligible patients (141 female) with a primary or secondary prevention indication for an ICD who were younger than age 60 years, had a cardiogenetic phenotype, or had prespecified risk factors for lead complications were electrocardiographically screened and 503 randomly assigned to S-ICD (251 patients) or transvenous ICD (TV-ICD) (252 patients). Mean follow-up was 2.5 years (SD, 1.1). Mean age was 49.0 years (SD, 11.5). Measurements:…

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…

DESCRIPTION: 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. METHODS: 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. RECOMMENDATION 1 (OUTPATIENT): 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). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or…

BACKGROUND: The adenoma detection rate (ADR) is an essential quality indicator for endoscopists performing colonoscopies for colorectal cancer (CRC) screening as it is associated with postcolonoscopy CRCs (PCCRCs). Currently, data on ADRs of endoscopists performing colonoscopies in fecal immunochemical testing (FIT)-based screening, the most common screening method, are scarce. Also, the association between the ADR and PCCRC has not been demonstrated in this setting. OBJECTIVE: To evaluate the association between the ADR and PCCRC risk in colonoscopies done after a positive FIT result. DESIGN: Population-based cohort. SETTING: Dutch, FIT-based, CRC screening program. PARTICIPANTS: Patients undergoing colonoscopy, done by accredited endoscopists, after a positive FIT result. MEASUREMENTS: Quality indicator performance and PCCRC incidence for colonoscopies in FIT-positive screenees were assessed. The PCCRCs were classified as interval, a cancer detected before recommended surveillance, or noninterval. The association between ADR and interval PCCRC was evaluated with a multivariable…

Description: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the diagnosis and management of acute left-sided colonic diverticulitis in adults. This guideline is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. Methods: The ACP Clinical Guidelines Committee (CGC) developed this guideline based on a systematic review on the use of computed tomography (CT) for the diagnosis of acute left-sided colonic diverticulitis and on management via hospitalization, antibiotic use, and interventional percutaneous abscess drainage. The systematic review evaluated outcomes that the CGC rated as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is adults with suspected or known acute left-sided colonic diverticulitis. Recommendation 1: ACP suggests that…

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.…

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: ), 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: , with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a…

BACKGROUND: The BNT162b2 (Pfizer-BioNTech) vaccine has been shown to be safe with regard to risk for severe cardiovascular events (such as myocardial infarction [MI], pulmonary embolism [PE], and stroke) in persons aged 75 years or older. Less is known about the safety of other COVID-19 vaccines or outcomes in younger populations. OBJECTIVE: To assess short-term risk for severe cardiovascular events (excluding myocarditis and pericarditis) after COVID-19 vaccination in France's 46.5 million adults younger than 75 years. DESIGN: Self-controlled case series method adapted to event-dependent exposure and high event-related mortality. SETTING: France, 27 December 2020 to 20 July 2021. PATIENTS: = 73 325 total events). MEASUREMENTS: Linkage between the French National Health Data System and COVID-19 vaccine databases enabled identification of hospitalizations for cardiovascular events (MI, PE, or stroke) and receipt of a first or second dose of the Pfizer-BioNTech, mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine. The relative incidence (RI) of…

Background: Despite increasing awareness of firearm-related deaths, evidence on the clinical and economic implications of nonfatal firearm injuries is limited. Objective: To measure changes in clinical and economic outcomes after nonfatal firearm injuries among survivors and their family members. Design: Cohort study. Setting: MarketScan Medicare and commercial claims data, 2008 to 2018. Participants: 6498 survivors of firearm injuries matched to 32 490 control participants and 12 489 family members of survivors matched to 62 445 control participants. Intervention: Exposure to nonfatal firearm injury as a survivor or family member of a survivor. Measurements: Changes in health care spending, use, and morbidity from preinjury through 1 year postinjury relative to control participants, on average and by type and severity of firearm injury. Results: After nonfatal firearm injury, medical spending increased $2495 per person per month (402%) and cost sharing increased $102 per person per month (176%) among survivors relative to control participants (P < 0.001) in the first year after…

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was recommended by the U.S. Preventive Services Task Force (USPSTF) in 2013, making approximately 8 million Americans eligible for screening. The demographic characteristics and adherence of persons screened in the United States have not been reported at the population level. OBJECTIVE: To define sociodemographic characteristics and adherence among persons screened and entered into the American College of Radiology's Lung Cancer Screening Registry (LCSR). DESIGN: Cohort study. SETTING: United States, 2015 to 2019. PARTICIPANTS: Persons receiving a baseline LDCT for LCS from 3625 facilities reporting to the LCSR. MEASUREMENTS: Age, sex, and smoking status distributions (percentages) were computed among persons who were screened and among respondents in the 2015 National Health Interview Survey (NHIS) who were eligible for screening. The prevalence between the LCSR and the NHIS was compared with prevalence ratios (PRs) and 95% CIs. Adherence to annual screening was defined as having a follow-up test…

Background: Racial/ethnic minority populations in the United States have increased rates of diabetes compared with White populations. The 2021 guidelines from the U.S. Preventive Services Task Force recommend diabetes screening for adults aged 35 to 70 years with a body mass index (BMI) of 25 kg/m2 or greater. Objective: To determine the BMI threshold for diabetes screening in major racial/ethnic minority populations with benefits and harms equivalent to those of the current diabetes screening threshold in White adults. Design: Cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey), 2011 to 2018. Participants: Nonpregnant U.S. adults aged 18 to 70 years (n = 19 335). Measurements: A logistic regression model was used to estimate diabetes prevalence at various BMIs for White, Asian, Black, and Hispanic Americans. For each racial/ethnic minority group, the equivalent BMI threshold was defined as the BMI at which the prevalence of diabetes in 35-year-old persons in that group is equal to that in 35-year-old White adults at a BMI of 25 kg/m2. Ranges…

BACKGROUND: 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. OBJECTIVE: To estimate inactivated vaccine effectiveness (VE) against the B.1.617.2 variant. DESIGN: Retrospective cohort study. SETTING: 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. PARTICIPANTS: 10 805 adult case patients with laboratory-confirmed infection and close contacts. MEASUREMENTS: 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: Results are reported in the order of outcome severity. Of 10 805 participants, 1.3% contracted infections, 1.2% developed…

LettersDecember 2022Incidence of Myocarditis/Pericarditis Following mRNA COVID-19 Vaccination Among Children and Younger Adults in the United StatesFREEKristin Goddard, MPH, Kayla E. Hanson, MPH, Ned Lewis, MPH, Eric Weintraub, MPH, Bruce Fireman, Nicola P. Klein, MD, PhDKristin Goddard, MPHKaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, California, Kayla E. Hanson, MPHMarshfield Clinic Research Institute, Marshfield, Wisconsin, Ned Lewis, MPHKaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, California, Eric Weintraub, MPHImmunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia, Bruce FiremanKaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, California, Nicola P. Klein, MD, PhDKaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CaliforniaAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-2274 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack…

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma…

DESCRIPTION: In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of major depressive disorder (MDD). This synopsis summarizes key recommendations. METHODS: Senior leaders within the VA and the DoD assembled a team to update the 2016 CPG for the management of MDD that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 36 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Select recommendations that were identified by the authors to represent key changes from the prior CPG are presented in this synopsis. RECOMMENDATIONS: The scope of the CPG is diverse; however, this synopsis focuses on key recommendations that the authors identified as important new evidence and changes to prior recommendations on…