JAMA

The emerging outbreak of the 2019 novel coronavirus (2019-nCoV) originated from Wuhan poses a great challenge to healthcare system in China.1 Primary care practitioners (PCPs) have an important role in district communicable disease control.2 However, because primary health-care system in China still needs to be substantially strengthened,3,4 whether PCPs are proactive and capable in responding to the outbreak remains unclear. Using an electronic questionnaire, we surveyed a national sample of PCPs to assess their response to novel coronavirus outbreak.

Background: The observational literature on comparative effectiveness is expanding rapidly but remains difficult to synthesize. Discordant findings often stem from structural differences in cohort definitions, inclusion criteria, and follow up windows, leaving stakeholders without a cohesive evidence base. Furthermore, studies typically focus on a narrow subset of outcomes, neglecting the broader needs of diverse healthcare stakeholders 1,2,3,4. Methods We developed a high throughput evidence generation workflow using linked EHR and administrative claims data. The cornerstone is a prespecified measurement architecture applied uniformly across clinical scenarios: six post index windows (acute to two year follow.up); 28 Elixhauser comorbidities; 14 healthcare resource utilization (HCRU) categories; 29 laboratory measures with 52 binary thresholds; and 42 adverse event categories. We generated unadjusted treatment comparisons across ~1,038 outcomes per scenario, including effect-measure modification (EMM) assessments across 130 baseline features. Results Across 40 clinical domains, the workflow produced approximately 32,982,552 outcome evaluations. An evaluation included a treatment comparison outcome population effect estimate with uncertainty bounds and supporting diagnostics. Approximately 5,000 narrative summaries underwent structured clinical and statistical quality control before dissemination. Conclusions Standardized, high throughput workflows can shift evidence generation away from fragmented studies toward comprehensive evidence packages. This shared evidence base supports precision medicine by making treatment effect heterogeneity visible across clinically meaningful subpopulations, reducing the need for redundant, stakeholder-specific studies.

IntroductionCase registries of pregnant women diagnosed with coronavirus disease (COVID-19) by polymerase chain reaction (PCR) have reported that the majority experienced mild infection, but up to 9% may require critical care.1 Most COVID-19 cases published were in the third trimester of pregnancy, which could reflect reporting bias, higher risk of infection or increased disease severity in late pregnancy.2 Seroprevalence studies may allow reliable estimates of the susceptibility to infection and clinical spectrum since they include asymptomatic and mild infections not tested for PCR. We evaluated the seroprevalence and clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women in the first and third trimester. MethodsThe study was approved by the Institutional Review Board at each institution and informed consent was obtained. We recruited 874 consecutive pregnancies attending for first trimester screening (10-16 weeks gestation, n=372) or delivery (n=502) from April 14 to May 5. All women were interviewed with a structured questionnaire for COVID-19 symptoms two months prior to sampling. SARS-CoV-2 IgG and IgM/IgA antibodies were tested (COVID-19 VIRCLIA(R) Monotest, Vircell Microbiologist, Spain; reported sensitivity 70% IgG and 89% IgM/IgA, and specificity 89% and 99% respectively). Indeterminate results were re-tested (VITROS(R) Immunodiagnostic Products Anti-SARS-CoV2 Total Tests, Ortho Clinical Diagnostics, USA; 100% sensitivity and specificity) and re-classified as positive or negative. Women with COVID-19 were diagnosed and managed according to standard protocols and guidelines3,4. Statistical differences were tested using the{chi} 2 test or Student t-test as appropriate (p<0.05). ResultsA total of 125 of 874 women (14.3%) were positive for either IgG or IgM/IgA SARS-CoV-2 antibodies, 54/372 (14.5%) in the first and 71/502 (14.1%) in the third trimester. A total of 75/125 (60%) reported no symptoms of COVID-19 in the past 2 months, whereas 44 (35.2%) reported one or more symptoms, of which 31 (24.8%) had at least 3 symptoms or anosmia and 8 (6.4%) dyspnea. Overall, 7 women (5.6%) were admitted for persistent fever (>38{degrees}) despite paracetamol and dyspnea, of which 3 had signs of pneumonia on chest radiography. All 3 had criteria for severity (bilateral chest condensation, respiratory rate>30 and leukopenia) and required oxygen support but not critical care or mechanical ventilation, and they were all discharged well. The rates of symptomatic infection, hospital admission or dyspnea were significantly higher in third trimester women (Table and Figure). O_TBL View this table: org.highwire.dtl.DTLVardef@1efd3f2org.highwire.dtl.DTLVardef@43e612org.highwire.dtl.DTLVardef@1b5e673org.highwire.dtl.DTLVardef@12cc985org.highwire.dtl.DTLVardef@1627bfd_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable.C_FLOATNO O_TABLECAPTIONBaseline characteristics and clinical features of pregnant women positive for SARS-CoV-2 infection (N=125) in the first versus third trimester. C_TABLECAPTION C_TBL O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/20134098v1_fig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@ba4ad6org.highwire.dtl.DTLVardef@8742a5org.highwire.dtl.DTLVardef@28788dorg.highwire.dtl.DTLVardef@1029911_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure.C_FLOATNO Clinical spectrum of SARS-CoV-2 infection in pregnant women in the first and third trimester. C_FIG DiscussionThe 14.3% seroprevalence of SARS-COV-2 in pregnant women in this study was substantially larger than the contemporary rates of PCR positive cases (0.78%) reported for women 20-40y in Barcelona.5 The data confirm that COVID-19 is asymptomatic in the majority of pregnant women6 and illustrate the value of seroprevalence studies to capture the high proportion of asymptomatic or mild infections. In this study, none of the 125 pregnant women with SARS-CoV-2 infection required critical care as compared to 9% reported in cases diagnosed with PCR.1 However, the proportion of infections with symptoms or dyspnea was remarkably higher in the third trimester, and these results are in line with COVID-19 registries, reporting that 81% of hospitalized women were in late pregnancy or peripartum.1 These results provide reassuring information that, even in settings with a high prevalence, SARS-CoV-2 infection in pregnancy mostly presents with asymptomatic or mild clinical forms. The susceptibility to infection seemed to be the same in the first and the third trimesters of gestation. The data further suggest that, as with other respiratory viruses, COVID-19 could be more severe and require increased surveillance in late pregnancy. These findings should be confirmed and extended with larger consecutive prevalence studies in pregnancy.

BackgroundCarotid artery stenosis is a notable risk factor for ischemic stroke. In 2021, the U.S. Preventive Services Task Force (USPSTF) published an updated evidence review on screening for asymptomatic carotid artery stenosis (ACAS). At the request of the Japan Preventive Services Task Force, we conducted a systematic review to adapt and update the USPSTF review by incorporating recent international evidence and Japanese-language literature. MethodsFollowing the USPSTF analytic framework, we evaluated the evidence on screening effectiveness, harms of screening or confirmatory testing, the incremental benefit of revascularization beyond current medical therapy, and harms of surgical interventions in asymptomatic individuals. The International Medical Information Center conducted literature searches in PubMed, the Cochrane Library, and Ichushi-Web. Searches were limited to English and Japanese studies. Two reviewers independently performed study selection, data extraction, and risk of bias assessment, with disagreements resolved by consensus. Newly identified studies were qualitatively synthesized with the 2021 USPSTF findings. ResultsNo eligible studies directly assessing the benefits and harms of screening for ACAS were identified. One RCT evaluated the benefits of revascularization, and harms were assessed in that RCT and five observational studies. The RCT (SPACE-2; n=513), which investigated the incremental benefit of revascularization, was terminated prematurely and had substantial methodological limitations. In five registry- or claims-based observational studies, the 30-day incidence of stroke or death following revascularization was 2.5% to 2.8%. Perioperative stroke, death, and myocardial infarction occurred in 0.9% to 2.3%, 0.3% to 0.9%, and 0.3% to 0.9% of patients, respectively, consistent with the 2021 USPSTF review. ConclusionsThere is no direct evidence evaluating the effectiveness and harms of screening for asymptomatic carotid artery stenosis. Evidence on the benefits and harms of adding revascularization to optimal medical therapy was limited by early trial termination and methodological concerns, reducing the internal validity of the available data.

The dominance of the COVID-19 Delta variant has renewed questions about the impact of K12 school policies, including the role of masks, on disease burden.1 A recent study showed masks and testing could reduce infections in students, but failed to address the impact on the community,2 while another showed masking is critical to slow disease spread in communities, but did not consider school openings under Delta.3 We project the impact of school-masking on the community, which can inform policy decisions, and support healthcare system planning. Our findings indicate that the implementation of masking policies in school settings can reduce additional infections post-school opening by 23-36% for fully-open schools, with an additional 11-13% reduction for hybrid schooling, depending on mask quality and fit. Masking policies and hybrid schooling can also reduce peak hospitalization need by 71% and result in the fewest additional deaths post-school opening. We show that given the current vaccination rates within the community, the best option for children and the general population is to employ consistent high-quality masking, and use social distancing where possible.

BackgroundAcute coronary syndrome at first contact in primary care must be recognised rapidly and safely--especially in women and in adults with diabetes, who more often present without classic chest pain and are at risk of under-triage. We synthesised evidence on symptom constellations and triage strategies--rapid electrocardiogram, high-sensitivity cardiac troponin pathways, and primary-care risk tools--that reduce missed or late recognition of acute coronary syndrome. MethodsTargeted review (Jan 1, 2007-May 31, 2025) of prospective cohorts, diagnostic or implementation studies, risk-tool derivations and validations, telephone-triage studies, and contemporary guidelines relevant to first-contact primary care (office, urgent or emergency primary care, and out-of-hours services). Prespecified outcomes were missed acute coronary syndrome, 30-day major adverse cardiac events, time to electrocardiogram, time to troponin and decision, emergency-department transfer or admission, length of stay, and diagnostic performance (sensitivity, specificity, negative and positive predictive value). Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies-2, Newcastle-Ottawa Scale, and Risk of Bias 2, and certainty of evidence with Grading of Recommendations, Assessment, Development and Evaluation. FindingsAcross 18 sources, symptom clusters alone were insufficient to safely rule out acute coronary syndrome; history-based rules showed heterogeneous sensitivity and are best used to structure history and trigger testing. Rapid electrocardiogram (with repeats when concern persists) and high-sensitivity cardiac troponin algorithms provided the greatest diagnostic safety. Ambulatory implementations of assay-specific strategies achieved very high negative predictive values (approximately 99-100%) for rule-out in low-risk populations and accelerated disposition; an emergency primary-care deployment of the European Society of Cardiology 0/1-hour high-sensitivity troponin pathway ruled out about 64% at 1 hour, yielded a conclusive decision for about 77% by 4 hours, and reduced length of stay by roughly 2.2 hours. Safety margins were lower in patients with known coronary artery disease (negative predictive value about 96-98%) and the rule-out fraction was smaller, supporting more conservative thresholds, brief observation, or adjunctive clinical risk scoring. Telephone and out-of-hours case-control data linked non-retrosternal descriptors and system factors to missed acute coronary syndrome, arguing for up-triage to in-person electrocardiogram and troponin testing or emergency medical services transfer. InterpretationFor adults first assessed in primary care--particularly women and people with diabetes--a protocolised pathway (electrocardiogram within minutes, serial high-sensitivity troponin using assay-specific delta thresholds, and clear escalation) offers high rule-out safety with faster, more equitable care. Known coronary artery disease is a caution zone, warranting stricter discharge thresholds or extended observation. Health systems should invest in clinic electrocardiogram access, point-of-care high-sensitivity troponin where laboratory turnaround is slow, emergency-medical-services-first scripts, and routine audit (time to electrocardiogram and troponin, rule-out at 1 and 4 hours, emergency-department transfer, and 30-day major adverse cardiac events) stratified by sex, diabetes status, and coronary artery disease. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched MEDLINE (via PubMed), Embase, and Web of Science from Jan 1, 2007, to May 31, 2025, using terms for acute coronary syndrome (ACS)/chest pain, primary care/general practice/out-of-hours services, women/sex differences, diabetes, high-sensitivity cardiac troponin (hs-cTn; 0/1-hour and very-low strategies), telephone triage, and primary-care risk scores (Marburg Heart Score, INTERCHEST, HEART/HEAR). We hand-searched guideline repositories and reference lists. Three signals consistently emerged: (1) guidelines endorse rapid electrocardiogram (ECG) and hs-cTn-based pathways; (2) symptom clusters alone--particularly in women and people with diabetes--are insufficient to rule out ACS; and (3) primary-care data are sparse and heterogeneous, with safety concerns in known coronary artery disease (CAD) when accelerated rule-out algorithms are used. Few studies linked findings to operational metrics important at the primary-care front door (time-to-ECG/hs-cTn, rule-out proportions, length of stay [LOS]). Added value of this studyWe integrate first-contact primary-care evidence across 18 sources into a single, implementable pathway centered on rapid ECG, assay-specific hs-cTn strategies (0/1-hour or single very-low when symptom onset [&ge;]3 h), and explicit escalation thresholds. We foreground women and adults with diabetes, quantify rule-out safety including the known-CAD caveat, and pair clinical accuracy with operational outcomes (time-to-test, rule-out at 1/4 h, emergency department transfers, LOS). We provide a concise summary table and figure plus an audit set that clinicians can deploy immediately, alongside formal risk-of-bias and GRADE certainty judgments. Implications of all the available evidencePrimary care can safely accelerate ACS evaluation by pairing ECG within 10 minutes and hs-cTn algorithms with conservative thresholds in known CAD and proactive escalation for non-chest presentations common in women and people with diabetes (e.g., dyspnea, epigastric discomfort, unusual fatigue). Health systems should invest in clinic ECG access, point-of-care hs-cTn where laboratory turnaround is slow, emergency medical services (EMS)-first triage scripts, and routine audit of time-to-ECG/hs-cTn, rule-out proportions, emergency department transfers, and 30-day major adverse cardiac events (MACE) stratified by sex, diabetes, and CAD. Research priorities include prospective, consecutive primary-care cohorts with adjudicated 30-day outcomes, pragmatic trials of point-of-care hs-cTn, decision support tailored to known CAD, and cluster-randomized improvements to telephone/virtual triage.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often comorbid with conditions subject to quality metrics (QM) used for hospital performance assessment and rate-setting. Although diagnostic coding change in response to financial incentives is well documented, no study has examined the association of QM with SARS-CoV-2 cause-of-death attribution (CODA). Calculations of excess all-cause deaths overlook the importance of accurate CODA and of distinguishing policy-related from virus-related mortality. ObjectiveExamine CODA, overall and for QM and non-QM diagnoses, in 3 pandemic periods: awareness (January 19-March 14), height (March 15-May 16), and late (May 17-June 20). MethodsRetrospective analysis of publicly available national weekly COD data, adjusted for population growth and reporting lags, October 2014-June 20, 2020. CODA in 5 pre-pandemic influenza seasons was compared with 2019-20. Suitability of the data to distinguish policy-related from virus-related effects was assessed. ResultsFollowing federal guidance permitting SARS-CoV-2 CODA without laboratory testing, mortality from the QM diagnoses cancer and chronic lower respiratory disease declined steadily relative to prior-season means, reaching 4.4% less and 12.1% less, respectively, in late pandemic. Deaths for non-QM diagnoses increased, by 21.0% for Alzheimers disease and 29.0% for diabetes during pandemic height. Increases in competing CODs over historical experience, suggesting SARS-CoV-2 underreporting, more than offset declines during pandemic height. However, in the late-pandemic period, declines slightly numerically exceeded increases, suggesting SARS-CoV-2 overreporting. In pandemic-height and late-pandemic periods, respectively, only 83.5% and 69.7% of increases in all-cause deaths were explained by changes in the reported CODs, including SARS-CoV-2, preventing assessment of policy-related mortality or of factors contributing to increased all-cause deaths. ConclusionsSubstitution of SARS-CoV-2 for competing CODs may have occurred, particularly for QM diagnoses and late in the pandemic. Continued monitoring of these trends, qualitative research on pandemic CODA, and the addition of place-of-death data and psychiatric CODs to the file would facilitate assessment of policy-related and virus-related effects on mortality. Ascertainment of the number of deaths from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is foundational to understanding the severity, scope, and spread of the infection. Despite its importance, estimation of SARS-CoV-2 deaths is challenging because advanced age, genetic polymorphisms, and obesity-related comorbidities that predispose to inflammatory states increase the likelihood of dysregulated immunological function, severe respiratory distress, and mortality from infectious respiratory illness.1,2 These host factors represent competing potential causes of death (COD). For example, 98.8% of Italys SARS-CoV-2 deaths occurred in persons with >1 comorbidity, 48.6% with >3 comorbidities, and median decedent age was 80 years.3 Similarly, of U.S. SARS-CoV-2 deaths reported as of May 28, 2020, 93% involved other CODs (mean 2.5 additional causes), and 60% occurred in persons aged >75 years.4 This pattern of multiple contributing CODs is common in respiratory infection-related mortality.5 In death certificate issuance during the pandemic, methods to account for this pattern varied, as no single standard for SARS-CoV-2-attributable death exists. In Italy, all deaths in patients testing positive for SARS-CoV-2 were attributed to the infection despite high prevalence rates for comorbid conditions, measured in early deaths: ischemic heart disease (30%), diabetes (36%), cancer (20%), and atrial fibrillation (25%).6 The U.S. National Center for Health Statistics (NCHS) issued death-certification guidance on March 4, 2020, indicating that SARS-CoV-2 should be reported if "the disease caused or is assumed to have caused or contributed to death."7 Follow-up guidance issued on April 3 indicated that it was "acceptable to report COVID-19 on a death certificate without [laboratory test] confirmation" if circumstances indicating likely infection were "compelling within a reasonable degree of certainty."8 This nonspecific guidance should be interpreted in light of previous research findings that COD attribution (CODA) errors are common on death certificates, particularly in infectious disease and septic shock.9,10 In one survey of New York City (NYC) resident physicians in 2010, 49% indicated they had knowingly reported an inaccurate COD on one or more certificates, often (54%) at the behest of hospital staff, and 70% reported they had at least once been unable to report septic shock "as an accepted cause of death" and had been "forced to list an alternate cause."9 In an audit of NYC data from 2010-2014, 67% of pneumonia death certificates contained >1 error, compared with 46% for cancer and 32% for diabetes.10 Such CODA ambiguities are often addressed by calculating "excess deaths," defined as all-cause deaths exceeding those projected from historical experience.11 This method, recently used to estimate that official tallies of SARS-CoV-2 deaths represented only about 66%-78% of the diseases true mortality impact,12,13 is potentially advantageous in estimating SARS-CoV-2 impact by accounting for deaths that may not have been explicitly coded as infection-related.14 Examples include deaths from cardiac events to which undetected SARS-CoV-2 may have contributed15 or out-of-hospital deaths occurring without medical care because of health-system overcrowding.16 Despite these advantages, the method is compromised by 3 considerations when applied to SARS-CoV-2 CODA, which should be quantified to inform future policy. First, the method should distinguish natural from societal causes to account for possible consequences of policy decisions and fears that, although prompted by anticipated effects of SARS-CoV-2, were not direct or inevitable viral sequelae. Examples include suicides from stay-at-home order-related labor market contraction17 and social isolation,18 increases in domestic violence,19 overdoses due to interruptions in substance use disorder treatment,20 and delays in emergency care for life-threatening conditions21-23 in geographic areas where health-system overcrowding was expected but not realized.24,25 To promote evidence-based public health policy, population-level disease-mitigation strategies that go beyond traditional practices of isolating the sick and quarantining those exposed to disease merit empirical investigation.26,27 Second, the method should reflect the effects that financial incentives around hospital quality metrics (QM), which are commonly associated with provider coding practices, may have on CODA.28-30 For example, in United Kingdom hospitals, increases in coding for palliative-care admissions produced a severity-adjusted mortality-rate decline of 50% over the 5-year period ending in 2009, while the crude death rate remained unchanged.31 Although we are not aware of studies linking QMs to CODA, it is known that CODA errors are more likely to occur in hospitals than elsewhere,32 with an 85% error rate reported in comparisons of death certificates with autopsy findings at one regional academic institution.33 The potential effect of financial incentives on CODA is particularly important for SARS-CoV-2 because several competing CODs, including chronic lower respiratory disease (CLRD), acute myocardial infarction, heart failure, pneumonia, and stroke, are included in Medicare 30-day mortality measures used to calculate prospective payment rates.34 All but one of these (CLRD) is included in Agency for Healthcare Research and Quality inpatient quality indicators.35 Sepsis and cancer, other competing causes of death, are also the target of QM.36-38 Although not affecting all-cause death counts, the incentive to substitute SARS-CoV-2 for another COD could affect the accuracy of the SARS-CoV-2-attributed count. Third, the method should account for baseline life expectancies among those whose deaths were reported as caused by SARS-CoV-2. For example, at age 80 years, the 1-year probability of death is 5.8% for males and 4.3% for females, higher in those with cardiovascular comorbidities.39,40 In that age group, the population-level risk of a SARS-CoV-2 death in New York City, a pandemic epicenter, was 1.5% in about 3 pandemic months through June 17, 2020.41 Thus, deaths from competing CODs would be expected to decline late in the pandemic and in subsequent months. From a policy perspective, quantifying this effect is consistent with the quality-adjusted life year approach in evidence-based medicine, which considers future life expectancy in assessing the effects of disease and disease-mitigation interventions.42 To permit assessments of SARS-CoV-2-related mortality, publicly available NCHS data include weekly aggregated totals for all-cause deaths, natural-cause deaths, and selected categories of CODs, reported as final data for 2014-2018 and provisional data for 2019-2020.4 These data, which are updated weekly, have important limitations. First, International Classification of Diseases (ICD)-10 diagnosis codes are grouped into broad categories, rather than the individual ICD-10 codes available in full COD files (Appendix 1). Second, only 11 selected diagnostic categories are reported. Third, although 63% of deaths are reported within 10 days, reporting lags vary by state.4 Reporting delays for injurious deaths are greater because they require investigation (e.g., forensic toxicology).43 Pending investigation, these deaths are often assigned ICD-10 code R99, "ill-defined and unknown cause of mortality."43 In this exploratory study, we used these files to provide preliminary evidence on the following: (1) change in CODA compared with historical experience; (2) association of CODA with QM; and (3) suitability of the files to distinguish policy-related from virus-related effects. All analyses were adjusted for population and reporting lags and based on comparisons of 2020 with equivalent weeks in the 5 most recent years. We hypothesized that if substitution of SARS-CoV-2 for alternative CODs occurred, death counts for competing diagnoses would decline relative to historical experience during the pandemic, especially after issuance of the NCHS death-certification guidance; these declines would be greater for QM than for other conditions; and they would accelerate late in the pandemic as earlier SARS-CoV-2 deaths offset later deaths from competing causes.

IntroductionBlack Americans have the highest prevalence of hypertension among all racial or ethnic groups in the United States.1 They are 40% more likely to have uncontrolled blood pressure2 and are five times more likely to die from hypertension compared to non-Hispanic whites.3,4 Experiences of discrimination in healthcare, clinician and institutional bias, and socioeconomic and environmental inequities driven by structural racism contribute to uncontrolled hypertension in this population.3,5-8 Multilevel, multicomponent interventions have effectively improved blood pressure control among Black Americans but remain inadequately implemented in the clinical setting. An integrated nursing/public health quality improvement study was designed to address this gap between evidence and integration into clinical practice. MethodsUsing a one group pre/posttest design, we examined the effect of an innovative, evidence-based 12-week intervention on blood pressure among Black Americans with uncontrolled hypertension aged 18 and older in the primary care setting. Intervention components included remote blood pressure monitoring, weekly phone coaching with culturally congruent care, medication intensification, and a standardized hypertension protocol. ResultsThe average age of the participants (n=35) was 64 years, and two thirds (n=23) were female (66%). The mean difference in systolic blood pressure from pre to post intervention decreased significantly (M=23, SD=14.0), t(34)= -9.7, p < .001. A significant reduction in the mean difference in diastolic blood pressure from pre to post intervention was also observed (M=11, SD=11.8), t(34)= -5.5, p < .001. At 12 weeks, 87% of participants had achieved blood pressure control. The intervention also improved medication adherence and hypertension knowledge (p <.001). ConclusionA multicomponent, culturally congruent quality improvement intervention significantly improved blood pressure among Black Americans. Health Equity ImplicationsScaled up implementation of equity-centered, culturally congruent approaches are needed to reduce racial disparities in hypertension control.

ObjectivesArtificial intelligence (AI)-enabled digital stethoscopes combine phonocardiography and electrocardiography to support detection of cardiac rhythm and structural abnormalities. This study evaluated the feasibility and exploratory diagnostic performance of AI-guided cardiac auscultation during routine general practice consultations and home visits. MethodsIn this prospective feasibility study, 50 consecutive patients aged [&ge;]65 years underwent AI-assisted auscultation using the Eko CORE 500 during routine care. Recordings were attempted at four standard cardiac positions. Feasibility outcomes included technical failure, workflow disruption, and proportion of analyzable recordings (defined as successful AI output based on combined ECG and phonocardiography signals). Exploratory diagnostic performance was assessed against previously established diagnoses of atrial fibrillation (AF), heart failure (HF), or valvular heart disease (VHD) documented in the electronic medical record. ResultsAI-guided cardiac auscultation was completed in all patients without device malfunction or meaningful workflow disruption (median acquisition time 1-2 minutes). At least one analyzable recording was obtained in 47/50 patients (94%), and complete four-position analyses in 42/50 (84%). Signal limitations were mainly attributable to obesity, chest hair, or excess breast tissue. Among 47 analyzable patients, 11 had known AF, HF, or VHD. Sensitivity for detecting these conditions was 81.8% and specificity 91.7%. One new case of clinically relevant mitral regurgitation was identified. ConclusionsAI-enabled digital auscultation was feasible in routine general practice, with high rates of analyzable recordings and minimal workflow impact. Larger studies with contemporaneous reference standards are warranted to determine clinical utility.

BackgroundLung cancer is the most common cause of cancer-related death in the United States (US), with most patients diagnosed at later stages (3 or 4). While most patients are diagnosed following symptomatic presentation, no studies have compared symptoms and physical examination signs at or prior to diagnosis from electronic health records (EHR) in the United States (US). ObjectiveTo identify symptoms and signs in patients prior to lung cancer diagnosis in EHR data. Study DesignCase-control study. MethodsWe studied 698 primary lung cancer cases in adults diagnosed between January 1, 2012 and December 31, 2019, and 6,841 controls matched by age, sex, smoking status, and type of clinic. Coded and free-text data from the EHR were extracted from 2 years prior to diagnosis date for cases and index date for controls. Univariate and multivariate conditional logistic regression were used to identify symptoms and signs associated with lung cancer. Analyses were repeated excluding symptom data from 1, 3, 6, and 12 months before the diagnosis/index dates. ResultsEleven symptoms and signs recorded during the study period were associated with a significantly higher chance of being a lung cancer case in multivariate analyses. Of these, seven were significantly associated with lung cancer six months prior to diagnosis: hemoptysis (OR 3.2, 95%CI 1.9-5.3), cough (OR 3.1, 95%CI 2.4-4.0), chest crackles or wheeze (OR 3.1, 95%CI 2.3-4.1), bone pain (OR 2.7, 95%CI 2.1-3.6), back pain (OR 2.5, 95%CI 1.9-3.2), weight loss (OR 2.1, 95%CI 1.5-2.8) and fatigue (OR 1.6, 95%CI 1.3-2.1). ConclusionsPatients diagnosed with lung cancer appear to have symptoms and signs recorded in the EHR that distinguish them from similar matched patients in ambulatory care, often six months or more before their diagnosis. These findings suggest opportunities to improve the diagnostic process for lung cancer in the US.

IntroductionPreventive counseling improves long-term health, but primary care clinicians face time constraints limiting patient education. In a prior emergency department pilot study, a brief passive video trended towards increased patients willingness to change health behaviors. The current trial, conducted at the primary care clinic, evaluates the feasibility and impact of a short, interactive prevention video delivered during a primary care office visit. Methods and analysisWe will conduct a prospective, randomized, non-blinded clinical trial among adult patients presenting to a primary care clinic. Immediately after their appointment, participants will be randomized to receive either the interactive prevention video with a practitioner or usual care. The video maintains engagement through simple in-video questions and adapts content based on patient responses (e.g., skipping smoking cessation for non-smokers). After the encounter, all participants will complete surveys assessing readiness and confidence to initiate lifestyle change including a transtheoretical "readiness ruler." Survey items will be drawn from validated instruments, including the Gillespie & Lenz Readiness and Confidence to Participate in Lifestyle Activities Surveys, the Pittsburgh Sleep Quality Index (PSQI), and select questions from the U.S. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) Survey. Patients will be asked for medical record access and permission for follow-up contact. OutcomesThe primary outcome is index-visit Lifestyle Readiness and Confidence to Change scores. Secondary outcomes include satisfaction with the clinic visit, intention to change specific lifestyle behaviors, and healthcare use outside the clinic at 30 days and 6 months, as assessed via record review. A 3-12-month follow-up survey will assess self-reported lifestyle changes and new diagnoses. Statistical plan and sample sizeAnalyses will follow intention-to-treat. Ordinal logistic regression will compare primary outcomes between arms, adjusting for Charlson Comorbidity Index, age, sex, gender, and prespecified predictors. Logistic regression will evaluate binary follow-up outcomes. Complete-case analyses will be used, and differential attrition will be reported. We plan to enroll approximately 350 patients. Trial registrationhttps://ClinicalTrials.gov NCT06730737.

The Mendelian Phenotype Search Engine (MPSE), a clinical decision support tool using Natural Language Processing and Machine Learning, helped neonatologists expedite decisions to whole genome sequencing (WGS) to diagnose patients in the Neonatal Intensive Care Unit. After the MPSE was introduced, utilization of WGS increased, time to ordering WGS decreased, and WGS diagnostic yield increased.

Purpose: We systematically reviewed the evidence for three questions on screening for lung cancer with computed tomography (CT): benefits (from randomized trials) and harms of screening versus no screening/minimal intervention or alternative screening approaches (e.g., selection criteria, screening intervals); relative importance that informed patients place on the potential benefits and harms of screening (patient preferences); and comparative effects from observational studies of different screening selection criteria (using risk prediction models) or nodule classification systems compared with those used in the screening trials. Methods: A working group of primary care and specialist clinicians (previously members of Canadian Task Force on Preventive Health Care) and topic experts provided input into the eligibility criteria and key potential effect moderators, rated outcomes for their importance to decision making, and developed decision thresholds for use when making conclusions and assessing certainty of the evidence. Critical outcomes of screening effects included all-cause mortality, lung-cancer mortality, and overdiagnosis (via excess cancer incidence from screening). For patient preferences, we sought direct preference data via (i) disutilities of relevant health states (measuring their impact on ones health-related quality of life on a scale of 0 [perfect health] to 1 [death], mainly using EQ-5D), and (ii) other preference-based data, such as outcome trade-offs, as well as indirect preference data via (iii) the relative importance of benefits versus harms inferred from attitudes, intentions, and behaviors towards screening among eligible patients informed with estimates of the outcomes. For screening benefits and harms and for patient preferences, we searched three databases (MEDLINE, Embase, and Central & MEDLINE, Scopus, and EconLit, respectively) to July 11, 2025. For screening studies published prior to 2015 we relied on searches for other reviews, and for patient preferences our search was limited to 2012-onwards. For comparative effects, we searched MEDLINE and Embase from 2019 to September 23, 2025, with reliance on other reviews for studies published 2012-2018. Reference lists were scanned and trial registries searched. For the main searches, two independent reviewers screened titles and abstracts and then full texts; for search updates we applied AI to assist with title and abstract screening. Data extraction and analysis were undertaken by single reviewers, with verification; risk of bias and GRADE certainty assessments were undertaken independently by at least two reviewers. Data were pooled where suitable using random effects methods appropriate to the outcome metric and prevalence. Subgroup analyses explored heterogeneity (e.g., sex, number of rounds, type of comparator, sensitivity of nodule management, type of utility measurement). When not pooled (e.g., patient preferences based on screening intentions) data were analyzed by grouping studies based on factors such as population, setting, exposure, and outcomes, with consideration of study size and risk of bias. Conclusions and certainty assessments for screening effects were based on estimates of absolute effects. Results: We included 85 studies (N=640,537; 13 trials) on screening benefits and harms, 59 on patient preferences (33 [N=42,219] on disutilities and 26 [N=10,829] other studies), and 16 for comparing trial (National Lung Screening Trial [NLST]) and LungRADs nodule management, either directly (2 studies, N=26,978) or indirectly (14 studies, N=1,102,285). Screening benefits and harms: Findings from nine trials (N=94,530) examining low-dose CT (LDCT) screening on all-cause (RR 0.97, 95% CI 0.93 to 1.01; 3.7 fewer [8.5 fewer to 1.2 more] per 1000) and lung-cancer mortality (RR 0.87, 95% CI 0.79 to 0.96; 4.0 fewer [1.2 to 6.4 fewer] per 1000) offered low and moderate certainty, respectively, that screening previous/current 20-30 pack-year smokers 50-74 years old 3-4 times will probably result in at least 1 (all-cause) and 2 (cause-specific) fewer deaths per 1000 screened after 10-12 years. The absolute effects may not apply to participants at the lowest baseline risk for lung-cancer incidence (e.g., <1.5% over 6 years) or death. Seven trials (N=35,161) contributed to meta-analysis for overdiagnosis (RR 1.19, 95% CI 1.03 to 1.37; 8.4 [1.3 to 16.3] per 1000), and our certainty was moderate that LDCT screening 3-4 times will probably result in at least 2.5 cases of overdiagnosis per 1000 screened over 10 years. For important outcomes, we had high certainty that screening 3-4 times results in at least 75 people per 1000 screened (and probably at least 225) having at least one benign biopsy/false positive, 150 having one or more incidental findings (likely at least 450), and 50 (probably at least 100) having a clinically significant/actionable incidental finding, but probably does not have an important impact on major complications or death from invasive testing among those without cancer. Though undergoing a LDCT scan probably causes little-to-no psychosocial harm, having a positive screening result likely causes at least a small degree of harm (i.e., 4-8% change from baseline), especially for the 10-15% having to undergo invasive procedures where some may experience moderate harm. Among those without cancer, these effects may last for several months while the diagnostic process is underway, though moderate certainty evidence found little-to-no effects remaining after 6 months from diagnostic resolution. Comparative effects: Findings from applying different baseline predicted risks for lung-cancer incidence or mortality to the trial populations (i.e., alternative selection criteria) were considered with the effects from screening benefits and harms. Using LungRADs instead of NLST nodule management (among NLST eligible people) probably reduces the false positive rate substantially (about half), though the number of false positives still exceeded the decision threshold of 75 per 1000 and the effects for benefits or other harm outcomes are not known. Patient preferences: Findings showed little-to-no disutility (i.e., <0.04) from a positive screening test (moderate certainty) or a false positive result (low certainty). Low-certainty evidence found there may be little-to-no disutility from a stage I-IIIA cancer diagnosis (before treatment) but small but important disutilities from a stage IIIB/IV diagnosis, during first-line treatment of any stage (though possibly moderate disutility of about 0.09 for stage IIIB/IV), and after treatment for stage IIIB/IV but not stage I-IIIA (without progression) where effects were inconsistent but indicated that any disutility may not be long-lasting. Findings for stage I-IIIA are likely most relevant for understanding the consequences of overdiagnosis. For stated preferences between outcomes, there was low certainty evidence that a small majority (51-75%) of people may accept 69-122 false positives and at least 1.3 cases of overdiagnosis per prevented lung-cancer death, and think that the reduction in lung-cancer mortality is more important than experiencing one of the relevant harms. After being informed about anticipated benefits and harms from screening (with the largest screening effects shown to those at higher baseline risk), progressively more people preferred screening (mainly via intentions) as the net benefit of screening improved from low [25-50% preferred] to moderate [51-75%] to high [>75%]. Conclusions: This review provides contemporary data on the benefits and harms of LDCT screening after at least a decade of follow-up and makes conclusions based on absolute effects while considering thresholds for decision making. Across the reviews, findings indicate that screening those aged 50-74 years with 3-4 rounds of LDCT will lead to benefits and harms for which a majority, but not all, eligible people probably find acceptable and worthwhile. While current nodule management using LungRADs likely reduces false positives, whether it impacts the benefits of screening is less certain and worth further research. Further, comparative prospective studies are lacking to determine the effects from screening for those not meeting the minimum age (50 years) and smoking history criteria in the trials, despite having an equivalent risk for lung cancer.

BackgroundHypertension guidelines recommend the use of automated BP devices over manual devices to reduce observer bias, such as terminal digit preference. We aimed to evaluate systematic differences in BP readings and the association with incident stroke according to type of measurement. MethodsUsing de-identified electronic health record data from Optum Labs Data Warehouse from primary care visits in 2024, we classified providers BP measurement method using proportion of odd terminal digit preference as a proxy for manual devices (defined as <0.5% odd digits) and automated devices (defined as 45-55% odd digits). Patients from the manual and automated groups were matched on demographic and clinical covariates. We evaluated cross-sectional BP distributions by measurement modality, and compared mean BP and proportions meeting clinical thresholds using t-tests, and chi squared tests, respectively. In a separate 2019 cohort created using the same methods, we evaluated whether longitudinal associations between systolic BP and incident stroke differ by measurement method. ResultsAmong 336,634 matched patients, mean SBP in the automated group was 131.7 (19.3) mmHg and 125.9 (14.8) mmHg in the manual group. The absolute percentage of patients meeting BP clinical thresholds differed substantially (<130/80: automated 33.2% vs. manual 38.8%; <140/90: automated 61.2% vs. manual 70.9%). Among 686,482 matched patients in the 2019 cohort, the manual group had a 1.16-fold (1.10-1.22) higher risk of stroke at any given BP compared to the automated group. ConclusionManual BP measurement was associated with lower mean BP, BP control, and potential underestimation of stroke risk.

Before January 22, 2020, only one pediatric case of COVID-19 was reported in mainland China1,2. However, a retrospective surveillance study3 identified six children who had been hospitalized for COVID-19 in one of three central Wuhan hospitals between January 7th and January 15th. Given that Wuhan has over 395 other hospitals, there may have been far more severe pediatric cases than reported.

BackgroundThe Centers for Medicare and Medicaid Services (CMS) New Technology Add-on Payment (NTAP) program supports adoption of new, costly medical technologies demonstrating substantial clinical improvement. In 2021, CMS waived the "substantial clinical improvement" criterion for devices designated under the FDA Breakthrough Devices Program (BDP). This study characterized risk-standardized payments associated with hospitalizations in which Medicare beneficiaries received calcium modification during PCI for acute myocardial infarction (AMI) following the adoption of the Shockwave C2 Coronary Intravascular Lithotripsy (IVL) Catheter (Shockwave Medical) with BDP designation. MethodsWe analyzed Medicare beneficiaries hospitalized for AMI who underwent PCI between January 2021 and December 2022, stratifying them into four groups: no calcium modification, rotational atherectomy (RA), orbital atherectomy (OA), and coronary IVL. Risk-standardized Medicare payments at 30 days, including index facility, physician, and post-acute care costs, were assessed using non-parametric median and chi-square tests. ResultsAmong 87,238 patients, 76,462 (87.6%) received no calcium modification, 8,316 (9.5%) underwent RA, 793 (0.9%) underwent OA, and 1,668 (1.9%) underwent IVL. IVL use increased from 1.6% in October 2021 to 4.4% in December 2022. Median total risk-standardized Medicare payments were significantly higher for patients receiving calcium modification technologies ($27,579 for IVL, $27,353 for OA, $23,240 for RA) compared to those without ($19,115; p<0.001). Payment differences were largest for index facility payments. ConclusionCoronary IVL during PCI for Medicare patients hospitalized for AMI was associated with significantly increased Medicare payments. Further studies must determine whether IVL, and calcium modification technologies in general, improve outcomes for patients hospitalized for AMI undergoing PCI and thus warrant higher payments via NTAP.

IntroductionThe spring 2023 COVID-19 booster vaccination programme in England used both Pfizer BA.4-5 and Sanofi vaccines. All people aged 75 years or over and the clinically vulnerable were eligible to receive a booster dose. Direct comparisons of the effectiveness of these two vaccines in boosting protection against severe COVID-19 events have not been made in trials or observational data. MethodsWith the approval of NHS England, we used the OpenSAFELY-TPP database to compare effectiveness of the Pfizer BA.4-5 and Sanofi vaccines during the spring 2023 booster programme, between 1 April and 30 June 2023. We investigated two cohorts separately: those aged 75 or over (75+); and those aged 50 or over and clinically vulnerable (CV). In each cohort, vaccine recipients were matched on date of vaccination, COVID-19 vaccine history, age, and other characteristics. Effectiveness outcomes were COVID-19 hospital admission, COVID-19 critical care admission, and COVID-19 death up to 16 weeks after vaccination. Safety outcomes were pericarditis and myocarditis up to 4 weeks after vaccination. We report the cumulative incidence of each outcome, and compare safety and effectiveness using risk differences (RD), relative risks (RR), and incidence rate ratios (IRRs). Results492,642 people were 1-1 matched in the CV cohort, and 673,926 in the 75+ cohort, contributing a total of 7,423,251 and 10,173,230 person-weeks of follow-up, respectively. The incidence of COVID-19 hospital admission was higher for Sanofi than for Pfizer BA.4-5. In the CV cohort, 16-week risks per 10,000 people were 22.3 (95%CI 20.4 to 24.3) for Pfizer BA.4-5 and 26.4 (24.4 to 28.7) for Sanofi, with an IRR of 1.19 (95%CI 1.06 to 1.34). In the 75+ cohort, these were 17.5 (16.1 to 19.1) for Pfizer BA.4-5 and 20.4 (18.9 to 22.1) for Sanofi, with an IRR of 1.18 (1.05-1.32). These findings were similar across all pre-specified subgroups. More severe COVID-19 related outcomes (critical care admission and death), and safety outcomes at 4 weeks, were rare in both vaccines so we could not reliably compare effectiveness of the two vaccines. ConclusionThis observational study comparing effectiveness of Pfizer BA.4-5 and Sanofi vaccine during the spring 2023 programme in England in the two main eligible cohorts - people aged 75 and over and in clinically vulnerable people - found some evidence of superior effectiveness against COVID-19 hospital admission for Pfizer BA.4-5 compared with Sanofi within 16 weeks after vaccination.

Smoking Cessation Efforts for Patients with Asthma and COPD IntroductionSmoking cessation can alter the natural history of both COPD and asthma by reducing the frequency and severity of exacerbations and slowing disease progression. Accordingly, the Global Initiative for Asthma and the Global Initiative for Chronic Obstructive Lung Disease recommend that clinicians address smoking cessation at every visit using counseling and pharmacotherapy. MethodsThe Mount Sinai Health System includes seven hospitals and more than 400 outpatient locations in the New York metropolitan area, all using a unified electronic medical record (Epic). De-identified data from calendar year 2024 were extracted for individuals identified as current smokers via the EMR smoking status tool. Patients with asthma and/or COPD were identified using ICD-10 codes. Tobacco treatment was defined as receipt of counseling or pharmacotherapy, including varenicline, bupropion, or nicotine replacement therapy. ResultsAmong 961,997 patients, 58,566 (6.1%) were identified as current cigarette smokers. Across all health system encounters, 32.6% of smokers with both asthma and COPD were given any treatment, followed by 26.7% of smokers with COPD, 13.0% of smokers with asthma, and 9.9% of cigarette smokers without these conditions. Smokers seen in pulmonary clinics were the most likely to be given treatment (17.4%), followed next by primary care (6.6%).The most commonly used treatment for all cohorts and all treatment settings was nicotine with the exception of the pulmonary clinic where varenicline predominated. DiscussionDespite higher treatment rates among smokers with asthma and COPD, only one-third of those with either condition received cessation treatment over a full year, underscoring the need for sustained system-wide quality improvement efforts.

ObjectiveTo determine whether antibodies against the SARS-CoV-2 spike protein following BNT162B2 (Pfizer-BioNTech) COVID-19 mRNA vaccination cross-react with human syncytin-1 protein, and if BNT162B2 mRNA enters breast milk. MethodsIn this observational cohort study of female front-line workers with no history of COVID-19 infection, we amplified BNT162B2 mRNA in plasma and breast milk and assayed anti-SARS-CoV-2 neutralising antibodies and anti-human syncytin-1 binding antibodies in plasma, at early (1-4 days) and late (4-7 weeks) time points following first-dose vaccination. ResultsFifteen consented participants (mean age 40.4 years, various ethnicities) who received at least one dose of BNT162B2, including five breast-feeding women and two women who were inadvertently vaccinated in early pregnancy, were recruited. BNT162B2 mRNA, detected by amplifying part of the spike-encoding region, was detected in plasma 1-4 days following the first dose (n=13), but not 4-5 weeks later (n=2), nor was the mRNA isolated from aqueous or lipid breast milk fractions collected 0-7 days post-vaccination (n=5). Vaccine recipients demonstrated strong SARS-CoV-2 neutralising activity by at least four weeks after the first dose (n=15), including the two pregnant women. None had placental anti-syncytin-1 binding antibodies at either time-point following vaccination. ConclusionsBNT162B2-vaccinated women did not transmit vaccine mRNA to breast milk, and did not produce a concurrent humoral response to syncytin-1, suggesting that cross-reactivity to syncytin-1 on the developing trophoblast, or other adverse effects in the breast-fed infant from vaccine mRNA ingestion, are unlikely. What are the novel findings of this work?COVID-19 vaccination with BNT162B2 did not elicit a cross-reacting humoral response to human syncytin-1 despite robust neutralising activity to the SARS-CoV2 spike protein, and while vaccine mRNA was isolated from plasma, it was not found in breast milk. What are the clinical implications of this work?Our work directly addresses the fertility and breastfeeding concerns fuelling vaccine hesitancy among reproductive-age women, by suggesting that BNT162B2 vaccination is unlikely to cause adverse effects on the developing trophoblast, via cross-reacting anti-syncytin-1 antibodies, or to the breastfed neonate, via mRNA breast milk transmission.

BackgroundChildren and adolescents in England were offered BNT162b2 as part of the national COVID-19 vaccine roll out from September 2021. We assessed the safety and effectiveness of first and second dose BNT162b2 COVID-19 vaccination in children and adolescents in England. MethodsWith the approval of NHS England, we conducted an observational study in the OpenSAFELY-TPP database, including a) adolescents aged 12-15 years, and b) children aged 5-11 years and comparing individuals receiving i) first vaccination with unvaccinated controls and ii) second vaccination to single-vaccinated controls. We matched vaccinated individuals with controls on age, sex, region, and other important characteristics. Outcomes were positive SARS-CoV-2 test (adolescents only); COVID-19 A&E attendance; COVID-19 hospitalisation; COVID-19 critical care admission; COVID-19 death, with non-COVID-19 death and fractures as negative control outcomes and A&E attendance, unplanned hospitalisation, pericarditis, and myocarditis as safety outcomes. ResultsAmongst 820,926 previously unvaccinated adolescents, the incidence rate ratio (IRR) for positive SARS-CoV-2 test comparing vaccination with no vaccination was 0.74 (95% CI 0.72-0.75), although the 20-week risks were similar. The IRRs were 0.60 (0.37-0.97) for COVID-19 A&E attendance, 0.58 (0.38-0.89) for COVID-19 hospitalisation, 0.99 (0.93-1.06) for fractures, 0.89 (0.87-0.91) for A&E attendances and 0.88 (0.81-0.95) for unplanned hospitalisation. Amongst 441,858 adolescents who had received first vaccination IRRs comparing second dose with first dose only were 0.67 (0.65-0.69) for positive SARS-CoV-2 test, 1.00 (0.20-4.96) for COVID-19 A&E attendance, 0.60 (0.26-1.37) for COVID-19 hospitalisation, 0.94 (0.84-1.05) for fractures, 0.93 (0.89-0.98) for A&E attendance and 0.99 (0.86-1.13) for unplanned hospitalisation. Amongst 283,422 previously unvaccinated children and 132,462 children who had received a first vaccine dose, COVID-19-related outcomes were too rare to allow IRRs to be estimated precisely. A&E attendance and unplanned hospitalisation were slightly higher after first vaccination (IRRs versus no vaccination 1.05 (1.01-1.10) and 1.10 (0.95-1.26) respectively) but slightly lower after second vaccination (IRRs versus first dose 0.95 (0.86-1.05) and 0.78 (0.56-1.08) respectively). There were no COVID-19-related deaths in any group. Fewer than seven (exact number redacted) COVID-19-related critical care admissions occurred in the adolescent first dose vs unvaccinated cohort. Among both adolescents and children, myocarditis and pericarditis were documented only in the vaccinated groups, with rates of 27 and 10 cases/million after first and second doses respectively. ConclusionBNT162b2 vaccination in adolescents reduced COVID-19 A&E attendance and hospitalisation, although these outcomes were rare. Protection against positive SARS-CoV-2 tests was transient.