Effectiveness of BNT162b2 COVID-19 primary series vaccination in children aged 5-17 years in the United States: a cohort study.

BACKGROUND: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study's objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. METHODS: This cohort study identified children aged 5-17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. RESULTS: There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36-40%]) and hospital/ED-diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56-65%]). VE estimates were lowest among children 5-11 years and during the Omicron-variant era. CONCLUSIONS: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED-diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. REGISTRATION: The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

Validation of cardiovascular outcomes and risk factors in the Clinical Practice Research Datalink in the United Kingdom.

PURPOSE: Strategies to identify and validate acute myocardial infarction (AMI) and stroke in primary-care electronic records may impact effect measures, but to an unknown extent. Additionally, the validity of cardiovascular risk factors that could act as confounders in studies on those endpoints has not been thoroughly assessed in the United Kingdom Clinical Practice Research Datalink's (CPRD's) GOLD database. We explored the validity of algorithms to identify cardiovascular outcomes and risk factors and evaluated different outcome-identification strategies using these algorithms for estimation of adjusted incidence rate ratios (IRRs). METHODS: First, we identified AMI, stroke, smoking, obesity, and menopausal status in a cohort treated for overactive bladder by applying computerized algorithms to primary care medical records (2004-2012). We validated these cardiovascular outcomes and risk factors with physician questionnaires (gold standard for this analysis). Second, we estimated IRRs for AMI and stroke using algorithm-identified and questionnaire-confirmed cases, comparing these with IRRs from cases identified through linkage with hospitalization/mortality data (best estimate). RESULTS: For AMI, the algorithm's positive predictive value (PPV) was >90%. Initial algorithms for stroke performed less well because of inclusion of codes for prevalent stroke; algorithm refinement increased PPV to 80% but decreased sensitivity by 20%. Algorithms for smoking and obesity were considered valid. IRRs based on questionnaire-confirmed cases only were closer to IRRs estimated from hospitalization/mortality data than IRRs from algorithm-identified cases. CONCLUSIONS: AMI, stroke, smoking, obesity, and postmenopausal status can be accurately identified in CPRD. Physician questionnaire-validated AMI and stroke cases yield IRRs closest to the best estimate.

Review of Survival, Safety, and Clinical Outcomes in HER2+ Metastatic Gastric Cancer Following the Administration of Trastuzumab.

BACKGROUND: Therapies targeting human epidermal growth factor receptor 2 (HER2) have become a focus for improving treatment outcomes in patients with gastric cancer. This literature review sought to assesses clinical outcomes, including safety, survival, and treatment outcomes, of patients who received trastuzumab for the treatment of HER2+ metastatic gastric cancer. METHODS: Searches were conducted in PubMed and Embase to identify observational research studies investigating the clinical outcomes of trastuzumab and combination therapies for the treatment of HER2+ metastatic gastric cancer, published January 1, 2014-August 22, 2019. Article screening was a two-phase process, and the results of each screening level were documented in accordance with PRISMA. RESULTS: Twenty articles met the selection criteria for data extraction. Studies focused on treatment patterns or survival, safety, and clinical outcomes, as well as the natural history of disease. In the combined HER2+ patient populations included in this review, tumors were located in the stomach (33.7%), gastroesophageal junction (GEJ, 14.2%), unspecific GEJ or stomach (50.3%), or esophagus (1.9%). Studies observed increases in both overall survival and progression-free survival with the use of trastuzumab-based chemotherapy compared with chemotherapy treatment alone. Additionally, trastuzumab-based chemotherapy appeared to improve survival and clinical outcomes regardless of the presence of multi-organ metastases or tumor location. CONCLUSIONS: Trastuzumab-treated patients have longer survival times than those not treated with trastuzumab and tolerate treatment well, with few serious adverse events. New treatments for second- and subsequent-line therapies would increase regimen options. MINI-ABSTRACT: The treatment patterns and clinical outcomes observed in this literature review suggest patients treated with trastuzumab have longer survival times compared with chemotherapy treatment alone and tolerate treatment.

Patterns of use of antimuscarinic drugs to treat overactive bladder in Denmark, Sweden, and the United Kingdom.

PURPOSE: To describe the use of antimuscarinic drugs to treat overactive bladder (OAB) in Denmark, Sweden, and the United Kingdom (UK). METHODS: We identified new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium aged 18 years or older from the Danish National Registers (2004-2012), the Swedish National Registers (2006-2012), and UK Clinical Practice Research Datalink (2004-2012). Users were followed until disenrollment, cancer diagnosis, death, or study end. Treatment episodes, identified by linking consecutive prescriptions, were described with respect to duration, drug switch, and drug add-on. RESULTS: Mean age of OAB drug users was 66 years in Denmark (n = 72,917) and Sweden (n = 130,944), and 62 years in the UK (n = 119,912); 60% of Danish and Swedish patients and 70% of UK patients were female. In Denmark, of 224,680 treatment episodes, 39% were with solifenacin, and 35% with tolterodine; 2% were with oxybutynin. In Sweden, of 240,141 therapy episodes, 37% were with tolterodine and 35% with solifenacin; 5% were with oxybutynin. In the UK, of 245,800 treatment episodes, 28% were with oxybutynin, 27% with solifenacin, and 26% with tolterodine. In the three countries, 49%-52% of treatment episodes comprised one prescription and over 80% of episodes ended because of no refill; less than 20% ended because of a switch to another antimuscarinic. During the study years, we observed a change in OAB treatment preference from tolterodine to solifenacin. CONCLUSIONS: In these cohorts, persistence with antimuscarinic drugs was low. By 2012, the preferred drug was solifenacin; oxybutynin use was marginal in Nordic countries compared with the UK.

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.

STUDY OBJECTIVE: To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs). DESIGN: Retrospective cohort study. DATA SOURCE: United Kingdom's Clinical Practice Research Datalink. PATIENTS: A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012. MEASUREMENTS AND MAIN RESULTS: Sex-specific incidence rates per 1000 person-years and 95% confidence intervals (CIs) were estimated for each study cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma, pancreatic, prostate, renal, and uterine cancer) overall and stratified by time since cohort entry and by cumulative AMOAB dose. Among the 119,912 patients followed for 399,365 person-years, 4117 incident study cancers occurred. The incidence rate of prostate cancer was 14.2 (95% CI 12.9-15.5) in the year after cohort entry and decreased markedly thereafter. The incidence rate of bladder cancer was also higher in the year after cohort entry than subsequently (men: 5.5, 95% CI 4.8-6.4; women: 1.2, 95% CI 1.0-1.5). The incidence rates of both prostate and bladder cancer decreased with increasing cumulative dose of AMOAB. We observed no similar relations between incidence rates of other study cancers and time since cohort entry. CONCLUSION: High incidence rates of bladder and prostate cancer soon after AMOAB initiation and a negative correlation between incidence and cumulative AMOAB dose suggest that protopathic bias is a more likely explanation for these findings than causality. (Protopathic bias in this context means patients' urinary symptoms prompted treatment with an AMOAB, but the symptoms were actually due to a cancer that was already present, although not yet diagnosed or not yet recorded.) To avoid unnecessary delays in the diagnosis of prostate and bladder cancer, physicians should consider these diseases in patients for whom treatment with AMOABs is indicated.

Risk of acute liver injury associated with the use of moxifloxacin and other oral antimicrobials: a retrospective, population-based cohort study.

STUDY OBJECTIVE: To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials. DESIGN: Retrospective, observational cohort study with a nested case-control analysis. DATA SOURCE: HealthCore Integrated Research Database. PATIENTS: Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use. MEASUREMENTS AND MAIN RESULTS: Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29-42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2), moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7). CONCLUSION: The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.

Validation of acute liver injury cases in a population-based cohort study of oral antimicrobial users.

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Assessment of asthma control in primary care.

OBJECTIVE: To determine the prevalence of uncontrolled asthma in patients who are visiting their primary care provider for any reason. RESEARCH DESIGN AND METHODS: This multisite, cross-sectional survey was conducted between January 25 and May 2, 2008. Participants aged > or =18 years were recruited from 35 primary care provider sites. Eligible participants presented to the office for any acute medical, routine, follow-up, or nonmedical reason; had a self-reported physician diagnosis of asthma; used medication to treat asthma in the past year; and had no history of COPD. They completed the Asthma Control Test dagger (ACT) and provided information including demographics, health behaviors, medical history, and asthma medication use. Uncontrolled asthma was defined as ACT score < or =19. RESULTS: The overall weighted prevalence of uncontrolled asthma in 2238 patients in primary care was 58% (95% confidence interval [CI], 0.56-0.60). Among asthma patients seeking care for a respiratory complaint, 72% (95% CI, 0.68-0.75) had uncontrolled asthma compared to 48% (95% CI, 0.45-0.51) of asthma patients presenting for a non-respiratory reason. CONCLUSIONS: At the population level, over half of patients with asthma under primary care management had uncontrolled asthma at the time of an office visit. Surprisingly, nearly 50% of patients with asthma who presented for office visits not associated with respiratory-related complaints had uncontrolled asthma. The study results may be influenced by a seasonal effect of upper respiratory infections and by the insurance status of the study respondents. However identifying patients with uncontrolled asthma is important and remains a challenge. Therefore, health care providers should consider evaluating asthma control on a regular basis, regardless of reason for visit.