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 ).

Effectiveness of monovalent COVID-19 booster/additional vaccine doses in the United States.

Background: Monovalent booster/additional doses of COVID-19 vaccines were first authorized in August 2021 in the United States. We evaluated the real-world effectiveness of receipt of a monovalent booster/additional dose of COVID-19 vaccine compared with receiving a primary vaccine series without a booster/additional dose. Methods: Cohorts of individuals receiving a COVID-19 booster/additional dose after receipt of a complete primary vaccine series were identified in 2 administrative insurance claims databases (Optum, CVS Health) supplemented with state immunization information system data between August 2021 and March 2022. Individuals with a complete primary series but without a booster/additional dose were one-to-one matched to boosted individuals on calendar date, geography, and clinical factors. COVID-19 diagnoses were identified in any medical setting, or specifically in hospitals/emergency departments (EDs). Propensity score-weighted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models; vaccine effectiveness (VE) was estimated as 1 minus the HR by vaccine brand overall and within subgroups of variant-specific eras, immunocompromised status, and homologous/heterologous booster status. Results: Across both data sources, we identified 752,165 matched pairs for BNT162b2, 410,501 for mRNA-1273, and 11,398 for JNJ-7836735. For any medically diagnosed COVID-19, meta-analyzed VE estimates for BNT162b2, mRNA-1273, and JNJ-7836735, respectively, were: BNT162b2, 54% (95% CI, 53%-56%); mRNA-1273, 58% (95% CI, 56%-59%); JNJ-7836735, 34% (95% CI, 23%-44%). For hospital/ED-diagnosed COVID-19, VE estimates ranged from 70% to 76%. VE was generally lower during the Omicron era than the Delta era and for immunocompromised individuals. There was little difference observed by homologous or heterologous booster status. Conclusion: The original, monovalent booster/additional doses were reasonably effective in real-world use among the populations for which they were indicated during the study period. Additional studies may be informative in the future as new variants emerge and new vaccines become available.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).

Reasons for Guideline Nonadherence at Heart Failure Discharge.

Background Cardiology has advanced guideline development and quality measurement. Recognizing the substantial benefits of guideline-directed medical therapy, this study aims to measure and explain apparent deviations in heart failure ( HF ) guideline adherence by clinicians at hospital discharge and describe any impact on readmission rates. Methods and Results The extent of decongestion and prescription of neurohormonal therapy were recorded prospectively for 226 HF discharges, including 132 (58%) from an academic hospital and 94 (42%) from a community hospital. Among all discharges, 25% were discharged with residual congestion (30% academic versus 18% community, P=0.070). Among discharges of patients with HF with reduced ejection fraction, 37% (45% academic versus 18% community, P<0.001) were discharged without ß-blocker therapy or with lower doses than at admission. Moreover, 46% of patients with HF with reduced ejection fraction (48% academic versus 39% community, P=0.390) were discharged without an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker or with lower doses than at admission. Renal dysfunction was the most common reason for discharge with congestion, and hypotension the most common reason for discharge with no or decreased neurohormonal therapy. There was a trend toward higher 90-day readmission rates after discharge with residual congestion. Conclusions Clinicians frequently deviate from guidelines in both academic and community hospitals; however, this deviation may not always indicate poor quality. Application of guidelines recommended for stable populations is increasingly limited for hospitalized patients by hypotension, renal dysfunction, and inotrope use. Patients with renal dysfunction, hypotension, and recent inotrope use merit further study to determine best practices and possibly to adjust quality metrics for HF severity.

Implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) for Food Challenges.

BACKGROUND: Oral food challenges (OFCs) are routinely used to confirm ongoing food allergy. Serum-specific IgE (sIgE) and skin prick testing (SPT) are imperfect predictors of which patients will pass OFCs. OBJECTIVE: The objective of this study was to describe the design and implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) to study and iteratively improve sIgE and SPT thresholds to determine when and where to conduct OFCs for patients. METHODS: Allergists consulted recommended sIgE and SPT thresholds when ordering challenges although diversions were permitted. Criteria were iteratively improved after periodic analyses of challenge outcome and diversions. RESULTS: Over 3 years, allergists ordered 2368 food challenges for 1580 patients with histories of IgE-mediated reactions to food: 1386 in an outpatient clinic and 945 in a higher resource infusion center. Reactions to challenge were observed in 13% of clinic and 23% of infusion center challenges. Six patients challenged in clinic required treatment with epinephrine compared with 22 in the infusion center. The need for epinephrine was more common in patients with asthma-5% of asthmatic patients required epinephrine compared with 1% of nonasthmatic patients (P < .01). Recommended sIgE and SPT thresholds were incrementally changed and, using the control chart methodology, a significant decrease was noted in the proportion of challenges ordered in the higher resource location. CONCLUSIONS: By setting and continually refining sIgE and SPT recommendations using the SCAMP method, allergists can better determine the risk of severe reaction and triage patients to the appropriate setting for an OFC.

Association of PNC, BC, and PM2.5 measured at a central monitoring site with blood pressure in a predominantly near highway population.

Elevated blood pressure is an indicator of cardiovascular stress and increased risk of cardiovascular-related morbidity and mortality. There is emerging evidence suggesting air pollutants, including particulate matter (PM), could promote hypertension, thereby increasing cardiovascular disease risk. Repeated measurement analyses were conducted to examine the associations of three types of PM with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) in 220 participants, (mean age=58.5 years) from the Community Assessment of Freeway Exposure and Health study (CAFEH), most of whom live near a major highway. Ambient levels of air pollutants including particle number concentration (PNC; a measure of ultrafine particle (UFP) concentration), fine PM (PM2.5, Particle diameter<2.5 µm), and black carbon (BC) were measured at a central site<7 km from the study areas. Central sites are good at capturing short-term temporal trends in pollution associated with meteorological changes over regional areas. Linear mixed-effect models that accounted for repeated measures within one person were used to examine the associations between blood pressure variables and daily average of ambient PNC, PM2.5, or BC, controlling for demographic characteristics and major confounders including temperature. Our PNC model predicted that a higher PNC of 10,000 particles/cm3 was associated with higher DBP of 2.40 mmHg (p=0.03), independent of other factors in the model. There were no significant associations for PM2.5 or BC. Post hoc subgroup analyses by obesity status showed that positive associations of DBP with PNC were more pronounced among obese individuals than non-obese individuals. These results suggested that PNC levels are associated with increased blood pressure, which may contribute to cardiovascular disease risk. More research is needed to assess the relationship between PNC and blood pressure and to address possible residual confounding.

Intensity-modulated versus conventional radiation therapy for oropharyngeal carcinoma: long-term dysphagia and tumor control outcomes.

BACKGROUND: The purpose of this study was to determine the relative clinical benefits of intensity-modulated radiation therapy (IMRT) versus conventional radiotherapy (CRT) in the treatment of patients with oropharyngeal carcinoma. METHODS: We compared tumor control and toxicity outcomes in 132 patients with stage III to IVA/B oropharyngeal carcinoma treated with definitive chemoradiation in the human papillomavirus (HPV) era. RESULTS: Patients treated with IMRT had lower rates of xerostomia (p = .01) and shorter duration of gastrostomy-tube dependence (p < .0001), but increased risk of cervical esophageal stricture (p = .03). The overall rates of late dysphagia were not different between the 2 groups (p = .40). In multivariate analysis, IMRT was a significant predictor of decreased disease-specific mortality (hazard ratio [HR] = 0.24; p = .03) after adjustment for T-category and active smoking. After adjustment for T classification, IMRT use was associated with a trend toward a significant decrease in locoregional failure (HR = 0.17; p = .08). CONCLUSION: The incidence of late dysphagia is similar in IMRT and CRT, but the mechanism of dysphagia is different.

Positional error and time-activity patterns in near-highway proximity studies: an exposure misclassification analysis.

BACKGROUND: The growing interest in research on the health effects of near-highway air pollutants requires an assessment of potential sources of error in exposure assignment techniques that rely on residential proximity to roadways. METHODS: We compared the amount of positional error in the geocoding process for three different data sources (parcels, TIGER and StreetMap USA) to a "gold standard" residential geocoding process that used ortho-photos, large multi-building parcel layouts or large multi-unit building floor plans. The potential effect of positional error for each geocoding method was assessed as part of a proximity to highway epidemiological study in the Boston area, using all participants with complete address information (N = 703). Hourly time-activity data for the most recent workday/weekday and non-workday/weekend were collected to examine time spent in five different micro-environments (inside of home, outside of home, school/work, travel on highway, and other). Analysis included examination of whether time-activity patterns were differentially distributed either by proximity to highway or across demographic groups. RESULTS: Median positional error was significantly higher in street network geocoding (StreetMap USA = 23 m; TIGER = 22 m) than parcel geocoding (8 m). When restricted to multi-building parcels and large multi-unit building parcels, all three geocoding methods had substantial positional error (parcels = 24 m; StreetMap USA = 28 m; TIGER = 37 m). Street network geocoding also differentially introduced greater amounts of positional error in the proximity to highway study in the 0-50 m proximity category. Time spent inside home on workdays/weekdays differed significantly by demographic variables (age, employment status, educational attainment, income and race). Time-activity patterns were also significantly different when stratified by proximity to highway, with those participants residing in the 0-50 m proximity category reporting significantly more time in the school/work micro-environment on workdays/weekdays than all other distance groups. CONCLUSIONS: These findings indicate the potential for both differential and non-differential exposure misclassification due to geocoding error and time-activity patterns in studies of highway proximity. We also propose a multi-stage manual correction process to minimize positional error. Additional research is needed in other populations and geographic settings.

Clinical factors predicting for prolonged enteral supplementation in patients with oropharyngeal cancer treated with chemoradiation.

OBJECTIVES: The purpose of this study is to determine the pre-treatment clinical factors associated with prolonged enteral feeding in patients with oropharyngeal cancer treated with chemoradiation. MATERIALS AND METHODS: One hundred and nine patients with stage III-IVB oropharyngeal carcinoma treated with definitive chemoradiation were analyzed. Feeding tube usage was defined as the duration of active usage for nutritional purposes. RESULTS: Median follow-up was 4.4 years and median feeding tube usage was 2.5 months. On multivariate analysis, increasing duration of feeding tube usage was associated with narcotic use before treatment (p = 0.04), living alone at the time of treatment (p = 0.04), and larger pre-treatment decrease in body-mass index (p = 0.01). Prolonged feeding tube usage was associated with decreased overall survival (p = 0.06) and disease-free survival (p = 0.02) in univariate analysis. CONCLUSIONS: By identifying patients at risk for prolonged feeding tube usage, aggressive measures can be attempted to prevent feeding tube dependence.