Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Exploring Racial Disparities in the 1918 Influenza Pandemic: A Case Study of Durham, North Carolina.

The paradox of excess mortality among White Americans during the 1918 influenza pandemic has long puzzled historians and scientists. Recent scholarship has suggested that this disparity was not true for the country as a whole, but rather regional variation was observed. The factors influencing these disparities remain speculative. A case study was conducted of Durham, North Carolina, a city known nationally for the achievements of its Black middle class, to further explore these themes relying on numerous sources including newspapers and death certificates. Though Durham's overall mortality was lower than many places in North Carolina, the White mortality rate greatly exceeded that of the Black population. Previously described theories, including Alfred Crosby's exposure hypothesis and segregation, were explored. The most notable difference between Durham's pandemic narrative and other comparable towns was the robust healthcare response, which was made possible by the excellence of the Black nursing force from Lincoln Hospital. Nursing care was the best treatment available for the 1918 influenza, but most of the nation experienced severe nursing shortages due to the war effort. This study thus provides an example of how the Black health community has proven an active agent in countering the structural forces driving racial disparities.

Are Radiographs Associated With Patient Satisfaction After Scarf Bunionectomy?

There are over 350,000 bunion surgeries performed in the USA annually, making it one of the most common elective forefoot surgeries. Studies have suggested that as many as 10% of patients remain dissatisfied after bunion surgery. The purpose of this study is to evaluate if radiographic variables are associated with patient satisfaction at 1 year postoperatively. We performed a secondary analysis of prospectively collected data on 69 consecutive adult patients (mean age 45 ± 14 years, 91% female [63/69]) who underwent isolated hallux valgus surgery from January 2016 to January 2017. Subjects completed a standardized 4-item survey inquiring about their satisfaction with regards to pain relief, overall operative result, cosmetic appearance, and ability to wear desired shoe gear. Conventional radiographic indices for hallux valgus were examined preoperatively and 3 months postoperatively. An association model using backward stepwise logistic regression was utilized to determine which variables, if any, are most important in explaining patient satisfaction after surgery. Sixty-nine subjects completed the 4-item satisfaction survey with 53.6% (37/69) of subjects answering they were fully satisfied on all aspects of the survey at 12 months postoperatively. In the final regression model, no radiographic or demographic variables were associated with patient satisfaction including shoe gear, cosmetic appearance, pain relief, and overall operative result. Radiographic variables did not appear to be associated with patient satisfaction at one year postoperatively in our study. Factors such as quality of life, anxiety levels, fear of surgery, and/or preoperative expectations may offer more insight into satisfaction; however, further research should be performed to examine this further.

The Statistical Fragility of Foot and Ankle Surgery Randomized Controlled Trials.

Fragility index (FI) is a metric used to interpret the results of randomized controlled trials (RCTs), and describes the number of subjects that would need to be switched from event to non-event for a result to no longer be significant. Studies that analyze FI of RCTs in various orthopedic subspecialties have shown the RCTs to be largely underpowered and highly fragile. However, FI has not been assessed in foot and ankle RCTs. The MEDLINE and Embase online databases were searched from 1/1/2011 through 11/19/2021 for RCTs involving foot and ankle conditions. FI, fragility quotient (FQ), and difference between the FI and number of subjects lost to follow-up was calculated. Spearman correlation was performed to determine the relationship between sample size and FI. Overall, 1262 studies were identified of which 18 were included in the final analysis. The median sample size was 65 (interquartile range [IQR] 57-95.5), the median FI was 2 (IQR 1-2.5), and the median FQ was 0.026 (IQR 0.012-0.033). Ten of 15 (67%) studies with non-zero FI values had FI values less than the number of subjects lost to follow-up. There was linear association between FI and sample size (R2 = 0.495, p-value: .031). This study demonstrates that RCTs in the field of foot and ankle surgery are highly fragile, similar to other orthopedic subspecialties.

History of Medicine in the Clerkships: A Novel Model for Integrating Medicine and History.

The history of medicine has only unevenly been integrated into medical education. Previous attempts to incorporate the subject have focused either on the first year, with its already over-subscribed curriculum, or the fourth year in the form of electives that reach a small minority of students. Duke University provides an alternative model for other universities to consider. At our institution we have overcome many of the curricular limitations by including history during the mandatory third year clerkships. Reaching 100% of the medical school class, these sessions align with clinical disciplines, providing students a longitudinal perspective on what they are seeing and doing on the hospital wards. They are taught in conjunction with a medical history librarian and rely heavily on the utilization and interpretation of physical artifacts and archival manuscripts. The surgery, obstetrics/gynecology, and pediatrics rotations now feature successful and popular history of medicine sessions. Describing our lesson plans and featuring a list of both physical and online resources, we provide a model others can implement to increase the use, the framing, and the accessibility of history in their medical schools.

Biomanufacturing readiness levels [BRL]-A shared vocabulary for biopharmaceutical technology development and commercialization.

The Manufacturing Readiness Levels (MRLs) developed by the Department of Defense are well-established tools for describing the maturity of new technologies resulting from government-sponsored Research and Development programs, from the concept phase to commercial deployment. While MRLs are generally applicable to a wide range of industries and technologies, there is significant value in offering an industry-specific view on how the basic principles may be applied to biomanufacturing. This paper describes Biomanufacturing Readiness Levels (BRLs) developed by the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a public/private partnership that is part of the Manufacturing USA network. NIIMBL brings together private, federal, nonprofit, and academic stakeholders to accelerate the deployment of innovative technologies for biopharmaceutical production and to educate and train a world-leading biomanufacturing workforce. We anticipate that these BRLs will lay the groundwork for a shared vocabulary for assessment of technology maturity and readiness for commercial biomanufacturing that effectively meets the needs of this critical, specialized, and highly regulated industry.

Treatment of Lesser Metatarsophalangeal Joint Instability With Plantar Plate Repair: A Systematic Review and Meta-Analysis.

Recognition of metatarsophalangeal joint plantar plate injuries has improved over time as the condition has become more widely understood and identified. With the diagnosis of a plantar plate injury as a subset of metatarsalgia becoming more common place, there are multiple surgical options that have been utilized to address the condition. Direct repair of the plantar plate has emerged as the treatment of choice for foot surgeons with a tendency to favor a direct dorsal approach for the repair. We performed a systematic review and meta-analysis using preferred reporting items for systematic reviews and meta-analysis guidelines, to determine the magnitude of change that can be expected in visual analog scale pain and American Orthopedic Foot and Ankle Society scores postoperatively. A total of 12 studies involving 537 plantar plate tears were included who underwent direct repair of the plantar plate through either a dorsal (10 articles) or plantar approach (2 articles). Summary estimates were calculated which revealed improvement in visual analog scale pain (pooled mean change of -5.01 [95%CI -5.36, -4.66] pre-to postoperative) and improvement in American Orthopedic Foot and Ankle Society scores (pooled postoperative mean improvement 40.44 [95%CI 37.90, 42.97]) of patients within the included studies. Random effects models were used for summary estimates. I2 statistic was used to assess for heterogeneity. We concluded there is a predictable level of improvement in pain and function in patients undergoing a direct dorsal approach plantar plate repair with follow-up out to 2 years.

End-to-end collaboration to transform biopharmaceutical development and manufacturing.

An ambitious 10-year collaborative program is described to invent, design, demonstrate, and support commercialization of integrated biopharmaceutical manufacturing technology intended to transform the industry. Our goal is to enable improved control, robustness, and security of supply, dramatically reduced capital and operating cost, flexibility to supply an extremely diverse and changing portfolio of products in the face of uncertainty and changing demand, and faster product development and supply chain velocity, with sustainable raw materials, components, and energy use. The program is organized into workstreams focused on end-to-end control strategy, equipment flexibility, next generation technology, sustainability, and a physical test bed to evaluate and demonstrate the technologies that are developed. The elements of the program are synergistic. For example, process intensification results in cost reduction as well as increased sustainability. Improved robustness leads to less inventory, which improves costs and supply chain velocity. Flexibility allows more products to be consolidated into fewer factories, reduces the need for new facilities, simplifies the acquisition of additional capacity if needed, and reduces changeover time, which improves cost and velocity. The program incorporates both drug substance and drug product manufacturing, but this paper will focus on the drug substance elements of the program.

A scalable computational approach to assessing response to name in toddlers with autism.

BACKGROUND: This study is part of a larger research program focused on developing objective, scalable tools for digital behavioral phenotyping. We evaluated whether a digital app delivered on a smartphone or tablet using computer vision analysis (CVA) can elicit and accurately measure one of the most common early autism symptoms, namely failure to respond to a name call. METHODS: During a pediatric primary care well-child visit, 910 toddlers, 17-37 months old, were administered an app on an iPhone or iPad consisting of brief movies during which the child's name was called three times by an examiner standing behind them. Thirty-seven toddlers were subsequently diagnosed with autism spectrum disorder (ASD). Name calls and children's behavior were recorded by the camera embedded in the device, and children's head turns were coded by both CVA and a human. RESULTS: CVA coding of response to name was found to be comparable to human coding. Based on CVA, children with ASD responded to their name significantly less frequently than children without ASD. CVA also revealed that children with ASD who did orient to their name exhibited a longer latency before turning their head. Combining information about both the frequency and the delay in response to name improved the ability to distinguish toddlers with and without ASD. CONCLUSIONS: A digital app delivered on an iPhone or iPad in real-world settings using computer vision analysis to quantify behavior can reliably detect a key early autism symptom-failure to respond to name. Moreover, the higher resolution offered by CVA identified a delay in head turn in toddlers with ASD who did respond to their name. Digital phenotyping is a promising methodology for early assessment of ASD symptoms.

Frosted Intellectuals: How Dr. Leo Kanner Constructed the Autistic Family.

Dr. Leo Kanner, in his delineation of autism as a clinical entity, is also remembered for having created a powerful stereotype of parents of autistic children as highly educated, intelligent, and emotionally distant. As historians have come to understand that autism arose out of a preceding diagnosis, childhood schizophrenia, it has also become clear that the so-called "refrigerator mother" caricature arose out of the preceding notion of the cold "schizophrenogenic" mother. However, this does not explain Kanner's belief that parents (fathers as well as mothers) were highly educated and intelligent. This study is the first to compare Kanner's famous published case studies with case records of his patients in the Phipps Clinic at Johns Hopkins in order to discover how this stereotype was created. Contrary to his assertion in the published literature, Kanner did indeed see patients with autism whose parents who did not fit his stereotype, but he did not publish these cases. Kanner's stereotype of the "autistic parent" thus seems to have arisen through a process of confirmation bias. This continues to have ramifications to the present day, by linking autism in the popular mind to highly educated and professional parents, and by leading patients with nonstereotypical patients to go unrecognized.

Intramedullary Metatarsal Fixation for Treatment of Delayed Regenerate Bone in Lengthening of Brachymetatarsia.

Delayed regenerate healing after distraction osteogenesis can be a challenging problem for patients and surgeons alike. In the present study, we retrospectively reviewed the data from a cohort of patients with delayed regenerate healing during gradual lengthening treatment of brachymetatarsia. Additionally, we present a novel technique developed by 1 of us (B.M.L.) for the management of delayed regenerate healing. We hypothesized that application of intramedullary metatarsal fixation would safely and effectively promote healing of poor quality, atrophic regenerate during bone lengthening in brachymetatarsia correction. We formulated a study to retrospectively review the data from a cohort of patients with delayed regenerate healing after gradual lengthening for brachymetatarsia. All patients underwent temporary placement of intramedullary fixation after identification of delayed regenerate healing. Patient-related variables and objective measurements were assessed. We identified 10 patients with 13 metatarsals treated with intramedullary fixation for delayed regenerate healing. All 10 patients were female, with 6 (46.2%) right metatarsals and 7 (53.8%) left metatarsals treated. No complications developed with the use of this technique. All subjects progressed to successful consolidation of the regenerate bone at a mean of 44.5 ± 30.2 days after placement of intramedullary metatarsal fixation. No regenerate fracture or reoperations were noted. In conclusion, intramedullary metatarsal fixation is a safe and effective method for managing delayed regenerate healing encountered during distraction osteogenesis correction of brachymetatarsia.

Cost-Effectiveness Analysis of Primary Arthrodesis Versus Open Reduction Internal Fixation for Primarily Ligamentous Lisfranc Injuries.

The purpose of the present study was to determine whether surgical intervention with open reduction internal fixation (ORIF) or primary arthrodesis (PA) for Lisfranc injuries is more cost effective. We conducted a formal cost-effectiveness analysis using a Markov model and decision tree to explore the healthcare costs and health outcomes associated with a scenario of ORIF versus PA for 45 years postoperatively. The outcomes assessed included long-term costs, quality-adjusted life-years (QALYs), and incremental cost per QALY gained. The costs were evaluated from the healthcare system perspective and are expressed in U.S. dollars at a 2017 price base. ORIF was always associated with greater costs compared with PA and was less effective in the long term. When calculating the cost required to gain 1 additional QALY, the PA group cost $1429/QALY and the ORIF group cost $3958/QALY. The group undergoing PA overall spent, on average, $43,192 less than the ORIF group, and PA was overall a more effective technique. Strong dominance compared with ORIF was demonstrated in multiple scenarios, and the model's conclusions were unchanged in the sensitivity analysis even after varying the key assumptions. ORIF failed to show functional or financial benefits. In conclusion, from a healthcare system's standpoint, PA would clearly be the preferred treatment strategy for predominantly ligamentous Lisfranc injuries and dislocations.

Use of a Digital Modified Checklist for Autism in Toddlers - Revised with Follow-up to Improve Quality of Screening for Autism.

OBJECTIVES: To assess changes in quality of care for children at risk for autism spectrum disorders (ASD) due to process improvement and implementation of a digital screening form. STUDY DESIGN: The process of screening for ASD was studied in an academic primary care pediatrics clinic before and after implementation of a digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up with automated risk assessment. Quality metrics included accuracy of documentation of screening results and appropriate action for positive screens (secondary screening or referral). Participating physicians completed pre- and postintervention surveys to measure changes in attitudes toward feasibility and value of screening for ASD. Evidence of change was evaluated with statistical process control charts and χ2 tests. RESULTS: Accurate documentation in the electronic health record of screening results increased from 54% to 92% (38% increase, 95% CI 14%-64%) and appropriate action for children screening positive increased from 25% to 85% (60% increase, 95% CI 35%-85%). A total of 90% of participating physicians agreed that the transition to a digital screening form improved their clinical assessment of autism risk. CONCLUSIONS: Implementation of a tablet-based digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up led to improved quality of care for children at risk for ASD and increased acceptability of screening for ASD. Continued efforts towards improving the process of screening for ASD could facilitate rapid, early diagnosis of ASD and advance the accuracy of studies of the impact of screening.

Forefoot Adduction Is a Risk Factor for Jones Fracture.

Jones fractures are among the most common fractures of the foot; however, much remains unknown about their etiology. The purpose of the present study was to further examine the risk factors of forefoot and hindfoot alignment on Jones fractures using an epidemiologic study design. We used a retrospective, matched, case-control study design. Cases consisted of patients with acute, isolated Jones fractures confirmed on plain film radiographs seen at our institute from January 2009 to December 2013. Patients presenting with pain unrelated to metatarsal fractures served as controls. Controls were matched to cases by age (±2 years), gender, and year of presentation. Weightbearing foot radiographs were assessed for 13 angular relationships by a single rater. Conditional multivariable logistic regression was used to identify important risk factors. Fifty patients with acute Jones fractures and 200 controls were included. The only significant variables in the final multivariable model were the metatarsus adductus angle (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.08 to 1.25) and fourth/fifth intermetatarsal angle (OR 0.69, 95% CI 0.57 to 0.83)-both measures of static forefoot adduction. The presence of metatarsus adductus (defined as >15°) on foot radiographs was associated with a 2.4 times greater risk of a Jones fracture (adjusted OR 2.4, 95% CI 1.2 to 4.8). We have concluded that the risk of Jones fracture increases with an adducted forefoot posture. In our population, which consisted primarily of patients presenting after a fall (10 of 50; 20%) or misstep/inversion injury (19 of 50; 38%), the hindfoot alignment appeared to be a less important factor.

American College of Foot and Ankle Surgeons' clinical consensus statement: risk, prevention, and diagnosis of venous thromboembolism disease in foot and ankle surgery and injuries requiring immobilization.

The purpose of this document is to provide guidance for physicians regarding the risk, prevention, and diagnosis of venous thromboembolism disease after foot and ankle surgery and while caring for lower extremity injuries that require ankle immobilization. A panel composed of all authors of this document reviewed the published evidence and, through a series of meetings, reached consensus regarding the viewpoints contained herein. We conclude that routine chemical prophylaxis is not warranted; rather, patients should be stratified and have a prevention plan tailored to their individual risk level. An effective venous thromboembolism prevention program is typically multimodal and focuses on addressing any modifiable risk factors, use of mechanical prophylaxis, early mobilization, and careful consideration of the use of chemical prophylaxis. The final decision regarding use and method(s) of prophylaxis adopted should be agreed upon by both the clinician and patient after a discussion of the potential benefits and harms as they relate to the individual. This should take place preferably during the preoperative visit or in the immediate post-injury setting, and it may need to be revisited during the course of care if the patient's risk level changes. Prompt recognition of the signs and symptoms of deep venous thrombosis following surgery or injury is important. Patients suspected of deep venous thrombosis should receive further work-up with either a D-dimer test or duplex venous ultrasound of the symptomatic leg, depending on their pretest probability for the disease. The latter can be determined using a validated clinical decision-making tool (e.g., Well's criteria).

Successful treatment of an MTBE-impacted aquifer using a bioreactor self-colonized by native aquifer bacteria.

A field-scale fixed bed bioreactor was used to successfully treat an MTBE-contaminated aquifer in North Hollywood, CA without requiring inoculation with introduced bacteria. Native bacteria from the MTBE-impacted aquifer rapidly colonized the bioreactor, entering the bioreactor in the contaminated groundwater pumped from the site, and biodegraded MTBE with greater than 99 % removal efficiency. DNA sequencing of the 16S rRNA gene identified MTBE-degrading bacteria Methylibium petroleiphilum in the bioreactor. Quantitative PCR showed M. petroleiphilum enriched by three orders of magnitude in the bioreactor above densities pre-existing in the groundwater. Because treatment was carried out by indigenous rather than introduced organisms, regulatory approval was obtained for implementation of a full-scale bioreactor to continue treatment of the aquifer. In addition, after confirmation of MTBE removal in the bioreactor to below maximum contaminant limit levels (MCL; MTBE = 5 µg L(-1)), treated water was approved for reinjection back into the aquifer rather than requiring discharge to a water treatment system. This is the first treatment system in California to be approved for reinjection of biologically treated effluent into a drinking water aquifer. This study demonstrated the potential for using native microbial communities already present in the aquifer as an inoculum for ex-situ bioreactors, circumventing the need to establish non-native, non-acclimated and potentially costly inoculants. Understanding and harnessing the metabolic potential of native organisms circumvents some of the issues associated with introducing non-native organisms into drinking water aquifers, and can provide a low-cost and efficient remediation technology that can streamline future bioremediation approval processes.

Equivalent immunogenicity across three RSVpreF vaccine lots in healthy adults 18-49 years of age: Results of a randomized phase 3 study.

BACKGROUND: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots. METHODS: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed. RESULTS: Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots. CONCLUSIONS: These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208).

Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-µg doses were randomized to receive BNT162b2 30 µg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 µg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 µg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified.