Running Biomechanics and Clinical Features Among Adolescent Athletes With Lower Leg Chronic Exertional Compartment Syndrome.

OBJECTIVE: To compare clinical measures between patients with chronic exertional compartment syndrome (CECS) and healthy controls and evaluate running biomechanics, physical measurements, and exertional intracompartmental (ICP) changes in adolescent athletes with lower leg CECS. DESIGN: Cross-sectional case-control study. SETTING: Large tertiary care hospital and affiliated injury prevention center. PARTICIPANTS: Forty-nine adolescents with CECS (39 F, 10 M; age: 16.9 ± 0.8 years; body mass index (BMI): 23.1 ± 2.9 kg/m 2 ; symptom duration: 8 ± 12 months) were compared with 49 healthy controls (39 F, 10 M; age: 6.9 ± 0.8 years; BMI: 20.4 ± 3.7 kg/m 2 ). INTERVENTIONS: All participants underwent gait analyses on a force plate treadmill and clinical lower extremity strength and range of motion testing. Patients with chronic exertional compartment syndrome underwent Stryker monitor ICP testing. MAIN OUTCOME MEASURES: Symptoms, menstrual history, and ICP pressures of the patients with CECS using descriptive statistics. Mann-Whitney U and χ 2 analyses were used to compare CECS with healthy patients for demographics, clinical measures, and gait biomechanics continuous and categorical outcomes, respectively. For patients with CECS, multiple linear regressions analyses were used to assess associations between gait biomechanics, lower extremity strength and range of motion, and with ICP measures. RESULTS: The CECS group demonstrated higher mass-normalized peak ground reaction force measures (xBW) compared with controls (0.21 ± 0.05 xBW ( P < 0.001) and were more likely to have impact peak at initial contact ( P = 0.04). Menstrual dysfunction was independently associated with higher postexertion ICP (ß = 14.6; P = 0.02). CONCLUSIONS: The CECS group demonstrated increased total force magnitude and vertical impact transient peaks. In women with CECS, menstrual dysfunction was independently associated with increased postexertion ICP. These biomechanical and physiological attributes may play a role in the development of CECS.

Evaluation of cesarean delivery rates and factors associated with cesarean delivery among women enrolled in a pregnancy cohort study at two tertiary hospitals in Thailand.

BACKGROUND: Cesarean delivery rates have increased globally resulting in a public health concern. We estimate rates of cesarean deliveries among Thai women using the World Health Organization (WHO) Robson Classification system and compare rates by Robson group to the Robson guideline for acceptable rates to identify groups that might benefit most from interventions for rate reduction. METHODS: In 2017 and 2018, we established cohorts of pregnant women aged ≥ 18 years seeking prenatal care at two tertiary Thai hospitals and followed them until 6-8 weeks postpartum. Three in-person interviews (enrollment, end of pregnancy, and postpartum) were conducted using structured questionnaires to obtain demographic characteristics, health history, and delivery information. Cesarean delivery indication was classified based on core obstetric variables (parity, previous cesarean delivery, number of fetuses, fetal presentation, gestational week, and onset of labor) assigned to 10 groups according to the Robson Classification. Logistic regression was used to identify factors associated with cesarean delivery among nulliparous women with singleton, cephalic, term pregnancies. RESULTS: Of 2,137 participants, 970 (45%) had cesarean deliveries. The median maternal age at delivery was 29 years (interquartile range, 25-35); 271 (13%) participants had existing medical conditions; and 446 (21%) had pregnancy complications. The cesarean delivery rate varied by Robson group. Multiparous women with > 1 previous uterine scar, with a single cephalic pregnancy, ≥ 37 weeks gestation (group 5) contributed the most (14%) to the overall cesarean rate, whereas those with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars (group 9) contributed the least (< 1%). Factors independently associated with cesarean delivery included age ≥ 25 years, pre-pregnancy obesity, new/worsen medical condition during pregnancy, fetal distress, abnormal labor, infant size for gestational age ≥ 50th percentiles, and self-pay for delivery fees. Women with existing blood conditions were less likely to have cesarean delivery. CONCLUSIONS: Almost one in two pregnancies among women in our cohorts resulted in cesarean deliveries. Compared to WHO guidelines, cesarean delivery rates were elevated in selected Robson groups indicating that tailored interventions to minimize non-clinically indicated cesarean delivery for specific groups of pregnancies may be warranted.

Biomechanical changes identified during a marathon race among high-school aged runners.

BACKGROUND: Despite the increasing popularity of endurance running competitions among adolescent runners, there is currently limited information regarding expected biomechanical changes across the duration of a long-distance running event, and the relationship between young runners' biomechanics and running performance. Wearable technology offers an ecological means to continuously assess runners' biomechanical data during outdoor running competitions. RESEARCH QUESTION: Do adolescent athletes adopt changes in sensor-derived biomechanics throughout a marathon race, and are there relationships between race performance and biomechanical features among young marathoners? METHODS: Fourteen high-school aged runners (9 M, 5 F; age: 16 ± 1 years, height: 170.8 ± 7.5 cm; mass: 63.6 ± 9.4 kg) wore lace-mounted sensors to record step-by-step biomechanics during a marathon race. Official race segment completion times were extracted across 5 race segments (5-K, 15-K, Half Marathon [21.1-K], 35-K, Marathon [42.2-K]). Within-participant repeated measures of covariance (pace) were conducted to assess changes in biomechanics across the race, with Bonferroni post-hoc comparisons. Pearson's r correlations were performed to assess the relationship between race finish times and biomechanics. RESULTS: Pace was significantly slower (p-range: 0.002-0.005), contact times significantly longer, and stride lengths significantly shorter in the final segment compared to middle segments (p-range: 0.003-0.004). The rate of shock accumulation was significantly higher in the final race segment compared to the first three segments (p-range: 0.001-0.002). Moderate relationships existed between finish times and pace (r = -0.63), stride length (r = -0.62), and contact time (r = 0.51). SIGNIFICANCE: Adolescent runners altered their gait patterns in the final marathon segment compared to earlier segments. Spatiotemporal measures were moderately correlated with race finish times, suggesting a link between faster run pace, increased stride lengths, and reduced contact time for improved running performance during an endurance race.

The Effects of Injury Type on Health-Related Quality of Life in Youth Athletes: A Cross-Sectional Analysis.

OBJECTIVE: The relationship between health-related quality of life (HRQoL) and injury type has not been analyzed for young athletes. We hypothesized that there would be no difference in HRQoL between injured athletes, injured nonathletes, and normative data for healthy youth (NDHY) or among athletes with acute, overuse, or concussion injuries. DESIGN: Cross-sectional clinical cohort. SETTING: Primary care sports medicine clinics at 3 academic institutions. PARTICIPANTS: Patients aged 8 to 18 years presenting with injury. INDEPENDENT VARIABLES: Injury type and athletic participation. MAIN OUTCOME MEASURES: Health-related quality of life measured 1 month after injury through the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric-25 v2.0 assessed pain interference, peer relationships, depression, fatigue, anxiety, and mobility. One-way analysis of variance was performed with P values of <0.05 considered significant. Concussion Learning Assessment and School Survey (CLASS) evaluated academic performance. RESULTS: Three hundred fifty-seven patients (36% male), with average age of 14.2 years, completed HRQoL and CLASS surveys following injury. There were 196 overuse injuries (55%), 119 acute injuries (33%), and 42 concussions (12%). Ninety-four percent were athletes. Six percent were nonathletes; 90.5% of concussed patients reported grades worsening. Concussed athletes reported more fatigue (P = 0.008) compared with other injury types but no worse than NDHY. Athletes with overuse injuries had lower mobility (P = 0.005) than other injury types and NDHY. Patients with lower HRQoL were female, older age, or required surgery. No other domains had significant differences by injury type nor did HRQoL differ between the athletes, nonathletes, and NDHY. CONCLUSIONS: With the exception of injuries requiring surgery, HRQoL of injured young athletes was similar to NDHY in most domains.

Factors Associated with Symptom Resolution after Aerobic Exercise Intervention in Adolescent and Young Adults with Concussion.

BACKGROUND: Aerobic exercise facilitates postconcussion symptom resolution at the group level, but patient-level characteristics may affect the likelihood of treatment efficacy. PURPOSE: This study aimed to investigate demographic and clinical characteristics, which differentiate postconcussion aerobic exercise treatment efficacy from nonefficacy in the intervention arm of a randomized clinical trial. METHODS: Adolescent and young adult participants initiated a standardized aerobic exercise intervention within 14 d of concussion, consisting of self-selected exercise for 100 min·wk -1 at an individualized heart rate (80% of heart rate induced symptom exacerbation during graded exercise testing). Treatment efficacy was defined as symptom resolution within 28-d postconcussion. Treatment efficacy and nonefficacy groups were compared on demographics, clinical characteristics, intervention adherence, and persistent symptom risk using the Predicting Persistent Postconcussive Problems in Pediatrics (5P) clinical risk score. RESULTS: A total of 27 participants (16.1 ± 2.3 yr old; range, 11-21 yr; 52% female) began the intervention, with a mean of 9.5 ± 3.7 d after concussion; half ( n = 13; 48%) demonstrated treatment efficacy (symptom resolution within 28 d postconcussion). Those whose symptoms resolved within 28 d had significantly lower preintervention postconcussion symptom inventory scores (21.2 ± 13.2 vs 41.4 ± 22.2; P < 0.01), greater adherence to the intervention (77% vs 36%; P = 0.05), and longer average exercise duration (median [interquartile range], 49.7 [36.8-68.6] vs 30.4 [20.7-34.7] min; P < 0.01) than those whose symptoms lasted more than 28 d. Groups were similar in age, sex, timing of intervention, and preintervention 5P risk score. CONCLUSIONS: A standardized aerobic exercise intervention initiated within 14 d of concussion demonstrated efficacy for approximately half of participants, according to our definition of treatment efficacy. This multisite aerobic exercise intervention suggests that lower symptom severity, higher intervention adherence, and greater exercise duration are factors that increase the likelihood of symptoms resolving within 28 d of concussion.

Etiology of Acute Lower Respiratory Illness Hospitalizations Among Infants in 4 Countries.

Background: Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear. Methods: Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models. Results: An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites-ranging from 65.2% (95% credible interval, 46.3%-79.6%) in Albania to 34.9% (95% credible interval, 20.0%-49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%-27.1%) and human metapneumovirus (range, 6.3%-12.0%) were the next-highest contributors to ALRI hospitalizations. Conclusions: We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide.

Sport specialisation and performance-enhancing substance use by young athletes.

Objectives: To investigate the association of reported legal performance enhancing substance (PES) use and consideration of banned PES use among sport-specialised and non-sport-specialised young athletes. Methods and design: Cross-sectional study of 1049 young athletes enrolled in an injury prevention programme from 2013 to 2020. We used logistic regression modelling to determine the independent association between sports specialisation. We reported (1) legal PES use and (2) consideration of banned PES use after adjusting for the effects of gender, age, having a relative as a coach, unrestricted internet access, use of a weight training regimen, and weeknight hours of sleep. Results: The final cohort consisted of 946 athletes with a mean age of 14. 56% were female, and 80% were sport-specialised athletes. 14% reported legal PES use, and 3% reported consideration of banned PES use. No difference was found between sport-specialised athletes who reported legal PES use (OR=1.4; 95% CI 0.81 to 2.43; p=0.23) or consideration of banned PES use (OR=3.2; 95% CI 0.78 to 14.92; p=0.1) compared with non-sport-specialised athletes. Reported legal PES use was more common among athletes who were male, older, used weight training, and slept less. Reported consideration of banned PES use was more common among male and older athletes. Conclusions: PES use is not independently associated with sport specialisation in young athletes. Athlete sex, age, training, and sleep patterns are important factors for young athletes to consider in PES use.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

Development of a novel serological assay for the detection of mpox infection in vaccinated populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 104 nonendemic locations worldwide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

Adolescent and young adult hip and knee strength profiles relate to running gait biomechanics.

OBJECTIVES: Compare and assess relationships between strength and running biomechanics among healthy adolescents and young adult males and females. DESIGN: Retrospective cohort. SETTING: Clinic. PARTICIPANTS: 802 healthy participants (570 F, 232 M; 16.6 ± 2.3 years). MAIN OUTCOME MEASURES: Mass-normalized knee flexor and extensor strength, hip adductor and abductor strength, hamstrings-to-quadriceps (H:Q), and abductor-to-adductor (Abd:Add) ratios were obtained using hand-held dynamometry. Mass-normalized peak vertical ground reaction force (vGRF), %stance, cadence, and stride length were obtained using an instrumented treadmill. Multivariate analyses of variance were used to compare strength and biomechanics across ages and sexes. Linear regressions were used to assess the relationships between strength and biomechanics, accounting for speed, age, and sex. Independent t-tests were used to compare strength between strength ratio profiles. RESULTS: Strength and running biomechanics significantly differed between sexes (p-range: <0.001-0.05) and age groups (p-range: <0.001-0.02). Strength and strength ratios were significantly associated with increased cadence (p-range:0.001-0.04) and stride lengths (p-range:0.004-0.03), and decreased vGRF (p < 0.001). Lower H:Q ratios had significantly lower strength measures (p < 0.001). Higher Abd:Add ratios had significantly increased abductor strength (p < 0.001). CONCLUSIONS: Strength and running biomechanics differed by sexes and ages. Hip and knee strength and strength ratios were related to select spatiotemporal and kinetic biomechanical features.

Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study.

BACKGROUND: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. METHODS: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. FINDINGS: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6-33 days after the first dose and 5-40 days after the second dose. Mpox-convalescent samples were collected 20-102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20-102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. INTERPRETATION: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. FUNDING: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.

Immunogenicity of High-Dose Egg-Based, Recombinant, and Cell Culture-Based Influenza Vaccines Compared With Standard-Dose Egg-Based Influenza Vaccine Among Health Care Personnel Aged 18-65 Years in 2019-2020.

Background: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020). Methods: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4. Results: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes. Conclusions: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.

Respiratory Syncytial Virus Infection Among Hospitalized Infants in Four Middle-Income Countries.

BACKGROUND: Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. METHODS: Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015-2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth). RESULTS: Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4-6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6-6.5 for 0-2 compared to 9-11-months; P < .01), low weight-for-age z-score (aOR 1.9, 95% CI: 1.2-2.8; P < .01), ICU care after birth (aOR 1.6, 95% CI: 1.0-2.5; P = .048), and cesarean delivery (aOR 1.4, 95% CI: 1.0-1.8; P = .03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8-1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. CONCLUSIONS: RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries.

Development of a Novel Serological Assay for the Detection of Mpox Infection in Vaccinated Populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 103 non-endemic locations world-wide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay (MIA) using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important diagnostic tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

Effectiveness of Maternal Influenza Vaccination in Peru PRIME Cohort.

Background: Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. We used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine. Methods: Women at <28 weeks gestation were enrolled from 4 tertiary level hospitals in Lima, Peru at the start of the 2018 influenza season and followed until the end of their pregnancies. Participants had mid-turbinate nasal swabs collected and tested for influenza by reverse-transcription polymerase chain reaction (RT-PCR) with onset of ≥1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight. Results: We followed 1896 women for a median of 127 days (interquartile range [IQR], 86-174). Participants had a median age of 29 years (IQR, 24-34). Among the 1896 women, 49% were vaccinated with the 2018 influenza vaccine and 1039 (55%) developed influenza-like illness, 76 (7%) of whom had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100 000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% confidence interval, -64.1% to 62.9%). Conclusions: Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. Although the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries.

Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial.

BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers. RESULTS: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons. CLINICAL TRIALS REGISTRATION: NCT03722589.

Adolescent Marathon Training: Prospective Evaluation of Musculotendinous Changes During a 6-Month Endurance Running Program.

OBJECTIVES: Assess changes in lower extremity musculotendinous thickness, tissue echogenicity, and muscle pennation angles among adolescent runners enrolled in a 6-month distance running program. METHODS: We conducted prospective evaluations of adolescent runners' lower extremity musculotendinous changes at three timepoints (baseline, 3 months, and 6 months) throughout a progressive marathon training program. Two experienced researchers used an established protocol to obtain short- and long-axis ultrasound images of the medial gastrocnemius, tibialis anterior, flexor digitorum brevis, abductor hallicus, and Achilles and patellar tendons. ImageJ software was used to calculate musculotendinous thickness and echogenicity for all structures, and fiber pennation angles for the ankle extrinsic muscles. Repeated measures within-subject analyses of variance were conducted to assess the effect of endurance training on ultrasound-derived measures. RESULTS: We assessed 11 runners (40.7% of eligible runners; 6F, 5M; age: 16 ± 1 years; running experience: 3 ± 2 years) who remained injury-free and completed all ultrasound evaluation timepoints. Medial gastrocnemius muscle (F2,20  = 3.48, P = .05), tibialis anterior muscle (F2,20  = 7.36, P = .004), and Achilles tendon (F2,20  = 3.58, P = .05) thickness significantly increased over time. Echogenicity measures significantly decreased in all muscles (P-range: <.001-.004), and increased for the patellar tendon (P < .001) during training. Muscle fiber pennation angles significantly increased for ankle extrinsic muscles (P < .001). CONCLUSIONS: Adolescent runners' extrinsic foot and ankle muscles increased in volume and decreased in echogenicity, attributed to favorable distance training adaptations across the 6-month timeframe. We noted tendon thickening without concomitantly increased echogenicity, signaling intrasubstance tendon remodeling in response to escalating distance.

Relationship and Latent Factors Between Clinical Concussion Assessments and the Functional Standardized Assessment of Reaction Time (StART).

OBJECTIVE: To examine the relationships and latent factors within the Standardized Assessment of Reaction Time (StART), and between StART and current clinical assessments. DESIGN: Cross-sectional study. SETTING: Clinical medicine facility. PARTICIPANTS: Eighty-nine healthy collegiate student-athletes (63% male, age: 19.5 ± 0.9 years, 28% ≥1 concussion history). ASSESSMENT OF RISK FACTORS: Student-athletes completed StART and clinical assessments during preinjury testing. MAIN OUTCOME MEASURES: Standardized Assessment of Reaction Time consisted of 3 conditions (standing, single-leg balance, cutting) under 2 cognitive states (single task and dual task) for 3 trials each condition. Clinical assessments were the Sport Concussion Assessment Tool (SCAT) symptom checklist, Standardized Assessment of Concussion (SAC), tandem gait (single task and dual task), and Immediate PostConcussion Assessment and Cognitive Testing (ImPACT). We used Pearson- r correlation coefficients and exploratory factor analysis (EFA) to examine relationships and latent factors between StART and clinical assessments. RESULTS: Null to moderate correlations presented among the StART outcomes (r range: 0.06-0.70), and null to small correlations between StART and clinical assessments (r range: -0.16 to 0.34). The three-factor EFA for solely StART explained 70.6% total variance: functional movement (cutting), static dual-task (standing and single-leg balance), and static single task (standing and single-leg balance). The five-factor EFA for StART and clinical assessments explained 65.8% total variance: gait (single-task and dual-task tandem gait), functional movement (StART single-task and dual-task cutting), static dual-task (StART standing, single-leg balance), neurocognitive (ImPACT verbal memory, visual memory, visual-motor speed), and static single task (StART standing, single-leg balance). No other outcomes met the factor loading threshold. CONCLUSIONS: StART displayed 3 distinct categories and had minimal redundancy within its subtests. StART did not meaningfully correlate with clinical assessments, suggesting that StART provides unique information by examining more functional, reactive movement.

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.

In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies" (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. IMPORTANCE SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.

Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT): Protocol for a Multisite Longitudinal Cohort Study.

BACKGROUND: Assessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children are essential to inform policy and guide health care professionals in advising parents and caregivers of children who test positive for SARS-CoV-2. OBJECTIVE: This report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years, as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents. METHODS: The PROTECT multisite network was initiated in July 2021, which aims to enroll approximately 2305 children across four US locations and collect data over a 2-year surveillance period. The enrollment target was based on prospective power calculations and accounts for expected attrition and nonresponse. Study sites recruit parents and legal guardians of age-eligible children participating in the existing Arizona Healthcare, Emergency Response, and Other Essential Workers Surveillance (HEROES)-Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and parents/legal guardians' knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self-collected or collected by parents/legal guardians weekly, regardless of symptoms, for SARS-CoV-2 and influenza testing via reverse transcription-polymerase chain reaction (RT-PCR) assay, and the presence of COVID-like illness (CLI) is reported. Children who test positive for SARS-CoV-2 or influenza, or report CLI are monitored weekly by online surveys to report exposure and medical utilization until no longer ill. Children, with permission of their parents/legal guardians, may elect to contribute blood at enrollment, following SARS-CoV-2 infection, following COVID-19 vaccination, and at the end of the study period. PROTECT uses electronic medical record (EMR) linkages where available, and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries. RESULTS: Data collection began in July 2021 and is expected to continue through the spring of 2023. As of April 13, 2022, 2371 children are enrolled in PROTECT. Enrollment is ongoing at all study sites. CONCLUSIONS: As COVID-19 vaccine products are authorized for use in pediatric populations, PROTECT study data will provide real-world estimates of VE in preventing infection. In addition, this prospective cohort provides a unique opportunity to further understand SARS-CoV-2 incidence, clinical course, and key knowledge gaps that may inform public health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/37929.