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Carlos R Oliveira,1,2 Eugene D Shapiro,1,3 Daniel M Weinberger3 1Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA; 2Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA; 3Department of Epidemiology of Microbial Diseases, Yale University School of Public Health, New Haven, CT, USACorrespondence: Carlos R Oliveira, Yale University School of Medicine, 464 Congress Avenue, Suite 204, New Haven, CT, 06520, USA, Tel +1 203 785 5474, Email carlos.oliveira@yale.eduPurpose: Vaccine effectiveness (VE) studies are often conducted after the introduction of new vaccines to ensure they provide protection in real-world settings. Control of confounding is often needed during the analyses, which is most efficiently done through multivariable modeling. When many confounders are being considered, it can be challenging to know which variables need to be included in the final model. We propose an intuitive Bayesian model averaging (BMA) framework for this task.Patients and Methods: Data were used from a matched case–control study that aimed to assess the effectiveness of the Lyme vaccine post-licensure. Cases were residents of Connecticut, 15– 70 years of age with confirmed Lyme disease. Up to 2 healthy controls were matched to each case subject by age. All participants were interviewed, and medical records were reviewed to ascertain immunization history and evaluate potential confounders. BMA was used to systematically search for potential models and calculate the weighted average VE estimate from the top subset of models. The performance of BMA was compared to three traditional single-best-model-selection methods: two-stage selection, stepwise elimination, and the leaps and bounds algorithm.Results: The analysis included 358 cases and 554 matched controls. VE ranged between 56% and 73% and 95% confidence intervals crossed zero in < 5% of all candidate models. Averaging across the top 15 models, the BMA VE was 69% (95% CI: 18– 88%). The two-stage, stepwise, and leaps and bounds algorithm yielded VE of 71% (95% CI: 21– 90%), 73% (95% CI: 26– 90%), and 74% (95% CI: 27– 91%), respectively.Conclusion: This paper highlights how the BMA framework can be used to generate transparent and robust estimates of VE. The BMA-derived VE and confidence intervals were similar to those estimated using traditional methods. However, by incorporating model uncertainty into the parameter estimation, BMA can lend additional rigor and credibility to a well-designed study.Keywords: Bayesian model averaging, model uncertainty, vaccine effectiveness, Lyme vaccine

Objective: To examine attitudes and knowledge about vaccinations in postpartum mothers. Methods: This cross-sectional study collected data via written survey to postpartum mothers in a large teaching hospital in Connecticut. We used multivariable analysis to identify mothers who were less trusting with regard to vaccines. Results: Of 228 mothers who participated in the study, 29% of mothers worried about vaccinating their infants: 23% were worried the vaccines would not work, 11% were worried the doctor would give the wrong vaccine, and 8% worried that 'they' are experimenting when they give vaccines. Mothers reported that the most important reasons to vaccinate were to prevent disease in the baby (74%) and in society (11%). Knowledge about vaccination was poor; e.g., 33% correctly matched chicken pox with varicella vaccine. Mothers who were planning to breastfeed (P = .01), were primiparous (P = .01), or had an income <$40,000 but did not receive support from the women, infants, and children (WIC) program were less trusting with regard to vaccines (P = .03). Although 70% wanted information about vaccines during pregnancy, only 18% reported receiving such information during prenatal care. Conclusion: Although the majority of infants receive vaccines, their mothers have concerns and would like to receive immunization information earlier. Mothers who are primiparous, have low family incomes but do not qualify for the WIC program, or are breastfeeding may need special attention to develop a trusting relationship around vaccination. Mothers would benefit from additional knowledge regarding the risks and benefits of vaccines particularly during prenatal care. [ABSTRACT FROM AUTHOR]

After the manufacture of Lyme vaccine was discontinued in 2002, strategies to prevent Lyme disease (LD) have focused on personal protective measures. Effectiveness of these measures has not been conclusively demonstrated. The aim of our case-control study was to assess the effectiveness of personal preventive measures in a highly disease-endemic area. Case-patients were persons with LD reported to Connecticut's Department of Public Health and classified as having definite, possible, or unlikely LD. Age-matched controls without LD were identified. Study participants were interviewed to assess the practice of preventive measures and to obtain information on occupational and recreational risk factors. Use of protective clothing was 40% effective; routine use of tick repellents on skin or clothing was 20% effective. Checking one's body for ticks and spraying property with acaricides were not effective. We concluded that use of protective clothing and of tick repellents (on skin or clothing) are effective in preventing LD. [ABSTRACT FROM AUTHOR]

Context: Acute otitis media (AOM) is the most common diagnosis for which antibiotics are prescribed for children. Previous trials that have evaluated a "wait-and-see prescription" (WASP) for antibiotics, with which parents are asked not to fill the prescription unless the child either is not better or is worse in 48 hours, have excluded children with severe AOM. None of these trials were conducted in an emergency department.Objectives: To determine whether treatment of AOM using a WASP significantly reduces use of antibiotics compared with a "standard prescription" (SP) and to evaluate the effects of this intervention on clinical symptoms and adverse outcomes related to antibiotic use.Design, Setting, and Patients: A randomized controlled trial conducted between July 12, 2004, and July 11, 2005. Children with AOM aged 6 months to 12 years seen in an emergency department were randomly assigned to receive either a WASP or an SP. All patients received ibuprofen and otic analgesic drops for use at home. A research assistant, blinded to group assignment, conducted structured phone interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes.Main Outcome Measures: Filling of the antibiotic prescription and clinical course.Results: Overall, 283 patients were randomized either to the WASP group (n = 138) or the SP group (n = 145). Substantially more parents in the WASP group did not fill the antibiotic prescription (62% vs 13%; P<.001). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within the WASP group, both fever (relative risk [RR], 2.95; 95% confidence interval [CI], 1.75 - 4.99; P<.001) and otalgia (RR, 1.62; 95% CI, 1.26 - 2.03; P<.001) were associated with filling the prescription.Conclusion: The WASP approach substantially reduced unnecessary use of antibiotics in children with AOM seen in an emergency department and may be an alternative to routine use of antimicrobials for treatment of such children.Trial Registration: clinicaltrials.gov Identifier: NCT00250900. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the validity of retrieving data from a commercial, outpatient electronic medical record (EMR) to assess the management of pharyngitis, an important measure of quality of healthcare in pediatrics and a new measure for the Health Plan Employer Data and Information Set (HEDIS).Methods: For children ages 3-18 years, we electronically identified clinical encounters with diagnoses of pharyngitis using 3 different strategies (an EMR-based strategy, an administrative data-based strategy, and a reference strategy which used medical record review). By each strategy, we calculated the proportion of episodes of pharyngitis during 1 year for which management of pharyngitis adhered to published guidelines.Results: Among 479 total episodes of pharyngitis, 434 (91%) were from the EMR-based strategy and 281 (59%) from the administrative data-based strategy. Review of the records (the reference strategy) found that 391 of 479 (82%) were confirmed episodes of pharyngitis. A diagnostic test for group A streptococcus (GAS) was performed at 310 of 434 (71%) of episodes identified by the EMR-based strategy and at 214 of 281 (76%) of episodes by the administrative data-based strategy (P = 0.045). By the reference strategy, a diagnostic test was done in 301 of 391 (77%); more than at episodes found by the EMR-based strategy (71%, P < 0.001).Conclusions: The EMR-based strategy resulted in a statistically different proportion of episodes having diagnostic testing for GAS compared with a reference strategy. Complete evaluations to validate strategies for extracting data from electronic databases are necessary before assuming that measures of quality of care will be the same regardless of the source of data. [ABSTRACT FROM AUTHOR]

Context: Reports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine.Objective: To assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination.Design: Case-control study conducted from March 1997 through June 2003.Setting: Twenty different group practices in southern Connecticut.Participants: Case subjects, identified by active surveillance of all practices, consisted of 339 eligible children 13 months or older who were clinically diagnosed as having chickenpox and who also had a polymerase chain reaction (PCR) test result that was positive for varicella-zoster virus DNA. For each case subject, 2 controls were selected, matched by both age and pediatric practice.Main Outcome Measures: The effectiveness of the vaccine, especially the effects of time since vaccination and age at the time of vaccination, adjusted for possible confounders.Results: Although the adjusted overall effectiveness of the vaccine was 87% (95% confidence interval, 81%-91%; P<.001), there was a substantial difference in the vaccine's effectiveness in the first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P =.003). The vaccine's effectiveness in year 1 was substantially lower if the vaccine was administered at younger than 15 months (73%) than if it was administered at 15 months or older (99%, P =.01), although the difference in effectiveness overall for children immunized at younger than 15 months was not statistically significantly different than for those immunized at 15 months or older (81% vs 88%, P =.17). Most cases of chickenpox in vaccinees were mild.Conclusions: Although varicella vaccine is effective, its effectiveness decreases significantly after 1 year, although most cases of breakthrough disease are mild. If administered at younger than 15 months, the vaccine's effectiveness was lower in the first year after vaccination, but the difference in effectiveness was not statistically significant for subsequent years. [ABSTRACT FROM AUTHOR]

Long-term effects of Lyme disease, such as arthritis and neurologic abnormalities, present diagnostic difficulties. To complicate the issue, a host of nonspecific symptoms often are mistakenly attributed to persistent infection. The good news? Contrary to many parents' and pediatricians' fears, Lyme disease only rarely causes long-term problems in children. [ABSTRACT FROM AUTHOR]

To compare the sensitivity of a new ELISA for IgM antibodies to Borrelia burgdorferi that uses a recombinant outer surface protein C (rOspC) with those of a whole cell (WC) ELISA and an immunoblot assay for the diagnosis of early Lyme disease, serum specimens from 82 consecutive patients with physician-documented erythema migrans were analyzed. To compare the specificities of the three assays, serum specimens from 50 patients without a history of Lyme disease and from an area in which B. burgdorferi is not endemic were analyzed. The sensitivities of the WC ELISA, immunoblot assay, and IgM rOspC ELISA were 28%, 29%, and 46%, respectively, while the specificities were 100%, 100%, and 98%, respectively. The IgM rOspC ELISA is a convenient, readily automated, easily standardized serologic test that is significantly more sensitive for the diagnosis of early Lyme disease than either WC ELISA or immunoblot assay. [ABSTRACT FROM AUTHOR]

Because the incidence of inflicted traumatic brain injury (inflicted TBI) is low, even in populations at increased risk, very large samples are necessary to have adequate statistical power to conduct a randomized clinical trial of the effectiveness of a potential intervention to prevent inflicted TBI. This requirement for large samples, in addition to the logistic demands of prospective clinical trials, makes it prohibitively expensive to conduct such studies. Case-control studies provide a statistically efficient and logistically and economically feasible alternative approach to evaluating such interventions. However, because these are observational studies, they are susceptible to bias. Approaches are presented to conducting and analyzing case-control studies to evaluate interventions to prevent inflicted TBI while assessing and minimizing possible bias. [ABSTRACT FROM AUTHOR]

Lyme disease is caused by Borrelia species that are transmitted by Ixodes ticks prevalent in parts of the United States and Europe. A Lyme vaccine containing the OspA antigens from the single Borrelia species most prevalent in the United States was marketed in the 1990s, but was withdrawn because of unproven concerns about safety, which led to insufficient sales. Since then, the incidence of Lyme disease has increased in the United States owing to the geographical spread of infected ticks. Lyme disease due to multiple different species of Borrelia also is widely prevalent in many European countries. New Lyme vaccines, using OspA antigens from multiple species of American and European Borrelia, are in advanced clinical development, and one such vaccine is in phase 3 trials. When licensed, new vaccines are likely to have an impact in preventing Lyme disease, although the need for periodic boosters remains to be defined., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Functional somatic symptoms are associated with significant distress and impairment for children and their families. Despite the central role that families play in their children's care, there is little clinical research to guide how parents can support their children with functional somatic symptoms and promote better functioning. To address this gap, we developed a parent-based intervention for functional somatic symptoms in children and obtained preliminary data on acceptability, feasibility, treatment satisfaction, and clinical outcomes., Method: The intervention was adapted from SPACE (Supportive Parenting for Anxious Childhood Emotions), an evidence-based treatment for anxiety and related disorders in children. The intervention, SPACE-Somatic, was delivered to parents of 16 children (Mage = 14.50 years; 75% girls) with a range of functional somatic symptoms. Parents participated in seven weekly group sessions conducted via telehealth., Results: We found that SPACE-Somatic was acceptable, feasible, and satisfactory to parents. There were significant improvements in several clinical outcomes from baseline to posttreatment, including children's level of functional impairment, with some gains maintained at 3-month follow-up. Parents also reported improvements in their own stress and their accommodation of children's symptoms., Conclusion: This pilot study provides preliminary evidence that a parent-based intervention is viable and beneficial to children with functional somatic symptoms and their parents., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings., Objective: To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization., Design Setting and Participants: This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab-eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative., Exposure: Nirsevimab immunization, verified through state immunization registries., Main Outcomes and Measures: Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons., Results: The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible., Conclusions and Relevance: Nirsevimab provided substantial protection against RSV-related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program., Competing Interests: Competing interests: VEP was previously a member of the WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC). All other authors declare no conflicts of interest.

Background: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown., Objective: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests., Methods: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race)., Results: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03)., Conclusions: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose of Review: Because both incidence and awareness of tick-borne infections is increasing, review of major infections and recent advances related to their diagnosis and management is important., Recent Findings: A new algorithm, termed modified two-tier testing, for testing for antibodies to Borrelia burgdorferi , the cause of Lyme disease, has been approved and may replace traditional two-tier testing. In addition, doxycycline is now acceptable to use for treatment of and/or prophylaxis for Lyme disease for up to 21 days in children of any age. Borrelia miyamotoi , a bacterium in the relapsing fever type of Borrelia, is the first of this type of Borrelia that is transmitted by hard-bodied ticks such as Ixodes scapularis., Summary: Awareness of these infections and advances in their diagnosis and treatment is important to assure the best outcomes for affected patients. Table 1 contains a summary of infections discussed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Health care provider recommendations are among the most important factors influencing parents' decisions to vaccinate their adolescents. However, delivery of high-quality health care provider recommendations for vaccination is not universal. There is wide variation in the strength, timeliness and consistency of the delivery of recommendations for all adolescent vaccines. The factors that influence health care providers' recommendations are multi-level and can be conceptualized in much the same way as vaccine acceptance among parents. Health care providers are influenced by their own attitudes and beliefs about a vaccine and also by the patient they are treating and by the community in which they practice as well as state and national level vaccine policy. We propose a multi-level framework for understanding the factors that influence health care providers' recommendations at the individual, interpersonal and community level to both develop and adapt interventions to improve providers' recommendations., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Surveillance for respiratory syncytial virus (RSV) likely captures just a fraction of the burden of disease. Understanding the burden of hospitalizations and disparities between populations can help to inform upcoming RSV vaccine programs and to improve surveillance., Methods: We obtained monthly age-, ZIP code- and cause-specific hospitalizations in New York, New Jersey, and Washington from the US State Inpatient Databases (2005-2014). We estimated the incidence of respiratory hospitalizations attributable to RSV by age and by socioeconomic status using regression models. We compared the estimated incidence and the recorded incidence (based on ICD9-CM) of RSV hospitalizations to estimate the under-recorded ratio in different subpopulations., Results: The estimated annual incidence of respiratory hospitalizations due to RSV was highest among infants < 1 year of age with low socioeconomic status (2800, 95% CrI [2600, 2900] per 100,000 person-years). We also estimated a considerable incidence in older adults (≥ 65 years of age), ranging from 130 to 960 per 100,000 person-years across different socioeconomic strata. The incidence of hospitalization recorded as being due to RSV represented a significant undercount, particularly in adults. Less than 5% of the estimated RSV hospitalizations were captured for those ≥ 65 years of age., Conclusions: RSV causes a considerable burden of hospitalization in young children and in older adults in the US, with variation by socioeconomic group. Recorded diagnoses substantially underestimate the incidence of hospitalization due to RSV in older adults., (© 2022. The Author(s).)

We summarize studies of varicella vaccine's effectiveness for prevention of varicella and lessons learned during the first 25 years of the varicella vaccination program in the United States. One dose of varicella vaccine provided moderate protection (82%-85%) against varicella of any severity and high protection (100%) against severe varicella, with some waning of protection over time. The 1-dose program (1995-2006) had a substantial impact on the incidence both of varicella and of severe outcomes (71%-90% decrease) although it did not prevent low-level community transmission and some outbreaks continued to occur in highly vaccinated populations. Two doses of varicella vaccine improved the vaccine's effectiveness by at least 10% against varicella of any severity, with further declines in the incidence both of varicella and of severe outcomes as well as in both number and size of outbreaks. There is no evidence for waning of the effectiveness of 2 doses of the vaccine., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Medically minor but clinically important findings associated with physical child abuse, such as bruises in pre-mobile infants, may be identified by frontline clinicians yet the association of these injuries with child abuse is often not recognized, potentially allowing the abuse to continue and even to escalate. An accurate natural language processing (NLP) algorithm to identify high-risk injuries in electronic health record notes could improve detection and awareness of abuse. The objectives were to: 1) develop an NLP algorithm that accurately identifies injuries in infants associated with abuse and 2) determine the accuracy of this algorithm., Methods: An NLP algorithm was designed to identify ten specific injuries known to be associated with physical abuse in infants. Iterative cycles of review identified inaccurate triggers, and coding of the algorithm was adjusted. The optimized NLP algorithm was applied to emergency department (ED) providers' notes on 1344 consecutive sample of infants seen in 9 EDs over 3.5 months. Results were compared with review of the same notes conducted by a trained reviewer blind to the NLP results with discrepancies adjudicated by a child abuse expert., Results: Among the 1344 encounters, 41 (3.1%) had one of the high-risk injuries. The NLP algorithm had a sensitivity and specificity of 92.7% (95% confidence interval [CI]: 79.0%-98.1%) and 98.1% (95% CI: 97.1%-98.7%), respectively, and positive and negative predictive values were 60.3% and 99.8%, respectively, for identifying high-risk injuries., Conclusions: An NLP algorithm to identify infants with high-risk injuries in EDs has good accuracy and may be useful to aid clinicians in the identification of infants with injuries associated with child abuse., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Importance: The emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2 has led to increases in both infections and hospitalizations among adolescents. Little is known about the effectiveness of the BNT162b2 vaccine in adolescents in the general population, as opposed to a clinical trial population., Objective: To estimate the effectiveness of the BNT162b2 vaccine in adolescents aged 12 to 18 years., Design, Setting, and Participants: This was a matched case-control study among adolescents (aged 12-18 years) who had results from a SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test. Immunization histories, relevant clinical data, and RT-PCR test results were obtained from the Yale New Haven Health System's medical records between June 1, 2021, and August 15, 2021, when the Delta variant caused 92% of infections in Connecticut. Case participants were defined as adolescents who had a positive test result and an associated medical encounter. Control participants were defined as those who had a negative test result and were matched to a case participant by age, county of residence, and date of testing., Exposures: Adolescents were defined as fully immunized if they had received 2 doses of vaccine at least 14 days before focal time., Main Outcomes and Measures: The primary outcome measured was SARS-CoV-2 infection confirmed by RT-PCR. The vaccine's effectiveness (VE) was estimated using matched odds ratios from conditional logistic regression models. Secondary measures included estimated VE by clinical symptoms, number of vaccine doses received, and elapsed time from immunization., Results: A total of 6901 adolescents were tested for SARS-CoV-2. The final sample comprised 186 case participants and 356 matched control participants. The median age was 14 (IQR, 13-16) years, 262 (48%) identified as female, 81 (15%) as Black, 82 (15%) as Hispanic, and 297 (55%) as White. Overall, 134 (25%) were fully immunized (case participants, 10 [5%]; control participants, 124 [35%]). The median time between immunization and the SARS-CoV-2 test was 62 days (range, 17-129 days). Within 4 months of receiving 2 doses, VE against any infection was estimated to be 91% (95% CI, 80%-96%); against asymptomatic infection, 85% (95% CI, 57%-95%). Effectiveness after a single dose was estimated to be 74% (95% CI, 18%-92%)., Conclusions and Relevance: In this retrospective case-control study of US adolescents, 2 doses of BNT162b2 vaccine appeared to provide excellent protection for at least 4 months after immunization against both symptomatic and asymptomatic SARS-CoV-2 infections.

Lyme disease is an infection caused by Borrelia burgdorferi sensu lato, which is transmitted to humans through the bite of an infected Ixodes tick. The majority of patients recover without complications with antibiotic therapy. However, for a minority of patients, accompanying non-specific symptoms can persist for months following completion of therapy. The constellation of symptoms such as fatigue, cognitive dysfunction, and musculoskeletal pain that persist beyond 6 months and are associated with disability have been termed post-treatment Lyme disease syndrome (PTLDS), a subset of a broader term "chronic Lyme disease." Chronic Lyme disease is a broad, vaguely defined term that is used to describe patients with non-specific symptoms that are attributed to a presumed persistent Borrelia burgdorferi infection in patients who may or may not have evidence of either previous or current Lyme disease. The diagnoses of chronic Lyme disease and of PTLDS have become increasingly relevant to the practice of immunologists due to referrals for consultation or for intravenous immunoglobulin (IVIG) treatment. This review aims to explore the relationship between chronic Lyme disease, post-treatment Lyme disease syndrome, and the immune system. Here, we review the current literature on (1) issues in conventional and alternative diagnostic testing for Lyme disease, (2) the hypothesis that B. burgdorferi infection can persist despite appropriate use of recommended antibiotics, (3) current theories regarding B. burgdorferi's role in causing both immune dysregulation and protracted symptoms, and (4) the use of IVIG for the treatment of Lyme disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Volunteer Income Tax Assistance (VITA) program is an underutilized free taxpreparation service that directly addresses poverty by maximizing tax refunds. A pediatric medical home (PMH) with an embedded VITA site provides an excellent opportunity for a medical-financial partnership. We sought to assess the knowledge, attitudes, and practices of caregivers of children who used a PMH after embedding a VITA site. We found that a PMH-VITA site was a convenient, trusted, useful, and potentially tax-filing behaviorchanging intervention. Importantly, most caregivers who did not use the PMH-VITA site had no knowledge of availability of free tax filing services but would consider using one the following year. Improved marketing is needed to increase utilization in our target population.

Importance: Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in young children. RSV largely disappeared in 2020 owing to precautions taken because of the COVID-19 pandemic. Estimating the timing and intensity of the reemergence of RSV and the age groups affected is crucial for planning for the administration of prophylactic antibodies and anticipating hospital capacity., Objective: To examine the association of different factors, including mitigation strategies, duration of maternal-derived immunity, and importation of external infections, with the dynamics of reemergent RSV epidemics., Design, Setting, and Participants: This simulation modeling study used mathematical models to reproduce the annual epidemics of RSV before the COVID-19 pandemic in New York and California. These models were modified to project the trajectory of RSV epidemics from 2020 to 2025 under different scenarios with varying stringency of mitigation measures for SARS-CoV-2. Simulations also evaluated factors likely to affect the reemergence of RSV epidemics, including introduction of the virus from out-of-state sources and decreased transplacentally acquired immunity in infants. Models using parameters fitted to similar inpatient data sets from Colorado and Florida were used to illustrate these associations in populations with biennial RSV epidemics and year-round RSV circulation, respectively. Statistical analysis was performed from February to October 2021., Main Outcomes and Measures: The primary outcome of this study was defined as the estimated number of RSV hospitalizations each month in the entire population. Secondary outcomes included the age distribution of hospitalizations among children less than 5 years of age, incidence of any RSV infection, and incidence of RSV lower respiratory tract infection., Results: Among a simulated population of 19.45 million people, virus introduction from external sources was associated with the emergence of the spring and summer epidemic in 2021. There was a tradeoff between the intensity of the spring and summer epidemic in 2021 and the intensity of the epidemic in the subsequent winter. Among children 1 year of age, the estimated incidence of RSV hospitalizations was 707 per 100 000 children per year in the 2021 and 2022 RSV season, compared with 355 per 100 000 children per year in a typical RSV season., Conclusions and Relevance: This simulation modeling study found that virus introduction from external sources was associated with the spring and summer epidemics in 2021. These findings suggest that pediatric departments should be alert to large RSV outbreaks in the coming seasons, the intensity of which could depend on the size of the spring and summer epidemic in that location. Enhanced surveillance is recommended for both prophylaxis administration and hospital capacity management.

Objectives: Decisions about the management of febrile infants ≤60 days old may be well suited for shared decision making (SDM). Our objectives were to learn about parents' experiences with receiving and understanding information in the emergency department (ED) and their perspectives on SDM, including for decisions about lumbar puncture (LP)., Methods: We conducted semistructured interviews with 23 parents of febrile infants ≤60 days old evaluated in the pediatric ED at an urban, academic medical center. Interviews assessed parents' experiences in the ED and their perspectives on communication and SDM. Two investigators coded the interview transcripts, refined codes, and identified themes using the constant comparative method., Results: Parents' unmet need for information negatively impacted parents' understanding, stress, and trust in the physician. Themes for parents' perspectives on SDM included the following: (1) giving parents the opportunity to express their opinions and concerns builds confidence in the decision making process, (2) parents' preferences for participation in decision making vary considerably, and (3) different perceptions about risks influence parents' preferences about having their infant undergo an LP. Although some parents would defer decision making to the physician, they still wanted to be able to express their opinions. Other parents wanted to have the final say in decision making. Parents valued risks and benefits of having their child undergo an LP differently, which influenced their preferences., Conclusions: Physicians need to adequately inform parents to facilitate parents' understanding of information and gain their trust. Shared decision making may be warranted for decisions about whether to perform an LP, although parents' preferences for participating in decision making vary., Competing Interests: Disclosure: The authors declare no conflict of interest and no financial relationships relevant to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar's primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)

Background: Vaccine receipt among mid-adults remains low, with only one quarter of adults being up to date for all recommended vaccines. It is important to understand the myriad factors that influence vaccine receipt among mid-adult women to address these low rates., Methods: We conducted a cross-sectional analysis of data from women ages 24-45 years collected as part of an ongoing case-control study of the effectiveness of HPV vaccine. We examined associations between demographic characteristics and healthcare utilization and receipt of individual vaccines and combinations of multiple vaccines using logistic regression analyses for three routinely recommended vaccines: tetanus, influenza and HPV., Results: Among the 309 women enrolled in the study, only 19 (6.2%) were up to date for all three recommended vaccines and 41 (13.3%) had not received any of the recommended vaccines. A greater number of health care visits in the past year was associated with receipt of influenza (aOR = 6.37, 95% CI = 2.53, 16.1) and tetanus (aOR = 2.17, 95% CI = 1.14, 4.12) vaccines. White women were more likely to have received HPV vaccine (aOR = 2.39, 95% CI = 1.07, 5.36)., Conclusions: Uptake of recommended vaccines is low among young and mid-adult women. There is a need for greater understanding of the underlying factors influencing vaccine receipt in this population.

Introduction: Rates of immunization with human papillomavirus (HPV) vaccine among adolescent and young adult females remain suboptimal. There is a continued need to focus on catch-up immunization. Some hospitals in the United States have implemented inpatient postpartum HPV immunization programs (IPP-HPV) as part of a strategy to improve rates of catch-up immunization. Patients' perspectives are critical to facilitating broad adoption of IPP-HPV. The objectives of this study were to understand the experiences and perspectives of postpartum women recommended to receive HPV vaccine before hospital discharge and to identify facilitators of and barriers to program implementation., Methods: We conducted in-depth semistructured interviews with postpartum women eligible for IPP-HPV. We used purposive sampling to ensure representation across race, ethnicity, and language. Interviews were analyzed using an iterative thematic approach., Results: The median age of participants (n = 24) was 22 years (range, 15-26 years), and six had declined the inpatient dose of HPV vaccine. Overall, women viewed IPP-HPV favorably. Facilitators of program implementation included viewing HPV vaccine as prevention, normalization of the vaccine, convenience of IPP-HPV, and the experience of a patient-centered approach. Barriers included the peripartum environment and associated stress, vaccine hesitancy, and a lack of both awareness of and knowledge about HPV vaccine., Conclusions: IPP-HPV immunization is a strategy well-received by women for improving rates of catch-up immunization. The implementation of such programs may be optimized by increasing awareness that the vaccine is available and recommended for postpartum women, and by using a patient-centered approach that is sensitive to the needs of postpartum patients., (Copyright © 2021 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Introduction: In 2006, the first human papillomavirus (HPV) vaccine was approved by the Food and Drug Administration in the USA based on pre-licensure clinical trials that found it to be highly efficacious at preventing persistent infection and precancerous, high-grade cervical lesions (HGCLs) caused by viral types the vaccine protects against. However, the real-world effectiveness of HPV vaccines as used in clinical practice may be quite different from the efficacy found in pre-licensure clinical trials. More than 10 years have passed since the introduction of the vaccine programme. It is critical to determine if the full benefits of HPV are being realised in real-world settings., Methods and Analysis: The objectives of this study were to estimate the effectiveness of HPV vaccines as used in real-world clinical settings and to determine the degree to which the vaccine's effectiveness varies based on age at the time of immunisation and the number of doses received. The study will be a population-based, matched case-control study. Cases will be women with newly diagnosed HGCL associated with HPV types 16 and 18. Matched controls will be women with a normal Pap test result, matched individually to cases in a 2:1 ratio by age, a practice and date of testing. Medical records will be reviewed to determine dates of receipt of the HPV vaccine for all participants. We will use multivariate conditional logistic regression to control for potential confounders., Ethics and Dissemination: This protocol presents minimal risk to the subjects. This protocol has received approval from the Institutional Review Board of Yale University (HIC: 1502015308), and a Health Insurance Portability and Accountability Act (HIPAA) Waiver of Authorisation has been granted to allow investigators to recruit subjects for the study. Findings will be disseminated through peer-reviewed, open-access scientific journals and conference presentations., Competing Interests: Competing interests: Dr Niccolai has served as Scientific Advisor for Merck. Dr Sheth receives Gardasil 9 from Merck at no cost for research and has served as a consultant for Merck. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We conducted a matched case-control study to assess the effectiveness of Lyme vaccine (LYMErix) as it was used in clinical practice. We found ≥3 doses to be 71% effective against Lyme disease. This is the first study to show that the Lyme vaccine is effective in a real-world setting., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Emergency care for children is provided predominantly in community emergency departments (CEDs), where abusive injuries frequently go unrecognized. Increasing access to regional child abuse experts may improve detection of abuse in CEDs. In three CEDs, we intervened to increase involvement of a regional hospital child protection team (CPT) for injuries associated with abuse in children < 12 months old. We aimed to increase CPT consultations about these infants from the 3% baseline to an average of 50% over 12 months., Methods: We interviewed CED providers to identify barriers and facilitators to recognizing and reporting abuse. Providers described difficulties differentiating abusive from nonabusive injuries and felt that a second opinion would help. Using a plan-do-study-act approach, beginning in April 2018, we tested, refined, and implemented interventions to increase the frequency of CPT consultation, including leadership and champion engagement, provider training, clinical pathway implementation, and an audit and feedback process. Data were collected for 15 months before and 17 months after initiation of interventions. We used a statistical process control chart to track CPT consultations about children < 1 year old with high-risk injuries, use of skeletal surveys (SSs), and reports to child protective services (CPS)., Results: Evidence of special cause was identified beginning in June 2018, with a shift of 8 points to one side of the center line. For the subsequent 8-month period, the CPT was consulted for a mean of 47.5% of children with high-risk injuries; this was sustained for an additional 7 months. The average percentage of infants with high-risk injuries who received a SS increased from 6.7% to 18.9% and who were reported to CPS increased from 10.7% to 32.6%., Conclusion: Targeted interventions in CEDs increased the frequency of CPT consultation, SS use, and reports to CPS for infants with high-risk injuries. Such interventions may improve recognition of physical abuse., (© 2020 by the Society for Academic Emergency Medicine.)

Objectives: We aimed to develop and test a tool to engage parents of febrile infants ≤ 60 days of age evaluated in the emergency department (ED). The tool was designed to improve communication for all parents and to support shared decision-making (SDM) about whether to perform a lumbar puncture (LP) for infants 29 to 60 days of age., Methods: We conducted a multiphase development and testing process: 1) individual, semistructured interviews with parents and clinicians (pediatric and general emergency medicine [EM] physicians and pediatric EM nurses) to learn their preferences for a communication and SDM tool; 2) design of a "storyboard" of the tool with design impression testing; 3) development of a software application (i.e., app) prototype, called e-Care; and 4) usability testing of e-Care, using qualitative assessment and the system usability scale (SUS)., Results: We interviewed 27 parents and 23 clinicians. Interviews revealed several themes, including that a communication tool should augment but not replace verbal communication; a Web-based format was preferred; and information about infections and testing, including the rationales for specific tests, would be valuable. We then developed separate versions of e-Care for infants ≤ 28 days and 29 to 60 days of age, in both English and Spanish. The e-Care app includes four sections: 1) homepage; 2) why testing is done; 3) what tests are done; and 4) what happens after testing, including a table for parents of infants 29 to 60 days of age to compare the risks/benefits of LP in preparation for an SDM conversation. Parents and clinicians reported that e-Care was understandable and helpful. The mean SUS score was 90.3 (95% confidence interval = 84 to 96.6), representing "excellent" usability., Conclusions: The e-Care app is a useable and understandable tool to support communication and SDM with parents of febrile infants ≤ 60 days of age in the ED., (© 2020 by the Society for Academic Emergency Medicine.)