Search

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

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.