The association between influenza vaccine effectiveness and egg-based manufacturing technology: literature review and US expert consensus.

BACKGROUND: Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses. METHODS: This study replicated the methodology used in a 2020 literature review and European consensus, providing an updated review and consensus opinion of 10 US experts on the evidence for a mechanistic basis for reduction of VE due to egg-based manufacturing methods. A mechanistic basis was assumed if sufficient evidence was found for underlying principles proposed to give rise to such an effect. Evidence for each principle was brought forward from the 2020 review and identified here by structured literature review and expert panel. Experts rated the strength of support for each principle and a mechanistic basis for reduction of VE due to egg-based influenza vaccine manufacture in a consensus method (consensus for strong/very strong evidence = ≥ 3.5 on 5-point Likert scale). RESULTS: Experts assessed 251 references (from previous study: 185; this study: 66). The majority of references for all underlying principles were rated as strong or very strong supporting evidence (52-86%). Global surveillance, WHO candidate vaccine virus selection, and manufacturing stages involving eggs were identified as most likely to impact influenza VE. CONCLUSION: After review of extensive evidence for reduction of VE due to egg-based influenza vaccine manufacture, influenza experts in the US joined those in Europe in unanimous agreement for a mechanistic basis for the effect. Vaccine providers and administrators should consider use of non-egg-based influenza vaccine manufacture to reduce the risk of egg adaptations and likely impact on VE.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 Guideline on Diagnosis and Management of Acute Bacterial Arthritis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute bacterial arthritis (ABA) in children was developed by a multidisciplinary panel representing the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with ABA, including specialists in pediatric infectious diseases and orthopedics. The panel's recommendations for the diagnosis and treatment of ABA are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of ABA in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) (see Figure 1). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Restoring Trust: The Need for Precision Medicine in Infectious Diseases, Public Health and Vaccines.

There are limited data on precision medicine in infectious diseases and vaccines; however, precise management of infectious diseases plays a critical role in trust for government, health-care organizations, science, and pharma. The improvement in biomedical technologies, availability of large clinical and -omic data and appropriate application of artificial intelligence may allow precision in vaccines and public health and restore trust. This is an invited editorial on the role of precision medicine in infectious diseases and vaccines.

Power Reimagined: Advancing Women Into Emerging Leadership Positions.

Academic medicine is evolving from the traditional model of a medical school and teaching hospital owned by the same entity to one with complex academic medical centers and health systems. This increased complexity is evident not only in the funding streams and organizational priorities of these growing health systems but also in the evolution of leadership roles toward more matrixed positions and more individuals who hold both medical school and health system roles. Given this changing landscape, the authors of this commentary raise the following questions: Will the levers of power remain in the hands of those in traditional academic roles? Or are they moving toward those in roles that are more aligned with the clinical enterprise and health system? Then, if this shift is occurring, what is needed to prepare women to be competitive candidates for these new roles? Because of the long history of and current gender imbalance in academic leadership roles, professional development programs have traditionally focused on preparing women to advance through the faculty ranks and for department chair and decanal roles. With the shift to more complicated health systems, the definitions, responsibilities, and types of leadership roles in academic medicine are also evolving to include nontraditional academic positions in the health system, such as c-suite and other senior executive roles. In parallel to the gender inequities in traditional roles, women are also underrepresented in health system leadership roles. Therefore, it is critical to explicitly identify emerging roles in health care leadership, address systemic barriers, and actively train and prepare women with the knowledge, skills, and experience required for these positions. Only with consistent attention to outcomes and the implementation of intentional systems to engage, prepare, and advance women will the gender gap be closed.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus (RSV) Vaccine in Healthy RSV-Seropositive Children 12-23 Months of Age.

BACKGROUND: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12-23-month-old RSV-seropositive children followed up for 2 years after vaccination. METHODS: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti-RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2. RESULTS: Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1. CONCLUSIONS: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. CLINICAL TRIALS REGISTRATION: NCT02927873.

Respiratory syncytial virus (RSV) is among the main causes of bronchiolitis and pneumonia regularly leading to hospitalization in children. A safe and effective vaccine to prevent RSV infection in this age group has not yet been found, despite great efforts over several decades. This study tested a new candidate RSV vaccine, expressing 3 important pieces of the virus, in toddlers who already had a previous RSV infection. The vaccine was generally well tolerated. Vaccination triggered antibodies against RSV that were able to block the virus in laboratory tests and that persisted for 1 year.

Organizations in science and medicine must hold each other accountable for discriminatory practices.

Many organizations persist in working with others that engage in known, remediable structural discrimination. We name this practice interorganizational structural discrimination (ISD) and argue it is a pivotal contributor to inequities in science and medicine. We urge organizations to leverage their relationships and demand progress from collaborators.

Factors Influencing Retirement Decisions of Senior Faculty at U.S. Medical Schools: Are There Gender-Based Differences?

Purpose: Women comprise almost one-third of academic medicine faculty 60 years of age and older. Gender disparities have been documented across many measures in medicine, including salary, promotion rates, and leadership positions and may impact long-term career and retirement decisions. The authors sought to describe gender differences in retirement decisions among late-career, full-time medical school faculty. Materials and Methods: The authors conducted a secondary analysis of cross-sectional survey data from a 2017 survey of faculty 55 years of age and older at 14 U.S. Medical Schools. Responses were compared for differences by gender using bivariate and multivariable analyses. Results: Among the 2,126 respondents (41% response rate), the majority were male (67%) and the average age was 62. Less than half (45%) had current plans to retire and 50% reported that they would consider working part time. Women faculty were less likely to be professors or on a tenure track and more likely to be single and report past and current caregiving responsibilities. Women differed from men in the personal and professional factors influencing retirement decisions with women more likely to identify health insurance, sense of burnout, lack of access to career advancing resources and opportunities, feeling devalued at work, and caregiving responsibilities as important issues. Conclusions: Women late-career faculty report unique and salient factors influencing retirement plans that may reflect cumulative gender-based career differences and disparities. Institutions should be aware of these differences and work to support women during late career and retirement transitions, including creating opportunities for faculty to remain engaged in meaningful work during retirement transitions if they desire to do so.

Lasting Solutions for Advancement of Women of Color.

Despite efforts to improve parity in the biomedical workforce, gender bias persists related to equitable pay, promotion, speaking opportunities, journal editorial positions, research funding, and leadership positions. This bias becomes more prominent for women of color and women with other intersectional identities who come from underrepresented groups. It is critical to understand the barriers that women face and why the pathway is especially challenging for women of color. In this commentary, the authors cite research related to the effects of institutional gender bias in academic medicine, including research on bias against women of color. As academic leaders who come from underrepresented groups, the authors are aware that traditional approaches to reducing this bias have not worked well, and they instead highlight promising strategies aimed at filling the pathway to leadership with women of color who are qualified and ready to take the helm. They address solutions to ensure the academic pathway is supportive. They also provide several recommendations, including: offering more opportunities for mentorship and sponsorship, improving access to formal leadership programming, modeling successful upstander initiatives, recognizing the growing role of minority-based medical societies, implementing early-career education, increasing journal editorial board representation, and expanding promotion criteria. Appropriate training, education, and partnership with internal and external stakeholders are necessary to advance leadership equity for women of color in academic medicine.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Clinical practice guideline by the pediatric infectious diseases society and the Infectious diseases society of america: 2021 guideline on diagnosis and management of Acute Hematogenous Osteomyelitis in pediatrics

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Current State of Respiratory Syncytial Virus Disease and Management.

Respiratory syncytial virus (RSV) is a major cause of hospitalizations due to pneumonia and bronchiolitis. Substantial morbidity and socioeconomic burden are associated with RSV infection worldwide. Populations with higher susceptibility to developing severe RSV include premature infants, children with chronic lung disease of prematurity (CLDP) or congenital heart disease (CHD), elderly individuals aged > 65 years, and immunocompromised individuals. In the pediatric population, RSV can lead to long-term sequelae such as wheezing and asthma, which are associated with increased health care costs and reduced quality of life. Treatment for RSV is mainly supportive, and general preventive measures such as good hygiene and isolation are highly recommended. Although vaccine development for RSV has been a global priority, attempts to date have failed to yield a safe and effective product for clinical use. Currently, palivizumab is the only immunoprophylaxis (IP) available to prevent severe RSV in specific high-risk pediatric populations. Well-controlled, randomized clinical trials have established the efficacy of palivizumab in reducing RSV hospitalization (RSVH) in high-risk infants including moderate- to late-preterm infants. However, the American Academy of Pediatrics (AAP), in its 2014 policy, stopped recommending RSV IP use for ≥ 29 weeks' gestational age infants. Revisions to the AAP policy for RSV IP have largely narrowed the proportion of pediatric patients eligible to receive RSV IP and have been associated with an increase in RSVH and morbidity. On the other hand, after reviewing the recent evidence on RSV burden, the National Perinatal Association, in its 2018 clinical practice guidelines, recommended RSV IP use for a wider pediatric population. As the AAP recommendations drive insurance reimbursements for RSV IP, they should be revised to help further mitigate RSV disease burden.

Late-Career Expectations: A Survey of Full-Time Faculty Members Who Are 55 or Older at 14 U.S. Medical Schools.

PURPOSE: The average age of full-time faculty members at U.S. medical schools accredited by the Liaison Committee on Medical Education was 49.5 in 2017, yet the academic medicine community knows little about late-career faculty. The authors sought to characterize full-time faculty members 55 or older and assess their work-life expectations. METHOD: The authors conducted a survey (May-September 2017) of faculty 55+ at 14 U.S. medical schools. RESULTS: Of the 5,204 faculty members invited, 2,126 (40.8%) responded. The average age of respondents was 62.3, and among those responding to the relevant questions, most identified as male (1,425; 67.2%), white (1,841; 88.3%), and married/partnered (1,803; 85.5%). Fewer than half (915; 45.2%) indicated they had begun thinking about full-time retirement, estimating that they would do so at a mean age of 67.8 (standard deviation = 4.3). Half the respondents (1,004; 50.0%) would consider moving to part-time status. The top 3 personal factors likely to affect retirement decisions were health, postretirement plans, and spouse's/partner's plans. The top 3 professional factors were phased retirement or part-time options, changes in institutional leadership, and presence of a successor. Faculty indicated that they would, post retirement, be interested in ongoing work in teaching/education and research/scholarship and that they wanted health insurance, email, and part-time teaching opportunities. CONCLUSIONS: U.S. medical schools employ a rapidly aging workforce. These data indicate that neither faculty members nor institutions are prepared. Faculty affairs and develop ment leaders should champion efforts to engage with late-career faculty to prepare for this changing landscape.

Late-Career Faculty: A Survey of Faculty Affairs and Faculty Development Leaders of U.S. Medical Schools.

PURPOSE: Individuals 55 or older constitute 28.5% of the U.S. population but 32% of full-time faculty at U.S. medical schools accredited by the Liaison Committee on Medical Education (LCME). The academic medicine community knows little about the policies, programs, and resources for faculty in pre- and post-retirement stages. The authors sought to inventory the range of institutional resources for late-career faculty development and retirement planning in U.S. LCME-accredited medical schools. METHOD: The authors surveyed 138 medical school faculty affairs deans and leaders in May 2017 to ascertain (1) priorities around retirement, succession planning, and workforce development/support; (2) retirement policies; (3) late-career and retirement resources; and (4) perceived factors impacting faculty retirement. RESULTS: Of those invited, 84 (60.9%) responded to the survey, and of these, 44 (52.4%) disagreed or strongly disagreed that retirement planning and support was a top priority in their offices. Less than half (n = 35 [41.7%]) reported that their institution had a retirement policy. The 5 most common late-career and retirement-related resources offered were emeriti or honorific appointments, academic benefits for retirees, phased retirement, retirement counseling, and financial planning. More than half the respondents noted that the following factors impact faculty retirements: physician burnout (43/75 respondents [57.3%]), decreased grant funding (42/75 [56.0%]), and changes in productivity requirements (38/75 [50.7%]). CONCLUSIONS: These data highlight a distinct, startling gap between the needs of a fast-growing population of late-career faculty and the priorities of their institutions. Faculty affairs/faculty development offices must meet these growing needs.

Women's Representation Among Members and Leaders of National Medical Specialty Societies.

PURPOSE: National medical specialty societies speak for their respective fields in policy debates, influence research, affect trainees' specialization decisions, provide career development opportunities, and confer awards and recognitions. This study provides a comprehensive overview of the gender demographics of society members and leaders. METHOD: In 2016, the Group on Women in Medicine and Science (of the Association of American Medical Colleges) sought to characterize the gender of members and leaders of specialty societies from 2000 to 2015. This report provides descriptive data, including how many of the responding societies (representing each of 30 major medical specialties) had substantial (> 10%) increases in women's representation among leadership between the first and second halves of the study period. RESULTS: The average proportion of full members who were female in responding societies was 25.4% in 2005 and 29.3% in 2015. The proportion of women among those serving as the highest-ranking elected leader between 2000 and 2015 in each specialty ranged from 0% to 37.5% (mean, 15.8%). The mean proportion of women on governing boards ranged from 0% to 37.3% (mean of means, 18.8%) in 2000-2007 and from 0% to 47.6% (mean of means, 25.2%) in 2008-2015. In 9 specialties, the mean percentage of women serving on governing boards increased by over 10% from the first to the second half of the study period. CONCLUSIONS: Although many women are full members of specialty societies, women still constitute a minority of leaders. This report establishes a baseline from which to evaluate the effect of societies' efforts to improve diversity, equity, and inclusion.

Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies.

BACKGROUND: Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti-HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. METHODS: Serum anti-HPV-16/18 antibodies were determined at baseline and every 12 months in baseline DNA-negative women (N = 2687 for HPV-16 and 2705 for HPV-18) by enzyme-linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6-months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7-year period. The association between the risk of type-specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. RESULTS: Risk of newly detected HPV-16-associated 6-month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC-US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV-16-associated incident infections (HR = 0.81 [0.56; 1.16]) and 12-month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV-18-seropositive vs -seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6-month PIs, HR = 0.31 [0.07; 1.36] for 12-month PIs, and HR = 0.61 [0.23; 1.61] for ASC-US+). CONCLUSIONS: Naturally acquired anti-HPV-16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15- to 25-year-old women.

A Timely Problem: Parental Leave During Medical Training.

Shifting demographics and concerns about burnout prevention merit a reexamination of existing structures and policies related to leaves of absence that may be necessary during medical training. In this Invited Commentary, the authors address the issue of parental leave for medical students and residents. Discussion about parental leave for these trainees is not new. Despite decades of dialogue, leave policies throughout the undergraduate and graduate medical education continuum lack standardization and are currently ill defined and inadequate. There are a number of barriers to implementation. These include stigma, financial concerns, workforce and duty hours challenges, and the historically rigid timeline for progression from one stage of medical training to the next. Potential solutions include parent-friendly curricular innovations, competency-based medical education, and provision of short-term disability insurance. Most important, adopting more flexible approaches to graduation requirements and specialty board examination eligibility must be addressed at the national level. The authors identify cultural and practical challenges to standardizing parental leave options across the medical education continuum and issue a call to action for implementing potential solutions.

The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease.

BACKGROUND: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10-20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients. OBJECTIVES: The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience. METHODS: The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5-18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm. CONCLUSION: This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.