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.

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.

Collaborating to Enhance Faculty Development through Structured Funding.

PROBLEM: Faculty development is critical to individual career growth and success in academic medicine and it enhances the overall academic climate of an institution. Despite these well-recognized benefits, time and financial constraints often limit participation of faculty members. To address this issue, the University of South Dakota Sanford School of Medicine (SSOM) developed a novel policy and process to support participation in faculty development programs. APPROACH: In 2014, the SSOM Office of Continuing Professional Development (OCPD) implemented a process for funding faculty members' participation in external career and educational development programs. A subcommittee of the Faculty Development Committee reviewed and selected applications based on the benefit to the applicant's career and the SSOM as whole. Selected applicants were required to disseminate new knowledge from the external programs to other SSOM faculty, staff, and trainees. OUTCOMES: With the implementation of this program, 17 faculty members received funding. The race/ethnicities of the selected applicants reflected the overall demographics of the larger SSOM community. The majority of the selected applicants were female (n=12, 70 percent), assistant professors (n=9, 53 percent), and members of clinical departments (n=12, 70 percent). Upon completion of the program, five participants achieved academic promotion. This novel funding mechanism greatly increased faculty participation in external programs and participants reported enhanced networking opportunities, leadership experience, and career opportunities. NEXT STEPS: Challenges observed with implementation of the program have led to revision of the application process, tracking of participant demographic data, and confirmation of knowledge dissemination.

Evaluation of a Formal Pediatric Faculty Mentorship Program.

INTRODUCTION: The purpose of this article is to describe how a formal mentoring program in pediatrics can prepare new physicians and scientists for their roles and conflicting responsibilities within a community-based medical school. While research supports the impact of faculty mentoring, quality partnerships are reportedly low in academic medicine and can negatively affect junior faculty who are preparing for certifying examinations, orienting to a new role and balancing career and personal life. METHODS: Data were collected from mentors and mentees in six rollouts (71 pairs) of a formal mentoring program in the Department of Pediatrics of the University of South Dakota Sanford School of Medicine/Sanford Children's Specialty Clinic in Sioux Falls, South Dakota. Specifically, focus groups, surveys and objective data (promotion, retention and board pass rates) were used for formative and summative evaluation and reported in this article. RESULTS: The results indicated high program satisfaction including 97 percent of participants would recommend the program to other faculty. Reported benefits included career development, retention, promotion and academic productivity. Challenges identified were lack of time, promotion criteria ambiguity and poor mentee initiative. CONCLUSIONS: Although the sample sizes were small for pre-post comparisons, the results provided a longitudinal evaluation and program best practices. Overall, a structured mentoring program was of value to faculty and resulted in partnerships that likely would not occur otherwise. The findings suggest that programs should assist junior faculty with onboarding and enculturation, career goals and focus, time management, work-life balance and promotion clarification and preparation.

Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study.

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA.

Update on Adolescent Immunizations.

Timely and complete adolescent vaccination remains an elusive public health goal. Three infections for which routine adolescent vaccination is recommended in the U.S. are pertussis, meningococcal disease and human papillomavirus (HPV). These infections and the Tdap, meningococcal and HPV vaccines recommended for adolescents are reviewed in this article.

Strategies for Prevention of Methicillin Resistant Staphylococcus aureus (MRSA) Infections and Decolonization.

Methicillin resistant Staphylococcus aureus (MRSA) invasive infections can be severe in the pediatric population with high morbidity and mortality. MRSA colonization can predispose to recurrent skin and soft tissue infections and invasive MRSA disease and is a frequent challenge faced by clinicians. This article reviews the importance of MRSA as a pathogen, MRSA colonization and various MRSA decolonization strategies.

Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.

BACKGROUND: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. METHODS: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. FINDINGS: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. INTERPRETATION: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. FUNDING: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study.

BACKGROUND: Although adolescent girls are the main population for prophylactic human papillomavirus (HPV) vaccines, adult women who remain at risk of cervical cancer can also be vaccinated. We report data from the interim analysis of the ongoing VIVIANE study, the aim of which is to assess the efficacy, safety, and immunogenicity of the HPV 16/18 AS04-adjuvanted vaccine in adult women. METHODS: In this phase 3, multinational, double-blind, randomised controlled trial, we randomly assigned healthy women older than 25 years to the HPV 16/18 vaccine or control (1:1), via an internet-based system with an algorithm process that accounted for region, age stratum, baseline HPV DNA status, HPV 16/18 serostatus, and cytology. Enrolment was age-stratified, with about 45% of participants in each of the 26-35 and 36-45 years age strata and 10% in the 46 years and older stratum. Up to 15% of women in each age stratum could have a history of HPV infection or disease. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or higher (CIN1+) associated with HPV 16/18. The primary analysis was done in the according-to-protocol cohort for efficacy, which consists of women who received all three vaccine or control doses, had negative or low-grade cytology at baseline, and had no history of HPV disease. Secondary analyses included vaccine efficacy against non-vaccine oncogenic HPV types. Mean follow-up time was 40·3 months. This study is registered with ClinicalTrials.gov, number NCT00294047. FINDINGS: The first participant was enrolled on Feb 16, 2006, and the last study visit for the present analysis took place on Dec 10, 2010; 5752 women were included in the total vaccinated cohort (n=2881 vaccine, n=2871 control), and 4505 in the according-to-protocol cohort for efficacy (n=2264 vaccine, n=2241 control). Vaccine efficacy against HPV 16/18-related 6-month persistent infection or CIN1+ was significant in all age groups combined (81·1%, 97·7% CI 52·1-94·0), in the 26-35 years age group (83·5%, 45·0-96·8), and in the 36-45 years age group (77·2%, 2·8-96·9); no cases were seen in women aged 46 years and older. Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. We also noted significant cross-protective vaccine efficacy against 6-month persistent infection with HPV 31 (79·1%, 97·7% CI 27·6-95·9) and HPV 45 (76·9%, 18·5-95·6]) Serious adverse events occurred in 285 (10%) of 2881 women in the vaccine group and 267 (9%) of 2871 in the control group; five (<1%) and eight (<1%) of these events, respectively, were believed to be related to vaccination. INTERPRETATION: In women older than 25 years, the HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45. FUNDING: GlaxoSmithKline Biologicals SA.

Respiratory pathogen testing.

Respiratory tract infections (RTIs) are common in the pediatric population and contribute to a large portion of health care expenditure. A variety of modalities currently exist for testing for these pathogens in patients and as technology advances new, more efficient and specific tests are becoming available. This article reviews the most common causes of respiratory tract infections and the available testing modalities.

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate: a phase III randomized controlled trial in children.

BACKGROUND: Mismatch between circulating influenza B viruses (Yamagata and Victoria lineages) and vaccine strains occurs frequently. METHODS: In a randomized controlled trial, immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate (QIV) versus trivalent inactivated influenza vaccine (TIV)-Victoria(Vic) and TIV-Yamagata(Yam) in children 3-17 years of age was evaluated. In an open-label study arm, QIV only was assessed in children 6-35 months of age. RESULTS: A total of 3094 children (932 QIV, 929 TIV-Vic, 932 TIV-Yam, and 301 QIV only) were vaccinated. QIV was noninferior to the TIVs for shared strains (A/H3N2 and A/H1N1) based on hemagglutination-inhibition (HI) antibodies 28 days after last vaccination, and superior for the unique B strains Victoria and Yamagata (geometric mean titer ratios 2.61, 3.78; seroconversion rate differences 33.96%, 44.63%). Among children in the randomized trial, adverse event rates were similar except for injection site pain (dose 1: 65.4% QIV, 54.6% TIV-Vic, 55.7% TIV-Yam). CONCLUSION: QIV elicited superior HI responses to the added B strains compared to TIV controls, potentially improving its effectiveness against influenza B. HI responses were similar between QIV and TIV controls for the shared strains. QIV had an acceptable safety profile relative to TIVs. CLINICAL TRIALS REGISTRATION: NCT01198756.

Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation.

BACKGROUND: Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. METHODS: Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. RESULTS: In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. CONCLUSIONS: The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.

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.

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.