Prioritization of Randomized Clinical Trial Questions for Children Hospitalized With Common Conditions: A Consensus Statement.

Importance: There is a lack of randomized clinical trial (RCT) data to guide many routine decisions in the care of children hospitalized for common conditions. A first step in addressing the shortage of RCTs for this population is to identify the most pressing RCT questions for children hospitalized with common conditions. Objective: To identify the most important and feasible RCT questions for children hospitalized with common conditions. Design, Setting, and Participants: For this consensus statement, a 3-stage modified Delphi process was used in a virtual conference series spanning January 1 to September 29, 2022. Forty-six individuals from 30 different institutions participated in the process. Stage 1 involved construction of RCT questions for the 10 most common pediatric conditions leading to hospitalization. Participants used condition-specific guidelines and reviews from a structured literature search to inform their development of RCT questions. During stage 2, RCT questions were refined and scored according to importance. Stage 3 incorporated public comment and feasibility with the prioritization of RCT questions. Main Outcomes and Measures: The main outcome was RCT questions framed in a PICO (population, intervention, control, and outcome) format and ranked according to importance and feasibility; score choices ranged from 1 to 9, with higher scores indicating greater importance and feasibility. Results: Forty-six individuals (38 who shared demographic data; 24 women [63%]) from 30 different institutions participated in our modified Delphi process. Participants included children's hospital (n = 14) and community hospital (n = 13) pediatricians, parents of hospitalized children (n = 4), other clinicians (n = 2), biostatisticians (n = 2), and other researchers (n = 11). The process yielded 62 unique RCT questions, most of which are pragmatic, comparing interventions in widespread use for which definitive effectiveness data are lacking. Overall scores for importance and feasibility of the RCT questions ranged from 1 to 9, with a median of 5 (IQR, 4-7). Six of the top 10 selected questions focused on determining optimal antibiotic regimens for 3 common infections (pneumonia, urinary tract infection, and cellulitis). Conclusions and Relevance: This consensus statementhas identified the most important and feasible RCT questions for children hospitalized with common conditions. This list of RCT questions can guide investigators and funders in conducting impactful trials to improve care and outcomes for hospitalized children.

Community Pediatric Hospitalist Workload: Results from a National Survey.

As a newly recognized subspecialty, understanding programmatic models for pediatric hospital medicine (PHM) programs is vital to lay the groundwork for a sustainable field. Although variability has been described within university-based PHM programs, there remains no national benchmark for community-based PHM programs. In this report, we describe the workload, clinical services, employment, and perception of sustainability of 70 community-based PHM programs in 29 states through a survey of community site leaders. The median hours for a full-time hospitalist was 1,882 hours/year with those employed by community hospitals working 8% more hours/year and viewing appropriate morning pediatric census as 20% higher than those employed by university institutions. Forty-three out of 70 (63%) site leaders perceived their programs as sustainable, with no significant difference by employer structure. Future studies should further explore root causes for workload discrepancies between community and academic employed programs along with establishing potential standards for PHM program development.

Development of performance tracking for a pediatric hospitalist division.

OBJECTIVES: Our goal was to develop a comprehensive performance tracking process for a large pediatric hospitalist division. We aimed to use established dimensions and theory of health care quality to identify measures relevant to common inpatient diagnoses, reflective of current standards of clinical care, and applicable to individual physician performance. We also sought to implement a reproducible data collection strategy that minimizes manual data collection and measurement bias. METHODS: Washington University Division of Pediatric Hospital Medicine provides clinical care in 17 units within 3 different hospitals. Hospitalist services were grouped into 5 areas, and a task group was created of divisional leaders representing clinical services. The group was educated on the health care quality theory and tasked to search clinical practice standards and quality resources. The groups proposed a broad spectrum of performance questions that were screened for electronic data availability and modified into measurable formulas. RESULTS: Eighty-seven performance questions were identified and analyzed for their alignment with known clinical guidelines and value in measuring performance. Questions were distributed across quality domains, with most addressing safety. They reflected structure, outcome, and, most commonly, process. Forty-seven questions were disease specific, and 79 questions reflected individual physician performance; 52 questions had electronically available data. CONCLUSIONS: We describe a systematic approach to the development of performance indicators for a pediatric hospitalist division that can be used to measure performance on a division and physician level. We outline steps to develop a broad-spectrum quality tracking process to standardize clinical care and build invaluable resources for quality improvement research.

Survey of academic pediatric hospitalist programs in the US: organizational, administrative, and financial factors.

BACKGROUND: Many pediatric academic centers have hospital medicine programs. Anecdotal data suggest that variability exists in program structure. OBJECTIVE: To provide a description of the organizational, administrative, and financial structures of academic pediatric hospital medicine (PHM). METHODS: This online survey focused on the organizational, administrative, and financial aspects of academic PHM programs, which were defined as hospitalist programs at US institutions associated with accredited pediatric residency program (n = 246) and identified using the Accreditation Council for Graduate Medical Education (ACGME) Fellowship and Residency Electronic Interactive Database. PHM directors and/or residency directors were targeted by both mail and the American Academy of Pediatrics Section on Hospital Medicine LISTSERV. RESULTS: The overall response rate was 48.8% (120/246). 81.7% (98/120) of hospitals reported having an academic PHM program, and 9.1% (2/22) of hospitals without a program reported plans to start a program in the next 3 years. Over a quarter of programs provide coverage at multiple sites. Variability was identified in many program factors, including hospitalist workload and in-house coverage provided. Respondents reported planning increased in-house hospitalist coverage coinciding with the 2011 ACGME work-hour restrictions. Few programs reported having revenues greater than expenses (26% single site, 4% multiple site). CONCLUSIONS: PHM programs exist in the majority of academic centers, and there appears to be variability in many program factors. This study provides the most comprehensive data on academic PHM programs and can be used for benchmarking as well as program development.

Ascorbic acid is a requirement for the morphogenesis of the human filarial parasite Brugia malayi.

The nematode parasites Wuchereria bancrofti, Brugia malayi, and B. timori cause a disease in humans known as lymphatic filariasis, which afflicts approximately 120 million people worldwide. The parasites enter the human host from the mosquito either as L3 or as infective larvae and subsequently differentiate through 2 molts. In this article, we show that B. malayi depends on an exogenous source of vitamin C to complete the L3 to L4 molt, a critical morphogenic step in its life cycle. Brugia malayi apparently belongs to a small group of living organisms that depend on an exogenous source of vitamin C. This group includes only primates (including man) and guinea pigs among mammals.

Primed peritoneal B lymphocytes are sufficient to transfer protection against Brugia pahangi infection in mice.

Lymphatic filariasis is a tropical disease caused by the nematode parasites Wuchereria bancrofti and Brugia malayi. Whereas the protective potential of T lymphocytes in filarial infection is well documented, investigation of the role of B lymphocytes in antifilarial immunity has been neglected. In this communication, we examine the role of B lymphocytes in antifilarial immunity, using Brugia pahangi infections in the murine peritoneal cavity as a model. We find that B lymphocytes are required for clearance of primary and challenge infections with B. pahangi third-stage larvae (L3). We assessed the protective potential of peritoneal B lymphocytes by adoptive transfer experiments. Primed but not naïve peritoneal B cells from wild-type mice that had been immunized with B. pahangi L3 protected athymic recipients from challenge infection. We evaluated possible mechanisms by which B cells mediate protection. Comparisons of cytokine mRNA expression between B-lymphocyte-deficient and immunocompetent mice following B. pahangi infection suggest that B cells are required for the early production of Th2-type cytokines by peritoneal cells. In addition, B-cell-deficient mice demonstrate a defect in inflammatory cell recruitment to the peritoneal cavity following B. pahangi infection. The data demonstrate a critical role of B lymphocytes in antifilarial immunity in naïve mice and in the memory response in primed mice.

Cellular immunity, but not gamma interferon, is essential for resolution of Babesia microti infection in BALB/c mice.

A new strain of Babesia microti (KR-1) was isolated from a Connecticut resident with babesiosis by hamster inoculation and adapted to C3H/HeJ and BALB/c mice. To examine the relative importance of humoral and cellular immunity for the control of B. microti infection, we compared the course of disease in wild-type BALB/c mice with that in BALB/c SCID mice, JHD-null (B-cell-deficient) mice, and T-cell receptor alphabeta (TCRbeta(-/-)) or gamma interferon (IFN-gamma) (IFN-gamma(-/-)) knockout mice following inoculation with the KR-1-strain. SCID mice and TCRalphabeta knockouts sustained a severe but nonlethal parasitemia averaging 35 to 45% infected erythrocytes. IFN-gamma-deficient mice developed a less severe parasitemia but were able to clear the infection. In contrast, in six of eight JHD-null mice, the levels of parasitemia were indistinguishable from those in the wild-type animals. These data indicate that cellular immunity is critical for the clearance of B. microti in BALB/c mice but that disease resolution can occur even in the absence of IFN-gamma.

Brugian infections in the peritoneal cavities of laboratory mice: kinetics of infection and cellular responses.

Standard, immunocompetent, inbred strains of mice are non-permissive for infection with the human filarial nematode, Brugia malayi or the closely related Brugia pahangi. This non-permissiveness allows one to address the mechanism(s) that might be used by mammalian hosts to eliminate large, multicellular, metazoan, extracellular invertebrate pathogens. We describe here the time course of intraperitoneal Brugian infections in naïve and primed +/+ mice from two commonly used, inbred laboratory strains (C57BL/6J and BALB/cByJ). We believe that this documentation of the course of infection in normal mice will serve as a reference for future studies using mice with gene-targeted immunological deficits or which have been pharmacologically or immunologically manipulated to manifest such deficits. Our data show that even though both strains of mice eliminate the parasite before the onset of patency, there are significant differences in the time course of infection and in the fractions of input larvae that can be recovered at any time after infection. In a secondary infection, the time course of elimination is accelerated. We examined the cells in the peritoneal cavity, the site of infection, by flow microfluorimetry using forward and side scatter properties and cell surface antigen expression using fluorescent antibodies. These studies reveal a complex cellular pattern, predominated by B lymphocytes, macrophages, and eosinophils. The most notable gross morphological findings at necropsy during the phase of elimination of the parasite are nodules of tissue containing larvae, which appear viable in some cases and undergoing various stages of disintegration in others. These nodules, which are histologically granulomas, are primarily composed of macrophages and eosinophils, with few if any lymphocytes. Transmission electron micrographs reveal that eosinophils can penetrate under the cuticles of the larvae and be seen in close approximation with internal structures. These granulomas may represent an important mechanism by which worms are eliminated.