Effect of Haemophilus influenzae Type b and 13-Valent Pneumococcal Conjugate Vaccines on Childhood Pneumonia Hospitalizations and Deaths in Botswana.

BACKGROUND: Globally, pneumonia is the leading cause of death among children. Few data exist regarding the effect of Haemophilus influenzae type b (Hib) vaccine and 13-valent pneumococcal conjugate vaccine (PCV-13) on the burden of childhood pneumonia in African settings. METHODS: We collected data on children aged 1 to 59 months at 3 hospitals in Botswana. Hib vaccine and PCV-13 were introduced in Botswana in November 2010 and July 2012, respectively. We compared pneumonia hospitalizations and deaths prevaccine (January 2009 to October 2010) with postvaccine (January 2013 to December 2017) using seasonally adjusted, interrupted time-series analyses. RESULTS: We identified 6943 pneumonia hospitalizations and 201 pneumonia deaths. In the prevaccine period, pneumonia hospitalizations and deaths increased by 24% (rate, 1.24; 95% CI, .94-1.64) and 59% (rate, 1.59; 95% CI, .87-2.90) per year, respectively. Vaccine introduction was associated with a 48% (95% CI, 29-62%) decrease in the number of pneumonia hospitalizations and a 50% (95% CI, 1-75%) decrease in the number of pneumonia deaths between the end of the prevaccine period (October 2010) and the beginning of the postvaccine period (January 2013). During the postvaccine period, pneumonia hospitalizations and deaths declined by 6% (rate, .94; 95% CI, .89-.99) and 22% (rate, .78; 95% CI, .67-.92) per year, respectively. CONCLUSIONS: Pneumonia hospitalizations and deaths among children declined sharply following introduction of Hib vaccine and PCV-13 in Botswana. This effect was sustained for more than 5 years after vaccine introduction, supporting the long-term effectiveness of these vaccines in preventing childhood pneumonia in Botswana.

Pediatric provider perspectives and practices regarding health policy discussions with families: a mixed methods study.

BACKGROUND: Advocacy regarding child health policy is a core tenet of pediatrics. Previous research has demonstrated that most pediatric providers believe collective advocacy and political involvement are essential aspects of their profession, but less is known about how pediatric providers engage with families about policy issues that impact child health. The objectives of this study were to examine providers' perceptions and practices with regards to discussing health policy issues with families and to identify provider characteristics associated with having these discussions. METHODS: In this cross-sectional mixed methods study, pediatric resident physicians, attending physcians, and nurse practitioners at primary care clinics within a large academic health system were surveyed to assess (1) perceived importance of, (2) frequency of, and (3) barriers to and facilitators of health policy discussions with families. Multivariable ordinal regression was used to determine provider characteristics (including demographics, practice location, and extent of civic engagement) associated with frequency of these discussions. A subset of providers participated in subsequent focus groups designed to help interpret quantitative findings. RESULTS: The overall survey response rate was 155/394 (39%). The majority of respondents (76%) felt pediatricians should talk to families about health policy issues affecting children, but most providers (69%) reported never or rarely having these discussions. Factors associated with discussing policy issues included being an attending physician/nurse practitioner (OR 8.22, 95% CI 2.04-33.1) and urban practice setting (OR 3.85, 95% CI 1.03-14.3). Barriers included feeling uninformed about relevant issues and time constraints. In provider focus groups, four key themes emerged: (1) providers felt discussing policy issues would help inform and empower families; (2) providers frequently discussed social service programs, but rarely discussed policies governing these programs; (3) time constraints and concerns about partisan bias were a barrier to conversations; and (4) use of support staff and handouts with information about policy changes could help facilitate more frequent conversations. CONCLUSIONS: Pediatric providers felt it was important to talk to families about child health policy issues, but few providers reported having such conversations in practice. Primary care practices should consider incorporating workflow changes that promote family engagement in relevant health policy discussions.

Pediatric Intersession: An Upfront Flipped-Classroom Curriculum to Promote Pediatric Clerkship Readiness.

OBJECTIVES: Best practices for content selection, mode of delivery, and timing of pediatric clerkship readiness curricula for medical students have, by and large, not been established. Capitalizing on changes in structure of the clinical clerkships during the COVID-19 pandemic, we created an upfront clerkship readiness curriculum, termed Pediatric Intersession (PI), to replace the existing weekly lecture-based clerkship didactics. METHODS: Our goal was to develop an interactive curriculum with innovative instructional design methodology intended to promote broad foundational pediatric knowledge and clerkship preparedness using case-based learning. We first conducted a needs assessment and crafted curriculum content using guiding principles from the 2019 Council on Medical Student Education in Pediatrics (COMSEP) curriculum. We then organized material into four daily modules prior to the start of the clerkship and employed flipped classroom (FC) methodology. RESULTS: Sixty-six percent of students completed course evaluations, and >90% of the 100 respondents reported that the PI enhanced their clinical learning. Pre-/post-testing demonstrated some knowledge gain following the small-group sessions and there was no change on the National Board of Medical Examiners (NBME) Subject Exam mean scores compared to prior cohorts of students. CONCLUSIONS: The global pandemic provided an opportunity to re-envision our pediatric clerkship didactics content, while also incorporating instructional design methodology preferred by students. Our curriculum promotes a small group-based, interactive approach to clerkship readiness that fosters learning in the clinical environment that can be adapted for various settings. Our evaluation suggests that the transition to a FC readiness curriculum can be done successfully while effectively preparing students for their pediatric clerkship.

Factors Associated With Inpatient Subspecialty Consultation Patterns Among Pediatric Hospitalists.

Importance: Subspecialty consultation is a frequent, consequential practice in the pediatric inpatient setting. Little is known about factors affecting consultation practices. Objectives: To identify patient, physician, admission, and systems characteristics that are independently associated with subspecialty consultation among pediatric hospitalists at the patient-day level and to describe variation in consultation utilization among pediatric hospitalist physicians. Design, Setting, and Participants: This retrospective cohort study of hospitalized children used electronic health record data from October 1, 2015, through December 31, 2020, combined with a cross-sectional physician survey completed between March 3 and April 11, 2021. The study was conducted at a freestanding quaternary children's hospital. Physician survey participants were active pediatric hospitalists. The patient cohort included children hospitalized with 1 of 15 common conditions, excluding patients with complex chronic conditions, intensive care unit stay, or 30-day readmission for the same condition. Data were analyzed from June 2021 to January 2023. Exposures: Patient (sex, age, race and ethnicity), admission (condition, insurance, year), physician (experience, anxiety due to uncertainty, gender), and systems (hospitalization day, day of week, inpatient team, and prior consultation) characteristics. Main Outcomes and Measures: The primary outcome was receipt of inpatient consultation on each patient-day. Risk-adjusted consultation rates, expressed as number of patient-days consulting per 100, were compared between physicians. Results: We evaluated 15 922 patient-days attributed to 92 surveyed physicians (68 [74%] women; 74 [80%] with ≥3 years' attending experience) caring for 7283 unique patients (3955 [54%] male patients; 3450 [47%] non-Hispanic Black and 2174 [30%] non-Hispanic White patients; median [IQR] age, 2.5 ([0.9-6.5] years). Odds of consultation were higher among patients with private insurance compared with those with Medicaid (adjusted odds ratio [aOR], 1.19 [95% CI, 1.01-1.42]; P = .04) and physicians with 0 to 2 years of experience vs those with 3 to 10 years of experience (aOR, 1.42 [95% CI, 1.08-1.88]; P = .01). Hospitalist anxiety due to uncertainty was not associated with consultation. Among patient-days with at least 1 consultation, non-Hispanic White race and ethnicity was associated with higher odds of multiple consultations vs non-Hispanic Black race and ethnicity (aOR, 2.23 [95% CI, 1.20-4.13]; P = .01). Risk-adjusted physician consultation rates were 2.1 times higher in the top quartile of consultation use (mean [SD], 9.8 [2.0] patient-days consulting per 100) compared with the bottom quartile (mean [SD], 4.7 [0.8] patient-days consulting per 100; P < .001). Conclusions and Relevance: In this cohort study, consultation use varied widely and was associated with patient, physician, and systems factors. These findings offer specific targets for improving value and equity in pediatric inpatient consultation.

Opportunities for Diagnostic Improvement Among Pediatric Hospital Readmissions.

OBJECTIVES: Diagnostic errors, termed "missed opportunities for improving diagnosis" (MOIDs), are known sources of harm in children but have not been well characterized in pediatric hospital medicine. Our objectives were to systematically identify and describe MOIDs among general pediatric patients who experienced hospital readmission, outline improvement opportunities, and explore factors associated with increased risk of MOID. PATIENTS AND METHODS: Our retrospective cohort study included unplanned readmissions within 15 days of discharge from a freestanding children's hospital (October 2018-September 2020). Health records from index admissions and readmissions were independently reviewed and discussed by practicing inpatient physicians to identify MOIDs using an established instrument, SaferDx. MOIDs were evaluated using a diagnostic-specific tool to identify improvement opportunities within the diagnostic process. RESULTS: MOIDs were identified in 22 (6.3%) of 348 readmissions. Opportunities for improvement included: delay in considering the correct diagnosis (n = 11, 50%) and failure to order needed test(s) (n = 10, 45%). Patients with MOIDs were older (median age: 3.8 [interquartile range 1.5-11.2] vs 1.0 [0.3-4.9] years) than patients without MOIDs but similar in sex, primary language, race, ethnicity, and insurance type. We did not identify conditions associated with higher risk of MOID. Lower respiratory tract infections accounted for 26% of admission diagnoses but only 1 (4.5%) case of MOID. CONCLUSIONS: Standardized review of pediatric readmissions identified MOIDs and opportunities for improvement within the diagnostic process, particularly in clinician decision-making. We identified conditions with low incidence of MOID. Further work is needed to better understand pediatric populations at highest risk for MOID.

Opportunities to improve diagnosis in emergency transfers to the pediatric intensive care unit.

BACKGROUND: Late recognition of in-hospital deterioration is a source of preventable harm. Emergency transfers (ET), when hospitalized patients require intensive care unit (ICU) interventions within 1 h of ICU transfer, are a proximal measure of late recognition associated with increased mortality and length of stay (LOS). OBJECTIVE: To apply diagnostic process improvement frameworks to identify missed opportunities for improvement in diagnosis (MOID) in ETs and evaluate their association with outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: A single-center retrospective cohort study of ETs, January 2015 to June 2019. ET criteria include intubation, vasopressor initiation, or ≥ $\ge \phantom{\rule{}{0ex}}$ 60 mL/kg fluid resuscitation 1 h before to 1 h after ICU transfer. The primary exposure was the presence of MOID, determined using SaferDx. Cases were screened by an ICU and non-ICU physician. Final determinations were made by an interdisciplinary group. Diagnostic process improvement opportunities were identified. MAIN OUTCOME AND MEASURES: Primary outcomes were in-hospital mortality and posttransfer LOS, analyzed by multivariable regression adjusting for age, service, deterioration category, and pretransfer LOS. RESULTS: MOID was identified in 37 of 129 ETs (29%, 95% confidence interval [CI] 21%-37%). Cases with MOID differed in originating service, but not demographically. Recognizing the urgency of an identified condition was the most common diagnostic process opportunity. ET cases with MOID had higher odds of mortality (odds ratio 5.5; 95% CI 1.5-20.6; p = .01) and longer posttransfer LOS (rate ratio 1.7; 95% CI 1.1-2.6; p = .02). CONCLUSION: MOID are common in ETs and are associated with increased mortality risk and posttransfer LOS. Diagnostic improvement strategies should be leveraged to support earlier recognition of clinical deterioration.

The delivery of essential newborn care in conflict settings: A systematic review.

Introduction: Although progress has been made over the past 30 years to decrease neonatal mortality rates, reductions have been uneven. Globally, the highest neonatal mortality rates are concentrated in countries chronically affected by conflict. Essential newborn care (ENC), which comprises critical therapeutic interventions for every newborn, such as thermal care, initiation of breathing, feeding support, and infection prevention, is an important strategy to decrease neonatal mortality in humanitarian settings. We sought to understand the barriers to and facilitators of ENC delivery in conflict settings. Methods: We systematically searched Ovid/MEDLINE, Embase, CINAHL, and Cochrane databases using terms related to conflict, newborns, and health care delivery. We also reviewed grey literature from the Healthy Newborn Network and several international non-governmental organization databases. We included original research on conflict-affected populations that primarily focused on ENC delivery. Study characteristics were extracted and descriptively analyzed, and quality assessments were performed. Results: A total of 1,533 abstracts were screened, and ten publications met the criteria for final full-text review. Several barriers emerged from the reviewed studies and were subdivided by barrier level: patient, staff, facility, and humanitarian setting. Patients faced obstacles related to transportation, cost, and access, and mothers had poor knowledge of newborn danger signs. There were difficulties related to training and retaining staff. Facilities lacked supplies, protocols, and data collection strategies. Conclusions: Strategies for improved ENC implementation include maternal and provider education and increasing facility readiness through upgrades in infrastructure, guidelines, and health information systems. Community-based approaches may also play a vital role in strengthening ENC.

Diagnostic Reasoning of Resident Physicians in the Age of Clinical Pathways.

Background: Development of skills in diagnostic reasoning is paramount to the transition from novice to expert clinicians. Efforts to standardize approaches to diagnosis and treatment using clinical pathways are increasingly common. The effects of implementing pathways into systems of care during diagnostic education and practice among pediatric residents are not well described. Objective: To characterize pediatric residents' perceptions of the tradeoffs between clinical pathway use and diagnostic reasoning. Methods: We conducted a qualitative study from May to December 2019. Senior pediatric residents from a high-volume general pediatric inpatient service at an academic hospital participated in semi-structured interviews. We utilized a basic interpretive qualitative approach informed by a dual process diagnostic reasoning framework. Results: Nine residents recruited via email were interviewed. Residents reported using pathways when admitting patients and during teaching rounds. All residents described using pathways primarily as management tools for patients with a predetermined diagnosis, rather than as aids in formulating a diagnosis. As such, pathways primed residents to circumvent crucial steps of deliberate diagnostic reasoning. However, residents relied on bedside assessment to identify when patients are "not quite fitting the mold" of the current pathway diagnosis, facilitating recalibration of the diagnostic process. Conclusions: This study identifies important educational implications at the intersection of residents' cognitive diagnostic processes and use of clinical pathways. We highlight potential challenges clinical pathways pose for skill development in diagnostic reasoning by pediatric residents. We suggest opportunities for educators to leverage clinical pathways as a framework for development of these skills.

Risk factors for mortality in a hospitalised neonatal cohort in Botswana.

OBJECTIVES: A disproportionate number of neonatal deaths occur in low/middle-income countries, with sepsis a leading contributor of mortality. In this study, we investigate risk factors for mortality in a cohort of high-risk hospitalised neonates in Botswana. Independent predictors for mortality for infants experiencing either a sepsis or a non-sepsis-related death are described. METHODS: This is a prospective observational cohort study with infants enrolled from July to October 2018 at the neonatal unit (NNU) of Princess Marina Hospital (PMH) in Gaborone, Botswana. Data on demographic, clinical and unit-specific variables were obtained. Neonates were followed to death or discharge, including transfer to another hospital. Death was determined to be infectious versus non-infectious based on primary diagnosis listed on day of death by lead clinician on duty. RESULTS: Our full cohort consisted of 229 patients. The overall death rate was 227 per 1000 live births, with cumulative proportion of deaths of 22.7% (n=47). Univariate analysis revealed that sepsis, extremely low birth weight (ELBW) status, hypoxic ischaemic encephalopathy, critical illness and infants born at home were associated with an increased risk of all-cause mortality. Our multivariate model revealed that critical illness (HR 3.07, 95% CI 1.56 to 6.03) and being born at home (HR 4.82, 95% CI 1.76 to 13.19) were independently associated with all-cause mortality. Low birth weight status was independently associated with a decreased risk of mortality (HR 0.24, 95% CI 0.11 to 0.53). There was a high burden of infection in the cohort with more than half of infants (140, 61.14%) diagnosed with sepsis at least once during their NNU admission. Approximately 20% (n=25) of infants with sepsis died before discharge. Our univariate subanalysis of the sepsis cohort revealed that ELBW and critical illness were associated with an increased risk of death. These findings persisted in the multivariate model with HR 3.60 (95% CI 1.11 to 11.71) and HR 2.39 (95% CI 1 to 5.77), respectively. CONCLUSIONS: High rates of neonatal mortality were noted. Urgent interventions are needed to improve survival rates at PMH NNU and to prioritise care for critically ill infants at time of NNU admission, particularly those born at home and/or of ELBW.

Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

Impact of patient race/ethnicity on emergency department management of pediatric gastroenteritis in the setting of a clinical pathway.

BACKGROUND: Acute gastroenteritis (AGE) is a common pediatric diagnosis in emergency medicine, accounting for 1.7 million visits annually. Little is known about racial/ethnic differences in care in the setting of standardized care models. METHODS: We used quality improvement data for children 6 months to 18 years presenting to a large, urban pediatric emergency department (ED) treated via a clinical pathway for AGE/dehydration between 2011 and 2018. Race/ethnicity was evaluated as a single variable (non-Hispanic [NH]-White, NH-Black, Hispanic, and NH-other) related to ondansetron and intravenous fluid (IVF) administration, ED length of stay (LOS), hospital admission, and ED revisits using multivariable regression. RESULTS: Of 30,849 ED visits for AGE/dehydration, 18.0% were NH-White, 57.2% NH-Black, 12.5% Hispanic, and 12.3% NH-other. Multivariable mixed-effects generalized linear regression controlling for age, sex, triage acuity, payer, and language revealed that, compared to NH-White patients, NH-other patients were more likely to receive ondansetron (adjusted odds ratio [95% CI] = 1.30 [1.17 to 1.43]). NH-Black, Hispanic, and NH-other patients were significantly less likely to receive IVF (0.59 [0.53 to 0.65]; 0.74 [0.64 to 0.84]; 0.74 [0.65 to 0.85]) or be admitted to the hospital (0.54 [0.45 to 0.64]; 0.62 [0.49 to 0.78]; 0.76 [0.61 to 0.94]), respectively. NH-Black and Hispanic patients had shorter LOS (median = 245 minutes for NH-White, 176 NH-Black, 199 Hispanic, and 203 NH-other patients) without significant differences in ED revisits. CONCLUSIONS: Despite the presence of a clinical pathway to guide care, NH-Black, Hispanic, and NH-other children presenting to the ED with AGE/dehydration were less likely to receive IVF or hospital admission and had shorter LOS compared to NH-White counterparts. There was no difference in patient revisits, which suggests discretionary overtreatment of NH-White patients, even with clinical guidelines in place. Further research is needed to understand the drivers of differences in care to develop interventions promoting equity in pediatric emergency care.

Reproducible breath metabolite changes in children with SARS-CoV-2 infection.

SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid non-invasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compounds (VOCs) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2-infected and -uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2-infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.

Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection.

SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid noninvasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compound (VOC) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2 infected and uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2 infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.

Continuous Intragastric Dextrose: A Therapeutic Option for Refractory Hypoglycemia in Congenital Hyperinsulinism.

Feeding problems are frequent in infants with congenital hyperinsulinism (HI) and may be exacerbated by continuous enteral nutrition (EN) used to maintain euglycemia. Our center's HI team uses dextrose solution given continuously via gastric tube (intrasgastric dextrose, IGD) for infants not fully responsive to conventional medical therapy or pancreatectomy. Here, we describe our practice as well as growth, feeding, and adverse events in infants with HI exposed to IGD. METHODS: This was a retrospective cohort of infants with HI treated with IGD from 2009-2017. Primary outcomes were weight-for-length and body mass index Z-scores (WFL-Z and BMI-Z) in the year following IGD initiation. Secondary outcomes included EN use and adverse events. We used multivariable regression to assess covariates of interest. RESULTS: We studied 32 subjects (13 female) with a median age at IGD initiation of 73 days (range 17-367); median follow-up was 11.2 months (range 5.0-14.2). WFL-Z did not change significantly over time (p > 0.05). EN use decreased significantly over time, i.e., at 0 months: 72% (95% CI 53-85) vs. at 12 months 39% (95% CI 22-59). No potential adverse events led to discontinuation of IGD. CONCLUSIONS: Over a median follow-up of nearly 1 year, IGD was well-tolerated, with no change in WFL-Z or BMI-Z from baseline.