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BACKGROUND AND OBJECTIVES: Reutilization following discharge is costly to families and the healthcare system. Singular measures of the social determinants of health (SDOH) have been shown to impact utilization, however the SDOH are multifactorial. The Childhood Opportunity Index (COI) is a validated approach for comprehensive estimation of the SDOH. Using the COI, we aimed to describe the association between SDOH and 30-day revisit rates. METHODS: This retrospective study included children 0–17 years within 48 children’s hospitals using the Pediatric Health Information System from 1/1/2019 – 12/31/2019. The main exposure was a child’s ZIP code level COI. The primary outcome was unplanned readmissions and ED revisits within 30 days of discharge. Primary outcomes were summarized by COI category and compared using chi-square or Kruskal-Wallis tests. Adjusted analysis used generalized linear mixed effects models with adjustments for demographics, clinical characteristics, and hospital clustering. RESULTS: Of 728,997 hospitalizations meeting inclusion criteria, 30-day unplanned returns occurred for 96,007 children (13.2%). After adjustment, the patterns of returns were significantly associated with COI. For example, 30-day returns occurred for 19.1% (95% CI: 18.2, 20.0) of children living within very low opportunity areas, with a gradient-like decrease as opportunity increased (15.5%, 95% CI: 14.5, 16.5 for very high). The relative decrease in utilization as COI increased was more pronounced for ED revisits. CONCLUSIONS: Children living in low opportunity areas had greater 30-day readmissions and ED revisits. Our results suggest that a broader approach, including policy and system-level change, is needed to effectively reduce readmissions and ED revisits.

Using National Immunization Survey Child and Teen (2008-2017), we associated state vaccination requirements with hepatitis A (Hep A) vaccination rates in children and adolescents. States with school entry or both childcare and school entry requirements were associated with 35%-40% higher Hep A vaccination rates, compared with states without such requirements.

Background: Older adults are at risk of pneumococcal disease and associated morbidity and mortality. This phase 3 study (V114-020) assessed lot-to-lot consistency across safety and immunogenicity outcomes for V114, a 15-valent pneumococcal conjugate vaccine (PCV), in healthy adults aged ≥ 50 years. Methods: Adults were randomized in a 3:3:3:1 ratio to receive a single dose of one of three lots of V114 or 13-valent PCV (PCV13), stratified by age (50–64 years, 65–74 years, and ≥ 75 years). Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated at baseline (Day 1) and 30 days post-vaccination. Non-serious and serious adverse events (AEs) were evaluated post-vaccination through 14 days and Month 6, respectively. Results: Of 2340 participants enrolled, 2282 (97.5%) completed the study. Proportions of participants experiencing ≥ 1 AE were 81.0%, 77.4%, and 78.0% for V114 lots 1, 2, and 3, respectively. Comparison of V114 combined lots with PCV13 showed that proportions of participants experiencing AEs, solicited AEs, and serious AEs were comparable for both vaccines, with the exception of injection-site pain (more frequently reported with V114). OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) at 30 days post-vaccination were comparable across V114 lots, and all lots met predefined equivalence criteria for all 15 vaccine serotypes (lower and upper limits of the 95% confidence intervals of serotype-specific OPA GMT ratios for all possible pairwise comparisons across the three lots were within the equivalence margin of 0.5–2.0). Serotype-specific OPA GMTs and IgG GMCs were comparable in the V114 combined lots and PCV13 groups for the 13 shared serotypes and higher in the V114 group for serotypes unique to V114 (22F and 33F). Conclusions: V114 is well tolerated with a consistent safety profile and immune response across manufacturing lots. Clinical trials registration: NCT03950856 (www.clinicaltrials.gov); 2018-004266-33 (EudraCT).

OBJECTIVES To evaluate safety and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine [PCV] containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9 V, 14, 18C, 19A, 19F, 22F, 23F, and 33F), followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks later, in adults living with HIV. DESIGN In this phase 3 study (V114-018; NCT03480802), pneumococcal vaccine-naive adults with HIV (CD4+ count ≥50 cells/μl, plasma HIV RNA

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Ageing is characterized by a progressive loss of cellular function that leads to a decline in tissue homeostasis, increased vulnerability and adverse health outcomes. Important advances in ageing research have now identified a set of nine candidate hallmarks that are generally considered to contribute to the ageing process and that together determine the ageing phenotype, which is the clinical manifestation of age-related dysfunction in chronic diseases. Although most rheumatic diseases are not yet considered to be age related, available evidence increasingly emphasizes the prevalence of ageing hallmarks in these chronic diseases. On the basis of the current evidence relating to the molecular and cellular ageing pathways involved in rheumatic diseases, we propose that these diseases share a number of features that are observed in ageing, and that they can therefore be considered to be diseases of premature or accelerated ageing. Although more data are needed to clarify whether accelerated ageing drives the development of rheumatic diseases or whether it results from the chronic inflammatory environment, central components of age-related pathways are currently being targeted in clinical trials and may provide a new avenue of therapeutic intervention for patients with rheumatic diseases.

BACKGROUND: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease. METHODS: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks. The primary end points were the changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary end points included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT). RESULTS: Of the 357 enrolled participants, 100 were assigned to the control group, 55 to the 250-mg cinpanemab group, 102 to the 1250-mg group, and 100 to the 3500-mg group. The trial was stopped after the week 72 interim analysis owing to lack of efficacy. The change to week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, -0.3 points [95% confidence interval {CI}, -4.9 to 4.3], P = 0.90; 0.5 points [95% CI, -3.3 to 4.3], P = 0.80; and 0.1 point [95% CI, -3.8 to 4.0], P = 0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was -0.9 points (95% CI, -5.6 to 3.8) for the 250-mg dose, 0.6 points (95% CI, -3.3 to 4.4) for the 1250-mg dose, and -0.8 points (95% CI, -4.6 to 3.0) for the 3500-mg dose. Results for secondary end points were similar to those for the primary end points. DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis, and falls. CONCLUSIONS: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. (Funded by Biogen; SPARK ClinicalTrials.gov number, NCT03318523.).

Gamma irradiation (GI) is included in the CDC guidance on inactivation procedures to render a group of select agents and toxins nonviable. The Ebola virus falls within this group because it potentially poses a severe threat to public health and safety. To evaluate the impact of GI at a target dose of 50 kGy on neutralizing antibody titers induced by the rVSVΔG-ZEBOV-GP vaccine (V920), we constructed a panel of 48 paired human serum samples (GI-treated versus non–GI-treated) from healthy participants selected from a phase 3 study of V920 (study V920-012; NCT02503202). Neutralizing antibody titers were determined using a validated plaque-reduction neutralization test. GI of sera from V920 recipients was associated with approximately 20% reduction in postvaccination neutralizing antibody titers. GI was not associated with any change in pre-vaccination neutralizing antibody titers.

BACKGROUND Currently, non-surgical treatments for glenohumeral osteoarthritis (GH-OA) mainly aim to reduce pain. Autologous conditioned serum (ACS), Orthokine, an interleukin-1 inhibitor from the patient's own blood has an anti-inflammatory effect. The objective was to determine whether intra-articular injections of this ACS improved symptoms in patients with GH-OA and delayed the need for a shoulder replacement. METHODS A total of 36 consecutive patients, 40 shoulders, with OA received up to 6-weekly intra-articular injections of ACS were included. Imaging of GH-OA, range of motion, visual analogue scale (VAS) pain, Shoulder Pain And Disability Index (SPADI), American Shoulder and Elbow Surgeons and Constant scores were assessed pre-injection and post treatment at 3 months. At a minimum of 2 years, VAS and SPADI scores and whether anyone had progressed to a shoulder replacement were recorded. RESULTS Outcomes 3 months post-ACS injections demonstrated on average statistically significant improvement (P

Lower rates of diagnostic imaging have been observed among Black children compared with White children in pediatric emergency departments. Although the racial composition of the pediatric population served by each hospital differs, it is unclear whether this is associated with overall imaging rates at the hospital level, and in particular how it may be associated with the difference in imaging rates between Black and White children at a given hospital.To examine the association between the diversity of the pediatric population seen at each pediatric ED and variation in diagnostic imaging.Cross-sectional analysis of ED visits by patients younger than 18 years at 38 children's hospitals from January 1, 2016, through December 31, 2019, using data from the Pediatric Health Information System. Data were analyzed from April to September 2021.Proportion of patients from minoritized groups cared for at each hospital.The primary outcome was receipt of an imaging test defined as radiography, ultrasonography, computed tomography, or magnetic resonance imaging; adjusted odds ratios (aORs) were calculated to measure differences in imaging by race and ethnicity by hospital, and the correlation between the proportion of patients from minoritized groups cared for at each hospital and the aOR for receipt of diagnostic imaging by race and ethnicity was examined.There were 12 310 344 ED visits (3 477 674 [28.3%] among Hispanic patients; 3 212 915 [26.1%] among non-Hispanic Black patients; 4 415 747 [35.9%] among non-Hispanic White patients; 6 487 660 [52.7%] among female patients) by 5 883 664 pediatric patients (mean [SD] age, 5.84 [5.23] years) to the 38 hospitals during the study period, of which 3 527 866 visits (28.7%) involved at least 1 diagnostic imaging test. Diagnostic imaging was performed in 1 508 382 visits (34.2%) for non-Hispanic White children, 790 961 (24.6%) for non-Hispanic Black children, and 907 222 (26.1%) for Hispanic children (P .001). Non-Hispanic Black patients were consistently less likely to receive diagnostic imaging than non-Hispanic White patients at each hospital, and for all imaging modalities. There was a significant correlation between the proportion of patients from minoritized groups cared for at the hospital and greater imaging difference between non-Hispanic White and non-Hispanic Black patients (correlation coefficient, -0.37; 95% CI, -0.62 to -0.07; P = .02).In this cross-sectional study, hospitals with a higher percentage of pediatric patients from minoritized groups had larger differences in imaging between non-Hispanic Black and non-Hispanic White patients, with non-Hispanic White patients consistently more likely to receive diagnostic imaging. These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine.

Study objective Acute chest syndrome is a leading cause of mortality in patients with sickle cell disease (SCD). Because early detection of acute chest syndrome is directly tied to prognosis, young patients with SCD undergo countless chest radiography screenings throughout their lifetime for commonly occurring acute chest syndrome risk factors such as fever, chest pain, or cough. Chest radiography is not an ideal screening method because it is associated with radiation exposure, which accumulates with repeated imaging. Point-of-care lung ultrasonography is a nonradiating imaging modality that has been used to identify other lung pathology and may have a role in SCD. The goal of this study was to determine the accuracy of point-of-care lung ultrasound to identify an infiltrate suggestive of acute chest syndrome in patients with SCD compared to chest radiography as the gold standard. Methods This was a prospective observational study in 2 urban pediatric emergency departments to evaluate the accuracy of point-of-care lung ultrasonography in identifying patients with SCD who were aged 0 to 21 years and had an infiltrate suggestive of acute chest syndrome compared with chest radiography. Clinicians and trainees with point-of-care lung ultrasonographic training obtained informed consent and performed investigational point-of-care lung ultrasonography to evaluate for lung consolidation. A blinded point-of-care lung ultrasonographic expert reviewed results for quality assurance and agreement. Accuracy, sensitivity, specificity, likelihood ratios, and positive and negative predictive value were calculated for point-of-care lung ultrasonography test performance characteristics, with chest radiography as a reference standard. Results Point-of-care lung ultrasonography was performed on 191 SCD patients with a mean age of 8 years; 41% were female patients, and there was a 17% prevalence of acute chest syndrome. Accuracy of point-of-care lung ultrasonography to detected acute chest syndrome was 92%, sensitivity was 88%, and specificity was 93% compared with that for chest radiography. Conclusion Point-of-care lung ultrasonography is a feasible alternative to chest radiography for screening for acute chest syndrome in young patients with SCD. Further studies are needed to determine how this test performs within clinical practice.

Locked-up and unloaded firearm storage is a tenet of injury prevention campaigns to decrease children’s access to firearms. This study cohort describes the reported presence of, storage mechanisms for, and children’s perceived access to firearms. Parent-child dyads (n = 297) were recruited from pediatric emergency departments in Atlanta, GA. Gun owners were 25% of cohort; 53% reported storing some firearms insecurely. Gun owners were more likely to believe their child could access a firearm versus non–gun owners (11% vs 3%). Children of gun owners versus non-gun owners indicated increased ability to acquire a gun (14% vs 4%). Fifty-nine percent of children could not identify a real versus toy gun in a picture. This study highlights a plurality of parents storing firearms insecurely with a significant portion of children reporting gun access and demonstrating inability to recognize actual guns. This disconnect points to the importance of public health interventions to decrease access to firearms in this vulnerable population.

OBJECTIVES High-flow nasal cannula (HFNC) is an oxygen delivery device that provides heated humidified air with higher flow rates. The purpose of this survey is to look at institutional practice patterns of HFNC initiation, weaning, and disposition for pediatric patients across the United States. METHODS Survey was sent via electronic listservs to pediatric physicians in emergency medicine, hospital medicine, critical care, and urgent care. The questionnaire was divided into demographics and HFNC practices (initiation, management, and weaning). One response per institution was included in the analysis. RESULTS Two hundred twenty-four responses were included in the analysis, composed of 40% pediatric emergency medicine physicians, 46% pediatric hospitalists, 13% pediatric intensive care unit (PICU) physicians, and 1% pediatric urgent care physicians. Ninety-eight percent of the participants have HFNC at their institution. Thirty-seven percent of the respondents had a formal guideline for HFNC initiation. Nearly all guideline and nonguideline institutions report HFNC use in bronchiolitis. Guideline cohort is more likely to have exclusion criteria for HFNC (42% in the guideline cohort vs 17% in the nonguideline cohort; P < 0.001) and less frequently mandates PICU admissions once on HFNC (11% in the guideline cohort vs 56% in the nonguideline cohort; P < 0.001). Forty-six percent of guideline cohort had an objective scoring system to help determine the need for HFNC, and 73% had a weaning guideline. CONCLUSIONS Although there is general agreement to use HFNC in bronchiolitis, great practice variation remains in the initiation, management, and weaning of HFNC across the United States. There is also a discordance on PICU use when a patient is using HFNC.

The recombinant vesicular stomatitis virus - Zaire Ebola virus envelope glycoprotein (rVSVΔG-ZEBOV-GP) vaccine is a live recombinant vesicular stomatitis virus (VSV) where the VSV G protein is replaced with ZEBOV-GP. To better understand the immune response after receiving the rVSVΔG-ZEBOV-GP vaccine, the current analyses evaluated different definitions of seroresponse that differentiate vaccine and placebo recipients enrolled in a placebo-controlled clinical trial (PREVAIL; NCT02344407) in which a subset of the study participants had elevated baseline titers. Alternative values for serostatus cutoff (SSCO; 200-500 EU/mL) and/or fold rise (two- to five-fold) were applied to compare their ability to distinguish between participants receiving rVSVΔG-ZEBOV-GP or placebo. The results indicate that an SSCO of 200 EU/mL can be used to define seropositivity at baseline (i.e. pre-vaccination). The use of dual criteria of the same SSCO (200 EU/mL) together with a two-fold rise in antibody level from baseline provided the definition of seroresponse that maximized the statistical significance between vaccine recipients and placebo recipients post-vaccination. Clinical trial registration: NCT02344407.

The use of telehealth technology to connect with patients has expanded significantly over the past several years, particularly in response to the global coronavirus disease 2019 pandemic. This technical report describes the present state of telehealth and its current and potential applications. Telehealth has the potential to transform the way care is delivered to pediatric patients, expanding access to pediatric care across geographic distances, leveraging the pediatric workforce for care delivery, and improving disparities in access to care. However, implementation will require significant efforts to address the digital divide to ensure that telehealth does not inadvertently exacerbate inequities in care. The medical home model will continue to evolve to use telehealth to provide high-quality care for children, particularly for children and youth with special health care needs, in accordance with current and evolving quality standards. Research and metric development are critical for the development of evidence-based best practices and policies in these new models of care. Finally, as pediatric care transitions from traditional fee-for-service payment to alternative payment methods, telehealth offers unique opportunities to establish value-based population health models that are financed in a sustainable manner.

BackgroundChildren who experience a mild Traumatic Brain Injury (mTBI) may encounter cognitive and behavioral changes that often negatively impact school performance. Communication linkages between the various healthcare systems and school systems are rarely well-coordinated, placing children with an mTBI at risk for prolonged recovery, adverse impact on learning, and mTBI re-exposure. The objective of this study is to rigorously appraise the pediatric Mild Traumatic Brain Injury Evaluation and Management (TEaM) Intervention that was designed to enhance diagnosis and management of pediatric mTBI through enhanced patient discharge instructions and communication linkages between school and primary care providers.MethodsThis is a combined randomized and 2 × 2 quasi-experimental study design with educational and technology interventions occurring at the clinician level with patient and school outcomes as key endpoints. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will be utilized as a mix methods approach to appraise a multi-disciplinary, multi-setting intervention with the intent of improving outcomes for children who have experienced mTBI.DiscussionUtilization of the RE-AIM framework complemented with qualitative inquiry is suitable for evaluating effectiveness of the TEaM Intervention with the aim of emphasizing priorities regarding pediatric mTBI. This program evaluation has the potential to support the knowledge needed to critically appraise the impact of mTBI recovery interventions across multiple settings, enabling uptake of the best-available evidence within clinical practice.

Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by MerckCo., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries.We evaluated data from three Phase 2/3 clinical trials conducted in Liberia (PREVAIL), Guinea (FLW), and Sierra Leone (STRIVE) during the 2013-2016 West African EVD outbreak to assess immune responses using validated assays. We performed a post hoc analysis of the association of vaccine response with sex, age (18-50 yrs50 yrs), and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (200≥200 EU/mL), including individual study (PREVAIL, FLW, or STRIVE) data and pooled data from all 3 studies. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 28, 180, and 365 postvaccination.In the overall pooled population, in all subgroups, and in each trial independently, GP-ELISA and PRNT geometric mean titers increased from BL, generally peaking at Day 28 and persisting through Day 365. Immune responses were greater in women and participants with BL GP-ELISA ≥ 200 EU/mL, but did not differ across age groups.These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response through 12 months postvaccination in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in women and participants with pre-existing immunity are consistent with those described previously and for other vaccines. Trials were registered as follows: PREVAIL: ClinicalTrials.gov NCT02344407; FLW: Pan African Clinical Trials Registry PACTR201503001057193; STRIVE: ClinicalTrials.gov NCT02378753. Protocols V920-009, 011, and 018.

Pediatric primary health care (PPHC) is of principal importance to the health and development of all children, helping them reach their true potential. Pediatricians, as the clinicians most intensively trained and experienced in child health, are the natural leaders of PPHC within the context of the medical home. Given the rapidly evolving models of pediatric health care delivery, including the explosion of telehealth in the wake of the COVID-19 pandemic, pediatricians, together with their representative national organizations such as the American Academy of Pediatrics (AAP), are the most capable clinicians to guide policy innovations on both the local and national stage.

Background The aim of this study is to describe and quantitatively analyze the histopathology of proximal long head biceps (LHB) tendinopathy in patients who have undergone LHB tenodesis. The hypothesis is that severe histopathologic changes of the LHB tendon (LHBT) will most likely be reflected with improved postoperative clinical outcomes. Methods The study included patients with isolated LHB tendinopathy or LHB tendinopathy associated with concomitant shoulder pathologies. All had failed conservative treatment (12 months) and had a positive pain response (> 50% reduction) pre-operatively after LHB tendon injection with local anesthetic. All underwent biceps tenodesis procedure between 2008 and 2014. Tendon specimens were collected and histologically analyzed with the semi-quantitative Bonar scoring system. Minimum follow-up time was 1 year. A subset of patients was retrospectively reviewed postoperatively and evaluated employing visual analogue score (VAS), short form survey (SF-12), American Shoulder and Elbow Surgeon (ASES) score, Disability of Arm, Shoulder and Hand (DASH) score, and Oxford Shoulder Score (OSS) and postoperative return to work status. Results Forty-five biceps tendon specimens were obtained from 44 patients (mean age 50 ± 9.6 years). Histopathological analyses demonstrated advanced degenerative changes with myxoid degeneration and marked collagen disorganization. Minimal inflammation was identified. There were no regional differences in histopathological changes. Clinical outcomes did not correlate significantly with severity of histopathologic changes. Conclusions This study confirms that LHBT specimens in patients undergoing tenodesis demonstrate with the use of the Bonar score histopathologic changes of chronic degeneration and not inflammation. The correct histopathologic terminology for this process is LHB tendinosis. The histopathological changes appear uniform throughout the entire length of the LHBT which may inform the nature of the procedure performed.

Institutions are adopting the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines for pediatric esophageal button battery ingestion (EBBI). Our objective was to evaluate the guidelines' impact on in-hospital resource utilization and short-term clinical outcomes in hemodynamically stable patients after endoscopic battery removal.A single-center retrospective review of all EBBI admissions from 2010 to 2020. Patients were divided into two groups based on adoption of national guidelines: pre-guideline (2010-2015) and post-guideline (2016-2020).Sixty-five patients were studied (pre-guideline n = 23; post-guideline n = 42). Compared with pre-guideline, post-guideline use of magnetic resonance imaging (MRI) increased (2/23 [8.7%]; 30/42 [71.4%]; p 0.001). Post-guideline increases resulted for median days (IQR) receiving antibiotics (0 [0, 4]; 6 [3, 8]; p = 0.01), total pediatric intensive care unit admission (0 [0, 1]; 3 [0, 6]; p 0.001), and total hospital length of stay (5 [2, 11]; 11.5 [4, 17]; p = 0.02). Two patients in the post-guideline group had delayed presentations despite normal imaging: one with TEF and one with aorto-esophageal fistula. All survived to discharge.In EBBI cases managed using the consensus based NASPHAGN guidelines, we report increased resource utilization without improved patient outcomes. Further research should evaluate post-guideline costs and resource utilization.

All children and adolescents deserve access to quality health care regardless of their race/ethnicity, health conditions, financial resources, or geographic location. Despite improvements over the past decades, severe disparities in the availability and access to high-quality health care for children and adolescents continue to exist throughout the United States. Economic and racial factors, geographic maldistribution of primary care pediatricians, and limited availability of pediatric medical subspecialists and pediatric surgical specialists all contribute to inequitable access to pediatric care. Robust, comprehensive telehealth coverage is critical to improving pediatric access and quality of care and services, particularly for under-resourced populations.

BACKGROUND Despite growth in value-based payment, attributes of nephrology care associated with payer-defined value remains unexplored. METHODS Using national health insurance claims data from private preferred provider organization plans, we ranked nephrology practices using total cost of care and a composite of common quality metrics. Blinded to practice rankings, we conducted site visits at four highly ranked and three average ranked practices to identify care attributes more frequently present in highly ranked practices. A panel of nephrologists used a modified Delphi method to score each distinguishing attribute on its potential to affect quality and cost of care and ease of transfer to other nephrology practices. RESULTS Compared with average-value peers, high-value practices were located in areas with a relatively higher proportion of black and Hispanic patients and a lower proportion of patients aged >65 years. Mean risk-adjusted per capita monthly total spending was 24% lower for high-value practices. Twelve attributes comprising five general themes were observed more frequently in high-value nephrology practices: preventing near-term costly health crises, supporting patient self-care, maximizing effectiveness of office visits, selecting cost-effective diagnostic and treatment options, and developing infrastructure to support high-value care. The Delphi panel rated four attributes highly on effect and transferability: rapidly adjustable office visit frequency for unstable patients, close monitoring and management to preserve kidney function, early planning for vascular access, and education to support self-management at every contact. CONCLUSIONS Findings from this small-scale exploratory study may serve as a starting point for nephrologists seeking to improve on payer-specified value measures.

To determine the characteristics of children who met the risk criteria for potential neurotoxicity defined by the US Food and Drug Administration (FDA; 2016 warning) in a procedural sedation (PS) service.A single-center retrospective review of all infants and children aged3 years receiving PS outside the operating room from 2014 to 2016. Demographics, duration of, and the reason for PS were analyzed.A total of 2950 patients with 3653 sedation encounters were included. Median age was 19 (range, 11-26) months. Most PS (86.4%) were for magnetic resonance imaging (MRI). The median number of sedation procedures per patient was 1 (25th-75th: 1-7), and median duration of sedation was 72 minutes (25th-75th: 55-98 minutes). Forty patients (1.4%) required prolonged sedations3 hours, in a single encounter (median, [25th-75th] of 196 minutes [185-214 minutes]), and 298 patients (10.1%) had multiple sedation exposures during the study period. Overall, 327 patients, 11.1% (95% confidence interval, 10.0%-12.3%) required repeated and/or prolonged sedation. The most common reasons for repeated or prolonged sedation were MRI of the brain and neurologic concerns.Multiple and prolonged PS commonly occurs outside the operating room in this young and potentially vulnerable population. Although certain imaging cannot be avoided, other cases may have the potential to be delayed until the child is3 years old or to have alternate imaging that may not require prolonged PS. Family and provider awareness of the FDA warnings regarding potential neurotoxicity of sedation in all settings, both inside and outside the operating room, is critical.

OBJECTIVE: Adult patients are increasingly receiving care in pediatric emergency departments (PEDs), but little is known about the epidemiology of these visits. The goal of this study was to examine the characteristics of adult patients (≥ 21 years) treated in PEDs, and to describe the variation in resource utilization across centers. METHODS: We conducted a cross-sectional study examining visits to 30 PEDs (2012–2016) using the Pediatric Health Information System. Visits were categorized using All Patient Refined Diagnosis Related Groups and compared between age cohorts. We used multivariable logistic models to examine variation in demographics, utilization, testing, treatment, and disposition. RESULTS: There were 12,958,626 visits to the 30 PEDs over 5 years; 70,636 (0.6%) were by adults. Compared with children, adult patients had more laboratory testing (49% vs. 34%), diagnostic imaging (32% vs. 29%) and procedures (48% vs. 31%), and were more often admitted (17% vs. 11%) or transferred (21% vs. 0.7%) (p

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (

Background This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP). Methods Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed. Results ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination. Conclusions Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development. Clinical Trials Registration NCT02503202., Immune responses to rVSVΔG-ZEBOV-GP, measured by ZEBOV-GP immunoglobulin G enzyme-linked immunosorbent assay and plaque reduction neutralization test, were robust and persisted up to 24 months. Together with the favorable safety profile, the immunogenicity results support continued rVSVΔG-ZEBOV-GP development.

Despite extensive efforts, overall readmission rates at US children's hospitals have not materially declined over the past decade, raising questions about how to direct future efforts. Using measures of prevalence and performance variation we describe readmission rates by condition and identify priority conditions for future intervention.Retrospective cohort study of 49 US children's hospitals in the Pediatric Health Information System in 2017. Conditions were classified using All Patients Refined Diagnosis Related Groups. 30-day unadjusted and risk-adjusted readmission rates were calculated for each hospital/condition using the Pediatric All Cause Readmission measure. We ranked the highest volume conditions by rate variation (RV, interquartile range divided by the median) for each condition across hospitals.The sample included 811,434 index hospitalizations with 50,196 (6.2%) 30-day readmissions. The RV across hospitals/conditions was between 0 and 2.8 (median = 0.7). Common reasons for admission had low RVs across hospitals, for example, bronchiolitis (readmission rate = 5.6%, RV = 0.4), seizure (readmission rate = 6.6%, RV = 0.3), and asthma (readmission rate = 3.1%, RV = 0.4). We identified 33 conditions with high variation in readmission rates across hospitals, which accounted for 18% of all discharges and 11% of all pediatric readmissions. These conditions may serve as candidates for future readmission reduction activities.Many common childhood conditions have little variation in readmission rates across children's hospitals, suggesting limited future improvement opportunities. Conditions with high rate variation may provide opportunities for quality improvement; however, these conditions account for a relatively small share of total discharges suggesting modest potential impacts on national rates.

Importance Differences in lifetime earning potential between pediatric subspecialties may contribute to shortages in the subspecialty workforce. Objectives To evaluate the association between lifetime earning potential and workforce distribution and to investigate the potential role of a pediatric subspecialist–specific loan repayment program (LRP) in workforce expansion. Design, Setting, and Participants This study was performed on publicly available mean debt and compensation data from national physician surveys from 2018 to 2019 of pediatric subspecialists in academic practice. Linear regression analysis was used to evaluate the association between lifetime earning potential and measures of workforce distribution in 2019, including distance to subspecialists, percentage of hospital referral regions with a subspecialist, and ratio of subspecialists to the regional child population as well as between lifetime earning potential in 2018 to 2019 and mean subspecialty fellowship fill rates between 2014 and 2018. The association between the change in lifetime earning potential from 2007 to 2018 and the change in workforce distribution metrics from 2003 to 2019 was also examined. The potential role of a pediatric subspecialist–specific LRP was modeled. Exposures Lifetime earning potential by subspecialty. Main Outcomes and Measures Measures of workforce distribution and fellowship fill rates. Results This study included mean compensation data representing 7539 pediatric subspecialists, workforce distribution data representing 24 375 pediatric subspecialists, and fellowship fill rates representing a mean of 1344 pediatric subspecialty fellows per year. Higher lifetime earning potential was associated with shorter distance to subspecialists (−0.59 miles/$100 000 increase in lifetime earning potential; 95% CI, –1.10 to –0.09), higher percentage of hospital referral regions with a subspecialist (+1.17%/$100 000 increase in lifetime earning potential; 95% CI, 0.34-2.00), and higher ratio of subspecialists to regional child population (+0.11 subspecialists/100 000 children/$100 000 increase in lifetime earning potential; 95% CI, 0.04-0.19). The subspecialties for which lifetime earning potential increased the least between 2007 and 2018 experienced the least growth in the ratio of subspecialists to regional child population from 2003 to 2019 (+0.11 subspecialists/100 000 children/$100 000 increase in lifetime earning potential; 95% CI, 0.07-0.16). Higher lifetime earning potential was associated with higher mean fellowship fill rates (+0.96% spots filled/$100 000 increase in lifetime earning potential; 95% CI, 0.15-1.77). Implementing a pediatric subspecialist–specific LRP could increase fellowship fill rates and improve workforce distribution. Conclusions and Relevance Lifetime earning potential based on subspecialty may contribute to imbalances in both the current and future pediatric subspecialty workforce. Pediatric subspecialist–specific LRPs, especially for underfilled subspecialties, are potential tools for policy makers to target workforce shortages.

Surgical navigation systems have demonstrated improvements in alignment accuracy in a number of arthroplasty procedures, but they have not yet been widely adopted for use in total shoulder arthroplasty (TSA). We believe this is due in part to the obtrusiveness of conventional optical tracking systems, as well as the need for additional intraoperative steps such as calibration and registration. The purpose of this study is to evaluate the feasibility of adapting a less-intrusive dental navigation system for use in TSA.We developed a proof-of-concept system based on validated laser-engraved surgical tools recently introduced for use in dental surgery that are calibrated once when manufactured and not recalibrated at time of use. The design also features a notably smaller bone-mounted tracker that can be tracked from a wide range of viewing angles. To assess our system's performance, we modified the dental surgical software to support guidance of a TSA procedure. We then conducted a user study in which three participants with varying surgical experience used the system to drill 30 holes in a glenoid model. Using a coordinate measuring machine, we determined the resulting drilled trajectory and compared this to the pre-planned trajectory. Since we used a model glenoid rather than anatomical specimens, we report on targeting precision rather than overall procedure precision or accuracy.We found targeting precision 1 mm (standard deviation) for locating the entry hole and ~ 1° (SD) for both version and inclination. The latter value was markedly lower than the end-to-end angular precision achieved by previously reported TSA navigation systems (approximately 3°-5° SD).We conclude that variability during the targeting phase represents a small fraction of the overall variability exhibited by existing systems, so a less obtrusive navigation system for TSA based on laser-engraved tooling is likely feasible, which could improve the uptake rates of surgical navigation for TSA, thereby potentially leading to improved overall surgical outcomes.

OBJECTIVES Compare lifetime earning potential between academic pediatric and adult medicine generalists and subspecialists. Evaluate the effect of decreasing the length of training for pediatric subspecialties whose length of training is longer than that for the adult medicine counterpart. METHODS Using compensation and debt data from national physician surveys for 2019–2020, we estimated and compared the lifetime earning potential for academic pediatric and adult physicians. RESULTS Lifetime earning potential was higher for adult physicians than for pediatric physicians across all comparable areas of both general and subspecialty academic practice. The lifetime earning potentials for adult physicians averaged 25% more, or $1.2 million higher, than those of the corresponding pediatric physicians. These differences predominantly were not attributable to unequal training length: when we modeled a shortened length of training for pediatric subspecialists, lifetime earning potential for adult subspecialists still averaged 19% more than that for pediatric subspecialists. For both pediatric and adult medicine, the primarily inpatient, procedure-oriented subspecialties had higher lifetime earning potential than the outpatient, less procedure-oriented subspecialties. CONCLUSIONS Wide differences in lifetime earning potential between pediatric and adult physicians reflected lower compensation in pediatrics, rather than any differences in training length. Inpatient-based, more procedure-oriented subspecialties had higher lifetime earning potential than outpatient-based, less procedure-oriented subspecialties. Interventions that improve the lifetime earning potential of general pediatrics and the pediatric subspecialties, as well as the less procedure-oriented subspecialties across both pediatric and adult medicine, have the potential to impact both clinical practice and access to care.

BACKGROUND/OBJECTIVES Firearm injuries are converging with motor vehicle collisions (MVC) as the number one cause of death for children in the United States. Thus we examine differences in hospital cost and hospital resource utilization between motor vehicle and firearm injury. METHODS This retrospective, cross-sectional study compares hospital costs and resource utilization of motor vehicle and firearm-injured children aged 0 to 19 years of age over a 5-year time frame (January 1, 2013-December 31, 2017) in 35 freestanding children's hospitals that submitted data to the Pediatric Health Information System. The primary outcome was hospital-adjusted comparative cost per patient presentation. Generalized linear mixed models were used to quantify the relationship between the type of injury and each outcome, adjusting for patient characteristics and hospital. RESULTS There were 89,133 emergency department (ED) visits attributed to MVCs and 3,235 for firearm injury. Of the youths who presented for firearm injury, 49% were hospitalized versus 14% of youths presenting with MVC (adjusted odds ratio [aOR] = 6.6, 95% confidence interval [CI] = 6.1 to 7.2). Youths with firearm injury were more likely to be admitted to an intensive care unit (aOR = 6.7, 95% CI = 5.9 to 7.7) and had longer lengths of stays (aOR = 2.2, 95% CI = 1.9 to 2.6) compared to their MVC counterparts. Children admitted for firearm injury had more imaging and ED return visits, along with subsequent inpatient admission within 3 days (aOR = 3.4, 95% CI = 2.1 to 5.5) and 1 year (aOR = 2.5, 95% CI = 2.1 to 2.9). The mean relative per-patient costs were nearly fivefold higher for the firearm-injured group. CONCLUSIONS Hospital costs and markers of resource utilization were higher for youths with firearm injury compared to MVC. High medical resource utilization is one of several important reasons to advocate for a comparable national focus and funding on firearm-related injury prevention.

OBJECTIVES: Our 2011 report, reflecting data from 2007–2008, demonstrated that, for many pediatric subspecialties, pursuing fellowship training was a negative financial decision when compared with practicing as a general pediatrician. We provide an updated analysis on the financial impact of pediatric fellowship training and model interventions that can influence the results. METHODS: We estimated the financial returns a graduating pediatric resident might anticipate from fellowship training followed by a career as a pediatric subspecialist and compared them with the returns expected from starting a career as a general pediatrician immediately after residency. We evaluated the potential effects of eliminating medical school debt, shortening the length of fellowship training, and implementing a federal loan repayment program for pediatric subspecialists. We compared the financial returns of subspecialty training in 2018–2019 to those from our previous report. RESULTS: Pursuing fellowship training generated widely variable financial returns when compared with general pediatrics that ranged from +$852 129 for cardiology to −$1 594 366 for adolescent medicine. Twelve of 15 subspecialties analyzed yielded negative financial returns. The differences have become more pronounced over time: the spread between the highest and lowest earning subspecialties widened from >$1.4 million in 2007–2008 to >$2.3 million in 2018–2019. The negative financial impact of fellowship training could be partially ameliorated by shortening the length of training or by implementing pediatric subspecialist specific loan repayment programs. CONCLUSIONS: This report can be used to help guide trainees, educators, and policy makers. The interventions discussed could help maintain an adequate and balanced pediatric workforce.

Background COVID-19 was declared a global emergency in the first quarter of 2020. It is has resulted in and continues in over a million deaths worldwide and halted medical systems and particularly elective surgeries worldwide. The aim of this study was to identify the effect of the initial COVID-19 pandemic months on orthopaedic surgeons in British Columbia. Methods The study surveyed (June until August 2020) 187 orthopaedic surgeons in British Columbia affiliated with the University of British Columbia or the British Columbia Orthopaedic Association using an online survey to help identify the impact of COVID-19 on patient care, work and personal life. Results Eighty-seven out of 187 (46.5%) orthopaedic surgeons participated in the online survey. All types of surgeries were completely cancelled for 23 respondents. Elective surgeries were cancelled for most respondents (in-hospital n = 38 and/or ambulatory n = 32). Trauma cases were reduced according to 35 respondents. Outpatient clinics were stopped initially and transferred in virtual clinics (telemedicine). Approximately 40% of respondents were afraid of infecting others (patients, family) and 25% admitted to drink more heavily. Ninety percent of respondents reported an income loss of > 15% (range 0–100%). Conclusion Orthopaedic surgeons and their patients have been significantly affected by the COVID-19 pandemic. Cancellation of surgeries has created an increased backlog of 32,400 orthopaedic surgeries in British Columbia. However, the COVID-19 pandemic has expedited the implementation of telemedicine, which will be a long-lasting benefit in providing healthcare.

Objective To examine whether the presence of clinical guidelines and clinical decision support (CDS) for mild traumatic brain injury (mTBI) are associated with lower use of head computed tomography (CT). Study design We conducted a cross-sectional study of 45 pediatric emergency departments (EDs) in the Pediatric Hospital Information System from 2015 through 2019. We included children discharged with mTBI and surveyed ED clinical directors to ascertain the presence and implementation year of clinical guidelines and CDS. The association of clinical guidelines and CDS with CT use was assessed, adjusting for relevant confounders. As secondary outcomes, we evaluated ED length of stay and rates of 3-day ED revisits and admissions after revisits. Results There were 216 789 children discharged with mTBI, and CT was performed during 20.3% (44 114/216 789) of ED visits. Adjusted hospital-specific CT rates ranged from 11.8% to 34.7% (median 20.5%, IQR 17.3%, 24.3%). Of the 45 EDs, 17 (37.8%) had a clinical guideline, 9 (20.0%) had CDS, and 19 (42.2%) had neither. Compared with EDs with neither a clinical guideline nor CDS, visits to EDs with CDS (aOR 0.52 [0.47, 0.58]) or a clinical guideline (aOR 0.83 [0.78, 0.89]) had lower odds of including a CT for mTBI. ED length of stay and revisit rates did not differ based on the presence of a clinical guideline or CDS. Conclusions Clinical guidelines for mTBI, and particularly CDS, were associated with lower rates of head CT use without adverse clinical outcomes.

Rotator cuff repair is a commonly performed shoulder procedure. In the past 20 years, there has been a shift from mini-open towards arthroscopic repair, and many units exclusively use arthroscopic techniques for rotator cuff surgery. The aim of this study was to find out whether withholding antibiotics had any effect on the infection rate in patients undergoing arthroscopic rotator cuff repair.A retrospective analysis of 336 consecutive patients with an arthroscopic rotator cuff repair (RCR) and a minimum 2-year follow-up was performed. The control group received prophylactic antibiotics (controls) and the cases of interest did not receive perioperative antibiotics. A power analysis was performed according to literature regarding infection proportions. The primary outcome was an infection (superficial or deep) in the operated shoulder.There were 336 patients who underwent a RCR. Two-hundred-and-twelve in the control group and 124 in the non-antibiotic group. Average ages were 57.3 ± 12.5 and 56.8 ± 13.2 years in each group, respectively. The follow-up times ranged from 24 to 76 months. Equipment used and surgical techniques were identical, only operating times were statistically different between the groups (control 77.2 ± 41.3 min versus no antibiotic cases 52.9 ± 16.7 min) (p = 0.000009). There was no recorded infection in either group.Infection following arthroscopic surgery is uncommon. Small incisions, constant lavage with saline, minimal hardware insertion and short operating times all combine to minimise the risks. Current results point towards no detriment in withholding prophylactic antibiotics in low-risk patients undergoing routine rotator cuff repair surgery. Therefore, judicious use of prophylactic antibiotics in patients undergoing this procedure is advocated to prevent potential harm to those it is administered to.Level III.

VAQTA™ (Hepatitis A Vaccine, inactivated [HAVi]; Merck & Co., Inc., Kenilworth, NJ, USA) is currently licensed for prevention of disease caused by hepatitis A virus in persons ≥12 months of age. This report summarizes statistical models developed to evaluate the long-term persistence and duration of detectable hepatitis A antibody (total antibody levels with no distinction on class) after receipt of HAVi in healthy children and adolescents (V251-023 and V251-035) and in healthy adults (V251-034). The statistical models presented, conducted separately for each of the three studies, are based on models that have been used in the literature to estimate the duration of antibody to protect against human papillomavirus (HPV) disease. In the absence of observed study data on hepatitis A antibody persistence for vaccine recipients over several decades, an extrapolation from a kinetic model of antibody decay was used to estimate the duration of detectable antibody. Extrapolation of observed antibody titers from postvaccination, Year 2.5–3.5, Year 5–6, and Year 10 in 165 children and adolescents who received HAVi at Day 0 and Week 24 in V251-023 suggests that detectable levels of antibody may persist after the second dose for many years. This model suggests that 25 to 50 years Postdose 1 in a two-dose series of HAVi, 99.4% of the study population will have detectable levels of hepatitis A antibody.

BACKGROUND:In several states, payers penalize hospitals when an inpatient readmission follows an inpatient stay. Observation stays are typically excluded from readmission calculations. Previous studies suggest inconsistent use of observation designations across hospitals. We sought to describe variation in observation stays and examine the impact of inclusion of observation stays on readmission metrics.METHODS:We conducted a retrospective cohort study of hospitalizations at 50 hospitals contributing to the Pediatric Health Information System database from January 1, 2018, to December 31, 2018. We examined prevalence of observation use across hospitals and described changes to inpatient readmission rates with higher observation use. We described 30-day inpatient-only readmission rates and ranked hospitals against peer institutions. Finally, we included observation encounters into the calculation of readmission rates and evaluated hospitals’ change in readmission ranking.RESULTS:Most hospitals (n = 44; 88%) used observation status, with high variation in use across hospitals (0%–53%). Readmission rate after index inpatient stay (6.8%) was higher than readmission after an index observation stay (4.4%), and higher observation use by hospital was associated with higher inpatient-only readmission rates. When compared with peers, hospital readmission rank changed with observation inclusion (60% moving at least 1 quintile).CONCLUSIONS:The use of observation status is variable among children’s hospitals. Hospitals that more liberally apply observation status perform worse on the current inpatient-to-inpatient readmission metric, and inclusion of observation stays in the calculation of readmission rates significantly affected hospital performance compared with peer institutions. Consideration should be given to include all admission types for readmission rate calculation.

Respiratory diphtheria, characterized by a firmly adherent pseudomembrane, is caused by toxin-producing strains of Corynebacterium diphtheriae, with similar illness produced occasionally by toxigenic Corynebacterium ulcerans or, rarely, Corynebacterium pseudotuberculosis. While diphtheria laboratory confirmation requires culture methods to determine toxigenicity, real-time PCR (RT-PCR) provides a faster method to detect the toxin gene (tox). Nontoxigenic tox-bearing (NTTB) Corynebacterium isolates have been described, but impact of these isolates on the accuracy of molecular diagnostics is not well characterized. Here, we describe a new triplex RT-PCR assay to detect tox and distinguish C. diphtheriae from the closely related species C. ulcerans and C. pseudotuberculosis. Analytical sensitivity and specificity of the assay were assessed in comparison to culture using 690 previously characterized microbial isolates. The new triplex assay characterized Corynebacterium isolates accurately, with 100% analytical sensitivity for all targets. Analytical specificity with isolates was 94.1%, 100%, and 99.5% for tox, Diph_rpoB, and CUP_rpoB targets, respectively. Twenty-nine NTTB Corynebacterium isolates, representing 5.9% of 494 nontoxigenic isolates tested, were detected by RT-PCR. Whole-genome sequencing of NTTB isolates revealed varied mutations putatively underlying their lack of toxin production, as well as eight isolates with no mutation in tox or the promoter region. This new Corynebacterium RT-PCR method provides a rapid tool to screen isolates and identify probable diphtheria cases directly from specimens. However, the sporadic occurrence of NTTB isolates reinforces the viewpoint that diphtheria culture diagnostics continue to provide the most accurate case confirmation.

The Centers for Disease Control and Prevention (CDC) recommend universal human immunodeficiency virus (HIV) screening starting at 13 years, which has been implemented in many general U.S. emergency departments (EDs) but infrequently in pediatric EDs. We aimed to 1) implement a pilot of routine adolescent HIV screening in a pediatric ED and 2) determine the unique barriers to CDC-recommended screening in this region of high HIV prevalence.This was a prospective 4-month implementation of a routine HIV screening pilot in a convenience sample of adolescents 13 to 18 years at a single pediatric ED, based on study personnel availability. Serum-based fourth-generation HIV testing was run through a central laboratory. Parents were allowed to remain in the room for HIV counseling and testing. Data were collected regarding patient characteristics and HIV testing quality metrics. Comparisons were made using chi-square and Fisher's exact tests. Regression analysis was performed to assess for an association between parent presence at the time of enrollment and adolescent decision to participate in HIV screening.Over 4 months, 344 of 806 adolescents approached consented to HIV screening (57% female, mean ± SD = 15.1 ± 1.6 years). Adolescents with HIV screening were more likely to be older than those who declined (p = 0.025). Other blood tests were collected with the HIV sample for 21% of adolescents; mean time to result was 105 minutes (interquartile range = 69 to 123) and 79% were discharged before the result was available. Having a parent present for enrollment was not associated with adolescent participation (adjusted odds ratio = 1.07, 95% CI = 0.67 to 1.70). Barriers to testing included: fear of needlestick, time to results, cost, and staff availability. One of 344 tests was positive in a young adolescent with Stage 1 HIV.Routine HIV screening in adolescents was able to be implemented in this pediatric ED and led to the identification of early infection in a young adolescent who would have otherwise been undetected at this stage of disease. Addressing the unique barriers to adolescent HIV screening is critical in high-prevalence regions and may lead to earlier diagnosis and treatment in this vulnerable population.

Gender-based disparities in compensation in academic medicine are recognized, but their estimated impacts on early career earning potential and strategies to mitigate them have not been well studied.To compare earning potential between female and male academic physicians in the first 10 years of posttraining employment and to evaluate the estimated impact of promotion timing, starting salary, and salary growth rate on earning potential.Using publicly available mean debt and compensation data for full-time employed academic physicians in the US from 2019 to 2020, starting salary, salary in year 10 of employment, annual salary growth rate, and overall earning potential in the first 10 years of employment were estimated for each gender by subspecialty. The estimated impacts of promotion timing and potential interventions, including equalizing starting salaries and annual salary growth rates, were modeled. Data analysis was performed from March to May 2021.Gender and subspecialty.Starting salary, annual salary growth rate, year-10 salary, and earning potential in first 10 years of employment.This cross-sectional study included compensation data from 24 593 female and 29 886 male academic physicians across 45 subspecialties. Women had lower starting salaries in 42 of 45 subspecialties (93%), year-10 salaries in 43 of 45 subspecialties (96%), mean annual salary growth rates in 22 of 45 subspecialties (49%), and earning potential in 43 of 45 subspecialties (96%) (median [IQR], $214 440 [$130 423-$384 954], or 10%, less). A 1-year delay in promotion from assistant to associate professor reduced women's earning potential by a median (IQR) of $26 042 ($19 672-$35 671), but failure to be promoted at all reduced it by a median (IQR) of $218 724 ($176 317-$284 466). Equalizing starting salaries could increase women's earning potential by a median (IQR) of $250 075 ($161 299-$381 799) in the subspecialties for which starting salaries for women were lower than those for men. Equalizing annual salary growth rates could increase women's earning potential by a median (IQR) of $53 661 ($24 258-$102 892) in the subspecialties for which mean annual salary growth rates were lower for women than for men.The findings of this study suggest that gender-based disparities in starting salary and early career earning potential are pervasive in academic medicine in the US. Equalizing starting salaries would address the majority of the differences in earning potential.

Background. The American Academy of Pediatrics and pediatric community recognize the importance of addressing social determinants of health. There are limited data on the prevalence of food insecurity or literature establishing protocols assessing food insecurity in the emergency department (ED). Methods. Two anonymous surveys were administered, one to families during their ED visit and another to ED staff to assess perceptions on the ED’s role in providing social support. Results. Thirty-three of 214 respondents (15.4%) reported food insecurity and are associated with economic risk factors ( P < .0001) and a lack of primary care ( P = .008). Overall, 83.2% of the ED staff believed knowing information about families’ social risk factors would help patient care and 77.6% believed that the ED staff should address families’ social needs. Conclusions. Food insecurity affects a significant portion of ED families across income ranges. Screening for food insecurity in the ED is important given association with lack of primary care. Hospital staff supports screening and intervention.

Background The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naive adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1–2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response. Methods In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera. Results There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = −0.56, p Discussion Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection. Clinical trials registration: NCT01895855.

Objectives Interventions to reduce frequent emergency department (ED) use in children are often limited by the inability to predict future risk. We sought to develop a population-based model for predicting Medicaid-insured children at risk for high frequency (HF) of low-resource-intensity (LRI) ED visits. Methods We conducted a retrospective cohort analysis of Medicaid-insured children (aged 1–18 years) included in the MarketScan Medicaid database with ≥1 ED visit in 2013. LRI visits were defined as ED encounters with no laboratory testing, imaging, procedures, or hospitalization; and HF as ≥3 LRI ED visits within 365 days of the initial encounter. A generalized linear regression model was derived and validated using a split-sample approach. Validity testing was conducted examining model performance using 3 alternative definitions of LRI. Results Among 743,016 children with ≥1 ED visit in 2013, 5% experienced high-frequency LRI ED use, accounting for 21% of all LRI visits. Prior LRI ED use (2 visits: adjusted odds ratio = 3.5; 95% confidence interval, 3.3, 3.7; and ≥3 visits: adjusted odds ratio = 7.7; 95% confidence interval, 7.3, 8.1) and presence of ≥3 chronic conditions (adjusted odds ratio = 1.7; 95% confidence interval, 1.6, 1.8) were strongly associated with future HF-LRI ED use. A model incorporating patient characteristics and prior ED use predicted future HF-LRI ED utilization with an area under the curve of 0.74. Conclusions Demographic characteristics and patterns of prior ED use can predict future risk of HF-LRI ED use in the following year. Interventions for reducing low-value ED use in these high-risk children should be considered.

Anxiety and depression are prevalent among cancer patients, with significant negative impact. Many patients prefer herbs for symptom relief to conventional medications which have limited efficacy/side effects. We identified single-herb medicines that may warrant further study in cancer patients. Our search included PubMed, Allied and Complementary Medicine, Embase, and Cochrane databases, selecting only single-herb randomized controlled trials between 1996 and 2016 in any population for data extraction, excluding herbs with known potential for interactions with cancer treatments. One hundred articles involving 38 botanicals met our criteria. Among herbs most studied (≥6 randomized controlled trials each), lavender, passionflower, and saffron produced benefits comparable to standard anxiolytics and antidepressants. Black cohosh, chamomile, and chasteberry are also promising. Anxiety or depressive symptoms were measured in all studies, but not always as primary endpoints. Overall, 45% of studies reported positive findings with fewer adverse effects compared with conventional medications. Based on available data, black cohosh, chamomile, chasteberry, lavender, passionflower, and saffron appear useful in mitigating anxiety or depression with favorable risk-benefit profiles compared to standard treatments. These may benefit cancer patients by minimizing medication load and accompanying side effects. However, well-designed larger clinical trials are needed before these herbs can be recommended and to further assess their psycho-oncologic relevance.

The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, re-developed as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies. We performed a phase 3, placebo controlled, double blind, multi-center study to further assess the safety, immunogenicity, and lot-to-lot consistency of PXVX0200. Adult volunteers 18–45 years of age were randomized 8:1 to receive a single dose of 1 × 109 CFU of PXVX0200 from three production lots or saline placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1–8, unsolicited adverse events through day 29 and serious adverse events through day 181. A total of 3146 participants were enrolled, including 2795 vaccine and 351 placebo recipients. The SVA seroconversion rates at day 11 were 94% and 4% in the PXVX0200 and placebo recipients, respectively (P Clinical Trials Registration: Clinicaltrials.gov NCT02094586.

The 2014-2016 Ebola outbreak caused over 28,000 cases and 11,000 deaths. Merck & Co. Inc., Kenilworth, NJ USA and NewLink Genetics are working with private and public partners to develop and license an Ebola vaccine that was evaluated extensively during the outbreak. The vaccine referred to as V920 is a recombinant vesicular stomatitis virus (rVSV) in which the VSV-G envelope glycoprotein (GP) is completely replaced by the Zaire ebolavirus GP (rVSVΔG-ZEBOV-GP). Eight Phase I and four Phase II/III clinical trials enrolling approximately 17,000 subjects were conducted in parallel to the outbreak to assess the safety, immunogenicity, and/or efficacy of V920. Immunogenicity data demonstrate that anti-GP antibodies are generally detectable by ELISA by 14days postvaccination with up to 100% seroconversion observed by 28days post dose. In addition, the results of a ring vaccination trial conducted by the WHO and their partners in Guinea suggest robust vaccine efficacy within 10days of receipt of a single dose of vaccine. The vaccine is generally well-tolerated when administered to healthy, non-pregnant adults. The development of this vaccine candidate in the context of this unprecedented epidemic has involved the close cooperation of large number of international partners and highlights what we as a public health community can accomplish when working together towards a common goal. Study identification: V920-001 to V920-012. CLINICALTRIALS.GOV identifiers: NCT02269423; NCT02280408; NCT02374385; NCT02314923; NCT02287480; NCT02283099; NCT02296983; NCT02344407; NCT02378753; NCT02503202.

Background Return visits (RVs) and RVs with admission (RVAs) are commonly used emergency department quality measures. Visit- and patient-level factors, including several social determinants of health, have been associated with RV rates, but hospital-specific factors have not been studied. Objective To identify what hospital-level factors correspond with high RV and RVA rates. Setting Multicenter mixed-methods study of hospital characteristics associated with RV and RVA rates. Data source Pediatric Health Information System with survey of emergency department directors. Measurements Adjusted return rates were calculated with generalized linear mixed-effects models. Hospitals were categorized by adjusted RV and RVA rates for analysis. Results Twenty-four hospitals accounted for 1,456,377 patient visits with an overall adjusted RV rate of 3.7% and RVA rate of 0.7%. Hospitals with the highest RV rates served populations that were more likely to have government insurance and lower median household incomes and less likely to carry commercial insurance. Hospitals in the highest RV rate outlier group had lower pediatric emergency medicine specialist staffing, calculated as full-time equivalents per 10,000 patient visits: median (interquartile range) of 1.9 (1.5-2.1) versus 2.9 (2.2-3.6). There were no differences in hospital population characteristics or staffing by RVA groups. Conclusion RV rates were associated with population social determinants of health and inversely related to staffing. Hospital-level variation may indicate population-level economic factors outside the control of the hospital and unrelated to quality of care.