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Background : One of the most competitive surgical sub-specialty fellowships remains Pediatric Surgery (PS), which requires candidates to develop a strong and research-oriented curriculum vitae. Although some objective factors of matriculation are known, factors for the interview selection and ranking per the program directors (PDs) have not been reviewed in over a decade. Methods : A web-based survey of US and Canadian PS program directors (PDs) (n=58) was used to evaluate a comprehensive list of factors in the selection criteria for PS fellowships. A mix of dichotomous, ranking, five-point Likert scale, and open-ended questions evaluated applicant characteristics, ABSITE scores, research productivity, interview day, and rank order criteria. Results : Fifty-five programs responded to the survey for a 95% participation rate. PDs desired an average of two years in dedicated research and weighted first authorship and total number of publications heavily. Only 38% of programs used an ABSITE score cutoff for offering interviews; however, the majority agreed that an overall upward trend was important. Quality letters of recommendation, especially from known colleagues, carried weight when deciding to offer interviews. Interview performance, being a team player, observed interpersonal interactions, perceived operative skills and patient care, and leadership were some of the notable factors when finalizing rank lists. Conclusions : A multitude of factors define a successful matriculant, including quality of letters of recommendation, quality and quantity of publications, supportive phone calls, observed interactions, interview performance, perceptions of being team player with leadership skills as well as perceptions of good operative skills and patient care.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla...

OBJECTIVE: Long-Segment Hirschsprung Disease (LSHD) differs clinically from short-segment disease. This review article critically appraises current literature on the definition, management, outcomes, and novel therapies for patients with LSHD. METHODS: Four questions regarding the definition, management, and outcomes of patients with LSHD were generated. English-language articles published between 1990 and 2018 were compiled by searching PubMed, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar. A qualitative synthesis was performed. RESULTS: 66 manuscripts were included in this systematic review. Standardized nomenclature and preoperative evaluation for LSHD are recommended. Insufficient evidence exists to recommend a single method for the surgical repair of LSHD. Patients with LSHD may have increased long-term gastrointestinal symptoms, including Hirschsprung-associated enterocolitis (HAEC), but have a quality of life similar to matched controls. There are few surgical technical innovations focused on this disorder. CONCLUSIONS: A standardized definition of LSHD is recommended that emphasizes the precise anatomic location of aganglionosis. Prospective studies comparing operative options and long-term outcomes are needed. Translational approaches, such as stem cell therapy, may be promising in the future for the treatment of long-segment Hirschsprung disease. LEVEL OF EVIDENCE: Level 3, 4

Background Motor vehicle collisions (MVCs) are a significant safety issue in the United States. Young children are disproportionally impacted by car accidents and suffer high rates of injuries and mortality. When used properly, car seats have been found to reduce the severity of injuries. However, individuals from low-income areas often do not have access to education or car seats compared to those in suburban or higher income areas. Therefore, the goal of the present study was to measure the effectiveness of a car seat program in an urban, Level I Pediatric Trauma Center on caregiver car seat knowledge. Methods Caregivers (N = 200) attended a single, one-hour car seat educational program with a Child Passenger Safety Technician (CPST). The sessions included educational and hands-on components, where caregivers were asked to complete a seven-item pre-post knowledge assessment. For completion of the course, caregivers received a car seat for their child. Results A paired t-test revealed that the workshop significantly increased caregiver knowledge from pre-post: t (199) = − 12.56, p d = 1.27. McNemar’s Chi-Square analyses displayed that caregivers increased in all knowledge categories (p Conclusions While caregivers in urban areas or in low-income areas may have less access to resources, hospital-led car seat courses can increase knowledge of proper car seat usage in these communities. These findings should be used to establish programs in hospitals in areas where these resources are not readily available to caregivers.

Alemany, JA, Pierce, JR, Bornstein, DB, Grier, TL, Jones, BH, and Glover, SH. Comprehensive physical activity assessment during U.S. Army Basic Combat Training. J Strength Cond Res XX(X): 000-000, 2021-Physical activity (PA) volume, intensity, and qualitative contextual information regarding activity type and loads carried are limited during U.S. Army Basic Combat Training (BCT). The purpose of this study was to characterize daily (05:00-20:00 hours) PA during BCT using a comprehensive approach. During 2 10-week BCT cycles (n = 40 trainees per cycle), pedometers, accelerometers, and direct observation were used to estimate daily step count, PA volume, and intensity. Physical activity intensity was categorized by metabolic equivalents (METs) such as "sedentary" (1-2 METs), "light" (2-3 METs), "moderate" (3-6 METs), or "vigorous" (≥6 METs). Daily PA data were analyzed longitudinally using linear mixed models, with significance set at p ≤ 0.05. The mean daily step count was 13,459 ± 4,376 steps, and the mean daily accelerometer-assessed PA volume and intensity were as follows: sedentary: 505 ± 98 minutes, light: 190 ± 78 minutes, moderate: 168 ± 51 minutes, and vigorous: 14 ± 14 minutes, with no differences between cycles for all measures (p > 0.50). Cumulative time on feet (∼50%) and sitting (20-25%) accounted for most daily activity types during both cycles. Trainees, on average, carried between 3 and 9 kg, and ≥9 kg, for 60% and 10% of the monitored day, respectively. Basic Combat Training's physical demands are high, where trainees achieved 1.7 to 2.7 times greater daily ambulation and 6 times the recommended weekly moderate-to-vigorous PA compared with civilian counterparts and performed weight-bearing load carriage for nearly half of the day. Basic Combat Training-associated PA may increase injury risk among trainees unaccustomed to arduous PA and exercise. Implementing national PA policies to improve physical fitness and facilitate acclimatization to BCT's high physical demands could reduce public health burdens and military nonreadiness.

IntroductionMilitary studies have investigated acute injuries associated with parachute jumps, but the literature does not address paratroopers’ cumulative microtraumatic (CMT) injury risk, nor does it compare injury risks between paratroopers and the rest of the military population. This study determined whether US active duty Army paratroopers experienced greater injury risks than their non-paratrooper soldier counterparts and whether their injuries cost more to treat suggesting greater injury severity.MethodsThis retrospective study evaluated electronic medical records (2016–2018) for 31 621 paratroopers and a randomly selected comparison group of 170 715 non-paratrooper soldiers. Analyses included univariate and multivariate regression to quantify odds of injuries associated with risk variables and additional descriptive statistics.ResultsParatroopers had a 57% increase in the odds of experiencing one or more injuries (OR=1.57, 95% CI: 1.52 to 1.62) after controlling for sex, race and age, with a greater proportion of acute injuries (OR=1.38, 95% CI: 1.34 to 1.42), relative to comparison group soldiers. Injury types proportionally higher among paratroopers included head trauma and shoulder injuries. Average injury cost among paratroopers was 13% lower than for non-paratroopers ($2470 vs $2830 per injury). Among both populations, acute injury costs were notably higher than for CMT injuries (paratroopers, $1710/$630; non-paratroopers, $1860/$880 per injury).ConclusionsParatroopers were more likely to incur injury, especially an acute injury, than non-paratroopers. However, paratroopers’ average injury costs were less. This may be due to higher return-to-duty motivations, fitness levels, and/or facility-specific cost of care. Future studies should investigate causes of injuries found to be proportionally higher among paratroopers.

Introduction: The aims of this study were to investigate the potential impact of age, sex and body mass index (BMI) upon the incidence of arrhythmias pre- and post- diving, and to identify the prevalence of left ventricular hypertrophy (LVH) in older recreational divers. Methods: Divers aged ≥ 40 years participating in group dive trips had ECG rhythm and echocardiograph recordings before and after diving. Arrhythmias were confirmed by an experienced human reader. LVH was identified by two-dimensional echocardiography. Weighted (0.5 fractional) values were used to account for participation by seven divers in 14 trips. Results: Seventy-seven divers undertook 84 dive trips and recorded 677 dives. Among divers with no pre-trip arrhythmias (n = 55), we observed that 6.5 (12%) recorded post-trip arrhythmias and the median increase was 1.0 arrhythmia. In divers with pre-trip arrhythmias, 14.5 had a median of 1.0 fewer post-trip arrhythmias, 2.0 had no change and 5.5 had a median of 16.0 greater. Age, but neither sex nor BMI, was associated with change in the number of arrhythmias before and after dive trips (P = 0.02). The relative risk for experiencing a change in the frequency of arrhythmias after a diver trip, was 2.1 for each additional 10 years of age (95% CI 1.1, 4.0). Of the 60 divers with imaging of their heart, five had left ventricular hypertrophy. Conclusions: We observed a higher than expected prevalence of arrhythmias. Divers with pre-trip arrhythmias tended to be older than divers without pre-trip arrhythmias (P = 0.02). The prevalence of LVH in our cohort was one quarter of that found post-mortem in scuba fatalities.

BACKGROUND: Pica is characterized as repeatedly eating or chewing a non-nutritious substance including, but not limited to ice, clay and dirt, starch, raw pasta, chalk, coal, paint, or paper. Pica symptoms can be intense and addiction-like and disrupt quality of life. It is strongly linked to iron deficiency. Since substantial iron loss occurs during blood donation, blood donors may be susceptible to development of pica behaviors. METHODS: We investigated demographic, clinical, hematological, and biochemical factors associated with pica using univariable and multivariable logistic regression analysis in a cohort of 11,418 racially diverse blood donors. Pica was defined by questionnaire responses as consuming at least 8 oz of ice daily and/or consumption of non-ice substances regardless of the amount and frequency. RESULTS: Pica was present in 2.2% of the donors. The sensitivity and specificity of pica in iron-deficient donors were 36% and 82%, respectively. Lower ferritin (p = .001), non-Asian race (p < .001), higher red cell distribution width (p < .001), younger age, and restless legs syndrome (p = .008) were independently associated with pica. Female sex is associated with iron deficiency but was not an independent predictor of pica suggesting that iron deficient males and females were equally susceptible to the development of pica behaviors. Donors with normal ferritin levels also reported pica, reinforcing the role of non-iron related factors in its presentation. CONCLUSIONS: We have identified demographic, clinical, and biochemical predictors of pica that help identify those most at risk for developing pica behaviors, and thereby assist in its clinical diagnosis and treatment.

Complicated urinary tract infection (cUTI) is a frequent cause of morbidity. In this multinational retrospective cohort study, we aimed to demonstrate risk factors for enterococcal UTI. Univariate and multivariate analyses of risk factors for enterococcal infection were performed. Among 791 hospitalized patients with cUTI, enterococci accounted for approximately 10% of cases (78/791). Risk factors for enterococcal UTI in multivariable analysis were male gender, age range of 55-75 years, catheter-associated UTI, and urinary retention. This information may assist treating physicians in their decision-making on prescribing empiric anti-enterococcus treatment to hospitalized patients presenting with cUTI and thus improve clinical outcomes.

Funder: Scottish Government; doi: https://doi.org/10.13039/100012095, Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.

Objectives Trains can cause severe injuries in pediatric patients requiring significant resource utilization. We sought to review train injuries in Pennsylvania to determine the burden of these injuries on the pediatric trauma system. Methods We queried the Pennsylvania Trauma Outcomes Study Database to identify patients younger than 18 years injured by trains between 2007 and 2016. Demographics, hospital course, outcomes, and resource utilization were reviewed. Results Thirty-five children from 17 Pennsylvania counties were included. Three counties accounted for 48.6% of injured children. The median age was 15.0 years, and most patients were White (60.0%) and male (77.1%). The median length of stay was 8.0 days and overall mortality 8.6%. Intensive care unit admission was required for 65.7%. The median Injury Severity and Functional Status at Discharge scores were 14.0 and 18.0, respectively. Major orthopedic injuries (fracture or amputation) were the most common (57.1%) followed by traumatic brain injury (45.7%), pneumothorax (14.3%), and solid organ injury (14.3%). Operative management was common with 65.7% undergoing surgery. Conclusions Injuries caused by trains can be severe and are most commonly orthopedic or traumatic brain injuries. Targeted safety interventions may be possible given the common mechanisms and geographic clustering of these injuries.

The most common congenital lung malformations are congenital pulmonary airway malformations and pulmonary sequestrations. Many surgeons advocate resection to prevent complications of infection, malignancy, and pneumothorax. The standard of care is lobectomy, but segmentectomy and embolization alone have been reported. These methods avoid the complications of lobectomy but are not widely practiced due to concerns about incomplete resection or involution of the lesion. We present a novel approach to the treatment of a pulmonary sequestration in a 7-month-old male using preoperative embolization followed by a sublobar pulmonary resection. The embolization clearly demarcated the affected lung intraoperatively, thereby facilitating complete removal of the lesion with a segmental lung resection rather than complete lobectomy.

BACKGROUND: Red blood cells (RBCs) derived from patients who receive testosterone replacement therapy (TRT) may be considered eligible for component production and transfusion. The aim of this study was to identify testosterone-dependent changes in RBC metabolism and to evaluate its impact on susceptibility to hemolysis during cold storage. STUDY DESIGN AND METHODS: We characterized stored RBCs from two cohorts of TRT patients who were matched with control donors (no TRT) based upon sex, age, and ethnicity. We further evaluated the impact of testosterone deficiency (orchiectomy) on RBC metabolism in FVB/NJ mice. RBC metabolites were quantified by ultra-high-pressure liquid chromatography-mass spectrometry. RBC storage stability was determined in RBC units from TRT and controls by quantifying storage, osmotic, and oxidative hemolysis. RESULTS: Orchiectomy in mice was associated with significant (P < 0.05) changes in RBC metabolism as compared with intact males including increased levels of acyl-carnitines, long-chain fatty acids (eg, docosapentaenoic acids), arginine, and dopamine. Stored RBCs from TRT patients exhibited higher levels of pentose phosphate pathway metabolites, glutathione, and oxidized purines (eg, hypoxanthine), suggestive of increased activation of antioxidant pathways in this group. Further analyses indicated significant changes in free fatty acids and acyl-carnitines in response to testosterone therapies. With regard to hemolysis, TRT was associated with enhanced susceptibility to osmotic hemolysis. Correlation analyses identified acyl-carnitines as significant modifiers of RBC predisposition to osmotic and oxidative hemolysis. CONCLUSIONS: These observations provide new insights into testosterone-mediated changes in RBC metabolome and biology that may impact the storage capacity and posttransfusion efficacy of RBCs from TRT donors.

OBJECTIVE: To test associations between grades 3 or 4 (severe) intraventricular hemorrhage (IVH) and single nucleotide polymorphisms (SNPs) associated with coagulation, inflammation, angiogenesis, and organ development in an exploratory study. STUDY DESIGN: Extremely low-birthweight (ELBW) infants enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network’s (NRN) Cytokines Study were included if they had cranial ultrasound (CUS) and genotyping data available in the NRN Anonymized DNA Repository and Database. Associations between SNPs and IVH severity were tested with multivariable logistic regression analysis. RESULT: One hundred thirty-nine infants with severe IVH and 687 infants with grade 1 or 0 IVH were included. One thousand two hundred seventy-nine SNPs were genotyped. Thirteen were preliminarily associated with severe IVH including five related to central nervous system (CNS) neuronal and neurovascular development. CONCLUSION: Genetic variants for CNS neuronal and neurovascular development may be associated with severe IVH in premature infants.

In 2018, 21 (41%) jurisdictions had begun reporting gender identity for sexually transmitted disease case notifications sent to the Centers for Disease Control and Prevention. Among jurisdictions with ≥70% of cases with reported gender identity and sex, 1.0% of primary and secondary syphilis cases were identified as transgender and 71% of transgender women with syphilis were concurrently coded as being male sex.

Introduction Necrotizing enterocolitis (NEC) causes significant neonatal morbidity. A subset of infants experience precipitous decline and death from fulminant-NEC (F-NEC). We sought to determine the effect of feeding practices on the development of this more virulent form of NEC. Materials and Methods Premature neonates developing Bell's stage II or III NEC between May 2011 and June 2017 were reviewed. Infants were stratified as having NEC or F-NEC, defined as NEC-totalis or NEC causing rapid decline and death within 72 hours. Risk factors extracted included demographics, gestational age, and weight at NEC diagnosis. Feeding data extracted included age at first feed, caloric density, type of feed (breast milk or formula), and whether full volume feeds were reached. Univariate analysis and multivariate analysis were performed. Results A total of 98 patients were identified, of which 80 were included. In total, 57 patients had NEC and 23 had F-NEC. Reaching full volume feeds was associated with F-NEC on both univariate and multivariate analysis (37.9 vs. 4.5%; odds ratio: 67, 95% confidence interval: 6.606–2041, p = 0.003). Infants developing F-NEC achieved full feeds earlier (22.5 vs. 19.8 days, p = 0.025) on univariate but not multivariate analysis. There was no difference in the rates of NEC and F-NEC among infants receiving breast milk (standard or fortified) or formula (standard or increased caloric density; p = 0.235). Conclusion Among premature neonates with NEC, reaching full volume feedings was associated with a nearly 70-fold increased risk of F-NEC. Assuming it was possible to predict an infant's development of NEC, alternative feeding regimens might reduce the risk of F-NEC in this population.

IntroductionFalls/near falls are the second leading cause of hospitalisation and outpatient visits among US Army soldiers. While numerous studies have evaluated fall-related or near fall-related injuries among elderly adults, few have evaluated this association among young adults. The objective of this study is to describe the characteristics and risk factors associated with fall-related or near fall-related injuries among male US Army soldiers.MethodsThis is a cross-sectional study of male US Army Airborne Division soldiers (n=5187). Electronic surveys captured demographic, lifestyle, physical training (PT), fitness and injury data during spring/summer of 2016. Multiple logistic regression was used to identify independent risk factors of fall-related or near fall-related injuries, adjusting for potential confounders.ResultsPrimary findings indicated that activities and risk factors associated with fall-related or near fall-related injuries among soldiers included younger age (≤35 years), holding a job that required minimal lifting activities, slower 2-mile run times and not running during personal PT.ConclusionsThe findings from this study suggest that male US Army soldiers and other physically active men may benefit from (1) obtaining and/or maintaining higher aerobic endurance and muscular strength, and (2) training focused on preventing fall-related injuries during PT, road marching and sports/recreational activities. Moreover, prevention strategies and education should further target younger soldiers (≤35 years old), as younger age is not modifiable.

Background Limb-threatening lower extremity traumatic injuries can be devastating events with a multifaceted impact on patients. Therefore, evaluating patient-reported outcomes (PROs) in addition to traditional surgical outcomes is important. However, currently available instruments are limited as they were not developed specific to lower extremity trauma patients and lack content validity. The LIMB-Q is being developed as a novel PRO instrument to meet this need, with the goal to measure all relevant concepts and issues impacting amputation and limb-salvage patients after limb-threatening lower extremity trauma. Methods This is a qualitative interview-based study evaluating content validity for the LIMB-Q. Patients aged 18 years and older who underwent amputation, reconstruction, or amputation after failed reconstruction were recruited using purposeful sampling to maximize variability of participant experiences. Expert opinion was solicited from a variety of clinical providers and qualitative researchers internationally. Preliminary items and scales were modified, added, or removed based on participant and expert feedback after each round of participant interviews and expert opinion. Results Twelve patients and 43 experts provided feedback in a total of three rounds, with changes to the preliminary instrument made between each round. One scale was dropped after round one, one scale was added after round two, and only minor changes were needed after round three. Modifications, additions and removal of items, instructions, and response options were made after each round using feedback gathered. Conclusion The LIMB-Q was refined and modified to reflect feedback from patients and experts in the field. Content validity for the LIMB-Q was established. Following a large-scale field test, the LIMB-Q will be ready for use in research and clinical care.

Background Cigarette smoking is a frequent habit across blood donors (approx. 13% of the donor population), that could compound biologic factors and exacerbate oxidant stress to stored red blood cells (RBCs). Study design and methods As part of the REDS-III RBC-Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell-Omics) study, a total of 599 samples were sterilely drawn from RBC units stored under blood bank conditions at Storage Days 10, 23, and 42 days, before testing for hemolysis parameters and metabolomics. Quantitative measurements of nicotine and its metabolites cotinine and cotinine oxide were performed against deuterium-labeled internal standards. Results Donors whose blood cotinine levels exceeded 10 ng/mL (14% of the tested donors) were characterized by higher levels of early glycolytic intermediates, pentose phosphate pathway metabolites, and pyruvate-to-lactate ratios, all markers of increased basal oxidant stress. Consistently, increased glutathionylation of oxidized triose sugars and lipid aldehydes was observed in RBCs donated by nicotine-exposed donors, which were also characterized by increased fatty acid desaturation, purine salvage, and methionine oxidation and consumption via pathways involved in oxidative stress-triggered protein damage-repair mechanisms. Conclusion RBCs from donors with high levels of nicotine exposure are characterized by increases in basal oxidant stress and decreases in osmotic hemolysis. These findings indicate the need for future clinical studies aimed at addressing the impact of smoking and other sources of nicotine (e.g., nicotine patches, snuff, vaping, secondhand tobacco smoke) on RBC storage quality and transfusion efficacy.

Background Severe lower extremity injuries are challenging to treat. The aspects of limb salvage and amputation most important to patients are not well-defined. This study's aim is to develop a conceptual framework for a patient-reported outcome instrument for lower extremity trauma patients, by defining issues and concepts most important to this patient population. Methods This is an interpretative description of transcripts collected from semistructured qualitative interviews at a single institution. High-energy lower extremity trauma patients were recruited by means of purposeful sampling to maximize variability. Thirty-three participant interviews were needed to reach content saturation. These participants were aged 19 to 79 years; 21 were men (63.6 percent); participation was after reconstruction [n= 15 (45.5 percent)], after amputation [n = 11 (33.3 percent)], or after amputation after failed reconstruction [n = 7 (21.2 percent)]. Interviews were recorded, transcribed, and coded line-by-line. Concepts were labeled with major and minor themes and refined through a process of constant comparison. Analysis led to the development of a conceptual framework and item pool to inform the development of a patient-reported outcome measure. Results In total, 2430 unique codes were identified and used to generate the conceptual framework covering 10 major themes: appearance, environment, finances, physical, process of care, prosthesis, psychological, sexual, social, and treatment. Conclusions This study establishes a comprehensive set of concepts, identifying what is most important to severe lower extremity trauma patients. These findings can be used to inform and focus research and clinical care, and provides the framework to develop a lower extremity trauma-specific patient-reported outcome instrument: the LIMB-Q.

Background The calcium-selective channel TRPV6 (transient receptor potential cation channel subfamily V member 6) is crucial for maternal-fetal calcium transport across the placenta. TRPV6 mutations have recently been associated with an antenatally severe under-mineralising skeletal dysplasia accompanied by postnatal biochemical abnormalities. This is the first post-mortem report in a patient with TRPV6 skeletal dysplasia. Case presentation The female infant had severe antenatal and postnatal skeletal abnormalities by 20 weeks gestation and was ventilator-dependent from birth. These skeletal abnormalities were apparent at an earlier gestational age than in previous reported cases and a more severe clinical course ensued. Biochemical and skeletal abnormalities, including bone density, improved postnatally but cardiac arrest at 4 months of age led to withdrawal of intensive care. Compound heterozygous TRPV6 variants (c.1978G > C p.(Gly660Arg) and c.1528C > T p.(Arg510Ter)) were identified on exome sequencing. Post-mortem identified skeletal abnormalities but no specific abnormalities in other organ systems. No placental pathology was found, multi-organ histological features reflected prolonged intensive care only. Post-mortem macroscopic examination indicated reduced thoracic size and short, pale and pliable ribs. Histological examination identified reduced number of trabeculae in the diaphyses (away from the growth plates), whereas metaphyses showed adequate mineralisation and normal number of trabeculae, but with slightly enlarged reactive chondrocytes, indicating post-natal skeletal growth recovery. Post-mortem radiological findings demonstrated improved bone density, improved rib width, healed fractures, although ribs were still shorter than normal. Long bones (especially humerus and femur) had improved from initial poorly defined metaphyses and reduced bone density to sharply defined metaphyses, prominent growth restart lines in distal diaphyses and bone-in-bone appearance along diaphyses. Conclusions This case provide bone histological confirmation that human skeletal development is compromised in the presence of TRPV6 pathogenic variants. Post-mortem findings were consistent with abnormal in utero skeletal mineralisation due to severe calcium deficit from compromised placental calcium transfer, followed by subsequent phenotypic improvement with adequate postnatal calcium availability. Significant skeletal recovery occurs in the early weeks of postnatal life in TRPV6 skeletal dysplasia.

Contains fulltext : 249882.pdf (Publisher’s version ) (Closed access) ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.

BACKGROUND RBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness. METHODS This is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness. RESULTS Blood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours. CONCLUSION Donor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products. FUNDING Funding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).

Background Currently there is no consensus on the management of patients with a concussion and negative computed tomography (CT) of the head. This study examined the necessity of admitting pediatric patients with concussive symptoms. The purpose of this study was to determine if pediatric patients evaluated in the emergency department (ED) for concussion with a negative head CT scan require routine hospital admission. Materials and methods A retrospective chart review of pediatric trauma patients admitted to the hospital for a concussion from 2010 to 2017 was conducted after IRB approval (1709005621). Only patients with a negative head CT were included. Demographic information, ED evaluation, and hospital course were reviewed. Results A total of 90 patients (Mage = 10 y; 72.2% male) were included in the analysis. The average Glasgow coma scale was 14.6 (range 9-15). Loss of consciousness was reported by 36.7% (n = 33) of patients. Reported symptoms included nausea/emesis in 35.5% (n = 32) and altered mental status in 40% (n = 36). Following admission, 94.4% of patients were discharged within 24 h of admission. Of the four patients (4.4%) that stayed longer than 24 h, only two hospitalizations were related to the concussion (inability to tolerate diet). One patient had a fever unrelated to the concussion and one stayed because of social issues. Average length of stay for these patients was 2.75 d (range 2-4 d). There was no difference in Glasgow coma scale in comparison to patients who were discharged within 24 h. Conclusions Although there are a large number of pediatric patients evaluated in the ED for concussion injuries, very few of these patients require any further care. Our study suggests that patients with concussion and a negative head CT who tolerate a diet can be safely discharged home.

PURPOSE The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

1205 Figure 1Respondents indicated which factors would have a positive influence on their likelihood of getting vaccinated against COVID-19;more than two-thirds of respondents indicated they would be more likely to pursue vaccination if they were presented with evidence of COVID-19 vaccine safety in lupus.[Figure omitted. See PDF]ConclusionsThese results indicate an opportunity for healthcare professionals and patient advocacy organizations to assuage unfounded patient concerns, such as vaccine interactions with medications or food allergies being a contraindication to COVID-19 vaccination, while reassuring patients that vaccine-triggered flares are rare.AcknowledgementWe would like to thank the Lupus Foundation of American for their partnership in this research.

OBJECTIVES To evaluate newborn pulse oximetry screening (POS) outcomes at a large community hospital and the impact of the recommended revised POS algorithm. METHODS A retrospective cohort study was performed to evaluate the results of POS in the well-infant nursery between 2012 and 2020. The POS results were obtained from an electronic platform. Chart review was completed for newborns with failed screens. The recommended revision to POS, no second rescreen, was applied to the data to evaluate screening outcomes. RESULTS Of the total 65 414 infants admitted to the well-infant nursery during this 8-year period, >99% (n = 64 780) received POS. Thirty-one infants failed POS (4.6 per 10 000 screened). All infants who failed POS were found to have a disorder, with 12 (39%) having critical congenital heart disease (CCHD), 9 (29%) having non-CCHD requiring further follow-up, and 10 (32%) having noncardiac conditions. One false-negative screen result was identified through the Maryland Department of Health Newborn Screening Follow-up Program. The positive predictive value of POS for those screened was 39% for CCHD, with a specificity of 99.97%. Eliminating the second rescreen in the POS algorithm would have resulted in an additional 5 newborns without CCHD failing POS, increasing the false-positive rate from 0.03% to 0.04%. CONCLUSIONS POS is an effective tool for identifying CCHD and secondary conditions. POS was successfully implemented with few missed screens and was highly specific. Elimination of the second rescreen in the pulse oximetry algorithm would have resulted in a minimal increase in false-positive results and faster evaluation of newborns with CCHD.

INTRODUCTION AND OBJECTIVE:Durability is an important consideration for any BPH treatment, including minimally invasive therapies. PUL durability has been demonstrated to 5 years in the LIFT pivota...

Aim To capture pandemic experiences of people with opioid use disorder (OUD) to better inform the programs that serve them. Design We designed, conducted, and analyzed semi-structured qualitative interviews using grounded theory. We conducted interviews until theme saturation was reached and we iteratively developed a codebook of emerging themes. Individuals with lived experience of substance use provided feedback at all steps of the study. Setting We conducted phone or in-person interviews in compliance with physical distancing and public health regulations in outdoor Vancouver parks or well-ventilated indoor spaces between June to September 2020. Participants Using purposive sampling, we recruited participants (n = 19) who were individuals with OUD enrolled in an intensive community outreach program, had visited one of two emergency departments, were over 18, lived within catchment, and were not already receiving opioid agonist therapy. Measurements We audio-recorded interviews, which were later transcribed verbatim and checked for accuracy while removing all identifiers. Interviews explored participants’ knowledge of COVID-19 and related safety measures, changes to drug use and healthcare services, and community impacts of COVID-19. Results One third of participants were women, approximately two thirds had stable housing, and ages ranged between 23 and 59 years old. Participants were knowledgeable on COVID-19 public health measures. Some participants noted that fear decreased social connection and reluctance to help reverse overdoses; others expressed pride in community cohesion during crisis. Several participants mentioned decreased access to housing, harm reduction, and medical care services. Several participants reported using drugs alone more frequently, consuming different or fewer drugs because of supply shortages, or using more drugs to replace lost activities. Conclusion COVID-19 had profound effects on the social lives, access to services, and risk-taking behaviour of people with opioid use disorder. Pandemic public health measures must include risk mitigation strategies to maintain access to critical opioid-related services.

While Escherichia coli is a common cause of urinary tract infections and pyelonephritis, there are few documented cases of extended-spectrum β-lactamase (ESBL)-producing and extensively drug-resistant (XDR) isolates from the community resulting in infection requiring hospitalization, especially in individuals lacking risk factors. In the United States, exposure to ESBL-producing E. coli is typically nosocomial, whereas patients from developing countries often encounter ESBL-producing E. coli in the community through the consumption of contaminated food or water. Considering the rarity at which XDR E. coli isolates are encountered, there is also a scarcity of literature describing the successful treatment of ESBL-producing XDR E. coli. Here we present a case of an otherwise healthy 28-year-old female delicatessen worker infected with ESBL-producing and XDR E. coli without recent travel, antibiotic use, or healthcare contact, who required admission to the intensive care unit (ICU) with pyelonephritis and septic shock. Treatment with intravenous meropenem through a peripherally inserted central catheter (PICC) line at home was curative and follow up thereafter unremarkable. Given the patient’s lack of obvious exposure to and risk factors for an ESBL-producing XDR E. coli infection and the specific lack of risk factors for severe pyelonephritis requiring hospitalization, this case represents a unique addition to the literature and is of value to clinicians by describing successful treatment.

Introduction Priapism is the persistent and painful erection of the penis and is a common sickle cell disease (SCD) complication. Aim The goal of this study was to characterize clinical and genetic factors associated with priapism within a large multi-center SCD cohort in Brazil. Methods Cases with priapism were compared to SCD type-matched controls within defined age strata to identify clinical outcomes associated with priapism. Whole blood single nucleotide polymorphism genotyping was performed using a customized array, and a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms associated with priapism. Main Outcome Measure Of the 1,314 male patients in the cohort, 188 experienced priapism (14.3%). Results Priapism was more common among older patients (P = .006) and more severe SCD genotypes such as homozygous SS (P < .0001). In the genotype- and age-matched analyses, associations with priapism were found for pulmonary hypertension (P = .05) and avascular necrosis (P = .01). The GWAS suggested replication of a previously reported candidate gene association of priapism for the gene transforming growth factor beta receptor 3 (TGFBR3) (P = 2 × 10−4). Clinical Implications Older patients with more severe genotypes are at higher risk of priapism, and there is a lack of consensus on standard treatment strategies for priapism in SCD. Strengths & Limitations This study characterizes SCD patients with any history of priapism from a large multi-center cohort. Replication of the GWAS in an independent cohort is required to validate the results. Conclusion These findings extend the understanding of risk factors associated with priapism in SCD and identify genetic markers to be investigated in future studies to further elucidate priapism pathophysiology.

Background Dexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown. Methods We evaluated children with osteosarcoma (OS) on two Children’s Oncology Group trials with higher dose doxorubicin (375–600 mg/m2) preceded by dexrazoxane (10:1 dexrazoxane:doxorubicin dosing). They were evaluated after the minimum expected treatment time (METT), defined as 28 weeks. Cardiotoxicity was identified by echocardiography and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Second malignant neoplasm (SMN) data was collected. Results All children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness Z-scores (P Z-scores (P Z-scores were significantly smaller for girls (P P = 0.06). Girls had significantly smaller LV end-diastolic dimension Z-scores normalized to BSA (P Conclusions Dexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity. Trial registrations ClinicalTrials.gov: NCT00003937 (P9754) registered 1 Nov 1999, and NCT00023998 (AOST0121) registered 13 Sept 2001.

Policy actors design and implement targeted interventions to eliminate disparities that exist between groups. Although necessary for achieving health equity, the use of targeting as a policy tool carries the potential for political backlash and social debate, which may influence whether and how policy actors use it. In this research, the authors examine policy actor perceptions regarding the use of targeting in the implementation of health policy. The authors conduct elite interviews with policy actors to better understand their work to design and implement interventions to address health disparities. Findings identify key tensions and trade-offs faced by policy actors related to targeting and reveal sociopolitical influences that shape whether and how targeted programs are considered, who receives them, and by what means they are delivered. The authors discuss the implications of the findings for the use of targeting and related marketing practices by policy actors to address health disparities and other significant public health concerns.

Introduction: This study expands results from recent prostatic urethral lift (PUL) clinical trials by examining outcomes within a large unconstrained multicenter data set. Methods: Retrosp...

Objective Clinical trials, prospective research studies on human participants carried out by a distributed team of clinical investigators, play a crucial role in the development of new treatments in health care. This is a complex and expensive process where investigators aim to enroll volunteers with predetermined characteristics, administer treatment(s), and collect safety and efficacy data. Therefore, choosing top-enrolling investigators is essential for efficient clinical trial execution and is 1 of the primary drivers of drug development cost. Materials and Methods To facilitate clinical trials optimization, we propose DeepMatch (DM), a novel approach that builds on top of advances in deep learning. DM is designed to learn from both investigator and trial-related heterogeneous data sources and rank investigators based on their expected enrollment performance on new clinical trials. Results Large-scale evaluation conducted on 2618 studies provides evidence that the proposed ranking-based framework improves the current state-of-the-art by up to 19% on ranking investigators and up to 10% on detecting top/bottom performers when recruiting investigators for new clinical trials. Discussion The extensive experimental section suggests that DM can provide substantial improvement over current industry standards in several regards: (1) the enrollment potential of the investigator list, (2) the time it takes to generate the list, and (3) data-informed decisions about new investigators. Conclusion Due to the great significance of the problem at hand, related research efforts are set to shift the paradigm of how investigators are chosen for clinical trials, thereby optimizing and automating them and reducing the cost of new therapies.

Background Cervical spine injuries (CSI) are rare within the pediatric population. Due to the significant consequences of missed CSI, children are often imaged excessively. In an attempt to decrease imaging of the cervical spine in children, we reviewed abnormal cervical radiographs (XR) to determine if the diagnosis of CSI could be made using a single-lateral cervical radiograph (LAT). Furthermore, we reviewed cervical computed tomography (CT) and magnetic resonance imaging (MRI) to ensure there were no missed CSI. Methods Electronic medical records of trauma patients treated at a Level I Pediatric Trauma Center with abnormal XR findings followed by confirmatory CT or MRI between 2012 and 2017 were reviewed. All abnormal imaging on XR was compared with the LAT. In addition, all abnormal CTs and MRIs were reviewed to ensure there were no false negative XR. Results A total of 3,735 XR were performed with 26 abnormal interpretations. All bony CSI were visualized on LAT. Confirmatory imaging found 13 (50%) were false positive and 13 (50%) were true positive. Secondary analysis of CT identified 12 injuries with prior XR; 8 of 12 LAT identifying the injury and 4 of 12 false positive on CT. Secondary analysis of MRI identified nine injuries with prior XR; 5 of 9 LAT identifying the injury. The four false-negative reads on MRI were ligamentous injuries. Conclusion Radiographs are commonly performed when evaluating CSI. In our population, initial assessment with a single LAT was equivalent to a multiple view XR. On secondary review, the only false-negative LAT reports were due to ligamentous injuries. This data suggests limiting exposure to LAT would accomplish the goal of reducing imaging without missing bony CSI and when ligamentous injury is suspected MRI should be the confirmatory study rather than CT. Level of evidence Diagnostic Test, level III.

The incidence of choledocholithiasis is increasing. The diagnosis of common bile duct (CBD) obstruction is based on abnormal CBD size. Establishing norms for CBD size in children would improve diagnostic accuracy. We analyzed ultrasounds (US) to determine normal pediatric CBD size based on age and then validated this against patients with choledocholithiasis.A retrospective review was conducted for children less than 21 years of age with US defined CBD size. Patients were stratified into age groups by ANOVA statistical analysis. Secondary analysis included patients with confirmed choledocholithiasis in comparison to the normal cohort.A total of 778 patients had US without pathology. Group 1 (1 year) had a mean CBD of 1.24±0.54 mm, group 2 (1-10 years) 1.97±0.71 mm, and group 3 (10 years) 2.98±1.17 mm, p0.05. Fourteen additional patients were found to have choledocholithiasis with a mean CBD size of 8.1 mm. All patients with choledocholithiasis had CBD sizes outside of our normal range, but only 50% of patients had enlarged CBD size based on adult normal range of values.Normal CBD size in children is less than a normal adult patient. More accurate normal values will aid in determining if a child needs further evaluation for possible obstruction of the CBD.diagnostic Level of evidence: III.

Background Treatment of the neonate with long gap esophageal atresia (LGEA) is one of the most challenging scenarios facing pediatric surgeons today. Contributing to this challenge is the variability in case definition, multiple approaches to management, and heterogeneity of the reported outcomes. This necessitates a clear summary of existing evidence and delineation of treatment controversies. Methods The American Pediatric Surgical Association Outcomes and Evidence Based Practice Committee drafted four consensus-based questions regarding LGEA. These questions concerned the definition and determination of LGEA, the optimal method of surgical management, expected long-term outcomes, and novel therapeutic techniques. A comprehensive search strategy was crafted and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to identify, review and report salient articles. Results More than 3000 publications were reviewed, with 178 influencing final recommendations. In total, 18 recommendations are provided, primarily based on level 4–5 evidence. These recommendations provide detailed descriptions of the definition of LGEA, treatment techniques, outcomes and future directions of research. Conclusions Evidence supporting best practices for LGEA is currently low quality. This review provides best recommendations based on a critical evaluation of the available literature. Based on the lack of strong evidence, prospective and comparative research is clearly needed. Type of study Treatment study, prognosis study and study of diagnostic test. Level of evidence Level II–V.

Background This study aimed to characterize the physiological demands of working dives on volunteer divers at a public aquarium in the USA. Aims To estimate the workloads associated with volunteer dives in a US aquarium. Methods Participants completed a medical and diving history questionnaire. Measurements included blood pressure before and after diving and continuous ECG (Holter) monitoring during diving. Dive profiles were recorded using loggers. Mean workload was estimated from total air consumption. Results Twenty-seven divers recorded 49 air dives over 5 days. Two-thirds were male and ages ranged from 40 to 78 years. Typically, each diver made two dives with a 30-60 min surface interval. Mean heart rate while diving was 100 beats per minute (bpm). Mean estimated workload during the dives recorded during this study was 5.8 metabolic equivalents (METS), with a range from 4.1 to 10.5. The highest mean recorded heart rate was 120 bpm over 40 min, vacuuming the floor in the shark exhibit. Conclusions Given the mean age of this sample and the prevalence of cardiovascular risk factors (body mass index, high cholesterol and hypertension), it may be prudent for aquariums to regularly monitor SAC/kg and heart rate in volunteer divers, to identify which tasks require the highest workload intensity. Divers with existing cardiovascular risk factors might then be employed in dives with lighter workloads. In conclusion, volunteer dives at this aquarium required a mean workload intensity that was described by recreational divers as moderate. The highest workload, at 10 METS for 23 min, would be considered by many recreational divers as exhausting.

Introduction The probability of surviving a cardiac arrest remains low. International resuscitation guidelines state that extracorporeal cardiopulmonary resuscitation (ECPR) may have a role in selected patients suffering refractory cardiac arrest. Identifying these patients is challenging. This project systematically reviewed the evidence comparing the outcomes of ECPR over conventional-CPR (CCPR), before examining resuscitation-specific parameters to assess which patients might benefit from ECPR. Method Literature searches of studies comparing ECPR to CCPR and the clinical parameters of survivors of ECPR were performed. The primary outcome examined was survival at hospital discharge or 30 days. A secondary analysis examined the resuscitation parameters that may be associated with survival in patients who receive ECPR (no-flow and low-flow intervals, bystander-CPR, initial shockable cardiac rhythm, and witnessed cardiac arrest). Results Seventeen of 948 examined studies were included. ECPR demonstrated improved survival (OR 0.40 (0.27–0.60)) and a better neurological outcome (OR 0.10 (0.04–0.27)) over CCPR during literature review and meta-analysis. Characteristics that were associated with improved survival in patients receiving ECPR included an initial shockable rhythm and a shorter low-flow time. Shorter no-flow, the presence of bystander-CPR and witnessed arrests were not characteristics that were associated with improved survival following meta-analysis, although the quality of input data was low. All data were non-randomised, and hence the potential for bias is high. Conclusion ECPR is a sophisticated treatment option which may improve outcomes in a selected patient population in refractory cardiac arrest. Further comparative research is needed clarify the role of this potential resuscitative therapy.

Background Self-reported injury data are frequently used in epidemiologic investigations. These data provide useful information about the activities and mechanisms of injuries because injury cause-coding is often not required for outpatient medical visits. Objectives The purpose of this evaluation is to determine the accuracy of self-reported military injuries when compared to injuries in outpatient medical records. Method Injuries reported by survey were compared to diagnoses for injuries (International Classification of Diseases (ICD-9-CM 800–999)) and injury-related musculoskeletal disorders (selected ICD-9-CM 710–739) obtained from medical records. Self-reported injury responses from military personnel were matched to diagnoses by date and body part. A new methodology for including secondary matching body parts was proposed and implemented. Results Infantry Soldiers (n = 5490) completed surveys that requested details about their most recent injury. About one-quarter (24%, n = 1336) reported injuries on the survey and had an injury diagnosis in their medical record in a six month period. Seventy-five percent of the self-reported injuries (n = 996 of 1336) were confirmed by medical records with a date match within 3 months and an identical or nearby body part. Common self-reported injuries were ankle sprains (10%), knee sprains (9%), lower back strains (4%), shoulder strains (3%), and lower back pain (3%). Conclusions A high percentage of self-reported injuries were accurate when compared with medical records, substantiating the use of survey data for the evaluation of injury outcomes. This is the first effort to validate self-reported injuries and musculoskeletal disorders with medical records in a large military population.

BACKGROUND The major aims of the RBC-Omics study were to evaluate the genomic and metabolomic determinants of spontaneous and stress-induced hemolysis during RBC storage. This study was unique in scale and design to allow evaluation of RBC donations from a sufficient number of donors across the spectrum of race, ethnicity, sex, and donation intensity. Study procedures were carefully piloted, optimized, and controlled to enable high-quality data collection. METHODS The enrollment goal of 14,000 RBC donors across four centers, with characterization of RBC hemolysis across two testing laboratories, required rigorous piloting and optimization and establishment of a quality assurance (QA) and quality control (QC) program. Optimization of WBC elution from leukoreduction (LR) filters, development and validation of small-volume transfer bags, impact of manufacturing and sample-handling procedures on hemolysis parameters, and testing consistency across laboratories and technicians and over time were part of this quality assurance/quality control program. RESULTS LR filter elution procedures were optimized for obtaining DNA for analysis. Significant differences between standard and pediatric storage bags led to use of an alternative LR-RBC transfer bag. The impact of sample preparation and freezing methods on metabolomics analyses was evaluated. Proficiency testing monitored and documented testing consistency across laboratories and technicians. CONCLUSION Piloting and optimization, and establishment of a robust quality assurance/quality control program documented process consistency throughout the study and was essential in executing this large-scale multicenter study. This program supports the validity of the RBC-Omics study results and a sample repository that can be used in future studies.

Background Many aspects of transfusion medicine are affected by genetics. Current single-nucleotide polymorphism (SNP) arrays are limited in the number of targets that can be interrogated and cannot detect all variation of interest. We designed a transfusion medicine array (TM-Array) for study of both common and rare transfusion-relevant variations in genetically diverse donor and recipient populations. Study design and methods The array was designed by conducting extensive bioinformatics mining and consulting experts to identify genes and genetic variation related to a wide range of transfusion medicine clinical relevant and research-related topics. Copy number polymorphisms were added in the alpha globin, beta globin, and Rh gene clusters. Results The final array contains approximately 879,000 SNP and copy number polymorphism markers. Over 99% of SNPs were called reliably. Technical replication showed the array to be robust and reproducible, with an error rate less than 0.03%. The array also had a very low Mendelian error rate (average parent-child trio accuracy of 0.9997). Blood group results were in concordance with serology testing results, and the array accurately identifies rare variants (minor allele frequency of 0.5%). The array achieved high genome-wide imputation coverage for African-American (97.5%), Hispanic (96.1%), East Asian (94.6%), and white (96.1%) genomes at a minor allele frequency of 5%. Conclusions A custom array for transfusion medicine research has been designed and evaluated. It gives wide coverage and accurate identification of rare SNPs in diverse populations. The TM-Array will be useful for future genetic studies in the diverse fields of transfusion medicine research.

Background Readmissions of infants younger than 28 days back into hospital are highly undesirable. It is upsetting for the families and puts babies at risk of hospital acquired infection. We have subjectively noted an increase in readmissions, so decided to research the number of readmissions and reflect on the factors associated with these Objectives To study the number of readmissions in infants under 28 days into the paediatric wards, and to see whether there has been an increase compared to 2019. To compare the data between the hospitals in our region. Methods The project was done as a retrospective study in 3 separate hospitals in Northern Ireland- Antrim Area Hospital, Craigavon Area Hospital and the Royal Belfast Hospital for Sick Children (RBHSC). We looked at the neonatal readmissions in infants under 28 days of age, we excluded infants needing intensive care after birth. The timeline we studied was between 1st April and 1st July in 2020, which was the height of the first wave of the Coronavirus pandemic in Northern Ireland. We looked at the main reason for readmission in each infant, comparing the data with the readmission rates and causes in 2019. We also looked at the NIMATS documents of the infants who were readmitted to establish their length of stay in the postnatal ward before discharge. Results Overall, the number of neonatal readmissions varied among the three hospitals studied. In Craigavon Area Hospital, the total number of readmissions was 50 in 2020, and 40 in 2019. This signifies a 20% increase in neonatal readmissions. In Antrim Area Hospital, the total number of neonatal readmissions was 46 in 2020, compared to 62 in 2019. The RBHSC, the tertiary centre, also noted a decrease of neonatal readmissions, from 37 in 2019 to 25 in 2020. In regard to the length of postnatal ward stay, in all of the hospitals studied, it was reduced in 2020. In Antrim hospital, the mean length of stay in postnatal ward in the infants needing readmitted went from 44.3 hours in 2020, to 37.5 hours in 2019. In Craigavon, the mean length of stay in postnatal ward was 44.7 hrs in 2019, compared to 38.5 hrs in 2020. In the RBHSC, the mean length of stay was 45.2 in 2019 and reduced to 29.1 hrs in 2020. The leading cause of readmissions was jaundice in both Craigavon Area hospital and Antrim Area hospital in 2020 and 2019. Conclusions It was interesting to see such variation in neonatal readmissions among three hospitals in the same country. There has been an overall increase of readmissions for infants with poor feeding, which could be explained by less support available for mums during the pandemic. This could have been due to overall shorter stay in the postnatal ward, dads not being allowed into the postnatal ward, and less frequent midwife visits. A decrease of conditions such as bronchiolitis could be explained by less mixing of newborn infants with older children.

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge–Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13–1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03–1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10–2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20–1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17–1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92–1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.

[Background] Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality., [Methods] This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy., [Results] Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens., [Conclusions] In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.