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Objective: Nasal Intermittent Positive Pressure Ventilation (NIPPV) is an effective therapy for infants in respiratory distress. We here report the safety of a novel, low-cost, non-electric bubble NIPPV device in comparison with bubble NCPAP., Study Design: At Paramitha Children's Hospital (Hyderabad, India), preterm (n = 60) neonates with moderate respiratory distress were pragmatically allocated to bubble NCPAP (5-8 cm H 2 O) or bubble NIPPV (P high 8-12 cm H 2 O/P low 5-8 cm H 2 O) based on staff and equipment availability. Primary outcomes to assess safety included clinically relevant pneumothorax, nasal septal necrosis, or abdominal distention., Results: One patient in each arm developed minor nasal septal injury (grade 3 on NCPAP, grade 2 on NIPPV); no patients in either arm developed a clinically significant pneumothorax or abdominal distention., Conclusion: The similar rates of nasal septal injury, pneumothorax and abdominal distention suggest that bubble NIPPV has a similar safety profile as bubble NCPAP for preterm infants in respiratory distress., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Acute Bilirubin Encephalopathy (ABE) is common in Nigeria. Parents' inability to recognize jaundice and delays in seeking care are significant barriers to its prevention., Methods: We compared associations of (1) interactive antenatal maternal jaundice instruction with postnatal reinforcement, (2) standard postnatal instruction, and (3) no maternal instruction with the incidence of ABE among 647 jaundice admissions stratified for risk factors identified in initial descriptive analysis., Results: Eighty-three (83/647;12.8%) admissions developed ABE including eleven jaundice-related deaths. ABE was present at admission in 20/22 (90.9%) if mothers received no jaundice instruction and no antenatal care, 42/182 (23.1%) if received antenatal care but no instruction, 16/95 (16.8%) if received postnatal instruction only, and 4/337 (1.2%) if mothers received both antenatal and postnatal instruction (p < .001). ABE was highly associated with out-of-hospital delivery, number of antenatal clinic visits, and birth attendant, but these risks were mitigated by antenatal/postnatal instruction. Admission rates with bilirubin levels below treatment guidelines (12 mg/dL) were higher following instruction (30.7%) than with no instruction (14.4%). Limiting subjects to those meeting admission criteria increased ABE rates in all groups without altering conclusions., Conclusion: Interactive antenatal instruction with postnatal reinforcement resulted in timely care seeking and a lower incidence of ABE., Impact: Empowering mothers to participate in neonatal jaundice management is critical in low-income countries where jaundice monitoring and follow up are unreliable. Instructing mothers about jaundice in antenatal clinics with postnatal reinforcement is more effective than standard postpartum instruction in facilitating jaundice detection, timely care seeking, and lowering the incidence of acute bilirubin encephalopathy (ABE). Antenatal training also mitigates risks for ABE associated with out-of-hospital deliveries, limited antenatal care, and unskilled birth attendants., Impact: Adding structured jaundice instruction in antenatal clinics could greatly reduce bilirubin induced brain injury in countries where ABE is common., (© 2023. The Author(s).)

An ability to effectively self-manage medications is the result of several factors influencing a person's decision to take medications. The need for new approaches to medication self-management are evident in the persistent trends of ineffective medication use and unfortunate consequences, referred to as drug-related morbidity and mortality. Fortunately, pioneering initiatives have emerged to reshape our approach for developing a rational organizational paradigm so that patients can confidently self-manage medications. Favorable outcomes of studies pertaining to the delivery of comprehensive medication therapy management services within the practice of pharmaceutical care prompts the question, 'Can patients and family members apply a consistent and systematic 4-step pharmacotherapy assessment process to better organize their decision-making and confidence in medication self-management?' To answer this question an Effective Medication Self-Management Toolkit based on this 4-step process, and a Medication Management Self-efficacy Checklist, were developed and evaluated for feasibility, acceptability, and internal consistency reliability. The first evaluation established the preliminary acceptability and feasibility of the toolkit using a convenience sample of 39 residents of independent living facilities in focus group sessions. All participants indicated they perceive that the 4-step process can help individuals successfully self-manage medications. At the conclusion of the focus group sessions, all 39 participants completed the 7-item post-session checklist. This paper presents the second evaluation to establish the internal consistency reliability of the toolkit's Medication Management Self-efficacy Checklist using Cronbach's alpha. There was good internal consistency of the self-efficacy checklist with a Cronbach's alpha value of 0.82. This investigation of a novel approach for applying the 4-step pharmacotherapy assessment process by patients suggests that the medication self-efficacy checklist provides a reliable and useful measure of a patient's confidence in self-managing medications., (© Individual authors.)

Background: Severe adolescent idiopathic scoliosis (AIS) can be treated with instrumented fusion, but the number of anchors needed for optimal correction is controversial., Methods: We conducted a multicenter, randomized study that included patients undergoing spinal fusion for single thoracic curves between 45° and 65°, the most common form of operatively treated AIS. Of the 211 patients randomized, 108 were assigned to a high-density screw pattern and 103, to a low-density screw pattern. Surgeons were instructed to use ≥1.8 implants per spinal level fused for patients in the high-implant-density group or ≤1.4 implants per spinal level fused for patients in the low-implant-density group. The primary outcome measure was the percent correction of the coronal curve at the 2-year follow-up. The power analysis for this trial required 174 patients to show equivalence, defined as a 95% confidence interval (CI) within a ±10% correction margin with a probability of 90%., Results: In the intention-to-treat analysis, the mean percent correction of the coronal curve was equivalent between the high-density and low-density groups at the 2-year follow-up (67.6% versus 65.7%; difference, -1.9% [95% CI: -6.1%, 2.2%]). In the per-protocol cohorts, the mean percent correction of the coronal curve was also equivalent between the 2 groups at the 2-year follow-up (65.0% versus 66.1%; difference, 1.1% [95% CI: -3.0%, 5.2%]). A total of 6 patients in the low-density group and 5 patients in the high-density group required reoperation (p = 1.0)., Conclusions: In the setting of spinal fusion for primary thoracic AIS curves between 45° and 65°, the percent coronal curve correction obtained with use of a low-implant-density construct and that obtained with use of a high-implant-density construct were equivalent., Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H763 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: Despite the critical role that quantitative scientists play in biomedical research, graduate programs in quantitative fields often focus on technical and methodological skills, not on collaborative and leadership skills. In this study, we evaluate the importance of team science skills among collaborative biostatisticians for the purpose of identifying training opportunities to build a skilled workforce of quantitative team scientists., Methods: Our workgroup described 16 essential skills for collaborative biostatisticians. Collaborative biostatisticians were surveyed to assess the relative importance of these skills in their current work. The importance of each skill is summarized overall and compared across career stages, highest degrees earned, and job sectors., Results: Survey respondents were 343 collaborative biostatisticians spanning career stages (early: 24.2%, mid: 33.8%, late: 42.0%) and job sectors (academia: 69.4%, industry: 22.2%, government: 4.4%, self-employed: 4.1%). All 16 skills were rated as at least somewhat important by > 89.0% of respondents. Significant heterogeneity in importance by career stage and by highest degree earned was identified for several skills. Two skills ("regulatory requirements" and "databases, data sources, and data collection tools") were more likely to be rated as absolutely essential by those working in industry (36.5%, 65.8%, respectively) than by those in academia (19.6%, 51.3%, respectively). Three additional skills were identified as important by survey respondents, for a total of 19 collaborative skills., Conclusions: We identified 19 team science skills that are important to the work of collaborative biostatisticians, laying the groundwork for enhancing graduate programs and establishing effective on-the-job training initiatives to meet workforce needs., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023.)

The fact that nearly one-half of patients take medications differently than as prescribed, combined with the predisposition of older persons to adverse events, suggests a need for new strategies supporting medication self-management for older persons. This pilot study describes the development, acceptability and feasibility of a novel toolkit approach focusing on a systematic 4-step process for ensuring medication appropriateness. A preliminary qualitative assessment of the toolkit's acceptability and feasibility was carried out using a convenience sample of 39 residents aged 62-97 years in two senior living facilities convened in focus groups. A facilitator guided participants through discussions of the 4-step process. All participants indicated they perceive that the toolkit's systematic 4-step process can help older persons successfully self-manage medications. The most common medication use challenges cited by participants were related to effectiveness (35%), followed by intended medical use (27%), safety (23%), and ability to take medications (15%). This preliminary investigation suggests that older adults resonate with use of this 4-step process to confidently self-manage medications and find it feasible and acceptable to use in assessing the appropriateness of their medications. More research is needed to establish the reliability and validity of this toolkit with more diverse populations of older adults., Competing Interests: Declaration of Competing Interest The authors declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Haiti remains a principal placement country for intercountry adoptees to the United States. This project reports the health status of children adopted from Haiti arriving to the U.S. and compares them to intercountry adoptees from other regions., Methods: A retrospective chart review was conducted of adoptees placed in the U.S. from Haiti (n=87), age and sex matched with intercountry adoptees placed in the U.S. from Asia (n=87) and Latin America (n=87) between January 2010 and November 2019. Data on immunization status, contagious diseases, and nutrition and growth were analyzed via linear, logistic, and multinomial regression., Results: After adjusting for age, sex, and standardized height, children adopted from Haiti, compared to adoptees from Latin America and Asia, demonstrated a lack of immunity to hepatitis B (OR=5.89;6.87), increased immunity to hepatitis A (OR=0.38;0.30), infection by two or more parasites (OR=8.43;38.48), high lead levels (OR=23.79;7.04), and anemia (OR=15.25;9.18). Unexpectedly, children adopted from Haiti had greater standardized height (-1.28 vs. -1.82 and -2.13) and standardized weight (-0.32 vs. -0.57 and -1.57) than their counterparts from Latin America and Asia., Conclusions: Children adopted from Haiti face complex medical challenges undoubtedly related to the country's low socioeconomic status (SES) and the impact of recurrent natural disasters and governmental neglect on public health infrastructure. Appropriate care is critical in preventing and avoiding transmission of infectious diseases in adoptees and family members. The high incidence of anemia and elevated lead levels may further exacerbate the developmental effects of early institutional deprivation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lower respiratory tract infections (LRTIs) are the leading cause of death in young children globally. Most of the global burden of mortality from LRTIs occurs in low-resource settings (LRSs), where obtaining and maintaining respiratory support devices such as commercial bubble continuous positive airway pressure (bCPAP) can be prohibitive. Low-cost bCPAP devices exist, such as the homemade WHO-style bCPAP design, but the safety of this design has been called into question. Based on our team's experience with homemade bCPAP, the side effects of the high pressures described in recent studies are not commonly encountered. Therefore, we sought feedback via an international survey about various complications including pneumothorax from practitioners in LRSs who use two forms of homemade bCPAP. In our qualitative survey, we did not find a convincing pattern in the recall of complications between commercial bCPAP and homemade bCPAP with narrow- or wide-bore expiratory limb in neonates or older children.

Children in foster care have complex health concerns that often interplay with their childhood experiences, environment and access to care. Studies suggest that foster care youth are at an increased risk for mental health disorders and physical disabilities. Although traditionally associated with insufficient bone development, the implications of vitamin D deficiency are broadening to encompass behavioral, neurodevelopmental, and psychological phenomena. Due to its association with diet, prenatal factors, and the prevalence of nutrition related deficiencies in foster care patients, we hypothesize that foster care patients exhibit lower levels of total 25-hydroxy vitamin D [25(OH)D] than the general pediatric population. A retrospective cross-sectional chart review of foster care patients and similar-aged non-fostered controls screened for vitamin D deficiency was conducted between January 2013 and May 2018 (n=407). Twenty-five (OH)D levels were comparable between foster care children and controls (p=0.771). A univariate analysis of risk factors within the foster care group found that higher BMI, older age, ADHD, and number of transitions was associated with decreased levels of 25(OH)D. Recognition and treatment of low 25(OH)D in foster care patients with specific risk factors may serve as an adjunct for meeting their medical and psychosocial needs., Competing Interests: Conflict of Interest The authors declare no competing financial interests.

Objective: To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs)., Study Design: Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared., Results: The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05)., Conclusions: In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: This study sought to determine pharmacy students' self-assessment of their level of competency in specified global health statements across various schools. It also evaluated attributes associated with competency and perception of importance, as well as explored students' perspectives on how best to incorporate global health content into pharmacy education., Methods: Cross-sectional survey administered online to pharmacy students from three pharmacy schools in the United States., Results: The self-assessed competency of pharmacy students in global health topic areas was low. Current or prior exposures outside of the PharmD curriculum to the global health content presented in the survey were significant indicators of self-assessed competency scores. Within individual participating schools, demographic characteristics such as gender, age category, speaking a non-English language, and progression through the PharmD curriculum were also significantly associated with competency scores reported. Most respondents (96%) agreed that relevant global health education should be incorporated into the pharmacy curriculum., Conclusions: Pharmacy students generally perceive global health competencies to be of great importance in practice, but acknowledge their deficiencies in this area. The current burden of global health education at the schools surveyed relies on individual student experience rather than curricular support. Ensuring that future pharmacists understand their role in global health teams and are able to achieve the necessary level of competency to function in interdisciplinary initiatives will require more strategic incorporation of relevant content into the curriculum., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial., Methods: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2-5-year-olds with FASD. Participants include 31 children (16 placebo; 15 choline) seen 4 years after trial completion. The mean age at follow-up was 8.6 years. Diagnoses were 12.9% fetal alcohol syndrome (FAS), 41.9% partial FAS, and 45.1% alcohol-related neurodevelopmental disorder. The follow-up included measures of intelligence, memory, executive functioning, and behavior., Results: Children who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions., Conclusions: These data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories., Trial Registration: ClinicalTrials.Gov #NCT01149538; Registered: June 23, 2010; first enrollment July 2, 2010.

Background: Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia., Methods: We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 μmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%., Findings: Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 μW/cm 2 /nm (IQR 21·4-56·4) in the FSPT group and 50·4 μW/cm 2 /nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates., Interpretation: FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants., Funding: Thrasher Research Fund and National Center for Advancing Translational Sciences., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Scoliosis in patients with neurofibromatosis type I (NF1) can manifest as dystrophic or nondystrophic curves. Dystrophic scoliosis is rapidly progressive, rendering treatment challenging. Radiographic characteristics have been reported to predict dystrophic scoliosis, but their reliability and predictive value have not been well described. The purpose of this study is to assess the interobserver reliability for eight radiographic characteristics of dystrophic scoliosis and to evaluate the sensitivity and specificity of these characteristics relative to the gold standard of a definitive clinical diagnosis., Methods: Spine radiographs of 122 NF1 patients from multiple institutions were graded by five spine surgeons as dystrophic or nondystrophic, based on eight radiographic characteristics of dystrophic modulation: rib penciling, vertebral rotation, scalloping, wedging, spindling of transverse processes, short sharp angular curve, widened interpedicular distance, and atypical location. The curves were classified by each submitting institution as dystrophic or nondystrophic based on clinical outcome. Interobserver reliability analysis was performed using Fleiss kappa., Results: For the 122 cases, the interrater agreement among the five readers for the diagnosis of dystrophic scoliosis was good at 0.61. The agreement for individual radiographic characteristic ranged from 0.62 for wedging to 0.14 (poor) for scalloping. Surgeons underestimated the number of dystrophic curves, rating from 45% to 67% of the curve patterns as dystrophic, compared to the gold standard, which revealed 68% of the curves to be dystrophic. On multivariate analysis, rib penciling, vertebral rotation, vertebral wedging, and atypical location were significantly associated with true dystrophic status (odds ratios of 2.4, 3.0, 2.4, and 3.0, respectively)., Conclusion: Overall dystrophic diagnosis can be assessed by radiographic characteristics. Better understanding of the predictive value of specific radiographic features may assist in early diagnosis of patients with dystrophic NF and assist surgeons in identifying dystrophic curve patterns and instituting prompt, appropriate treatment., Level of Evidence: Level III., (Copyright © 2018 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate initial tissue hemoglobin oxygen saturation (StO 2 ) in dogs presenting to an emergency room (ER) for acute hemorrhage., Design: Prospective, observational study., Setting: University veterinary teaching hospital., Animals: Thirty-eight dogs with acute hemorrhage were enrolled between July 2009 and October 2010. Seventy-eight normal dogs from a previous observational study were included to represent healthy controls ("no shock")., Interventions: Tissue oxygen saturation measurement was obtained at enrollment on dogs presented to the ER for acute hemorrhage. Baseline clinicopathologic (CBC, serum biochemical profile, prothrombin time, and activated partial thromboplastin time) and physiologic (plasma lactate concentration, venous blood gas, blood pressure, and hemoglobin oxygen saturation by pulse oximetry) data were recorded from all patients with hemorrhage. An ER clinician blinded to the StO 2 value guided patient management. Patient survival to discharge from the hospital in the study group was recorded. Once data collection was complete, 3 emergency and critical care clinicians blinded to the StO 2 data retrospectively classified patients into 1 of 4 shock categories (no shock, mild, moderate, or severe shock)., Measurements and Main Results: The historical group of healthy dogs had higher StO 2 concentrations compared to the dogs classified with shock at all 3 levels (mild, moderate, and severe, P = 0.0006, <0.0001, and 0.0018, respectively); however, there was no statistical difference in StO 2 between the levels of shock. A cut-off StO 2 value of 87.6% identified a patient as having shock (area under the curve: 0.824, 95% confidence interval 0.749, 0.899)., Conclusions: Dogs with hemorrhagic shock have lower StO 2 than a population of healthy dogs., (© Veterinary Emergency and Critical Care Society 2018.)

Background: Determining the incidence, disease-associated serotypes and antimicrobial susceptibility of invasive pneumococcal disease (IPD) among children in Africa is essential in order to monitor the impact of these infections prior to widespread introduction of the pneumococcal conjugate vaccine (PCV)., Methods: To provide updated estimates of the incidence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae causing disease in Africa, we performed a systematic review of articles published from 2000 to 2015 using Ovid Medline and Embase. We included prospective and surveillance studies that applied predefined diagnostic criteria. Meta-analysis for all pooled analyses was based on random-effects models., Results: We included 38 studies consisting of 386,880 participants in 21 countries over a total of 350,613 person-years. The pooled incidence of IPD was 62.6 (95% CI 16.9, 226.5) per 100,000 person-years, including meningitis which had a pooled incidence of 24.7 (95% CI 11.9, 51.6) per 100,000 person-years. The pooled prevalence of penicillin susceptibility was 78.1% (95% CI 61.9, 89.2). Cumulatively, PCV10 and PCV13 included 66.9% (95% CI 55.9, 76.7) and 80.6% (95% CI 66.3, 90.5) of IPD serotypes, respectively., Conclusions: Our study provides an integrated and robust summary of incidence data, serotype distribution and antimicrobial susceptibility for S. pneumoniae in children ≤5years of age in Africa prior to widespread introduction of PCV on the continent. The heterogeneity of studies and wide range of incidence rates across the continent indicate that surveillance efforts should be intensified in all regions of Africa to improve the integrity of epidemiologic data, vaccine impact and cost benefit. Although the incidence of IPD in young children in Africa is substantial, currently available conjugate vaccines are estimated to cover the majority of invasive disease-causing pneumococcal serotypes. These data provide a reliable baseline from which to monitor the impact of the broad introduction of PCV., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Medical education increasingly involves online learning experiences to facilitate the standardization of curriculum across time and space. In class, delivering material by lecture is less effective at promoting student learning than engaging students in active learning experience and it is unclear whether this difference also exists online. We sought to evaluate medical student preferences for online lecture or online active learning formats and the impact of format on short- and long-term learning gains. Students participated online in either lecture or constructivist learning activities in a first year neurologic sciences course at a US medical school. In 2012, students selected which format to complete and in 2013, students were randomly assigned in a crossover fashion to the modules. In the first iteration, students strongly preferred the lecture modules and valued being told "what they need to know" rather than figuring it out independently. In the crossover iteration, learning gains and knowledge retention were found to be equivalent regardless of format, and students uniformly demonstrated a strong preference for the lecture format, which also on average took less time to complete. When given a choice for online modules, students prefer passive lecture rather than completing constructivist activities, and in the time-limited environment of medical school, this choice results in similar performance on multiple-choice examinations with less time invested. Instructors need to look more carefully at whether assessments and learning strategies are helping students to obtain self-directed learning skills and to consider strategies to help students learn to value active learning in an online environment.

Background: Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown., Methods: We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn., Results: We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 μW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0°C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion., Conclusions: Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810.).

Background: The methods of evidence-based medicine are a relatively recent development in the understanding of clinical practice. They are criticized as not providing support for interventions long held to be highly effective based on experience that predated the availability of evidence-based analysis., Objective: To determine if the methods of evidence-based medicine can be successfully applied to interventions established before those methods were developed., Methods: Systematic review of English language literature on the natural history and treated prognosis of acute epidural hematoma and analysis of existing data on mortality associated with parachute use., Data Sources: Sources of data included Medline, Old Medline, Science Citation Index, British and US Parachute Associations, and Federal Aviation Administration and National Transportation Safety Board databases (both of the United States). Also included were national databases reporting mortality and total number of parachute uses., Results: The estimated mortality of falling from an airplane with an ineffective parachute is 74% (69-79). Mortality associated with effective parachute deployment is between 0.0011% and 0.0017%. For acute epidural hematoma, estimated mortality is 98.54% (95.1-99.9) without treatment and 12.9% (10.5-15.3) with treatment. The number needed to treat to prevent 1 death for the parachute is estimated to be 1.35 (1.27-1.45) and for epidural hematoma 1.17 (1.13-1.22) (95% binomial confidence intervals in parentheses)., Conclusion: The methods of evidence-based medicine are robust and can deal with interventions of great face validity and those considered well established before such methods were well developed. We propose initial criteria for evaluating the quality of evidence supporting long-established interventions.

Objectives: Evaluate safety and efficacy of filtered-sunlight phototherapy (FS-PT)., Methods: Term/late preterm infants #14 days old with clinically significant jaundice, assessed by total bilirubin (TB) levels, were recruited from a maternity hospital in Lagos, Nigeria. Sunlight was filtered with commercial window-tinting films that remove most UV and significant levels of infrared light and transmit effective levels of therapeutic blue light. After placing infants under an FS-PT canopy, hourly measurements of axillary temperatures, monitoring for sunburn, dehydration, and irradiances of filtered sunlight were performed. Treatment was deemed safe and efficacious if infants were able to stay in FS-PT for $5 hours and rate of rise of TB was ,0.2 mg/dL/h for infants #72 hours of age or TB decreased for infants .72 hours of age., Results: A total of 227 infants received 258 days of FS-PT. No infant developed sunburn or dehydration. On 85 (33%) of 258 treatment days, infants were removed briefly from FS-PT due to minor temperature-related adverse events. No infant met study exit criteria. FS-PT was efficacious in 92% (181/197) of evaluable treatment days. Mean 6 SD TB change was –0.06 6 0.19 mg/dL/h. The mean 6 SD (range) irradiance of FS-PT was 38 6 22 (2–115) mW/cm2/nm, measured by the BiliBlanket Meter II., Conclusions: With appropriate monitoring, filtered sunlight is a novel, practical, and inexpensive method of PT that potentially offers safe and efficacious treatment strategy for management of neonatal jaundice in tropical countries where conventional PT treatment is not available.

Background: Severe neonatal jaundice and its progression to kernicterus is a leading cause of death and disability among newborns in poorly-resourced countries, particularly in sub-Saharan Africa. The standard treatment for jaundice using conventional phototherapy (CPT) with electric artificial blue light sources is often hampered by the lack of (functional) CPT devices due either to financial constraints or erratic electrical power. In an attempt to make phototherapy (PT) more readily available for the treatment of pathologic jaundice in underserved tropical regions, we set out to test the hypothesis that filtered sunlight phototherapy (FS-PT), in which potentially harmful ultraviolet and infrared rays are appropriately screened, will be as efficacious as CPT., Methods/design: This prospective, non-blinded randomized controlled non-inferiority trial seeks to enroll infants with elevated total serum/plasma bilirubin (TSB, defined as 3 mg/dl below the level recommended by the American Academy of Pediatrics for high-risk infants requiring PT) who will be randomly and equally assigned to receive FS-PT or CPT for a total of 616 days at an inner-city maternity hospital in Lagos, Nigeria. Two FS-PT canopies with pre-tested films will be used. One canopy with a film that transmits roughly 33% blue light (wavelength range: 400 to 520 nm) will be used during sunny periods of a day. Another canopy with a film that transmits about 79% blue light will be used during overcast periods of the day. The infants will be moved from one canopy to the other as needed during the day with the goal of keeping the blue light irradiance level above 8 μW/cm²/nm., Primary Outcome: FS-PT will be as efficacious as CPT in reducing the rate of rise in bilirubin levels. Secondary outcome: The number of infants requiring exchange transfusion under FS-PT will not be more than those under CPT., Conclusion: This novel study offers the prospect of an effective treatment for infants at risk of severe neonatal jaundice and avoidable exchange transfusion in poorly-resourced settings without access to (reliable) CPT in the tropics., Trial Registration: ClinicalTrials.gov Identifier: NCT01434810.

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway., (© 2013.)

Background: The CYP4503A5*1 genotype is associated with lower tacrolimus concentrations. Although its effect is important, it incompletely explains the variability in tacrolimus concentrations and has a relatively low minor allele frequency in whites relative to African Americans (AA)., Methods: We studied clinical and recipient genetic correlates of dose-normalized tacrolimus troughs (n=12,277) in the first 6 months posttransplant using a customized single-nucleotide polymorphism chip with 2722 variants in a large, ethnically diverse (144 AA and 551 non-AA) adult kidney transplant population through a seven-center consortium., Results: During the 6-month study, AAs had consistently lower median (interquartile range) troughs than non-AAs, 6.2 (4.4-8.4) ng/mL vs. 8.3 (6.4-10.4) ng/mL (P<0.0001), despite 60% higher daily doses, 8 (5-10) mg vs. 5 (4-7) mg (P<0.0001). The median tacrolimus trough concentration in week 1 posttransplant was particularly low in AAs (2.1 [1.2-3.5] ng/mL) compared with non-AAs (5.0 [3.1-8.2] ng/mL) (P<0.0001), despite similar initial doses. In single-variant analysis, CYP3A5*3 (rs776746) was the top variant (P=2.4×10) associated with troughs. After adjustment for CYP3A5*3, clinical factors and race, 35 additional variants were identified (P<0.01, not significant at false discovery rate 20%). In the final multivariant, regression models beginning with these variants and clinical factors, seven variants were identified in the non-AA and seven variants in the AA group towards the first trough concentrations. Rs776746 (CYP3A5), rs2239393 (COMT) and diabetes were the only factors common in both populations., Conclusion: We identified variants beyond CYP3A5*3, which may further explain pharmacokinetic variability of tacrolimus and demonstrated that important variants differ by race.

Objectives: Few studies have described the survival of low-birth-weight infants weighing less than 1.5 kg at operation for a cardiac malformation. Our goal was to determine if body weight at surgery affects survival., Methods: This was a retrospective cohort study using outcome data from the Pediatric Cardiac Care Consortium between 1982 and 2006., Results: We reviewed the outcomes of 450 consecutive infants with a cardiac anomaly and a birth weight of less than 1.5 kg, and weight of less than 2.5 kg at surgery. Of these, 179 patients had undergone surgery with a weight of less than 1.5 kg and 271 patients weighed 1.5 to 2.5 kg at surgery. The 30-day survival rate was 83% for cohort 1 and 86% for cohort 2. For patients not requiring cardiopulmonary bypass, the 30-day survival rate was 86% for cohort 1 and 92% for cohort 2. For patients requiring cardiopulmonary bypass, the 30-day survival rate was 69% for cohort 1 and 73% for cohort 2. No notable improvement in the outcomes occurred over time., Conclusions: For low-birth-weight infants (weight < 1.5 kg) undergoing a major cardiac procedure, the survival of infants weighing less than 1.5 kg at surgery is comparable to that of infants who weighed 1.5 to 2.5 kg. We conclude that, in our series, weight was not an independent risk factor for mortality, and, therefore, operative delay because of patient weight might be unwarranted., (Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)