Safety of bubble nasal intermittent positive pressure ventilation (NIPPV) versus bubble nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress.

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 H2O) or bubble NIPPV (Phigh 8-12 cm H2O/Plow 5-8 cm H2O) 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.

The Effect of Implant Density on Adolescent Idiopathic Scoliosis Fusion: Results of the Minimize Implants Maximize Outcomes Randomized Clinical Trial.

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.

Antenatal jaundice instruction and acute bilirubin encephalopathy in Nigeria.

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.

Essential team science skills for biostatisticians on collaborative research teams.

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.

Assessing feasibility of a novel approach to effective medication self-management for older persons.

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.

Reported Complications of Bubble Continuous Positive Airway Pressure Systems in Low-Resource Settings: An International Survey.

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.

Health of Post-Institutionalized Haitian Children Adopted to the United States.

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.

Vitamin D Deficiency in a Minnesota-Based Foster Care Population: A Cross Sectional Study.

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.

High Prevalence of Iron Deficiency Despite Standardized High-Dose Iron Supplementation During Recombinant Erythropoietin Therapy in Extremely Low Gestational Age Newborns.

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.

Students' perceptions of global health competencies in the doctor of pharmacy (PharmD) curriculum.

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.

Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder.

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.

Filtered sunlight versus intensive electric powered phototherapy in moderate-to-severe neonatal hyperbilirubinaemia: a randomised controlled non-inferiority trial.

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/cm2/nm (IQR 21·4-56·4) in the FSPT group and 50·4 µW/cm2/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.

Tissue oxygen saturation in dogs with acute hemorrhage.

OBJECTIVE: To evaluate initial tissue hemoglobin oxygen saturation (StO2 ) 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 StO2 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 StO2 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 StO2 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 StO2 between the levels of shock. A cut-off StO2 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 StO2 than a population of healthy dogs.

Predictive Value and Interrater Reliability of Radiographic Factors in Neurofibromatosis Patients With Dystrophic Scoliosis.

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.

Childhood pneumococcal disease in Africa - A systematic review and meta-analysis of incidence, serotype distribution, and antimicrobial susceptibility.

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.

A Randomized Crossover Design to Assess Learning Impact and Student Preference for Active and Passive Online Learning Modules.

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.

Choline supplementation in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects. OBJECTIVE: Our primary goal was to determine whether postnatal choline supplementation has the potential to improve neurocognitive functioning, particularly hippocampal-dependent memory, in children with FASDs. DESIGN: The study was a double-blind, randomized, placebo-controlled pilot trial in children (aged 2.5-5 y at enrollment) with FASDs (n = 60) who received 500 mg choline or a placebo daily for 9 mo. Outcome measures were Mullen Scales of Early Learning (primary) and the elicited imitation (EI) memory paradigm (secondary). RESULTS: The administration proved feasible, and choline was well tolerated. Participants received a dose on 88% of enrolled days. The only adverse event linked to choline was a fishy body odor. Choline supplementation improved the secondary outcome (EI) only after immediate recall performance was controlled for, and the outcome was moderated by age. The treatment effect on EI items recalled was significant in the younger participants (2.5- to ≤4.0-y-olds); the young choline group showed an increase of 12-14 percentage points greater than that of the young placebo group on delayed recall measures during treatment. However, there was a marginal baseline difference in delayed item recall between the young choline and placebo groups as well as a potential ceiling effect for item recall, both of which likely contributed to the observed treatment effect. We also observed a trend toward a negative effect of choline supplementation on the immediate EI recall of ordered pairs; the young placebo group showed an increase of 8-17 percentage points greater than that of the choline group during treatment. There was an inverse relation between choline dose (in mg/kg) and memory improvement (P = 0.041); the data suggest that weight-adjusted doses may be a better alternative to a fixed dose in future studies. Limitations included trend-level baseline differences in performance, the post-hoc determination of age moderation, and potential ceiling effects for the memory measure. CONCLUSIONS: This pilot study suggests that an additional evaluation of choline supplementation as an intervention for memory functioning in children with FASDs is warranted. The observed interaction between age and choline's effect on EI suggests that potential sensitive periods should be considered in future work. This trial was registered at clinicaltrials.gov as NCT01149538.

A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates.

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.).

Evidence-based assessment of well-established interventions: the parachute and the epidural hematoma.

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.

Safety and efficacy of filtered sunlight in treatment of jaundice in African neonates.

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 (2­115) 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.