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BACKGROUND: Improving breastfeeding rates among African American (AA) families is an important public health goal. Breastfeeding self-efficacy, a known predictor of breastfeeding behavior, has seldom been assessed among AAs, in relation to breastfeeding intensity (% breastfeeding relative to total feeding) or as a protective factor in combating the historical breastfeeding challenges faced by people of color. We aimed to test the association between breastfeeding self-efficacy assessed during pregnancy and breastfeeding intensity assessed in the early postpartum period. METHODS: This was a secondary data analysis of a randomized controlled feasibility trial of breastfeeding support and postpartum weight management. AA women were recruited during pregnancy from a prenatal clinic in Detroit, MI. Data presented, in this study, were collected at enrollment (n = 50) and ∼6 weeks postpartum (n = 31). Linear regression models were used, adjusting for potential confounders. RESULTS: There were no differences in breastfeeding intensity by study arm; data are from all women with complete data on targeted variables. Age ranged from 18 to 43 years, 52% were Women, Infant's, and Children program enrollees, and 62% had ≥ some college. Breastfeeding self-efficacy during pregnancy was a significant predictor of breastfeeding intensity in the early postpartum period (β = 0.125, p

Brain systems supporting body movement are active during music listening in the absence of overt movement. This covert motor activity is not well understood, but some theories propose a role in auditory timing prediction facilitated by motor simulation. One question is how music-related covert motor activity relates to motor activity during overt movement. We address this question using scalp electroencephalogram by measuring mu rhythms—cortical field phenomena associated with the somatomotor system that appear over sensorimotor cortex. Lateralized mu enhancement over hand sensorimotor cortex during/just before foot movement in foot versus hand movement paradigms is thought to reflect hand movement inhibition during current/prospective movement of another effector. Behavior of mu during music listening with movement suppressed has yet to be determined. We recorded 32-channel EEG (n = 17) during silence without movement, overt movement (foot/hand), and music listening without movement. Using an independent component analysis-based source equivalent dipole clustering technique, we identified three mu-related clusters, localized to left primary motor and right and midline premotor cortices. Right foot tapping was accompanied by mu enhancement in the left lateral source cluster, replicating previous work. Music listening was accompanied by similar mu enhancement in the left, as well as midline, clusters. We are the first, to our knowledge, to report, and also to source-resolve, music-related mu modulation in the absence of overt movements. Covert music-related motor activity has been shown to play a role in beat perception (Ross JM, Iversen JR, Balasubramaniam R. Neurocase 22: 558–565, 2016). Our current results show enhancement in somatotopically organized mu, supporting overt motor inhibition during beat perception. NEW & NOTEWORTHY We are the first to report music-related mu enhancement in the absence of overt movements and the first to source-resolve mu activity during music listening. We suggest that music-related mu modulation reflects overt motor inhibition during passive music listening. This work is relevant for the development of theories relating to the involvement of covert motor system activity for predictive beat perception.

Objectives Research suggests that a recent concussion increases subsequent lower extremity injury risk; however, data in high school athletes is limited. This study evaluates the association between concussion and subsequent injury risk among male, collision sport, high school athletes over a single season. Design Retrospective cohort study. Methods Data were obtained from 2005/06–2014/15 in the High School Reporting Information Online database. A two stage, multi-method matching process was used to identify athletes who suffered multiple injuries over a single athletic season. Demographics and injury characteristics were compared with Chi square and Student's t-tests. Multiple Cox Proportional Hazards regression analysis was used to test whether index injury type was associated with hazard of subsequent injury following return to play from index injury. Results Overall 1364 HS athletes sustained 2 injuries over a single athletic season (subsequent injury within 45 days of the index injury). Index injuries included 686 (50.2%) lower extremity injuries, 417 (30.6%) upper extremity injuries, and 261 (19.1%) concussions. Hazard of subsequent concussion was increased in the index concussion group relative to the index lower extremity injury group [hazard ratio (HR): 1.60, 95% CI: 1.15–2.23, p = 0.0052]. Hazard of a subsequent lower extremity injury was not significantly different for the index lower extremity injury group relative to the index concussion group [HR: 1.27, 95% CI: 0.98–1.65, p = 0.0728]. Conclusions History of recent concussion or recent lower extremity injury are both risk factors for subsequent lower extremity injury in male, collision sport, high school athletes.

To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE.Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system.Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs -14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P .001) than those without acute abnormalities.Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.ClinicalTrials.gov: NCT02811263.

In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs.To assess the use and safety of outpatient management of acute appendicitis.This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020.Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively.Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared.Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores.These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care.ClinicalTrials.gov Identifier: NCT02800785.

Objectives Studies that evaluate the effectiveness of concussion laws often use only a single variable (ie, presence of the law), failing to account for law complexity. We examined the association between multiple design elements of state concussion laws and rates of sports-related concussion reporting among US high school athletes. Methods We derived 3 design elements of concussion laws from the 2009-2017 LawAtlas database: (1) strength of law, (2) number of law revisions, and (3) speed of law adoption. We examined the association between these design elements and rates of new and recurrent sports-related concussion reporting from the 2009-2010 through 2016-2017 academic years in a nationally representative sample of high school athletes participating in High School Report Information Online, an online data collection tool. Results A total of 7064 sports-related concussions (6332 [89.6%] new and 732 [10.4%] recurrent concussions) were reported during the study period, with an overall rate of 39.7 sports-related concussions per 100 000 athletic exposures (eg, game or practice). Rates of new concussion reporting were higher among high schools in states with medium- or high-strength concussion laws than in states with low-strength concussion laws and in states with at least 1 concussion law revision than in states with no concussion law revisions. Rates of recurrent concussion reporting were lower among high schools in states with ≥2 concussion law revisions than in states with Conclusion Our findings may help inform legislators of the public health effect of concussion laws.

The human gut microbiome has been classified into three distinct enterotypes (Bacteroides, Prevotella, and Ruminococcus). The relationship between probiotics and gut enterotype is not yet clear. Cayenne pepper is effective in vitro as a prebiotic for Bifidobacteria and Lactobacilli, so cayenne ingestion with probiotics may lead to more profound gut microbial shifts. We aimed to determine whether probiotics (with or without cayenne pepper) alter gut bacterial community composition and if these changes are associated with the original gut enterotype of the individual. A total of 27 adult participants provided three fecal samples: prior to probiotic treatment (baseline), post probiotic treatment (probiotic), and post probiotic plus cayenne pepper treatment (probiotic + cayenne). DNA was extracted, amplified, and the V4 region sequenced on the Illumina MiSeq platform using V2 chemistry. Sequence reads were processed in mothur and assigned using the SILVA reference by phylotype. Three enterotypes characterized the study population-Bacteroides (B; n = 6), Prevotella (P; n = 11), and Ruminoccocus (R; n = 10). There was no significant increase in probiotic genera in fecal samples after treatment periods. Alpha diversity scores were significantly lower in B-type but not in P- or R-type individuals after probiotic treatment. For the majority of individuals, their enterotype remained constant regardless of probiotic (and cayenne) treatment. This suggests that baseline gut community characteristics and enterotype classification influence responsiveness to probiotic treatment, but that enterotype is stable across administration of prebiotic and probiotics. PRACTICAL APPLICATION: A person's gut microbial community influences their responsiveness to probiotics and prebiotic ingredients. Consumers must understand that it is difficult to shift their gut microbiota even with simultaneous administration of prebiotic and probiotic. Greater understanding of these phenomena will enable consumers to choose the most efficacious products for their needs.

The phosphatidylinositol 3′ kinase (PI3K)‐related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair, meiotic sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during meiotic prophase I. Despite its central roles in meiosis, the ATR-dependent meiotic signaling network remains largely unknown. Here, we used phosphoproteomics to define ATR signaling events in testes from mice following chemical and genetic ablation of ATR signaling. Quantitative analysis of phosphoproteomes obtained after germ cell-specific genetic ablation of the ATR activating 9-1-1 complex or treatment with ATR inhibitor identified over 14,000 phosphorylation sites from testes samples, of which 401 phosphorylation sites were found to be dependent on both the 9-1-1 complex and ATR. Our analyses identified ATR-dependent phosphorylation events in crucial DNA damage signaling and DNA repair proteins including TOPBP1, SMC3, MDC1, RAD50, and SLX4. Importantly, we identified ATR and RAD1-dependent phosphorylation events in proteins involved in mRNA regulatory processes, including SETX and RANBP3, whose localization to the sex body was lost upon ATR inhibition. In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.

Breastfeeding and introduction of solid food are the two major components of infant feeding practices that influence gut microbiota composition in early infancy. However, it is unclear whether additional factors influence the microbiota of infants either exclusively breastfed or not breastfed. We obtained 194 fecal samples from infants at 3–9 months of age, extracted DNA, and sequenced the V4 region of the 16S rRNA gene. Feeding practices and clinical information were collected by questionnaire and abstraction of birth certificates. The gut microbiota of infants who were exclusively breastfed displayed significantly lower Shannon diversity (p-adjust < 0.001) and different gut microbiota composition compared to infants who were not breastfed (p-value = 0.001). Among the exclusively breastfed infants, recipients of vitamin D supplements displayed significantly lower Shannon diversity (p-adjust = 0.007), and different gut microbiota composition structure than non-supplemented, breastfed infants (p-value = 0.02). MaAslin analysis identified microbial taxa that associated with breastfeeding and vitamin D supplementation. Breastfeeding and infant vitamin D supplement intake play an important role in shaping infant gut microbiota.

Vulnerability to poor sexual health among U.S. Latinx populations is poorly understood, despite high STI rates. We examined how vulnerability typologies differ in their STI preventive behaviors. Using data from the 2016 National Health Interview Survey, we performed latent class analysis to test the association between sexual health vulnerability and HIV testing, hepatitis testing or vaccination, and HPV vaccination from a subsample of Latinx adults. Three classes emerged: Under-Employed Females with Health Care Access, Slightly Under-Employed Females with Some Health Care Access, and Employed Males without Health Care Access. Slightly Under-Employed Females with Some Health Care Access were associated with lack of HIV testing, hepatitis B and C testing, and HPV vaccination. Employed Males without Health Care Access were associated with lack of HIV testing and HPV vaccination. Sexual health vulnerability may be associated with certain STI preventive behaviors, which can inform and refine sexual health promotion programming.

ImportanceDermatologists with specialty training in pediatric dermatology are scarce, which can mean extended wait times and reduced access to care for patients. Lower compensation for pediatric dermatology visits compared with adult visits may affect physician career choice and contribute to workforce shortages.ObjectiveTo evaluate differences in work relative value units (wRVUs) generated by pediatric and adult outpatient dermatology encounters.Design, Setting, and ParticipantsThis cross-sectional study used data from outpatient dermatology encounters at a single-site academic center in Atlanta, Georgia, from September 1, 2016, to March 31, 2020. Encounters with patients younger than 18 years were classified as pediatric, and encounters with those 18 years or older were classified as adult. Encounters with missing data were excluded as were those generating 0 wRVUs, inpatient visits, nursing visits, postoperative encounters, cosmetic procedures, phototherapy visits, and Mohs surgery encounters.Main Outcomes and MeasuresWork relative value units generated per encounter type were assessed through multivariable linear regression models adjusted for the potential confounder of sex.ResultsThe study included 12 989 pediatric dermatology encounters (mean [SD] age, 7.3 [5.2] years; 7586 [58.4%] girls) and 78 057 adult dermatology encounters (mean [SD] age, 54.9 [18.9] years; 45 724 [58.6%] women). Pediatric encounters were associated with 0.23 (95% CI, 0.21-0.25; P P Conclusions and RelevanceThis cross-sectional study found significant differences in wRVUs generated between adult and pediatric dermatology encounters that were largely attributable to biopsies and destruction of premalignant lesions. Policies that increase the value of cognitive services to be on par with procedural care may mitigate wRVU differences and improve reimbursement for pediatric dermatologists.

Objectives To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age. Study design The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models. Results One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age. Conclusions Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

OBJECTIVES: To determine the incidence, timing, progression, and risk factors for intracranial hemorrhage (ICH) in infants 24–0/7 to 27–6/7 weeks’ gestational age (GA), and to characterize the association between ICH and death or neurodevelopmental impairment (NDI) at 2 years corrected age (CA). STUDY DESIGN: Infants enrolled in the Preterm Erythropoietin Neuroprotection Trial had serial cranial ultrasounds performed on day 1, day 7–9, and 36-weeks postmenstrual age (PMA) to evaluate ICH. Potential risk factors for development of ICH were examined. Outcomes included death or severe NDI as well as Bayley Scales of Infant and Toddler Developmental, 3(rd) Edition (BSID-III) at 2-years CA. RESULTS: ICH was identified in 38% (n=339) of 883 enrolled infants. Multiple gestation and cesarean delivery reduced the risk of any ICH on day 1. Risk factors for development of bilateral Grade 2, or Grade 3 or 4 ICH at day 7–9 included any ICH at day 1, and two or more doses of prenatal steroids decreased risk. Bilateral Grade 2, Grade 3, or Grade 4 ICH at 36-weeks were associated with prior ICH at day 7–9. Bilateral Grade 2, any Grade 3, and any Grade 4 ICH at 7–9 days or 36-weeks PMA were associated with increased risk of death or severe NDI and lower BSID-III scores. CONCLUSION: Risk factors for ICH varied by timing of bleed. Bilateral and increasing grade of ICH were associated with death or NDI in infants born extremely preterm.

Hurley, E, Comstock, BA, Haile, L, and Beyer, KS. Relative age effect in collegiate soccer: influence of nationality, playing position, and class. J Strength Cond Res 33(12): 3295-3301, 2019-The purpose of this study was to evaluate the existence of relative age effects (RAEs) in collegiate soccer. In addition, the impact of nationality, position, class, and National Collegiate Athletic Association (NCAA) tournament qualification status on the prevalence of RAEs was assessed. Birth dates from male NCAA Division I soccer athletes (n = 4,082) from the 2017/2018 season were categorized into quarters based on calendar and scholastic quarters. All athlete birth-date distributions were compared with the expected birth-date distributions for the United States. International-born athletes (INT) displayed a significant difference in birth-date distribution when assessed with calendar quarters, whereas American-born athletes (USA) showed a significant difference in birth-date distributions when assessed with scholastic quarters. Furthermore, INT showed significant RAEs for midfielders and defenders, whereas USA showed significant RAEs midfielders and goalkeepers. In terms of class, INT had significant RAEs for all classes, whereas USA had significant RAEs only for freshmen and sophomores. All INT had significant RAEs regardless of tournament qualification status; however, USA had significant RAEs only for nontournament teams. In summary, significant RAEs exist in male Division I college soccer; however, the presence of RAEs is influenced by nationality, position, class, and NCAA tournament qualification status. Coaches should be aware of RAEs during the recruitment process to avoid potential selection bias.

Background/aim:Cost-efficient methods are essential for successful participant recruitment in clinical trials. Patient portal messages are an emerging means of recruiting potentially eligible patients into trials. We assessed the response rate and complaint rate from direct-to-patient, targeted recruitment through patient portals of an electronic medical record for a clinical trial, and compared response rates by differences in message content.Methods:The Study to Understand Fall Reduction and Vitamin D in You (STURDY) trial is a National Institutes of Health–sponsored, community-based study of vitamin D supplementation for fall prevention in older adults conducted at Johns Hopkins. Potential participants were identified using the Epic electronic medical record at the Johns Hopkins Health System based on age (≥70 years), ZIP code (30-mile radius of study site), and prior activation of a patient portal account. We prepared a shorter message and a longer message. Both had basic information about study participation, but the longer message also contained information about the significance of the study and a personal invitation from the STURDY principal investigator. The Hopkins Institutional Review Board did not require prior consent from the patient or their providers. We calculated the response rate and tracked the number of complaints and requests for removal from future messages. We also determined response rate according to message content.Results:Of the 5.5 million individuals receiving care at the Johns Hopkins Health System, a sample of 6896 met our inclusion criteria and were sent one patient portal recruitment message between 6 April 2017 and 3 August 2017. Assessment of enrollment by this method ended on 1 December 2017. There were 116 patients who expressed interest in the study (response rate: 1.7%). Twelve (0.2%) recipients were randomized. There were two complaints (0.03%) and one request to unsubscribe from future recruitment messages (0.01%). Response rate was higher with the longer message than the shorter message (2.1% vs 1.2%; p = 0.005).Conclusion:Patient portal messages inviting seniors to participate in a randomized controlled trial resulted in a response rate similar to commercial email marketing and resulted in very few complaints or opt-out requests. Furthermore, a longer message with more content enhanced response rate. Recruitment through patient portals might be an effective strategy to enroll trial participants.

Cerebral and cerebellar hemispheres are known to be asymmetrical in structure and function, and previous literature supports that asymmetry extends to the neural dopamine systems. Using in vivo fixed-potential amperometry with carbon-fiber microelectrodes in anesthetized mice, the current study assessed hemispheric lateralization of stimulation-evoked dopamine in the nucleus accumbens (NAc) and the influence of the cerebellum in regulating this reward-associated pathway. Our results suggest that cerebellar output can modulate mesolimbic dopamine transmission, and this modulation contributes to asymmetrically lateralized dopamine release. Dopamine release did not differ between hemispheres when evoked by medial forebrain bundle (MFB) stimulation; however, dopamine release was significantly greater in the right NAc relative to the left when evoked by electrical stimulation of the cerebellar dentate nucleus (DN). Furthermore, cross-hemispheric talk between the left and right cerebellar DN does not seem to influence mesolimbic release given that lidocaine infused into the DN opposite to the stimulated DN did not alter release. These studies may provide a neurochemical mechanism for studies identifying the cerebellum as a relevant node for reward, motivational behavior, saliency, and inhibitory control. An increased understanding of the lateralization of dopaminergic systems may reveal novel targets for pharmacological interventions in neuropathology of the cerebellum and extending projections.

Minimal residual disease (MRD) has become an increasingly prevalent and important entity in multiple myeloma (MM). Despite deepening responses to frontline therapy, roughly 75% of MM patients never become MRD-negative to ≤10(−5), which is concerning because MRD-negative status predicts significantly longer survival. MM is highly heterogeneous, and MRD persistence may reflect survival of isolated single cells and small clusters of treatment-resistant subclones. Virtually all MM clones are exquisitely sensitive to radiation, and the α-emitter astatine-211 ((211)At) deposits prodigious energy within 3 cell diameters, which is ideal for eliminating MRD if effectively targeted. CD38 is a proven MM target, and we conjugated (211)At to an anti-CD38 monoclonal antibody to create an (211)At-CD38 therapy. When examined in a bulky xenograft model of MM, single-dose (211)At-CD38 at 15 to 45 µCi at least doubled median survival of mice relative to untreated controls (P < .003), but no mice achieved complete remission and all died within 75 days. In contrast, in a disseminated disease model designed to reflect low-burden MRD, 3 studies demonstrated that single-dose (211)At-CD38 at 24 to 45 µCi produced sustained remission and long-term survival (>150 days) for 50% to 80% of mice, where all untreated mice died in 20 to 55 days (P < .0001). Treatment toxicities were transient and minimal. These data suggest that (211)At-CD38 offers the potential to eliminate residual MM cell clones in low-disease-burden settings, including MRD. We are optimistic that, in a planned clinical trial, addition of (211)At-CD38 to an autologous stem cell transplant (ASCT) conditioning regimen may improve ASCT outcomes for MM patients.

Objective To examine whether a primary care provider (PCP) follow-up visit after emergency department evaluation of concussion improved the children's likelihood of receiving academic support. Study design This was a prospective cohort study. Concussed children, aged 8-18 years, presenting to a regional pediatric trauma center emergency department (n = 160) were contacted 7 and 30 days after injury to gather data on PCP follow-up, symptoms, quality of life, and receipt of academic support instituted after and because of the concussion. Bivariate comparisons of demographics, concussion characteristics, quality of life, and symptoms were made between children who did and did not receive support using independent samples t tests, Wilcoxon rank sum tests, or χ2 tests. ORs and 95% CIs were calculated using multivariable logistic regression with backwards elimination to test the association between attending an outpatient follow-up visit and the receipt of academic support for variables where P Results Overall, 51.3% (n = 82) received academic support; of these, 84.2% attended a follow-up visit compared with 71.8% of 78 children who attended a follow-up visit but did not receive support (P = .06). Children who received support were more likely to have commercial insurance; experience a sports-related injury mechanism; have parents whose primary language was English; suffer from learning disabilities and migraines; and be non-Hispanic (P Conclusions Although the majority of children received academic support postconcussion, accommodations were associated with several demographic, medical history, and injury characteristics, but not attending a PCP follow-up visit.

Objectives: In this study, we sought to determine the accuracy of energy expenditure (EE) esti- mation for the Fitbit Charge HR 2 (Fitbit) and the Apple Watch. Design: An observational study. Methods: Thirty young adults (15 men and 15 women, aged 23.5 ± 2.96 years) completed the Bruce treadmill protocol. We measured gross EE by a PARVO metabolic cart (MetCart) and concurrently estimated by the Fitbit and Apple Watch. We calculated concordance correlation coefficients (CCC, rc) and relative error rates to indicate the difference between each device and the MetCart system. Results: For the Apple Watch and Fitbit, the relative error rate was 24.3%, 20.1% for the pooled sample, 18.6%, 24.2% for men, and 29.9%, 16.7% for women, respectively. The Apple Watch overestimated EE for women and underestimated EE for men; the Fitbit underestimated EE for both. Moderate CCCs between estimated EEs and MetCart measured EEs were found for both Apple Watch (rc =0.65, 0.43, and 0.39 overall, men and women, respectively) and Fitbit (rc =0.53, 0.39, and 0.21 overall, men and women, respectively). Conclusion: Neither device showed accurate results compared with EE measured by a MetCart. Users should consider these results when designing programs or personal training plans where physical activity EE is a key outcome assessed with a wearable device.

Context Although sport-related internal organ injuries among athletes are relatively infrequent, combining data sources enables a more comprehensive examination of their incidence. Objective To describe the incidence and characteristics of sport-related internal organ injuries due to direct-contact mechanisms among high school (HS) and collegiate athletes from 2005–2006 through 2014–2015. Design Descriptive epidemiology study. Setting United States HS and collegiate sports data from 3 national sports injury-surveillance systems: High School Reporting Information Online (HS RIO), the National Collegiate Athletic Association Injury Surveillance Program (ISP), and the National Center for Catastrophic Sport Injury Research. Patients or Other Participants High school and collegiate athletes in organized sports. Main Outcome Measure(s) Characteristics of the athlete, event, and injury were examined and stratified by data source and sport. Descriptive statistics of internal organ injuries via direct-contact mechanisms consisted of frequencies and incidence rates (IRs) per 1 000 000 athlete-exposures and 95% confidence intervals (CIs). Results During the 10-year period, 174 internal organ injuries were captured: 124 in HS RIO and 41 in the ISP; 9 were catastrophic. Most noncatastrophic injuries occurred among males (RIO = 85%, ISP = 89%), in football (RIO = 65%, ISP = 58%), and during competitions (RIO = 67%, ISP = 49%) and were due to player-player contact (RIO = 78%, ISP = 68%). The highest injury rates were in male contact sports: RIO football (IR = 11.7; 95% CI = 9.1, 14.2) and lacrosse (IR = 10.0; 95% CI = 3.1, 16.9); ISP: football (IR = 8.3; 95% CI = 5.0, 11.6) and ice hockey (IR = 7.9; 95% CI = 1.0, 14.7). A quarter of noncatastrophic injuries were season ending (RIO = 25%, ISP = 23%). Of the 9 catastrophic injuries, most occurred in HS (7/9) and football (7/9) and were due to player-player contact (6/9). Four resulted in death. Conclusions Direct-contact internal organ injuries occur infrequently; yet when they do occur, they may result in severe outcomes. These findings suggest that early recognition and a better understanding of the activities associated with the event and use or nonuse of protective equipment are needed.

This study compared heart rate (HR) measurements for the Fitbit Charge HR 2 (Fitbit) and the Apple Watch devices with HR measurements for electrocardiogram (ECG). Thirty young adults (15/15 females/males, age 23.5 ± 3.0 years) completed the Bruce Protocol. HR measurements were recorded from the ECG and both devices every minute. Average HR for each participant was calculated for very light, light, moderate, vigorous and very vigorous intensities based on ECG-measured HR. A concordance correlation coefficient (CCC) was calculated to examine the strength of the relationship between ECG measured HR and HR measured by each device. Relative error rates (RER) were also calculated to indicate the difference between each device and ECG. An equivalence test was conducted to examine the equivalence of HRs measured by devices and ECG. The Apple Watch showed lower RER (2.4-5.1%) compared with the Fitbit (3.9-13.5%) for all exercise intensities. For both devices, the strongest relationship with ECG-measured HR was found for very light PA with very high CCC (.90) and equivalence. The strength of the relationship declined as exercise intensity increased for both devices. These findings indicate that the accuracy of real-time HR monitoring by the Apple Watch and Fitbit Charge HR2 is reduced as exercise intensity increases.

BACKGROUND Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. METHODS We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). RESULTS We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. CONCLUSIONS The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. IMPACT Urine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.

Guiding treatment decisions for women with ductal carcinoma in situ (DCIS) requires understanding patient preferences and the influence of preoperative magnetic resonance imaging (MRI) and surgeon recommendation.To identify factors associated with surgery preference and surgery receipt among a prospective cohort of women with newly diagnosed DCIS.A prospective cohort study was conducted at 75 participating institutions, including community practices and academic centers, across the US between March 25, 2015, and April 27, 2016. Data were analyzed from August 2 to September 24, 2021. This was an ancillary study of the ECOG-ACRIN Cancer Research Group (E4112). Women with recently diagnosed unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. Participants who had documented surgery and completed the baseline patient-reported outcome questionnaires were included in this substudy.Women received preoperative MRI and surgeon consultation and then underwent wide local excision or mastectomy. Participants will be followed up for recurrence and overall survival for 10 years from the date of surgery.Patient-reported outcome questionnaires assessed treatment goals and concerns and surgery preference before MRI and after MRI and surgeon consultation.Of the 368 participants enrolled 316 (86%) were included in this substudy (median [range] age, 59.5 [34-87] years; 45 women [14%] were Black; 245 [78%] were White; and 26 [8%] were of other race). Pre-MRI, age (odds ratio [OR] per 5-year increment, 0.45; 95% CI, 0.26-0.80; P = .007) and the importance of keeping one's breast (OR, 0.48; 95% CI, 0.31-0.72; P .001) vs removal of the breast for peace of mind (OR, 1.35; 95% CI, 1.04-1.76; P = .03) were associated with surgery preference for mastectomy. After MRI and surgeon consultation, MRI upstaging (48 of 316 [15%]) was associated with patient preference for mastectomy (OR, 8.09; 95% CI, 2.51-26.06; P .001). The 2 variables with the highest ORs for initial receipt of mastectomy were MRI upstaging (OR, 12.08; 95% CI, 4.34-33.61; P .001) and surgeon recommendation (OR, 4.85; 95% CI, 1.99-11.83; P .001).In this cohort study, change in patient preference for DCIS surgery and surgery received were responsive to MRI results and surgeon recommendation. These data highlight the importance of ensuring adequate information and ongoing communication about the clinical significance of MRI findings and the benefits and risks of available treatment options.

Background Chronic nausea in adolescents with functional gastrointestinal disorders is an increasingly reported but poorly understood symptom that negatively affects quality of life. Functional gastrointestinal disorders are known to correlate closely with slow wave rhythm disturbances. The ability to characterize gastric electrophysiologic perturbations in functional nausea patients could provide potential diagnostic and therapeutic tools for nausea patients. Methods We used high-resolution electrogastrograms (HR-EGG) to measure gastric slow wave parameters in pediatric chronic nausea patients and healthy subjects both pre- and postprandial. We computed the dominant frequency, percentage power distribution, gastric slow wave propagation direction, and speed from HR-EGG. Key results We observed significant differences in the dominant frequency and power distributed in normal and bradyarrhythmia frequency ranges when comparing patients and healthy subjects. Propagation patterns in healthy subjects were predominantly anterograde, while patients exhibited a variety of abnormalities including retrograde, anterograde, and disrupted patterns. There was a significant difference in the preprandial mean slow wave direction between healthy subjects (222° ± 22°) and patients (103° ± 66°; p ˂ 0.01), although the postprandial mean direction between healthy subjects and patients was similar (p = 0.73). No significant difference in slow wave propagation speed was found between patients and healthy subjects in either pre- (p = 0.21) or postprandial periods (p = 0.75). Conclusions and inferences The spatiotemporal characterization of gastric slow wave activity using HR-EGG distinguishes symptomatic chronic nausea patients from healthy subjects. This characterization may in turn inform and direct clinical decision-making and lead to further insight into its pathophysiology.

Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis.We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith.In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50).For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

Background: In the Preterm Erythropoietin (Epo) NeUroproTection (PENUT) Trial, potential biomarkers of neurological injury were measured to determine their association with outcomes at two years of age and whether Epo treatment decreased markers of inflammation in extremely preterm (

Key Points Question What is the impact of including benchmark prevalence data of common findings in reports of spinal imaging ordered by primary care clinicians? Findings In this randomized clinical trial that included 250 401 adults, no overall decrease in subsequent spine-related health care utilization after the intervention was observed. However, there was a significant decrease in opioid prescriptions at 1 year in the intervention group compared with the control group. Meaning The findings of this study suggest that including epidemiological benchmarks on spinal imaging reports has little impact on subsequent spine-related utilization overall but may reduce subsequent opioid prescriptions., This randomized clinical trial evaluates the impact of including benchmark prevalence data in routine spinal imaging reports on subsequent spine-related health care utilization and opioid prescriptions., Importance Lumbar spine imaging frequently reveals findings that may seem alarming but are likely unrelated to pain. Prior work has suggested that inserting data on the prevalence of imaging findings among asymptomatic individuals into spine imaging reports may reduce unnecessary subsequent interventions. Objective To evaluate the impact of including benchmark prevalence data in routine spinal imaging reports on subsequent spine-related health care utilization and opioid prescriptions. Design, Setting, and Participants This stepped-wedge, pragmatic randomized clinical trial included 250 401 adult participants receiving care from 98 primary care clinics at 4 large health systems in the United States. Participants had imaging of their backs between October 2013 and September 2016 without having had spine imaging in the prior year. Data analysis was conducted from November 2018 to October 2019. Interventions Either standard lumbar spine imaging reports (control group) or reports containing age-appropriate prevalence data for common imaging findings in individuals without back pain (intervention group). Main Outcomes and Measures Health care utilization was measured in spine-related relative value units (RVUs) within 365 days of index imaging. The number of subsequent opioid prescriptions written by a primary care clinician was a secondary outcome, and prespecified subgroup analyses examined results by imaging modality. Results We enrolled 250 401 participants (of whom 238 886 [95.4%] met eligibility for this analysis, with 137 373 [57.5%] women and 105 497 [44.2%] aged >60 years) from 3278 primary care clinicians. A total of 117 455 patients (49.2%) were randomized to the control group, and 121 431 patients (50.8%) were randomized to the intervention group. There was no significant difference in cumulative spine-related RVUs comparing intervention and control conditions through 365 days. The adjusted median (interquartile range) RVU for the control group was 3.56 (2.71-5.12) compared with 3.53 (2.68-5.08) for the intervention group (difference, −0.7%; 95% CI, −2.9% to 1.5%; P = .54). Rates of subsequent RVUs did not differ between groups by specific clinical findings in the report but did differ by type of index imaging (eg, computed tomography: difference, −29.3%; 95% CI, −42.1% to −13.5%; magnetic resonance imaging: difference, −3.4%; 95% CI, −8.3% to 1.8%). We observed a small but significant decrease in the likelihood of opioid prescribing from a study clinician within 1 year of the intervention (odds ratio, 0.95; 95% CI, 0.91 to 1.00; P = .04). Conclusions and Relevance In this study, inserting benchmark prevalence information in lumbar spine imaging reports did not decrease subsequent spine-related RVUs but did reduce subsequent opioid prescriptions. The intervention text is simple, inexpensive, and easily implemented. Trial Registration ClinicalTrials.gov Identifier: NCT02015455

Author(s): Rogal, Shari S; Yakovchenko, Vera; Gonzalez, Rachel; Park, Angela; Lamorte, Carolyn; Gibson, Sandra P; Chartier, Maggie; Ross, David; Comstock, Emily; Bajaj, Jasmohan S; Morgan, Timothy R | Abstract: Background and aimsThe Veterans Health Administration (VA) cares for over 80,000 Veterans with cirrhosis annually. Given the importance of understanding patient reported outcomes in this complex population, we aimed to assess the associations between attitudes towards care, disease knowledge, and health related quality of life (HRQoL) in a national sample.MethodsIn this cross-sectional study, we mailed paper surveys to a random sample of Veterans with cirrhosis, oversampling those with decompensated disease. Surveys included the Veterans RAND 12-Item Health Survey (measuring HRQoL) and questions about demographics, characteristics of care, satisfaction with care ("attitudes towards care"), and symptoms of cirrhosis. Those who reported being "unsure" about whether they had decompensation events were defined as "unsure about cirrhosis symptoms" ("disease knowledge"). We used multivariable regression models to assess the factors associated with HRQoL.ResultsOf 1374 surveys, 551 (40%) completed surveys were included for analysis. Most Veterans (63%) were "satisfied" or "very satisfied" with VA liver care. Patients often self-reported being unsure about whether they had experienced hepatic decompensation events (34%). Overall average physical (PCS) and mental (MCS) component scores of HRQoL were 30±11 and 41±12. In multivariable regression models, hepatic decompensation (PCS:β = -3.8, MCS:β = -2.2), medical comorbidities (β = --2.0, β = -1.7), and being unsure about cirrhosis symptoms (β = -1.9, β = -3.3) were associated with worse HRQoL, while age (β = 0.1, β = 0.2) and satisfaction with care (β = 0.6; β = 1.6) were associated with significantly better HRQoL.ConclusionsHepatic decompensation, lower satisfaction with care, and being unsure about cirrhosis symptoms were associated with reduced QOL scores in this national cohort.

Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions.The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019.In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks.Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein.A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P .001).These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants.ClinicalTrials.gov Identifier: NCT01378273.

Trial design This was a randomized controlled trial. Background Intraoperative errors correlate with surgeon skill and skill declines with intervals of inactivity. The goals of this research were to identify the optimal virtual reality (VR) warm-up curriculum to prime a surgeon's technical skill and validate benefit in the operating room. Materials and methods Surgeons were randomized to receive six trial sessions of a designated set of VR modules on the da Vinci Skills Simulator to identify optimal VR warm-up curricula to prime technical skill. After performing their curricula, warm-up effect was assessed based on performance on a criterion task. The optimal warm-up curriculum was chosen from the group with the best task time and video review–based technical skill. Robot-assisted surgery–experienced surgeons were then recruited to either receive or not receive warm-up before surgery. Skill in the first 15 min of surgery was assessed by blinded surgeon and crowdworker review as well as tool motion metrics. The intervention was performing VR warm-up before human robot-assisted surgery. Warm-up effect was measured using objective performance metrics and video review using the Global Evaluative Assessment of Robotic Skills tool. Linear mixed effects models with a random intercept for each surgeon and nonparametric modified Friedman tests were used for analysis. Results The group performing only a Running Suture task on the simulator was on average 31.3 s faster than groups performing other simulation tasks and had the highest Global Evaluative Assessment of Robotic Skills scores from 41 surgeons who participated. This was chosen as the optimal curriculum. Thereafter, 34 surgeons completed 347 surgeries with corresponding video and tool motion data. No statistically significant differences in skill were observed with the warm-up intervention. Conclusions We conclude that a robotic VR warm-up before performing the early stages of surgery does not impact the technical skill of the surgeon.

Introduction: The Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial sought to determine the safety and efficacy of early high-dose Epo as a potential neuroprotective treatment. We hypothesized that Epo would not increase the incidence or severity of retinopathy of prematurity (ROP). Methods: A total of 941 infants born between 24–0/7 and 27–6/7 weeks’ gestation were randomized to 1,000 U/kg Epo or placebo intravenously for 6 doses, followed by subcutaneous or sham injections of 400 U/kg Epo 3 times a week through 32 weeks post-menstrual age. In this secondary analysis of PENUT trial data, survivors were evaluated for ROP. A modified intention-to-treat approach was used to compare treatment groups. In addition, risk factors for ROP were evaluated using regression methods that account for multiples and allow for adjustment for treatment and gestational age at birth. Results: Of 845 subjects who underwent ROP examination, 503 were diagnosed with ROP with similar incidence and severity between treatment groups. Gestational age at birth, birth weight, prenatal magnesium sulfate, maternal antibiotic exposure, and presence of heart murmur at 2 weeks predicted the development of any ROP, while being on high-frequency oscillator or high-frequency jet ventilation (HFOV/HFJV) at 2 weeks predicted severe ROP. Conclusion: Early high-dose Epo followed by maintenance dosing through 32 weeks does not increase the risk of any or severe ROP in extremely low gestational age neonates. Gestational age, birth weight, maternal treatment with magnesium sulfate, antibiotic use during pregnancy, and presence of a heart murmur at 2 weeks were associated with increased risk of any ROP. Treatment with HFOV/HFJV was associated with an increased risk of severe ROP.

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22–26 months corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs. placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22–26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95(th) percentile for age, and 40% had a diastolic blood pressure (DBP) >95(th) percentile for age. SBP >90(th) percentile occurred less often among recipients of erythropoietin (p95(th) percentile or DBP >90(th) or >95(th) percentiles. CONCLUSIONS: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22–26 months cGA. Recombinant erythropoietin (rhEpo) may protect ELGANs against long-term elevated SBP, but does not appear to protect from AKI, low eGFR, albuminuria or elevated DBP at 22–26 months cGA.

The purpose of this study was to compare injury patterns between recreational skiers and snowboarders. Injured skiers (n = 3,961) and snowboarders (n = 2,428) presented to a mountainside medical clinic, 2012/13-2016/17. Variables investigated for analysis included demographics/characteristics, injury event information, and injury information. Skiers were older than snowboarders (34.3 ± 19.3 vs. 23.2 ± 10.5 years, p 0.001); a greater proportion of skiers were female (46.3% vs. 27.8%, p 0.001). Most skiers (84.4%) and snowboarders (84.5%) were helmeted at the time of injury (p = 0.93). Snowboarders were most frequently beginners (38.9%), skiers were intermediates (37.8%). Falls to snow (skiers = 72.3%, snowboarders = 84.8%) and collisions with natural objects (skiers = 9.7%, snowboarders = 7.4%) were common injury mechanisms. Common skiing injuries were knee sprains (20.5%) and head trauma (8.9%); common snowboarding injuries were wrist fractures (25.7%), shoulder separations (9.1%), and head trauma (9.0%). Given that injury patterns significantly differ between sports, it is important for clinicians, ski patrollers, and resorts to develop and deliver sport-specific injury prevention interventions to most effectively decrease injury burden.

Bacteroides species are abundant in the human intestine and provide numerous beneficial properties to their hosts. The ability of Bacteroides species to convert host and dietary glycans and polysaccharides to energy is paramount to their success in the human gut. We know a great deal about the molecules that these bacteria extract from the human gut but much less about how they convert those molecules into energy. Here, we show that B. fragilis has a complex respiratory pathway with two different enzymes that transfer electrons from NADH to quinone and a third enzyme complex that may use an electron donor other than NADH. Although fermentation has generally been believed to be the main mechanism of energy generation in Bacteroides, we found that a mutant lacking one of the NADH:quinone oxidoreductases was unable to compete with the wild type in the mammalian gut, revealing the importance of respiration to these abundant gut symbionts., In bacteria, the respiratory pathways that drive molecular transport and ATP synthesis include a variety of enzyme complexes that utilize different electron donors and acceptors. This property allows them to vary the efficiency of energy conservation and to generate different types of electrochemical gradients (H+ or Na+). We know little about the respiratory pathways in Bacteroides species, which are abundant in the human gut, and whether they have a simple or a branched pathway. Here, we combined genetics, enzyme activity measurements, and mammalian gut colonization assays to better understand the first committed step in respiration, the transfer of electrons from NADH to quinone. We found that a model gut Bacteroides species, Bacteroides fragilis, has all three types of putative NADH dehydrogenases that typically transfer electrons from the highly reducing molecule NADH to quinone. Analyses of NADH oxidation and quinone reduction in wild-type and deletion mutants showed that two of these enzymes, Na+-pumping NADH:quinone oxidoreductase (NQR) and NADH dehydrogenase II (NDH2), have NADH dehydrogenase activity, whereas H+-pumping NADH:ubiquinone oxidoreductase (NUO) does not. Under anaerobic conditions, NQR contributes more than 65% of the NADH:quinone oxidoreductase activity. When grown in rich medium, none of the single deletion mutants had a significant growth defect; however, the double Δnqr Δndh2 mutant, which lacked almost all NADH:quinone oxidoreductase activity, had a significantly increased doubling time. Despite unaltered in vitro growth, the single nqr deletion mutant was unable to competitively colonize the gnotobiotic mouse gut, confirming the importance of NQR to respiration in B. fragilis and the overall importance of respiration to this abundant gut symbiont.

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p

Practice variability exists in the use of corticosteroids to treat or prevent bronchopulmonary dysplasia in extremely preterm infants, but there is limited information on longer-term impacts.To describe the use of corticosteroids in extremely preterm infants and evaluate the association with neurodevelopmental outcomes.This cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) randomized clinical trial, conducted at 19 participating sites and 30 neonatal intensive care units (NICUs) in the US. Inborn infants born between 24 0/7 and 27 6/7 weeks gestational age between December 2013 and September 2016 were included in analysis. Data analysis was conducted between February 2021 and January 2022.Cumulative dose of dexamethasone and duration of therapy for dexamethasone and prednisolone or methyl prednisolone were evaluated.Demographic and clinical characteristics were described in infants who did or did not receive corticosteroids of interest and survived to discharge. Neurodevelopmental outcomes at 2 years of age were evaluated using the Bayley Scales of Infant Development-Third Edition (BSID-III) at corrected age 2 years.A total of 828 extremely preterm infants (403 [49%] girls; median [IQR] gestational age, 26 [25-27] weeks) born at 19 sites who survived to discharge were included in this analysis, and 312 infants (38%) were exposed to at least 1 corticosteroid of interest during their NICU stay, including 279 exposed to dexamethasone, 137 exposed to prednisolone or methylprednisolone, and 79 exposed to both. Exposed infants, compared with nonexposed infants, had a lower birth weight (mean [SD], 718 [168] g vs 868 [180] g) and were born earlier (mean [SD] gestational age, 25 [1] weeks vs 26 [1] weeks). The median (IQR) start day was 29 (20-44) days for dexamethasone and 53 (30-90) days for prednisolone or methylprednisolone. The median (IQR) total days of exposure was 10 (5-15) days for dexamethasone and 13 (6-25) days for prednisolone or methylprednisolone. The median (IQR) cumulative dose of dexamethasone was 1.3 (0.9-2.8) mg/kg. After adjusting for potential confounders, treatment with dexamethasone for longer than 14 days was associated with worse neurodevelopmental outcomes, with mean scores in BSID-III 7.4 (95% CI, -12.3 to -2.5) points lower in the motor domain (P = .003) and 5.8 (95% CI, -10.9 to -0.6) points lower in the language domain (P = .03), compared with unexposed infants.These findings suggest that long duration and higher cumulative dose of dexamethasone were associated with worse neurodevelopmental scores at corrected age 2 years. Potential unmeasured differences in the clinical conditions of exposed vs unexposed infants may contribute to these findings. Improved standardization of treatment and documentation of indications would facilitate replication studies.

Context The advent of Web-based sports injury surveillance via programs such as the High School Reporting Information Online system and the National Collegiate Athletic Association Injury Surveillance Program has aided the acquisition of wrestling injury data. Objective To describe the epidemiology of injuries sustained in high school boys' wrestling in the 2005–2006 through 2013–2014 academic years and collegiate men's wrestling in the 2004–2005 through 2013–2014 academic years using Web-based sports injury surveillance. Design Descriptive epidemiology study. Setting Online injury surveillance from wrestling teams of high school boys (annual average = 100) and collegiate men (annual average = 11). Patients or Other Participants Male wrestlers who participated in practices and competitions during the 2005–2006 through 2013–2014 academic years in high school or the 2004–2005 through 2013–2014 academic years in college. Main Outcome Measure(s) Athletic trainers collected time-loss (≥24 hours) injuries and exposure data during this time period. Injury rates per 1000 athlete-exposures (AEs), injury rate ratios with 95% confidence intervals, and injury proportions by body site and diagnosis were calculated. Results The High School Reporting Information Online documented 3376 time-loss injuries during 1 416 314 AEs; the National Collegiate Athletic Association Injury Surveillance Program documented 2387 time-loss injuries during 257 297 AEs. The total injury rate was higher in college than in high school (9.28 versus 2.38/1000 AEs; injury rate ratio = 3.89; 95% confidence interval = 3.69, 4.10). In high school, the most commonly injured body parts for both practices and competitions were the head/face (practices = 19.9%, competitions = 21.4%) and shoulder/clavicle (practices = 14.1%, competitions = 21.0%). In college, the most frequently injured body parts for both practices and competitions were the knee (practices = 16.7%, competitions = 30.4%) and head/face (practices = 12.1%, competitions = 14.6%). Conclusions Injury rates were higher in collegiate than in high school players, and the types of injuries sustained most often differed. Based on these results, continued study of primary and secondary prevention of injury in wrestlers across levels of competition is warranted.

Context The sex-based differences in the structure and rules of boys' and girls' lacrosse result in very different styles of play, which may have significant implications for the rates and patterns of injuries. Objective To compare the epidemiology of injuries sustained by boys' and girls' lacrosse players. Design Descriptive epidemiology study. Setting Web-based online surveillance system. Patients or Other Participants The High School Reporting Information Online database was used to analyze injuries reported by certified athletic trainers from 2008–2009 through 2015–2016. Main Outcome Measure(s) Practice and competition injury rates, body site, diagnosis, and mechanism. Results Boys had a higher injury rate than girls (20.9 versus 15.7 per 10 000 athlete-exposures, respectively; rate ratio = 1.3, 95% confidence interval = 1.2, 1.4). The most commonly injured body sites for boys and girls, respectively, were the lower extremities (38.0%, 56.4%) and the head/neck (28.3%, 29.8%). More specifically, the most frequently diagnosed injuries for both boys and girls, respectively, in competitions were concussions (23.1%, 25.6%), ankle ligament sprains (7.8%, 15.3%), upper leg strains (4.8%, 6.7%), and knee ligament sprains (4.2%, 6.7%). The most cited mechanism of injury overall was contact with another player (22.0%); among boys, it was contact with a stick (14.8%) and among girls, the most frequent mechanisms were overuse (25.0%) and contact with a stick (14.7%). Conclusions Injury rates and mechanisms of injuries differed between high school boys' and girls' lacrosse players. Boys had a higher rate of injury, with the most common mechanism of injury being contact with another player compared with overuse in girls. However, similarities were seen between sexes for the most frequently injured body sites and injury diagnoses. Future authors should continue to compare differences in injury rates, equipment upgrades, and rule changes in boys' and girls' lacrosse.

Context: The advent of Web-based sports injury surveillance via programs such as the High School Reporting Information Online system and the National Collegiate Athletic Association Injury Surveillance Program has aided the acquisition of boys' and men's soccer injury data. Objective: To describe the epidemiology of injuries sustained in high school boys' soccer in the 2005–2006 through 2013–2014 academic years and collegiate men's soccer in the 2004–2005 through 2013–2014 academic years using Web-based sports injury surveillance. Design: Descriptive epidemiology study. Setting: Online injury surveillance from soccer teams of high school boys (annual average = 100) and collegiate men (annual average = 41). Patients or Other Participants: Boys' or men's soccer players who participated in practices and competitions during the 2005–2006 through 2013–2014 academic years in high school and the 2004–2005 through 2013–2014 academic years in college, respectively. Main Outcome Measure(s): Athletic trainers collected time-loss (≥24 hours) injury and exposure data. Injury rates per 1000 athlete-exposures (AEs), injury rate ratios (IRRs) with 95% confidence intervals (CIs), and injury proportions by body site and diagnosis were calculated. Results: High School Reporting Information Online documented 2912 time-loss injuries during 1 592 238 AEs; the National Collegiate Athletic Association Injury Surveillance Program documented 4765 time-loss injuries during 686 918 AEs. The injury rate was higher in college than in high school (6.94 versus 1.83/1000 AEs; IRR = 3.79; 95% CI = 3.62, 3.97). Injury rates increased with smaller school size for high schools and were higher in Division I than in Divisions II and III. The injury rate was higher during competitions than during practices in both high school (IRR = 3.55; 95% CI = 3.30, 3.83) and college (IRR = 3.45; 95% CI = 3.26, 3.65). Most injuries were to the lower extremity. However, concussion was a common injury, particularly in collegiate goalkeepers and at all positions for high school players. Concussions accounted for more than one-fifth of injuries in high school games. Conclusions: Injury-prevention interventions should be tailored to reflect variations in the incidence and type of injury by level of competition, event type, and position.

Background Context Although back pain is common among older adults, there is relatively little research on the course of back pain in this age group. Purpose Our primary goals were to report 2-year outcomes of older adults initiating primary care for back pain and to examine the relative importance of patient factors versus medical interventions in predicting 2-year disability and pain. Study Design/Setting This study used a predictive model using data from a prospective, observational cohort from a primary care setting. Patient Sample The study included patients aged ≥65 years at the time of new primary care visits for back pain. Outcome Measures Self-reported 2-year disability (Roland-Morris Disability Questionnaire [RDQ]) and back pain (0–10 numerical rating scale [NRS]). Methods We developed our models using a machine learning least absolute shrinkage and selection operator approach. We evaluated the predictive value of baseline characteristics and the incremental value of interventions that occurred between 0 and 90 days, and the change in patient disability and pain from 0 to 90 days. Limitations included confounding by indication and unmeasured confounding. Results Of 4,665 patients (89%) with follow-up, both RDQ (from mean 9.6 [95% confidence interval {CI} 9.4–9.7] to mean 8.3 [95% CI 8.0–8.5]) and back pain NRS (from mean 5.0 [95% CI 4.9–5.1] to mean 3.5 [95% CI 3.4–3.6]) scores improved slightly. Only 16% (15%-18%) reported no back pain-related disability or back pain at 2 years after initial visits. Regression model parameters explained 40% of the variation (R2) in 2-year RDQ scores, and the addition of 0- to 3-month change in RDQ score and pain improved prediction (R2=51%). The most consistent predictors of 2-year RDQ scores and back pain NRS scores were 0- to 90-day change in each respective outcome and patient confidence in improvement. Patients experienced 50% and 43% improvement in back pain and disability, respectively, 2 years after their initial visit. However, fewer than 20% of patients had complete resolution of their back pain and disability at that time. Conclusions Baseline patient factors were more important than early interventions in explaining disability and pain after 2 years.

Background There has been an evolution in the treatment of chronic hepatitis C (HCV) due to highly effective direct-acting antivirals, however, restriction of treatment to medical specialists hinders escalation of HCV treatment. This is particularly true in resource-limited settings (RLS), which disproportionately represent the burden of HCV worldwide. The ASCEND study in Washington, DC, demonstrated that complete task-shifting can safely and effectively overcome a low provider-to-patient ratio and expand HCV treatment. However, this model has not been applied internationally to RLS. Method The validated ASCEND model was translated to an international clinical program in Kigali, Rwanda, aimed at training general medicine providers on HCV management and obtaining HCV prevalence data. Results The didactic training program administered to 11 new HCV providers in Rwanda increased provider’s knowledge about HCV management. Through the training program, 26% of patients seen during the follow-up period were screened for HCV and a prevalence estimate of 2% was ascertained. Of these patients, 30% were co-infected with hepatitis B. Conclusion The ASCEND paradigm can be successfully implemented in RLS to escalate HCV care, in a self-sustaining fashion that educates more providers about HCV management, while increasing the public’s awareness of HCV and access to treatment.