Effect of Glycocalyx-targeted Therapy on Vascular Function in Older Adults: A Randomized Controlled Trial.

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro{trade mark, serif}, could improve both glycocalyx thickness and endothelial function in older adults, however, this has yet to be tested. We hypothesized that Endocalyx Pro{trade mark, serif} supplementation would increase glycocalyx thickness and endothelial function in older adults. Twenty-three older adults aged 66±7 years (52% female) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-week Endocalyx Pro{trade mark, serif} supplementation (3,712 mg/day) on glycocalyx thickness and endothelial function. Glycocalyx thickness was assessed using the GlycoCheck and endothelial function was determined via brachial artery flow-mediated dilation (FMD). Between-group comparisons revealed Endocalyx Pro{trade mark, serif} did not increase glycocalyx thickness in microvessels 4-25µm (P=0.33), 4-7µm (P=0.07), or 10-25µm (P=0.47) in diameter when compared with placebo. Additionally, Endocalyx Pro did not significantly improve FMD [mean ratio (95% CI) for between-group comparisons, 1.16 (0.77-1.74); P=0.48]. However, Endocalyx Pro{trade mark, serif} improved FMD normalized to shear rate area under the curve [mean ratio (95% CI) for between-group comparisons, 2.41 (1.14,4.13); P=0.001]. Moreover, Endocalyx Pro{trade mark, serif} increased capillary glycocalyx thickness more than placebo in individuals not taking anti-hypertensive medication [mean difference (95% CI) for between-group comparison, -0.08 (-0.15,-0.01); P=0.02]. Our pilot study suggests that Endocalyx Pro{trade mark, serif} supplementation is feasible in older adults but had no measurable effect on overall glycocalyx thickness and FMD. However, Endocalyx Pro{trade mark, serif} may have select effects on capillary glycocalyx thickness and FMD normalized to shear rate among older adults, but further investigation is warranted.

Availability and use of institutional support programs for emergency department healthcare personnel during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic placed health care personnel (HCP) at risk for stress, anxiety, burnout, and post-traumatic stress disorder (PTSD). To address this, hospitals developed programs to mitigate risk. The objectives of the current study were to measure the availability and use of these programs in a cohort of academic emergency departments (EDs) in the United States early in the pandemic and identify factors associated with program use. METHODS: Cross-sectional survey of ED HCP in 21 academic EDs in 15 states between June and September 2020. Site investigators provided data on the availability of 28 programs grouped into 9 categories. Individual support programs included: financial, workload mitigation, individual COVID-19 testing, emotional (e.g., mental health hotline), and instrumental (e.g., childcare) Clinical work support programs included: COVID-19 team communication (e.g., debriefing critical incident), patient-family communication facilitation, patient services (e.g., social work, ethics consultation), and system-level exposure reduction. Participants provided corresponding data on whether they used the programs. We used generalized linear mixed models clustered on site to measure the association between demographic and facility characteristics and program use. RESULTS: We received 1,541 survey responses (96% response rate) from emergency physicians or advanced practice providers, nurses, and nonclinical staff. Program availability in each of the 9 categories was high (>95% of hospitals). Program use was variable, with clinical work support programs used more frequently (28-50% of eligible HCP across categories) than individual employee support programs (6-13% of eligible HCP across categories). Fifty-seven percent of respondents reported that the COVID-19 pandemic had affected their stress and anxiety, and 12% were at elevated risk for PTSD. Program use did not significantly differ for HCP who reported symptoms of anxiety and/or stress compared to those who did not. CONCLUSIONS: Early in the pandemic, support programs were widely available to ED HCP, but program use was low. Future work will focus on identifying barriers and facilitators to use and specific programs most likely to be effective during periods of highest occupational stress.

Enhanced Spine Stability and Survival Lead to Increases in Dendritic Spine Density as an Early Response to Local Alpha-Synuclein Overexpression in Mouse Prefrontal Cortex.

Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. However, the impact of local pathology in the cortex is unknown. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used in vivo 2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC of Thy1-YFP transgenic mice at 1-week intervals from 1 to 2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow-up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.

Catheter salvage from central line-related bloodstream infections in pediatric intestinal failure.

OBJECTIVES: Patients with intestinal failure require central venous access which puts them at risk for central line-associated bloodstream infections (CLABSI). Maintaining vascular patency is critical for this population to receive nutrition support. When CLABSIs occur line salvage can help maintain vascular access. The aim of this study is to assess factors associated with safe and successful central venous catheter salvage. METHODS: Retrospective cohort study of patients with intestinal failure at two tertiary care institutions between 2012 and 2020. The study examined the rates of attempted salvage, factors associated with successful salvage, and complications associated with salvage attempts. RESULTS: Over the study period, 76 patients with intestinal failure were include while central venous access was in place. There were a total of 94 CLABSIs. Salvage was more likely to be attempted when patients were under the direct care of an intestinal rehabilitation service (95% vs. 68%, p = 0.04). The overall successful salvage rate was 91.6% (n = 77). Gram-positive, Gram-negative, and polymicrobial infections had successful salvage rates of 97%, 92%, and 94% respectively. The successful salvage rate for fungal infections was 40%. There was no difference in 30-day complication rates for hospital readmission, intensive care unit admission, and death between patients who underwent salvage attempt and those who did not. CONCLUSIONS: Central line salvage can be safely attempted for many infections in patients with intestinal failure, leading to vascular access preservation.

Increased Maternal BMI at Time of Delivery Associated with Poor Maternal and Neonatal Outcomes.

OBJECTIVE: Current literature on the risks and outcomes of obesity in pregnancy almost exclusively utilizes prepregnancy body mass index (BMI). Given the rising obesity rate across the United States along with a paucity of available information on the relationship between delivery BMI and maternal and neonatal outcomes, our study aimed to determine the association of maternal BMI at delivery with antepartum, intrapartum, and neonatal complications at an academic referral hospital. STUDY DESIGN: This study is a secondary analysis of data collected for a prospective cohort study of Coronavirus Disease-2019 (COVID-19) in pregnancy. This analysis included all patients who delivered term singleton infants between May 1, 2020, and April 30, 2021, at the University of Iowa Hospitals and Clinics. Demographic and clinical data were obtained from the electronic medical record. The relationship between maternal BMI and maternal and neonatal characteristics of interest was assessed using logistic regression models. A statistical significance threshold of 0.05 was used for all comparisons. RESULTS: There were 1,996 women who delivered term singleton infants during the study period. The median BMI at delivery was 31.7 kg/m2 (interquartile range 27.9, 37.2), with 61.1% of women having a BMI ≥ 30.0 kg/m2. Increasing BMI was significantly associated with nonreassuring fetal status, unscheduled cesarean birth, overall cesarean birth rate, postpartum hemorrhage, prolonged postpartum stay, hypertensive diseases of pregnancy, neonatal hypoglycemia, neonatal intensive care unit admission, decreased APGAR score at 1 minute, and increasing neonatal birth weight. Even when controlling for preexisting hypertension in a multivariate model, increasing BMI was associated with gestational hypertension and preeclampsia. CONCLUSION: Increased maternal BMI at delivery was associated with adverse perinatal outcomes. These findings have implications for clinical counseling regarding risks of pregnancy and delivery for overweight and obese patients and may help inform future studies to improve safety, especially by examining reasons for high cesarean rates. KEY POINTS: · Sixty-one percent of delivering patients had a BMI330 kg/m2 at delivery.. · There was a higher cesarean rate with increasing delivery BMI.. · For every 5-unit increase in maternal BMI, neonatal weight increased by 0.47 g..

Somatic growth outcomes in response to an individualized neonatal sodium supplementation protocol.

Objective: Evaluate the impact of a sodium (Na) supplementation protocol based upon urine Na concentration on growth parameters and morbidities. Study Design: Retrospective cohort study of infants 260/7-336/7 weeks gestational age (GA) cared for before (2012-15, n = 225) and after (2016-20, n = 157) implementation of the protocol. Within- and between-group changes over time were assessed using repeated measures generalized linear models. Results: For infants 260/7-296/7 weeks GA, utilization of the protocol was associated with increased mean body weight z-score at 8-weeks postnatal age, increased mean head circumference z-score at 16-weeks postnatal age, and decreased time on mechanical ventilation (all p < 0.02). No impact on growth was identified for infants 30-336/7 weeks GA. Incidences of hypertension, hypernatremia, bronchopulmonary dysplasia, and culture positive sepsis were unaffected by the protocol. Conclusion: Protocolized Na supplementation results in improved growth and reduced time on invasive mechanical ventilation in extremely preterm infants without increasing incidence of morbidities.

Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact.

Autism spectrum disorders (ASD) involve brain wide abnormalities that contribute to a constellation of symptoms including behavioral inflexibility, cognitive dysfunction, learning impairments, altered social interactions, and perceptive time difficulties. Although a single genetic variation does not cause ASD, genetic variations such as one involving a non-canonical Wnt signaling gene, Prickle2, has been found in individuals with ASD. Previous work looking into phenotypes of Prickle2 knock-out (Prickle2-/-) and heterozygous mice (Prickle2-/+) suggest patterns of behavior similar to individuals with ASD including altered social interaction and behavioral inflexibility. Growing evidence implicates the cerebellum in ASD. As Prickle2 is expressed in the cerebellum, this animal model presents a unique opportunity to investigate the cerebellar contribution to autism-like phenotypes. Here, we explore cerebellar structural and physiological abnormalities in animals with Prickle2 knockdown using immunohistochemistry, whole-cell patch clamp electrophysiology, and several cerebellar-associated motor and timing tasks, including interval timing and eyeblink conditioning. Histologically, Prickle2-/- mice have significantly more empty spaces or gaps between Purkinje cells in the posterior lobules and a decreased propensity for Purkinje cells to fire action potentials. These structural cerebellar abnormalities did not impair cerebellar-associated behaviors as eyeblink conditioning and interval timing remained intact. Therefore, although Prickle-/- mice show classic phenotypes of ASD, they do not recapitulate the involvement of the adult cerebellum and may not represent the pathophysiological heterogeneity of the disorder.

Accuracy of patient-reported spell duration: A comparative study.

Clinicians rely heavily on patient histories to make medical diagnoses, most of which are inherently subjective and prone to inaccuracies. The aim of this study is to compare the subjective versus objective duration of spells through a retrospective chart review of patients admitted to the epilepsy monitoring unit at our tertiary care medical center. One hundred patients were analyzed. Differences in the accuracy of subjective estimations versus objective duration were compared by age, sex, focal versus generalized, location (frontal versus non-frontal), and spell type (focal aware versus impaired awareness and epileptic versus non-epileptic). Our data show that patients are poor subjective estimators, with 73% of patients overestimating the duration of their spells. We did not find differences in estimated duration by age, sex, seizure location or spell type. A notable exception was patients with generalized convulsive seizures, who accurately reported spell duration to within 17 s. This is likely because these seizures are stereotypical, and patients/family time them. Moreover, patients with non-epileptic spells were worse estimators of their spell duration than those with epileptic spells. In addition, although the prefrontal lobe plays a role in time estimation, we did not find that patients with frontal lobe seizures were worse estimators than those with non-frontal seizures, but invasive monitoring can more precisely localize seizures within areas of the frontal lobe responsible for time estimation. Our data emphasize the importance of not relying solely on patient-reported time estimation in diagnosing and developing treatment plans and instead instructing patients to time their spells.

COVID-19 outcomes in persons with hemophilia: results from a US-based national COVID-19 surveillance registry.

BACKGROUND: Hypercoagulable state contributing to thrombotic complications worsens COVID-19 severity and outcomes, whereas anticoagulation improves outcomes by alleviating hypercoagulability. OBJECTIVES: To examine whether hemophilia, an inherent hypocoagulable condition, offers protection against COVID-19 severity and reduces venous thromboembolism (VTE) risk in persons with hemophilia (PwH). METHODS: A 1:3 propensity score-matched retrospective cohort study used national COVID-19 registry data (January 2020 through January 2022) to compare outcomes between 300 male PwH and 900 matched controls without hemophilia. RESULTS: Analyses of PwH demonstrated that known risk factors (older age, heart failure, hypertension, cancer/malignancy, dementia, and renal and liver disease) contributed to severe COVID-19 and/or 30-day all-cause mortality. Non-central nervous system bleeding was an additional risk factor for poor outcomes in PwH. Odds of developing VTE with COVID-19 in PwH were associated with pre-COVID VTE diagnosis (odds ratio [OR], 51.9; 95% CI, 12.8-266; p < .001), anticoagulation therapy (OR, 12.7; 95% CI, 3.01-48.6; p < .001), and pulmonary disease (OR, 16.1; 95% CI, 10.4-25.4; p < .001). Thirty-day all-cause mortality (OR, 1.27; 95% CI, 0.75-2.11; p = .3) and VTE events (OR, 1.32; 95% CI, 0.64-2.73; p = .4) were not significantly different between the matched cohorts; however, hospitalizations (OR, 1.58; 95% CI, 1.20-2.10; p = .001) and non-central nervous system bleeding events (OR, 4.78; 95% CI, 2.98-7.48; p < .001) were increased in PwH. In multivariate analyses, hemophilia did not reduce adverse outcomes (OR, 1.32; 95% CI, 0.74-2.31; p = .2) or VTE (OR, 1.14; 95% CI, 0.44-2.67; p = .8) but increased bleeding risk (OR, 4.70; 95% CI, 2.98-7.48; p < .001). CONCLUSION: After adjusting for patient characteristics/comorbidities, hemophilia increased bleeding risk with COVID-19 but did not protect against severe disease and VTE.

Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes.

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09). CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

Effects of rurality and distance to care on perinatal outcomes over a 1-year period during the COVID-19 pandemic.

PURPOSE: Our aim was to investigate the roles of rurality and distance to care on adverse perinatal outcomes and COVID-19 seroprevalence at the time of delivery over a 1-year period. METHODS: Data were collected from the electronic medical record on all pregnant patients who delivered at a single, large, Midwest academic medical center over 1 year. Rurality was classified using standard Rural-Urban Commuting Area codes. Geographic Information System tools were used to map outcomes. Data were analyzed with univariate and multivariate models, controlling for Body Mass Index (BMI), insurance status, and parity. FINDINGS: A total of 2,497 patients delivered during the study period; 20% of patients were rural (n = 499), 18.6% were micropolitan (n = 466), and 61.4% were metropolitan (n = 1,532). 10.4% of patients (n = 259) were COVID-19 seropositive. Rural patients did not experience higher rates of any measured adverse outcomes than metropolitan patients; micropolitan patients had increased odds of preterm labor (OR = 1.41, P = .022) and pre-eclampsia (OR = 1.78, P<.001). Patients living 30+ miles away from the medical center had increased odds of preterm labor (OR = 1.94, P<.001), pre-eclampsia (OR = 1.73, P = .002), and infant admission to the neonatal intensive care unit (OR = 2.12, P<.001), as well as lower gestational age at delivery (ß = -9.2 days, P<.001) and birth weight (ß = -206 grams, P<.001). CONCLUSION: Distance to care, rather than rurality, was the key predictor of multiple adverse perinatal outcomes in this cohort of deliveries over a 1-year period. Our study suggests that rurality should not be used as a standalone indicator of access to care without further knowledge of the specific barriers affecting a given population.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status.

BACKGROUND: Widely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on disorder sub-type (BDI vs II), depressed mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task. RESULTS: Results suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power during the task compared to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, depressed mood, or antipsychotic medication use. CONCLUSIONS: This work suggests that BD sub-type, depressed mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

Enhanced spine stability and survival lead to increases in dendritic spine density as an early response to local alpha-synuclein overexpression in mouse prefrontal cortex.

Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. Patients with LBDs develop cognitive changes, including abnormalities in executive function, attention, hallucinations, slowed processing, and cognitive fluctuations. The causes of these non-motor symptoms remain unclear; however, accumulation of alpha-Synuclein aggregates in the cortex and subsequent interference of synaptic and cellular function could contribute to psychiatric and cognitive symptoms. It is unknown how the cortex responds to local pathology in the absence of significant secondary effects of alpha-Synuclein pathology in the brainstem. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used in vivo 2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC of Thy1-YFP transgenic mice at 1-week intervals from 1-2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.

Effect of Resveratrol on Endothelial Function in Patients with CKD and Diabetes: A Randomized Controlled Trial.

BACKGROUND: Patients with CKD and diabetes are at higher risk of developing cardiovascular disease, in part, because of impaired endothelial function. Cardioprotective compounds such as resveratrol could improve endothelial function and attenuate the cardiovascular burden in patients with CKD and diabetes. We hypothesized that resveratrol supplementation would improve endothelial function in patients with CKD and diabetes. METHODS: Twenty-eight adults aged 68±7 years (84% men) with stage 3 CKD and diabetes were enrolled in a randomized, double-blind, placebo-controlled, crossover study to investigate the effects of 6-week resveratrol supplementation (400 mg/d) on endothelial function. Endothelial function was determined through brachial artery flow-mediated dilation. RESULTS: The mean values for eGFR and hemoglobin A 1c were 40±9 ml/min per 1.73 m 2 and 7.36%±0.72%, respectively. Compared with placebo, resveratrol supplementation increased flow-mediated dilation (ratio of geometric mean changes and 95% confidence interval for between-group comparisons, 1.43 (1.15 to 1.77); P value = 0.001). eGFR, hemoglobin A 1c , BP, and nitroglycerin-mediated dilation were unchanged with resveratrol or placebo ( P = 0.15), suggesting the observed change in flow-mediated dilation was likely independent of changes in traditional cardiovascular risk factors. CONCLUSIONS: Resveratrol supplementation improved endothelial function in patients with CKD and diabetes. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Resveratrol and Vascular Function in CKD, NCT03597568 .

Rates and predictors of teen driver crash culpability.

BACKGROUND: Motor-vehicle crash risk is highest among teen drivers. Despite a wealth of research on the topic, there are still many contributors to these crashes that are not well understood. The current study sought to examine the contribution of graduated driver licensing (GDL) restrictions, sex, age, roadway circumstances, and citation history to teen drivers' crash culpability. METHOD: Crash system data from the Iowa Department of Transportation were linked with traffic-related charges from the Iowa Court Information System. Crashes involving teens aged 14 to 17 years between 2016 and 2019 were analyzed (N = 19,847). Culpability was determined using the driver contributing circumstances from the crash report. Moving and non-moving traffic citations issued prior to the date of each crash were considered. A multivariable logistic regression model was constructed to examine predictors of crash culpability. RESULTS: Teen drivers were determined to be culpable for more than two thirds of crashes (N = 13,604, 68.54%). Culpability was more prevalent among males, younger teens, in rural areas, in the presence of reported roadway contributing circumstances, during hours of restricted nighttime driving, and among teens with citation histories that included both moving and non-moving citations. Similarly, multivariable model results indicated that the likelihood of culpability was higher among males, in rural areas, and at each stage of GDL compared to teen drivers with unrestricted licenses. While drivers with a history of both moving and non-moving violations were more likely to be culpable, those with a history of only moving or only non-moving violations were less likely to be culpable compared to those with no violation history. CONCLUSION: Sex, crash location, and GDL stage were associated with teen driver crash culpability. A singular prior moving or non-moving violation may play a protective role in teen crash culpability.

Discovering novel barriers to eBook implementation.

BACKGROUND: Medical errors when managing inpatient paediatric patients with diabetes mellitus can lead to significant morbidity and mortality, necessitating improvement in training of medical trainees. Previous educational interventions have focused on time and resource intensive methods, restricting their applicability to teaching in time-limited scenarios. We chose a blended learning approach to create and implement a novel eBook for use by trainees and then aimed to determine the efficacy and potential barriers to that implementation. APPROACH: We grounded our work in complex adaptive systems theory and used the framework of complex adaptive blended learning system (CABLS) to shape both our implementation and evaluation. We utilised an embedded mixed methodology to quantitatively evaluate efficacy via knowledge acquisition and self-reported confidence and to qualitatively evaluate barriers via open-ended questions. EVALUATION: Between 2022 and 2023, the study enrolled 72 learners and 12 educators. There was no statistically significant difference in change in knowledge acquisition and self-reported confidence between learners who did and did not have access to the eBook. Learners and educators identified several unique and novel barriers to eBook implementation, which were mapped to the CABLS framework. IMPLICATIONS: Our results on the efficacy of implementation are inconclusive, possibly due to the small participant size and implying a need for multi-institutional evaluation. Our qualitative results demonstrated previously unknown barriers to eBook implementation. This knowledge can assist other medical specialties as they implement their own eBooks. We also hope to use these barriers to improve implementation in our next iteration: the outpatient setting.

Disruption of the circadian rhythm of melatonin: A biomarker of critical illness severity.

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status.

Background : Widely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on BD sub-type (BDI vs II), mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task. Results : Results suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power compared during the task to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, mood, or antipsychotic medication use. Conclusions : his work suggests that BD sub-type, mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

How Effective Was the 2014 AUA Cryptorchidism Guideline? A Multi-institutional Evaluation.

INTRODUCTION: In 2014, the AUA published guidelines regarding the evaluation of cryptorchidism. This multi-institutional study aims to determine if these guidelines reduced the age of referral and the utilization of ultrasound in boys with cryptorchidism. We hypothesize that delayed referral continues, and utilization of ultrasound remains unchanged. METHODS: A retrospective review of boys referred for the evaluation of cryptorchidism was performed at 4 academic institutions, collecting data for 1 year prior (2013) and 2 nonconsecutive years following guideline creation (2015 and 2019). Across these time frames, we compared median ages at evaluation and surgery, and rates of patient comorbidities, orchiopexy, and preevaluation ultrasound. RESULTS: A total of 3,293 patients were included. The median age at initial pediatric urology evaluation in all cohorts was 39 months (IQR: 14-92 months). Following publication of the AUA Guidelines, there was no difference (P = .08) in the median age at first evaluation by a pediatric urologist between 2013 and 2015, and an increase (P = .03) between 2013 and 2019. Overall, 21.2% of patients received an ultrasound evaluation prior to referral, with no significant difference between 2013 and 2015 (P = .9) or 2019 (P = .5) cohorts. CONCLUSIONS: Our data suggest that, despite publication of the AUA Guidelines on evaluation and treatment of cryptorchidism, there has been no reduction in the age of urological evaluation or the utilization of imaging in boys with undescended testis. Finding alternative avenues to disseminate these evidence-based recommendations to referring providers and exploring barriers to guideline adherence is necessary to improve care for patients with cryptorchidism.

Interictal respiratory variability predicts severity of hypoxemia after generalized convulsive seizures.

OBJECTIVE: Severe respiratory dysfunction induced by generalized convulsive seizures (GCS) is now thought to be a common mechanism for sudden unexpected death in epilepsy (SUDEP). In a mouse model of seizure-induced death, increased interictal respiratory variability was reported in mice that later died of respiratory arrest after GCS. We studied respiratory variability in epilepsy patients as a predictive tool for severity of postictal hypoxemia, a potential biomarker for SUDEP risk. We then explored the relationship between respiratory variability and central CO2 drive, measured by the hypercapnic ventilatory response (HCVR). METHODS: We reviewed clinical, video-electroencephalography, and respiratory (belts, airflow, pulse oximeter, and HCVR) data of epilepsy patients. Mean, SD, and coefficient of variation (CV) of interbreath interval (IBI) were calculated. Primary outcomes were: (1) nadir of capillary oxygen saturation (SpO2 ) and (2) duration of oxygen desaturation. Poincaré plots of IBI were created. Covariates were evaluated in univariate models, then, based on Akaike information criteria (AIC), multivariate regression models were created. RESULTS: Of 66 GCS recorded in 131 subjects, 30 had interpretable respiratory data. In the multivariate model with the lowest AIC value, duration of epilepsy was a significant predictor of duration of oxygen desaturation. Duration of tonic phase and CV of IBI during the third postictal minute correlated with SpO2 nadir, whereas CV of IBI during non-rapid eye movement sleep had a negative correlation. Poincaré plots showed that long-term variability was significantly greater in subjects with ≥200 s of postictal oxygen desaturation after GCS compared to those with <200 s desaturation. Finally, HCVR slope showed a negative correlation with measures of respiratory variability. SIGNIFICANCE: These results indicate that interictal respiratory variability predicts severity of postictal oxygen desaturation, suggesting its utility as a potential biomarker. They also suggest that interictal respiratory control may be abnormal in some patients with epilepsy.