Loss-of-Function Variants in CUL3 Cause a Syndromic Neurodevelopmental Disorder.

OBJECTIVE: De novo variants in cullin-3 ubiquitin ligase (CUL3) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism. METHODS: Genetic data and detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells. RESULTS: We assembled a cohort of 37 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 35 have loss-of-function (LoF) and 2 have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugates in vitro. Notably, we show that 4E-BP1 (EIF4EBP1), a prominent substrate of CUL3, fails to be targeted for proteasomal degradation in patient-derived cells. INTERPRETATION: Our study further refines the clinical and mutational spectrum of CUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism. ANN NEUROL 2024.

Sex differences in stroke reperfusion therapy in Aotearoa (New Zealand).

BACKGROUND AND AIMS: Stroke is a leading cause of death in Aotearoa (New Zealand), and stroke reperfusion therapy is a key intervention. Sex differences in stroke care have previously been asserted internationally. This study assessed potential differences in stroke reperfusion rates and quality metrics by sex in Aotearoa (New Zealand). METHODS: This study used data from three overlapping sources. The National Stroke Reperfusion Register provided 4-year reperfusion data from 2018 to 2021 on all patients treated with reperfusion therapy (intravenous thrombolysis and thrombectomy), including time delays, treatment rates, mortality and complications. Linkage to Ministry of Health administrative and REGIONS Care study data provided an opportunity to control for confounders and explore potential mechanisms. T-test and Wilcoxon rank-sum analyses were used for continuous variables, while the chi-squared test and logistic regression were used for comparing dichotomous variables. RESULTS: Fewer women presented with ischaemic stroke (12 186 vs 13 120) and were 4.2 years older than men (median (interquartile range (IQR)) 79 (68-86) vs 73 (63-82) years). Women were overall less likely to receive reperfusion therapy (13.9% (1704) vs 15.8% (2084), P < 0.001) with an adjusted odds ratio of 0.83 (0.77-0.90), P < 0.001. The adjusted odds ratio for thrombolysis was lower for women (0.82 (0.76-0.89), P < 0.001), but lower rates of thrombectomy fell just short of statistical significance ((0.89 (0.79-1.00), P = 0.05). There were no significant differences in complications, delays or documented reasons for non-thrombolysis. CONCLUSIONS: Women were less likely to receive thrombolysis, even after adjusting for age and stroke severity. We found no definitive explanation for this disparity.

Global variability of vascular and peritoneal access for chronic dialysis.

AIM: Vascular and peritoneal access are essential elements for sustainability of chronic dialysis programs. Data on availability, patterns of use, funding models, and workforce for vascular and peritoneal accesses for dialysis at a global scale is limited. METHODS: An electronic survey of national leaders of nephrology societies, consumer representative organizations, and policymakers was conducted from July to September 2018. Questions focused on types of accesses used to initiate dialysis, funding for services, and availability of providers for access creation. RESULTS: Data from 167 countries were available. In 31 countries (25% of surveyed countries), >75% of patients initiated haemodialysis (HD) with a temporary catheter. Seven countries (5% of surveyed countries) had >75% of patients initiating HD with arteriovenous fistulas or grafts. Seven countries (5% of surveyed countries) had >75% of their patients starting HD with tunnelled dialysis catheters. 57% of low-income countries (LICs) had >75% of their patients initiating HD with a temporary catheter compared to 5% of high-income countries (HICs). Shortages of surgeons to create vascular access were reported in 91% of LIC compared to 46% in HIC. Approximately 95% of participating countries in the LIC category reported shortages of surgeons for peritoneal dialysis (PD) access compared to 26% in HIC. Public funding was available for central venous catheters, fistula/graft creation, and PD catheter surgery in 57%, 54% and 54% of countries, respectively. CONCLUSION: There is a substantial variation in the availability, funding, workforce, and utilization of vascular and peritoneal access for dialysis across countries regions, with major gaps in low-income countries.

Global variations in funding and use of hemodialysis accesses: an international report using the ISN Global Kidney Health Atlas.

BACKGROUND: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. METHODS: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. RESULTS: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). CONCLUSIONS: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

In-Hospital Formula Supplementation in Appalachian Women Intending to Exclusively Breastfeed.

OBJECTIVE: In-hospital formula supplementation places infants at risk for early breastfeeding cessation. The study's aim was to identify predictive and protective factors for in-hospital formula supplementation in individuals documented as wanting to exclusively breastfeed and residing in a geographic region with adverse social determinants of health and low breastfeeding rates. Additionally, we wished to determine if lactation consultation served as a protective factor against supplementation. METHODS: In this cross-sectional study, we retrospectively reviewed 500 randomly selected charts of newborns born in a 12 month period at a regional tertiary care hospital. We included healthy, full-term neonates having a recorded maternal decision to exclusively breastfeed. Maternal-newborn dyad characteristics were compared between those exclusively breastfeeding and those with in-hospital formula supplementation. RESULTS: Of the 500 charts, 70% of individuals desired to exclusively breastfeed. Overall, 41% of breastfed newborns were supplemented with formula before discharge, and 32% of women met with lactation consultants prior to supplementation. No statistically significant association was present between exclusive breastfeeding at discharge and meeting with a hospital lactation consultant (p = 0.55). When controlling for the confounders of maternal demographics and lactation consultation, significant associations with formula supplementation included Cesarean delivery (odd ratio: 2.08, 95% confidence interval: 1.04-4.16), primiparity (2.48, 1.27-4.87), and high school level of education (2.78, 1.33-5.78). CONCLUSIONS: Maternal characteristics of high school level educational, primiparity, and Caesarean delivery place individuals at risk for in-hospital formula supplementation in individuals wishing to exclusively breastfeed. Addressing barriers to exclusive breastfeeding is essential to enhance maternal and newborn health equity.

Intersection of Community Violence and Prenatal Substance Exposure: A Spatiotemporal Analysis.

OBJECTIVES: Maternal substance use during pregnancy is a known risk factor for poor birth outcomes and lifelong health consequences. In addition, exposure to domestic and community violence can be associated with adverse birth outcomes. Due to limited research examining public health challenges linked to prenatal substance exposure (PSE)/neonatal abstinence syndrome (NAS) at the population level, we examined possible geographic and temporal intersections between (1) community violence and PSE/NAS, and (2) community gun violence and PSE/NAS. STUDY DESIGN: We conducted a study using abstracted records of neonates born at a tertiary referral hospital from 2012 to 2019 having a diagnosis code for PSE/NAS (n = 1,523). Cases of community violence were identified using a hospital-based Trauma Registry during the 2012 to 2019 period (n = 1,580). We identified zones of spatial clustering and geographic overlap between community violence and PSE/NAS using emerging hot spot analysis. RESULTS: Geographic and temporal clustering of PSE/NAS occurred. PSE/NAS had statistically significant zones of overlap with community assault cases (New Hot Spot 15 zones, Consecutive 5 zones, Sporadic Hot Spot 62 zones with a p < 0.01). PSE/NAS also clustered with community gun violence (New Hot Spot 11 zones, Consecutive Hot Spot 90 zones, Intensifying Hot Spot 13 zones, Sporadic Hot Spot 20 zones with a p < 0.01). CONCLUSION: Spatiotemporal overlap occurred between community violence and the adverse neonatal event of PSE/NAS. By allocating resources to identified geographic areas of increased risk, the health of vulnerable communities can be improved. KEY POINTS: · PSE/NAS geographically and temporally clusters with community violence.. · PSE/NAS geographically and temporally clusters with community gun violence.. · Resources should be provided to communities with increased risk.. · By allocating resources, communities members' health can be improved..

Epigenome-Wide Association Study of Depressive Symptoms in Black Women in the InterGEN Study.

(1) The prevalence of depression is two times higher in women than men. Black women have an increased risk of depression due to stressors such as low socioeconomic status and perceived discrimination. Depression is likely influenced by both genetic and environmental factors. Psychosocial stressors can influence DNA methylation (DNAm), leading to changes in gene expression and ultimately, depression. The objective of this study was to examine associations between DNAm and depressive symptoms in Black women. (2) This study was a secondary analysis of data from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) Study. Perceived discrimination was assessed using Krieger's Experiences of Discrimination and Waelde's Race-Related Events Scale, and participants were screened for depressive symptoms with the Beck Depression Inventory. Raw data from saliva samples were analyzed using the Illumina Infinium Epic (850 K) BeadChip and then preprocessed in RStudio. (3) Differential methylation analysis identified DNAm sites and regions associated with depressive symptoms. Six DNAm sites had a q-value less than 0.05. Additionally, of the 25 regions identified, 12 were associated with neurological diseases or disorders. (4) These findings suggest that there is a neurological component to depression, which should be considered during treatment.

Comparison of Stroke Care Costs in Urban and Nonurban Hospitals and Its Association With Outcomes in New Zealand: A Nationwide Economic Evaluation.

BACKGROUND: Although geographical differences in treatment and outcomes after stroke have been described, we lack evidence on differences in the costs of treatment between urban and nonurban regions. Additionally, it is unclear whether greater costs in one setting are justified given the outcomes achieved. We aimed to compare costs and quality-adjusted life years in people with stroke admitted to urban and nonurban hospitals in New Zealand. METHODS: Observational study of patients with stroke admitted to the 28 New Zealand acute stroke hospitals (10 in urban areas) recruited between May and October 2018. Data were collected up to 12 months poststroke including treatments in hospital, inpatient rehabilitation, other health service utilization, aged residential care, productivity, and health-related quality of life. Costs in New Zealand dollars were estimated from a societal perspective and assigned to the initial hospital that patients presented to. Unit prices for 2018 were obtained from government and hospital sources. Multivariable regression analyses were conducted when assessing differences between groups. RESULTS: Of 1510 patients (median age 78 years, 48% female), 607 presented to nonurban and 903 to urban hospitals. Mean hospital costs were greater in urban than nonurban hospitals ($13 191 versus $11 635, P=0.002), as were total costs to 12 months ($22 381 versus $17 217, P<0.001) and quality-adjusted life years to 12 months (0.54 versus 0.46, P<0.001). Differences in costs and quality-adjusted life years remained between groups after adjustment. Depending on the covariates included, costs per additional quality-adjusted life year in the urban hospitals compared to the nonurban hospitals ranged from $65 038 (unadjusted) to $136 125 (covariates: age, sex, prestroke disability, stroke type, severity, and ethnicity). CONCLUSIONS: Better outcomes following initial presentation to urban hospitals were associated with greater costs compared to nonurban hospitals. These findings may inform greater targeted expenditure in some nonurban hospitals to improve access to treatment and optimize outcomes.

Determining mating type and ploidy in Rhodotorula toruloides and its effect on growth on sugars from lignocellulosic biomass.

Rhodotorula toruloides is being developed for the use in industrial biotechnology processes because of its favorable physiology. This includes its ability to produce and store large amounts of lipids in the form of intracellular lipid bodies. Nineteen strains were characterized for mating type, ploidy, robustness for growth, and accumulation of lipids on inhibitory switchgrass hydrolysate (SGH). Mating type was determined using a novel polymerase chain reaction (PCR)-based assay, which was validated using the classical microscopic test. Three of the strains were heterozygous for mating type (A1/A2). Ploidy analysis revealed a complex pattern. Two strains were triploid, eight haploid, and eight either diploid or aneuploid. Two of the A1/A2 strains were compared to their parents for growth on 75%v/v concentrated SGH. The A1/A2 strains were much more robust than the parental strains, which either did not grow or had extended lag times. The entire set was evaluated in 60%v/v SGH batch cultures for growth kinetics and biomass and lipid production. Lipid titers were 2.33-9.40 g/L with a median of 6.12 g/L, excluding the two strains that did not grow. Lipid yields were 0.032-0.131 (g/g) and lipid contents were 13.5-53.7% (g/g). Four strains had significantly higher lipid yields and contents. One of these strains, which had among the highest lipid yield in this study (0.131 ± 0.007 g/g), has not been previously described in the literature. SUMMARY: The yeast Rhodotorula toruloides was used to produce oil using sugars extracted from a bioenergy grass.

Advancing Exercise Science for Better Health Outcomes Across the Spectrum of Chronic Kidney Disease.

Despite over 30 years of evidence for improvements in physical function, physical fitness, and health-related quality of life with exercise training in individuals with chronic kidney disease, access to dedicated exercise training programs remains outside the realm of standard of care for most kidney care programs. In this review, we explore possible reasons for this by comparing approaches in other chronic diseases where exercise rehabilitation has become the standard of care, identifying enablers and factors that need to be addressed for continued growth in this area, and discussing knowledge gaps for future research. For exercise rehabilitation to be relevant to all stakeholders and become a sustainable component of kidney care, a focus on the effect of exercise on clinically relevant outcomes that are prioritized by individuals living with kidney disease, use of evidence-based implementation strategies for diverse settings and populations, and approaching exercise as a medical therapy are required.

A roadmap for social determinants of health and biological nursing research in the National Institute of Nursing Research 2022-2026 Strategic Plan: Optimizing health and advancing health equity using antiracist framing.

BACKGROUND: Health equity is essential for improving the well-being of all individuals and groups, and research remains a critical element for understanding barriers to health equity. While considering how to best support research that acknowledges current health challenges, it is crucial to understand the role of social justice frameworks within health equity research and the contributions of minoritized researchers. Additionally, there should be an increased understanding of the influence of social determinants of health on biological mechanisms. PURPOSE: Biological health equity research seeks to understand and address health disparities among historically excluded populations. DISCUSSION: While there are examples of studies in this area led by minoritized researchers, some individuals and groups remain understudied due to underfunding. Research within minoritized populations must be prioritized to authentically achieve health equity. Furthermore, there should be increased funding from National Institutes of Health to support minoritized researchers working in this area.

Pre-COVID-19 predictors of low-income women's COVID-19 appraisal, coping, and changes in mental health during the pandemic.

Study examined predictors and mental health consequences of appraisal (threat, support satisfaction) and coping (active, avoidant) in a sample of low-income women during coronavirus disease 2019 (COVID-19). Pre-COVID-19 contextual risk and individual resources and COVID-19-specific risk factors were examined as predictors of COVID-19 appraisal and coping, which, in turn, were tested as predictors of changes in depression and anxiety across the pandemic. Pre-COVID-19 resilience predicted more active coping, whereas pre-COVID-19 anxiety and depression predicted more avoidant coping and lower support satisfaction, respectively. Increases in anxiety were predicted by lower pre-COVID-19 self-compassion and higher concurrent threat appraisal and avoidant coping. Increases in depression were related to lower pre-COVID-19 self-compassion, active coping and support satisfaction, and higher COVID-19 hardships and health risk. Findings highlight contextual and individual factors and processes that contribute to mental health problems in a vulnerable population during community-level stressors, with implications for prevention and intervention.

Maternal mental health mediates the effects of pandemic-related stressors on adolescent psychopathology during COVID-19.

BACKGROUND: This study examined whether COVID-19-related maternal mental health changes contributed to changes in adolescent psychopathology. METHODS: A community sample of 226 adolescents (12 years old before COVID-19) and their mothers were asked to complete COVID-19 surveys early in the pandemic (April-May 2020, adolescents 14 years) and approximately 6 months later (November 2020-January 2021). Surveys assessed pandemic-related stressors (health, financial, social, school, environment) and mental health. RESULTS: Lower pre-pandemic family income-to-needs ratio was associated with higher pre-pandemic maternal mental health symptoms (anxiety, depression) and adolescent internalizing and externalizing problems, and with experiencing more pandemic-related stressors. Pandemic-related stressors predicted increases in maternal mental health symptoms, but not adolescent symptoms when other variables were covaried. Higher maternal mental health symptoms predicted concurrent increases in adolescent internalizing and externalizing. Maternal mental health mediated the effects of pre-pandemic income and pandemic-related stressors on adolescent internalizing and externalizing problems. CONCLUSIONS: Results indicate that adolescent mental health is closely tied to maternal mental health during community-level stressors such as COVID-19, and that pre-existing family economic context and adolescent symptoms increase risk for elevations in symptoms of psychopathology.

Addressing feasibility challenges to delivering intradialytic exercise interventions: a theory-informed qualitative study.

BACKGROUND: Intradialytic exercise (IDE) may improve physical function and health-related quality of life. However, incorporating IDE into standard hemodialysis care has been slow due to feasibility challenges. We conducted a multicenter qualitative feasibility study to identify potential barriers and enablers to IDE and generate potential solutions to these factors. METHODS: We conducted 43 semistructured interviews with healthcare providers and patients across 12 hospitals in Ontario, Canada. We used the Theoretical Domains Framework and directed content analysis to analyze the data. RESULTS: We identified eight relevant domains (knowledge, skills, beliefs about consequences, beliefs about capabilities, environmental context and resources, goals, social/professional role and identity, and social influences) represented by three overarching categories: knowledge, skills and expectations: lack of staff expertise to oversee exercise, uncertainty regarding exercise risks, benefits and patient interest, lack of knowledge regarding exercise eligibility; human, material and logistical resources: staff concerns regarding workload, perception that exercise professionals should supervise IDE, space, equipment and scheduling conflict concerns; and social dynamics of the unit: local champions and patient stories contribute to IDE sustainability. We developed a list of actionable solutions by mapping barriers and enablers to behavior change techniques. We also developed a feasibility checklist of 47 questions identifying key factors to address prior to IDE launch. CONCLUSIONS: Evidence-based solutions to identified barriers to and enablers of IDE and a feasibility checklist may help recruit and support units, staff and patients and address key challenges to the delivery of IDE in diverse clinical and research settings.

Physical Activity in Renal Disease and the Effect on Hypertension: A Randomized Controlled Trial.

INTRODUCTION: Exercise is an effective strategy for blood pressure (BP) reduction in the general population, but its efficacy for the management of hypertension in chronic kidney disease (CKD) is not known. We evaluated the difference in 24-h ambulatory systolic BP (SBP) with exercise training in people with moderate to severe CKD. METHODS: Participants with an estimated glomerular filtration rate (eGFR) of 15-44 mL/min per 1.73 m2 and SBP >120 mm Hg were randomized to receive thrice-weekly moderate-intensity aerobic-based exercise over 24 weeks, or usual care. Phase 1 included supervised in-center and home-based sessions for 8 weeks. Phase 2 was 16 weeks of home-based sessions. BP, arterial stiffness, cardiorespiratory fitness, and markers of cardiovascular (CV) risk were analyzed using mixed linear regression. RESULTS: We randomized 44 people; 36% were female, the median age was 69 years, 55% had diabetes, and the median eGFR was 28 mL/min per 1.73 m2. Compared with usual care, there was no significant change in 24-ambulatory SBP at 8 weeks (2.96 mm Hg; 95% confidence interval (CI): -2.56, 8.49) or 24 weeks. Peak oxygen uptake improved by 1.9 mL/kg/min in the exercise group (95% CI: 0.03, 3.79) at 8 weeks with a trend toward higher body mass index 1.84 kg/m2 (95% CI: -0.10, 3.78) and fat free mass, but this was not sustained at 24 weeks. Markers of CV risk were unchanged. CONCLUSIONS: Despite an improvement in peak aerobic capacity and body composition, we did not detect a change in 24-h ambulatory SBP in people with moderate-to-severe CKD.

The case for increased peritoneal dialysis utilization in low- and lower-middle-income countries.

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

A prospective, randomized study comparing ultrasound versus fluoroscopic guided femoral arterial access in noncardiac vascular patients.

OBJECTIVE: The aim of our prospective, single-center, randomized study was to compare the procedural outcomes and complication rates of ultrasound (US)-guided common femoral artery (CFA) access to fluoroscopic guidance in noncardiac procedures. METHODS: A total of 635 patients undergoing femoral access for noncardiac diagnostic or interventional procedures were randomized 1:1 to receive either fluoroscopic or US-guided access. The primary end point of the study was successful CFA cannulation. Secondary end points included the first-pass success rate, time to sheath insertion, and accidental venipunctures rate. Both short (24 hours) and midterm (30-90 days postprocedure) access complications were assessed by practitioners blinded to patient randomization. RESULTS: Successful CFA cannulation occurred in 93% of US-guided procedures compared with 86% of fluoroscopy-guided access (P = .002). US guidance was associated with increased rates of first-attempt success (74% vs 42%; P < .001), fewer inadvertent venipunctures (2% vs 10 %; P < .001), and decreased median time to cannulation (80 vs 100 seconds; P < .001) compared with fluoroscopy. Rates of complications did not differ at 24 hours (1% vs 1%; P = .99) or 30 to 90 days (2% vs 4%; P = .15) in fluoroscopy vs US-guided access. When access was performed by vascular surgery trainees (residents and fellows), US guidance retained superior rates of successful CFA cannulation compared to fluoroscopy guided access (n = 298; 96% vs 89%; P = .03). Trainees' time to achieve CFA cannulation was similar to attendings' when using US guidance (median, 85 vs 77 seconds; P = .14); however, with fluoroscopy, trainees' times were significantly longer than those of attendings (137 vs 86 seconds; P = .001). CONCLUSIONS: In comparison to fluoroscopy, US-guided CFA cannulation had a higher rate of success, faster cannulation, and fewer venipunctures in the absence of increased complications.

Bladder and ureteral injuries during benign hysterectomy: an observational cohort analysis in New York State.

PURPOSE: Hysterectomy (Hys) is the most common non-urologic surgery associated with iatrogenic genitourinary (GU) injury. We present the largest known population-based evaluation of GU injury related to benign Hys. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) was queried by ICD-9 and CPT codes. SPARCS for women from 1995 to 2014, who underwent laparoscopic or robotic Hys (minimally invasive surgery = MIS), abdominal Hys (AH), and vaginal Hys (VH) for benign diagnoses. Bladder and ureteral repairs were captured based on the procedure codes. Codes for ureteroneocystotomy (UNC) were compared to any other ureteral repairs, to elucidate injury patterns. Statistical analysis was conducted using Chi squared test, ANOVA, Mann-Whitney test and Poisson Regression and multivariable analysis were performed. RESULTS: 516,340 women underwent Hys for a benign etiology. 69% were AH, 25% VH, and 6% were MIS. 7490 patients (1.45%) had a concomitant GU injury. Compared to VH, MIS and AH were associated with greater odds of bladder and ureteral injury (p < 0.001). MIS and AH, compared to VH, were associated with reduced odds of UNC compared to complex reconstruction (OR 0.27, p < 0.001 and OR 0.12, p < 0.00, respectively). The injured cohort had higher total mean charges ($29,889 vs $15,808) and length of hospitalization (6.32 vs 3.56 days) (p < 0.001). CONCLUSIONS: Bladder and ureteral injuries during hysterectomy are uncommon in contemporary practice and are lower than historical rates. GU injury increases hospitalization cost. VH is associated with the lowest rate of GU injury, and thus appears to be a valuable approach, when feasible.

Pathways from early adversity to later adjustment: Tests of the additive and bidirectional effects of executive control and diurnal cortisol in early childhood.

Additive and bidirectional effects of executive control and hypothalamic-pituitary-adrenal (HPA) axis regulation on children's adjustment were examined, along with the effects of low income and cumulative risk on executive control and the HPA axis. The study utilized longitudinal data from a community sample of preschool age children (N = 306, 36-39 months at Time 1) whose families were recruited to overrepresent low-income contexts. We tested the effects of low income and cumulative risk on levels and growth of executive control and HPA axis regulation (diurnal cortisol level), the bidirectional effects of executive control and the HPA axis on each other, and their additive effects on children's adjustment problems, social competence and academic readiness. Low income predicted lower Time 4 executive control, and cumulative risk predicted lower Time 4 diurnal cortisol level. There was little evidence of bidirectional effects of executive control and diurnal cortisol. However, both executive control and diurnal cortisol predicted Time 4 adjustment, suggesting additive effects. There were indirect effects of income on all three adjustment outcomes through executive control, and of cumulative risk on adjustment problems and social competence through diurnal cortisol. The results provide evidence that executive control and diurnal cortisol additively predict children's adjustment and partially account for the effects of income and cumulative risk on adjustment.