Association Between the Dialysate Bicarbonate and the Pre-dialysis Serum Bicarbonate Concentration in Maintenance Hemodialysis: A Retrospective Cohort Study.

Background: It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration. Objective: The objective is to examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration. Design: This is a retrospective cohort study. Setting: The study was performed using linked administrative health care databases in Ontario, Canada. Patients: Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included. Measurements: Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level. Methods: We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model. Results: All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval [CI] = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease. Limitations: We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible. Conclusions: We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.

Contexte: On ignore si des concentrations plus élevées de bicarbonate dans le dialysat sont associées à des changements cliniquement significatifs dans le taux de bicarbonate sérique prédialyse. Objectif: Examiner l'association entre la prescription de bicarbonate du dialysat et le taux de bicarbonate sérique prédialyse. Conception: Étude de cohorte rétrospective. Cadre: Étude réalisée en Ontario (Canada) à partir des données administratives de santé. Sujets: Ont été inclus les adultes prévalents qui recevaient une hémodialyse chronique en centre le 1er avril 2020 (n=5 414). Mesures: Les sujets ont été regroupés dans les catégories suivantes de concentration en bicarbonate dans le dialysat utilisée dans leur unité de dialyse: individualisée (ajustée selon le taux de bicarbonate sérique prédialyse) ou normalisée (même concentration pour >90% des sujets). La catégorie « standardisée ¼ a été stratifiée selon la concentration: 35 mmol/L, 36 à 37 mmol/L et ≥38 mmol/L. Le principal critère d'évaluation était le taux moyen de bicarbonate sérique prédialyse en ambulatoire au niveau du patient. Méthodologie: Nous avons examiné l'association entre la catégorie de concentration en bicarbonate du dialysat et le taux de bicarbonate sérique prédialyse à l'aide d'un modèle linéaire mixte corrigé. Résultats: Pour toutes les catégories de concentration en bicarbonate du dialysat, le taux moyen de bicarbonate sérique prédialyse était dans la plage normale. Dans la catégorie « individualisée ¼, 91% des sujets avaient un taux de bicarbonate sérique prédialyse de ≥22 mmol/L, comparativement à 87% dans la catégorie « standardisée ¼. Les patients de la catégorie « standardisée ¼ tendaient à avoir un taux de bicarbonate sérique de 0,25 mmol/L (IC 95%: -0,93 à 0,43) inférieur à celui des patients de la catégorie « individualisée ¼. Comparé aux patients de la catégorie 35 mmol/L, les patients des catégories 36 à 37 mmol/L et ≥38 mmol/L tendaient respectivement à avoir un taux de bicarbonate sérique de 0,70 mmol/L (IC 95%: -0,30 à 1,70) et de 0,87 mmol/L (IC 95%: 0,14 à 1,60) plus élevé. L'âge, le sexe ou les antécédents de maladie pulmonaire chronique n'ont pas semblé modifier l'effet. Limites: Il n'a pas été possible de confirmer directement que toutes les mesures de laboratoire avaient été effectuées avant la dialyse. Les données sur les concentrations de bicarbonate prescrites pour les séances de dialyse individuelles n'étaient pas disponibles, ce qui peut avoir conduit à une classification erronée. De plus, l'observance d'une pratique d'individualisation n'a pas pu être mesurée. Une confusion résiduelle est possible. Conclusion: Nous n'avons observé aucune différence significative dans les taux de bicarbonate sériques prédialyse, qu'on ait utilisé une concentration individualisée ou standardisée de bicarbonate dans le dialysat. L'utilisation d'un dialysat à ≥38 mmol/L (c. 35 mmol/L) de bicarbonate peut entraîner une hausse de 0,9 mmol/L du taux de bicarbonate sérique prédialyse.

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.

Capacity for the management of kidney failure in the International Society of Nephrology North America and the Caribbean region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.

The race-based stress reduction intervention (RiSE) study on African American women in NYC and Chicago: Design and methods for complex genomic analysis.

RiSE study aims to evaluate a race-based stress-reduction intervention as an effective strategy to improve coping and decrease stress-related symptoms, inflammatory burden, and modify DNA methylation of stress response-related genes in older AA women. This article will describe genomic analytic methods to be utilized in this longitudinal, randomized clinical trial of older adult AA women in Chicago and NYC that examines the effect of the RiSE intervention on DNAm pre- and post-intervention, and its overall influence on inflammatory burden. Salivary DNAm will be measured at baseline and 6 months following the intervention, using the Oragene-DNA kit. Measures of perceived stress, depressive symptoms, fatigue, sleep, inflammatory burden, and coping strategies will be assessed at 4 time points including at baseline, 4 weeks, 8 weeks, and 6 months. Genomic data analysis will include the use of pre-processed and quality-controlled methylation data expressed as beta (ß) values. Association analyses will be performed to detect differentially methylated sites on the targeted candidate genes between the intervention and non-intervention groups using the Δß (changes in methylation) with adjustment for age, health behaviors, early life adversity, hybridization batch, and top principal components of the probes as covariates. To account for multiple testing, we will use FDR adjustment with a corrected p-value of <0.05 regarded as statistically significant. To assess the relationship between inflammatory burden and Δß among the study samples, we will repeat association analyses with the inclusion of individual inflammation protein measures. ANCOVA will be used because it is more statistically powerful to detect differences.

Exercise perceptions and practices of people receiving peritoneal dialysis: An international cross-sectional survey.

BACKGROUND: Low physical activity and functional impairment are prevalent and unaddressed in people receiving peritoneal dialysis (PD). Exercise has been shown to improve physical function and mental health for people with kidney disease. METHODS: Cross-sectional descriptive survey aimed at identifying the exercise and physical activity perceptions and practice patterns of people receiving PD. The survey was developed and pretested with persons living with kidney disease, PD clinicians and exercise specialists. RESULTS: There were 108 respondents (people receiving PD) with the majority from Canada (68%) and the United Kingdom (25%). Seventy-one per cent were engaged in physical activity two or more times per week. Most (91.8%) believed that physical activity is beneficial, and 61.7% reported healthcare provider discussion about physical activity. Perceptions regarding weightlifting restrictions varied: 76% were told not to lift weight with a maximum amount ranging from 2 kg to 45 kg. Few (28%) were instructed to drain PD fluid prior to physical activity. Mixed advice regarding swimming ability was common (44% were told they could swim and 44% were told they should not). CONCLUSIONS: Knowledge gaps suggest that education for both healthcare providers and patients is needed regarding the practice of exercise for people living with PD. Common areas of confusion include the maximum weight a person should lift, whether exercise was safe with or without intrabdominal PD fluid in situ and whether swimming is allowed. Further research is needed to provide patients with evidence-based recommendations rather than defaulting to restricting activity.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

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.

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.

Association Between Arterial Stiffness and Measures of Autonomic Dysfunction in People With Chronic Kidney Disease.

Background: Autonomic nervous system (ANS) dysfunction and vascular stiffness increase cardiovascular risk in people with chronic kidney disease (CKD). Chronic elevations in sympathetic activity can lead to increased arterial stiffness; however, the relationship between these variables is unknown in CKD. Objective: To explore the association between measures of autonomic function and arterial stiffness in patients with moderate-to-severe CKD. Methods: This study was a prespecified secondary analysis of a randomized controlled trial. This included the following measures: 24-hour ambulatory blood pressure (BP), carotid-femoral and carotid-radial pulse wave velocity (PWV), and postexercise heart rate recovery (HRR). We used mixed effect linear regression models with Bayesian information criteria (BIC) to assess the contribution of ANS measurements. Results: Forty-four patients were included in the analysis. Mean carotid-femoral and carotid-radial PWV were 7.12 m/s (95% CI 6.13, 8.12) and 8.51 m/s (7.90, 9.11), respectively. Mean systolic dipping, calculated as percentage change in mean systolic readings from day to night, was 10.0% (95% CI 7.79, 12.18). Systolic dipping was independently associated with carotid-radial PWV, MD -0.09 m/s (95% CI -0.15, -0.02) and had the lowest BIC. Conclusions: Systolic dipping was associated with carotid-radial PWV in people with moderate-to-severe CKD; however, there was no association with carotid-femoral PWV. Systolic dipping may be a feasible surrogate of ANS function, as the association with carotid-radial PWV was consistent with the minimal clinically important difference (MCID). Future studies are needed to define the relationship between ANS function, arterial stiffness, and CV events over time in people with CKD.

Contexte: Le dysfonctionnement du système nerveux autonome (SNA) et la rigidité artérielle augmentent le risque d'événements cardiovasculaires chez les personnes atteintes d'insuffisance rénale chronique (IRC). Les élévations chroniques de l'activité sympathique peuvent accroître la rigidité artérielle, mais on ne connaît pas le lien entre ces variables en contexte d'IRC. Objectif: Explorer l'association entre les mesures de la fonction autonome et la rigidité artérielle chez les patients atteints d'IRC modérée ou grave. Méthodologie: Cette étude était l'analyze secondaire prédéfinie d'un essai contrôlé randomisé. Mesures incluses: le suivi de la pression artérielle (PA) ambulatoire sur 24 heures, la vitesse de l'onde de pouls (VOP) carotido-fémorale et carotido-radiale, et la récupération de la fréquence cardiaque (HRR­Heart Rate Recovery) après l'effort. Nous avons eu recours à des modèles de régression linéaire à effets mixtes avec critères d'information bayésiens (BIC ­ Bayesian Information Criteria) pour évaluer la contribution des mesures du SNA. Résultats: Quarante-quatre patients sont inclus dans l'analyze. La valeur moyenne des VOP carotido-fémorale et carotido-radiale était respectivement de 7,12 m/s (IC 95 %: 6,13 à 8,12) et de 8,51 m/s (IC 95 %: 7,90 à 9,11). La chute systolique moyenne, calculée en pourcentage de variation entre les valeurs systoliques moyennes du jour et de la nuit, était de 10,0 % (IC 95 %: 7,79 à 12,18). La chute systolique a été indépendamment associée à la VOP carotido-radiale, avec un écart moyen de -0,09 m/s (IC 95 %: -0,15 à -0,02) et a présenté les plus faibles BIC. Conclusion: La chute systolique a été associée à la VOP carotido-radiale chez les personnes atteintes d'IRC modérée ou grave, mais aucune association n'a été observée avec la VOP carotido-fémorale. La chute systolique pourrait être un substitut de la fonction du SNA, car l'association avec la VOP carotido-radiale était cohérente avec la différence minimale cliniquement importante (DMCI). D'autres études sont nécessaires pour mieux définir la relation entre la fonction du SNA, la rigidité artérielle et les événements cardiovasculaires au fil du temps chez les personnes atteintes d'IRC.

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.

Measurement properties of performance-based measures to assess physical function in chronic kidney disease: recommendations from a COSMIN systematic review.

Background: There is wide heterogeneity in physical function tests available for clinical and research use, hindering our ability to synthesize evidence. The aim of this review was to identify and evaluate physical function measures that could be recommended for standardized use in chronic kidney disease (CKD). Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL, Scopus and Web of Science were searched from inception to March 2022, identifying studies that evaluated a clinimetric property (validity, reliability, measurement error and/or responsiveness) of an objectively measured performance-based physical function outcomes using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) based recommendations. Studies with individuals of all ages and of any stage of CKD were included. Results: In total, 50 studies with 21 315 participants were included. Clinimetric properties were reported for 22 different physical function tests. The short physical performance battery (SPPB), Timed-up-and-go (TUG) test and Sit-to-stand tests (STS-5 and STS-60) had favorable properties to support their use in CKD and should be integrated into routine use. However, the majority of studies were conducted in the hemodialysis population, and very few provided information regarding validity or reliability. Conclusion: The SPPB demonstrated the highest quality of evidence for reliability, measurement error and construct validity amongst transplant, CKD and dialysis patients. This review is an important step towards standardizing a core outcome set of tools to measure physical function in research and clinical settings for the CKD population.

Skeletal Surveys in Suspected Non-accidental Trauma: Examining the Yield and Current Clinical Practices at a Regional Referral Center in West Virginia.

Introduction Non-accidental trauma (NAT) is a leading cause of pediatric injury and death. When NAT is suspected in children under the age of 24 months, the American Academy of Pediatrics (AAP) recommends using skeletal surveys (SS) to identify acute, healing, or old fractures and to repeat the SS approximately two weeks after initial imaging as acute fractures can sometimes not be seen on initial imaging. In this study, we determined the yield of initial and follow-up SS obtained for suspected NAT in children under the age of 24 months at a regional referral hospital. Methods We reviewed charts of children younger than 24 months who received SS imaging, due to physical abuse suspicion, at our hospital system between 2017 and 2022. We used convenient sampling to examine all SS occurring at the Charleston Area Medical Center Healthcare System. Results A total of 61 of the 126 initial SS showed fractures. Only 9% of children received follow-up SS. Repeat SS performed approximately two weeks after positive initial SS showed signs of healing, including new fractures not reported on the initial scan. Follow-up SS performed within eight weeks after initial negative scans continued to be negative. Lastly, consults from child abuse pediatricians were found to be underutilized as only 48% of patients received consultations. Conclusion Follow-up SS and child abuse pediatrician consults were found to be underutilized. Follow-up SS and consulting child abuse specialists should not be overlooked, irrespective of positive or negative initial SS, to provide optimal management of NAT.

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.

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.

Atrial fibrillation and anticoagulation in patients hospitalised for stroke in the REGIONS Care Study.

AIM: To describe atrial fibrillation (AF) patient characteristics and anticoagulation patterns in stroke patients in Aotearoa. METHODS: Reducing Ethnic and Geographic Inequities to Optimise New Zealand Stroke (REGIONS) Care study is a prospective, nation-wide observational study of consecutive adult stroke patients admitted to hospital between 1 May and 31 October 2018. AF and anticoagulation prescribing, intracerebral haemorrhage (ICH) and differences by Maori ethnicity and hospital location are described. RESULTS: Of 2,379 patients, 807 (34.3%) had a diagnosis of AF. AF patients were older than non-AF patients (mean 79.9 [SD 11] versus 72.5 [14.2], p<0.0001). AF was diagnosed before stroke in 666 patients (82.5%), of whom 442 (66.4%) were taking an anticoagulant. The most common documented reasons for non-anticoagulation were prior bleeding (20.5%), patient preference (18.1%), frailty, comorbidities/side effects (13.2%) and falls (6.8%). The ICH rate was similar for AF patients on versus not on an anticoagulant (adjusted odds ratio [aOR] 0.99, 95% confidence interval [CI] 0.55-1.80). Rates and reasons for oral anticoagulant non-prescribing were similar for Maori, non-Maori, urban and non-urban populations. CONCLUSIONS: Although anticoagulation prescribing in AF has improved, one third of stroke patients with known AF were not taking an anticoagulant prior to admission and the majority did not appear to have an absolute contraindication offering a multidisciplinary opportunity for improvement. There were no significant differences for Maori and non-urban populations in anticoagulant prescribing.

Exercise Rehabilitation for People With End-Stage Kidney Disease: Who Will Fill the Gaps?

Exercise rehabilitation is a well established therapy for reducing morbidity and mortality and improving quality of life and function across chronic conditions. People with dialysis-dependent kidney failure have a high burden of comorbidity and symptoms, commonly characterised as fatigue, dyspnoea, and the inability to complete daily activities. Despite more than 30 years of exercise research in people with kidney disease and its established benefit in other chronic diseases, exercise programs are rare in kidney care and are not incorporated into routine management at any stage. In this review, we describe the mechanisms contributing to exercise intolerance in those with end-stage kidney disease and outline the role of exercise rehabilitation in addressing the major challenges to kidney care: cardiovascular disease, symptom burden, and physical frailty. We also draw on existing models of exercise rehabilitation from other chronic conditions to inform the way forward and challenge the status quo of exercise rehabilitation in both practice and research.

Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder.

Purpose: De novo variants in CUL3 (Cullin-3 ubiquitin ligase) 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 multi-center 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 35 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two 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 . Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells. Conclusion: 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.

Frailty and Clinical Outcomes in Patients Treated With Hemodialysis: A Prospective Cohort Study.

Rationale and Objective: Frailty is common among people with kidney failure treated with hemodialysis (HD). The objective was to describe how frailty evolves over time in people treated by HD, how improvements in frailty and frailty markers are associate with clinical outcomes, and the characteristics that are associated with improvement in frailty. Study Design: Prospective cohort study. Setting and Participants: Adults initiating thrice weekly in-center HD in Canada. Exposure: We classified frailty using a 5-point score (3 or more indicates frailty) based on physical inactivity, slowness or weakness, poor endurance or exhaustion, and malnutrition. We categorized the frailty trajectory as never present, improving, deteriorating, and always present. Outcomes: All-cause death, hospitalizations, and placement into long-term care. Analytical Approach: We examined the association between time-varying frailty measures and these outcomes using Cox and negative binomial models, after adjustment for potential confounders. Results: 985 participants were included and followed up for a median of 33 months; 507 (51%) died, 761 (77%) experienced ≥1 hospitalization and 115 (12%) entered long-term care. Overall, 760 (77%) reported frailty during follow-up. Three-quarters (78%) of those with frailty at baseline remained frail throughout the follow-up, 46% without baseline frailty became frail, and 23% with baseline frailty became nonfrail. Higher frailty scores were associated with an increased risk of mortality (fully adjusted HR, 1.58 per unit; 95% CI, 1.39-1.80) and an increased rate of hospitalization (RR, 1.16 per unit; 95% CI, 1.09-1.23). Compared with those who were frail throughout the follow-up, participants with frailty at baseline but improving during follow-up showed a lower mortality (HR, 0.59; 95% CI, 0.42-0.81), and a lower rate of hospitalization (RR, 0.70; 95% CI, 0.56-0.87). Limitations: There was missing data on frailty at baseline and during follow-up. Conclusions: Frailty was associated with a higher risk of poor outcomes compared with those without frailty, and participants whose status improved from frail to nonfrail showed better clinical outcomes than those who remained frail. These findings emphasize the importance of identifying and implementing effective treatments for frailty in patients receiving maintenance HD.

Prevalence and Spatial Distribution of Gastroschisis in an Industrial Watershed.

The relationship between the congenital defect of gastroschisis and environmental toxins is poorly understood. We examined gastroschisis incidence, risk factors, and spatial association in a geographic region with known environmental pollution and hazardous waste sites. An observational study of fetal and neonatal gastroschisis diagnosed from 1/1/2006 to 12/31/2020 was conducted in a southern West Virginia (WV) tertiary care hospital. Emerging hot spot analysis and Ripley's K-Function examined the spatial relationship between gastroschisis cases and Environmental Protection Agency (EPA) Federal Registry Sites (FRS). A total of 63 gastroschisis cases provided a prevalence rate of 14.6 per 10000 live births. Gastroschisis was associated with younger maternal age, decreased pre-pregnancy BMI, and increased maternal tobacco use. Relative to FRS sites, spatial clusters were identified with emerging hot spot analysis. Observed Ripley K was higher at all measured bands. Results suggest a potential geographic association between gastroschisis cases and EPA-designated hazardous waste sites.