Sibling adjustment to diabetes and educational needs: A literature review.

ABSTRACT: As cases of type 1 diabetes mellitus (T1DM) increase, so do their impact on sibling relationships. This literature review of four databases from 2010 to 2024 discusses findings from five studies and the themes that emerged: education needs and family functioning. Improvements in family-centered care and education are needed for siblings of children with T1DM.

Incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease in patients with multiple sclerosis initiating disease-modifying therapies: Retrospective cohort study using a frequentist model averaging statistical framework.

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.

The heterogeneous genetic architectures of orofacial clefts.

Orofacial clefts (OFCs) are common, affecting 1:1000 live births. OFCs occur across a phenotypic spectrum - including cleft lip (CL), cleft lip and palate (CLP), or cleft palate (CP) - and can be further subdivided based on laterality, severity, or specific structures affected. Herein we review what is known about the genetic architecture underlying each of these subtypes, considering both shared and subtype-specific risks. While there are more known genetic similarities between CL and CLP than CP, recent research supports both shared and subtype-specific genetic risk factors within and between phenotypic classifications of OFCs. Larger sample sizes and deeper phenotyping data will be of increasing importance for the discovery of novel genetic risk factors for OFCs and various subtypes going forward.

Clinicians' perspectives and usage of rehabilitation technology: a survey.

PURPOSE: The aim of this study was to investigate clinicians' perspectives regarding their usage of rehabilitation technology in their day-to-day practice and uncover the factors that impact clinicians' use of rehabilitation technology in their daily practice. MATERIALS AND METHODS: An online survey was used to gather cross-sectional data from American occupational therapists, occupational therapy assistants, physical therapists, physical therapy assistants, and speech language pathologists. This survey used Likert-scale, multiple choice, and free-response questions. RESULTS: Approximately half (n = 56/105, 53.3%) of our clinicians reported using rehabilitation in their daily practice. Less than 20% (n = 18/105, 17.1%) of the respondents strongly agreed that they felt comfortable implementing new rehabilitation technology, and few reported that their workplace encouraged (n = 16/85, 18.8%) or strongly encouraged (n = 14/85, 16.5%) the use of rehabilitation technology in practice. Additionally, excluding the 2011-2020 graduate clinicians that reported that they had not learned about rehabilitation technology in school or fieldwork, few reported feeling prepared (n = 14/97, 14.4%) or very prepared (n = 4/97, 4.1%) to use rehabilitation technology after graduation. CONCLUSIONS: Our findings have revealed a sizable knowledge-to-practice gap in regard to clinicians' preparedness to engage with and advocate for rehabilitation technology in their day-to-day practice.

There is a great need for more robust educational instruction at the scholastic level for students in order to prepare future clinicians to engage with rehabilitation technology in the field.For practicing professionals in the workplace, in-service training, clear training protocols, and technology support for clinicians are needed to remediate the current knowledge-to-practice gap.

Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate.

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We performed a genome-wide association study using transmission disequilibrium tests of 435 case-parent trios to evaluate broad risks for any cleft palate (ACP) (n = 435), and subtype-specific risks for any cleft soft palate (CSP), (n = 259) and any cleft hard palate (CHP) (n = 125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p = 4.24 × 10-8) associated with CHP. One gene at this locus, angiopoietin-like 2 (ANGPTL2), plays a role in osteoblast differentiation. It is expressed both in craniofacial tissue of human embryos and developing mouse palatal shelves. We found 19 additional loci reaching suggestive significance (p < 5 × 10-6), of which only one overlapped between groups (chromosome 17q24.2, ACP and CSP). Odds ratios for the 20 loci were most similar across all 3 groups for SNPs associated with the ACP group, but more distinct when comparing SNPs associated with either subtype. We also found nominal evidence of replication (p < 0.05) for 22 SNPs previously associated with orofacial clefts. Our study to evaluate CP risks in the context of its subtypes and we provide newly reported associations affecting the broad risk for CP as well as evidence of subtype-specific risks.

Rare variant modifier analysis identifies variants in SEC24D associated with orofacial cleft subtypes.

As one of the most common structural birth defects, orofacial clefts (OFCs) have been studied for decades, and recent studies have demonstrated that there are genetic differences between the different phenotypic presentations of OFCs. However, the contribution of rare genetic variation genome-wide to different subtypes of OFCs has been understudied, with most studies focusing on common genetic variation or rare variation within targeted regions of the genome. Therefore, we used whole-genome sequencing data from the Gabriella Miller Kids First Pediatric Research Program to conduct a gene-based burden analysis to test for genetic modifiers of cleft lip (CL) vs cleft lip and palate (CLP). We found that there was a significantly increased burden of rare variants in SEC24D in CL cases compared to CLP cases (p = 6.86 [Formula: see text] 10-7). Of the 15 variants within SEC24D, 53.3% were synonymous, but overlapped a known craniofacial enhancer. We then tested whether these variants could alter predicted transcription factor binding sites (TFBS), and found that the rare alleles destroyed binding sites for 9 transcription factors (TFs), including Pax1 (p = 0.0009), and created binding sites for 23 TFs, including Pax6 (p = 6.12 [Formula: see text] 10-5) and Pax9 (p = 0.0001), which are known to be involved in normal craniofacial development, suggesting a potential mechanism by which these synonymous variants could have a functional impact. Overall, this study indicates that rare genetic variation may contribute to the phenotypic heterogeneity of OFCs and suggests that regulatory variation may also contribute and warrant further investigation in future studies of genetic variants controlling risk to OFC.

Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting.

PURPOSE: Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls. METHODS: We evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria. RESULTS: 9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance. CONCLUSION: These results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.

Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate.

Orofacial clefts (OFCs) are the most common craniofacial birth defects and are often categorized into two etiologically distinct groups: cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP). CP is highly heritable, but there are still relatively few established genetic risk factors associated with its occurrence compared to CL/P. Historically, CP has been studied as a single phenotype despite manifesting across a spectrum of defects involving the hard and/or soft palate. We performed GWAS using transmission disequilibrium tests using 435 case-parent trios to evaluate broad risks for any cleft palate (ACP, n=435), as well as subtype-specific risks for any cleft soft palate (CSP, n=259) and any cleft hard palate (CHP, n=125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p=4.24×10 -8 ) associated with CHP. One gene at this locus, angiopoietin-like 2 ( ANGPTL2 ), plays a role in osteoblast differentiation. It is expressed in craniofacial tissue of human embryos, as well as in the developing mouse palatal shelves. We found 19 additional loci reaching suggestive significance (p<5×10 -6 ), of which only one overlapped between groups (chromosome 17q24.2, ACP and CSP). Odds ratios (ORs) for each of the 20 loci were most similar across all three groups for SNPs associated with the ACP group, but more distinct when comparing SNPs associated with either the CSP or CHP groups. We also found nominal evidence of replication (p<0.05) for 22 SNPs previously associated with cleft palate (including CL/P). Interestingly, most SNPs associated with CL/P cases were found to convey the opposite effect in those replicated in our dataset for CP only. Ours is the first study to evaluate CP risks in the context of its subtypes and we provide newly reported associations affecting the broad risk for CP as well as evidence of subtype-specific risks.

Rare genetic variants in SEC24D modify orofacial cleft phenotypes.

As one of the most common structural birth defects, orofacial clefts (OFCs) have been studied for decades, and recent studies have demonstrated that there are genetic differences between the different phenotypic presentations of OFCs. However, the contribution of rare genetic variation genome-wide to different subtypes of OFCs has been understudied, with most studies focusing on common genetic variation or rare variation within targeted regions of the genome. Therefore, we used whole-genome sequencing data from the Gabriella Miller Kids First Pediatric Research Program to conduct a gene-based burden analysis to test for genetic modifiers of cleft lip (CL) vs cleft lip and palate (CLP). We found that there was a significantly increased burden of rare variants in SEC24D in CL cases compared to CLP cases (p=6.86×10-7). Of the 15 variants within SEC24D, 53.3% were synonymous, but overlapped a known craniofacial enhancer. We then tested whether these variants could alter predicted transcription factor binding sites (TFBS), and found that the rare alleles destroyed binding sites for 9 transcription factors (TFs), including Pax1 (p=0.0009), and created binding sites for 23 TFs, including Pax6 (p=6.12×10-5) and Pax9 (p= 0.0001), which are known to be involved in normal craniofacial development, suggesting a potential mechanism by which these synonymous variants could have a functional impact. Overall, this study demonstrates that rare genetic variation contributes to the phenotypic heterogeneity of OFCs and suggests that regulatory variation may also contribute and warrant further investigation in future studies of genetic variants controlling risk to OFC.

Magnitude of the Potential Screening Gap for Fabry Disease in Manitoba: A Population-Based Retrospective Cohort Study.

Background: Fabry disease is a rare disorder caused by the deficient activity of α-galactosidase A (GLA) that often leads to organ damage. Fabry disease can be treated with enzyme replacement or pharmacological therapy, but due to its rarity and nonspecific manifestations, it often goes undiagnosed. Mass screening for Fabry disease is impractical; however, a targeted screening program for high-risk individuals may uncover previously unknown cases. Objective: Our objective was to use population-level administrative health databases to identify patients at high risk of Fabry disease. Design: Retrospective cohort study. Setting: Population-level health administrative databases housed at the Manitoba Centre for Health Policy. Patients: All residents of Manitoba, Canada, between 1998 and 2018. Measurements: We ascertained the evidence of GLA testing in a cohort of patients at high risk of Fabry disease. Methods: Individuals without a hospitalization or prescription indicative of Fabry disease were included if they had evidence of 1 of 4 high-risk conditions for Fabry disease: (1) ischemic stroke <45 years of age, (2) idiopathic hypertrophic cardiomyopathy, (3) proteinuric chronic kidney disease or kidney failure of unknown cause, or (4) peripheral neuropathy. Patients were excluded if they had known contributing factors to these high-risk conditions. Those who remained and had no prior GLA testing were assigned a 0% to 4.2% probability of having Fabry disease depending on their high-risk condition and sex. Results: After applying exclusion criteria, 1386 individuals were identified as having at least 1 high-risk clinical condition for Fabry disease in Manitoba. There were 416 GLA tests conducted during the study period, and of those, 22 were conducted in individuals with at least 1 high-risk condition. This leaves a screening gap of 1364 individuals with a high-risk clinical condition for Fabry disease in Manitoba who have not been tested. At the end of the study period, 932 of those individuals were still alive and residing in Manitoba, and if screened today, we expect between 3 and 18 would test positive for Fabry disease. Limitations: The algorithms we used to identify our patients have not been validated elsewhere. Diagnoses of Fabry disease, idiopathic hypertrophic cardiomyopathy, and peripheral neuropathy were only available via hospitalizations and not physician claims. We were only able to capture GLA testing processed through public laboratories. Patients identified to be at high risk of Fabry disease by the algorithm did not undergo GLA testing due to a clinical rationale that we were unable to capture. Conclusions: Administrative health databases may be a useful tool to identify patients at higher risk of Fabry disease or other rare conditions. Further directions include designing a program to screen high-risk individuals for Fabry disease as identified by our administrative data algorithms.

Contexte: La maladie de Fabry est un trouble rare causé par une activité déficiente de α-galactosidase A (GLA) qui conduit fréquemment à des dommages aux organes. La maladie de Fabry peut être traitée par remplacement enzymatique ou par traitement pharmacologique, mais elle passe souvent inaperçue en raison de sa rareté et de ses manifestations non spécifiques. Le dépistage de masse de la maladie de Fabry est irréalisable, mais un programme de dépistage ciblé pour les personnes présentant un risque élevé pourrait révéler des cas auparavant inconnus. Objectif: Notre objectif était d'utiliser les bases de données administratives sur la santé des populations pour recenser les patients présentant un risque élevé de maladie de Fabry. Conception: Étude de cohorte rétrospective. Cadre: Les bases de données administratives sur la santé des populations hébergées au Manitoba Centre for Health Policy. Sujets: Tous les résidents du Manitoba (Canada) entre 1998 et 2018. Mesures: Nous avons examiné les preuves d'un dosage de la GLA dans une cohorte de patients présentant un risque élevé de maladie de Fabry. Méthodologie: Les individus sans hospitalisation ou ordonnance indicative de la maladie de Fabry ont été inclus s'ils présentaient une des quatre affections suivantes, jugées à haut risque pour la maladie de Fabry: 1) accident vasculaire cérébral ischémique avant 45 ans; 2) cardiomyopathie hypertrophique idiopathique; 3) insuffisance rénale chronique protéinurique ou insuffisance rénale de cause inconnue; 4) neuropathie périphérique. Les patients ont été exclus s'ils présentaient des facteurs de contribution connus à ces maladies à haut risque. Les personnes restantes qui n'avaient pas de preuves d'un dosage antérieur de la GLA ont reçu une probabilité de 0 à 4,2 % d'avoir la maladie de Fabry, selon leur maladie à risque élevé et leur sexe. Résultats: Après l'application des critères d'exclusion, 1 386 personnes ont été identifiées au Manitoba comme ayant au moins une affection clinique présentant un risque élevé pour la maladie de Fabry. Pendant la période de l'étude, 416 dosages de GLA ont été effectués, dont 22 chez des individus présentant au moins une affection à risque élevé; soit un déficit de dépistage pour 1 364 Manitobains présentant un risque élevé de maladie de Fabry à qui aucun dosage n'avait été fait. À la fin de la période de l'étude, 932 de ces personnes étaient encore vivantes et résidaient toujours au Manitoba. Si ces individus étaient dépistés aujourd'hui, on pourrait s'attendre à obtenir entre 3 et 18 dosages positifs pour la maladie de Fabry. Limites: Les algorithmes que nous avons utilisés pour identifier nos sujets n'avaient pas été validés ailleurs. Les diagnostics de maladie de Fabry, de cardiomyopathie hypertrophique idiopathique et de neuropathie périphérique n'étaient disponibles que par une hospitalisation et non par demande d'un médecin. Seuls les dosages de la GLA effectués par des laboratoires publics ont pu être saisis. Les patients répertoriés par l'algorithme comme présentant un risque élevé de maladie de Fabry n'avaient pas subi de dosage de la GLA en raison d'une justification clinique qu'il nous a été impossible de saisir. Conclusion: Les bases de données administratives sur la santé peuvent s'avérer un bon outil pour recenser les patients présentant un risque plus élevé de développer la maladie de Fabry ou d'autres maladies rares. Les orientations futures comprennent la conception d'un programme de dépistage des individus présentant un risque élevé pour la maladie de Fabry, tels que recensés par nos algorithmes de données administratives.

Improving longitudinal research in geospatial health: An agenda.

All aspects of public health research require longitudinal analyses to fully capture the dynamics of outcomes and risk factors such as ageing, human mobility, non-communicable diseases (NCDs), climate change, and endemic, emerging, and re-emerging infectious diseases. Studies in geospatial health are often limited to spatial and temporal cross sections. This generates uncertainty in the exposures and behavior of study populations. We discuss a research agenda, including key challenges and opportunities of working with longitudinal geospatial health data. Examples include accounting for residential and human mobility, recruiting new birth cohorts, geoimputation, international and interdisciplinary collaborations, spatial lifecourse studies, and qualitative and mixed-methods approaches.

Elimination of PBB-153; findings from a cohort of Michigan adults.

BACKGROUND: An industrial accident led to the widespread contamination of polybrominated biphenyl (PBB), a flame retardant, into the food system in Michigan in the 1970's. PBB continues to be detected in Michiganders' blood some forty years later. It is necessary to understand the elimination rate and half-life of PBB because it may provide clues on how to hasten the elimination of it from the human body. METHODS: Serum samples were taken from young adult and adult participants of the Michigan PBB registry from 1974 to 2019. A single compartment model was assumed for the elimination rate for PBB-153 in young adults and adults (≥16 years). Generalized linear mixed models were used to estimate the average elimination rate of PBB-153 and allowed for a random intercept and slope for the time between measurements. Models were adjusted for age at exposure, body mass index (BMI) at initial measurement, and smoking. Models were also stratified by demographic characteristics. RESULTS: In total, 1974 participants contributed 4768 samples over a forty-year span. The median initial PBB-153 level was 1.542 parts per billion (ppb) (Range: 0.001-1442.48 ppb). The adjusted median participant-specific half-life for PBB-153 was 12.23 years. The half-life of PBB-153 was lengthened by higher initial PBB level (∼1.5 years), younger age at exposure (∼5.4 years), higher BMI (∼1.0 years), and increased gravidity (∼7.3 years). Additionally, the half-life of PBB-153 was shortened by smoking status (∼-2.8 years) and breastfeeding (∼-3.5 years). CONCLUSIONS: Consistent with previous studies, PBB-153 has been demonstrated to have a long half-life in the human body and may be modified by some demographic characteristics. These updated estimates of half-life will further support evaluation of health effects associated with PBB exposure. Investigations into mechanisms to accelerate elimination and reduce body burdens of PBB-153, especially those related to body weight, are needed.

The mouth and oral health in the field of dementia.

An ageing population, an estimated 47 million people currently living with dementia, and predictions of a threefold increase in people living with a diagnosis by 2050 have led the WHO to declare dementia a public health priority. Emerging research also suggests that dementia is linked to poor oral health and that oral health declines alongside cognitive decline. Drawing on Bourdieu's concepts of field and capital, this paper presents an analysis of interview data from participants with dementia, carers and carer/diagnosed dyads participating in a qualitative study of the mouth and oral health. We argue that Bourdieu's conceptual toolkit provides a way of contextualising experiences of oral health within dementia and un-picking the multi-layered impact of structure, institutions, biology, resource mobilisation and self in the context of a progressive disease which ultimately challenges knowledge of the self and the ability to interact with the world around us.

Dietary Patterns and Perceptions in Older Adults With Chronic Kidney Disease in the Canadian Frailty Observation and Interventions Trial (CanFIT): A Mixed-Methods Study.

Background: People living with chronic kidney disease (CKD) have identified diet as an important aspect of their life and care. Understanding current consumption patterns in this population, and how they relate to patient perspectives of dietary recommendations, may help identify and design potential dietary intervention strategies in CKD. Objective: To investigate the dietary intake patterns of people with advanced-stage CKD, as well as subjective perspectives regarding dietary recommendations from participants and their caregivers. Design: Mixed-methods study with a sequential explanatory design. Setting: Manitoba, Canada. Participants: Individuals with late-stage CKD (CKD stages G4-G5, including dialysis) participating in the Canadian Frailty Observation and Interventions Trial (CanFIT). Methods: First, quantitative data were collected via a cross-sectional dietary assessment, using three 24-hour dietary recalls, a 36-question short diet questionnaire (SDQ), and a Nutrition Quality of Life (NQoL) tool (n = 59). Second, qualitative data were collected during 2 focus groups (n 1 = 12 and n 2 = 7) held with a subsample of individuals who had completed the dietary surveys, along with their caregivers. Focus groups explored topics related to diet and CKD; transcribed data were analyzed thematically. In the interpretation stage, the qualitative findings were combined with the quantitative results to help explain the latter and reach a deeper understanding of the subjective experiences of adults with CKD. Results: Quantitatively, nearly all (48/51; 94%) participants (mean age 70.8 ± 10.8 years) reported energy intakes below recommendations and most (86%) did not achieve recommended fiber intake. In addition, 15/21 (71%) of patients on dialysis had low protein intake. Qualitatively, 2 themes were identified: (1) Lacking/Needing dietary guidance-incomplete "information overload," and (2) Experiencing difficulty in adapting to restrictions. Within the former theme, participants spoke of getting too much information at once, often at the wrong time. Within the latter theme, participants spoke of a loss of appetite, and cheating on their dietary recommendations. Limitations: Potential recall bias recalling dietary patterns, small sample size limiting generalizability, self-selection bias. Conclusion: Despite the reported lifestyle changes made by individuals with CKD, which negatively impacted their lives, many had suboptimal nutrition, especially in terms of energy and fiber. In addition, those on dialysis were not eating enough protein, which could be due to changing dietary recommendations as CKD progresses. Qualitative findings provided additional insight into how requisite CKD-dietary changes were perceived and how participants coped with these changes. The timing and delivery of the dietary education within CKD care in Manitoba may not be working for people with CKD as they progress through the disease.

Contexte: Les personnes atteintes d'IRC mentionnent le régime alimentaire comme un aspect important de leur vie et de leurs soins. Mieux comprendre les habitudes alimentaires actuelles de cette population et leur lien avec la façon dont les patients perçoivent les recommandations diététiques pourrait contribuer à orienter et concevoir de potentielles stratégies d'intervention diététique en contexte d'IRC. Objectif: Examiner les habitudes alimentaires des personnes atteintes d'IRC à un stade avancé, ainsi que les perspectives subjectives des participants et de leurs soignants sur les recommandations alimentaires. Conception: Étude par méthode mixte avec une conception séquentielle explicative. Cadre: Manitoba, Canada. Sujets: Les personnes atteintes d'IRC de stade avancé (stades G4-G5, y compris les patients sous dialyse) qui participent à l'essai CanFIT (Canadian Frailty Observation and Interventions Trial). Méthodologie: Des données quantitatives ont d'abord été colligées au moyen d'une évaluation transversale du régime alimentaire pour trois périodes de 24 heures, d'un questionnaire abrégé de 36 questions sur le régime alimentaire et d'un outil évaluant la qualité de vie liée à l'alimentation (n=59). Des données qualitatives ont ensuite été recueillies lors de deux groupes de discussion (n1 = 12 et n2 = 7) avec un sous-échantillon constitué de personnes ayant terminé les enquêtes sur l'alimentation et leurs soignants. Les groupes de discussion ont examiné des sujets liés à l'alimentation et à l'IRC; les données transcrites ont été analysées par thème. Au stade de l'interprétation, les résultats qualitatifs ont été combinés aux résultats quantitatifs pour aider à expliquer ces derniers et mieux comprendre les expériences subjectives des adultes atteints d'IRC. Résultats: Quantitativement, presque tous les participants (48/51; 94 %) (âge moyen: 70,8 ans ±10,8 ans) ont signalé des apports énergétiques inférieurs aux recommandations et la plupart (86 %) n'atteignaient pas l'apport recommandé en fibres. Sur les 21 patients sous dialyse, 15 (71 %) consommaient peu de protéines. Qualitativement, deux thèmes ont été dégagés: 1) le manque/besoin de directives alimentaires ­ « surcharge d'information ¼ ou information incomplète; 2) la difficulté de s'adapter aux restrictions. Pour le premier thème, les participants ont mentionné recevoir trop d'informations en même temps, souvent au mauvais moment. Pour le deuxième thème, les participants ont parlé de perte d'appétit et de tricherie par rapport aux recommandations alimentaires. Limites: Un possible biais de rappel pour les habitudes alimentaires; petite taille de l'échantillon qui limite la généralisabilité; biais d'auto-sélection. Conclusion: Malgré les changements signalés par les personnes atteintes d'IRC, lesquels ont eu des répercussions négatives sur leur vie, nombre d'entre elles avaient un régime alimentaire sous-optimal, surtout en ce qui concerne l'énergie et les fibres. En outre, les patients sous dialyse ne consommaient pas suffisamment de protéines, ce qui peut être attribuable aux changements dans les recommandations alimentaires au fur et à mesure que l'IRC progresse. Les résultats qualitatifs ont permis de mieux comprendre la façon dont les restrictions alimentaires nécessaires à l'IRC ont été perçues par les participants, et la façon dont ceux-ci ont fait face à ces changements. Le moment et le mode de prestation de l'information diététique dans le cadre des soins de l'IRC au Manitoba ne conviennent peut-être pas aux personnes atteintes d'IRC à mesure qu'elles progressent dans leur maladie. Enregistrement de l'essai: L'enregistrement n'est pas nécessaire pour cet essai.

The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Gender-affirming hormone therapy modifies body composition and lean muscle mass in transgender persons. We sought to characterize the change in serum creatinine, other kidney function biomarkers, and GFR in transgender persons initiating masculinizing and feminizing gender-affirming hormone therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to September 16, 2020 for randomized controlled trials, observational studies, and case series that evaluated the change in serum creatinine, other kidney function biomarkers, and GFR before and after the initiation of gender-affirming hormone therapy in adult transgender persons. Two reviewers independently screened and abstracted data, and disagreements were resolved by a third reviewer. A random effects meta-analysis was performed to determine the change in outcomes over follow-up of 3, 6, and 12 months. RESULTS: Of the 4758 eligible studies, 26 met the inclusion criteria, including nine studies that recruited 488 transgender men and 593 women in which data were meta-analyzed. There was heterogeneity in study design, populations, gender-affirming hormone therapy routes, and dosing. At 12 months after initiating gender-affirming hormone therapy, serum creatinine increased by 0.15 mg/dl (95% confidence interval, 0.00 to 0.29) in 370 transgender men and decreased by -0.05 mg/dl (95% confidence interval, -0.16 to 0.05) in 361 transgender women. No study reported the effect of gender-affirming hormone therapy on albuminuria, proteinuria, cystatin C, or measured GFR. CONCLUSIONS: Gender-affirming hormone therapy increases serum creatinine in transgender men and does not affect serum creatinine in transgender women. The effect on gender-affirming hormone therapy on other kidney function biomarkers and measured GFR is unknown. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Change in Kidney Function Biomarkers in Transgender Persons on Gender Affirmation Hormone Therapy-A Systematic Review and Meta-Analysis, CRD42020214248.

The Effects of Resistant Starch Consumption in Adult Patients With Chronic Kidney Disease: A Systematic Review.

Background: Resistant starches (RSs) are not digested by human digestive enzymes and pass through the upper digestive tract to become substrates for colonic bacteria. Resistant starch supplementation has shown promising results in altering the microbiota of animal models of chronic kidney disease (CKD). Resistant starch consumption may influence the production of uremic toxins in CKD. Objective: To conduct a systematic review to determine whether the consumption of RS reduces the progression of kidney disease in adult patients with CKD. Design: We included randomized controlled trials comparing RS supplementation to placebo, no treatment, or standard care. Cochrane Central, Embase, MEDLINE, Web of Science, and CINAHL databases were searched. There was no limitation on publication date, but only English manuscripts were included. The search was conducted in July 2020. Patients: Adult outpatient populations with CKD, using any recognized diagnostic criteria. Measurements: The primary outcome was change in glomerular filtration rate (GFR) from baseline through the end of the trial in patients not on dialysis; secondary outcomes included change in uremic toxin concentrations (p-cresol/p-cresyl sulfate [p-CS], indoxyl sulfate [IS]) and inflammatory markers (tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], interleukin 6 [IL-6]) from baseline through the end of the trial, and changes in self-reported symptom scores. Methods: The Cochrane Collaboration Risk of Bias tool was used to assess risk of bias in included studies. The systematic review results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: We identified 4 unique studies, reported in 9 publications that met our inclusion criteria, including a total of 215 enrolled participants. Results were calculated using data from the longest reported follow-up time. The primary outcome of changes in kidney function markers was only studied in 1 trial; this trial reported an increase in creatinine and a decrease in blood urea nitrogen; no changes in GFR were reported. A review of the secondary outcomes showed an overall decline in IS, TNF-α, and IL-6, in RS groups, but with mixed results in p-CS and CRP/high-sensitivity CRP. Safety data showed that RS was well tolerated with no reports of excessive side effects. Limitations: We determined a meta-analysis was not feasible due to clinical heterogeneity between study populations and differences in reported outcomes in the included studies. Conclusion: There is limited and inconsistent evidence on the impact of RS in adult patients with CKD. Further research is needed to determine the safety and efficacy of RS supplementation in this population.

Contexte: Les amidons résistants ne sont pas dégradés par les enzymes digestives humaines; ils traversent le tube digestif supérieur et deviennent des substrats pour les bactéries du côlon. La supplémentation en amidons résistants a montré des résultats prometteurs dans la modification du microbiote chez les modèles animaux d'insuffisance rénale chronique (IRC). Dans ce contexte, la consommation d'amidons résistants pourrait avoir une incidence sur la production de toxines urémiques. Objectif: Procéder à une revue systématique afin de déterminer si la consommation d'amidons résistants limite la progression de la maladie chez les adultes atteints d'IRC. Conception de l'étude: Ont été inclus les essais contrôlés randomisés qui comparaient la supplémentation en amidons résistants à un placebo, à l'absence de traitement ou aux soins courants. La recherche a été effectuée en juillet 2020 dans les bases de données Cochrane Central, Embase, Medline, Web of Science et CINAHL. La date de publication n'était pas limitée, mais seuls les articles rédigés en anglais ont été inclus. Sujets: Des adultes atteints d'IRC et suivis en ambulatoire, selon tout critère de diagnostic reconnu. Mesures: Le principal critère d'évaluation était un changement dans le taux de filtration glomérulaire entre le début et la fin de l'essai chez les patients non dialysés. Les résultats secondaires comprenaient un changement, entre le début et la fin de l'essai, dans les concentrations de toxines urémiques (sulfate de p-crésol/crésyle, sulfate d'indoxyle) et de marqueurs d'inflammation (TNFα, CRP, IL-6), ainsi que dans les scores de symptômes auto-déclarés. Méthodologie: L'outil de Risque de Biais de la Collaboration Cochrane a été utilisé pour évaluer le risque de biais dans les études incluses. Les résultats de la revue systématique sont présentés conformément aux directives PRISMA. Résultats: Quatre études uniques, présentées dans neuf publications et portant sur un total de 215 patients, répondaient à nos critères d'inclusion. Les résultats ont été calculés à partir des données de la plus longue période de suivi rapportée. Un seul de ces essais avait examiné le critère principal d'évaluation, soit un changement dans les marqueurs de la fonction rénale. On y rapportait une augmentation du taux de créatinine et une diminution du taux de l'urée dans le sang. Aucun changement dans le débit de filtration glomérulaire n'avait été signalé. Un examen des résultats secondaires a révélé une diminution globale du sulfate d'indoxyle, du TNF alpha et d'IL-6 dans les groupes de patients qui prenaient des suppléments d'amidon résistants, mais des résultats mitigés en ce qui concerne les taux de p-CS et de CRP/hsCRP. Les données de sécurité montraient que les amidons résistants étaient bien tolérés, aucun effet secondaire important n'ayant été rapporté. Limites: Une méta-analyse n'était pas réalisable en raison de l'hétérogénéité clinique entre les populations étudiées et des différences dans les résultats rapportés dans les études incluses. Conclusion: Les données sur les effets d'une supplémentation en amidons résistants chez les adultes atteints d'IRC sont limitées et manquent d'uniformité. D'autres recherches examinant la sécurité et l'efficacité d'une supplémentation en amidons résistants dans cette population sont nécessaires.

Comprehensiveness of Testing Among Herpes Simplex Virus Infected Infants: A Multicenter Cohort Study.

Despite clear testing recommendations for herpes simplex virus (HSV) infection in infants, few data exist on the comprehensiveness of HSV testing in practice. In a 23-center study of 112 infants with confirmed HSV disease, less than one-fifth had all recommended testing performed, highlighting the need for increased awareness of and adherence to testing recommendations for this vulnerable population.

Common risk variants for epilepsy are enriched in families previously targeted for rare monogenic variant discovery.

BACKGROUND: The epilepsies are highly heritable conditions that commonly follow complex inheritance. While monogenic causes have been identified in rare familial epilepsies, most familial epilepsies remain unsolved. We aimed to determine (1) whether common genetic variation contributes to familial epilepsy risk, and (2) whether that genetic risk is enriched in familial compared with non-familial (sporadic) epilepsies. METHODS: Using common variants derived from the largest epilepsy genome-wide association study, we calculated polygenic risk scores (PRS) for patients with familial epilepsy (n = 1,818 from 1,181 families), their unaffected relatives (n = 771), sporadic patients (n = 1,182), and population controls (n = 15,929). We also calculated separate PRS for genetic generalised epilepsy (GGE) and focal epilepsy. Statistical analyses used mixed-effects regression models to account for familial relatedness, sex, and ancestry. FINDINGS: Patients with familial epilepsies had higher epilepsy PRS compared to population controls (OR 1·20, padj = 5×10-9), sporadic patients (OR 1·11, padj = 0.008), and their own unaffected relatives (OR 1·12, padj = 0.01). The top 1% of the PRS distribution was enriched 3.8-fold for individuals with familial epilepsy when compared to the lowest decile (padj = 5×10-11). Familial PRS enrichment was consistent across epilepsy type; overall, polygenic risk was greatest for the GGE clinical group. There was no significant PRS difference in familial cases with established rare variant genetic etiologies compared to unsolved familial cases. INTERPRETATION: The aggregate effects of common genetic variants, measured as polygenic risk scores, play an important role in explaining why some families develop epilepsy, why specific family members are affected while their relatives are not, and why families manifest specific epilepsy types. Polygenic risk contributes to the complex inheritance of the epilepsies, including in individuals with a known genetic etiology. FUNDING: National Health and Medical Research Council of Australia, National Institutes of Health, American Academy of Neurology, Thomas B and Jeannette E Laws McCabe Fund, Mirowski Family Foundation.