Government of Ontario, Canada

Oculogastrointestinal neurodevelopmental syndrome (OGIN; OMIN #619318) is a rare autosomal recessive disorder resulting from pathogenic variants in the CAPN15 gene. OGIN syndrome has been previously seen to affect many different body systems and has been described to cause coloboma, imperforate anus, structural cardiac defects, and horseshoe kidneys. There is still little information about the phenotypic spectrum of this disease. This case series aims to describe the phenotypic spectrum and development of affected individuals. Our study includes eight patients—five patients previously described, and three newly identified patients from centers in Ontario and Quebec ranging from three to 15 years of age. All the French‐Canadian patients in our cohort were homozygous for the c. 1838C>T (p. Ser613Leu) variant. We also describe a non‐French‐Canadian patient who is compound heterozygous for the variants c.1957G>A (p. Gly653Ser) (paternally inherited) and c.2520delC p. Val841Trpfs133 (maternally inherited). Through this cohort, we describe some rare manifestations of OGIN syndrome; all four female patients had vaginal fistulae, and four of the patients had sensorineural hearing loss. All eight patients had pancreatic insufficiency requiring pancreatic enzyme replacement. More research is needed to investigate the genotype–phenotype correlation, as well as assess long‐term complications and natural history of the disease.

Aims To conduct a multi‐study, cross‐country examination of diabetes stigma among adults with type 1 and type 2 diabetes (T1D, T2D). Methods Pre‐existing, cross‐sectional studies of adults (aged ≥18) completing the T1D or T2D Diabetes Stigma Assessment Scales (DSAS‐1/DSAS‐2) were collated. Descriptive statistics were calculated for (sub)scale and item scores. Variance‐components linear random‐effect multi‐level modelling (nested random intercepts for country and study) estimated overall mean (sub)scale scores, 95% confidence intervals, intraclass correlation coefficients (ICC) and 95% prediction intervals. Likelihood ratio (LR) tests provided inference for country‐ and study‐specific heterogeneity. Results Eleven studies were included from six countries (Australia k = 2, Canada k = 1, Japan k = 2, New Zealand k = 1, UAE k = 1, USA k = 4) in four languages (Arabic k = 1, English k = 7, Japanese k = 2, Spanish k = 1). Six studies included n = 3114 adults with T1D (insulin pump: 42%; 75% aged <60 years). Ten studies included n = 6586 adults with T2D (insulin‐treated: 37%; 44% aged <60 years). Most reported ≥1 experience of diabetes stigma (T1D = 91%; study range: 84%–96%; T2D = 77%; 69%–89%). In 10 studies, the ‘blame and judgment’ subscale was most endorsed (T1D = 83%; 62%–89%, T2D = 70%; 53%–79%). Most adults with T1D reported ‘identity concerns’ (73%; 62%–80%), and 47% of adults with T2D reported ‘self‐stigma’ (30–60%). Being ‘treated differently’ was least common (T1D = 46%; 40%–54%, T2D = 37%; 28%–47%). Low levels of heterogeneity were observed in mean [SE] total scores (DSAS‐1: 54 [0.94] ICC = 0.02, p < 0.001; DSAS‐2: 44 [1.1], ICC ≤0.4, p < 0.001). Conclusions Findings suggest a high and relatively consistent prevalence of diabetes stigma across studies and within and across countries, supporting calls for local and global action.

Shared decision-making supports person-centred care. Our team of Inuit-led and/or -focused organizations and researchers field-tested a strategy called Not Deciding Alone to support health decision-making. Guided by aajiiqatigiingniq, a principle of collective decision-making and consensus-building, we co-produced a mixed-methods study to: (1) train Qikiqtani region community health representatives (CHRs) with a workshop, (2) develop a radio show and survey, and (3) assess the radio show with Inuit community members in the health system. We evaluated participant experiences using forms, case studies, and an online survey. The workshop was delivered to 13 CHRs; seven (54%) provided evaluation data. All (100%) reported positive experiences with the content, activities, and facilitation. One (14%) said the workshop was too short; four (57%) agreed there was enough discussion time. Six (86%) reported new learning. Three radio show events were held with 33 survey respondents, the majority women (n = 25, 76%). Most found the show informative (n = 29, 88%) and helpful for future decision-making (n = 27, 82%), and said it would improve their confidence (n = 27, 82%). Not Deciding Alone was found to be an acceptable, useful, and relevant strategy for supporting health decision-making among Inuit community members.

Background A decline in driving skills is well documented in people with dementia. Objective To provide a current estimate and future forecast of drivers with dementia in Ontario, Canada, taking into account sex differences and longitudinal estimates of driving cessation in dementia. Methods We used historical provincial licensing data, population estimates and projections, as well as estimates of diagnosable dementia from the Landmark study of the Alzheimer's Society of Canada to create current estimates and forecasts of drivers with dementia in the province of Ontario, the most populous province of Canada, from 2024 to 2046. Sensitivity analyses were used to determine the impact of sex and assumptions regarding the rate of driving cessation. Results Assuming that an estimated 35% of people with diagnosable dementia stop driving very shortly after symptom onset followed by a more gradual decline over time, and that females stop driving twice as fast as men, we forecast approximately 154,000 drivers with dementia in the province of Ontario in 2046. Conclusions As dementia prevalence increases, our study provides a novel set of projections for drivers with dementia over the coming two decades, estimating a 221% to 226% increase. This work adds to the myriad of concerns about health and public services that will be needed to treat and support this population effectively, to detect early signs of dangerous driving among the cognitively impaired, and to provide alternative transportation options, once driving is no longer viable.

Bullous pemphigoid (BP) is a chronic autoimmune blistering disease primarily affecting the elderly population. While awaiting the results from randomized clinical trials to assess the effect of dupilumab in patients with BP, clinicians have begun to introduce dupilumab into their therapeutic arsenal, with few data supporting their clinical decisions. The objectives were to assess time to disease control, predictors of response, achievement of disease control, disease recurrence, and occurrence of adverse events. Randomized and non-randomized studies of interventions (NRSIs) from Medline and Embase were reviewed. A total of 315 studies were identified and 5 NRSIs (167 participants with moderate-to-severe BP) meeting our inclusion criteria were found. Dupilumab was significantly associated with shorter time to disease control compared with the control group (HR 2.71 [95% CI, 1.85–3.96; I2 = 35%; 127 participants; 4 studies]). The overall strength of the evidence was graded as very low due to serious risk of bias and imprecision of effect measures. There were insufficient data to inform conclusions regarding BP recurrence and adverse events. Evidence was found that dupilumab reduces time to disease control in BP. It was not possible to assess predictors of response using pre-planned meta-regression. Randomized controlled trials are needed to determine dupilumab’s place in therapeutic algorithms for BP. PROSPERO number: CRD42024599235

Long-distance migratory ducks play a critical role in the maintenance and dissemination of A(H5N1) viruses. Comparative pathogenicity studies were conducted on blue-winged teal (BWTE; Anas discors ) using three distinct genotypes of A(H5N1) clade 2.3.4.4b viruses (A1, B1.3, and B4.1) isolated from wild ducks in Canada. Twenty-four hours post-intranasal infection of BWTE, contact turkeys and chickens were introduced into each of the groups to evaluate viral transmission. The levels of viral shedding in BWTE increased from 3 to 7 days post-infection (dpi) and continued at lower levels until 14 dpi. The A1 genotype virus (MALL/NS/22) was found to be the least pathogenic to BWTE compared to the reassortant genotypes, B4.1 (RBME/BC/22) and B1.3 (BWTE/MB/22). The B1.3 genotype was the most virulent to BWTE and caused 66.7% mortality compared to 12.5% mortality caused by the B4.1 genotype. The extent of transmission from infected BWTE to contact turkeys and chickens showed variations. Turkeys housed with BWTE infected with either virus died within 6 to 10 days post-contact (dpc). Conversely, the transmission and mortality among contact chickens varied. The highest mortality (3 out of 5) occurred in chickens exposed to BWTE infected with the B1.3 genotype. Whilst in the B4.1 genotype, 2 out of 6 chickens died, none of the chickens in the A1 genotype succumbed to infection. No shedding or seroconversion was noted in all surviving chickens. This research underscores variations in the pathogenic traits and transmissibility among the different genotypes of A(H5N1) clade 2.3.4.4b viruses. This finding is vital for understanding the role of migratory birds in the epidemiology of A(H5N1) and the need for continuous monitoring of these viruses. IMPORTANCE The recurrent incursions of A(H5N1) clade 2.3.4.4b viruses into North America have resulted in the emergence of reassortant virus genotypes. These genotypes exhibit variations in pathogenicity and host ranges. Blue-winged teal (BWTE) are the most common dabbling ducks in North America and play a crucial role in maintaining and dispersing influenza A viruses (IAVs). In some areas, the migratory pathways of BWTE overlap with densely populated commercial poultry facilities. Despite this, the role of BWTE in the maintenance and spread of A(H5N1) is not well understood, and there is limited data on their susceptibility to A(H5N1) clade 2.3.4.4b viruses. Our study demonstrates differences in BWTE susceptibility to distinct genotypes of A(H5N1) clade 2.3.4.4b viruses. The virus transmission from infected BWTE and lethality in turkeys and chickens were also influenced by the virus genotypes. The findings suggest that BWTE could contribute to the maintenance and spread of highly pathogenic avian influenza (HPAI) viruses, and active surveillance in BWTE is essential.

Introduction Haemorrhage is the leading preventable cause of death following traumatic injury, additionally affecting morbidity and mortality in a variety of other conditions. Timely intervention with blood products and definitive management is essential. In Northern Ontario, limited access to care poses challenges in managing these conditions. The objective of our study was to describe the prevalence with which patients suffering from known or suspected haemorrhage, transported by air ambulance in Northern Ontario, received a blood transfusion. Methods This was a retrospective cohort study of patients in Northern Ontario with known or suspected haemorrhage, transported by air ambulance to hospital. Patients included had a primary problem of trauma, gastrointestinal (GI) bleeding, obstetrical haemorrhage or vascular and other bleeding, and met pre-defined physiologic indications for transfusion. Data were abstracted from electronic patient care records. Results A total of 1165 patients were included, with a mean age of 48.5 years and 54.8% being male. The most common reasons for transfusion included traumatic injury (46.1%), GI bleeding (29.5%) and vascular/other etiologies (13.8%). Only 233 (20%) patients received a transfusion. Patients with GI haemorrhage most frequently received transfusion, accounting for 46.8% of patients, while those suffering from traumatic injury accounted for 28.7% of the total transfusions. Conclusions Eighty percent of patients who may have required a transfusion did not receive one, illustrating the importance of expanded access to blood products in rural and remote communities across Ontario. Further investigation into mechanisms that support residents of these communities who may suffer from haemorrhage is required. Introduction L’hémorragie est la principale cause évitable de décès à la suite d’une blessure traumatique. Elle affecte également la morbidité et la mortalité dans une variété d’autres conditions. Une intervention rapide avec des produits sanguins et une prise en charge définitive sont essentielles. Dans le nord de l’Ontario, l’accès limité aux soins pose des problèmes pour la prise en charge de ces pathologies. L’objectif de notre étude était de décrire la fréquence avec laquelle les patients souffrant d’une hémorragie connue ou présumée, transportés par ambulance aérienne dans le nord de l’Ontario, ont reçu une transfusion sanguine. Méthodes Il s’agit d’une étude de cohorte rétrospective de patients du nord de l’Ontario présentant une hémorragie connue ou présumée, transportés par ambulance aérienne à l’hôpital. Les patients inclus avaient un problème primaire de traumatisme, d’hémorragie gastro-intestinale, d’hémorragie obstétricale, d’hémorragie vasculaire ou d’autres formes d’hémorragies et répondaient à des indications physiologiques prédéfinies pour la transfusion. Les données ont été extraites des dossiers électroniques des patients. Résultats Au total, 1165 patients ont été inclus, avec un âge moyen de 48.5 ans et 54,8% d’hommes. Les raisons les plus fréquentes de la transfusion étaient des lésions traumatiques (46,1%), des hémorragies gastro-intestinales (29,5%) et des étiologies vasculaires/autres (13,8%). Seuls 233 patients (20%) ont reçu une transfusion. Les patients souffrant d’hémorragie gastro-intestinale ont le plus souvent reçu une transfusion, soit 46,8% des patients, tandis que ceux souffrant de lésions traumatiques représentaient 28,7% du total des transfusions. Conclusions 80% des patients susceptibles d’avoir besoin d’une transfusion sanguine n’en ont pas reçu, ce qui illustre l’importance d’un accès élargi aux produits sanguins pour les patients des communautés rurales et éloignées de l’Ontario. Il est nécessaire de poursuivre les recherches sur les mécanismes qui soutiennent les résidents de ces communautés susceptibles de souffrir d’une hémorragie.

Importance Current topical treatments for scalp psoriasis are limited by formulation, efficacy, and/or safety. Objective To assess safety and efficacy of roflumilast foam, 0.3%, in patients with psoriasis of the scalp and body. Design, Setting, and Participants This was a phase 3 double-blinded, vehicle-controlled randomized clinical trial conducted between August 24, 2021, and June 3, 2022, at 49 sites in Canada and the US. Eligible participants were 12 years and older with plaque psoriasis affecting up to 25% of the scalp and body, at least 10% of the scalp, and up to 20% of nonscalp areas, with a minimum Scalp−Investigator Global Assessment (S-IGA) score of 3 (moderate), and minimum Body−IGA (B-IGA) score of 2 (mild). Data analyses were performed from September 9 to December 30, 2022. Interventions Once-daily roflumilast foam, 0.3%, or vehicle for 8 weeks. Main Outcomes and Measures Coprimary end points were S-IGA and B-IGA success (clear [0] or almost clear [1] plus ≥2-grade improvement) at week 8. Secondary end points included S-IGA success at weeks 2 and 4, change in Scalp Itch−Numeric Rating Scale (SI-NRS), and SI-NRS and Worst Itch−NRS (WI-NRS) success (≥4-point improvement in patients with baseline score of ≥4). Safety and tolerability were also assessed. Results A total of 432 patients (mean [SD] age, 47.3 [14.8] years; 243 women [56.3%]) were randomized to roflumilast foam (n = 281) or vehicle (n = 151). At week 8, 66.4% of the roflumilast group achieved S-IGA success vs 27.8% of the vehicle group ( P < .001); and 45.5% of the roflumilast group achieved B-IGA success compared with 20.1% of the vehicle group ( P < .001). Rates for S-IGA success at week 2 and SI-NRS and WI-NRS success at weeks 2, 4, and 8 were significantly higher for roflumilast vs vehicle. Improvements in SI-NRS were greater for the roflumilast vs the vehicle group as early as the first assessment (24 hours after the first application). Both study groups had low rates of adverse events and favorable tolerability profiles. Conclusions and Relevance This randomized clinical trial found that roflumilast foam, 0.3%, improved signs and symptoms of psoriasis on the scalp and body, including pruritus, with low rates of adverse events in patients 12 years and older. These results demonstrate the potential of roflumilast foam, 0.3%, as monotherapy for patients with psoriasis of the scalp and body. Trial Registration ClinicalTrials.gov Identifier: NCT05028582

Aims and background In the pivotal ZUMA-7 trial, second-line (2L) treatment with axicabtagene ciloleucel (axi-cel) had superior clinical outcomes compared to standard of care (SOC; salvage chemoimmunotherapy followed by high-dose therapy and autologous stem cell transplant in responders) in patients with large B-cell lymphoma (LBCL) who were refractory or relapsed (r/r) within 12 months of completion of frontline therapy. The aim of this analysis was to evaluate the cost-effectiveness of axi-cel compared to SOC for 2L LBCL in Canada. Methods A 3-health state partitioned-survival model was used to estimate the cost-effectiveness of axi-cel vs. SOC from a Canadian healthcare system perspective. Clinical outcomes were informed by ZUMA-7. The model calculated expected quality-adjusted life years (QALYs), total costs, and the incremental cost-effectiveness ratio (ICER). Results Over a lifetime horizon, the model estimated a total of 9.48 and 7.25 QALYs, and total costs of $569,168 and$337,906 for axi-cel and SOC, respectively, resulting in an ICER of $103,810/QALY. When adjusting for the substantial proportion of patients in the SOC arm who received cellular therapy as subsequent treatment, the ICER was reduced to$78,555/QALY. Conclusions Treatment with axi-cel in 2L is a cost-effective option that addresses an important unmet clinical need for Canadian patients with r/r LBCL.

Aim To comprehensively review the experiences and support needs of internationally educated nurses in healthcare settings for older people, identify current supportive interventions for internationally educated nurses in gerontological nursing practice and determine research gaps in the existing literature on their experiences and support needs. The review includes all types of nurses, except those focusing solely on undergraduate nurses who have yet to practise and nursing assistants. Methods A scoping review by a Canadian review group followed the methodological framework outlined by Arksey and O'Malley (2005) and later refined by Levac, Colquhoun, and O'Brien (2010). Articles of any publication date were included. A two‐stage screening process was conducted independently to determine eligibility. Data extraction was performed using a piloted charting form. We also conducted a consultative exercise with Canadian nurses. Thematic and descriptive analyses were employed to analyse the extracted data. Data Sources Seven databases (PubMed, PsycINFO, PsychArticles, CINAHL, Scopus, Web of Science and EThOS) were systematically searched on April 27, 2024. Grey literature was searched using Google search engines, OpenGrey, ProQuest Sociological Abstracts and ProQuest ERIC, Healthcare Management Information Consortium, Open Grey repository, Proceedings First, Canada Health and Council for Allied Health Professions Research, and through expert consultation. Results The scoping review identified 11 articles from Canada, Germany, Ireland, the Netherlands, New Zealand, Norway and the United Kingdom, highlighting positive experiences and challenges internationally educated nurses face in healthcare settings for older people. Nurses were primarily registered nurses. Challenges included workplace interpersonal issues, language barriers and organisational constraints, while positive experiences included being valued by older adults and colleagues. Conclusion The findings highlight the need for supportive interventions like mentorship, cultural competency training and organisation‐led initiatives to improve internationally educated nurses' integration and retention in geriatric care, enhancing care quality for older persons. Implications for Practice Enhancing mentorship programs, cultural competency training, and organization‐led support initiatives can improve the integration, retention, and overall well‐being of internationally educated nurses in geriatric care, ultimately enhancing the quality of care for older adults. Trial Registration: osf.io/cwjem

Importance Ivarmacitinib, a selective oral Janus kinase 1 (JAK1) inhibitor, has demonstrated efficacy for treating adults with moderate to severe atopic dermatitis (AD) in a phase 2 trial. Objective To evaluate the efficacy and adverse events of ivarmacitinib in adolescents and adults with moderate to severe AD. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial included patients aged 12 to 75 years with moderate to severe AD. Patients were enrolled from 53 sites in Canada and China from April 2021 to April 2022. Data were analyzed from July 11 to September 27, 2023. Interventions Patients were randomized (1:1:1) to receive once-daily 4- or 8-mg ivarmacitinib or placebo for 16 weeks. Main Outcomes and Measures Co-primary end points were the proportions of patients achieving an Investigator Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-grade improvement from baseline and an Eczema Area and Severity Index score improvement of 75% (EASI-75) at week 16. Results Of 336 randomized patients (mean [SD] age, 31.1 [15.4] years; 213 [63.4%] male; 286 [85.1%] Asian), 113 received 4-mg ivarmacitinib, 112 received 8-mg ivarmacitinib, and 111 received placebo. At week 16, significantly more patients in the 4-mg ivarmacitinib group (41 of 113 [36.3%]; 95% CI, 27.5%-45.9%; P < .001) and the 8-mg ivarmacitinib group (47 of 112 [42.0%]; 95% CI, 32.7%-51.7%; P < .001) achieved an IGA score of 0 or 1 with at least a 2-grade improvement compared to the placebo group (10 of 111 [9.0%]; 95% CI, 4.4%-15.9%). EASI-75 responses were also significantly higher in the ivarmacitinib groups: 61 patients (54.0%; 95% CI, 44.4%-63.4%; P < .001) in the 4-mg group, and 74 (66.1%; 95% CI, 56.5%-74.8%; P < .001) in 8-mg group compared to 24 patients (21.6%; 95% CI, 14.4%-30.4%) in the placebo group. Treatment-emergent adverse events were reported by 78 patients (69.0%) in the 4-mg group, 74 (66.1%) in the 8-mg group, and 72 (64.9%) in the placebo group. Serious treatment-emergent adverse events occurred in 3 patients (2.7%) in the 4-mg group, 2 (1.8%) in the 8-mg group, and 3 (2.7%) in the placebo group. Conclusions and Relevance This phase 3 randomized clinical trial determined that once-daily ivarmacitinib demonstrated significant efficacy and a favorable risk-benefit profile for treating moderate to severe AD in adults and adolescents. These results support the potential of ivarmacitinib as a new therapeutic option. Trial Registration ClinicalTrials.gov Identifier: NCT04875169

The National Society of Genetic Counselors (NSGC) planned to develop an evidence‐based guideline on the outcomes of genetic counseling for individuals at risk for hereditary cancer. The practice guideline workgroup used Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology including ranking the importance of outcomes of genetic counseling for individuals at risk for hereditary cancer. However, due to evidence gaps in the literature, particularly the limited availability of high quality and well‐designed studies for many important outcomes of genetic counseling, the NSGC identified a need for additional research prior to guideline development. Herein, we describe a “call to action” for future research, particularly for health services‐related outcomes of genetic counseling in diverse populations. Identified research priorities include conducting high‐quality studies that separate the outcomes of genetic counseling from genetic testing, assessing outcomes associated with pre‐ and/or post‐test genetic counseling, measuring patient‐reported and health system‐reported outcomes, comparing genetic counseling by certified genetic counselors versus non‐genetics‐trained providers, differentiating need in various hereditary cancer indications, and identifying barriers to genetic counseling in historically excluded patient communities.

Topic This review assesses the effectiveness of intravenous sedation compared to non-intravenous sedation for routine cataract surgery. Clinical Relevance Cataract surgery is a safe and routinely performed surgery. Sedation practices vary, with centers providing either intravenous (IV), oral or no sedation for surgery. Improving sedation practices may have significant implications for patient safety, patient experience and health system efficiency. Methods Medline, Embase, Cochrane Library, BIOSIS, Web of Science, and CINAHL were searched from inception to July 2024 for relevant articles containing original data. Randomized controlled trials that compared IV to oral or no sedation and 1) used a validated pain scale to report on pain or 2) reported on perioperative complications were included. A random effects meta-analysis was conducted. Odds ratios, standard mean differences, 95% confidence intervals (CIs), and I ² statistics were reported. The review was registered in PROSPERO (CRD42024582495) and PRISMA guidelines were followed. Results 12 randomized controlled trials including 1130 patients were included in the meta-analysis. IV sedation was associated with significantly decreased pain compared to no sedation (SMD = -0.98, 95% CI -1.68 to -0.29). Comparing IV and oral sedation, however, there was no difference in patient reported pain (SMD = -0.54, 95% CI -1.60 to 0.52). Analysis of intraoperative complications showed that there was no significant difference in complications between patients receiving IV and oral sedation (OR = 0.68, 95% CI 0.27 to 1.73). Conclusion For routine cataract surgery, IV sedation was associated with less pain than no sedation, but oral and IV sedation provided comparable pain control. Perioperative complications occur at similar rates regardless of sedation modality. These findings may help to inform sedation practices for cataract surgery.

In the first analysis purporting to causally link environmental pollution to personality, Schwaba and colleagues leveraged a natural experiment driven by the United States. They used the Clean Air Act to assess the impact of decreased atmospheric lead on the “big five” personality traits. Using data from an online personality test taken by more than 1.2 million U.S. residents, Schwaba et al. reported that people born after lead levels had peaked in their county of birth had more mature, psychologically healthy personalities in adulthood (higher agreeableness and conscientiousness, and lower neuroticism) than cohorts born earlier and exposed to higher levels of atmospheric lead. One concern with their findings is that personality differences among people born in different periods could come from factors unrelated to lead, for example, access to abortion and birth control, or demographic, cultural, or technological changes. Schwaba et al. recognized this possibility but did not fully explore it. When we account for cohort-wide changes by introducing birth year fixed effects into Schwaba et al. ’s models, the estimated effects of the lead phaseout on personality largely disappear, becoming indistinguishable from zero while remaining precise. Meanwhile, the estimated birth year fixed effects are jointly significant, suggesting differences in personality traits across cohorts. These results indicate that any effects of the lead phaseout on more mature, psychologically healthy adult personalities are not consistently observable in the data used by Schwaba et al. More broadly, they caution against making causal inferences without controlling for time period effects.

Background and Objectives Spinocerebellar ataxias (SCA) represent a clinically and genetically heterogeneous group of progressive neurodegenerative diseases with prominent cerebellar atrophy. Recently, a novel pathogenic repeat expansion in intron 1 of FGF14 was identified, causing adult‐onset SCA (SCA27B). We aimed to determine the proportion of our unsolved adult‐onset ataxia cohort harboring this expansion using several technologies, and to characterize the phenotypic presentation within our population. Methods Individuals presenting with adult‐onset ataxia (> 30 years old) and negative previous genetic testing were selected from the Care4Rare patient repository. Affected individuals were from all ethnicities, and 90% had a family history suggestive of dominant ataxia, representing 19 of the 23 families included. We used multiple tools (PCR, long‐read genome sequencing and optical genome mapping (OGM)) to identify the pathogenic GAA repeat in FGF14. Results Of the 23 families included in this study, 65.2% harbored a pathogenic GAA expansion in FGF14. Individuals of French‐Canadian descent (FC) represented most of our cohort and had a 64.7% diagnostic yield. Affected individuals presented with gaze‐evoked nystagmus, gait ataxia, cerebellar dysarthria, and early episodic features. The GAA expansion in FGF14 was visible by OGM in all individuals tested. Interpretation Our diagnostic yield demonstrates this expansion may be the most common cause of adult‐onset SCA in dominant families of FC ancestry. Our FC participants have a phenotype distinct from previously published FC patients, with gaze‐evoked nystagmus being the most common eye anomaly. From a diagnostic standpoint, the pathogenic GAA repeat can be identified by OGM, but additional tests are required to complement the interpretation.

This work presents the application of zinc oxide (ZnO) and zinc ferrite (ZnFe2O4) for electrochemical pH sensing. ZnO and ZnFe2O4 are synthesized by auto-combustion synthesis method. Field emission scanning electron microroscopic (FESEM) images revealed that ZnO particles have pyramid- and spherical-shaped morphology with micrometer dimensions, while ZnFe2O4 particles have spherical shape at the nanoscale. The surface-modified screen-printed electrodes with ZnO and ZnFe2O4 particles are initially characterized by the ferri/ferrocyanide redox couple. Significant improvement in sensitivity (bare carbon: $6.3~\pm ~0.4~\mu$ A/mM, ZnO: $8.5~\pm ~0.3~\mu$ A/mM, ZnFe2O4: $8.9~\pm ~0.5~\mu$ A/mM) and rate constant (bare carbon: $10~\pm ~1~{\text {ms}}^{-{1}}$ , ZnO: $46~\pm ~4~{\text {ms}}^{-{1}}$ , ZnFe2O4: $42~\pm ~3~{\text {ms}}^{-{1}}$ ) is observed with the surface-modified sensors. Chronopotentiometric pH response of the sensors showed hysteresis behavior with pH loop. No interference effects are observed, and the pH sensitivity of the bare carbon sensor ( $23.9~\pm ~1.4$ mV/pH) is increased by the introduction of ZnO ( $38.1~\pm ~1.3$ mV/pH) and ZnFe2O4 ( $37.2~\pm ~1.1$ mV/pH) particles. Stability of the pH response is discussed, and ways for its improvement are proposed.

Introduction Safer opioid supply (SOS) is a harm reduction approach to prescribing pharmaceutical opioids to people at high risk of overdose from the toxic unregulated drug supply. Previous research demonstrates positive health outcomes and reductions in overdose mortality among SOS clients; however few reports describe previous opioid agonist treatment history prior to initiating SOS, or the medication combinations and doses prescribed within SOS programs. Methods We used convenience sampling to collect survey data from 95 SOS program clients in London, Canada. We use descriptive statistics to analyze survey data and report on OAT history prior to initiating SOS, including maximum methadone dose. We also report on current SOS medication combinations and doses. Findings Previous experience with OAT was common and reported by 87 % of SOS clients. Mean highest dose of methadone ever received was 95 mg (range: 20–200 mg), with close to 40 % reporting doses of ≥ 120 mg. 95 % of SOS clients reported prescriptions for immediate-release tablet hydromorphone; 28 % were receiving hydromorphone monotherapy; 68 % were receiving hydromorphone alongside a long-acting opioid, and 5 % receiving hydromorphone alongside 2 long-acting opioids. Total average milligram morphine equivalent (MME) doses of combination SOS prescriptions (MME 1616) were similar to high dose methadone (120 mg = MME 1440). Conclusions Previous high dose OAT experience was common among SOS clients prior to enrollment in the SOS program. Our results may inform the individualization of high dose opioid prescriptions for people with high tolerance due to exposure to unregulated fentanyl.