Move&Connect-Caregivers: A virtual group intervention for caregivers of youth experiencing persisting symptoms after concussion.

Caregivers play a critical role in supporting youth experiencing persisting symptoms after concussion (PSAC). However, there are limited empirically validated interventions tailored to the specific needs of caregivers, such as improving concussion knowledge and supporting psychosocial wellbeing. This study aims to describe the development of a virtual group intervention for caregivers of youth experiencing PSAC, Move&Connect-Caregivers (M&C-C), and examine its feasibility. Nine mothers participated across two M&C-C groups. Feasibility metrics and semi-structured interviews were collected and analyzed using descriptive and qualitative content analysis. Results suggest that M&C-C is a feasible intervention. By merging social support, concussion psychoeducation, and active skill building, M&C-C is meaningful for caregivers supporting their children experiencing PSAC.

Improving Functional Muscle Regeneration in Volumetric Muscle Loss Injuries by Shifting the Balance of Inflammatory and Pro-Resolving Lipid Mediators.

Severe tissue loss resulting from extremity trauma, such as volumetric muscle loss (VML), poses significant clinical challenges for both general and military populations. VML disrupts the endogenous tissue repair mechanisms, resulting in acute and unresolved chronic inflammation and immune cell presence, impaired muscle healing, scar tissue formation, persistent pain, and permanent functional deficits. The aberrant healing response is preceded by acute inflammation and immune cell infiltration which does not resolve. We analyzed the biosynthesis of inflammatory and specialized pro-resolving lipid mediators (SPMs) after VML injury in two different models; muscle with critical-sized defects had a decreased capacity to biosynthesize SPMs, leading to dysregulated and persistent inflammation. We developed a modular poly(ethylene glycol)-maleimide hydrogel platform to locally release a stable isomer of Resolvin D1 (AT-RvD1) and promote endogenous pathways of inflammation resolution in the two muscle models. The local delivery of AT-RvD1 enhanced muscle regeneration, improved muscle function, and reduced pain sensitivity after VML by promoting molecular and cellular resolution of inflammation. These findings provide new insights into the pathogenesis of VML and establish a pro-resolving hydrogel therapeutic as a promising strategy for promoting functional muscle regeneration after traumatic injury.

Neural mechanisms driving speech and language recovery following childhood stroke: a scoping review.

PURPOSE: This scoping review aimed to inform future research priorities by collating evidence on neural correlates of speech and language recovery following childhood stroke. METHODS: Neuroimaging, motor speech, or language outcomes following childhood stroke (28 days to 18 years age) in the subacute to chronic community stages (care occurring after acute medical management, including inpatient and outpatient rehabilitation, and community-based programs) were identified and extracted from Medline, Embase, PsycInfo, and Clinical databases. RESULTS: Of the 3990 studies screened, 11 met the inclusion criteria. Of the included articles, no papers formally assessed speech outcomes, 11 articles reported language outcomes through standardized testing, 11 utilized structural imaging (CT, MRI), and four reported functional neuroimaging outcomes (fMRI). INTERPRETATION: This review revealed a rudimentary accounting of speech and language profiles in children post-stroke; limited by the use of varied and incomplete speech and language assessment batteries, inconsistent reporting of lesion locations associated with speech and language outcomes, a dearth of functional neuroimaging studies, and lack of information about speech and language function throughout the rehabilitation period, a time when the brain is most plastic and receptive to therapy. Future research should provide complete and accurate accounts of speech and language function and their neural correlates throughout rehabilitation and recovery to inform care, education, and employment planning.

Although stroke is a top 10 cause of mortality in children, the current literature contains a rudimentary accounting of the speech and language profiles, and their neural correlates, following stroke in children.For rehabilitation professionals, our review demonstrates the need for comprehensive speech and language assessment in the subacute stage of recovery from childhood stroke.A complete and accurate account of speech and language functions, and their neural correlates, spanning recovery from childhood stroke is needed to inform clinical care.

Motivators and barriers for studying podiatry in Australia and New Zealand: A mixed methods study.

BACKGROUND: Podiatry enrolments at Australian and New Zealand universities have decreased by 17.3% since 2015, which threatens the profession's sustainability and the health and wellbeing of Australian and New Zealand people and communities. Reasons for this decline remain unclear due to insufficient evidence on factors influencing career choices. The overarching aim of this study was to identify motivators and barriers for studying podiatry in Australia and New Zealand. METHODS: This study used a convergent mixed methods design. Students enrolled in (i) podiatry and (ii) relevant non-podiatry health, sport or science programs at nine Australian and one New Zealand university, were invited to participate in an online survey. First-year podiatry students were also invited to participate in an online workshop. Quantitative data were analysed using descriptive statistics and linear/logistic regression models. Three independent assessors used inductive thematic analysis for the qualitative data. RESULTS: Overall, 278 podiatry students (mean age 24.9 ± 8.5 years, 65.1% female) and 553 non-podiatry students (mean age 24.8 ± 8.2 years, 75.4% female; 32.2% from physiotherapy and 29.1% from occupational therapy) responded to the survey. Interest in a health-related career, wanting to make a difference to people's health, and opportunity to care for people from different backgrounds/age groups were key motivating factors among podiatry students. Barriers to studying podiatry were encountered by 28.1% of podiatry students. Thematic analysis identified seven themes concerning career choice, which are as follows: (i) awareness of profession and scope of practice; (ii) stereotypes and negative perceptions of the profession; (iii) awareness of career pathways; (iv) job prospects and earning potential; (v) working with people and building relationships; (vi) podiatry is not the first preference; and (vii) barriers which limit student enrolment. CONCLUSIONS: There are a variety of factors that motivate and influence students to study podiatry, however, altruistic reasons are most highly rated. Allied health students have limited understanding of the scope of practice and career opportunities in podiatry. Additionally, the podiatry profession often faces negative stereotypes. Further work is required to reverse the negative stereotypes and perceptions of podiatry and build knowledge of the profession's scope of practice, career pathways/opportunities, job prospects and earning potential.

Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.

BACKGROUND: Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1. METHODS: 15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study. All patients received unilateral subretinal injections of ATSN-101. In the dose-escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1·0 × 1010 vg/eye (low dose), 3·0 × 1010 vg/eye (middle dose), and 1·0 × 1011 vg/eye (high dose). In the dose-expansion phase, one adult cohort (n=3) and one paediatric cohort (n=3) were treated at the high dose. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints included full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also done. Data through the 12-month main study period are reported. FINDINGS: Patients were enrolled between Sept 12, 2019, and May 5, 2022. A total of 68 TEAEs were observed, 56 of which were related to the surgical procedure. No serious TEAE was related to the study drug. Ocular inflammation was mild and reversible with steroid treatment. For patients who received the high dose, mean change in dark-adapted FST was 20·3 decibels (dB; 95% CI 6·6 to 34·0) for treated eyes and 1·1 dB (-3·7 to 5·9) for untreated eyes at month 12 (white stimulus); improvements were first observed at day 28 and persisted over 12 months (p=0·012). Modest improvements in BCVA were also observed (p=0·10). Three of six patients who received the high dose and did the MLMT achieved the maximum score in the treated eye. INTERPRETATION: ATSN-101 is well tolerated 12 months after treatment, with no drug-related serious adverse events. Clinically significant improvements in retinal sensitivity were sustained in patients receiving the high dose. FUNDING: Atsena Therapeutics.

Canadian beach cohort study: protocol of a prospective study to assess the burden of recreational water illness.

BACKGROUND: Recreational water activities at beaches are popular among Canadians. However, these activities can increase the risk of recreational water illnesses (RWI) among beachgoers. Few studies have been conducted in Canada to determine the risk of these illnesses. This protocol describes the methodology for a study to determine the risk and burden of RWI due to exposure to fecal pollution at beaches in Canada. METHODS: This study will use a mixed-methods approach, consisting of a prospective cohort study of beachgoers with embedded qualitative research. The cohort study involves recruiting and enrolling participants at public beaches across Canada, ascertaining their water and sand contact exposure status, then following-up after seven days to determine the incidence of acute RWI outcomes. We will test beach water samples each recruitment day for culture-based E. coli, enterococci using rapid molecular methods, and microbial source tracking biomarkers. The study started in 2023 and will continue to 2025 at beaches in British Columbia, Manitoba, Ontario, and Nova Scotia. The target enrollment is 5000 beachgoers. Multilevel logistic regression models will be fitted to examine the relationships between water and sand contact and RWI among beachgoers. We will also examine differences in risks by beachgoer age, gender, and beach location and the influence of fecal indicator bacteria and other water quality parameters on these relationships. Sensitivity analyses will be conducted to examine the impact of various alternative exposure and outcome definitions on these associations. The qualitative research phase will include focus groups with beachgoers and key informant interviews to provide additional contextual insights into the study findings. The study will use an integrated knowledge translation approach. DISCUSSION: Initial implementation of the study at two Toronto, Ontario, beaches in 2023 confirmed that recruitment is feasible and that a high completion rate (80%) can be achieved for the follow-up survey. While recall bias could be a concern for the self-reported RWI outcomes, we will examine the impact of this bias in a negative control analysis. Study findings will inform future recreational water quality guidelines, policies, and risk communication strategies in Canada.

Approximated gene expression trajectories for gene regulatory network inference on cell tracks.

The study of pattern formation has benefited from our ability to reverse-engineer gene regulatory network (GRN) structure from spatiotemporal quantitative gene expression data. Traditional approaches have focused on systems where the timescales of pattern formation and morphogenesis can be separated. Unfortunately, this is not the case in most animal patterning systems, where pattern formation and morphogenesis are co-occurring and tightly linked. To elucidate patterning mechanisms in such systems we need to adapt our GRN inference methodologies to include cell movements. In this work, we fill this gap by integrating quantitative data from live and fixed embryos to approximate gene expression trajectories (AGETs) in single cells and use these to reverse-engineer GRNs. This framework generates candidate GRNs that recapitulate pattern at the tissue level, gene expression dynamics at the single cell level, recover known genetic interactions and recapitulate experimental perturbations while incorporating cell movements explicitly for the first time.

Efficacy of arch contouring foot orthoses for midfoot osteoarthritis: Protocol for a randomised controlled trial.

INTRODUCTION: Midfoot osteoarthritis (OA) is a painful and disabling condition. Arch contouring foot orthoses have been recommended for midfoot OA, yet there is no high-quality evidence from randomised controlled trials to support their use. This clinical trial aims to evaluate the efficacy of arch contouring foot orthoses for midfoot OA. METHODS: This will be a parallel-group randomised controlled superiority trial. One-hundred and forty community-dwelling people with painful midfoot OA will be randomised to receive either arch contouring foot orthoses or flat sham inserts. Outcome measures will be obtained at baseline, 4, 8 and 12 weeks; the primary endpoint for assessing efficacy being 12 weeks. The primary outcome measure will be average midfoot pain whilst walking over the last 7 days on an 11-point numerical rating scale. Secondary outcome measures include function (walking/standing subscale of the Manchester-Oxford Foot Questionnaire), participants' perception of overall treatment effect (self-reported global rating of change on a 15-point Likert scale), physical activity (Incidental and Planned Exercise Questionnaire), general health-related quality of life (Short Form-12 Version® 2.0), use of co-interventions and adverse events. DISCUSSION: This trial will evaluate the efficacy of arch contouring foot orthoses for relieving pain and improving function, physical activity and health-related quality of life in people with midfoot OA. The findings will provide high-quality evidence as to whether arch contouring foot orthoses are efficacious and will help to inform clinical guidelines about the use of foot orthoses for midfoot OA. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ACTRN12623000953639).

TUBB4B is essential for the cytoskeletal architecture of cochlear supporting cells and motile cilia development.

Microtubules are essential for various cellular processes. The functional diversity of microtubules is attributed to the incorporation of various α- and ß-tubulin isotypes encoded by different genes. In this work, we investigated the functional role of ß4B-tubulin isotype (TUBB4B) in hearing and vision as mutations in TUBB4B are associated with sensorineural disease. Using a Tubb4b knockout mouse model, our findings demonstrate that TUBB4B is essential for hearing. Mice lacking TUBB4B are profoundly deaf due to defects in the inner and middle ear. Specifically, in the inner ear, the absence of TUBB4B lead to disorganized and reduced densities of microtubules in pillar cells, suggesting a critical role for TUBB4B in providing mechanical support for auditory transmission. In the middle ear, Tubb4b-/- mice exhibit motile cilia defects in epithelial cells, leading to the development of otitis media. However, Tubb4b deletion does not affect photoreceptor function or cause retinal degeneration. Intriguingly, ß6-tubulin levels increase in retinas lacking ß4B-tubulin isotype, suggesting a functional compensation mechanism. Our findings illustrate the essential roles of TUBB4B in hearing but not in vision in mice, highlighting the distinct functions of tubulin isotypes in different sensory systems.

Promotion of endoplasmic reticulum retrotranslocation by overexpression of E3 ubiquitin-protein ligase synoviolin 1 reduces endoplasmic reticulum stress and preserves cone photoreceptors in cyclic nucleotide-gated channel deficiency.

Cone photoreceptor cyclic nucleotide-gated (CNG) channels play an essential role in phototransduction and cellular Ca2+ homeostasis. Mutations in genes encoding the channel subunits CNGA3 and CNGB3 are associated with achromatopsia, progressive cone dystrophy, and early-onset macular degeneration. Cone loss in patients with achromatopsia and cone dystrophy associated with CNG channel mutations has been documented by optical coherence tomography and in mouse models of CNG channel deficiency. Cone death in CNG channel-deficient retinas involves endoplasmic reticulum (ER) stress-associated apoptosis, dysregulation of cellular/ER Ca2+ homeostasis, impaired protein folding/processing, and impaired ER-associated degradation (ERAD). The E3 ubiquitin-protein ligase synoviolin 1 (SYVN1) is the primary component of the SYVN1/SEL1L ER retrotranslocon responsible for ERAD. Previous studies have shown that manipulations that protect cones and reduce ER stress/cone death in CNG channel deficiency, such as increasing ER Ca2+ preservation or treatment with an ER chaperone, increase the expression of SYVN1 and other components of the ER retrotranslocon. The present work investigated the effects of SYVN1 overexpression. Intraocular injection of AAV5-IRBP/GNAT2-Syvn1 resulted in overexpression of SYVN1 in cones of CNG channel-deficient mice. Following treatment, cone density in Cnga3-/- mice was significantly increased, compared with untreated controls, outer segment localization of cone opsin was improved, and ER stress/apoptotic cell death was reduced. Overexpression of SYVN1 also led to increased expression levels of the retrotranslocon components, degradation in ER protein 1 (DERL1), ERAD E3 ligase adaptor subunit (SEL1L), and homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1). Moreover, overexpression of SYVN1 likely enhanced protein ubiquitination/proteasome degradation in CNG channel-deficient retinas. This study demonstrates the role of SYVN1/ERAD in cone preservation in CNG channel deficiency and supports the strategy of promoting ERAD for cone protection.

Qualitative evaluation of a package of implementation strategies codesigned to support the introduction of multiple micronutrient supplementation (MMS) for pregnant women in Bamako, Mali.

Mali national policy recommends that women take iron and folic acid supplements (IFA) from the time of the first antenatal care (ANC) visit, throughout pregnancy and during the first 3 months after delivery. In 2020, the World Health Organization (WHO) updated their ANC guidelines to recommend the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formulation of multiple micronutrient supplements (MMS) in the context of rigorous research, including implementation research. In Bamako, Mali, a codesign process was used to tailor antenatal care MMS packaging and counselling materials aimed at optimizing delivery and uptake of and adherence to MMS. This paper presents the codesign process along with the results of a post-intervention qualitative assessment to evaluate the behaviour change intervention. At the conclusion of the intervention, we conducted semistructured qualitative interviews with 24 women who had received the intervention and six pharmacy managers from the six health centres participating in the study. We conducted two focus groups with midwives who had delivered the intervention and two group discussions with family members of women who had received the intervention. Respondent perspectives reveal an easy experience transitioning from previously used IFA. Women and providers concur that the intervention counselling materials and visual aids were instrumental in influencing the perceived benefit and uptake of MMS. Family members play an influential role in pregnant women's decision-making regarding MMS uptake. MMS and the associated implementation strategies developed through the codesign process were found to be a highly acceptable intervention.

PET imaging of [52 Mn]Mn-DOTATATE and [52 Mn]Mn-DOTA-JR11.

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [68Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [68Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake. The goal of this study was to label both DOTATATE and DOTA-JR11 peptides with 52Mn in high radiochemical yields (RCY) and sufficient specific activity. A comparison of these two compounds was performed in in vitro and in vivo studies in animals with somatostatin receptor-positive xenografts to characterize differences in cell, tumor, and tissue uptake. Radiolabeling of DOTATATE and DOTA-JR11 was carried out by combining varying concentrations of the peptides with [52Mn]MnCl2. In vitro stability of the radiotracers was determined in mouse serum. In vitro cell uptake and internalization assays were performed in SSTR2 + AR42J cells and negative controls. In vivo biodistribution and longitudinal PET imaging was evaluated in mice bearing AR42J tumors. Both [52Mn]Mn-DOTATATE and [52Mn]Mn-DOTA-JR11showed affinity for SSTR2 in AR42J cells. However, the uptake of [52Mn]Mn-DOTATATE was higher (11.95 ± 0.71%/ mg) compared to [52Mn]Mn-DOTA-JR11 (7.31 ± 0.38%/ mg) after 2 h incubation. After 4 h incubation, 53.13 ± 1.83% of the total activity of [52Mn]Mn-DOTATATE was internalized, whereas only 20.85 ± 0.59% of the total activity of [52Mn]Mn-DOTA-JR11 was internalized. The PET images revealed similar biodistribution results, with [52Mn]Mn-DOTATATE showing a significant tumor uptake of 11.16 ± 2.97% ID/g, while [52Mn]Mn-DOTA-JR11 exhibited a lower tumor uptake of 2.11 ± 0.30% ID/g 4 h post-injection. The synthesis of both radiotracers was accomplished with high RCY and purity. The cell uptake and internalization of [52Mn]Mn-DOTATATE showed higher levels compared to [52Mn]Mn-DOTA-JR11. PET images of the radiotracers in AR42J tumor bearing mice demonstrated similar biodistribution in all organs except the tumor, with [52Mn]Mn-DOTATATE showing higher tumor uptake compared to [52Mn]Mn-DOTA-JR11. The variations in properties of these tracers could be used to guide further imaging and treatment studies.

Randomized Clinical Trial of ICECaP (Individualized Coordination and Empowerment for Care Partners of Persons with Dementia): Primary Mental Health and Burden Outcomes.

Efficacy of the Individualized Coordination and Empowerment for Care Partners of Persons with Dementia (ICECaP), an intervention that involves one-on-one individualized support from a dementia care coordinator for a dementia care partner, compared to an active control group. At least once monthly contact is made from a dementia care coordinator to the dementia care partner by telephone, video conferencing, email, or in-person support at clinical visits for the person with dementia. In this pilot randomized unblinded control trial of ICECaP, n=61 (n=90 randomized) care partners completed 12-months of the ICECaP intervention and n=69 (n=92 randomized) care partners received routine clinical support (controls) in an outpatient memory care clinic at an academic medical center, from which the participants were recruited (ClinicalTrials.gov: NCT04495686, funded by Department of Defense and Virginia Department for Aging and Rehabilitative Services). Early termination endpoints (death and higher level of care) and trial drop out were comparable across groups. Primary efficacy outcomes were evaluated by comparing changes in care partner mental health, burden, and quality of life from baseline to 12-months between ICECaP and controls. Linear-mixed ANCOVA revealed no significant group differences in longitudinal changes on measures of caregiving burden, care partner depression, anxiety, quality of life, or reactions to the behavioral symptoms of the person with dementia. Hypothesized reasons for lack of initial efficacy on primary 12-month outcomes are discussed.

Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females.

Obesity has been implicated in the rise of autoimmunity in women. We report that obesity induces a serum protein signature that is associated with T helper 1 (Th1), interleukin (IL)-17, and multiple sclerosis (MS) signaling pathways selectively in human females. Females, but not male mice, subjected to diet-induced overweightness/obesity (DIO) exhibited upregulated Th1/IL-17 inflammation in the central nervous system during experimental autoimmune encephalomyelitis, a model of MS. This was associated with worsened disability and a heightened expansion of myelin-specific Th1 cells in the peripheral lymphoid organs. Moreover, at steady state, DIO increased serum levels of interferon (IFN)-α and potentiated STAT1 expression and IFN-γ production by naive CD4+ T cells uniquely in female mice. This T cell phenotype was driven by increased adiposity and was prevented by the removal of ovaries or knockdown of the type I IFN receptor in T cells. Our findings offer a mechanistic explanation of how obesity enhances autoimmunity.

Evaluating iSibWorks: A virtual cognitive-behavioural intervention for siblings of children with disabilities.

Objectives: 1) Examine if participation in iSibWorks, a group-based virtual intervention for siblings of children with disabilities, impacted siblings' perception of quality of life (QoL) and social support; and 2) Explore siblings' feedback on iSibWorks. Methods: Thirty-eight children participated in iSibWorks and completed questionnaires (Pediatric Quality of Life [PedsQL™], Social Support Scale for Children [SSSC]) one week pre- and post-intervention. Conventional content analysis was used to explore siblings' open-ended responses on a post-participation feedback form. Results: No significant differences in PedsQL™ and SSSC scores were observed after participating in iSibWorks. Despite this, siblings had positive feedback about iSibWorks and discussed: 1) Engaging in group learning and activities, 2) Meeting other siblings, and 3) Applying iSibWorks content to their daily life. Conclusion: Factors related to the COVID-19 pandemic such as family stress, school closures, virtual learning, and social distancing likely impacted study results. Although there were no significant changes in QoL and social support, siblings found iSibWorks to be fun, meaningful, and engaging. Innovation: Siblings of children with disabilities can experience psychosocial challenges and there are few virtual interventions designed for this population. iSibWorks was adapted to address this gap and increase access and support for siblings of children with disabilities.

Non-Ergot Dopamine Agonists and the Risk of Heart Failure and Other Adverse Cardiovascular Reactions in Parkinson's Disease.

Reports suggest possible risks of adverse cardiovascular reactions, including heart failure, associated with non-ergot dopamine agonist (DA) use in Parkinson's disease (PD). The objectives of our review were to evaluate the risk of heart failure and other adverse cardiovascular reactions in PD patients who received a non-ergot DA compared with other anti-PD pharmacological interventions, placebo, or no intervention. Studies were identified via searches of six bibliographic databases. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were eligible for study inclusion. Random-effect meta-analyses were performed to estimate adverse cardiovascular reaction risks. Quality of evidence was assessed using GRADE. In total, forty-four studies (thirty-six RCTs and eight NRS) satisfied our inclusion criteria. A single RCT found no significant difference in the risk of heart failure with ropinirole compared with bromocriptine (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.07 to 2.04; low certainty). Conversely, three case-control studies reported a risk of heart failure with non-ergot DA treatment. The quality of evidence for the risk of heart failure was judged as low or very low. Findings suggest that non-ergot DA use may be associated with adverse cardiovascular outcomes, including heart failure. Studies are needed to better understand cardiovascular risks associated with PD treatment.

A Missed Opportunity: Evaluating Immunization Status and Barriers in Hospitalized Children.

OBJECTIVE: Hospitalized children are a potentially underimmunized population. We sought to determine the proportion of patients admitted to our pediatric medicine inpatient units who are underimmunized or unimmunized and to identify barriers to immunization faced by families of children admitted to hospital. METHODS: We conducted a prospective study of children aged 2 months to 18 years admitted to our pediatric medicine inpatient units between July 2021 and October 2022. Immunization and demographic data were collected from electronic medical charts. Immunization status of each child was categorized as up-to-date if they had received all eligible vaccine doses in accordance with the provincial immunization schedule. Caregivers completed a survey on barriers to immunizations; results were compared between caregivers of children whose vaccines were up-to-date and those who were not. RESULTS: Hospitalized children were missing more doses of the preschool vaccines than the general population based on published provincial data. Only 142 of 244 (58.2%) of study patients were up-to-date on all their immunizations. Caregivers of children whose immunizations were not up-to-date reported significantly more barriers to vaccination in all survey categories: access to shots, concerns about shots, and importance of shots. CONCLUSIONS: There is a disparity in immunization status between children admitted to hospital in a Canadian setting compared with national targets and community immunization rates. Caregivers of underimmunized hospitalized children cited significantly more barriers to immunization when compared with hospitalized children who are up-to-date. Pursuing a hospital-based immunization strategy could lead to improved immunization status for hospitalized children.

Impact of a Multidisciplinary Service Line and Program for Transcatheter Device Closure of the Neonatal Ductus Arteriosus.

Outline a quality initiative establishing an institutional service line for neonatal transcatheter device closure of the patent ductus arteriosus (TDC-PDA). A retrospective descriptive observational study surrounds programmatic approach to TDC-PDA in premature neonates with process measure spanning education, implementation, referral, and post-procedural care. Metrics tracked pre- and post-program creation with statistical analyses performed. Neonatal TDC-PDA referrals increased exponentially since program inception (n = 13 in year prior; n = 42 year 1; n = 74 year 2), especially in patients weighing less than 1.3 kg (12.5%; 55%; 50%), and were associated with an increased procedural success rate (81%; 95%; 99%). Procedural checklist creation decreased procedural "out of isolette" time (median 93 min; 59; 52), and procedural-related complication or clinical sequelae (19%; 12%; 4%). A multidisciplinary service line and program dedicated to neonatal TDC-PDA can result in a significant increase in referrals as well as procedural efficacy and safety for this medically fragile population.

Regional differences in pediatric pneumococcal vaccine schedules for Indigenous children in Canada: an environmental scan.

BACKGROUND: Streptococcus pneumoniae bacteria causes substantial morbidity and mortality worldwide, especially in children under 5 years of age. Prevention of these outcomes by pneumococcal conjugate vaccines (PCV) is an important public health initiative, supported by publicly funded vaccination programs in Canada. While the National Advisory Committee on Immunization (NACI) provides national recommendations for vaccination schedules, decisions on vaccination program delivery are made regionally, creating potential for variability across the country. In addition, defining the groups that are most at risk has become a complex endeavor for provinces and territories in Canada, specifically considering Indigenous children. METHODS: In this environmental scan, we reviewed policy documents, provincial/territorial and international PCV schedules, and scientific literature, and consulted with vaccination program stakeholders and experts from across the country, in order to understand the evolution of PCV vaccination guidelines and policies in Canada and identify whether and how the needs of Indigenous children are addressed. RESULTS: As of March 2023, most regions do not specify particular vaccination requirements for Indigenous children; however, three provinces identify Indigenous children as "high risk" and use varying language to recommend a four dose, rather than the routine three dose, schedule. Our results also draw attention to evidence gaps supporting a differing practice for Indigenous populations. CONCLUSIONS: Future PCV program innovation requires inclusive and clear policies as well as definitive evidence-based policies and practices in order to improve equitable population health.

In vivo examination of pathogenicity and virulence in environmentally isolated Vibrio vulnificus.

Human exposure to Vibrio vulnificus, a gram-negative, halophilic environmental pathogen, is increasing. Despite this, the mechanisms of its pathogenicity and virulence remain largely unknown. Each year, hundreds of infections related to V. vulnificus occur, leading to hospitalization in 92% of cases and a mortality rate of 35%. The infection is severe, typically contracted through the consumption of contaminated food or exposure of an open wound to contaminated water. This can result in necrotizing fasciitis and the need for amputation of the infected tissue. Although several genes (rtxA1, vvpE, and vvhA) have been implicated in the pathogenicity of this organism, a defined mechanism has not been discovered. In this study, we examine environmentally isolated V. vulnificus strains using a zebrafish model (Danio rerio) to investigate their virulence capabilities. We found significant variation in virulence between individual strains. The commonly used marker gene of disease-causing strains, vcgC, did not accurately predict the more virulent strains. Notably, the least virulent strain in the study, V. vulnificus Sept WR1-BW6, which tested positive for vcgC, vvhA, and rtxA1, did not cause severe disease in the fish and was the only strain that did not result in any mortality. Our study demonstrates that virulence varies greatly among different environmental strains and cannot be accurately predicted based solely on genotype.