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Background: Given the significance of motor competence (MC) for healthy development and as a cornerstone for lifelong physical activity (PA), it is crucial to understand the manifold factors that are associated with MC. Thus, the aim of the present study was to investigate correlates of children's MC and their fundamental movement skills (FMS) within their daily life from a comprehensive biopsychosocial-ecological perspective., Methods: This is a cross-sectional sub-study of the 'Physical Literacy for Communities (PL4C)' WAVES cohort study conducted in the West Vancouver School District, Canada. Motor competence was assessed using the PLAYfun tool including overall MC score and five FMS category scores, namely, running, locomotor skills, upper and lower body control and balance skills. By means of structural equation modeling (SEM), direct associationswith MC and with the specific FMS categories addressing physical activity behavior, self-perceived physical literacy, parenting, and school ground design were investigated., Results: A total of 355 children with a mean age of 7.5 years and 111.1 min of MVPA per day participated. The group comprised 51% boys and 47% girls from 14 elementary schools. Most children were at an emerging MC-level (71%), while those at a competent MC-level exhibited significantly more daily minutes of MVPA (123 versus 109, p = 0.001). Additionally, they played outdoors more frequently and engaged in more instructor-led PA. The results revealed that logistical support from parents had not only a direct positive association with overall MC, both for girls and boys, but also with most of the FMS categories. However, the correlates of MC varied between genders and showed different patterns across the five FMS categories. While time spent in sports or coach-/instructor-led physical activities had a significant SEM generated direct effect only for boys' MC and for locomotor, upper body object control and balance, the aesthetic design of the school grounds was only associated with girls' MC and those same three FMS categories. Multivariate SEM could explain 26% of variance for girls' MC and 30% for boys'., Conclusions: This exploratory baseline assessment revealed parental logistical support as an important correlate of MC, irrespective of gender. There were distinct gender patterns across biopsychosocial-ecological correlates influencing MC and FMS. Despite the heterogeneity of the results, our findings indicate a potential role of school ground design in supporting the development of children's MC, especially for girls., (© 2024. The Author(s).)

Background: A better understanding of the neural mechanisms regulating impaired satiety to palatable foods is essential to treat hyperphagia linked with obesity. The satiation hormone amylin signals centrally at multiple nuclei including the ventral tegmental area (VTA). VTA-to-medial prefrontal cortex (mPFC) projections encode food reward information to influence behaviors including impulsivity. We hypothesized that modulation of VTA-to-mPFC neurons underlies amylin-mediated decreases in palatable food-motivated behaviors., Methods: We used a variety of pharmacological, behavioral, genetic, and viral approaches (n = 4-16/experiment) to investigate the anatomical and functional circuitry of amylin-controlled VTA-to-mPFC signaling in rats., Results: To first establish that VTA amylin receptor (calcitonin receptor) activation can modulate mPFC activity, we showed that intra-VTA amylin decreased food-evoked mPFC cFos. VTA amylin delivery also attenuated food-directed impulsive behavior, implicating VTA amylin signaling as a regulator of mPFC functions. Palatable food activates VTA dopamine and mPFC neurons. Accordingly, dopamine receptor agonism in the mPFC blocked the hypophagic effect of intra-VTA amylin, and VTA amylin injection reduced food-evoked phasic dopamine levels in the mPFC, supporting the idea that VTA calcitonin receptor activation decreases dopamine release in the mPFC. Surprisingly, calcitonin receptor expression was not found on VTA-to-mPFC projecting neurons but was instead found on GABAergic (gamma-aminobutyric acidergic) interneurons in the VTA that provide monosynaptic inputs to this pathway. Blocking intra-VTA GABA signaling, through GABA receptor antagonists and DREADD (designer receptor exclusively activated by designer drugs)-mediated GABAergic neuronal silencing, attenuated intra-VTA amylin-induced hypophagia., Conclusions: These results indicate that VTA amylin signaling stimulates GABA-mediated inhibition of dopaminergic projections to the mPFC to mitigate impulsive consumption of palatable foods., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Fibromuscular dysplasia (FMD) is a rare nonatherosclerotic, noninflammatory vascular disease affecting mostly renal and carotid arteries and is the second most frequent cause of renal artery stenosis. The symptomatology is dominated by arterial hypertension due to the frequent involvement of the renal arteries and depends on the location of the lesions. Most of the cases are middle-aged women of Caucasian origin. There are two subtypes based on angiographic aspect: multifocal FMD (80% of the cases) and focal FMD (rarer with a more balanced sex ratio). Angioplasty of the renal arteries is generally disappointing with less than 50% cure of hypertension. It appears necessary to improve our knowledge of the FMD and to optimize the selection of eligible patients for revascularization with transdisciplinary collegial therapeutic decision.

Background: We used nationally representative data to explore associations among location of residence (rural/urban) and perceived barriers to physical activity (PA) in Canadian youth., Methods: We analyzed the 2017 Canadian Community Health Survey, Barriers to Physical Activity Rapid Response data for 12- to 17-year-old youth. Nine items from the survey assessing perceived barriers to PA were combined into 3 barrier domains: resources, motivational, and socioenvironmental. The likelihood of reporting barriers to PA based on rural-urban location was examined using survey-weighted binary logistic regression following a model fitting approach. Sociodemographic factors were modeled as covariates and tested in interaction with location. For each barrier domain, we derived the best-fitting model with fewest terms., Results: There were no location-specific effects related to reporting any barrier or motivation-related PA barriers. We found a sex by location interaction predicting the likelihood of reporting resource-related barriers. Rural boys were less likely to report resource-related barriers compared with urban boys (odds ratio [OR] = 0.42 [0.20, 0.88]). Rural girls were more likely to report resource-related barriers compared with boys (OR = 3.72 [1.66, 8.30]). Regarding socioenvironmental barriers, we observed a significant body mass index by location interaction demonstrating that rural youth with body mass index outside the "normal range" showed a higher likelihood of reporting socioenvironmental barriers compared with urban youth (OR = 2.38 [1.32, 4.30]). For urban youth, body mass index was unrelated to reporting socioenvironmental barriers (OR = 1.07 [0.67, 1.71])., Conclusion: PA barriers are not universal among Canadian youth. Our analyses highlight the importance of testing interactions in similar studies as well as considering key sociodemographic characteristics when designing interventions.

Free polymannose-type oligosaccharides (fOS) are processed by cytosolic enzymes to generate Man5GlcNAc which is transferred to lysosomes and degraded. Lysosomal fOS import was demonstrated in vitro but is poorly characterized in part due to lack of convenient substrates. As chitooligosaccharides (COS, oligomers β1,4-linked GlcNAc) block [3H]Man5GlcNAc transport into lysosomes, we asked if COS are themselves transported and if so, can they be chemically modified to generate fluorescent substrates. We show that COS are degraded by lysosomal hydrolases to generate GlcNAc, and robust ATP-dependent transport of [3H]COS2/4 di and tetrasaccharides into intact rat liver lysosomes was observed only after blocking lysosomal [3H]GlcNAc efflux with cytochalasin B. As oligosaccharides with unmodified reducing termini are the most efficient inhibitors of [3H]COS2/4 and [3H]Man5GlcNAc transport, the non-reducing GlcNAc residue of COS2-4 was de-N-acetylated using Sinorhizobium meliloti NodB, and the resulting amine substituted with rhodamine B (RB) to yield RB-COS2-4. The fluorescent compounds inhibit [3H]Man5GlcNAc transport and display temperature-sensitive, ATP-dependent transport into a sedimentable compartment that is ruptured with the lysosomotropic agent L-methyl methionine ester. Once in this compartment, RB-COS3 is converted to RB-COS2 further identifying it as the lysosomal compartment. RB-COS2/3 and [3H]Man5GlcNAc transports are blocked similarly by competing sugars, and are partially inhibited by the vacuolar ATPase inhibitor bafilomycin and high concentrations of the P-type ATPase inhibitor orthovanadate. These data show that Man5GlcNAc, COS2/4 and RB-COS2/3 are transported into lysosomes by the same or closely related mechanism and demonstrate the utility of COS modified at their non-reducing terminus to study lysosomal oligosaccharide transport., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in some infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C. auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pelletier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To qualitatively describe experiences of chronic disease management and prevention in older adults (age ≥65 years) during COVID-19., Approach: Qualitative descriptive approach., Setting: Data collected online via telephone and video-conferencing technologies to participants located in various cities in British Columbia, Canada. Data analyzed by researchers in the cities of Vancouver and Kelowna in British Columbia., Participants: Twenty-four community-living older adults (n = 24) age ≥65 years., Methods: Each participant was invited to complete a 30-to-45-minute virtual, semi-structured, one-on-one interview with a trained interviewer. Interview questions focused on experiences managing health prior to COVID-19 and transitioning experiences of practicing health management and prevention strategies during COVID-19. Audio recordings of interviews were transcribed verbatim and analyzed thematically., Results: The sample's mean age was 73.4 years (58% female) with 75% reporting two or more chronic conditions (12.5% none, 12.5% one). Three themes described participants' strategies for chronic disease management and prevention: (1) having a purpose to optimize health (i.e., managing health challenges and maintaining independence); (2) internal self-control strategies (i.e., self-accountability and adaptability); and (3) external support strategies (i.e., informational support, motivational support, and emotional support)., Conclusion: Helping older adults identify purposes for their own health management, developing internal control strategies, and optimizing social support opportunities may be important person-centred strategies for chronic disease management and prevention during unprecedented times like COVID-19., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Little is known about how intersecting social privilege and disadvantage contribute to inequities in COVID-19 information use and vaccine access. This study explored how social inequities intersect to shape access to and use of COVID-19 information and vaccines among parents in Canada., Methods: We conducted semi-structured interviews on COVID-19 vaccination information use with ethnically diverse parents of children ages 11 to 18 years from April to August 2022. We purposefully invited parents from respondents to a national online survey to ensure representation across diverse intersecting social identities. Five researchers coded transcripts in NVivo using a discourse analysis approach informed by intersectionality. Our analysis focused on use of vaccine information and intersecting privileges and oppressions, including identifying with equity-denied group(s)., Results: Interview participants (N = 48) identified as ethnically diverse non-Indigenous (n = 40) and Indigenous (n = 8) Peoples from seven Canadian provinces. Racialized minority or Indigenous participants reflected on historical and contemporary events of racism from government and medical institutions as barriers to trust and access to COVID-19 information, vaccines, and the Canadian healthcare system. Participants with privileged social locations showed greater comfort in resisting public health measures. Despite the urgency to receive COVID-19 vaccines, information gaps and transportation barriers delayed vaccination among some participants living with chronic medical conditions., Conclusion: Historicization of colonialism and ongoing events of racism are a major barrier to trusting public health information. Fostering partnerships with trusted leaders and/or healthcare workers from racialized communities may help rebuild trust. Healthcare systems need to continuously implement strategies to restore trust with Indigenous and racialized populations., (© 2024. The Author(s).)

In Quebec (Canada), the roll-out of the vaccination started slowly in December 2020 due to limited vaccine supply. While the first and second doses were well-accepted among adults and vaccine uptake was above 90%, in late 2021 and 2022, vaccine acceptance decreased for children vaccination and receipt of a 3rd or a 4th dose. In the autumn of 2022, four focus groups were conducted with vaccine-hesitant parents of children aged 0-4 and adults who expressed little intention to receive a booster dose. The objective of this study was to gather participants' perspectives on vaccination in general, on the COVID-19 vaccination campaign and the information available, and to gain insights into the underlying reasons for their low intention of either having their child(ren) vaccinated, or receiving an additional dose of vaccine. A total of 35 participants took part in the focus groups. While participants expressed a certain level of trust and confidence in public health and government authorities regarding pandemic management and the vaccination campaign, they were also concerned that transparent information was lacking to support an informed decision on booster doses and children's vaccination. Many participants felt adequately protected against the infection during the focus groups, citing a lack of perceived benefits as the primary reason for refusing a booster dose. Parents who refused to administer the COVID-19 vaccine to their young children felt that the vaccine was not useful for children and were concerned about potential side effects. The majority reported that their opinions regarding other recommended vaccines had not changed since the beginning of the pandemic. While these results are reassuring, our findings highlight the importance of transparency in public health communications about vaccines to increase confidence and to develop strategies to address vaccine fatigue and complacency toward COVID-19 vaccines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pelletier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Physical activity improves the well-being of persons living with dementia but few exercise programs include them. The Dementia-Inclusive Choices for Exercise (DICE) toolkit aims to improve exercise providers' understanding of dementia and ability to support persons living with dementia in physical activity. We evaluated the co-designed DICE toolkit with exercise providers using a mixed-methods approach comprising pre/post questionnaires and interviews and reflection diaries. Among 16 participants, self-efficacy for exercise delivery to persons living with dementia and both knowledge and attitudes toward dementia significantly improved. Thematic analysis suggested participants (a) had a deeper understanding of the variability of dementia, (b) were planning for equitable access for persons living with dementia, (c) planned to promote social connection through exercise, and (d) were optimistic for future engagement with persons living with dementia. The DICE toolkit may improve exercise providers' knowledge and confidence to plan proactively to support persons living with dementia in programs and services.

Persons with spinal cord injury (SCI) experience gains in fitness, physical and mental health from regular participation in exercise and physical activity. Due to changes in physiological function of the cardiovascular, nervous, and muscular systems, general population physical activity guidelines and traditional exercise prescription methods are not appropriate for the SCI population. Exercise guidelines specific to persons with SCI recommend progressive training beginning at 20 min of moderate to vigorous intensity aerobic exercise twice per week transitioning to 30 min three times per week, with strength training of the major muscle groups two times per week. These population-specific guidelines were designed considering the substantial barriers to physical activity for persons with SCI and can be used to frame an individual exercise prescription. Rating of perceived exertion (i.e., perceptually regulated exercise) is a practical way to indicate moderate to vigorous intensity exercise in community settings. Adapted exercise modes include arm cycle ergometry, hybrid arm-leg cycling, and recumbent elliptical equipment. Body weight-supported treadmill training and other rehabilitation modalities may improve some aspects of health and fitness for people with SCI if completed at sufficient intensity. Disability-specific community programs offer beneficial opportunities for persons with SCI to experience quality exercise opportunities but are not universally available., Competing Interests: The author declares there are no competing interests.

Introduction: Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE., Methods: We identified adults in the USA with an EE diagnosis between January  1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs., Results: Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs., Conclusions: Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use., (© 2023. The Author(s).)

Background: Physical activity occurs across various domains including leisure/recreation, for transportation, or for work or household reasons. Rural and urban active living environments are characterized by different opportunities for physical activity within each domain which may translate into different patterns of behavior. The aim of this study was to compare rural-urban differences in physical activity across different domains, and explore interactions between sociodemographic factors, physical activity domains, and rurality., Methods: We used self-reported data collected across three physical activity domains (active transportation, recreation, occupational/household) and relevant sociodemographic variables from the Canadian Community Health Survey. Adjusting for sociodemographic factors, we did two separate cross-sectional analyses: 1) binary logistic regression to determine the odds of reporting any activity in each domain, and 2) ordinary least squares regression using the sub-samples reporting > 0 min per week of activity to compare how much activity was reported in each domain., Results: Our final survey weighted sample of Canadian adults (mean age 47.4 years) was n = 25,669,018 (unweighted n = 47,266). Rural residents were less likely to report any active transportation (OR = 0.59, 95% CI [0.51, 0.67], p < .0001). For recreational physical activity, rural males had lower odds (OR = 0.75, 95% CI [0.67, 0.83], p < .0001) and rural females had higher odds (OR = 1.19, 95% CI [1.08, 1.30], p = .0002) of reporting any participation compared to urban residents. Rural males (OR = 1.90, 95% CI [1.74, 2.07], p < .0001) and females (OR = 1.33, 95% CI [1.21, 1.46], p < .0001) had higher odds of reporting any occupational or household physical activity., Conclusions: Urban residents tend to participate in more active transportation, while rural residents participate in more occupational or household physical activity. Location-based differences in physical activity are best understood by examining multiple domains and must include appropriate sociodemographic interactions, such as income and sex/gender., (© 2023. The Author(s).)

Objective: To evaluate access to prenatal care for pregnant patients receiving medication for opioid use disorder (MOUD) under Medicaid coverage in Florida., Methods: A cross-sectional, secret shopper study was conducted in which calls were made to randomly selected obstetric clinicians' offices in Florida. Callers posed as a 14-week-pregnant patient with Medicaid insurance who was receiving MOUD from another physician and requested to schedule a first-time prenatal care appointment. Descriptive statistics were used to report our primary outcome, the callers' success in obtaining appointments from Medicaid-enrolled physicians' offices. Wait time for appointments and reasons the physician offices refused appointments to callers were collected., Results: Overall, 2,816 obstetric clinicians are enrolled in Florida Medicaid. Callers made 1,747 attempts to contact 1,023 randomly selected physicians' offices from June to September 2021. Only 48.9% of medical offices (n=500) were successfully reached by phone, of which 39.4% (n=197) offered a prenatal care appointment to the caller. The median wait time until the first appointment was 15 days (quartile 1: 7; quartile 3: 26), with a range of 0-55 days. However, despite offering an appointment, 8.6% of the medical offices stated that they do not accept Medicaid insurance payment or would accept only self-pay. Among the 60.6% of callers unable to secure an appointment, the most common reasons were that the clinician was not accepting patients taking methadone (34.7%) or was not accepting any new patients with Medicaid insurance (23.8%) and that the pregnancy would be too advanced by the time of the first available appointment (7.3%)., Conclusion: This secret shopper study found that the majority of obstetric clinicians' offices enrolled in Florida Medicaid do not accept pregnant patients with Medicaid insurance who are taking MOUD. Policy changes are needed to ensure access to adequate prenatal care for patients with opioid use disorder., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Autosomal dominant Alzheimer's disease (ADAD) is a rare early-onset form of Alzheimer's disease, caused by dominant mutations in one of three genes: presenilin 1, presenilin 2, and amyloid β precursor protein (APP). Mutations in the presenilin 1 gene ( PSEN1 ) account for the majority of cases, and individuals who inherit a single-mutant PSEN1 allele go on to develop early-onset dementia, ultimately leading to death. The presenilin 1 protein (PS1) is the catalytic subunit of the γ-secretase protease, a tetrameric protease responsible for cleavage of numerous transmembrane proteins, including Notch and the APP. Inclusion of a mutant PS1 subunit in the γ-secretase complex leads to a loss of enzyme function and a preferential reduction of shorter forms of Aβ peptides over longer forms, an established biomarker of ADAD progression in human patients. In this study, we describe the development of a gene therapy vector expressing a wild-type (WT) copy of human PSEN1 to ameliorate the loss of function associated with PSEN1 mutations. We have carried out studies in mouse models using a recombinant AAV9 vector to deliver the PSEN1 gene directly into the central nervous system (CNS) and shown that we can normalize γ-secretase function and slow neurodegeneration in both PSEN1 conditional knockout and PSEN1 mutant knockin models. We have also carried out biodistribution studies in nonhuman primates (NHPs) and demonstrated the ability to achieve broad PS1 protein expression throughout the cortex and the hippocampus, two regions known to be critically involved in ADAD progression. These studies demonstrate preclinical proof of concept that expression of a WT human PSEN1 gene in cells harboring a dominant PSEN1 mutation can correct the γ-secretase dysfunction. In addition, direct administration of the recombinant AAV9 into the NHP brain can achieve broad expression at levels predicted to provide efficacy in the clinic.

Background: Psoriasis is a common autoimmune dermatologic condition which has a pronounced negative impact on patient quality of life and disease burden. Currently, there are a number of treatments available for psoriasis, with differences in efficacy, mechanism of action, mode of administration, adverse effects, and tolerability. However, a reliable, validated patient-reported instrument to address patient expectations and of psoriasis treatment has not been developed. This project was undertaken with the aim of developing a fit-for-purpose self-reported instrument to inform patient expectations and preferences of psoriasis treatments., Methods: Two studies, both utilizing qualitative and quantitative methods, were conducted in patients within the entire spectrum of psoriasis severity. In Study 1, a group concept mapping (GCM) exercise was conducted with dermatologists and moderate-to-severe psoriasis patients to identify concepts important in the treatment of psoriasis. In Study 2, a preliminary Treatment Acceptability Questionnaire (TAQ) was developed using GCM-derived concepts from Studies 1 and 2, followed by cognitive debriefing (CD) telephone interviews of the preliminary TAQ. In Study 2, another GCM exercise was conducted with mild and newly diagnosed psoriasis patients. Psychometric analyses were performed on the TAQ to evaluate validity and reliability., Results: The Study 1 GCM exercise generated 43 concepts from moderate-to-severe psoriasis patients (n = 20) and dermatologists (n = 10). In Study 2, 37 GCM concepts were generated from mild and newly diagnosed psoriasis patients (n = 20). From the 2 GCM exercises, 28 concepts were selected to form the preliminary TAQ; CD interviews indicated strong understanding and relevance of TAQ items among patients with disease ranging from mild to severe. The final TAQ consisted of 20 items; psychometric analysis demonstrated strong validity and reliability of the TAQ., Conclusions: The TAQ is a novel psychometrically validated patient-reported instrument to inform healthcare providers of patients' expectations of and preferences for treatment of their psoriasis and can help in shared decision making between patients and physicians., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In Canada, the first COVID-19 vaccine was approved for use in December 2020, marking the beginning of a large vaccination campaign. The campaign was not only unprecedented in terms of reach, but also with regards to the amount of information about vaccines that circulated in traditional and social media. This study's aim was to describe COVID-19 vaccine related discourses in Canada through an analysis of editorial cartoons. We collected 2172 cartoons about COVID-19 published between January 2020 and August 2022 in Canadian newspapers. These cartoons were downloaded and a first thematic analysis was conducted using the WHO-EPIWIN taxonomy (cause, illness, treatment, interventions, and information). From this, 389 cartoons related to COVID-19 vaccines were identified under the treatment category. These were subjected to a second thematic analysis to assess main themes (e.g., vaccine development, campaign progress, etc.), characters featured (e.g., politicians, public figures, public) and position with respect to vaccine (favorable, unfavorable, neutral). Six main themes emerged: Research and development of vaccines; Management of the vaccination campaign; Perceptions of and experiences with vaccination services; Measures and incentives to increase COVID-19 vaccine uptake; Criticism of the unvaccinated; and Effectiveness of vaccination. Our analysis revealed a shift in attitudes toward COVID-19 vaccination from high hopes to disenchantment, which may reflect some vaccine fatigue. In the future, public health authorities could face some challenges in maintaining confidence and high COVID-19 vaccine uptake., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Physical literacy (PL) is considered an important determinant of children's physical activity through which health benefits may be derived. The purpose of this study is to describe a sample of Canadian children's baseline levels of PL and movement behaviors, and explore whether the associations between PL and their mental wellbeing, if any, are mediated by moderate-to-vigorous physical activity (MVPA)., Methods: All grade two children in 14 elementary schools in the West Vancouver School District, Canada were invited to participate in a two-year longitudinal project. PL was assessed through PLAYfun and PLAYself tools. Physical activity was measured by wrist-worn accelerometers (GT3X + BT) for seven days. Children's mental well-being was assessed using the Strengths and Difficulties Questionnaire (SDQ). A score of total difficulties was aggregated for internalizing and externalizing problems., Results: A total of 355 children aged 7-9 (183 boys, 166 girls, 6 non-binary) participated with 258 children providing valid accelerometer data. Children exhibited an average of 111.1 min of MVPA per day, with 97.3% meeting the physical activity guidelines. Approximately 43% (108/250) of participants were meeting the Canadian 24-h movement guidelines. Children were at an 'emerging' level of overall physical competence (45.8 ± 5.6) and reported a mean score of 68.9 (SD = 12.3) for self-perceived PL, with no significant differences between boys and girls. PL was significantly associated with MVPA (r = .27) and all SDQ variables (rs = -.26-.13) except for externalizing problems. Mediation analyses showed PL was negatively associated with internalizing problems and total difficulties when the association with MVPA was considered. However, the mediating role of MVPA was found only between PL and internalizing problems, β = -.06, 95%CI [-.12, -.01]., Conclusions: Although most of our sample was physically active and showed higher adherence to 24-H movement guidelines than comparable population data, the motor competence and self-perceived PL of our sample were similar to those of previous studies. PL has an independent association with children's internalizing problems and total difficulties. Ongoing assessment will investigate the relationships between PL and children's mental health from a longitudinal perspective., (© 2023. The Author(s).)

Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce., Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time., Design: A comprehensive literature review and time-trend analysis., Data Sources and Methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model., Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years ( p  = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included ( p  = 0.3910)., Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan., Competing Interests: Dr. Moss has been a consultant for Takeda, has served on advisory boards for RedHill Biopharma and Phathom Pharmaceuticals regarding novel H. pylori therapies, and is a consultant for and has received research support from American Molecular Laboratories regarding molecular diagnostics for H. pylori. Dr. Chey reported being a Board member of the American College of Gastroenterology, GI on Demand, International Foundation of Functional GI Disorders, and the Rome Foundation; compensation as a consultant from AbbVie, BioAmerica, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and stock options in Dieta, Kiwi Bioscience, Isothrive, and Modify Health; and patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Malfertheiner has served as a speaker for Aboca, Bayer, Biocodex, Biohit, Malesci, Menarini, Luvos, and Mayoly-Spindler, a consultant for Aboca, Bayer, Danone, and an advisory board member for Bayer, Danone, Imevax, and Phathom. Dr. Pelletier, Dr. Jacob, and Dr. Leifke are employees of Phathom Pharmaceuticals. Dr. Tremblay and Dr. Hubscher are employees of Cytel, Inc, which served as a consultant on this project. Mr. Daniele was an employee of Cytel at the time of writing., (© The Author(s), 2023.)

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori ( H. pylori ) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns., Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns., Design: Retrospective matched cohort., Methods: We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period., Results: Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori- related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p  < 0.001]. Over 80% of patients received a post-treatment test for H. pylori . Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p  < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p  < 0.001) between 31 days and 12 months after the index date., Conclusion: Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori -related HCRU, and lower healthcare costs than patients treated with PPI-based therapy., Competing Interests: ES, EEC, and HG are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Phathom Pharmaceuticals, which funded the development and conduct of this study and manuscript. KY was an employee of Analysis Group, Inc. at the time of study conduct. CP and RJ are employees of Phathom Pharmaceuticals. CWH is a consultant for Phathom Pharmaceuticals, RedHill Biopharma, Allakos, Ironwood, Neurogastrx, ISOThrive, and EndoStim. He is a speaker for RedHill Biopharma, Phathom, and Alnylman. He owns stock in Antibe Therapeutics. KS is a consultant for Fuji Film Inc., Biofermin Pharma, and Pathom Pharmaceuticals. He received lecture fees from Takeda Pharmaceutical, Mylan Inc., Japan, Zeria Pharmaceuticals, Biofermin Pharma, and Astra-Zeneca Japan., (© The Author(s), 2023.)

Background: Many projects related to technology implementation in the context of chronic diseases have been developed over the years to better manage lifestyle medicine interventions and improve patient care. However, technology implementation in primary care settings remains challenging., Objective: The aim is to carry out a strengths, weaknesses, opportunities, and threats (SWOT) analysis (1) to assess satisfaction among patients with type 2 diabetes using an activity tracker to increase motivation for physical activity (PA) and (2) to explore the research and health care team's perceptions of this technology's implementation in a primary care setting., Methods: A 3-month hybrid type 1 study, which included 2 stages, was conducted in an academic primary health center in Quebec City, Quebec, Canada. In stage 1, a total of 30 patients with type 2 diabetes were randomized to the intervention (activity tracker) group or the control group. In stage 2, a SWOT analysis was performed on both patients and health care professionals to determine the components of successful technology implementation. Two questionnaires were used to gather feedback: a satisfaction and acceptability questionnaire concerning an activity tracker (15 patients in the intervention group) and a questionnaire based on the SWOT elements (15 patients in the intervention group and 7 health care professionals). Both questionnaires contained quantitative and qualitative questions. Qualitative variables from open questions were synthesized in a matrix and ranked according to apparition frequency and global importance. A thematic analysis was performed by the first author and validated by 2 coauthors separately. The information gathered was triangulated to propose recommendations that were then approved by the team. Both quantitative (randomized controlled trial participants) and qualitative (randomized controlled trial participants and team) results were combined for recommendations., Results: In total, 86% (12/14) of the participants were satisfied with their activity tracker use and 75% (9/12) felt that it incited them to stick to their PA program. The main strengths of the team members' perspectives were the project initiation and involvement of a patient partner, the study design, the team, and the device. The weaknesses were the budgetary constraints, the turnover, and the technical issues. The opportunities were the primary care setting, the loan of equipment, and common technology. The threats were recruitment issues, administrative challenges, technological difficulties, and a single research site., Conclusions: Patients with type 2 diabetes were satisfied with their activity tracker used to improve motivation for PA. Health care team members agreed that implementation can be done in primary care, but some challenges remain in using this technological tool in clinical practice regularly., Trial Registration: ClinicalTrials.gov NCT03709966; https://clinicaltrials.gov/ct2/show/NCT03709966., (©Cynthia Pelletier, Christian Chabot, Marie-Pierre Gagnon, Caroline Rhéaume. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.03.2023.)

Background: COVID-19 public health restrictions (i.e. physical distancing) compromise individuals' ability to self-manage their health behaviours and may increase the risks of adverse health events., Objectives: To evaluate the student-delivered Community Outreach teleheAlth program for Covid education and Health promotion (COACH) on health-directed behaviour (self-management) among older adults (≥65 years of age, n = 75). Secondary objectives estimated the influence of COACH on perceived depression, anxiety, and stress; social support; health-related quality of life; health promotion self-efficacy; and other self-management domains., Methods: COACH was developed to provide chronic disease management and prevention support among older adults via telephone or videoconferencing platforms (i.e. Zoom). In this single-group, pre-post study, our primary outcome was measured using the health-directed behaviour subscale of the Health Education Impact Questionnaire. Secondary measures included the Depression, Anxiety and Stress Scale, Medical Outcomes Study: Social Support Survey, MOS Short Form-36, and Self-Rated Abilities for Health Practices Scale. Paired sample t-tests were used to analyse outcome changes., Results: Mean age of participants was 72.4 years (58.7% female; 80% ≥2 chronic conditions). Health-directed behaviour significantly improved after COACH (P < 0.001, d = 0.45). Improved health promotion self-efficacy (P < 0.001, d = 0.44) and decreased mental health were also observed (P < 0.001, d = -1.69)., Discussion: COACH likely contributed to improved health-directed behaviour and health promotion self-efficacy despite the diminished mental health-related quality of life during COVID-19. Our findings also highlight the benefits of using health professional students for the delivery of virtual health promotion programs., Clinical Trial Information: ClinicalTrials.gov ID: NCT04492527., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Approximately 36% of the United States (US) population is infected with Helicobacter pylori (HP), a known major risk factor for peptic ulcer disease and gastric cancer. HP eradication reduces the rate of complications; however, the benefits are undermined by rising rates of HP eradication treatment failure. This real-world observational cohort analysis aims to describe HP diagnostic and treatment patterns among insured patients in the US. Using diagnoses, lab results, and treatment patterns, we identified adults (18+) with new diagnoses of HP in the Veradigm Health Insights EHR Database linked to Komodo claims data (1/1/2016-12/31/2019). Patients were required to have ≥ 12 months of data pre-/post-index. We captured patient characteristics, HP-related diagnostic testing, and the use of US guideline-recommended HP eradication regimens. HP eradication rates following first-line eradication treatment were measured among patients with available lab results. Overall, 31.8% of the 60,593 included patients did not receive guideline-recommended treatment. Among the 68.2% (41,340) with first-line treatment, 80.2% received clarithromycin-based triple therapy, and 6.6% received bismuth quadruple therapy. Of the 4569 patients with a repeated course of eradication therapy, 53.4% received the same regimen as their first-line, the majority (90.7%) of whom received two rounds of clarithromycin-based triple therapy. Among the 2455 patients with results of HP non-serology testing following first-line treatment, the 180-day eradication rate was 80.2% overall, with differences based on treatments and demographics. This study highlights gaps between guideline-recommended HP management and real-world patterns, underscoring the need to improve HP testing, treatment, and follow-up practices., (© 2023. The Author(s).)

Wearable robotic devices (WRD) are still struggling to fulfill their vast potential. Inadequate daily life usability is one of the main hindrances to increased technology acceptance. Improving usability evaluation practices during the development of WRD could help address these limitations. In this work, we present the design and validation of a novel online platform aiming to fill this gap, the Interactive Usability Toolbox (IUT). This platform consists of a public website that offers an interactive, context-specific search within a database of 154 user research methods and educational information about usability. In a dedicated study, the effect of this platform to support usability evaluation was investigated. Twelve WRD experts were asked to complete the task of defining usability evaluation protocols for two specific use cases. The platform was provided to support one of the use cases. The quality and composition of the proposed protocols were assessed by (i) two blinded reviewers, (ii) the participants themselves, and (iii) the study coordinators. We showed that using the IUT significantly affected the proposed evaluation focus, shifting protocols from mainly effectiveness-oriented to more user-focused studies. The protocol quality, as rated by the external reviewers, remained equivalent to those designed with conventional strategies. A mixed-method usability evaluation of the platform yielded an overall positive image, with detailed suggestions for further improvements. The IUT is expected to positively affect the evaluation and development of WRD through its educational value, the context-specific recommendations supporting ongoing benchmarking endeavors, and highlighting the value of qualitative user research., Competing Interests: The authors declare no competing interests exist., (© The Author(s) 2023.)

Aims: The study objectives were to 1) characterize the cost drivers of patients with Helicobacter pylori (HP) and 2) estimate HP-related cost savings following lab-confirmed HP eradication with US guideline-recommended treatment compared to failed eradication., Methods: We identified adults newly diagnosed with HP between 1/1/2016-12/31/2019 in the Veradigm Electronic Health Record Database linked to claims data (earliest HP diagnosis = index date). For the overall costs analysis, we required patients to have data available for ≥12 months before and after the index date. Then, we used multivariable modeling to assess the marginal effects of comorbidities on all cause-healthcare costs in the 12 months following HP diagnosis. For the eradication savings analysis, we identified patients with ≥1 HP eradication regimen, a subsequent HP lab test result, and ≥1 year of data after the test result. Then we used multivariable modeling to estimate HP-related cost while adjusting for eradication status, demographics, post-testing HP-related clinical variables, and the interactions between eradication status and each HP-related clinical variable., Results: The overall cost analysis included 60,593 patients with HP (mean age 54.2 years, 65.5% female). Mean (SD) 12-month unadjusted all-cause costs were $23,693 ($78,089). Rare comorbidities demonstrated the highest marginal effect. The marginal effects of gastric cancer and PUD were $15,705 and $7,323, respectively. In the eradication savings analysis, 1,835 (80.0%) of the 2295 patients had lab test-confirmed HP eradication. Compared to failed eradication, there were significant one-year cost savings among patients with successful HP eradication and select conditions: $1,770 for PUD, $518 for atrophic gastritis, $494 for functional dyspepsia, and $352 for gastritis., Conclusions: The healthcare costs of patients with HP are partially confounded by their burden of high-cost comorbidities. In the subset of patients with available results, confirmed vs. failed eradication of HP was associated with short-term cost offsets among those with specific to HP-related sequelae.

The Pfizer-BioNTech COVID-19 vaccine was recently authorized for Canadian children aged 5 to 11 years old. Previous studies have indicated that low parental vaccination intention can be anticipated. To better understand drivers of vaccine hesitancy among parents of 5-11 years old children, four focus group discussions were conducted. Interviewed parents generally showed little concern about the risk of COVID-19 for their child(ren) and many mentioned that children are at low risk of complications from COVID-19. Out of 28 participants, seven intended to vaccinate their child(ren) while the remaining were unsure or unwilling. Even if parents were themselves vaccinated, many hesitated for their child(ren). These parents perceived that it was unnecessary (due to low risk of complications) and were concerned about risks of side effects. Clear communication on vaccine safety and usefulness will be critical to reassure parents and foster vaccine acceptance.

Objectives: Communication during a pandemic is key in ensuring adoption of preventive behaviours and limiting disease transmission. The aim of the study was to explore how communication specialists working in health and governmental institutions and healthcare professionals have communicated about COVID-19, and how different groups of the public have perceived official communications on COVID-19., Methods: We conducted an exploratory qualitative study. Data were collected via individual semi-structured interviews and focus-group discussions. The Crisis and Emergency Risk Communication (CERC) model was used as a theoretical framework to guide data interpretation., Results: We interviewed 6 communication specialists and 5 healthcare professionals. Three focus groups were held with 23 participants (8 young adults, 9 Quebecers of Asian ethnicity, and 6 Quebecers who suffered harshly from economic consequences of the pandemic and measures). Although daily press conferences were rapidly implemented in Quebec, participants highlighted several communication challenges, including accuracy and credibility of information in a context of uncertainties and rapidly evolving knowledge. Participants also identified paternalism, stigmatization of some communities, and issues with promoting action and mobilization of some subpopulations as communication challenges., Conclusion: Our study showed that the six core CERC principles have not all been applied systematically in communication interventions in Quebec. Despite some limitations, messages about COVID-19 risk were clearly and consistently communicated and were generally well understood by most Quebecers., (© 2022. The Author(s) under exclusive license to The Canadian Public Health Association.)

Considering interactions between barriers to physical activity, sociodemographic factors, and rurality can support an equity-focused approach to physical activity promotion. In this cross-sectional analysis of the Canadian Community Health Survey Barriers to Physical Activity Rapid Response module, we compared self-reported individual and social-environmental correlates of physical activity between rural and urban residents and explored interactions with sociodemographic factors. Lack of social support was associated with lower odds of meeting physical activity guidelines for rural residents (OR = 0.71 [0.57,0.89], p = 0.003), but not for urban residents (OR = 0.99 [0.84,1.17], p =.931). Limited access to low-cost facilities was associated with lower odds of meeting physical activity guidelines (OR = 0.85 [0.73,0.98], p = 0.030) regardless of location, but was reported more commonly as a barrier by rural males (27.3 % vs 8.6 % urban) and females (30.0 % vs 9.1 % urban). Inadequate social support was associated with lower odds of meeting physical activity guidelines in females (OR = 0.79 [0.66,0.94], p =.009), but not males (OR = 0.99 [0.84,1.17], p =.931). Individual-level barriers such as time, costs, enjoyment, and confidence were associated with meeting physical activity guidelines for both rural and urban residents. Social-environmental factors appear to be the main contributors to physical activity inequities between rural and urban residents. Interventions designed to bolster social connectedness may support physical activity engagement for people living in rural communities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Whole-genome sequencing is widely used to better understand the transmission dynamics, the evolution and the emergence of new variants of viral pathogens. This can bring crucial information to stakeholders for disease management. Unfortunately, aquatic virus genomes are usually difficult to characterize because most of these viruses cannot be easily propagated in vitro . Developing methodologies for routine genome sequencing of aquatic viruses is timely given the ongoing threat of disease emergence. This is particularly true for pathogenic viruses infecting species of commercial interest that are widely exchanged between production basins or countries. For example, the ostreid herpesvirus type 1 (OsHV-1) is a Herpesvirus widely associated with mass mortality events of juvenile Pacific oyster Crassostrea gigas . Genomes of Herpesviruses are large and complex with long direct and inverted terminal repeats. In addition, OsHV-1 is unculturable. It therefore accumulates several features that make its genome sequencing and assembly challenging. To overcome these difficulties, we developed a tangential flow filtration (TFF) method to enrich OsHV-1 infective particles from infected host tissues. This virus purification allowed us to extract high molecular weight and high-quality viral DNA that was subjected to Illumina short-read and Nanopore long-read sequencing. Dedicated bioinformatic pipelines were developed to assemble complete OsHV-1 genomes with reads from both sequencing technologies. Nanopore sequencing allowed characterization of new structural variations and major viral isomers while having 99,98 % of nucleotide identity with the Illumina assembled genome. Our study shows that TFF-based purification method, coupled with Nanopore sequencing, is a promising approach to enable in field sequencing of unculturable aquatic DNA virus.

Introduction: Erosive esophagitis (EE) occurs when refluxate from the stomach causes T-lymphocyte infiltration of the esophageal mucosa, resulting in mucosal breaks. Currently, therapy with proton-pump inhibitors (PPIs) is the standard treatment for EE in the United States, but few comprehensive reviews exist on the efficacy of PPIs in US populations. Here, we present the most contemporary, thorough analysis of PPI efficacy rates, and identify and characterize patient subgroups at risk for poor healing outcomes., Areas Covered: We searched the literature to identify studies reporting rates of endoscopic healing and maintained healing of EE with PPI therapies in the US and found a paucity of recent evidence and real-world evidence. Twenty-two studies from 2009 and earlier were included in the final dataset., Expert Opinion: Rates of EE healing with PPIs were highest after 8 weeks of treatment, with over 80% of patients in most treatment arms demonstrating endoscopic healing, compared to lower efficacy (<80%) at 4 weeks. Rates of maintained healing with PPIs at 6 and 12 months were mostly lower than 80%, although the data were limited. Symptomatic patients and those with severe EE were less likely to achieve healing. Obese patients experienced similar healing rates as non-obese patients.

New inhibitors of the bacterial transferase MraY from Aquifex aeolicus (MraY AA ), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the O -acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraY AA transferase activity. Although with poor antibacterial activity, nine out of the ten compounds revealed the inhibition of the MraY AA activity in the range of 0.8 µM to 27.5 µM., Competing Interests: The authors declare no conflict of interest.

Background: A systematic review of epidemiological studies of primary dystonia from 1985 and 2010 found an overall prevalence of 16.43 per 100,000 (95% CI = 12.09-22.32)., Methods: We performed a systematic review of studies from 2010 and 2022 to determine if there are important differences in epidemiology between these time periods., Results: Nineteen studies were included. Incidence of cervical dystonia, blepharospasm, and oromandibular dystonia were each reported in one study; one study reported incidence for all adult onset idiopathic focal dystonias combined. Using data from 11 studies, we performed random effects meta-analyses of the prevalence of cervical dystonia (9.95 per 100,000; 95% CI = 3.51-28.17), blepharospasm (2.82 per 100,000; 95% CI = 1.12-7.12), laryngeal dystonia (0.40 per 100,000; 95% CI = 0.09-1.83), upper limb dystonia (1.27 per 100,000; 95% CI = 0.36-4.52), oromandibular dystonia (0.57 per 100,000; 95% CI = 0.15-2.15), and idiopathic or inherited isolated dystonia all subtypes combined (30.85 per 100,000; 95% CI = 5.06-187.74). All studies reported more cases of dystonia in females. There was no significant difference in prevalence by subgroup analysis based on time of study publication (1985-2010 vs. 2010-2022). Subgroup analysis of differences in prevalence by dystonia subtype by continent using all studies published (1985-2022) revealed significant regional differences in the prevalence of cervical and laryngeal dystonia., Conclusion: The incidence and prevalence of idiopathic or inherited isolated dystonia in the last decade was not significantly different from earlier reports. Population-based studies across multiple geographic areas are needed to obtain a clearer understanding of the epidemiology of this condition., (© 2022 Her Majesty the Queen in Right of Canada. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Reproduced with the permission of the Minister of Public Health Agency of Canada.)

Physical activity promotion in health care settings is poorly understood and has limited uptake among health care providers. The environmental and health care context of rural communities is unique from urban areas and may interact to influence intervention delivery and success. The aim of this rapid realist review was to synthesize knowledge related to the promotion of physical activity in rural health and social care settings. We searched Medline EBSCO, CINAHL, PsychINFO, and SPORTDiscus for relevant publications. We included qualitative or quantitative studies reporting on an intervention to promote physical activity in rural health (e.g., primary or community care) or social (e.g., elder support services) care settings. Studies without a rural focus or well-defined physical activity/exercise component were excluded. Populations of interest included adults and children in the general population or clinical sub-population. Intervention mechanisms from included studies were mapped to the Behaviour Change Wheel (capability, opportunity, motivation (COM-B)). Twenty studies were included in our review. Most interventions focused on older adults or people with chronic disease risk factors. The most successful intervention strategies leading to increased physical activity behaviour included wearable activity trackers, and check-ins or reminders from trusted sources. Interventions with mechanisms categorized as physical opportunity, automatic motivation, and psychological capability were more likely to be successful than other factors of the COM-B model. Successful intervention activities included a method for tracking progress, providing counselling, and follow-up reminders to prompt behaviour change. Cultivation of necessary community partnerships and adaptations for implementation of interventions in rural communities were not clearly described and may support successful outcomes in future studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objective: Management of erosive oesophagitis (EE) remains suboptimal, with many patients experiencing incomplete healing, ongoing symptoms, and relapse despite proton pump inhibitor (PPI) treatment. The Study of Acid-Related Disorders investigated patient burden of individuals with EE in a real-world setting., Design: US gastroenterologists (GIs) or family physicians (FPs)/general practitioners (GPs) treating patients with EE completed a physician survey and enrolled up to four patients with EE for a patient survey, with prespecified data extracted from medical records., Results: 102 GIs and 149 FPs/GPs completed the survey; data were available for 73 patients (mean age at diagnosis, 45.4 years). Omeprazole was healthcare professional (HCP)-preferred first-line treatment (60.8% GIs; 56.4% FPs/GPs), and pantoprazole preferred second line (29.4% and 32.9%, respectively). Price and insurance coverage (both 55.5% HCPs) and familiarity (47.9%) key drivers for omeprazole; insurance coverage (52.0%), price (50.0%), familiarity (48.0%), initial symptom relief (46.0%), and safety (44.0%) key drivers for pantoprazole. Only 49.3% patients took medication as instructed all the time; 56.8% independently increased medication frequency some of the time. Despite treatment, 57.5% patients experienced heartburn and 30.1% regurgitation; heartburn was the most bothersome symptom. 58.9% patients believed that their symptoms could be better controlled; only 28.3% HCPs were very satisfied with current treatment options. 83.6% patients wanted long-lasting treatment options. Fast symptom relief for patients was a top priority for 66.1% HCPs, while 56.6% would welcome alternatives to PPIs., Conclusion: This real-world multicentre study highlights the need for new, rapidly acting treatments in EE that reduce symptom burden, offer durable healing and provide symptom control., Competing Interests: Competing interests: CP and RJ are employees of Phathom Pharmaceuticals. All other authors are consultants to Phathom Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Effective acid suppression is a crucial component of Helicobacter pylori ( H. pylori ) eradication regimens. Approved treatments include dual, triple, and quadruple therapies composed of certain antibiotics in combination with proton pump inhibitors (PPIs). Vonoprazan, a potassium-competitive acid blocker, provides more potent and durable acid suppression than PPIs. We compared the efficacy of vonoprazan-based therapies vs approved standard regimens using new evidence from the phase 3 pHalcon HP trial in North America and Europe., Methods: Studies reporting first-line H. pylori eradication rates from empiric treatment with Food and Drug Administration-approved therapies and vonoprazan-containing therapies were identified via bibliographic searches of systematic literature reviews and a subsequent MEDLINE/Embase search using index terms for H. pylori and eradication. Randomized controlled trials comparing 2 or more relevant comparators were included in Bayesian network meta-analyses for grouped and distinct therapies., Results: Twenty-three distinct regimens from 42 trials including 12,773 patients were identified. Vonoprazan-based triple therapy showed the highest relative efficacy (odds ratio: 2.73, 95% credible interval 2.11, 3.54) and 72.1% probability of being the best. North American, Western, and global scenarios were largely consistent. Vonoprazan-based therapies demonstrated higher odds of H. pylori eradication than each PPI-based triple therapy. Furthermore, vonoprazan-based triple therapy was superior to bismuth subcitrate quadruple therapy (odds ratio: 1.60, 95% credible interval: 1.07, 2.38)., Conclusion: Vonoprazan-based eradication regimens represent novel treatments for H. pylori infection on a global scale, offering efficacy that, in this analysis, is superior to PPI-based triple therapy and comparable or better than bismuth quadruple therapy., (© 2022 The Authors.)

Objective: In recognition that engagement in physical activities for persons living with dementia can be challenging in rural and northern communities, the objective of this study was to explore the factors influencing physical activity participation among persons living with dementia in rural/northern communities and to identify the locally-driven mitigation strategies participants used to address barriers to physical activity., Setting: Interviews and focus groups were conducted in two locations in northern British Columbia, Canada including a rural community (<10 000 persons) and a medium-sized geographically isolated city (<80 000 persons). Both communities are located at substantial distances (>700 km) from larger urban centres., Participants: Twenty-nine individuals participated including healthcare providers (n=8), community exercise professionals (n=12), persons living with dementia (n=4) and care partners (n=5)., Results: Rural and northern contextual factors including aspects of the built and natural environment were the main drivers of physical activity for persons living with dementia. Limited capacity in the health system to support physical activity due to a lack of referrals, poor communication mechanisms and limited resources for programming created challenges for physical activity participation. At the community level, local champions filled gaps in physical activity programming by leveraging informal networks to organise opportunities. Programme-level factors included a lack of consistency in staff, and challenges defining programme scope given limited population size and the fear of stigma for persons living with dementia., Conclusions: Environmental context and limited access to specialised programming affect the opportunities for persons living with dementia to engage in physical activities. Rural and northern communities showed resiliency in providing physical activity opportunities yet remained fragile due to human resource challenges. Without reliable resources and sustained support from the health system, local champions remain vulnerable to burnout. Enhancing support for local champions may provide greater stability and support to physical activity promotion in rural and northern communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is a need for a reliable and validated method to estimate dietary potassium intake in chronic kidney disease (CKD) patients to improve prevention of cardiovascular complications. This study aimed to develop a clinical tool to estimate potassium intake using 24-h urinary potassium excretion as a surrogate of dietary potassium intake in this high-risk population. Data of 375 adult CKD-patients routinely collecting their 24-h urine were included to develop a prediction tool to estimate potassium diet. The prediction tool was built from a random sample of 80% of patients and validated on the remaining 20%. The accuracy of the prediction tool to classify potassium diet in the three classes of potassium excretion was 74%. Surprisingly, the variables related to potassium consumption were more related to clinical characteristics and renal pathology than to the potassium content of the ingested food. Artificial intelligence allowed to develop an easy-to-use tool for estimating patients' diets in clinical practice. After external validation, this tool could be extended to all CKD-patients for a better clinical and therapeutic management for the prevention of cardiovascular complications.

The genetic diversity of viral populations is a key driver of the spatial and temporal diffusion of viruses; yet, studying the diversity of whole genomes from natural populations still remains a challenge. Phylodynamic approaches are commonly used for RNA viruses harboring small genomes but have only rarely been applied to DNA viruses with larger genomes. Here, we used the Pacific oyster mortality syndrome (a disease that affects oyster farms around the world) as a model to study the genetic diversity of its causative agent, the Ostreid herpesvirus 1 (OsHV-1) in the three main French oyster-farming areas. Using ultra-deep sequencing on individual moribund oysters and an innovative combination of bioinformatics tools, we de novo assembled twenty-one OsHV-1 new genomes. Combining quantification of major and minor genetic variations, phylogenetic analysis, and ancestral state reconstruction of discrete traits approaches, we assessed the connectivity of OsHV-1 viral populations between the three oyster-farming areas. Our results suggest that the Marennes-Oléron Bay represents the main source of OsHV-1 diversity, from where the virus has dispersed to other farming areas, a scenario consistent with current practices of oyster transfers in France. We demonstrate that phylodynamic approaches can be applied to aquatic DNA viruses to determine how epidemiological, immunological, and evolutionary processes act and potentially interact to shape their diversity patterns., (© The Author(s) 2022. Published by Oxford University Press.)

Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for Cystic Fibrosis (CF). The most common CF-causing mutation is the deletion of the 508th amino-acid of CFTR (F508del), leading to dysregulation of the epithelial fluid transport in the airway's epithelium and the production of a thickened mucus favoring chronic bacterial colonization, sustained inflammation and ultimately respiratory failure. c407 is a bis-phosphinic acid derivative which corrects CFTR dysfunction in epithelial cells carrying the F508del mutation. This study aimed to investigate c407 in vivo activity in the F508del Cftr tm1Eur murine model of CF. Using nasal potential difference measurement, we showed that in vivo administration of c407 by topical, short-term intraperitoneal and long-term subcutaneous route significantly increased the CFTR dependent chloride (Cl - ) conductance in F508del Cftr tm1Eur mice. This functional improvement was correlated with a relocalization of F508del-cftr to the apical membrane in nasal epithelial cells. Importantly, c407 long-term administration was well tolerated and in vitro ADME toxicologic studies did not evidence any obvious issue. Our data provide the first in vivo preclinical evidence of c407 efficacy and absence of toxicity after systemic administration for the treatment of Cystic Fibrosis., (© 2022. The Author(s).)

Meeting the physical activity (PA) and recreational screen time recommendations for children and young people is associated with several health benefits. The purpose of this study was to compare the odds of meeting PA and recreational screen time recommendations between the Canadian youth living in urban versus rural communities. We analyzed nationally representative cross-sectional data collected as part of the 2017-2018 cycles of the Canadian Community Health Survey among young people aged 12-17 years. PA and screen time were self-reported. Sex-specific multivariable logistic regression models were used to estimate the odds of meeting individual and combined PA and recreational screen time recommendations by rural and urban status after adjusting for individual, socioeconomic, and seasonal covariates. The odds of meeting the PA recommendation were not statistically significantly different among males (OR = 1.01, 95% CI: 0.86-1.18) or females (OR 1.05, 95% CI: 0.99-1.11) living in urban versus rural communities. The odds of meeting the recreational screen time recommendations were statistically significantly lower among male (OR = 0.71, 95% CI: 0.65-0.77) and female (OR = 0.71, 95% CI: 0.59-0.86) youth living in urban compared to those in rural communities. The odds of meeting the combined PA and screen time recommendations were statistically significantly lower among urban males (OR = 0.75, 95% CI: 0.71-0.81) but not females (OR = 0.82, 95% CI: 0.58-1.15) than those from rural communities. These findings suggest that residential context (i.e., urban versus rural) may have a differential impact on meeting the combined PA and screen time recommendations among the male and female Canadian youth. Future research should investigate these differences using device-based measures.