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ABSTRACT: Background: Low back pain (LBP) is a highly prevalent, disabling condition affecting millions of people. Patients with an identifiable anatomic pain generator and resulting neuropathic lower extremity symptoms often undergo spine surgery, but many patients lack identifiable and/or surgically corrective pathology. Nonoperative treatment options often fail to provide sustained relief. Spinal cord stimulation (SCS) is sometimes used to treat these patients, but the lack of level 1 evidence limits its widespread use and insurance coverage. The DISTINCT RCT study evaluates the efficacy of passive recharge burst SCS compared to conventional medical treatment (CMM) in alleviating chronic, refractory axial low back pain. Methods: This prospective, multicenter, randomized, study with an optional 6-month crossover involved patients who were not candidates for lumbar spine surgery. The primary and secondary endpoints evaluated improvements in low back pain intensity (NRS), back pain-related disability (ODI), pain catastrophizing (PCS), and healthcare utilization. Patients were randomized to SCS therapy or CMM at 30 US study sites. Results: The SCS arm reported an 85.3% NRS responder rate (≥ 50% reduction) compared to 6.2% (5/81) in the CMM arm. After the 6M primary endpoint, SCS patients elected to remain on assigned therapy and 66.2% (49/74) of CMM patients chose to trial SCS (crossover). At the 12M follow-up, SCS and crossover patients reported 78.6% and 71.4% NRS responder rates. Secondary outcomes indicated significant improvements in ODI, PCS, and reduced healthcare utilization. Six serious adverse events were reported and resolved without sequelae. Conclusion: DISTINCT chronic low back pain patients with no indication for corrective surgery experienced a significant and sustained response to burst SCS therapy for up to 12 months. CMM patients who crossed over to the SCS arm reported profound improvements after 6 months. This data advocates for a timely consideration of SCS therapy in patients unresponsive to conservative therapy.

Abstract Background In 2009, Yvonne Steinert et al., at McGill University, published a study exploring barriers to faculty development (FD) participation among urban faculty. Over a decade later, we set out to replicate and expand on that study to learn what has changed in continued professional development (CPD) and what the current barriers are to participation in CPD for specialists and family physicians in rural and urban locations. Methods Informed by a collaborative inquiry research framework, we invited faculty across rural and urban Saskatchewan to focus groups and interview sessions. The results were analyzed for themes. Results Thirty-four faculty members from both rural and urban areas participated in this study. Of these, 50% were female, 74% practiced in urban areas, and 56% had over 20 years of experience. Frequently cited reasons for nonparticipation included time constraints, organizational and logistical challenges, poor resonance with material and presenters, and lack of recognition for teaching provided. Racism contributed to feelings of disconnectedness among physician faculty members. Conclusion Even after more than a decade, our research uncovered consistent reasons for nonparticipation in locally organized CPD events. New findings highlighted feelings of disconnectedness, notably stemming from racism and workplace discrimination. However, with recent societal developments brought about by the COVID-19 pandemic, can we ride these major waves of change to a new future of engagement? The pandemic led to a shift to virtual and hybrid professional development programs, presenting both benefits and challenges. Additionally, the peri-COVID anti-racism movement may positively address previously unidentified reasons for nonattendance. Harnessing these major changes could lead to a new future of engagement for continued professional development.

AbstractBackground & Objective: Negative health effects from occupational whole-body vibration (WBV) exposure during machinery operation include alterations in proprioception, vestibular function, reaction time, stress, motor response, and decrements in musculoskeletal health. To reduce WBV exposure during machinery operation, it may be possible to incorporate short rest break activities throughout the day. This study aims to determine if there are intervention activities that can minimize decrements in cognitive, proprioceptive, and musculoskeletal effects related to WBV exposure during machine operation.Materials & Methods Eleven healthy adults participated in four 1-hour sessions of ecologically valid WBV exposure followed by one of four 5-minute activities: sitting, walking, 2 min of gaze stabilization exercise (GSE) coupled with 3 min of trunk mobility exercise (GSE + MOBIL), or 2 min of GSE coupled with a 3-minute walk (GSE + WALK). Baseline and post-activity measurements (rating of perceived discomfort, balance and postural sway measurements, 5-minute psychomotor vigilance task test) were submitted to a paired t-test to determine the effect of WBV exposure and activities on physical, cognitive, and sensorimotor systems and to a repeated measures ANOVA to determine any differences across activities.Results We observed degradation of the slowest 10% reaction speed outcomes between baseline and post-activity after walking (7.3%, p

Abstract Background Indigenous youth in Canada face profound health inequities which are shaped by the rippling effects of intergenerational trauma, caused by the historical and contemporary colonial policies that reinforce negative stereotypes regarding them. Moreover, wellness promotion strategies for these youth are replete with individualistic Western concepts that excludes avenues for them to access holistic practices grounded in their culture. Our scoping review explored strategies, approaches, and ways health and wellness can be enhanced by, for, and with Indigenous youth in Canada by identifying barriers/roadblocks and facilitators/strengths to enhancing wellness among Indigenous youth in Canada. Methods We applied a systematic approach to searching and critically reviewing peer-reviewed literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews [PRISMA-ScR] as a reporting guideline. Our search strategy focused on specific keywords and MeSH terms for three major areas: Indigenous youth, health, and Canada. We used these keywords, to systematically search the following electronic databases published in English between January 01, 2017, to May 22, 2021: Medline [Ovid], PubMed, ERIC, Web of Science, Scopus, and iportal. We also used hand-searching and snowballing methods to identify relevant articles. Data collected were analysed for contents and themes. Results From an initial 1695 articles collated, 20 articles met inclusion criteria for this review. Key facilitators/strengths to enhancing health and wellness by, for, and with Indigenous youth that emerged from our review included: promoting culturally appropriate interventions to engage Indigenous youth; using strength-based approaches; reliance on the wisdom of community Elders; taking responsibility; and providing access to wellness supports. Key barriers/roadblocks included: lack of community support for wellness promotion activities among Indigenous youth; structural/organizational issues within Indigenous communities; discrimination and social exclusion; cultural illiteracy among youth; cultural discordance with mainstream health systems and services; and addictions and risky behaviours. Conclusion This scoping review extracted 20 relevant articles about ways to engage Indigenous youth in health and wellness enhancement. Our findings demonstrate the importance of promoting health by, and with Indigenous youth, by engaging them in activities reflexive of their cultural norms, rather than imposing control measures that are incompatible with their value systems.

Background: Community-dwelling adults who can perform self-care behaviors related to making treatment decisions and participating in treatment have been found to use less emergency care. In this exploratory study, we examined the relationships in older adults between five social determinants (urban/rural residence, sex, age, marital status, and education) and the perceived importance, desirability, and ability to perform 11 self-care behaviors related to making good treatment decisions and participating in treatment. Methods: This cross-sectional study surveyed 123 community-dwelling older adults living in the southern United States in 2015–2016. All participants were 65 years or older. Data were collected using the Patient Action Inventory for Self-Care and analyzed using descriptive, univariate, and multivariate logistic regression analyses. Results: The social determinants (identified as barriers) of self-care behaviors related to making good treatment decisions and participating in treatment were: having less than a high school education, being 75 years or older, and being separated from a spouse. Sex and residence were found to be neither barriers nor facilitators. Conclusions: Our findings suggest that, in older adults, attending to the needs related to health literacy education and improving social support might increase self-care behaviors related to making good treatment decisions and participating in treatment. Future research will compare the differences across diverse populations to validate our study findings.

Background: This exploratory survey study examined the relationship between older adults’ five socio-demographic determinants (urban/rural residence, gender, age, marital status, and education) and their self-reported perception of importance, desire to perform, and ability to perform nine self-care behaviors related to promoting health and getting preventive health care. Methods: We reported a secondary analysis of a dataset from an exploratory survey project; we analyzed 2015–2016 retrospective data collected from a cross-sectional survey study, including 123 adults aged 65 years and older living in southern United States. Data were collected from the Patient Action Inventory for Self-Care and a demographic questionnaire and analyzed using binary and multiple logistic regression analyses. Results: Advancing age, marital separation, and holding less than a high school education were significantly associated with at least one of the unfavorable perceptions of the importance, the desire to perform, and the ability to perform three self-care behaviors. These three behaviors were: (1) creating habits that will improve health and prevent disease, (2) discussing the use of health screening tests with healthcare providers, and (3) joining in local health screening or wellness events. Gender and urban/rural residence were not significant. Conclusions: Comprehensive health care should include an individual’s socio-demographic context and self-care perception of importance, desire, and ability.

Burkholderia pseudomallei: is the etiological agent of the disease melioidosis and is a Tier 1 select agent. It survives and replicates inside phagocytic cells by escaping from the endocytic vacuole, replicating in the cytosol, spreading to other cells via actin polymerization and promoting the fusion of infected and uninfected host cells to form multinucleated giant cells. In this study, we utilized a proteomics approach to identify bacterial proteins produced inside RAW264.7 murine macrophages and host proteins produced in response to B. pseudomallei infection. Cells infected with B. pseudomallei strain K96243 were lysed and the lysate proteins digested and analyzed using nanoflow reversed-phase liquid chromatography and tandem mass spectrometry. Approximately 160 bacterial proteins were identified in the infected macrophages, including BimA, TssA, TssB, Hcp1 and TssM. Several previously uncharacterized B. pseudomallei proteins were also identified, including BPSS1996 and BPSL2748. Mutations were constructed in the genes encoding these novel proteins and their relative virulence was assessed in BALB/c mice. The 50% lethal dose for the BPSS1996 mutant was approximately 55-fold higher than that of the wild type, suggesting that BPSS1996 is required for full virulence. Sera from B. pseudomallei-infected animals reacted with BPSS1996 and it was found to localize to the bacterial surface using indirect immunofluorescence. Finally, we identified 274 host proteins that were exclusively present or absent in infected RAW264.7 cells, including chemokines and cytokines involved in controlling the initial stages of infection.

Background There is a growing attraction by youth to alternative tobacco products (ATPs) such as e-cigarettes and hookahs. This study investigated risk perceptions and demographic characteristics associated with ATP use in grade 8–10 students. Methods Data were drawn from the 2014/15 cycle of the CSTADS. The analytic sample included 1819 students from a total pool of 42 094 students who completed the survey. Logistic regression models were used to examine factors (demographic characteristics and risk perception) associated with ATP use in the past 30 days. Results 12% of students in grade 8–10 self-identified as having used ATPs in the past 30-days, with a majority of students in grade 10 (56%). Male students had higher odds of reporting ATP use when compared to females. Although a lesser proportion of Indigenous students reported ATP use in comparison to White students (31% vs 61%), Indigenous students were 2.42 (1.49, 3.93) times as likely to use ATPs as White students. Students who perceived smoking hookah once in a while as “no to slight risk” were 1.58 (1.09, 2.28) times more likely to report ATP use than students who perceived “moderate to great risk.” Also, students who perceived using e-cigarettes on a regular basis as “no to slight risk” were 2.21 (1.53, 3.21) times more likely to report ATP use as students who perceived “moderate-great risk.” Conclusion A significant number of grade 8–10 students use ATPs, especially e-cigarettes, with the misconception of minimal health risks. There remains the need to do more to counteract the rise in social and epidemiological alternative tobacco use trends among the youth.

Purpose: An important element in each teaching workshop for resident doctors at the University of Saskatchewan is the microteaching sessions, including feedback. We set out to test our observations that one condition for organizing the feedback increased the quality of feedback. In one condition, residents provide and receive feedback in all areas listed on our feedback form; while in the other condition, they provide and receive feedback in some areas. Methods: Over 115 residents participated in the teaching workshop in the 2019-2020 academic year. Each resident experienced both conditions for giving and receiving feedback—about half with one condition first and the other half in the opposite order. We developed and tested a simple survey that asked about the usefulness of the feedback. Results: We used the Mann-Whitney U test for differences between some areas or all areas. We found a statistically significant difference with small to moderate effect sizes (Cohen’s d) favouring the some areas condition. Conclusion: Residents found the usefulness of feedback given or received using the feedback condition in some areas greater than all areas. We will now only use the some areas condition and recommend that other teaching workshops that use microteaching practice sessions consider using this condition.

Abstract Aims This study examined associations between older adults’ demographic factors and their perceived importance of, desire to and ability to perform seven self‐care behaviours for communicating with healthcare professionals. Design This cross‐sectional survey study analysed subset data of 123 older adults 65 years and older, living in southern United States. Methods The Patient Action Inventory for Self‐Care (57 items, grouped into 11 categories) was used to collect self‐reported self‐care data. Demographic characteristics were also collected. Descriptive statistics and logistic regression analyses were used to tests for relationships between the variables relevant to the research objective. Results Regression findings showed that separated older adults felt less able to share ideas about their healthcare experiences compared to married older adults. Male older adults reported less desire to list issues to discuss and less desire to share ideas about their care experience with their healthcare professionals compared to their female counterparts.

ABSTRACT Burkholderia pseudomallei is an opportunistic pathogen that is responsible for the disease melioidosis in humans and animals. The microbe is a tier 1 select agent because it is highly infectious by the aerosol route, it is inherently resistant to multiple antibiotics, and no licensed vaccine currently exists. Naturally acquired infections result from contact with contaminated soil or water sources in regions of endemicity. There have been few reports investigating the molecular mechanism(s) utilized by B. pseudomallei to survive and persist in ecological niches harboring microbial competitors. Here, we report the isolation of Gram-positive bacteria from multiple environmental sources and show that ∼45% of these isolates are inhibited by B. pseudomallei in head-to-head competition assays. Two competition-deficient B. pseudomallei transposon mutants were identified that contained insertion mutations in the hmqA-G operon. This large biosynthetic gene cluster encodes the enzymes that produce a family of secondary metabolites called 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs). Liquid chromatography and mass spectrometry conducted on filter-sterilized culture supernatants revealed five HMAQs and N-oxide derivatives that were produced by the parental strain but were absent in an isogenic hmqD deletion mutant. The results demonstrate that B. pseudomallei inhibits the growth of environmental Gram-positive bacteria in a contact-independent manner via the production of HMAQs by the hmqA-G operon. IMPORTANCE Burkholderia pseudomallei naturally resides in water, soil, and the rhizosphere and its success as an opportunistic pathogen is dependent on the ability to persist in these harsh habitats long enough to come into contact with a susceptible host. In addition to adapting to limiting nutrients and diverse chemical and physical challenges, B. pseudomallei also has to interact with a variety of microbial competitors. Our research shows that one of the ways in which B. pseudomallei competes with Gram-positive environmental bacteria is by exporting a diverse array of closely related antimicrobial secondary metabolites.

BACKGROUND: Treatment of the complications arising from Prenatal Alcohol Exposure (PAE) has largely been focused on psychosocial and environmental approaches. Research on the use of medications, especially psychotropic medications, has lagged behind. OBJECTIVES: This systematic review sought to investigate psychotropic medication related findings and outcomes in those diagnosed with Fetal Alcohol Spectrum Disorder (FASD). METHODS: Comprehensive searches were conducted in seven major databases (Medline/PubMed, Scopus, Web of Knowledge, Embase, PsycINFO, Cochrane Library, and PsycARTICLES) up to February 2017. Key search terms with synonyms were mapped on these databases. There were no timeline restrictions and no grey literature searches. Two reviewers independently assessed 25 studies that met the inclusion criteria. Most studies were reviews of treatment and retrospective case series. RESULTS: Two crossover randomized trials were reported, and the findings were not amenable to meta-analysis. Several conditions (depression, agitation, seizures, and outburst) combined with the most frequent presentation, ADHD, to represent the rationale for prescribing psychotropic medications. Second-generation antipsychotics were found to improve social skills, but the paucity of data limited the extent of clinical guidance necessary for the field. CONCLUSIONS: The systematic review showed that there are some clinical evidence displaying the validity of psychopharmacological interventions in people with FASD, which varies across the spectrum of disease severity, age, and gender. There is a need for more clinical evidence-based studies in addition to clinical expert opinions to substantiate an optimal ground for individualized management of FASD. The study protocol for this review was registered in PROSPERO with registration number CRD42016045703.

Bartonella henselae (B. henselae) is a gram-negative bacterium that causes cat scratch disease, bacteremia, and endocarditis, as well as other clinical presentations. B. henselae has been shown to form a biofilm in vitro that likely plays a role in the establishment and persistence of the bacterium in the host. Biofilms are also known to form in the cat flea vector; hence, the ability of this bacterium to form a biofilm has broad biological significance. The release of B. henselae from a biofilm niche appears to be important in disease persistence and relapse in the vertebrate host but also in transmission by the cat flea vector. It has been shown that the BadA adhesin of B. henselae is critical for adherence and biofilm formation. Thus, the upregulation of badA is important in initiating biofilm formation, and down-regulation is important in the release of the bacterium from the biofilm. We summarize the current knowledge of biofilm formation in Bartonella species and the role of BadA in biofilm formation. We discuss the evidence that defines possible mechanisms for the regulation of the genes required for biofilm formation. We further describe the regulation of those genes in the conditions that mimic both the arthropod vector and the mammalian host for B. henselae. The treatment for persistent B. henselae infection remains a challenge; hence, a better understanding of the mechanisms by which this bacterium persists in its host is critical to inform future efforts to develop drugs to treat such infections.

Background: Many Indigenous communities in Canada live with high-risk drinking water systems and drinking water advisories and experience health status and water quality below that of the general population. A scoping review of research examining drinking water quality and its relationship to Indigenous health was conducted. Objective: The study was undertaken to identify the extent of the literature, summarize current reports and identify research needs. Design: A scoping review was designed to identify peer-reviewed literature that examined challenges related to drinking water and health in Indigenous communities in Canada. Key search terms were developed and mapped on five bibliographic databases (MEDLINE/PubMED, Web of Knowledge, SciVerse Scopus, Taylor and Francis online journal and Google Scholar). Online searches for grey literature using relevant government websites were completed. Results: Sixteen articles (of 518; 156 bibliographic search engines, 362 grey literature) met criteria for inclusion (contained keywords; publication year 2000–2015; peer-reviewed and from Canada). Studies were quantitative (8), qualitative (5) or mixed (3) and included case, cohort, cross-sectional and participatory designs. In most articles, no definition of “health” was given (14/16), and the primary health issue described was gastrointestinal illness (12/16). Challenges to the study of health and well-being with respect to drinking water in Indigenous communities included irregular funding, remote locations, ethical approval processes, small sample sizes and missing data. Conclusions: Research on drinking water and health outcomes in Indigenous communities in Canada is limited and occurs on an opportunistic basis. There is a need for more research funding, and inquiry to inform policy decisions for improvements of water quality and health-related outcomes in Indigenous communities. A coordinated network looking at First Nations water and health outcomes, a database to store and create access to research findings, increased funding and time frames for funding, and more decolonizing and community-based participatory research aimed at understanding the relationship between drinking water quality and health outcomes in First Nations communities in Canada are needed.

Background: It has been reported in the extant literature that the attributes of professionalism vary widely with gender, age, the level of education, cultures, and socioeconomic backgrounds and between professions. This study evaluated Nigerian physiotherapists’ knowledge and attributes of professionalism and also examined the influence of demographic variables on their professionalism. Methods: One hundred and forty-nine physiotherapists recruited from four randomly selected University Teaching Hospitals completed a Professionalism Inventory that assesses demographic variables, knowledge of professionalism and attributes of professionalism – clinical competence, a spirit of inquiry, accountability, autonomy, advocacy, innovation and visionary, collegiality and collaboration, and ethics/value. Results: The physiotherapists’ average knowledge of professionalism score was 62%, and the average attributes of professionalism score were 63/80 (79%). The physiotherapists who are married, older than 40 years, and with a doctorate, with 16–20 years of work experience, and employed in the neurology practice setting demonstrated significantly (p

On April 23, 2024, FDA granted accelerated approval to tovorafenib, a type II RAF kinase inhibitor, for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Efficacy was evaluated in FIREFLY-1 (NCT04775485), a single-arm, open-label, multicenter trial that enrolled patients 6 months to 25 years of age with relapsed or refractory pLGG with an activating BRAF alteration who had received prior systemic therapy. The major efficacy outcome measure was radiologic overall response rate (ORR), defined as the proportion of patients with complete response, partial response, or minor response as determined by blinded independent central review using Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. A key secondary endpoint was duration of response (DoR). In an efficacy population of 76 patients, the ORR was 51% (95% confidence interval (CI): 40, 63), and the median DoR was 13.8 months (95% CI: 11.3, not estimable). The required post-marketing clinical trial (FIREFLY-2) was well underway at the time of accelerated approval. This represents the first FDA approval of a systemic therapy for the treatment of patients with pLGG with BRAF fusions or rearrangements.

On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro, Bristol Myers Squibb Corporation) for the treatment of adult patients with locally advanced or metastatic receptor tyrosine kinase encoded by the ROS1 gene (ROS1)-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single-arm trial with multiple cohorts of patients with ROS1 fusion-positive (hereafter "ROS1-positive") NSCLC (NCT03093116), who were either treatment naïve or had received prior ROS1 tyrosine kinase inhibitor (TKI) and/or platinum-based chemotherapy. The primary efficacy outcome measure is objective response rate (ORR) assessed by blinded independent central review (BICR) using response evaluation criteria in solid tumors version 1.1. ORR was assessed in 71 patients who were ROS1 TKI naïve and 56 patients who had received a prior ROS1 TKI. Among the 71 patients who were ROS1 TKI naïve, the ORR was 79% (95% CI, 68-88), median duration of response was 34.1 months (95% CI, 26-NE). In patients who had received a prior ROS1 TKI and no prior chemotherapy, the ORR was 38% (95% CI, 25-52). The median duration of response was 14.8 months (95% CI, 7.6-NE); BICR-assessed responses were observed in CNS metastases in patients in both cohorts and in patients who developed resistance mutations following prior TKI therapy. The most common (>20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs., (©2024 American Association for Cancer Research.)