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The maternal care of infants poses a unique challenge for mothers, especially after discharge from the hospital. This review focused on the literature on maternal care of preterm infants at home after discharge from the hospital’s Neonatal Intensive Care Unit (NICU). A comprehensive literature search was conducted using keywords relevant to the topic. PubMed and EBSCO essential databases were searched for studies published between 2017 and 2023 (six years). Out of the 2903 retrieved studies, 7 were eligible and included in the review. The quality of available evidence was assessed using the Johns Hopkins Nursing Evidence Appraisal Tool (JHNEAT) and the Critical Appraisal Skills Programme (CASP) checklist. This review found that exclusive breastfeeding rates for preterm infants at home varied from 27% to 76% (Pooled prevalence of 48%) in data extracted from the studies conducted in Ethiopia (Africa), Brazil (South America), USA (North America), Denmark, and Italy (Europe). The practice of kangaroo mother care (KMC) for temperature regulation ranged from 41% to 83% (Pooled prevalence of 63%) in data extracted from studies conducted in Ethiopia (Africa) and Denmark (Europe). The review concluded that the care provided by mothers at home after discharge from the NICU was inadequate. Maternal and child health services providers should develop social media platforms to educate and encourage mothers to sustain exclusive breastfeeding and KMC practices after leaving the NICU.

Background: Research indicates that the psychological well-being of orthopedic patients can benefit from a robust social support system that offers emotional assistance both before and after surgery. However, the impact of social networks on mental health outcomes remains inconclusive due to variations in availability. Objectives: This study investigated the influence of support from family and friends in the relationship between post-traumatic stress disorder (PTSD) and emotional distress among orthopedic patients in Nigeria. Materials and Methods: The study employed a hospital-based research design, using the 17-item PTSD self-report measure (PCL-C) and depression anxiety stress scales (DASS-21) to assess psychological distress and dimensions of social support from friends and family, involving 542 orthopedic patients from the National Orthopedic Hospital in Enugu, Nigeria. Results: The findings revealed a significant association between PTSD and emotional distress (β = 0.866; t = 9.245; P < 0.001). Family support was found to exacerbate emotional distress among orthopedic patients (β = 0.448; t = 4.176; P < 0.001), while support from friends showed an inverse effect on emotional distress (β = −0.310; t = −2.880; P < 0.01). Moreover, moderation analysis indicated that high family support reduces the effect of PTSD on emotional distress for orthopedic patients (β = −0.035; t = −3.539; [CI: −0.055, −0.016], P < 0.01). Conclusion: The study recommends prompt intervention for orthopedic patients to enhance their well-being by leveraging the available support from family and friends to alleviate the emotional distress associated with PTSD. Additionally, it underscores the importance of educating families and friends of orthopedic patients on their role in supporting the patient’s recovery journey.

Summary: Background: Given the chronic immune activation and inflammatory milieu associated with Long COVID and HIV, we assessed the prevalence of Long COVID in adults living with HIV; and investigated whether adults living with HIV were associated with increased chance of developing Long COVID compared to adults living without HIV Methods: In this systematic review and meta-analysis, we searched Medline, EMBASE, CINHAL, PubMed and CENTRAL from inception until June 14th, 2024, for observational studies that measured the prevalence of Long COVID in adults living with HIV and the odds of developing Long COVID following a SARS-CoV-2 infection in people living with HIV compared to people living without HIV. Reviews, case reports, randomised control trials and editorials were excluded. The search was conducted without language restrictions. We performed meta-analysis of proportions to synthesise prevalence estimates using logit transformation and a sensitivity analysis using mixed-effects logistic regression. We used random-effects meta-analyses to summarize the odds ratio (OR) of developing Long COVID in adults living with HIV compared to adults living without HIV and conducted a sensitivity analysis including only studies with covariate-adjusted estimates that was planned a-priori. We used ROBINS-E for the risk of bias assessment and GRADE to rate the certainty of evidence. We identified statistical heterogeneity using Cochran's Q test and quantified it using the I2 statistic. For the Q test, a P

Background: In response to the inherent critical incident exposures experienced by firefighters, various mental health education programs have been developed. The purpose of this study was to explore the perceptions of firefighters who took such programs to understand differences/similarities across these programs. Methods: We recruited 14 participants, who had taken or delivered two or more programs for firefighters (Resilient Minds (RM), Road to Mental Readiness (R2MR), and Before Operational Stress (BOS)). Participants participated in semi-structured interviews, which explored information that they learned, recalled, used, and their preferences. Data was analysed using thematic analysis. Results: Participants believed that all programs had some shared teaching methods, goals, skills, and topics; however, each program had key focuses/distinctive features. RM was said to be largely group participation and focused on assisting yourself, peers, and citizens. R2MR and BOS was said to be largely lecture style with a focus on the self. 70 % of participants who took RM (n = 7) and one other course preferred RM due to the specificity of training to firefighters, more active teaching methods, and focus on practical skill development. Others (43 %) had no program preference. Participants suggest that a tiered approach to mental health education would benefit firefighters. Conclusions: All programs were seen as helpful. Despite some congruency in goals and content, most firefighters preferred RM because the content was fire-specific, and the pedagogical approach was seen as more active and engaging. Program characteristics are important to facilitate appropriate program selection, as such, programs should be explicit about these aspects.

Abstract N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved “SELILKR” motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70’s dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.

Background: Internet addiction (IA) is a global public health problem that significantly impacts adolescents’ well-being, with a notable increase in the rate of Internet use during the coronavirus disease 2019 (COVID-19) period. However, few studies have explored the rate and pattern of IA in a holiday camp, which provides an inclusive haven for adolescents from diverse backgrounds to interact together. Objective: To determine the prevalence and pattern of IA among adolescents in a holiday camp in Nigeria post-COVID-19 pandemic. Materials and Methods: Data on the demographic profile and the Internet addiction test (IAT) were collected using an IAT questionnaire, and analysis was conducted using STATA 16.0 with a significance level set at P < 0.05. Results: Of the 243 participants, 136 had IA, resulting in an IA prevalence of 56.0%; 71/243 (29.2%) had mild IA, 62/243 (25.5%) had moderate IA, and 3/243 (1.2%) had severe IA. The IA rate was higher among late adolescents (80.0%) compared to early (35.0%) and middle adolescents (55.0%) (p = 0.009). On logistic regression, late adolescence (odds ratio (OR) = 2.71; 95 CI 1.39–5.27), male sex (OR = 2.67; 95 CI 1.36–5.24), and spending more than 3 h online daily (OR = 13.67; 95 CI 6.24–29.91) were associated with increased risk of IA. Conclusion: As a result of the COVID-19 pandemic, there is a significant prevalence of IA among adolescents in a holiday camp in Nigeria, impacting 56% of the population. This addiction is strongly linked with late adolescence, male sex, and spending more than 3 h online each day.

Abstract Introduction Transforming growth factor beta (TGFβ) cytokines (TGFβ1, TGFβ2, and TGFβ3) play critical roles in tissue fibrosis. However, treatment with systemic pan-TGFβ inhibitors have demonstrated unacceptable toxicities. In this study, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7303509, a high-affinity, TGFβ3-specific, humanized immunoglobulin G1 monoclonal antibody, in healthy adult volunteers (HVs). Methods This phase 1a, randomized, double-blind trial included six cohorts for evaluation, with each cohort receiving single doses of placebo or RO7303509, administered intravenously (IV; 50 mg, 150 mg, 240 mg) or subcutaneously (SC; 240 mg, 675 mg, 1200 mg). The frequency and severity of adverse events (AEs) and RO7303509 serum concentrations were monitored throughout the study. We also measured serum periostin and cartilage oligomeric matrix protein (COMP) by immunoassay and developed a population pharmacokinetics model to characterize RO7303509 serum concentrations. Results The study enrolled 49 HVs, with a median age of 39 (range 18–73) years. Ten (27.8%) RO7303509-treated subjects reported 24 AEs, and six (30.8%) placebo-treated subjects reported six AEs. The most frequent AEs related to the study drug were injection site reactions and infusion-related reactions. Maximum serum concentrations (C max) and area under the concentration–time curve from time 0 to infinity (AUC0–inf) values for RO7303509 appeared to increase dose-proportionally across all doses tested. Serum concentrations across cohorts were best characterized by a two-compartment model plus a depot compartment with first-order SC absorption kinetics. No subjects tested positive for anti-drug antibodies (ADAs) at baseline; one subject (2.8%; 50 mg IV) tested positive for ADAs at a single time point (day 15). No clear pharmacodynamic effects were observed for periostin or COMP upon TGFβ3 inhibition. Conclusion RO7303509 was well tolerated at single SC doses up to 1200 mg in HVs with favorable pharmacokinetic data that appeared to increase dose-proportionally. TGFβ3-specific inhibition may be suitable for development as a chronic antifibrotic therapy. Trial Registration ISRCTN13175485.

The well-being of primary school teachers is vital for fostering effective teaching and learning, yet they face a range of challenges that negatively impact their occupational health. This phenomenological study explores the multifaceted factors influencing teacher occupational well-being, with a focus on classroom processes and school-related factors. Employing a qualitative phenomenological approach, this study gathered in-depth insights from Australian primary school teachers through semi-structured interviews. Participants were recruited from a variety of educational settings to capture diverse experiences and perspectives. Data were thematically analysed to identify key themes impacting teacher well-being. The findings revealed significant challenges impacting teacher well-being, including the demands of individualised student needs, classroom dynamics, the role of school leadership, resource limitations, and the complexities of parental involvement. Teachers expressed a need for more relevant professional development programs and highlighted the importance of supportive leadership and adequate resources. Additionally, workload and the balance between professional and personal life emerged as critical factors influencing teacher well-being. This study underscores the importance of addressing the complex and interconnected factors that contribute to teacher well-being. Implications for educational practice include the need for supportive and communicative leadership, adequate professional development tailored to teachers’ needs, and the provision of sufficient resources to manage classroom diversity and demands. The findings advocate for systemic changes to foster a supportive educational environment that values and nurtures teacher well-being. Future research could explore effective strategies to support primary school teachers in their professional journeys.

Background: Teaching is a physically and mentally challenging profession that demands high emotional involvement, often leading to stress and anxiety. Understanding how teachers cope with these demands is essential for enhancing their well-being and effectiveness. Objectives: This study aimed to (1) investigate personal and school-based well-being initiatives that teachers use for maintaining their occupational well-being, and (2) develop a coping strategy model that enhances teachers’ occupational well-being. Methods: This study utilised a qualitative phenomenological approach to explore the coping strategies of Australian primary school teachers. Results: The twenty-one participants interviewed employed ten diverse coping strategies classified into five personal and five school-based well-being-enabling initiatives. The personal strategies included setting boundaries, exercise and physical health, social support and interactions, mental health and mindfulness, and work–life balance. The school-based initiatives comprised supportive leadership, colleague support, flexibility and autonomy, resource availability, and proactive approaches to address challenges. A novel SHIELD model incorporating Support, Health, Interaction, Empathy, Leadership, and Development strategies was formulated as a holistic coping strategy for enhancing teachers’ occupational well-being. Conclusions: The findings highlight the necessity of a holistic approach to teacher well-being, integrating both personal and institutional support systems. Schools can enhance teacher well-being by fostering a supportive and empathetic culture, providing necessary resources, and encouraging healthy lifestyles. The SHIELD model offers a comprehensive framework for supporting teachers and improving educational outcomes.

Abstract Background Our objective was to summarize, synthesize, and integrate the evidence evaluating the effectiveness of biophysical agents compared to other conservative treatments, for the management of carpal tunnel syndrome (CTS). Methods This was an overview of systematic reviews (SRs). We searched several online databases and obtained SRs relating to managing CTS using biophysical agents. Two independent researchers screened and appraised the quality of the SRs using the A MeaSurement Tool to Assess systematic Reviews-2 appraisal tool. We extracted information related to study characteristics as well as the effectiveness of biophysical agents for CTS, the effect sizes, and between-group significances. We categorized the information based on the type of biophysical agent. We also performed a citation mapping and calculated the corrected covered area index. Results We found 17 SRs addressing 12 different biophysical agents. The quality of the SRs was mainly critically low (n = 16) or low (n = 1). The evidence was inconclusive for the effectiveness of Low-level Laser therapy and favorable for the short-term efficacy of non-thermal ultrasound in improving symptom severity, function, pain, global rating of improvement, satisfaction with treatment, and other electrophysiological measures compared to manual therapy or placebo. Evidence was inconclusive for Extracorporeal Shockwave therapy, and favorable for the short-term effectiveness of Shortwave and Microwave Diathermy on pain and hand function. The corrected covered area index was lower than 35% indicating a low overlap of the SRs. Conclusions The findings were based on low-quality primary studies, with an unclear or high risk of bias, small sample sizes, and short follow-ups. Therefore, no recommendations can be made for the long-term effectiveness of any biophysical agents. High-quality evidence is needed to support evidence-based recommendations on the use of biophysical agents in the management of CTS. PROSPERO registration number CRD42022319002, registered on 17/04/2022

Abstract Background Patients who identify as 2SLGBTQIA + report negative experiences with physiotherapy. The objectives were to evaluate student attitudes, beliefs and perceptions related to 2SLGBTQIA + health education and working with individuals who identify as 2SLGBTQIA + in entry-level physiotherapy programs in Canada and to evaluate physiotherapy program inclusiveness towards 2SLGBTQIA + persons. Methods We completed a nationwide, cross-sectional survey of physiotherapy students from Canadian institutions. We recruited students via email and social media from August-December 2021. Frequency results are presented with percentages. Logistic regression models (odds ratios [OR], 95%CI) were used to evaluate associations between demographics and training hours with feelings of preparedness and perceived program 2SLGBTQIA + inclusiveness. Results We obtained 150 survey responses (mean age = 25 years [range = 20 to 37]) from students where 35 (23%) self-identified as 2SLGBTQIA + . While most students (≥ 95%) showed positive attitudes towards working with 2SLGBTQIA + patients, only 20 students (13%) believed their physiotherapy program provided sufficient knowledge about 2SLGBTQIA + health and inclusiveness. Students believed more 2SLGBTQIA + training is needed (n = 137; 92%), believed training should be mandatory (n = 141; 94%) and were willing to engage in more training (n = 138; 92%). Around half believed their physiotherapy program (n = 80, 54%) and clinical placements (n = 75, 50%) were 2SLGBTQIA + -inclusive and their program instructors (n = 69, 46%) and clinical instructors (n = 47, 31%) used sex/gender-inclusive language. Discrimination towards 2SLGBTQIA + persons was witnessed 56 times by students and most (n = 136; 91%) reported at least one barrier to confronting these behaviours. Older students (OR = 0.89 [0.79 to 0.99]), individuals assigned female at birth (OR = 0.34 [0.15 to 0.77]), and students self-identifying as 2SLGBTQIA + (OR = 0.38 [0.15 to 0.94]) were less likely to believe their program was 2SLGBTQIA + inclusive. Older students (OR = 0.85 [0.76 to 0.94]) and 2SLGBTQIA + students (OR = 0.42 [0.23 to 0.76]) felt the same about their placements. Students who reported > 10 h of 2SLGBTQIA + training were more likely to believe their program was inclusive (OR = 3.18 [1.66 to 6.09]). Conclusions Entry-level physiotherapy students in Canada show positive attitudes towards working with 2SLGBTQIA + persons but believe exposure to 2SLGBTQIA + health and inclusiveness is insufficient in their physiotherapy programs. This suggests greater attention dedicated to 2SLGBTQIA + health would be valued.

Abstract There is strong interest in developing predictive models to better understand individual heterogeneity and disease progression in Alzheimer's disease (AD). We have built upon previous longitudinal AD progression models, using a nonlinear, mixed‐effect modeling approach to predict Clinical Dementia Rating Scale – Sum of Boxes (CDR‐SB) progression. Data from the Alzheimer's Disease Neuroimaging Initiative (observational study) and placebo arms from four interventional trials (N = 1093) were used for model building. The placebo arms from two additional interventional trials (N = 805) were used for external model validation. In this modeling framework, CDR‐SB progression over the disease trajectory timescale was obtained for each participant by estimating disease onset time (DOT). Disease progression following DOT was described by both global progression rate (RATE) and individual progression rate (α). Baseline Mini‐Mental State Examination and CDR‐SB scores described the interindividual variabilities in DOT and α well. This model successfully predicted outcomes in the external validation datasets, supporting its suitability for prospective prediction and use in design of future trials. By predicting individual participants' disease progression trajectories using baseline characteristics and comparing these against the observed responses to new agents, the model can help assess treatment effects and support decision making for future trials.

Abstract Background Individuals who identify as 2SLGBTQIA+ report worse health outcomes than heterosexual/cisgender counterparts, in part due to poor experiences with healthcare professionals. This may stem from inadequate 2SLGBTQIA+ health and inclusiveness training in health professional student education. The purpose of the study was to evaluate knowledge, behaviours, and training related to 2SLGBTQIA+ health education and inclusiveness for entry-level physiotherapy students in Canada. Methods We conducted a nationwide, cross-sectional survey with physiotherapy students from accredited Canadian physiotherapy programs. We administered the survey through Qualtrics and recruited students through targeted recruitment emails and social media posts on Twitter and Instagram between August and December 2021. Survey responses are reported as frequencies (percentage). We also completed multivariable logistic regressions to evaluate associations among question responses related to working with 2SLGBTQIA+ individuals (i.e., communication, feeling prepared and assessment competency). Covariates included training hours (

Controlled study designs widely report that exercise improves the health of individuals living with breast cancer. Still, many individuals living with breast cancer are not active enough to experience the benefits of exercise. The Activating Cancer Communities through an Exercise Strategy for Survivors study was developed to reach more individuals living with cancer. This report describes the effects of a 12-week individualized exercise program that models a standard-of-care approach on body composition, physical fitness, and patient-reported outcomes in individuals living with breast cancer. Individuals living with breast cancer were recruited for the study and completed an exercise program twice weekly overseen by a Clinical Exercise Physiologist. A total of 43 participants completed the exercise intervention, and 36 withdrew from the study. All participants had significantly improved aerobic fitness, waist circumference, hip circumference, lower body endurance, physical activity behaviour, health-related quality of life, emotional status, and fatigue levels after completing the program. Flexibility, balance, and sleep scores did not change. The results from the 12-week individualized exercise program largely align with the results from more controlled study designs. These results support future initiatives integrating exercise therapy into the standard of care for individuals living with breast cancer.

Abstract Background Exercise Induced Bronchospasm(EIB) is not equivalent to asthma. As many as 20%of school aged children are estimated to have EIB. In Nigeria, there is still a dearth of information on EIB as a clinical entity. This study determined the presence of EIB(using pre and post-exercise percentage difference in peak expiratory flow rate(PEFR) and associated factors such as age, gender, social class and nutritional status in primary school children in Nnewi, Anambra state, South-East Nigeria. The study also grouped those with EIB into those with asthma(EIBA) and those without asthma(EIBWA). Methods This was a community based cross-sectional study involving 6–12 year olds. The PEFR was taken at rest and after a 6 min free running test on the school play-ground using a Peak Flow Meter. A diagnosis of EIB was made if there was a decline of ≥ 10%. Those who had EIB were grouped further based on the degree of decline in post-exercise PEFR (a decline ≥ 10%

Public significance statements/highlights Research on how to mitigate posttraumatic stress injuries (PTSIs) among public safety personnel (PSP) who are exposed to potentially psychologically traumatic events is limited. The PSP PTSI Study has been designed to develop, implement, and assess the impact of tools and skills designed to proactively mitigate PTSIs. PSP recruited into the study to receive the augmented training are assessed before and after training, and again 1 year later. The PSP PTSI Study results are expected to benefit the mental health of all participants and other PSP by informing strategies to mitigate PTSI.

The nutritional and sensory quality of different flour blends for baked products has been investigated. However, there is paucity of information on the quality of the conventional all-purpose flour which is expected to be chiefly of wheat origin and thus very expensive. Comparative analysis of the microbial, proximate and sensory quality of bread produced from all-purpose flour and blends of locally made flour was undertaken. Composite breads were produced from all-purpose flour (APF) 100%, wheat flour (WF) 100%, potato flour (PF) 100% and WF:PF blend (50%:50%). The microbial, proximate and sensory qualities, as well as the shelf life of the bread samples were determined. Data was analyzed using SPSS software. The bacterial and fungal counts were less than the maximum of 100 cfu/g recommended by the Standard Organization of Nigeria. The moisture and ash content of the PF bread was significantly higher (p < 0.05) than the rest of the flour blends. Among the flour blends, APF recorded the lowest fiber, ash and protein content. There was no significant difference (p > 0.05) in the mean sensory scores of APF bread and WF:PF bread with respect to taste and overall acceptability. PF and WF:PF bread had the highest shelf life of 8 and 7 days respectively. The nutritional composition of the bread produced from 100% WF and 50%:50% WF:PF blends were higher than that produced using the conventional APF. Thus, PF could be blended with WF to improve the nutritional quality and minimize cost of bread and other baked products.

Poor internet infrastructure limits the use of computer-based nursing process forms in rural areas. This study aimed to configure a computer‑based nursing process form to support nursing diagnosis and care evaluation in rural healthcare clinics in Africa. This study utilized a methodological design. The design process utilized a three-stage procedure involving planning, configuration, and testing. Seven faculty members volunteered to participate in the laboratory verification process. Each simulation session lasted 45 min and span from patient admission to exit. The experts independently scored the software functionality dichotomously as Not Suitable (score 0) and Suitable (score 1) for nursing practice. The agreement between the faculty volunteers was 0.857. The configuration of a readily available Microsoft Access computer application to support nursing diagnosis without internet service is possible. Health facilities in rural areas without internet connectivity should resort to such local configurations to maximize the benefits of electronic‑based documentation.

Abstract The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances. Trial registration: ClinicalTrials.gov, a service of the US National Institute of Health (NCT 03030859). Registered on 22 January 2017.

Ning et al. report expression of a neural lineage gene signature in enzalutamide-resistant prostate cancer cells and datasets from patients with neuroendocrine prostate cancer. One of these genes, ARHGEF2, is associated with poor overall and disease-free survival in patients with castration-resistant disease and supports cell viability in vitro.

Drug development for idiopathic pulmonary fibrosis (IPF) has been challenging due to poorly understood disease etiology, unpredictable disease progression, highly heterogeneous patient populations, and a lack of robust pharmacodynamic biomarkers. Moreover, because lung biopsy is invasive and dangerous, making the extent of fibrosis as a direct longitudinal measurement of IPF disease progression unfeasible, most clinical trials studying IPF can only assess progression of fibrosis indirectly through surrogate measures. This review discusses current state-of-art practices, identifies knowledge gaps, and brainstorms development opportunities for preclinical to clinical translation, clinical populations, pharmacodynamic endpoints, and dose optimization strategies. This article highlights clinical pharmacology perspectives in leveraging real-world data as well as modeling and simulation, special population considerations, and patient-centric approaches for designing future studies.

Abstract The COVID-19 pandemic is impacting mental health, with some populations bearing a greater burden. In this cross-sectional online study, we examined the personal and intersectional factors associated with increased symptoms of anxiety and depression following the COVID-19 pandemic. We assessed pre- and post-pandemic levels of anxiety and depressive symptoms using the Generalized Anxiety Disorder-2 (GAD-2) and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. The study included 1847 participants, with an age range of 18 to 79 years and representing 43 countries. Variables with significance (p

Abstract Background The brief Michigan Hand Questionnaire (brief MHQ) is a 12-item self-reported measure of hand function for patients with hand disorders which has been validated using Classical Test Theory. Rasch analysis can provide more detailed psychometric information. The purpose of this Rasch analysis is to assess the psychometric properties of the brief MHQ for patients with thumb osteoarthritis, and to make recommendations for improvements to the questionnaire if needed. Methods The Michigan Hand Questionnaire and demographic data were collected from 923 thumb osteoarthritis patients treated in specialized clinics for hand surgery and therapy in the Netherlands. Rasch analysis was performed on the 12 items of the brief MHQ using RUMM 2030 to assess the fit of the brief MHQ to the Rasch model. To determine fit, analysis of fit summary statistics, individual person fit and individual item fit were assessed. Threshold distributions were assessed to identify if any items required rescoring. The Person Separation Index was calculated to measure reliability of the questionnaire. Differential item functioning was assessed to identify item bias, and Principal Component Analysis was performed to identify unidimensionality and local dependence. Results The brief MHQ showed misfit (χ2 = 1312.5, p

Abstract Background Previous neck-specific patient-reported outcome measures (PROMs) have tended to measure both symptoms and disability. This multi-staged study developed and evaluated a neck-specific PROM focusing on functional disability. Methods This study integrated findings from systematic reviews on neck-specific outcome measures, patient interviews, qualitative studies on neck disability, and iterative item testing to develop a 10-item measure of neck-related disability (ND10). Content validity was assessed by classifying items using the International Classification of Functioning, Disability and Health (ICF) and perspective linking. Patients (n = 78) with neck pain completed cognitive interviews, exploring items of the Neck Disability Index (NDI) and ND10, and completed structured questions related to literacy and relevance. Test–retest reliability and internal consistency were evaluated using intraclass correlation coefficients, Bland Altman graphs, and Cronbach’s alpha. Concurrent convergent validity was evaluated by comparing the ND10 to the NDI, Single Assessment Numeric Evaluation (SANE), and Disabilities of the Arm, Shoulder and Hand (DASH). Known group validity was determined by comparing ND10 scores from patients, who rated their neck as more or less than 1/2 of “normal” on the SANE, using t-tests. Results The ND10 requires respondents to make rational judgements about their neck-related body function and disability. It has high internal consistency (0.94) and re-test reliability (0.87; SEM = 3.2/100; MDC = 7.5); and no re-test bias (mean re-test difference of 0.6). It followed expected correlation patterns, being highly correlated with related multi-item PROMs (r = 0.85–0.91), and moderately correlated to the single-item SANE. More patients agreed that the ND10 was easily readable than did so for the NDI (84% vs 68%; p

Background Emerging data suggest that patients with enzalutamide-treated prostate cancer with increased programmed death-ligand 1 (PD-L1) expression may benefit from anti-PD-L1 treatment. Unfortunately, the Phase III IMbassador250 clinical trial revealed that the combination of atezolizumab (a PD-L1 inhibitor) and enzalutamide failed to extend overall survival in patients with castration-resistant prostate cancer (CRPC). However, the mechanisms underlying treatment failure remain unknown.Methods Human CRPC C4-2B cells and murine Myc-CaP cells were chronically exposed to increasing concentrations of enzalutamide and the cells resistant to enzalutamide were referred to as C4-2B MDVR and Myc-CaP MDVR, respectively. The mechanisms of action in drug-resistant prostate cancer cells were determined using RNA sequencing analyses, RNA interference, real-time PCR, western blotting, and co-culturing technologies. Myc-CaP and Myc-CaP MDVR tumors were established in syngeneic FVB mice, and tumor-infiltrating leukocytes were isolated after enzalutamide treatment. The stained immune cells were determined by flow cytometry, and the data were analyzed using FlowJo.Results Immune-related signaling pathways (interferon alpha/gamma response, inflammatory response, and cell chemotaxis) were suppressed in human enzalutamide-resistant prostate cancer cells. PD-L1 was overexpressed and negatively regulated by androgen receptor signaling in resistant cells and patient with CRPC cohorts. Enzalutamide treatment decreased CD8+ T-cell numbers but increased monocytic myeloid-derived suppressor cell (M-MDSC) populations and PD-L1 expression within murine Myc-CaP tumors. Similarly, chemotaxis and immune response-regulating signaling pathways were suppressed, and PD-L1 expression was also increased using enzalutamide-resistant Myc-CaP MDVR cells. Notably, MDSC populations were significantly increased in Myc-CaP MDVR orthotopic tumors compared with those in Myc-CaP parental tumors. Co-culturing bone marrow cells with Myc-CaP MDVR cells significantly promoted MDSC differentiation and shifted towards M2 macrophage skewing.Conclusions Our study suggests that immunosuppressive signaling can be promoted directly by enzalutamide-resistant prostate cancer cells and may be a potential means by which the efficacy of immune checkpoint inhibitors in enzalutamide-resistant prostate cancer is diminished.

Ubiquitin proteasome activity is suppressed in enzalutamide resistant prostate cancer cells, and the heat shock protein 70/STIP1 homology and U-box-containing protein 1 (HSP70/STUB1) machinery are involved in androgen receptor (AR) and AR variant protein stabilization. Targeting HSP70 could be a viable strategy to overcome resistance to androgen receptor signaling inhibitor (ARSI) in advanced prostate cancer. Here, we showed that a novel HSP70 allosteric inhibitor, JG98, significantly suppressed drug-resistant C4–2B MDVR and CWR22Rv1 cell growth, and enhanced enzalutamide treatment. JG98 also suppressed cell growth in conditional reprogramed cell cultures (CRCs) and organoids derived from advanced prostate cancer patient samples. Mechanistically, JG98 degraded AR/AR-V7 expression in resistant cells and promoted STUB1 nuclear translocation to bind AR-V7. Knockdown of the E3 ligase STUB1 significantly diminished the anticancer effects and partially restored AR-V7 inhibitory effects of JG98. JG231, a more potent analog developed from JG98, effectively suppressed the growth of the drug-resistant prostate cancer cells, CRCs, and organoids. Notably, the combination of JG231 and enzalutamide synergistically inhibited AR/AR-V7 expression and suppressed CWR22Rv1 xenograft tumor growth. Inhibition of HSP70 using novel small-molecule inhibitors coordinates with STUB1 to regulate AR/AR-V7 protein stabilization and ARSI resistance.

Background As the field of pain evaluation grows, newer and more targeted tools are being published for patient-centric evaluation of specific aspects of the pain experience. The Fremantle Back Awareness Questionnaire (FreBAQ) is intended to capture alterations in bodily awareness or perception. To date only region-specific (back, neck, shoulder, knee) versions have been published. Objectives The purpose of our study was to report on the properties of a new region-generic version of the FreBAQ, the FreBAQ-general. Structural validity, internal consistency, and convergent validity against external criteria were evaluated in a sample of Canadian military veterans with chronic pain, with results compared against those published for the region-specific FreBAQ versions. Methods Eligible participants were those that had prior military service, were at least 18 years of age and self-identified as having chronic pain. We used a split-sample approach to Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) on independent random samples. Factor structure, internal consistency, and associations with external criteria were used to compare against prior versions. Results 328 respondents (74% of consented) completed at least 7 of the 9 FreBAQ-general questions. EFA and CFA on two independent samples offered support for both 6- and 7-item versions. Comparisons against the external criteria (pain severity, interference, catastrophizing) indicated no statistical superiority of one over the other, so in the interest of parsimony the 6-item FreBAQ-general was endorsed. Conclusions The Fremantle Body Awareness Questionnaire (FreBAQ-general) showed psychometric properties very much in alignment with those previously reported for the region-specific versions, and sound factorial validity accomplished with fewer items (6 vs. 9). We believe this version can be implemented in practice for those seeking a shorter scale without the need to have multiple region-specific versions on hand, though suggest that those seeking direct comparability with previously published work will still wish to use the original versions.

BackgroundOccupational therapists (OTs) and physiotherapists (PTs) are expected to provide evidence-based services to individuals living with disabilities. Despite the emphasis on evidence-based practice (EBP) by professional entry-level programs and professional bodies, little is known about their EBP competencies upon entry to practice and over time or what factors impact EBP use. The aim of the study was to measure and understand how EBP evolves over the first three years after graduation among Canadian OTs and PTs, and how individual and organizational factors impact the continuous use of EBP.MethodsA longitudinal, mixed methods sequential explanatory study. We administered a survey questionnaire measuring six EBP constructs (knowledge, attitudes, confidence, resources, use of EBP and evidence-based activities) annually, followed by focus group discussions with a subset of survey participants. We performed group-based trajectory modeling to identify trajectories of EBP over time, and a content analysis of qualitative data guided by the Theoretical Domains Framework.ResultsOf 1700 graduates in 2016-2017, 257 (response rate = 15%) responded at baseline (T0) (i.e., at graduation), and 83 (retention rate = 32%), 75 (retention rate = 29%), and 74 (retention rate = 29%) participated at time point 1 (T1: one year into practice), time point 2 (T2: two years into practice, and time point 3 (T3: three years into practice) respectively. Group-based trajectory modeling showed four unique group trajectories for the use of EBP. Over 64% of participants (two trajectories) showed a decline in the use of EBP over time. Fifteen practitioners (7 OTs and 8 PTs) participated in the focus group discussions. Personal and peer experiences, client needs and expectations, and availability of resources were perceived to influence EBP the most.ConclusionsThough a decline in EBP may be concerning, it is unclear if this decline is clinically meaningful and whether professional expertise can offset such declines. Stakeholder-concerted efforts towards the common goal of promoting EBP in education, practice and policy are needed.

Abstract Alectinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK‐positive non‐small cell lung cancer. Population pharmacokinetic (PK) models were developed for alectinib and its major active metabolite M4 using phase I/II PK data in crizotinib‐failed patients (N = 138). The PK profiles were best described by two separate models with similar structure for both entities: open one‐compartment models with sequential zero/first‐order input and first‐order elimination rate. Body weight with fixed allometric scaling factor on clearance and volume of both entities was the only significant covariate. Bayesian feedback analyses of the PK data collected from Japanese and global treatment‐naïve patients in phase III studies (N = 334) confirmed the body weight effect. Landmark Cox proportional hazards analyses of progression‐free survival in treatment‐naïve patients identified the average molar concentrations of both entities alectinib and M4 during the first 6 weeks of treatment as a significant covariate, with an optimal response achieved for concentrations above 1040 nmol/L. With 600 mg twice daily (b.i.d.), 92% of global patients are above this threshold concentration, compared with only 43% of patients with 300 mg b.i.d. In Japan, where the body weight distribution is lower, the approved 300 mg b.i.d. dose brings about 70% of Japanese patients above this threshold. Logistic regression analyses found no significant relationship between the combined alectinib–M4 molar concentration and first occurrence of adverse events. These pharmacometric results were used to expedite and facilitate regulatory approvals of 600 mg b.i.d. for first‐line ALK‐positive NSCLC in the United States and European Union in 2017 and in China in 2018.

Abstract Background Understanding the profiles of different upper extremity fractures, particularly those presenting as a 1st incident can inform prevention and management strategies. The purpose of this population-level study was to describe first incident fractures of the upper extremity in terms of fracture characteristics and demographics. Methods Cases with a first adult upper extremity (UE) fracture from the years 2013 to 2017 were extracted from administrative data in Ontario. Fracture locations (ICD-10 codes) and associated characteristics (open/closed, associated hospitalization within 1-day, associated nerve, or tendon injury) were described by fracture type, age category and sex. Standardized mean differences of at least 10% (clinical significance) and statistical significance (p

IntroductionCognitive function is known to be associated with physical function, where greater walking capacity has been shown to have moderate to strong correlations with global cognitive function and other various domains of cognition in older adults with and without chronic conditions. Biological sex may moderate the relationship between cognitive and physical function, but whether sex differences exist in this association has not been examined in an aging population. The purpose of this study was to examine the associations between global cognitive function (Montreal Cognitive Assessment; MoCA), walking capacity (6-Minute Walk Test distance; 6 MWT) and sex in an aging population with broad ranges of cognitive and physical function.MethodsParticipants were assessed for global cognitive function (MoCA) and walking capacity (6 MWT). Multivariable regression analyses were performed to examine the interaction of sex in the association between MoCA and 6 MWT. First, we presented the unadjusted model (Model 1), then the model adjusted for age, history of stroke, and height (Model 2). To determine if there were sex-based differences in the association between global cognitive function and walking capacity, we included sex and an interaction term between sex*6 MWT distance in Models 3 and 4.ResultsTwenty-three females and 36 males were included in the multivariable regression analyses, respectively. Our sample represented broad ranges of cognitive and physical function levels, where MoCA scores ranged from 13 to 30, and 6 MWT distances from 203 to 750 m. 6 MWT distance was associated with MoCA in models unadjusted (R2 = 0.17; F(1,56) = 11.4; p

Objective:. To describe opioid use for a first upper extremity fracture in a cohort of patients who did not have recent opioid use. Design:. Descriptive epidemiological study. Setting:. Emergency Department, Hospital. Patients/Participants:. We obtained health administrative data records of adults presenting with a first adult upper extremity fracture from 2013 to 2017 in Ontario, Canada. We excluded patients with previous fractures, opioid prescription in the past 6 months or hospitalization >5 days after the fracture. Intervention:. Opioid prescription. Main Outcome Measurements:. We identified the proportion of patients filling an opioid prescription within 7 days of fracture. We described this based on different upper extremity fractures (ICD-10), Demographics (age, sex, rurality), comorbidity (Charlson Comorbidity Index, Rheumatoid arthritis, Diabetes), season of injury, and social marginalization (Ontario Marginalization Index-a data algorithm that combines a wide range of demographic indicators into 4 distinct dimensions of marginalization). We considered statistical differences (P< .01) that reached a standardized mean difference of 10% as being clinically important (standardized mean difference [SMD] ≥ 0.1). Results:. From 220,440 patients with a first upper extremity fracture (50% female, mean age 50), opioids were used by 34% of cases overall (32% in males, 36% in females, P< .001, SMD ≥ 0.1). Use varied by body region, with those with multiple or proximal fractures having the highest use: multiple shoulder 64%, multiple regions 62%, shoulder 62%, elbow 38%, wrist 31%, and hand 21%; and was higher in patients who had a nerve/tendon injury or hospitalization (P< .01, SMD ≥ 0.1). Social marginalization, comorbidity, and season of injury had clinically insignificant effects on opioid use. Conclusions:. More than one-third of patients who are recent-non-users will fill an opioid prescription within 7 days of a first upper extremity fracture, with usage highly influenced by fracture characteristics. Level of Evidence: Level II

The purpose of this study was to understand the experiences and factors that contribute to how refugee families support their children's educational success. Through their lived experiences, refugees bring various perspectives and insights into their families' pursuits in supporting their children. More attention needs to be paid to understanding how refugee backgrounds and experiences influence the way these families help their children educationally. Although some studies have examined how refugee families utilize their wealth of knowledge and navigational capital to support their young children's learning in a new educational system, there is growing need to contribute more into this literature. Semi-structured interviews with eleven refugee parents revealed that their previous educational experiences, linguistic strengths and challenges, and the presence of a support system influenced their families' navigation of new educational experiences. Results indicated that refugee parents rely on social, familial, linguistic, and navigational capital to persevere and support their children during the transition to the United States (U.S.) school system. This study adds to this literature and aims to offer suggestions to educators and professionals working with refugee families.

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is a significant neurodevelopment disorder among children and adolescents, with 5 % prevalence. Bone fractures account for 25 % of accidents and injuries among all children and adolescents. Considering the characteristics of inattention, hyperactivity, and impulsivity in children with ADHD, it is critical to examine bone fractures among these children. The objective of our meta-analysis was to determine the prevalence of bone fractures among children and adolescents with ADHD. Methods We completed a systematic review and meta-analysis using an electronic search of the following databases: CINAHL, EMBASE, PsycINFO, PubMed, and Scopus. The search terms used were: “attention deficit hyperactivity disorder OR attention deficit disorder” and “bone fracture*.” We included studies examining patients 18 years or younger who were diagnosed with ADHD and tracked (prospectively or retrospectively) for five or more years. Effect size (es), using a random effects model, was calculated. We registered the review protocol with PROSPERO (CRD42019119527). Results From 445 records retrieved, 31 full text articles were reviewed and 5 articles met inclusion criteria for meta-analysis. The summary es revealed the prevalence of bone fractures among children and adolescents with ADHD to be 4.83 % (95 % CI: 3.07–6.58 %). The location of bone fractures, using a subset of data, showed a distribution of 69.62 %, 22.85 %, and 7.53 % in the upper limbs, lower limbs, and other anatomical regions, respectively. Another subset of studies revealed a 2.55-fold increase in the prevalence of fractures among the children with ADHD compared to their counterparts. Conclusions Awareness of these findings is critical to physicians, parents, and policy makers to create safe environments and provide supports in order to optimize the health and safety of children and adolescents with ADHD.

This essay discusses the EdD Program design and qualitative research course sequence at Drexel University, a private, non-profit institution. This large program admits up to 140 EdD students annually with approximately 100 attending fully online and 40 attending hybrid offerings at the main campus and at a satellite program in Washington, DC. The essay features a qualitative course observation activity designed by Janesick (2011) to be used face-to-face and details how the activity has been adapted for virtual delivery at East Coast University. As a literature review revealed a paucity of published works on teaching observation qualitatively, the authors seek to contribute to the knowledge base with particular emphasis on faculty teaching in an online program. Based upon the East Coast University faculty’s use of this observation activity, students develop increased understanding of the roles of perception and perspective in qualitative observation.

Abstract Background Carpal tunnel syndrome (CTS) is the most common entrapment mononeuropathy of the upper extremity. The previous systematic review of the diagnostic tests for CTS was outdated. The objective of this study was to compile and appraise the evidence on the accuracy of sensory and motor tests used for the diagnosis of CTS. Methods MEDLINE, CINAHL, and Embase databases were searched on January 20, 2020. Studies assessing at least one diagnostic accuracy property of the sensory or motor tests for CTS diagnosis were selected by two independent reviewers. Diagnostic test accuracy extension of the PRISMA guidelines was followed. Risk of bias and applicability concerns were rated using QUADAS-2 tool. Any reported diagnostic accuracy property was summarized. Study characteristics and any information on the accuracy of the sensory and motor tests for CTS diagnosis were extracted. Results We included sixteen clinical studies, assessing thirteen different sensory or motor tests. The most sensitive test for CTS diagnosis was the Semmes-Weinstein monofilament test (with 3.22 in any radial digit as the normal threshold) with sensitivity from 0.49 to 0.96. The tests with the highest specificity (Sp) were palmar grip strength (Sp = 0.94), pinch grip strength (Sp from 0.78 to 0.95), thenar atrophy (Sp from 0.96 to 1.00), and two-point discrimination (Sp from 0.81 to 0.98). Conclusions The evidence was inconclusive on which sensory or motor test for CTS diagnosis had the highest diagnostic accuracy. The results suggest that clinicians should not use a single sensory or motor test when deciding on CTS diagnosis. Trial registration PROSPERO CRD42018109031 , on 20 December 2018.

Background: While sex- or gender-based differences in pain expression have been documented, exploration of traditionally genderized traits on pain has been hampered by the lack of strong measurement tools. This study evaluated the structural validity of a 16-item ?Gender personality traits? subscale of a recently developed Gender, Pain and Expectations Scale (GPES). Methods: Data were drawn from an existing database of 248 participants (65.7% female). Maximum likelihood-based confirmatory factor analysis was carried out while considering the conceptual meaningfulness of subscales to evaluate the factor structure identified by these traits. Construct validity was explored using a priori hypotheses regarding anticipated mean differences in scores between biological male and female participants. Results: A meaningful factor structure could not be defined with all 16 items. Through conceptual and statistical triangulation a three-factor structure informed by 10 items was identified that satisfied acceptable fit criteria. The factors were termed ?Emotive,? ?Relationship-Oriented,? and ?Goal-Oriented.? Evidence of construct validity was supported through significant sex-based differences (p???0.02) in the expected directions for all three subscales. Conclusions: Review of the items in the three factors led the researchers to endorse a move away from naming these ?masculine? and ?feminine,? rather focusing on the nature of the traits: ?Relationship-oriented,? ?Emotive,? and ?Goal-oriented.? Implications for researchers conducting sex/gender-based pain research are discussed. Clinical Trial Registration number: NCT02711085.

Abstract Introduction PAIN+ and PubMed are two electronic databases with two different mechanisms of evidence retrieval. PubMed is used to “Pull” evidence where clinicians can enter search terms to find answers while PAIN+ is a newly developed evidence repository where along with “Pull” service there is a “Push” service that alerts users about new research and the associated quality ratings, based on the individual preferences for content and altering criteria. Purpose The primary purpose of the study was to compare yield and usefulness of PubMed and PAIN+ in retrieving evidence to address clinical research questions on pain management. The secondary purpose of the study was to identify what search terms and methods were used by clinicians to target pain research. Study design Two-phase double blinded randomized crossover trial. Methods Clinicians (n = 76) who were exposed to PAIN+ for at least 1 year took part in this study. Participants were required to search for evidence 2 clinical question scenarios independently. The first clinical question was provided to all participants and thus, was multi-disciplinary. Participants were randomly assigned to search for evidence on their clinical question using either PAIN+ or PubMed through the electronic interface. Upon completion of the search with one search engine, they were crossed over to the other search engine. A similar process was done for a second scenario that was discipline-specific. The yield was calculated using number of retrieved articles presented to participants and usefulness was evaluated using a series of Likert scale questions embedded in the testing. Results Multidisciplinary scenario: Overall, the participants had an overall one-page yield of 715 articles for PAIN+ and 1135 articles for PubMed. The topmost article retrieved by PAIN+ was rated as more useful (p = 0.001). While, the topmost article retrieved by PubMed was rated as consistent with current clinical practice (p = 0.02). PubMed (48%) was preferred over PAIN+ (39%) to perform multidisciplinary search (p = 0.02). Discipline specific scenario: The participants had an overall one-page yield of 1046 articles for PAIN+ and 1398 articles for PubMed. The topmost article retrieved by PAIN+ was rated as more useful (p = 0.001) and consistent with current clinical practice (p = 0.02) than the articles retrieved by PubMed. PAIN+ (52%) was preferred over PubMed (29%) to perform discipline specific search. Conclusion Clinicians from different disciplines find both PAIN+ and PubMed useful for retrieving research studies to address clinical questions about pain management. Greater preferences and perceived usefulness of the top 3 retrieved papers was observed for PAIN+, but other dimensions of usefulness did not consistently favor either search engine. Trial registration Registered with ClinicalTrials.gov Identifier: NCT01348802 , Date: May 5, 2011.

Abstract Background Removal of immobilization is a critical phase of distal radius fracture (DRF) rehabilitation, typically occurring by 2 months post injury. This study examined the extent to which pain at rest (PAR), movement evoked pain (MEP), or the ratio between those (MEPR) assessed at 2-months after DRF predicts the occurrence of chronic pain or disability at 6- and 12-months after the injury. Methods This secondary analysis of a prospective cohort study was done at the Hand and Upper Limb Centre (HULC), London, Ontario, Canada. A total of 229 patients with DRF (159 (69.4%) women) were included. Scores for the pain and function subscales of the Patient-Rated Wrist Evaluation (PRWE) were extracted for 2, 6 and 12 months after DRF. Logistic as well as nonlinear quartile regression examined whether PAR and MEP predicted the severity of chronic pain and disability at 6- and 12-months after DRF. Receiver Operating Characteristics Curve were plotted, where area under the curve (AUC) examined the accuracy of the PAR and MEP scores in classifying those who experienced chronic pain and disability. Results Scores of ≥3 (AUC of 0.77) for PAR or ≥ 6 (AUC of 0.78) for MEP at 2 months after DRF predicted moderate to severe wrist pain at 6-months, whereas scores of ≥7 (AUC of 0.79) for MEP at 2-months predicted ongoing wrist disability at 6-months after the injury. The MEPR of 2 ≤ or ≥ 8 at 2-months was associated with adverse pain at 6-months and functional outcomes at 6- and 12-months (R-square = 0.7 and 0.04 respectively), but prediction accuracy was very poor (AUC ≤ 0.50). Conclusion Chronic wrist-related pain at 6-months can be predicted by either elevated PAR ≥ 3/10) or MEP (≥ 6/10) reported at 2-months after the injury, while disability experienced at 6-months after DRF is best predicted by MEP (≥7/10) reported at 2-months. The ratio of these two pain indicators increases assessment complexity and reduces classification accuracy.

Treatment of Mycobacterium tuberculosis (Mtb) infections is particularly arduous. One challenge to effectively treating tuberculosis is that drug efficacy in vivo often fails to match drug efficacy in vitro. This is due to multiple reasons, including inadequate drug concentrations reaching Mtb at the site of infection and physiological changes of Mtb in response to host derived stresses that render the bacteria more tolerant to antibiotics. To more effectively and efficiently treat tuberculosis, it is necessary to better understand the physiologic state of Mtb that promotes drug tolerance in the host. Towards this end, multiple studies have converged on bacterial central carbon metabolism as a critical contributor to Mtb drug tolerance. In this review, we present the evidence that changes in central carbon metabolism can promote drug tolerance, depending on the environment surrounding Mtb. We posit that these metabolic pathways could be potential drug targets to stymie the development of drug tolerance and enhance the efficacy of current antimicrobial therapy.

BackgroundTreatment of psychosis typically focuses on medication, but some of these medications can have unintended side effects, exercise has global health benefits, with minimal side effects. The purpose of this systematic review and meta-analysis is to investigate the effectiveness and safety of exercise and physical activity on psychotic symptoms, in people with psychosis when compared to usual care, in a hospital setting.MethodsA systematic electronic search of the literature was performed in June 2022, in PubMed, Scopus, and PsychINFO with no date restrictions. We included randomized trials (RCTs) with patients with psychosis that received an exercise intervention within a hospital setting. The primary outcome of interest was Positive and Negative Symptom Severity Scale (PANSS) overall score. Secondary outcomes were adverse or serious adverse events.ResultsA total of 24 trials were included in this systematic review, with 9 included in the meta-analysis, including 1,426 participants. Aerobic had more pronounced effects when compared to usual care in PANSS positive (−0.23, 95% CI −0.53 to 0.07), negative (−0.38, 95% CI −0.65 to −0.10), general (−0.42, 95% CI −0.71 to −0.13) and overall scores (−0.25, 95% CI −0.52 to 0.03). Yoga when compared to usual care had no difference in PANSS subscale and overall scores. We found no difference on relapsing of psychiatric symptoms or somatic hospitalization when we compared aerobic or yoga to usual care (Risk Ratio, 1.12 95% CI 0.44–2.81).ConclusionAerobic activity as an exercise modality in a hospital setting can be effective in decreasing negative and general psychosis symptom severity scores compared to usual care, however, it was uncertain if the effects were clinically important. More trials are needed to confirm the clinically benefit of aerobic exercise.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021224997].

Background: Worldwide, the COVID-19 pandemic has had a rapid disruption on work, social activities and family life. Pre-pandemic norms suggested that women spend more time in unpaid work roles and with childcare, while men spend more time in paid work roles. This study aims to understand: 1) the distribution of unpaid work roles within households, and 2) if there are certain factors that explain the unpaid work roles within a household during the pandemic. Methods: This study used a cross-sectional survey of people across the globe, during the pandemic. The survey, administered through a virtual platform of Qualtrics, consisted of the following sections: (a) consent, (b) location and job description (c) marital status and household numbers (d) age, sex, and gender (e) unpaid work roles and family responsibilities. Descriptive statistics and percentages were reported for all the data regarding the study variables. A multivariable regression model was used to understand which factors may explain the changes in unpaid work roles recalling before and during the pandemic Results: This survey was completed by 1847 participants. The mean age was 30 years old (standard deviation of 13.3). The majority of participants identified themselves as women (76.0%) and single (62.1%). The multivariable linear regression indicated that marital status (single, common-law, married, divorced), higher number of household members (1-8,12), older age, higher number of dependent children, and gender (female) were positive and significant predictors of baseline changes in unpaid work role scores, explaining 50% of the variance (R2 = 0.50). Discussion: All households experienced a significant increase in the amount of unpaid work roles during the pandemic. However, older women who were in a relationship and experienced additional household members such as dependent children or sick older adults, were faced with more changes in unpaid work roles during COVID-19, than other individuals.

Abstract In this paper, fixed point results for a newly introduced Geraghty quasi-contraction type mappings are proved in more general metric spaces called T-orbitally complete dislocated quasi-metric spaces. Geraghty quasi-contraction type mappings generalize, among others, Ciric’s quasi-contraction mappings and other Geraghty quasi-contractive type mappings in the literature. Fixed point results are obtained without imposing a continuity condition on the mapping, thereby further generalizing some other related work in the literature. An example is given to show the validity of results obtained.

Abstract Background Accurate diagnosis of carpal tunnel syndrome (CTS) is essential for directing appropriate treatment; and for making decisions about work injury claims. The Kamath and Stothard Questionnaire (KSQ) is a self-reported tool used for the diagnosis of CTS. Comprehensibility and comprehensiveness of this questionnaire are critical to diagnostic performance and need to be established. The purpose of the study was to describe how potential respondents, clinicians, and measurement researchers interpret KSQ questions in order to identify and resolve potential sources of misclassification. Methods Hand therapists, measurement researchers, participants with CTS, and a control group were interviewed using cognitive interviewing techniques (talk aloud, semi-structured interview probes) in Hamilton, Canada. All interviews were recorded and transcribed verbatim. A directed content analysis was done to analyze the interviews using a previously established framework. Findings Eighteen participants were interviewed. Areas, where questions were unclear to some participants, were recorded and categorized into five themes: Clarity and Comprehension (52%), Relativeness (38%), Inadequate Response Definition (4%), Perspective Modifiers (4%), and Reference Point (2%). Respondents also identified several symptoms of CTS that are not covered by the KSQ that might be of diagnostic value, e.g., weakness and dropping items. Conclusion The content validity of the current iteration of the KSQ was not established. The problematic questions identified in the study have been reported to have low specificity and negative predictive values in a previous quantitative study. The content validity issues identified may explain the poor performance. Recommendations were made to modify the wording of the KSQ and the potential addition of three new questions. Future studies should determine whether the modified questionnaire can provide better diagnostic accuracy and psychometric properties. The results of this study may assist in ruling in or out CTS diagnosis to a wide variety of target audience, such as hand specialists, physical and occupational therapists, as well as family doctors.

Abstract Background The Revised Short McGill Pain Questionnaire Version-2 (SF-MPQ-2) is a multidimensional outcome measure designed to capture, evaluate and discriminate pain from neuropathic and non-neuropathic sources. A recent systematic review found insufficient psychometric data with respect to musculoskeletal (MSK) health conditions. This study aimed to describe the reproducibility (test–retest reliability and agreement) and internal consistency of the SF-MPQ-2 for use among patients with musculoskeletal shoulder pain. Methods Eligible patients with shoulder pain from MSK sources completed the SF-MPQ-2: at baseline (n = 195), and a subset did so again after 3–7 days (n = 48), if their response to the Global Rating of Change (GROC) scale remained unchanged. Cronbach alpha (α) and intraclass correlation coefficient (ICC2,1), and their related 95% CI were calculated. Standard error of measurement (SEM), group and individual minimal detectable change (MDC90), and Bland–Altman (BA) plots were used to assess agreement. Results Cronbach α ranged from 0.83 to 0.95 suggesting very satisfactory internal consistency across the SF-MPQ-2 domains. Excellent ICC2,1 scores were found in support of the total scale (0.95) and continuous subscale (0.92) scores; the remaining subscales displayed good ICC2,1 scores (0.78–0.88). Bland–Altman analysis revealed no systematic bias between the test and retest scores (mean difference = 0.13–0.19). While the best agreement coefficients were seen on the total scale (SEM = 0.5; MDC90individual = 1.2 and MDC90group = 0.3), they were acceptable for the SF-MPQ-2 subscales (SEM: range 0.7–1; MDC90individual: range 1.7–2.3; MDC90group: range 0.4–0.5). Conclusion Good reproducibility supports the SF-MPQ-2 domains for augmented or independent use in MSK-related shoulder pain assessment, with the total scale displaying the best reproducibility coefficients. Additional research on the validity and responsiveness of the SF-MPQ-2 is still required in this population.

Abstract Background Recovery trajectories support early identification of delayed recovery and can inform personalized management or phenotyping of risk profiles in patients. The objective of this study was to investigate the trajectories in pain severity and functional interference following non-catastrophic musculoskeletal (MSK) trauma in an international, mixed injury sample. Methods A prospective longitudinal cohort (n = 241) was formed from patients identified within four weeks of trauma, from attendance at emergency or urgent care centres located in London, ON, Canada, or Chicago, IL, USA. Pain interference was measured via the Brief Pain Inventory (London cohort) or the Neck Disability Index (Chicago cohort). Pain severity was captured in both cohorts using the numeric pain rating scale. Growth mixture modeling and RM repeated measures ANOVA approaches identified distinct trajectories of recovery within pain interference and pain severity data. Results For pain interference, the three trajectories were labeled accordingly: Class 1 = Rapid recovery (lowest intercept, full or near full recovery by 3 months, 32.0% of the sample); Class 2 = Delayed recovery (higher intercept, recovery by 12 months, 26.7% of the sample); Class 3 = Minimal or no recovery (higher intercept, persistently high interference scores at 12 months, 41.3% of the sample). For pain severity, the two trajectories were labeled: Class 1 = Rapid recovery (lower intercept, recovery by 3 months, 81.3% of the sample); and Class 2 = Minimal or no recovery (higher intercept, flat curve, 18.7% of the sample). The “Minimal or No Recovery” trajectory could be predicted by female sex and axial (vs. peripheral) region of trauma with 74.3% accuracy across the 3 classes for the % Interference outcome. For the Pain Severity outcome, only region (axial trauma, 81.3% accuracy) predicted the “Minimal or No Recovery” trajectory. Conclusions These results suggest that three meaningful recovery trajectories can be identified in an international, mixed-injury sample when pain interference is the outcome, and two recovery trajectories emerge when pain severity is the outcome. Females in the sample or people who suffered axial injuries (head, neck, or low back) were more likely to be classed in poor outcome trajectories. Trial registration National Institutes of Health - clinicaltrials.gov ( NCT02711085 ; Retrospectively registered Mar 17, 2016).

Abstract Background The Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist/Hand Evaluation (PRWHE) and the Thumb Disability Exam (TDX) are patient-reported outcome measures (PROM) designed to assess pain and hand function in patients with hand arthritis, hand pain and disability, or thumb pathology respectively. This study evaluated the content validity of AUSCAN, PRWHE and TDX in people with hand arthritis. Methods This study enrolled participants with hand arthritis to rate the items of all 3 PROM in terms of relevance and clarity. The Content Validity Index (CVI) was computed for each item in each scale (I-CVI) as well as for the overall scale (S-CVI). Kappa was used to determine the inter-rater agreement among the raters. Results Overall, 64 individuals with hand arthritis (27% with OA, 67% with rheumatoid arthritis and 6% with psoriatic arthritis) participated in the study. The I-CVI for all items and all scales were very high (I-CVI > 0.76) and the modified Kappa agreement among the raters demonstrated excellent agreement (k > 0.76). The S-CVI for all PROMs was very high for relevance (AUSCAN = 0.92, 95% CI 0.90 to 0.94; PRWHE = 0.85, 95% CI 0.82 to 0.88 and TDX = 0.87, 95% CI 0.85 to 0.89) and for clarity (AUSCAN = 0.99, 95% CI 0.98 to 1.00; PRWHE = 0.95, 95% CI 0.93 to 0.97 and TDX = 0.91, 95% CI 0.89 to 0.94), respectively. Conclusions This study demonstrated very high content validity indices for the AUSCAN, PRWHE and TDX; with strong consensus across raters. This augments prior studies demonstrating appropriate statistical measurement properties, to provide confidence that all three measures assess important patient concepts of pain and disability.