A Functional Difficulty and Functional Pain Instrument for Hip and Knee Osteoarthritis

The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field

Development of Items Designed to Evaluate Activity Performance and Participation in Children and Adolescents with Spinal Cord Injury

Background/Objective. Outcomes-based data, whether used clinically or for research, are difficult to collect in the pediatric spinal cord injury (SCI) population due to a lack of appropriate assessment measures. The purpose of this paper is twofold: to describe the process by which two item pools were developed to evaluate activity performance and participation among children with SCI and to introduce the resultant items specific to pediatric SCI. Methods. The process of item development, including construct development, review of related assessment tools, chart review, item writing and refinement using focus groups, cognitive interviews, and further refinement, was used to create the items pools for activity and participation for children and adolescents with SCI. Results. A total of 347 items were written for the activity performance construct and 61 items were written for the participation construct. Several domains were established within each construct and items were written for both child and parent respondents. Conclusion. The process of detailed item development is the first step in the process of developing an outcomes instrument for children and adolescents with SCI to assess activity performance and participation. The items are representative of pediatric SCI because they address areas specific to children and adolescents with SCI such as wheeled mobility, upper extremity function with adaptive equipment, role performance, and socialization. After testing these items in calibration studies, we will determine if these items can be developed into effective computer-adaptive testing applications

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery in Youth with Cerebral Palsy.

BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP. METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed Up & Go test (TUG) before and after elective orthopaedic surgery in a convenience sample of 255 children, four to twenty years of age, who had CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III. Standardized response means (SRMs) and 95% confidence intervals (CIs) were calculated for all measures at six, twelve, and twenty-four months following surgery. RESULTS: SRM estimates for the LE CP-CAT were significantly greater than the SRM estimates for the PODCI Transfer/Mobility domain at twelve months, the PODCI Sports/Physical Functioning domain at twelve months, and the TUG at twelve and twenty-four months. When the results for the children at GMFCS levels I, II, and III were grouped together, the improvements in function detected by the LE CP-CAT at twelve and twenty-four months were found to be greater than the changes detected by the PODCI Transfer/Mobility and Sports/Physical Functioning scales. The LE CP-CAT outperformed the PODCI scales for GMFCS levels I and III at both of these follow-up intervals; none of the scales performed well for patients with GMFCS level II. CONCLUSIONS: The results of this study showed that the LE CP-CAT displayed superior sensitivity to change than the PODCI and TUG scales after musculoskeletal surgery in children with CP

A Functional Difficulty and Functional Pain Instrument for Hip and Knee Osteoarthritis

Introduction: The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field. Methods: We conducted an extensive literature review, focus groups, and cognitive testing to guide the construction of an item bank consisting of 125 functional activities commonly affected by hip and knee osteoarthritis. We recruited a convenience sample of 328 adults with confirmed hip and/or knee osteoarthritis. Subjects reported their degree of functional difficulty and functional pain in performing each activity in the item bank and completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Confirmatory factor analyses were conducted to assess scale uni-dimensionality, and IRT methods were used to calibrate the items and examine the fit of the data. We assessed the performance of OA-FUNCTION-CATs of different lengths relative to the full item bank and WOMAC using CAT simulation analyses. Results: Confirmatory factor analyses revealed distinct functional difficulty and functional pain domains. Descriptive statistics for scores from 5-, 10-, and 15-item CATs were similar to those for the full item bank. The 10-item OA-FUNCTION-CAT scales demonstrated a high degree of accuracy compared with the item bank (r = 0.96 and 0.89, respectively). Compared to the WOMAC, both scales covered a broader score range and demonstrated a higher degree of precision at the ceiling and reliability across the range of scores. Conclusions: The OA-FUNCTION-CAT provided superior reliability throughout the score range and improved breadth and precision at the ceiling compared with the WOMAC. Further research is needed to assess whether these improvements carry over into superior ability to measure change

Confidentiality considerations for use of social-spatial data on the social determinants of health: Sexual and reproductive health case study

Understanding whether and how the places where people live, work, and play are associated with health behaviors and health is essential to understanding the social determinants of health. However, social-spatial data which link a person and their attributes to a geographic location (e.g., home address) create potential confidentiality risks. Despite the growing body of literature describing approaches to protect individual confidentiality when utilizing social-spatial data, peer-reviewed manuscripts displaying identifiable individual point data or quasi-identifiers (attributes associated with the individual or disease that narrow identification) in maps persist, suggesting that knowledge has not been effectively translated into public health research practices. Using sexual and reproductive health as a case study, we explore the extent to which maps appearing in recent peer-reviewed publications risk participant confidentiality. Our scoping review of sexual and reproductive health literature published and indexed in PubMed between January 1, 2013 and September 1, 2015 identified 45 manuscripts displaying participant data in maps as points or small-population geographic units, spanning 26 journals and representing studies conducted in 20 countries. Notably, 56% (13/23) of publications presenting point data on maps either did not describe approaches used to mask data or masked data inadequately. Furthermore, 18% (4/22) of publications displaying data using small-population geographic units included at least two quasi-identifiers. These findings highlight the need for heightened education for researchers, reviewers, and editorial teams. We aim to provide readers with a primer on key confidentiality considerations when utilizing linked social-spatial data for visualizing results. Given the widespread availability of place-based data and the ease of creating maps, it is critically important to raise awareness on when social-spatial data constitute protected health information, best practices for masking geographic identifiers, and methods of balancing disclosure risk and scientific utility. We conclude with recommendations to support the preservation of confidentiality when disseminating results

Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease

SummaryThe SLX1-SLX4 endonuclease required for homologous recombination and DNA repair in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease subunit SLX1 is activated by association with a scaffolding protein SLX4. At the present time, little is known about the structure of SLX1-SLX4 or its mechanism of action. Here, we report the structural insights into SLX1-SLX4 by detailing the crystal structure of Candida glabrata (Cg) Slx1 alone and in combination with the C-terminal region of Slx4. The structure of Slx1 reveals a compact arrangement of the GIY-YIG nuclease and RING domains, which is reinforced by a long α helix. Slx1 forms a stable homodimer that blocks its active site. Slx1-Slx4 interaction is mutually exclusive with Slx1 homodimerization, suggesting a mechanism for Slx1 activation by Slx4

Lower-Third Standardized Letters of Evaluation in Emergency Medicine: Does Gender Make a Difference in Match Outcome?

Objective The purpose of this study was to determine whether gender influences the likelihood of receiving a lowerthird global assessment (GA) on the standardized letter of evaluation (SLOE) submitted as part of the emergency medicine (EM) application process as well as the impact of gender on ultimate match outcomes for applicants receiving a lower-third GA ranking. Our hypothesis was that female applicants with a lowerthird GA ranking have a higher risk of not matching. Methods We conducted a retrospective cohort study evaluating U.S.-based allopathic applicants to a single EM residency program in the Mid-Atlantic region during the 2017-2018 and 2018-2019 match cycles. GA SLOE rankings and gender for all applicants were extracted and compared to the National Resident Matching Program (NRMP) data for each applicant on match outcome. Comparative analyses were conducted between gender and SLOE GA rankings in order to obtain an odds ratio (OR) of gender and match outcomes. Results A total of 2,017 SLOEs were reviewed from 798 applicants in the 2018 and 2019 EM match cycles. Overall, 716 (90%) applicants successfully matched in EM, with 82 (10%) applicants failing to match into EM; 277 students had at least one lower-third GA ranking. For all applicants, having at least one lower-third GA ranking was associated with a significant risk of not matching (OR: 0.20; 95% CI: 0.12-0.34). Of the 277 students with at least one lower-third GA ranking, 85 (31%) were female and 192 (69%) were male. Of the female applicants with a lower-third GA ranking, 15 (18%) failed to match in EM, and 39 (20%) of the males failed to match in EM. For applicants with a lower-third GA ranking, female gender alone was not associated with a significantly increased risk of not matching (OR: 1.18; 95% CI: 0.61-2.21). Conclusions Female applicants receive a lower-third GA ranking less frequently than their male counterparts. One or more lower-third rankings on the GA significantly reduced an applicant’s chances of matching into an EM program. For those with a lower-third GA ranking, female gender alone does not significantly increase the risk of not matching into EM

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Minimising disability and falls in older people through a post-hospital exercise program: a protocol for a randomised controlled trial and economic evaluation

Background: Disability and falls are particularly common among older people who have recently been hospitalised. There is evidence that disability severity and fall rates can be reduced by well-designed exercise interventions. However, the potential for exercise to have these benefits in older people who have spent time in hospital has not been established. This randomised controlled trial will investigate the effects of a home-based exercise program on disability and falls among people who have had recent hospital stays. The cost-effectiveness of the exercise program from the health and community service provider's perspective will be established. In addition, predictors for adherence with the exercise program will be determined. Methods and design: Three hundred and fifty older people who have recently had hospital stays will participate in the study. Participants will have no medical contraindications to exercise and will be cognitively and physically able to complete the assessments and exercise program. The primary outcome measures will be mobility-related disability (measured with 12 monthly questionnaires and the Short Physical Performance Battery) and falls (measured with 12 monthly calendars). Secondary measures will be tests of risk of falling, additional measures of mobility, strength and flexibility, quality of life, fall-related self efficacy, health-system and community-service contact, assistance from others, difficulty with daily tasks, physical activity levels and adverse events. After discharge from hospital and completion of all hospital-related treatments, participants will be randomly allocated to an intervention group or usual-care control group. For the intervention group, an individualised home exercise program will be established and progressed during ten home visits from a physiotherapist. Participants will be asked to exercise at home up to 6 times per week for the 12-month study period. Discussion: The study will determine the impact of this exercise intervention on mobility-related disability and falls in older people who have been in hospital as well as cost-effectiveness and predictors of adherence to the program. Thus, the results will have direct implications for the design and implementation of interventions for this high-risk group of older people.7 page(s