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Novel therapies with the ability to delay disease progression are a gap in the care of people living with Parkinson disease (PD) today. Clinical outcomes assessments (COAs) that are sensitive to the earliest clinical changes in PD are deemed essential for a successful therapeutic development. To understand the current landscape of COAs use in clinical trials in PD and define priorities for future research in the field, a stakeholder roundtable meeting was held in November 2022. The current paper 1) proposes the collaborative development of patient-centric COAs that can adequately document the effectiveness of disease modification therapies in PD based on key priorities identified during this initial meeting, 2) summarizes the progress made in the subsequent 12 months, and 3) presents the deliverables expected in the near future. Key priorities include 1) the development of a consensus conceptual model of early PD experiences, 2) the adaptation of existing patient-reported outcomes (PROs), 3) the investigation of the role of observer-reported outcomes in addition to 4) enabling diversity in PD research and advocacy, 5) fostering data sharing, and 6) reaching consensus on a biological staging system for PD to drive the development of appropriate PROs for biologically defined populations.

Purpose: We report a patient with pseudoxanthoma elasticum (PXE) with angioid streaks near a scleral buckle site. Observations: A 46-year-old male with PXE presented for evaluation of blurry vision and was found to have classic PXE findings in both eyes and angioid streaks adjacent to the site of a scleral buckle in his left eye. He underwent multimodal imaging, genetic testing, and intravitreal aflibercept in the right eye. Conclusions and importance: Bruch's membrane is known to be fragile in PXE, and patients are often counseled about the heightened risk of playing contact sports. This report raises the question of whether tension from a scleral buckle in the setting of a calcified and brittle BM may increase the likelihood of angioid streaks near the buckle site. In the setting of retinal detachment, it may be worthwhile to carefully weigh the pros and cons of vitrectomy versus buckle for PXE patients.

Background: Alopecia areata (AA) is a disease of hair loss with multiple treatment options. Physicians play an important role in guiding patients during the decision-making process. Objective: Assess physicians’ values and attitudes when helping patients choose an AA treatment. Methods: Semi-structured qualitative interviews were conducted with dermatologists of varying practice type and location. Each interview was coded independently twice using inductive thematic analysis. Interrater reliability and code frequencies were determined. Results: Fourteen participants were interviewed. Interrater reliability was κ = 0.85 to 0.97. Dermatologists wanted patients to consider various treatment factors (ie, efficacy, safety, convenience of use, accessibility) and also assessed patients’ AA clinical severity and personality traits. Participants often encountered various barriers to effective communication with patients, which may be mitigated by shared decision-making. Shared decision-making tools were perceived to potentially improve patient care and communication, although physicians expressed concern about lack of individualization, limitations of time, and the appropriateness of information. Conclusion: AA treatment decision-making is a complex process that often utilizes the expertise of a dermatologist, during which shared decision-making tools may be of value to both patients and physicians.

Background: Alopecia areata (AA) is a disease of hair loss in which patients may benefit from comprehensive understanding of AA’s disease process and therapeutic options during treatment decision-making. Objective: Determine factors influencing patients’ AA treatment decision-making. Methods: Qualitative interviews were conducted using semi-structured interview guides. Interviews were coded using inductive thematic analysis. Results: Twenty-one participants with AA were interviewed. Coding interrater reliability was κ = 0.87-0.91, indicating strong-almost perfect agreement. Participants faced multiple barriers, including lack of access to health care (n = 10, 47.6%) and lack of transparency about their condition and treatment options (n = 9, 42.9%). Information about AA was sought from primarily the internet (n = 15, 71.4%) and physician recommendation (n = 15, 71.4%). When choosing AA treatments, patients often considered treatment efficacy (n = 21, 100%), safety (n = 21, 100%), and convenience of use (n = 20, 95.2%). Limitations: Referral and regional biases may be present and limit generalizability. Conclusions: Patients with AA face various challenges including medical uncertainty and lack of information. Patients need trustworthy and accessible sources of information regarding their treatment that also take into consideration their preferences and values.

Objectives Diabetes and obesity care for ethnocultural migrant communities is hampered by a lack of understanding of premigration and postmigration stressors and their impact on social and clinical determinants of health within unique cultural contexts. We sought to understand the role of cultural brokering in primary healthcare to enhance chronic disease care for ethnocultural migrant communities.Design and setting Participatory qualitative descriptive–interpretive study with the Multicultural Health Brokers Cooperative in a Canadian urban centre. Cultural brokers are linguistic and culturally diverse community health workers who bridge cultural distance, support relationships and understanding between providers and patients to improve care outcomes. From 2019 to 2021, we met 16 times to collaborate on research design, analysis and writing.Participants Purposive sampling of 10 cultural brokers representing eight different major local ethnocultural communities. Data include 10 in-depth interviews and two observation sessions analysed deductively and inductively to collaboratively construct themes.Results Findings highlight six thematic domains illustrating how cultural brokering enhances holistic primary healthcare. Through family-based relational supports and a trauma-informed care, brokering supports provider–patient interactions. This is achieved through brokers’ (1) embeddedness in community relationships with deep knowledge of culture and life realities of ethnocultural immigrant populations; (2) holistic, contextual knowledge; (3) navigation and support of access to care; (4) cultural interpretation to support health assessment and communication; (5) addressing psychosocial needs and social determinants of health and (6) dedication to follow-up and at-home management practices.Conclusions Cultural brokers can be key partners in the primary care team to support people living with diabetes and/or obesity from ethnocultural immigrant and refugee communities. They enhance and support provider–patient relationships and communication and respond to the complex psychosocial and economic barriers to improve health. Consideration of how to better enable and expand cultural brokering to support chronic disease management in primary care is warranted.

Objectives: To present the best and most up-to-date evidence on associations between built environment (BE) attributes and overall and specific domains of physical activity (PA) (i.e., leisure, transport, walking, and cycling) in older adults (≥60 years).Methods: An umbrella review was undertaken to compile evidence from systematic reviews using the Joanna Briggs Institute methodology. A comprehensive search (updated 16 August 2022), inclusion/exclusion of articles via title/abstract and full-text reviews, data extraction, and critical appraisal were completed. Only reviews with a good critical appraisal score were included.Results: Across three included systematic reviews, each BE attribute category was positively associated with ≥1 PA outcome. A larger number of significant associations with BE attributes were reported for transport walking (13/26), total walking (10/25), and total PA (9/26), compared to leisure walking (4/34) and transport cycling (3/12). Fewer associations have been examined for leisure cycling (1/2).Conclusion: Although the causality of findings cannot be concluded due to most primary studies being cross-sectional, these best and most up-to-date findings can guide necessary future longitudinal and experimental studies for the (re)design of age-friendly communities.

Abstract Background Providing contextually appropriate care and interventions for people with diabetes and/or obesity in vulnerable situations within ethnocultural newcomer communities presents significant challenges. Because of the added complexities of the refugee and immigrant context, a deep understanding of their realities is needed. Syndemic theory sheds light on the synergistic nature of stressors, chronic diseases and environmental impact on immigrant and refugee populations living in vulnerable conditions. We used a syndemic perspective to examine how the migrant ethnocultural context impacts the experience of living with obesity and/or diabetes, to identify challenges in their experience with healthcare. Methods This qualitative participatory research collaborated with community health workers from the Multicultural Health Brokers Cooperative of Edmonton, Alberta. Study participants were people living with diabetes and/or obesity from diverse ethnocultural communities in Edmonton and the brokers who work with these communities. We conducted 3 focus groups (two groups of 8 and one of 13 participants) and 22 individual interviews (13 community members and 9 brokers). The majority of participants had type 2 diabetes and 4 had obesity. We conducted a thematic analysis to explore the interactions of people’s living conditions with experiences of: 1) diabetes and obesity; and 2) healthcare and resources for well-being. Results The synergistic effects of pre- and post-immigration stressors, including lack of social network cultural distance, and poverty present an added burden to migrants’ lived experience of diabetes/obesity. People need to first navigate the challenges of immigration and settling into a new environment in order to have capacity to manage their chronic diseases. Diabetes and obesity care is enhanced by the supportive role of the brokers, and healthcare providers who have an awareness of and consideration for the contextual influences on patients’ health. Conclusions The syndemic effects of the socio-cultural context of migrants creates an additional burden for managing the complexities of diabetes and obesity that can result in inadequate healthcare and worsened health outcomes. Consequently, care for people with diabetes and/or obesity from vulnerable immigrant and refugee situations should include a holistic approach where there is an awareness of and consideration for their context.

Abstract Background In collaboration with building developers, the Housing for Health team is contributing to the design of community-based congregate living facilities to support healthy living in older adults. There may also be opportunities to improve the surrounding neighbourhoods by collaborating with the municipalities where the developments are located. We will evaluate whether one or more of these comprehensive interventions lead to changes in the perceived, microscale, and macroscale neighbourhood-built environment (BE) and amenities, and impacts on the physical activity (PA), healthy eating, and social connections of residents. In parallel, we will gather qualitative data to provide a more in-depth understanding of how the BE may facilitate or hinder resident’s healthy living outcomes. Methods This project employs a quasi-experimental pre-post design with at least one or more intervention and control sites. The quantitative BE evaluation will include pre- and post-intervention assessments of neighbourhood macroscale (e.g., layout of communities) and microscale (e.g., street details and characteristics) changes using Geographical Information Systems (GIS) and Microscale Audit Pedestrian Streetscapes (MAPS) audits, respectively. The quantitative resident evaluation will include self-report (i.e., surveys) and objective assessments (i.e., accelerometers, Global Positioning System [GPS]) of residents at baseline (3-6-months pre-move-in) and follow-up (3-6-months and 9-12-months post-move-in if possible). The qualitative resident-environment component will involve in-depth semi-structured interviews post-intervention with building residents, family members, and stakeholders involved in the design/development and/or operation of the intervention site(s). Participant observations will be completed in the building and neighbourhood environments of the intervention site(s). Discussion Findings will provide evidence on whether and how comprehensive changes to the BE and amenities of at least one congregate living facility and the surrounding neighbourhood can impact PA, healthy eating, and social connections of older adults. Successful intervention elements will be scaled up in future work. We will disseminate findings to a broad audience including the scientific community via peer-reviewed publications, conference presentations, and discussion panels; and the private, public, and not-for-profit sectors via reports, public presentations, and/or communications via our partners and their networks. Trial registration Protocol ID: 1819-HQ-000051. ClinicalTrials.gov ID: NCT05031273. Registered 29 June 2021 with ClinicalTrials.gov.

Abstract Background In response to supply shortages caused by the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or “masks”), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under “reuse” and “extended use” policies. However, the reusability of N95 masks is limited by degradation of fit. Possible substitutes, such as KN95 masks meeting Chinese standards, frequently fail fit testing even when new. The purpose of this study was to develop an inexpensive frame for damaged and poorly fitting masks using readily available materials and 3D printing. Results An iterative design process yielded a mask frame consisting of two 3D printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n = 45; average BMI = 25.4), underwent qualitative fit testing with and without mask frames wearing one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48 to 94 % (depending on mask model). For individuals who underwent testing using respirators with broken or defective straps, 80–100 % (average 85 %) passed fit testing with mask frames. Among individuals who failed fit testing with a KN95, ~ 50 % passed testing by using a frame. Conclusions Our study suggests that mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Use of frames made it possible for ~ 73 % of the test population to achieve a good fit based on qualitative and quantitative testing criteria, approaching the 85–90 % success rate observed for intact N95 masks. Frames therefore represent a simple and inexpensive way of expanding access to PPE and extending their useful life. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, fit testing with user-specific masks and PanFab frames is required.

Abstract Background To assess the performance of imaging features, including radiomics texture features, in predicting histopathologic tumor grade, AJCC stage, and outcomes [time to recurrence (TTR) and overall survival (OS)] in patients with intrahepatic cholangiocarcinoma (ICC). Methods Seventy-three patients (26 M/47F, mean age 63y) with pre-operative imaging (CT, n = 37; MRI, n = 21; CT and MRI, n = 15] within 6 months of resection were included in this retrospective study. Qualitative imaging traits were assessed by 2 observers. A 3rd observer measured tumor apparent diffusion coefficient (ADC), enhancement ratios (ERs), and Haralick texture features. Blood biomarkers and imaging features were compared with histopathology (tumor grade and AJCC stage) and outcomes (TTR and OS) using log-rank, generalized Wilcoxon, Cox proportional hazards regression, and Fisher exact tests. Results Median TTR and OS were 53.9 and 79.7 months. ICC recurred in 64.4% (47/73) of patients and 46.6% (34/73) of patients died. There was fair accuracy for some qualitative imaging features in the prediction of worse tumor grade (maximal AUC of 0.68 for biliary obstruction on MRI, p = 0.032, observer 1) and higher AJCC stage (maximal AUC of 0.73 for biliary obstruction on CT, p = 0.002, observer 2; and AUC of 0.73 for vascular involvement on MRI, p = 0.01, observer 2). Cox proportional hazards regression analysis showed that CA 19–9 [hazard ratio (HR) 2.44/95% confidence interval (CI) 1.31–4.57/p = 0.005)] and tumor size on imaging (HR 1.13/95% CI 1.04–1.22/p = 0.003) were significant predictors of TTR, while CA 19–9 (HR 4.08/95% CI 1.75–9.56, p = 0.001) and presence of metastatic lymph nodes at histopathology (HR 2.86/95% CI 1.35–6.07/p = 0.006) were significant predictors of OS. On multivariable analysis, satellite lesions on CT (HR 2.79/95%CI 1.01–7.15/p = 0.032, observer 2), vascular involvement on MRI (HR 0.10/95% CI 0.01–0.85/p = 0.032, observer 1), and texture feature MRI variance (HR 0.55/95% CI 0.31–0.97, p = 0.040) predicted TTR once adjusted for the independent predictors CA 19–9 and tumor size on imaging. Several qualitative and quantitative features demonstrated associations with TTR, OS, and AJCC stage at univariable analysis (range: HR 0.35–19; p 0.088). Conclusions There was reasonable accuracy in predicting tumor grade and higher AJCC stage in ICC utilizing certain qualitative and quantitative imaging traits. Serum CA 19–9, tumor size, presence of metastatic lymph nodes, and qualitative imaging traits of satellite lesions and vascular involvement are predictors of patient outcomes, along with a promising predictive ability of certain quantitative texture features.

Intrinsically disordered regions (IDRs) are protein regions that are unable to fold into stable tertiary structures, enabling their involvement in key signaling and regulatory functions via dynamic interactions with diverse binding partners. An understanding of IDRs and their association with biological function may help elucidate the pathogenesis of inherited retinal diseases (IRDs). The main focus of this work was to investigate the degree of disorder in 14 proteins implicated in IRDs and their relationship with the number of pathogenic missense variants. Metapredict, an accurate, high-performance predictor that reproduces consensus disorder scores, was used to probe the degree of disorder as a function of the amino acid sequence. Publicly available data on gnomAD and ClinVar was used to analyze the number of pathogenic missense variants. We show that proteins with an over-representation of missense variation exhibit a high degree of disorder, and proteins with a high amount of disorder tolerate a higher degree of missense variation. These proteins also exhibit a lower amount of pathogenic missense variants with respect to total missense variants. These data suggest that protein function may be related to the overall level of disorder and could be used to refine variant interpretation in IRDs.

Stair climbing is a readily available form of vigorous-intensity physical activity. Evidence indicates that placing stair prompt signs at points-of-decision (e.g. near elevators and stairways) is an inexpensive, effective strategy for increasing physical activity through stair use.This article aims to share the experience of the New York City Department of Health and Mental Hygiene (NYC DOHMH) in the outreach and implementation of a population-scale stair prompt initiative, including lessons learned from process evaluations, with other public health authorities conducting a similar program. Between May 2008 and August 2012, NYC DOHMH implemented a stair prompt initiative as one strategy in a comprehensive program to increase physical activity and healthy eating through physical improvements to NYC's buildings, streets and neighborhoods, particularly targeting facilities in underserved and low-income neighborhoods. Program evaluation was conducted using program planning documents to examine the process, and data from NYC information line call center, outreach tracking database, and site and phone audits to examine process outcomes.The initiative successfully distributed more than 30,000 stair prompts to building owners/managers of over 1000 buildings. Keys to success included multi-sector partnerships between NYC's Health Department and non-health government agencies and organizations (such as architecture and real estate organizations), a designated outreach coordinator, and outreach strategies targeting building owners/managers owning/managing multiple buildings and buildings serving underserved and at risk populations.A NYC citywide initiative successfully distributed stair prompts to the wider community to promote population-level health impacts; lessons learned may assist other jurisdictions considering similar initiatives to increase physical activity. Keywords: Obesity, Physical activity, Urban health, Program evaluation, City planning, Chronic disease, Prevention

Background. Budget impact analyses (BIAs) are an essential part of a comprehensive economic assessment of a health care intervention and are increasingly required by reimbursement authorities as part of a listing or reimbursement submission. Objectives: The objective of this report was to present updated guidance on methods for those undertaking such analyses or for those reviewing the results of such analyses. This update was needed, in part, because of developments in BIA methods as well as a growing interest, particularly in emerging markets, in matters related to affordability and population health impacts of health care interventions. Methods. The Task Force was approved by the International Society for Pharmacoeconomics and Outcomes Research Health Sciences Policy Council and appointed by its Board of Directors. Members were experienced developers or users of BIAs; worked in academia and industry and as advisors to governments; and came from several countries in North America and South America, Oceania, Asia, and Europe. The Task Force solicited comments on the drafts from a core group of external reviewers and, more broadly, from the membership of the International Society for Pharmacoeconomics and Outcomes Research. Results. The Task Force recommends that the design of a BIA for a new health care intervention should take into account relevant features of the health care system, possible access restrictions, the anticipated uptake of the new intervention, and the use and effects of the current and new interventions. The key elements of a BIA include estimating the size of the eligible population, the current mix of treatments and the expected mix after the introduction of the new intervention, the cost of the treatment mixes, and any changes expected in condition-related costs. Where possible, the BIA calculations should be performed by using a simple cost calculator approach because of its ease of use for budget holders. In instances, however, in which the changes in eligible population size, disease severity mix, or treatment patterns cannot be credibly captured by using the cost calculator approach, a cohort or patient-level condition-specific model may be used to estimate the budget impact of the new intervention, accounting appropriately for those entering and leaving the eligible population over time. In either case, the BIA should use data that reflect values specific to a particular decision maker’s population. Sensitivity analysis should be of alternative scenarios chosen from the perspective of the decision maker. The validation of the model should include at least face validity with decision makers and verification of the calculations. Data sources for the BIA should include published clinical trial estimates and comparator studies for the efficacy and safety of the current and new interventions as well as the decision maker’s own population for the other parameter estimates, where possible. Other data sources include the use of published data, well-recognized local or national statistical information, and, in special circumstances, expert opinion. Reporting of the BIA should provide detailed information about the input parameter values and calculations at a level of detail that would allow another modeler to replicate the analysis. The outcomes of the BIA should be presented in the format of interest to health care decision makers. In a computer program, options should be provided for different categories of costs to be included or excluded from the analysis. Conclusions. We recommend a framework for the BIA, provide guidance on the acquisition and use of data, and offer a common reporting format that will promote standardization and transparency. Adherence to these good research practice principles would not necessarily supersede jurisdiction-specific BIA guidelines but may support and enhance local recommendations or serve as a starting point for payers wishing to promulgate methodology guidelines.

Introduction: A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems. Methods: A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems. Results: A significant improvement was observed in the inter‐observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise. Conclusion: This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter‐observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders. [ABSTRACT FROM AUTHOR]

Purpose: To correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. Patients and methods: In this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0 T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. Results: 79 HCCs were assessed (mean size 2.5 cm). D, PF and ADC were significantly higher in HCC vs. liver (p 0.95, p

Glioblastoma (GBM) is the most devastating brain tumor, with associated poor prognosis. Despite advances in surgery and chemoradiation, the survival of afflicted patients has not improved significantly in the past three decades. Immunotherapy has been heralded as a promising approach in treatment of various cancers; however, the immune privileged environment of the brain usually curbs the optimal expected response in central nervous system malignancies. In addition, GBM cells create an immunosuppressive microenvironment and employ various methods to escape immune surveillance. The purpose of this review is to highlight the strategies by which GBM cells evade the host immune system. Further understanding of these strategies and the biology of this tumor will pave the way for developing novel immunotherapeutic approaches for treatment of GBM.

ObjectiveTo illuminate the key components of multi-sector reform to address the obesogenic environment in New York City during the administration of Mayor Michael Bloomberg from 2002 to 2013, we conducted a case study consisting of interviews with and a critical analysis of the experiences of leading decision makers and implementers.MethodKey informant interviews (N=41) conducted in 2014 were recorded, transcribed, coded and thematically analyzed. Participants included officials from the Health Department and other New York City Government agencies, academics, civil society members and private sector executives. ResultsParticipants described Mayor Bloomberg as a data-driven politician who wanted to improve the lives of New Yorkers. He appointed talented Commissioners and encouraged them and their staff to be bold, innovative and collaborative. Multiple programs spanning multiple sectors, with varied approaches and targets were supported. This study found that much of the work relied on loose coalitions across City Government, with single agencies responsible for their own agendas, some with health co-benefits. Many policies were implemented through non-legislative mechanisms such as executive orders and the Health Code. Despite support from academic and some civil society groups, strong lobbying from industry and an unfavorable media led to some reforms being modified, legally challenged or blocked completely, particularly food environment modifiers. In contrast, reforms of the physical environment were described as highly consultative across and outside government and resulted in slower but more sustained reform.ConclusionsThe Bloomberg administration was a window of opportunity with the imprimatur of the executive to progress a long-term, multi-faceted obesity prevention strategy which has successfully reversed childhood trends. Through the involvement of external researchers and the extensive use of empirical data from a wide range of participants, this study offers a distinctive insight into the ways in which this was achieved. Whilst some of the aspects of the reforms in New York City are unique to that setting at that time, there are important lessons that are transferable to other urban settings. These include: strong and consistent leadership; a commitment to innovative approaches and cross-sectoral collaboration and; and a context to support and encourage this approach.