Paving the path for implementation of clinical genomic sequencing globally: Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse. In this commentary, members of the Global Economics and Evaluation of Clinical Genomics Sequencing Working Group (GEECS) describe the global landscape of CGS in the context of health economics and policy and propose evidence-based solutions to address existing and future barriers to CGS implementation. The topics discussed are reflected as two overarching themes: (1) system readiness for CGS and (2) evidence, assessments, and approval processes. These themes highlight the need for health economics, public health, and infrastructure and operational considerations; a robust patient- and family-centered evidence base on CGS outcomes; and a comprehensive, collaborative, interdisciplinary approach.

Pleasurable and problematic receptive anal intercourse and diseases of the colon, rectum and anus.

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable.

Measuring the Impact of Patient Engagement in Health Research: An Exploratory Study Using Multiple Survey Tools.

Background: Studies report various ways in which patients are involved in research design and conduct. Limited studies explore the influence of patient engagement (PE) at each research stage in qualitative research from the perspectives of all stakeholders. Methods: We established two small research groups, a Patient Researcher-Led Group and an Academic Researcher-Led Group. We recruited patient research partners (PRP; n = 5), researchers (n = 5), and clinicians (n = 4) to design and conduct qualitative research aimed at identifying candidate attributes related to patient preferences for tapering biologic treatments in inflammatory bowel disease. We administered surveys before starting, two months into, and post-project work. The surveys contained items from three PE evaluation tools. We assessed the two groups regarding the influence and impact each stakeholder had during the different research stages. Results: PRPs had a moderate or a great deal of influence on the critical research activities across the research stages. They indicated moderate/very/extremely meaningful engagement and agreed/strongly agreed impact of PE. PRPs helped operationalize the research question; design the study and approach; develop study materials; recruit participants; and collect and interpret the data. Conclusion: The three tools together provide deeper insight into the influence of PE at each research stage. Lessons learnt from this study suggest that PE can impact many aspects of research including the design, process, and approach in the context of qualitative research, increasing the patient-centeredness of the study. More comprehensive validated tools are required that work with a more diverse subject pool and in other contexts.

Policies in Canada fail to address disparities in access to person-centred osteoarthritis care: a content analysis.

BACKGROUND: Women are disproportionately impacted by osteoarthritis (OA) but less likely than men to access OA care, particularly racialized women. One way to reduce inequities is through policies that can influence healthcare services. We examined how OA-relevant policies in Canada address equitable, person-centred OA care for women. METHODS: We used content analysis to extract data from English-language OA-relevant documents referred to as policies or other synonymous terms published in 2000 or later identified by searching governmental and other web sites. We used summary statistics to describe policy characteristics, person-centred care using McCormack's six-domain framework, and mention of OA prevalence, barriers and strategies to improve equitable access to OA care among women. RESULTS: We included 14 policies developed from 2004 to 2021. None comprehensively addressed all person-centred care domains, and few addressed individual domains: enable self-management (50%), share decisions (43%), exchange information (29%), respond to emotions (14%), foster a healing relationship (0%) and manage uncertainty (0%). Even when mentioned, content offered little guidance for how to achieve person-centred OA care. Few policies acknowledged greater prevalence of OA among women (36%), older (29%) or Indigenous persons (29%) and those of lower socioeconomic status (14%); or barriers to OA care among those of lower socioeconomic status (50%), in rural areas (43%), of older age (37%) or ethno-cultural groups (21%), or women (21%). Four (29%) policies recommended strategies for improving access to OA care at the patient (self-management education material in different languages and tailored to cultural norms), clinician (healthcare professional education) and system level (evaluate OA service equity, engage lay health leaders in delivering self-management programs, and offer self-management programs in a variety of formats). Five (36%) policies recommended research on how to improve OA care for equity-seeking groups. CONCLUSIONS: Canadian OA-relevant policies lack guidance to overcome disparities in access to person-centred OA care for equity-seeking groups including women. This study identified several ways to strengthen policies. Ongoing research must identify the needs and preferences of equity-seeking persons with OA, and evaluate the impact of various models of service delivery, knowledge needed to influence OA-relevant policy.

Studying How Patient Engagement Influences Research: A Mixed Methods Study.

BACKGROUND: There is evidence supporting the value of patient engagement (PE) in research to patients and researchers. However, there is little research evidence on the influence of PE throughout the entire research process as well as the outcomes of research engagement. The purpose of our study is to add to this evidence. METHODS: We used a convergent mixed method design to guide the integration of our survey data and observation data to assess the influence of PE in two groups, comprising patient research partners (PRPs), clinicians, and researchers. A PRP led one group (PLG) and an academic researcher led the other (RLG). Both groups were given the same research question and tasked to design and conduct an inflammatory bowel disease (IBD)-related patient preference study. We administered validated evaluation tools at three points and observed PE in the two groups conducting the IBD study. RESULTS: PRPs in both groups took on many operational roles and influenced all stages of the IBD-related qualitative study: launch, design, implementation, and knowledge translation. PRPs provided more clarity on the study design, target population, inclusion-exclusion criteria, data collection approach, and the results. PRPs helped operationalize the project question, develop study material and data collection instruments, collect data, and present the data in a relevant and understandable manner to the patient community. The synergy of collaborative partnership resulted in two projects that were patient-centered, meaningful, understandable, legitimate, rigorous, adaptable, feasible, ethical and transparent, timely, and sustainable. CONCLUSION: Collaborative and meaningful engagement of patients and researchers can influence all stages of qualitative research including design and approach, and outputs.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Background: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT. Objectives: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns. Design: This is a cross-sectional survey study. Methods: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns. Results: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT. Conclusion: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.

Background and aims: Fecal microbiota transplantation (FMT) is a promising new treatment for active ulcerative colitis. Questions remain around the benefits and risks of FMT treatment for patients with ulcerative colitis. Understanding how patients weigh the treatment features and how treatment features influence their decisions may improve shared decision-making and contribute to patient-centered care, which is especially important for novel treatments like FMT.Using an experimentally designed survey, we aimed to:1. Elicit patient preferences for features of active ulcerative colitis treatments, specifically FMT and biologics; and,2. Identify patient characteristics associated with different preference patterns. Results: We found that younger patients with more severe disease are more likely to try FMT for the treatment of active ulcerative colitis. Oral capsules/pills are the preferred mode of treatment administration. Conclusions: These findings can enhance patient-centered care by characterizing patients who are more likely to be interested in FMT. Aligning treatment with the features that are important to patients can potentially improve satisfaction with and adherence to treatments for active ulcerative colitis to maximize their effectiveness for individual patients.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Crohn's Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study.

BACKGROUND: We aimed to establish a cohort of persons with Crohn's disease (CD) enrolled from 14 Canadian centers to describe the contemporary presentation of CD in Canada. METHODS: All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, inflammatory bowel disease (IBD) and other surgeries, and use IBD and other therapies. RESULTS: Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 = 50.4%, B2 = 22.4%, B3 = 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1, 16.8% in L2, 48% in L3, and 0.4% in L4. There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ±â€…10.1; B2 = 19.4 ±â€…12.9; B3 = 18.9 ±â€…11.8, P < .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P < .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P < .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease-related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%. CONCLUSIONS: In exploring this large contemporary CD cohort we have determined that inflammatory disease is the main CD phenotype in Canada and that CD-related surgery remains very common.

Correction: Currie et al. Reality Check 2: The Cost-Effectiveness of Policy Disallowing Body Checking in Non-Elite 13- to 14-Year-Old Ice Hockey Players. Int. J. Environ. Res. Public Health 2021, 18, 6322.

There was an error in our original publication [...].

HTA community perspectives on the use of patient preference information: lessons learned from a survey with members of HTA bodies.

This research sought to assess whether and how patient preference (PP) data are currently used within health technology assessment (HTA) bodies and affiliated organizations involved in technology/drug appraisals and assessments. An exploratory survey was developed by the PP Project Subcommittee of the HTA International Patient and Citizen Involvement Interest Group to gain insight into the use, impact, and role of PP data in HTA, as well as the perceived barriers to its incorporation. Forty members of HTA bodies and affiliated organizations from twelve countries completed the online survey. PP data were reported to be formally considered as part of the HTA evidence review process by 82.5 percent of the respondents, while 39.4 percent reported that most of the appraisals and assessments within their organization in the past year had submitted PP data. The leading reason for why PP data were not submitted in most assessments was time/resource constraints followed by lack of clarity on PP data impact. Participants reported that PP data had a moderate level of influence on the deliberative process and outcome of the decision, but a higher level of influence on the decision's quality. Most (81.8 percent) felt patient advocacy groups should be primarily responsible for generating and submitting this type of evidence. Insights from the survey confirm the use of PP data in HTA but reveal barriers to its broader and more meaningful integration. Encouragingly, participants believe obstacles can be overcome, paving the way for a second phase of research involving in-depth collaborative workshops with HTA representatives.

Exploring patient perspectives on EQ-5D-5L data visualization within an individualized decision aid for total knee arthroplasty (TKA) in Alberta, Canada.

BACKGROUND: Decision aids can help patients set realistic expectations. In this study, we explored alternative presentations to visualise patient-reported outcomes (EQ-5D-5L) data within an online, individualized patient decision aid for total knee arthroplasty (TKA) that, in part, generates individualized comparisons based on age, sex and body mass index, to enhance usability prior to implementation into routine clinical practice. METHODS: We used data visualization techniques to modify the presentation of EQ-5D-5L outcomes data within the decision aid. The EQ-5D-5L data was divided into two parts allowing patients to compare themselves to similar individuals (1) pre-surgery and (2) 1-year post-surgery. We created 2 versions for each part and sought patient feedback on comprehension, usefulness, and visual appeal. Patients from an urban orthopedic clinic were recruited and their ratings and comments were recorded using a researcher-administered checklist. Data were managed using Microsoft Excel, R version 3.6.1 and ATLAS.ti V8 and analyzed using descriptive statistics and directed content analysis. RESULTS: A total of 24 and 25 patients participated in Parts 1 and 2, respectively. Overall, there was a slight preference for Version 1 in Part 1 (58.3%) and Version 2 in Part 2 (64%). Most participants demonstrated adequate comprehension for all versions (range 50-72%) and commented that the instructions were clear. While 50-60% of participants rated the content as useful, including knowing the possible outcomes of surgery, some participants found the information interesting only, were unsure how to use the information, or did not find it useful because they had already decided on a treatment. Participants rated visual appeal for all versions favorably but suggested improvements for readability, mainly larger font and image sizes and enhanced contrast between elements. CONCLUSIONS: Based on the results, we will produce an enhanced presentation of EQ-5D-5L data within the decision aid. These improvements, along with further usability testing of the entire decision aid, will be made before implementation of the decision aid in routine clinical practice. Our results on patients' perspectives on the presentation of EQ-5D-5L data to support decision making for TKA treatments contributes to the knowledge on EQ-5D-5L applications within healthcare systems for clinical care.

Priority strategies to reduce socio-gendered inequities in access to person-centred osteoarthritis care: Delphi survey.

OBJECTIVES: Osteoarthritis (OA) prevalence, severity and related comorbid conditions are greater among women compared with men, but women, particularly racialised women, are less likely than men to access OA care. We aimed to prioritise strategies needed to reduce inequities in OA management. DESIGN: Delphi survey of 28 strategies derived from primary research retained if at least 80% of respondents rated 6 or 7 on a 7-point Likert scale. SETTING: Online. PARTICIPANTS: 35 women of diverse ethno-cultural groups and 29 healthcare professionals of various specialties from across Canada. RESULTS: Of the 28 initial and 3 newly suggested strategies, 27 achieved consensus to retain: 20 in round 1 and 7 in round 2. Respondents retained 7 patient-level, 7 clinician-level and 13 system-level strategies. Women and professionals agreed on all but one patient-level strategy (eg, consider patients' cultural needs and economic circumstances) and all clinician-level strategies (eg, inquire about OA management needs and preferences). Some discrepancies emerged for system-level strategies that were more highly rated by women (eg, implement OA-specific clinics). Comments revealed general support among professionals for system-level strategies provided that additional funding or expanded scope of practice was targeted to only formally trained professionals and did not reduce funding for professionals who already managed OA. CONCLUSIONS: We identified multilevel strategies that could be implemented by healthcare professionals, organisations or systems to mitigate inequities and improve OA care for diverse women.

Stated-Preference Survey Design and Testing in Health Applications.

Following the conceptualization of a well-formulated and relevant research question, selection of an appropriate stated-preference method, and related methodological issues, researchers are tasked with developing a survey instrument. A major goal of designing a stated-preference survey for health applications is to elicit high-quality data that reflect thoughtful responses from well-informed respondents. Achieving this goal requires researchers to design engaging surveys that maximize response rates, minimize hypothetical bias, and collect all the necessary information needed to answer the research question. Designing such a survey requires researchers to make numerous interrelated decisions that build upon the decision context, selection of attributes, and experimental design. Such decisions include considering the setting(s) and study population in which the survey will be administered, the format and mode of administration, and types of contextual information to collect. Development of a survey is an interactive process in which feedback from respondents should be collected and documented through qualitative pre-test interviews and pilot testing. This paper describes important issues to consider across all major steps required to design and test a stated-choice survey to elicit patient preferences for health preference research.

Cost-effectiveness of system-level mental health strategies for young people in the Australian Capital Territory: a dynamic simulation modelling study.

BACKGROUND: Regional mental health planning is a key challenge for decision makers because mental health care is a complex, dynamic system. Economic evaluation using a system dynamics modelling approach presents an opportunity for more sophisticated planning and important evidence on the value of alternative investments. We aimed to investigate the cost-effectiveness of eight systems-based interventions targeted at improving the mental health and wellbeing of children, adolescents, and young adults in the Australian Capital Territory (ACT). METHODS: We assessed eight interventions for children and young people (aged ≤25 years) with low, moderate, and high-to-very-high psychological distress: technology-enabled integrated care, emergency department-based suicide prevention, crisis response service, family education programme, online parenting programme, school-based suicide prevention programme, trauma service for youths, and multicultural-informed care. We developed a system dynamics model for the ACT through a participatory process and calibrated the model with historical data, including population demographics, the prevalence of psychological distress, and mental health services provision. We calculated incremental cost-effectiveness ratios compared with business as usual for cost (AU$) per: quality-adjusted life-year (QALY), suicide death avoided, self-harm related hospital admissions avoided, and mental health-related emergency department presentation, using a 10-year time horizon for health-care and societal perspectives. We investigated uncertainty through probabilistic sensitivity analysis and deterministic sensitivity analysis, including using a 30-year timeframe. FINDINGS: From a societal perspective, increased investment in technology-enabled integrated care, family education, an online parenting programme, and multicultural-informed care were expected to improve health outcomes (incremental QALYs 4517 [95% UI -3135 to 14 507] for technology-enabled integrated care; 339 [91 to 661] for family education; 724 [114 to 1149] for the online parenting programme; and 137 [88 to 194] for multicultural-informed care) and reduce costs ($-91·4 million [-382·7 to 100·7]; $-12·8 million [-21·0 to -6·6]; $-3·6 million  [-6·3 to 0·2]; and $-3·1 million [-4·5 to -1·8], respectively) compared with business as usual using a 10-year time horizon. The incremental net monetary benefit for the societal perspective for these four interventions was $452 million (-351 to 1555), $40 million (14 to 74), $61 million (9 to 98), and $14 million (9 to 20), respectively, compared with business as usual, when QALYs were monetised using a willingness to pay of $79 930 per QALY. Synergistic effects are anticipated if these interventions were to be implemented concurrently. The univariate and probabilistic sensitivity analyses indicated a high level of certainty in the results. Although emergency department-based suicide prevention and school-based suicide prevention were not cost effective in the base case (41 QALYs [0 to 48], incremental cost $4·1 million [1·2 to 8·2] for emergency department-based suicide prevention; -234 QALYs [-764 to 12], incremental cost $90·3 million [72·2 to 111·0] for school-based suicide prevention) compared with business as usual, there were scenarios for which these interventions could be considered cost effective. A dedicated trauma service for young people (9 QALYs gained [4 to 16], incremental cost $8·3 million [6·8 to 10·0]) and a crisis response service (-11 QALYs gained [-12 to -10], incremental cost $7·8 million [5·1 to 11·0]) were unlikely to be cost effective in terms of QALYs. INTERPRETATION: Synergistic effects were identified, supporting the combined implementation of technology-enabled integrated care, family education, an online parenting programme, and multicultural-informed care. Synergistic effects, emergent outcomes in the form of unintended consequences, the capability to account for service capacity constraints, and ease of use by stakeholders are unique attributes of a system dynamics modelling approach to economic evaluation. FUNDING: BHP Foundation.

Dose and fractionation regimen for brachytherapy boost in cervical cancer in the US.

PURPOSE: Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. METHODS: We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018-2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. RESULTS: Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). CONCLUSIONS: In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

System dynamics simulation for evaluating implementation strategies of genomic sequencing: tutorial and conceptual model.

INTRODUCTION: Precision Medicine (PM), especially in oncology, involve diagnostic and complex treatment pathways that are based on genomic features. To conduct evaluation and decision analysis for PM, advanced modeling techniques are needed due to its complexity. Although System Dynamics (SD) has strong modeling power, it has not been widely used in PM and individualized treatment. AREAS COVERED: We explained SD tools using examples in cancer context and the rationale behind using SD for genomic testing and personalized oncology. We compared SD with other Dynamic Simulation Modelling (DSM) methods and listed SD's advantages. We developed a conceptual model using Causal Loop Diagram (CLD) for strategic decision-making in Whole Genome Sequencing (WGS) implementation. EXPERT OPINION: The paper demonstrates that SD is well-suited for health policy evaluation challenges and has useful tools for modeling precision oncology and genomic testing. SD's system-oriented modeling captures dynamic and complex interactions within systems using feedback loops. SD models are simple to implement, utilize less data and computational resources, and conduct both exploratory and explanatory analyses over time. If the targeted system has complex interactions and many components, deals with lack of data, and requires interpretability and clinicians' input, SD offers attractive advantages for modeling and evaluating scenarios.

Intended and unintended consequences of strategies to meet performance benchmarks for rheumatologist referrals in a centralized intake system.

RATIONALE: Timely assessment of a chronic condition is critical to prevent long-term irreversible consequences. Patients with inflammatory arthritis (IA) symptoms require diagnosis by a rheumatologist and intervention initiation to minimize potential joint damage. With limited rheumatologist capacity, meeting urgency wait time benchmarks can be challenging. We investigate the impact of the maximum wait time guarantee (MWTG) policy and referral volume changes in a rheumatology central intake (CI) system on meeting this challenge. METHODS: We applied a system simulation approach to model a high-volume CI rheumatology clinic. Model parameters were based on the referral and triage data from the CI and clinic appointment data. We compare the wait time performance of the current distribution policy MWTG and when referral volumes change. RESULTS: The MWTG policy ensures 100% of new patients see a rheumatologist within their urgency wait time benchmark. However, the average wait time for new patients increased by 51% (178-269 days). A 10% decrease in referrals resulted in a 76% decrease on average wait times (178-43 days) for new patients and an increase in the number of patients seen by a rheumatologist within 1 year of the initial visit. CONCLUSION: An MWTG policy can result in intended and unintended consequences-ensuring that all patients meet the wait time benchmarks but increasing wait times overall. Relatively small changes in referral volume significantly impact wait times. These relationships can assist clinic managers and policymakers decide on the best approach to manage referrals for better system performance.

Experiences of Irritable Bowel Syndrome Patients in a Virtual Yoga Program: Qualitative Findings from a Clinical Trial.

BACKGROUND AND AIMS: In-person yoga interventions have shown feasibility and effectiveness in improving the outcomes of patients with irritable bowel syndrome (IBS), but experiences in virtual yoga interventions have not been examined. This study aimed to explore patients' experiences of a virtually delivered yoga intervention for IBS. METHODS: An embedded qualitative substudy was included in a randomized controlled trial examining the feasibility and effectiveness of a virtual yoga program among adult patients with IBS. Semi-structured interviews captured participants' past and current experiences, program satisfaction, perceived impact on IBS symptoms and overall physical and mental health, facilitators and barriers to participation, perceptions of social support and supervised learning, and input on improving future programming. Data were coded and analyzed in duplicate using NVivo 12. An analytic template based on the interview guide was developed and thematic analysis identified themes, as well as the relationship between themes and subthemes. RESULTS: Among the 14 participants (all female, mean age 47.7 years), three major themes were identified: (1) positive experience in the yoga program, (2) incorporating yoga into IBS management post-study, and (3) recommendations for program improvement. CONCLUSION: Patients with IBS experience in a virtual yoga program was positive with improvements in physical and mental health outcomes. Considering the barriers and facilitators to participating in an online yoga program along with participant recommendations may improve future intervention design and delivery to increase self-efficacy and confidence among patients with IBS.

Evaluation of the diagnostic accuracy of exome sequencing and its impact on diagnostic thinking for patients with rare disease in a publicly funded health care system: A prospective cohort study.

PURPOSE: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases. METHODS: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests. RESULTS: Laboratories reported 105 molecular diagnoses and 165 uncertain results in known and novel genes. Of these, clinicians interpreted 102 of 105 (97%) molecular diagnoses and 6 of 165 (4%) uncertain results as clinical-molecular diagnoses. The 108 clinical-molecular diagnoses were in 104 families (35% diagnostic yield). Each eligibility criteria resulted in diagnostic yields of 30% to 40%, and higher yields were achieved when >2 eligibility criteria were met (up to 45%). Hypothetical tests would have identified 61% of clinical-molecular diagnoses. CONCLUSION: We demonstrate robustness in eligibility criteria and high clinical validity of laboratory results from ES testing. The importance of ES was highlighted by the potential 40% of patients that would have gone undiagnosed without this test.

Associations between pharmaceutical industry payments to physicians and prescription of PARP inhibitors in the United States.

PURPOSE: To evaluate the association between industry payments to physicians related to poly (ADP-ribose) polymerase inhibitors (PARPis) and physicians' prescribing behaviors for PARPis. METHODS: This panel-data analysis used the publicly accessible Open Payments Database and Medicare Part D database between 2017 and 2021. All physicians who reported >10 claims for either olaparib, rucaparib, or niraparib were included in this study. Non-research payments for the PARPis to the physicians from the PARPi manufacturers were extracted from the Open Payments Database. Associations between the physicians' receipt of payments and likelihood of prescribing PARPis were assessed with logistic generalized estimating equations (GEEs). Dose-response associations between the number of payments and prescription volumes and Medicare expenditures were evaluated with linear GEEs. RESULTS: Of the 1686 eligible physician prescribers, 68.7% received one or more non-research payments related to any of the three PARPis from the manufacturers between 2017 and 2021. Median annual payments per physician were $57 for olaparib, $39 for rucaparib, and $62 for niraparib. Receipt of payments for each PARPi was associated with higher odds of prescribing olaparib (odds ratio [OR]: 1.30 [95% CI: 1.14-1.48], p < 0.001), rucaparib (OR: 2.07 [95% CI: 1.58-2.72], p < 0.001), and niraparib (OR: 1.49 [95% CI: 1.22-1.81], p < 0.001). Dose-response effects were observed between the number of annual payments and the number of prescriptions and/or Medicare expenditures for olaparib and rucaparib. CONCLUSION: Non-research payments to physician prescribers of PARP inhibitors from the manufacturers were significantly associated with increased prescriptions and Medicare expenditures for olaparib and rucaparib in the United States.