Cost-effectiveness of pharmacogenomic-guided treatment for major depression.

BACKGROUND: Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants. METHODS: We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC. RESULTS: Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation. INTERPRETATION: Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.

Pharmacogenomic Testing for Major Depression: A Qualitative Study of the Perceptions of People with Lived Experience and Professional Stakeholders.

OBJECTIVES: With increasing evidence for the clinical utility of pharmacogenomic (PGx) testing for depression, there is a growing need to consider issues related to the clinical implementation of this testing. The perspectives of key stakeholders (both people with lived experience [PWLE] and providers) are critical, but not frequently explored. The purpose of this study was to understand how PWLE and healthcare providers/policy experts (P/HCPs) perceive PGx testing for depression, to inform the consideration of clinical implementation within the healthcare system in British Columbia (BC), Canada. METHODS: We recruited two cohorts of participants to complete individual 1-h, semi-structured interviews: (a) PWLE, recruited from patient and research engagement networks and organizations and (b) P/HCPs, recruited via targeted invitation. Interviews were audiotaped, transcribed verbatim, de-identified, and analysed using interpretive description. RESULTS: Seventeen interviews were completed with PWLE (7 with experience of PGx testing for depression; 10 without); 15 interviews were completed with P/HCPs (family physicians, psychiatrists, nurses, pharmacists, genetic counsellors, medical geneticists, lab technologists, program directors, and insurers). Visual models of PWLE's and P/HCP's perceptions of and attitudes towards PGx testing were developed separately, but both were heavily influenced by participants' prior professional and/or personal experiences with depression and/or PGx testing. Both groups expressed a need for evidence and numerous considerations for the implementation of PGx testing in BC, including the requirement for conclusive economic analyses, patient and provider education, technological and clinical support, local testing facilities, and measures to ensure equitable access to testing. CONCLUSIONS: While hopeful about the potential for therapeutic benefit from PGx testing, PWLE and P/HCPs see the need for robust evidence of utility, and BC-wide infrastructure and policies to ensure equitable and effective access to PGx testing. Further research into the accessibility, effectiveness, and cost-effectiveness of various implementation strategies is needed to inform PGx testing use in BC.

Adding epitope compatibility to deceased donor kidney allocation criteria: recommendations from a pan-Canadian online public deliberation.

BACKGROUND: The widening supply-demand imbalance for kidneys necessitates finding ways to reduce rejection and improve transplant outcomes. Human leukocyte antigen (HLA) epitope compatibility between donor and recipient may minimize premature graft loss and prolong survival, but incorporating this strategy to deceased donor allocation criteria prioritizes transplant outcomes over wait times. An online public deliberation was held to identify acceptable trade-offs when implementing epitope compatibility to guide Canadian policymakers and health professionals in deciding how best to allocate kidneys fairly. METHODS: Invitations were mailed to 35,000 randomly-selected Canadian households, with over-sampling of rural/remote locations. Participants were selected for socio-demographic diversity and geographic representation. Five two-hour online sessions were held from November-December 2021. Participants received an information booklet and heard from expert speakers prior to deliberating on how to fairly implement epitope compatibility for transplant candidates and governance issues. Participants collectively generated and voted on recommendations. In the final session, kidney donation and allocation policymakers engaged with participants. Sessions were recorded and transcribed. RESULTS: Thirty-two individuals participated and generated nine recommendations. There was consensus on adding epitope compatibility to the existing deceased donor kidney allocation criteria. However, participants recommended including safeguards/flexibility around this (e.g., mitigating declining health). They called for a transition period to epitope compatibility, including an ongoing comprehensive public education program. Participants unanimously recommended regular monitoring and public sharing of epitope-based transplant outcomes. CONCLUSIONS: Participants supported adding epitope compatibility to kidney allocation criteria, but advised safeguards and flexibility around implementation. These recommendations provide guidance to policymakers about incorporating epitope-based deceased donor allocation criteria.

Public values and guiding principles for implementing epitope compatibility in kidney transplantation allocation criteria: results from a Canadian online public deliberation.

BACKGROUND: Epitope compatibility in deceased donor kidney allocation is an emerging area of precision medicine (PM), seeking to improve compatibility between donor kidneys to transplant candidates in the hope of avoiding kidney rejection. Though the potential benefits of using epitope compatibility are promising, the implied modification of deceased organ allocation criteria requires consideration of significant clinical and ethical trade-offs. As a matter of public policy, these trade-offs should consider public values and preferences. We invited members of the Canadian public to participate in a deliberation about epitope compatibility in deceased donor kidney transplantation; to identify what is important to them and to provide recommendations to policymakers. METHODS: An online public deliberation was conducted with members of the Canadian public, in which participants were asked to construct recommendations for policymakers regarding the introduction of epitope compatibility to kidney allocation criteria. In the present paper, a qualitative analysis was conducted to identify the values reflected in participants' recommendations. All virtual sessions were recorded, transcribed, and analyzed using NVivo 12 software. RESULTS: Thirty-two participants constructed nine recommendations regarding the adoption of epitope compatibility into deceased donor kidney allocation. Five values were identified that drove participants' recommendations: Health Maximization, Protection/Mitigation of Negative Impacts, Fairness, Science/Evidence-based Healthcare, and Responsibility to Maintain Trust. Conflicts between these values were discussed in terms of operational principles that were required for epitope compatibility to be implemented in an acceptable manner: the needs for Flexibility, Accountability, Transparent Communication and a Transition Plan. All nine recommendations were informed by these four principles. Participant deliberations were often dominated by the conflict between Health Maximization and Fairness or Protection/Mitigation of Negative Impacts, which was discussed as the need for Flexibility. Two additional values (Efficient Use of Resources and Logic/Rationality) were also discussed and were reasons for some participants voting against some recommendations. CONCLUSIONS: Public recommendations indicate support for using epitope compatibility in deceased donor kidney allocation. A flexible approach to organ allocation decision-making may allow for the balancing of Health Maximization against maintaining Fairness and Mitigating Negative Impacts. Flexibility is particularly important in the context of epitope compatibility and other PM initiatives where evidence is still emerging.

Costs of major depression covered / not covered in British Columbia, Canada.

BACKGROUND: Major depressive disorder (MDD) is one of the world's leading causes of disability. Our purpose was to characterize the total costs of MDD and evaluate the degree to which the British Columbia provincial health system meets its objective to protect people from the financial impact of illness. METHODS: We performed a population-based cohort study of adults newly diagnosed with MDD between 2015 and 2020 and followed their health system costs over two years. The expenditure proportion of MDD-related, patient paid costs relative to non-subsistence income was estimated, incidences of financial hardship were identified and the slope index of inequality (SII) between the highest and lowest income groups compared across regions. RESULTS: There were 250,855 individuals diagnosed with MDD in British Columbia over the observation period. Costs to the health system totalled >$1.5 billion (2020 CDN), averaging $138/week for the first 12 weeks following a new diagnosis and $65/week to week 52 and $55/week for weeks 53-104 unless MDD was refractory to treatment ($125/week between week 12-52 and $101/week over weeks 53-104). The proportion of MDD-attributable costs not covered by the health system was 2-15x greater than costs covered by the health system, exceeding $700/week for patients with severe MDD or MDD that was refractory to treatment. Population members in lower-income groups and urban homeowners had disadvantages in the distribution of financial protection received by the health system (SII reached - 8.47 and 15.25, respectively); however, financial hardship and inequities were mitigated province-wide if MDD went into remission (SII - 0.07 to 0.6). CONCLUSIONS: MDD-attributable costs to health systems and patients are highest in the first 12 weeks after a new diagnosis. During this time, lower income groups and homeowners in urban areas run the risk of financial hardship.

Differential influence of habitual third-person vision of a body part on mental rotation of images of hands and feet.

Left/right judgement (LRJ) tasks involve determining the laterality of presented hand or feet images. Allocentric images (third-person perspective; 3PP) take longer to identify than egocentric images (first-person perspective; 1PP), supporting that implicit motor imagery (IMI)-mentally manoeuvring one's body to match the shown posture-is used. While numerous cognitive processes are involved during LRJs, it remains unclear whether features of the individual (e.g., visual exposure, experience, task-dependent use) influence the type of recognition strategy used during LRJs (IMI versus non-IMI). To investigate whether an individual's routine visual exposure to hands/feet in 3PP disrupts the typical perspective-reaction time (RT) relationship in LRJs, hand therapists, podiatrists, and healthy controls completed online LRJ tasks of hand and feet images. A group-specific reduction in RT for only allocentric images would represent a switch to non-IMI strategies. The results show that routine visual exposure to feet in 3PP (podiatrists) results in quicker RTs only for allocentric images of feet, suggesting a switch from IMI to non-IMI (e.g., visual object-based recognition) strategies. In contrast, routine visual exposure to hands in 3PP (hand therapists) does not alter RT for allocentric images, suggesting maintenance of IMI. However, hand therapists have quicker RTs (vs other groups) for egocentric hand images, supporting enhanced sensorimotor processing for the hand, consistent with task-dependent use (precise hand use). Higher accuracy in health professionals (vs control) on both tasks supports enhanced body schema. Combined, this suggests that 3PP visual exposure to body parts and task-dependent use contribute to LRJ performance/recognition strategy.

Brain-Heart Pathways to Blood Pressure-Related Hypoalgesia.

OBJECTIVE: High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain. METHODS: Eighteen participants (10 women; 32.7 (6.5) years) underwent BP monitoring for 1 week at home, and individual pain thresholds were determined in the laboratory. Subsequently, participants were administered unpredictable painful and nonpainful electrocutaneous shocks (stimulus type), timed to occur either at systole or at diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience. RESULTS: Subjective pain was lower for painful stimuli administered at systole compared with diastole, F(1, 2283) = 4.82, p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F(1, 2164) = 10.47, p < .0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type by cardiac phase interaction emerged except for a small cluster located in the right parietal cortex. CONCLUSIONS: We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral, and lingual gyrus, regions typically involved in the cognitive aspects of pain experience.

The Inclusion of Ethnic Minority Patients and the Role of Language in Telehealth Trials for Type 2 Diabetes: A Systematic Review.

BACKGROUND: Type 2 diabetes is a serious, pervasive metabolic condition that disproportionately affects ethnic minority patients. Telehealth interventions can facilitate type 2 diabetes monitoring and prevent secondary complications. However, trials designed to test the effectiveness of telehealth interventions may underrecruit or exclude ethnic minority patients, with language a potential barrier to recruitment. The underrepresentation of minorities in trials limits the external validity of the findings for this key patient demographic. OBJECTIVE: This systematic review examines (1) the research reporting practices and prevalence of ethnic minority patients included in telehealth randomized controlled trials (RCTs) targeting type 2 diabetes and the trial characteristics associated with recruiting a high proportion of minority patients, and (2) the proportion of included RCTs that report using English language proficiency as a patient screening criterion and how and why they do so. METHODS: Telehealth RCTs published in refereed journals targeting type 2 diabetes as a primary condition for adults in Western majority English-speaking countries were included. Ethnically targeted RCTs were excluded from the main review, but were included in a post hoc subgroup analysis. Abstract and full-text screening, risk of bias assessment, and data extraction were independently conducted by two reviewers. RESULTS: Of 3358 records identified in the search, 79 articles comprising 58 RCTs were included. Nearly two-thirds of the RCTs (38/58) reported on the ethnic composition of participants, with a median proportion of 23.5% patients (range 0%-97.7%). Fourteen studies (24%) that included at least 30% minority patients were all US-based, predominantly recruited from urban areas, and described the target population as underserved, financially deprived, or uninsured. Eight of these 14 studies (57%) offered intervention materials in a language other than English or employed bilingual staff. Half of all identified RCTs (29/58) included language proficiency as a participant-screening criterion. Language proficiency was operationalized using nonstandardized measures (eg, having sufficient "verbal fluency"), with only three studies providing reasons for excluding patients on language grounds. CONCLUSIONS: There was considerable variability across studies in the inclusion of ethnic minority patients in RCTs, with higher participation rates in countries with legislation to mandate their inclusion (eg, United States) than in those without such legislation (eg, United Kingdom). Less than 25% of the RCTs recruited a sizeable proportion of ethnic minorities, which raises concerns about external validity. The lack of objective measures or common procedures for assessing language proficiency across trials implies that language-related eligibility decisions are often based on trial recruiters' impressionistic judgments, which could be subject to bias. The variability and inconsistent reporting on ethnicity and other socioeconomic factors in descriptions of research participants could be more specifically emphasized in trial reporting guidelines to promote best practice. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews: CRD42015024899; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015024899 (Archived by WebCite at http://www.webcitation.org/6kQmI2bdF).

Being Human: A Qualitative Interview Study Exploring Why a Telehealth Intervention for Management of Chronic Conditions Had a Modest Effect.

BACKGROUND: Evidence of benefit for telehealth for chronic conditions is mixed. Two linked randomized controlled trials tested the Healthlines Service for 2 chronic conditions: depression and high risk of cardiovascular disease (CVD). This new telehealth service consisted of regular telephone calls from nonclinical, trained health advisers who followed standardized scripts generated by interactive software. Advisors facilitated self-management by supporting participants to use Web-based resources and helped to optimize medication, improve treatment adherence, and encourage healthier lifestyles. Participants were recruited from primary care. The trials identified moderate (for depression) or partial (for CVD risk) effectiveness of the Healthlines Service. OBJECTIVE: An embedded qualitative study was undertaken to help explain the results of the 2 trials by exploring mechanisms of action, context, and implementation of the intervention. METHODS: Qualitative interview study of 21 staff providing usual health care or involved in the intervention and 24 patients receiving the intervention. RESULTS: Interviewees described improved outcomes in some patients, which they attributed to the intervention, describing how components of the model on which the intervention was based helped to achieve benefits. Implementation of the intervention occurred largely as planned. However, contextual issues in patients' lives and some problems with implementation may have reduced the size of effect of the intervention. For depression, patients' lives and preferences affected engagement with the intervention: these largely working-age patients had busy and complex lives, which affected their ability to engage, and some patients preferred a therapist-based approach to the cognitive behavioral therapy on offer. For CVD risk, patients' motivations adversely affected the intervention whereby some patients joined the trial for general health improvement or from altruism, rather than motivation to make lifestyle changes to address their specific risk factors. Implementation was not optimal in the early part of the CVD risk trial owing to technical difficulties and the need to adapt the intervention for use in practice. For both conditions, enthusiastic and motivated staff offering continuity of intervention delivery tailored to individual patients' needs were identified as important for patient engagement with telehealth; this was not delivered consistently, particularly in the early stages of the trials. Finally, there was a lack of active engagement from primary care. CONCLUSIONS: The conceptual model was supported and could be used to develop further telehealth interventions for chronic conditions. It may be possible to increase the effectiveness of this, and similar interventions, by attending to the human as well as the technical aspects of telehealth: offering it to patients actively wanting the intervention, ensuring continuity of delivery by enthusiastic and motivated staff, and encouraging active engagement from primary care staff.

Are people with chronic diseases interested in using telehealth? A cross-sectional postal survey.

BACKGROUND: There is growing interest in telehealth-the use of technology to support the remote delivery of health care and promote self-management-as a potential alternative to face-to-face care for patients with chronic diseases. However, little is known about what precipitates interest in the use of telehealth among these patients. OBJECTIVE: This survey forms part of a research program to develop and evaluate a telehealth intervention for patients with two exemplar chronic diseases: depression and raised cardiovascular disease (CVD) risk. The survey was designed to explore the key factors that influence interest in using telehealth in these patient groups. METHODS: Thirty-four general practices were recruited from two different regions within England. Practice records were searched for patients with (1) depression (aged 18+ years) or (2) 10-year risk of CVD ≥20% and at least one modifiable risk factor (aged 40-74 years). Within each general practice, 54 patients in each chronic disease group were randomly selected to receive a postal questionnaire. Questions assessed five key constructs: sociodemographics, health needs, difficulties accessing health care, technology-related factors (availability, confidence using technology, perceived benefits and drawbacks of telehealth), and satisfaction with prior use of telehealth. Respondents also rated their interest in using different technologies for telehealth (phone, email and Internet, or social media). Relationships between the key constructs and interest in using the three mediums of telehealth were examined using multivariable regression models. RESULTS: Of the 3329 patients who were sent a study questionnaire, 44.40% completed it (872/1740, 50.11% CVD risk; 606/1589, 38.14% depression). Overall, there was moderate interest in using phone-based (854/1423, 60.01%) and email/Internet-based (816/1425, 57.26%) telehealth, but very little interest in social media (243/1430, 16.99%). After adjusting for health needs, access difficulties, technology-related factors, and prior use of telehealth, interest in telehealth had largely no association with sociodemographic variables. For both patient groups and for each of the three technology mediums, the most important constructs related to interest in telehealth were having the confidence to use the associated technology, as well as perceiving greater advantages and fewer disadvantages from using telehealth. To illustrate, greater confidence using phone technologies (b=.16, 95% CI 0.002-0.33), while also perceiving more benefits (b=.31, 95% CI 0.21-0.40) and fewer drawbacks (b=-.23, 95% CI -0.28 to -0.17) to using telehealth were associated with more interest in using phone-based telehealth technologies for patients with depression. CONCLUSIONS: There is widespread interest in using phone-based and email/Internet-based telehealth among patients with chronic diseases, regardless of their health status, access difficulties, age, or many other sociodemographic factors. This interest could be increased by helping patients gain confidence using technologies and through highlighting benefits and addressing concerns about telehealth. While the same pattern exists for social media telehealth, interest in using these technologies is minimal.

A Canadian Simulation Model for Major Depressive Disorder: Study Protocol.

BACKGROUND: Major depressive disorder (MDD) is a common, often recurrent condition and a significant driver of healthcare costs. People with MDD often receive pharmacological therapy as the first-line treatment, but the majority of people require more than one medication trial to find one that relieves symptoms without causing intolerable side effects. There is an acute need for more effective interventions to improve patients' remission and quality of life and reduce the condition's economic burden on the healthcare system. Pharmacogenomic (PGx) testing could deliver these objectives, using genomic information to guide prescribing decisions. With an already complex and multifaceted care pathway for MDD, future evaluations of new treatment options require a flexible analytic infrastructure encompassing the entire care pathway. Individual-level simulation models are ideally suited for this purpose. We sought to develop an economic simulation model to assess the effectiveness and cost effectiveness of PGx testing for individuals with major depression. Additionally, the model serves as an analytic infrastructure, simulating the entire patient pathway for those with MDD. METHODS AND ANALYSIS: Key stakeholders, including patient partners, clinical experts, researchers, and modelers, designed and developed a discrete-time microsimulation model of the clinical pathways of adults with MDD in British Columbia (BC), including all publicly-funded treatment options and multiple treatment steps. The Simulation Model of Major Depression (SiMMDep) was coded with a modular approach to enhance flexibility. The model was populated using multiple original data analyses conducted with BC administrative data, a systematic review, and an expert panel. The model accommodates newly diagnosed and prevalent adult patients with MDD in BC, with and without PGx-guided treatment. SiMMDep comprises over 1500 parameters in eight modules: entry cohort, demographics, disease progression, treatment, adverse events, hospitalization, costs and quality-adjusted life-years (payoff), and mortality. The model predicts health outcomes and estimates costs from a health system perspective. In addition, the model can incorporate interactive decision nodes to address different implementation strategies for PGx testing (or other interventions) along the clinical pathway. We conducted various forms of model validation (face, internal, and cross-validity) to ensure the correct functioning and expected results of SiMMDep. CONCLUSION: SiMMDep is Canada's first medication-specific, discrete-time microsimulation model for the treatment of MDD. With patient partner collaboration guiding its development, it incorporates realistic care journeys. SiMMDep synthesizes existing information and incorporates provincially-specific data to predict the benefits and costs associated with PGx testing. These predictions estimate the effectiveness, cost-effectiveness, resource utilization, and health gains of PGx testing compared with the current standard of care. However, the flexible analytic infrastructure can be adapted to support other policy questions and facilitate the rapid synthesis of new data for a broader search for efficiency improvements in the clinical field of depression.

Co-learning commentary: a patient partner perspective in mental health care research.

BACKGROUND: Although including patients as full, active members of research teams is becoming more common, there are few accounts about how to do so successfully, and almost none of these are written by patient partners themselves. Three patient partners contributed their lived experience to a three-year, multi-component mental health research project in British Columbia, Canada. As patient partners, we contributed to innovative co-learning in this project, resulting in mutual respect and wide-ranging benefits. To guide future patient partners and researchers seeking patient engagement, we outline the processes that helped our research team 'get it right'. MAIN BODY: From the outset, we were integrated into components of the project that we chose: thematically coding a rapid review, developing questions and engagement processes for focus groups, and shaping an economic model. Our level of engagement in each component was determined by us. Additionally, we catalyzed the use of surveys to evaluate our engagement and the perceptions of patient engagement from the wider team. At our request, we had a standing place on each monthly meeting agenda. Importantly, we broke new ground when we moved the team from using previously accepted psychiatric terminology that no longer fit the reality of patients' experiences. We worked diligently with the team to represent the reality that was appropriate for all parties. The approach taken in this project led to meaningful and successfully integrated patient experiences, fostered a shared understanding, which positively impacted team development and cohesion. The resulting 'lessons learned' included engaging early, often, and with respect; carving out and creating a safe place, free from stigma; building trust within the research team; drawing on lived experience; co-creating acceptable terminology; and cultivating inclusivity throughout the entire study. CONCLUSION: We believe that lived experience can and should go hand-in-hand with research, to ensure study outcomes reflect the knowledge of patients themselves. We were willing to share the truth of our lived experience. We were treated as co-researchers. Successful engagement came from the 'lessons learned' that can be used by other teams who wish to engage patient partners in health research.

Although including patients as members of research teams is becoming more common, there is little information about how to do this successfully. There are even fewer accounts written by patient partners themselves. We argue that successful patient engagement accepts and celebrates the patient partner experience. In this article, we reflect on and share our experiences as patient partners in a Canadian mental health research project. Early on in the project, we were asked to choose which streams of work we would like to work on. In addition, we helped develop surveys about patient engagement in the project. We also had time set aside at each meeting for patient updates. Importantly, we steered the team towards using different mental health terms because they had less stigma and better fit patients' experiences. We offer the following 'lessons learned' about how to engage patients successfully in mental health research, but they are also likely to apply to most health research studies: (1) Engage Early, Often, and with Respect; (2) Carve out and Create a Safe Place; (3) Draw on Lived Experience; (4) Build Trust in the Research Team; (5) Listen, Learn, then Find a New Language; and (6) Cultivate Inclusion Throughout the Project. We believe that the lived experience of patients can and should go hand-in-hand with research. This helps to make sure that the research findings reflect the actual experiences and knowledge of patients. We hope that this article will be a useful guide to other patients and researchers.

The Role of Artificial Intelligence in Colorectal Cancer Screening: Lesion Detection and Lesion Characterization.

Colorectal cancer remains a leading cause of cancer-related morbidity and mortality worldwide, despite the widespread uptake of population surveillance strategies. This is in part due to the persistent development of 'interval colorectal cancers', where patients develop colorectal cancer despite appropriate surveillance intervals, implying pre-malignant polyps were not resected at a prior colonoscopy. Multiple techniques have been developed to improve the sensitivity and accuracy of lesion detection and characterisation in an effort to improve the efficacy of colorectal cancer screening, thereby reducing the incidence of interval colorectal cancers. This article presents a comprehensive review of the transformative role of artificial intelligence (AI), which has recently emerged as one such solution for improving the quality of screening and surveillance colonoscopy. Firstly, AI-driven algorithms demonstrate remarkable potential in addressing the challenge of overlooked polyps, particularly polyp subtypes infamous for escaping human detection because of their inconspicuous appearance. Secondly, AI empowers gastroenterologists without exhaustive training in advanced mucosal imaging to characterise polyps with accuracy similar to that of expert interventionalists, reducing the dependence on pathologic evaluation and guiding appropriate resection techniques or referrals for more complex resections. AI in colonoscopy holds the potential to advance the detection and characterisation of polyps, addressing current limitations and improving patient outcomes. The integration of AI technologies into routine colonoscopy represents a promising step towards more effective colorectal cancer screening and prevention.

Evaluating treatment outcomes in pharmacogenomic-guided care for major depression: A rapid review and meta-analysis.

Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given the potential implications of these outcomes and recent proliferation of PGx studies, we conducted a systematic review to evaluate the effectiveness of PGx testing on clinical outcomes in patients with MDD as compared to treatment as usual (TAU). MEDLINE, Embase, PsycInfo, and CENTRAL were searched for English-language articles from 2000 to 2021 for randomized controlled trials (RCTs) comparing PGx-guided treatment vs. TAU in patients with MDD. Meta-analyses were conducted in R. Ten RCTs were included: eight reported remission and seven reported response. The best available evidence suggests that PGx-guided care for moderate-to-severe adult depression is more likely to result in remission and response than TAU (both risk ratios significant). However, there are limitations in the evidence base, including high risk of bias and inconsistency between trials. Despite the consequent very low certainty in the magnitude of effect, there is confidence in the direction. Though modest, the beneficial effects of PGx for adults with moderate-severe MDD could - as a result of the scope and scale of the condition and its impacts - have important ramifications for patients and the health system.

A Systematic Review of Kidney Transplantation Decision Modelling Studies.

BACKGROUND: Genome-based precision medicine strategies promise to minimize premature graft loss after renal transplantation, through precision approaches to immune compatibility matching between kidney donors and recipients. The potential adoption of this technology calls for important changes to clinical management processes and allocation policy. Such potential policy change decisions may be supported by decision models from health economics, comparative effectiveness research and operations management. OBJECTIVE: We used a systematic approach to identify and extract information about models published in the kidney transplantation literature and provide an overview of the status of our collective model-based knowledge about the kidney transplant process. METHODS: Database searches were conducted in MEDLINE, Embase, Web of Science and other sources, for reviews and primary studies. We reviewed all English-language papers that presented a model that could be a tool to support decision making in kidney transplantation. Data were extracted on the clinical context and modelling methods used. RESULTS: A total of 144 studies were included, most of which focused on a single component of the transplantation process, such as immunosuppressive therapy or donor-recipient matching and organ allocation policies. Pre- and post-transplant processes have rarely been modelled together. CONCLUSION: A whole-disease modelling approach is preferred to inform precision medicine policy, given its potential upstream implementation in the treatment pathway. This requires consideration of pre- and post-transplant natural history, risk factors for allograft dysfunction and failure, and other post-transplant outcomes. Our call is for greater collaboration across disciplines and whole-disease modelling approaches to more accurately simulate complex policy decisions about the integration of precision medicine tools in kidney transplantation.

Collaborating with Patient Partners to Model Clinical Care Pathways in Major Depressive Disorder: The Benefits of Mixing Evidence and Lived Experience.

BACKGROUND: Partnering with patients can enrich the design and development of models of clinical care pathways, yet the practice is not commonplace. Guidelines or "best practices" for patient involvement in modeling are scarce. OBJECTIVES: In this paper, we outline the steps we took to form an effective partnership with patients to design a robust microsimulation Markov model of major depressive disorder care pathways in British Columbia, Canada, with the aim of encouraging other teams to partner with patients in healthcare modeling endeavors. METHODS: We describe three unique phases of our collaborative process: uncertainty, mapping, and structured collaboration. We then explore the unique contributions the patient partners made, not only to the model itself, but to our process. Key perspectives are shared from both the modeler and the patient partners in their own words. RESULTS: The patient partners made distinct contributions by challenging and verifying modeling assumptions, noting limitations of the model, and suggesting areas for future research. Both the patient partners and the modelers saw great value in the partnership and agreed that the model was strengthened by the diversity of the team. CONCLUSIONS: We present our learning and key recommendations for future modeling teams in the absence of tested frameworks. We encourage more widespread adoption of patient involvement in modeling and the development of guidelines for such work to increase the democracy of scientific decision making.

Brief Interventions Influence the Quantity and Quality of Caregiver-Child Conversations in an Everyday Context.

Reading and arithmetic are difficult cognitive feats for children to master and youth from low-income communities are often less "school ready" in terms of letter and number recognition skills (Lee and Burkam, 2002). One way to prepare children for school is by encouraging caregivers to engage children in conversations about academically-relevant concepts by using numbers, recognizing shapes, and naming colors (Levine et al., 2010; Fisher et al., 2013). Previous research shows that caregiver-child conversations about these topics rarely take place in everyday contexts (Hassinger-Das et al., 2018), but interventions designed to encourage such conversations, like displaying signs in a grocery store, have resulted in significant increases in caregiver-child conversations (Ridge et al., 2015; Hanner et al., 2019). We investigated whether a similar brief intervention could change caregiver-child conversations in an everyday context. We observed 212 families in a volunteer-run facility where people who are food-insecure can select food from available donations. Volunteers greet all the clients as they pass through the aisles, offer food, and restock the shelves as needed. About 25% of the clients have children with them and our data consist of observations of the caregiver-child conversations with 2- to 10-year-old children. Half of the observation days consisted of a baseline condition in which the quantity and quality of caregiver-child conversation was observed as the client went through aisles where no signs were displayed, and volunteers merely greeted the clients. The other half of the observation days consisted of a brief intervention where signs were displayed (signs-up condition), where, volunteers greeted the clients and pointed out that there were signs displayed to entertain the children if they were interested. In addition, there was a within-subject manipulation for the intervention condition where each family interacted with two different categories of signs. Half of the signs had academically-relevant content and the other half had non-academically-relevant content. The results demonstrate that the brief intervention used in the signs-up condition increases the quantity of conversation between a caregiver and child. In addition, signs with academically-relevant content increases the quality of the conversation. These findings provide further evidence that brief interventions in an everyday context can change the caregiver-child conversation. Specifically, signs with academically-relevant content may promote school readiness.

What matters most to patients about primary healthcare: mixed-methods patient priority setting exercises within the PREFeR (PRioritiEs For Research) project.

OBJECTIVES: To identify patient-generated priority topics for future primary care research in British Columbia (BC), Canada within a diverse patient population. DESIGN: Mixed-methods priority setting exercises framed by the dialogue model, using the nominal group technique (rank-ordered scoring) and province-wide online surveys capturing importance ratings of the top 10 primary healthcare topics from patients and primary care providers. SETTING: BC, Canada. PARTICIPANTS: Topic identification was completed by 10 patient partners (7 female, 3 male) from the BC Primary Health Care Research Network Patient Advisory; online surveys were completed by 464 patients and 173 primary care providers. RESULTS: The 10 members recruited to the patient advisory provided over 80 experiences of what stood out for them in BC primary care, which were grouped thematically into 18 topics, 10 of which were retained in province-wide surveys. Top-rated survey topics for both patients (n=464) and providers (n=173) included being unable to find a regular family doctor/other primary healthcare provider, support for living with chronic conditions, mental health resources and information sharing, including electronic medical records. However, all 10 topics were rated important, on average, by both groups. CONCLUSIONS: The current project activities demonstrate the feasibility of including patients in priority setting exercises for primary healthcare in general, rather than focusing on a condition-specific population or disease area. There was considerable overlap between patient-generated topics and topics previously identified by other stakeholders, but patients identified two additional topics (mental health resources, improve and strengthen patient-provider communication). More similarities than differences in topic importance between patients and providers emerged in the online surveys. The project activities that follow (rapid literature reviews, multistakeholder dialogue) will highlight under-researched topics and inform the development of specific research questions.

Best emollients for eczema (BEE) - comparing four types of emollients in children with eczema: protocol for randomised trial and nested qualitative study.

INTRODUCTION: Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend 'leave-on' emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease 'flares'. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first. METHODS AND ANALYSIS: Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments). SETTING: general practitioner surgeries in England. PARTICIPANTS: children aged over 6 months and less than 12 years with mild-to-severe eczema and no known sensitivity to study emollients. INTERVENTIONS: study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care. FOLLOW-UP: 52 weeks. PRIMARY OUTCOME: validated patient-orientated eczema measure measured weekly for 16 weeks. SECONDARY OUTCOMES: eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact). SAMPLE SIZE: 520 participants (130 per group). ANALYSIS: intention-to-treat using linear mixed models for repeated measures.Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically. ETHICS AND DISSEMINATION: Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN84540529.

TEST (Trial of Eczema allergy Screening Tests): protocol for feasibility randomised controlled trial of allergy tests in children with eczema, including economic scoping and nested qualitative study.

BACKGROUND: Early onset eczema is associated with food allergy, and allergic reactions to foods can cause acute exacerbations of eczema. Parents often pursue dietary restrictions as a way of managing eczema and seek allergy testing for their children to guide dietary management. However, it is unclear whether test-guided dietary management improves eczema symptoms, and whether the practice causes harm through reduced use of conventional eczema treatment or unnecessary dietary restrictions. The aim of the Trial of Eczema allergy Screening Tests Study is to determine the feasibility of conducting a trial comparing food allergy testing and dietary advice versus usual care, for the management of eczema in children. METHODS AND ANALYSIS: Design: A single centre, two-group, individually randomised, feasibility randomised controlled trial (RCT) with economic scoping and a nested qualitative study. SETTING: General Practioner (GP) surgeries in the west of England. PARTICIPANTS: children aged over 3 months and less than 5 years with mild to severe eczema. INTERVENTIONS: allergy testing (structured allergy history and skin prick tests) or usual care. Sample size and outcome measures: we aim to recruit 80 participants and follow them up using 4-weekly questionnaires for 24 weeks. Nested qualitative study: We will conduct ~20 interviews with parents of participating children, 5-8 interviews with parents who decline or withdraw from the trial and ~10 interviews with participating GPs. Economic scoping: We will gather data on key costs and outcomes to assess the feasibility of carrying out a cost-effectiveness analysis in a future definitive trial. ETHICS AND DISSEMINATION: The study has been reviewed by the Health Research Authority and given a favourable opinion by the NHS REC (West Midlands - South Birmingham Research Ethics Committee, Reference Number 18/WM/0124). Findings will be submitted for presentation at conferences and written up for publication in peer-reviewed journals, which may include mixed-method triangulation and integration of the quantitative and qualitative findings. TRIAL REGISTRATION: ISRCTN15397185; Pre-results.