Mapping a research-advocacy-policy agenda on human rights and albinism: a mixed methods project.

BACKGROUND: Persons with albinism face challenges to their wellbeing, safety, and security, ranging from vision impairment and skin cancer to stigma and discrimination. In some regions, they also face human rights atrocities including mutilation and murder. Research on human rights and albinism is a relatively new field that has gained momentum since the United Nations appointment of an Independent Expert on the enjoyment of human rights by persons with albinism. In this paper, we present the results of a mixed methods study undertaken to identify priorities for research, advocacy, and policy on albinism and human rights. METHODS: The first component was a synthesis of peer-reviewed and grey literatures at the nexus of albinism, spiritual/cultural beliefs and practices, and human rights. We then conducted a priority-setting survey, informed by Delphi methods, on extant knowledge-practice gaps and research, advocacy, and policy priorities. Inclusion criteria included demonstrated expertise in the field (e.g., peer-reviewed publications, funded research), membership on national or international associations, or advocacy (civil society organizations) of more than 2 years in albinism and human rights. Thereafter, we gathered leading researchers, policy-makers, and civil society stakeholders for a Roundtable to gain consensus on these priorities. RESULTS: Access to skin and vision care, and education were not deemed high priority for research, likely because the evidence supporting the need for these is well established. However, they were priorities for advocacy and policy: what is needed is mobilization of this evidence through advocacy and implementation of such services (policy). Other social determinants of health (rurality, poverty, and gender equality) are present as subtext in the findings, more so than priorities for research, advocacy, or policy, despite their preponderance in the lives of persons with albinism. Research was prioritized on stigma and discrimination; advocacy; and witchcraft, but with some differentiation between Global North and Global South priorities. Priorities for research, advocacy, and policy vary in keeping with the explanatory frameworks at play, including how harmful practices and witchcraft are viewed. CONCLUSIONS: The lived experience of albinism is profoundly shaped by the social determinants of health (SDOH). Threats to the security and well-being of persons with albinism should be viewed through a human rights lens that encompasses the explanatory frameworks at play.

Quality of life of the Canadian population using the VR-12: population norms for health utility values, summary component scores and domain scores.

OBJECTIVES: To estimate Canadian population norms (health utility values, summary component scores and domain scores) for the VR-12. METHODS: English and French speaking Canadians aged 18 and older completed an online survey that included sociodemographic questions and standardized health status instruments, including the VR-12. Responses to the VR-12 were summarized as: (i) a health utility value; (ii) mental and physical component summary scores (MCS and PCS, respectively), and (iii) eight domain scores. Norms were calculated for the full sample and by gender, age group, and province/territory (univariate), and for several multivariate stratifications (e.g., age group and gender). Results were summarized using descriptive statistics, including number of respondents, mean and standard deviation (SD), median and percentiles (25th and 75th), and minimum and maximum. RESULTS: A total of 6761 people who clicked on the survey link completed the survey (83.4% completion rate), of whom 6741 (99.7%) were included in the analysis. The mean health utility score was 0.698 (SD = 0.216). Mean health utility scores tended to be higher in older age groups, ranging from 0.661 (SD = 0.214) in those aged 18-29 to 0.728 (SD = 0.310) in those aged 80+. Average MCS scores were higher in older age groups, while PCS scores were lower. Females consistently reported lower mean health utility values, summary component scores and domain scores compared with males. CONCLUSIONS: This is the first study to present Canadian norms for the VR-12. Health utility norms can serve as a valuable input for Canadian economic models, while summary component and domain norms can help interpret routinely-collected data.

Response shift results of quantitative research using patient-reported outcome measures: a descriptive systematic review.

PURPOSE: The objective of this systematic review was to describe the prevalence and magnitude of response shift effects, for different response shift methods, populations, study designs, and patient-reported outcome measures (PROM)s. METHODS: A literature search was performed in MEDLINE, PSYCINFO, CINAHL, EMBASE, Social Science Citation Index, and Dissertations & Theses Global to identify longitudinal quantitative studies that examined response shift using PROMs, published before 2021. The magnitude of each response shift effect (effect sizes, R-squared or percentage of respondents with response shift) was ascertained based on reported statistical information or as stated in the manuscript. Prevalence and magnitudes of response shift effects were summarized at two levels of analysis (study and effect levels), for recalibration and reprioritization/reconceptualization separately, and for different response shift methods, and population, study design, and PROM characteristics. Analyses were conducted twice: (a) including all studies and samples, and (b) including only unrelated studies and independent samples. RESULTS: Of the 150 included studies, 130 (86.7%) detected response shift effects. Of the 4868 effects investigated, 793 (16.3%) revealed response shift. Effect sizes could be determined for 105 (70.0%) of the studies for a total of 1130 effects, of which 537 (47.5%) resulted in detection of response shift. Whereas effect sizes varied widely, most median recalibration effect sizes (Cohen's d) were between 0.20 and 0.30 and median reprioritization/reconceptualization effect sizes rarely exceeded 0.15, across the characteristics. Similar results were obtained from unrelated studies. CONCLUSION: The results draw attention to the need to focus on understanding variability in response shift results: Who experience response shifts, to what extent, and under which circumstances?

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Patient-driven research priorities for patient-centered measurement.

BACKGROUND: Patient-centred measurement (PCM) emphasizes a holistic approach wherein the voices of patients are reflected in the standardized use of patient-reported outcome and experience measures and are represented throughout the continuum of measurement activities. Given the challenges of routinely integrating patient self-reports into clinical care decisions, the perspectives of all healthcare system stakeholders, especially patients, is necessary to advance the science of PCM. The purpose of the analysis we report on here was to identify patient-driven research priorities for advancing the science of PCM. METHODS: We analyzed data from seven focus groups that were conducted across British Columbia, Canada and that included a total of 73 patients, using qualitative inductive analysis and constant comparative methods. RESULTS: We found that the patients conveyed a desire for PCM to contribute to healthcare decisions, specifically that their individual healthcare needs and related priorities as they see them are always front and centre, guiding all healthcare interactions. The patients' commentaries highlighted intersecting priorities for research on advancing the science of PCM that would help transform care by (1) enhancing the patient-provider relationship, (2) giving voice to patients' stories, (3) addressing inclusivity, (4) ensuring psychological safety, (5) improving healthcare services and systems to better meet patient needs, and (6) bolstering healthcare system accountability. CONCLUSIONS: These priorities provide direction for future research efforts that would be positioned to make progress towards better health, better care, and better use of resources for individuals and for society.

Predictors of preparedness for recovery following colorectal cancer surgery: a latent class trajectory analysis.

AIM: With an interest in providing knowledge for person-centred care, our overall goal is to contribute a greater understanding of diversity among patients in terms of their preparedness before and up to six months after colorectal cancer surgery. Our aim was to describe and provide a tentative explanation for differences in preparedness trajectory profiles. MATERIAL AND METHODS: The study was explorative and used prospective longitudinal data from a previously published intervention study evaluating person-centred information and communication. The project was conducted at three hospitals in Sweden. Patient-reported outcomes measures, including the Longitudinal Preparedness for Colorectal Cancer Surgery Questionnaire, were collected before surgery, at discharge, and four to six weeks, three months, and six months after surgery. Clinical data were retrospectively obtained from patients' medical records. We used latent class growth models (LCGMs) to identify latent classes that distinguish subgroups of patients who represent different preparedness trajectory profiles. To determine the most plausible number of latent classes, we considered statistical information about model fit and clinical practice relevance. We used multivariable regression models to identify variables that explain the latent classes. RESULTS: The sample (N = 488) comprised people with a mean age of 68 years (SD = 11) of which 44% were women. Regarding diagnoses, 60% had colon cancer and 40% rectal cancer. The LCGMs identified six latent classes with different preparedness for surgery and recovery trajectories. The latent classes were predominantly explained by differences in age, sex, physical classification based on comorbidities, treatment hospital, global health status, distress, and sense of coherence (comprehensibility and meaningfulness). CONCLUSION: Contrary to the received view that emphasizes standardized care practices, our results point to the need for adding person-centred and tailored approaches that consider individual differences in how patients are prepared before and during the recovery period related to colorectal cancer surgery.

Measuring skill-based health literacy in chronic airway disease patients: the development and psychometric evaluation of the Vancouver airways health literacy tool (VAHLT).

PURPOSE: This article describes the development of the Vancouver airways health literacy tool (VAHLT), a novel measure of skill-based health literacy specific to chronic airway diseases (CADs). Across several phases, psychometric characteristics of the VAHLT were examined and used to guide its development. METHODS: An initial pool of 46 items was developed using input from patients, clinicians, researchers, and policy-makers. An initial patient sample (N = 532) was evaluated and used to inform item revisions. A revised 44-item pool was then evaluated using a second sample, the results of which aided in the selection of a final set of 30 items. The finalized 30-item VAHLT was then psychometrically evaluated using the second sample (N = 318). An item response theory approach was utilized to evaluate the VAHLT by assessing model fit, item parameter estimates, test and item information curves, and item characteristic curves. Reliability was assessed using ordinal coefficient alpha. We additionally assessed differential item functioning between asthma and COPD diagnoses. RESULTS: The VAHLT demonstrated a unidimensional structure and reasonably discriminated patients in the lower range of health literacy estimates. The tool demonstrated strong reliability (α = .920). Two of the 30 items were found to exhibit non-negligible differential item functioning. CONCLUSIONS: This study presents compelling evidence of validity in several areas for the VAHLT, including content and structural validity. Further external validation studies are needed and forthcoming. Overall, this work represents a strong first step towards a novel, skill-based, and disease-specific measure of CAD-related health literacy.

Patient-reported mental health and well-being trajectories in oncology patients during radiation therapy: an exploratory retrospective cohort analysis using the Ontario Cancer Registry.

PURPOSE: Mental health and well-being trajectories are not expected to be homogeneous in diverse clinical populations. This exploratory study aims to identify subgroups of patients with cancer receiving radiation therapy who have different mental health and well-being trajectories, and examine which socio-demographic, physical symptoms, and clinical variables are associated with such trajectories. METHODS: Retrospective analysis of radiation therapy patients diagnosed with cancer in 2017 was conducted using data from the Ontario Cancer Registry (Canada) and linked with administrative health data. Mental health and well-being were measured using items from the Edmonton Symptom Assessment System-revised questionnaire. Patients completed up to 6 repeated measurements. We used latent class growth mixture models to identify heterogeneous mental health trajectories of anxiety, depression, and well-being. Bivariate multinomial logistic regressions were conducted to explore variables associated with the latent classes (subgroups). RESULTS: The cohort (N = 3416) with a mean age of 64.5 years consisted of 51.7% females. Respiratory cancer was the most common diagnosis (30.4%) with moderate to severe comorbidity burden. Four latent classes with distinct anxiety, depression, and well-being trajectories were identified. Decreasing mental health and well-being trajectories are associated with being female; living in neighborhoods with lower income, greater population density, and higher proportion of foreign-born individuals; and having higher comorbidity burden. CONCLUSIONS: The findings highlight the importance of considering social determinants of mental health and well-being, in addition to symptoms and clinical variables, when providing care for patients undergoing radiation therapy.

Implications of the syntheses on definition, theory, and methods conducted by the Response Shift - in Sync Working Group.

PURPOSE: Our aim is to advance response shift research by explicating the implications of published syntheses by the Response Shift - in Sync Working Group in an integrative way and suggesting ways for improving the quality of future response shift studies. METHODS: Members of the Working Group further discussed the syntheses of the literature on definitions, theoretical underpinnings, operationalizations, and response shift methods. They outlined areas in need of further explication and refinement, and delineated additional implications for future research. RESULTS: First, the proposed response shift definition was further specified and its implications for the interpretation of results explicated in relation to former, published definitions. Second, the proposed theoretical model was further explained in relation to previous theoretical models and its implications for formulating research objectives highlighted. Third, ways to explore alternative explanations per response shift method and their implications for response shift detection and explanation were delineated. The implications of the diversity of the response shift methods for response shift research were presented. Fourth, the implications of the need to enhance the quality and reporting of the response shift studies for future research were sketched. CONCLUSION: With our work, we intend to contribute to a common language regarding response shift definitions, theory, and methods. By elucidating some of the major implications of earlier work, we hope to advance response shift research.

The Use of Generic Patient-Reported Outcome Measures in Emergency Department Surveys: Discriminant Validity Evidence for the Veterans RAND 12-Item Health Survey and the EQ-5D.

OBJECTIVES: This study aimed to compare discriminant validity evidence of 2 generic patient-reported outcome measures (PROMs), the Veterans RAND 12-Item Health Survey (VR-12) and level 5 of EQ-5D (EQ-5D-5L), for use in emergency departments (EDs). METHODS: Data were obtained via a cross-sectional survey of 5876 patients in British Columbia (Canada) who completed a questionnaire after visiting an ED in 2018. We compared the extent to which the VR-12 and the EQ-5D-5L distinguished among groups of ED patients with different levels of comorbidity burden and self-reported physical and mental or emotional health status. Multivariable logistic regression was used to evaluate the ability of the 2 PROMs to identify patients presenting with a mental health (MH) condition. RESULTS: All the measures produced small effect sizes (ESs) for discriminating comorbidity levels (R2 range: 0.00 [VR-12 mental component summary {MCS}] to 0.10 [VR-12 physical component summary score]). The EQ-5D visual analog scale offered the largest ES for discriminating self-reported physical health (R2 = 0.48), whereas the MCS, the VR-12 MH domain, and the EQ-5D-5L anxiety/depression dimension had the largest ESs for discriminating self-reported mental or emotional health (R2 = 0.42, 0.40, and 0.38, respectively). The MCS produced a medium ES (R2 = 0.42) along with the VR-12 utility score (R2 = 0.27) compared with the EQ-5D-5L index (R2 = 0.19). Having a MH condition was predominantly identified by the MCS (Pratt index = 0.56). CONCLUSIONS: The VR-12 PROM provides a more comprehensive measurement of MH than the EQ-5D-5L, which is important to inform healthcare service needs for patients who present in EDs with MH challenges.

Accuracy of mixture item response theory models for identifying sample heterogeneity in patient-reported outcomes: a simulation study.

PURPOSE: Mixture item response theory (MixIRT) models can be used to uncover heterogeneity in responses to items that comprise patient-reported outcome measures (PROMs). This is accomplished by identifying relatively homogenous latent subgroups in heterogeneous populations. Misspecification of the number of latent subgroups may affect model accuracy. This study evaluated the impact of specifying too many latent subgroups on the accuracy of MixIRT models. METHODS: Monte Carlo methods were used to assess MixIRT accuracy. Simulation conditions included number of items and latent classes, class size ratio, sample size, number of non-invariant items, and magnitude of between-class difference in item parameters. Bias and mean square error in item parameters and accuracy of latent class recovery were assessed. RESULTS: When the number of latent classes was correctly specified, the average bias and MSE in model parameters decreased as the number of items and latent classes increased, but specification of too many latent classes resulted in modest decrease (i.e., < 10%) in the accuracy of latent class recovery. CONCLUSION: The accuracy of MixIRT model is largely influenced by the overspecification of the number of latent classes. Appropriate choice of goodness-of-fit measures, study design considerations, and a priori contextual understanding of the degree of sample heterogeneity can guide model selection.

Knowledge translation resources to support the use of quality of life assessment tools for the care of older adults living at home and their family caregivers.

PURPOSE: To support the use of quality of life (QOL) assessment tools for older adults, we developed knowledge translation (KT) resources tailored for four audiences: (1) older adults and their family caregivers (micro), (2) healthcare providers (micro), (3) healthcare managers and leaders (meso), and (4) government leaders and decision-makers (macro). Our objectives were to (1) describe knowledge gaps and resources and (2) develop corresponding tailored KT resources to support use of QOL assessment tools by each of the micro-, meso-, and macro-audiences. METHODS: Data were collected in two phases through semi-structured interviews/focus groups with the four audiences in Canada. Data were analyzed using qualitative description analysis. KT resources were iteratively refined through formative evaluation. RESULTS: Older adults and family caregivers (N = 12) wanted basic knowledge about what "QOL assessment" meant and how it could improve their care. Healthcare providers (N = 13) needed practical solutions on how to integrate QOL assessment tools in their practice. Healthcare managers and leaders (N = 14) desired information about using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) in healthcare programs and quality improvement. Government leaders and decision-makers (N = 11) needed to know how to access, use, and interpret PROM and PREM information for decision-making purposes. Based on these insights and evidence-based sources, we developed KT resources to introduce QOL assessment through 8 infographic brochures, 1 whiteboard animation, 1 live-action video, and a webpage. CONCLUSION: Our study affirms the need to tailor KT resources on QOL assessment for different audiences. Our KT resources are available: www.healthyqol.com/older-adults .

Centredness in health care: A systematic overview of reviews.

INTRODUCTION: The introduction of effective, evidence-based approaches to centredness in health care is hindered by the fact that research results are not easily accessible. This is partly due to the large volume of publications available and because the field is closely linked to and in some ways encompasses adjoining fields of research, for example, shared decision making and narrative medicine. In an attempt to survey the field of centredness in health care, a systematic overview of reviews was conducted with the purpose of illuminating how centredness in health care is presented in current reviews. METHODS: Searches for relevant reviews were conducted in the databases PubMed, Scopus, Cinahl, PsychINFO, Web of Science and EMBASE using terms connected to centredness in health care. Filters specific to review studies of all types and for inclusion of only English language results as well as a time frame of January 2017-December 2018, were applied. RESULTS: The search strategy identified 3697 unique reviews, of which 31 were included in the study. The synthesis of the results from the 31 reviews identified three interrelated main themes: Attributes of centredness (what centredness is), Translation from theory into practice (how centredness is done) and Evaluation of effects (possible ways of measuring effects of centredness). Three main attributes of centeredness found were: being unique, being heard and shared responsibility. Aspects involved in translating theory into practice were sufficient prerequisites, strategies for action and tools used in safeguarding practice. Further, a variety and breadth of measures of effects were found in the included reviews. CONCLUSIONS: Our synthesis demonstrates that current synthesized research literature on centredness in health care is broad, as it focuses both on explorations of the conceptual basis and the practice, as well as measures of effects. This study provides an understanding of the commonalities identified in the reviews on centredness in healthcare overall, ranging from theory to practice and from practice to evaluation. PATIENT OR PUBLIC CONTRIBUTION: Patient representatives were involved during the initiation of the project and in decisions about its focus, although no patient or public representatives made direct contributions to the review process.

Relating person-centredness to quality-of-life assessments and patient-reported outcomes in healthcare: A critical theoretical discussion.

Engagement with the historical and theoretical underpinnings of measuring quality of life (QoL) and patient-reported outcomes (PROs) in healthcare is important. Ideas and values that shape such practices-and in the endgame, people's lives-might otherwise remain unexamined, be taken for granted or even essentialized. Our aim is to explicate and theoretically discuss the philosophical tenets underlying the practices of QoL assessment and PRO measurement in relation to the notion of person-centredness. First, we engage with the late-modern history of the concept of QoL and the act of assessing and measuring it. Working with the historical method of genealogy, we describe the development of both QoL assessments and PRO measures (PROMs) within healthcare by accounting for the contextual conditions for their possibility. In this way, the historical and philosophical underpinnings of these measurement practices are highlighted. We move on to analyse theoretical and philosophical underpinnings regarding the use of PROMs and QoL assessments in clinical practice, as demonstrated in review studies thereof. Finally, we offer a critical analysis regarding the state of theory in the literature and conclude that, although improved person-centredness is an implied driver of QoL assessments and PROMs in clinical practice, enhanced theoretical underpinning of the development of QoL assessments is called for.

Measuring Health Status in Long-Term Residential Care: Adapting the Veterans RAND 12 Item Health Survey (VR-12©).

Objectives: Measuring the perceived mental and physical health status of older adults living in long-term residential care (LTRC) is central to patient-centered care. This study examined the qualitative content validity of the Veterans RAND 12 Item Health Survey (VR-12) for LTRC and, based on the findings, the authors developed an adapted version of the generic patient-reported outcome measure for this population.Methods: Content validity was evaluated in two steps: (1) initial resident feedback (n = 9) and research team consensus discussions and (2) cognitive interviews with residents (n = 18) and a research team consensus discussion. The cognitive interviews examined comprehension, acceptability, and relevance of the VR-12 items.Results: Two VR-12 items had limited acceptability in the LTRC setting, the reference to "work" in items was irrelevant to residents, and the lack of a frame of reference ("During the past week … ") impacted comprehension of several items.Conclusions: Study findings informed the development of an adapted version of the VR-12 for older adults living in Canadian LTRC homes and provided content validity evidence regarding its relevance and appropriateness for this population.Clinical implications: Measuring the health status of older adults living in LTRC can help to monitor changes in health status over time and support person-centered care.

Quality of Life in Epilepsy: Same questions, but different meaning to different people.

OBJECTIVES: Patient-reported outcome measures (PROMs) are used widely to elicit patient's self-appraisal of their health status and quality of life. One fundamental assumption when measuring PROMs is that all individuals interpret questions about their health status in a consistent manner. However, subgroups of patients with a similar health condition may respond differently to PROM questions (ie, differential item functioning [DIF]), leading to biased estimates of group differences on PROM scores. Understanding these differences can help inform the clinical interpretation of PROMs. This study examined whether DIF affects 10-item Quality of Life in Epilepsy (QOLIE10) scores reported by patients with epilepsy in outpatient clinics. METHODS: Data were from the Calgary Comprehensive Epilepsy Program, a prospective registry of patients with epilepsy in Calgary, Alberta. Latent variable mixture models (LVMMs) based on standard two-parameter graded response models with increasing numbers of latent classes were applied to QOLIE10 item data. Model fit was assessed using the Bayesian Information Criterion (BIC) and latent class model entropy. Ordinal logistic regression was used to identify QOLIE10 items that exhibited DIF. RESULTS: In this cohort of 1143 patients, 567 (49.6%) were female and the median age was 37.0 (interquartile range [IQR] 27.0) years. A two-class LVMM, which provided the best fit to the data, identified two subgroups of patients with different response patterns to QOLIE10 items, with class proportions of 0.62 and 0.38. The two subgroups differed with respect to antiseizure polytherapy, reported medication side effects, frequency of seizures, and psychiatric comorbidities. QOLIE10 items on the physical and psychological side effects of medication exhibited large DIF effects. SIGNIFICANCE: Our study revealed two different response patterns to quality-of-life instruments, suggesting heterogeneity in how patients interpret some of the questions. Researchers and users of PROMs in epilepsy need to consider the differential interpretation of items for various instruments to ensure valid understanding and comparisons of PROM scores.

Cognitive subgroups in first episode bipolar I disorder: Relation to clinical and brain volumetric variables.

OBJECTIVE: Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by 'early neurodevelopmental' (low premorbid IQ and intracranial volume) versus 'later neurodevelopmental' (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology. METHODS: Recently recovered first manic episode BDI patients (n = 91) and healthy controls (HC, n = 63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non-verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes. RESULTS: Three cognitive subgroups emerged: (i) globally impaired (GI, n = 31), scoring 0.5-1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n = 47), with predominant processing speed deficits and (iii) high performing (HP, n = 13), with above-average cognitive performance. GI patients showed a 'later neurodevelopmental' pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p = 0.003). GI patients had higher left frontal pole GM versus HC (p < 0.05, FWE corrected). CONCLUSIONS: A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.

Growth mixture models: a case example of the longitudinal analysis of patient-reported outcomes data captured by a clinical registry.

BACKGROUND: An assumption in many analyses of longitudinal patient-reported outcome (PRO) data is that there is a single population following a single health trajectory. One approach that may help researchers move beyond this traditional assumption, with its inherent limitations, is growth mixture modelling (GMM), which can identify and assess multiple unobserved trajectories of patients' health outcomes. We describe the process that was undertaken for a GMM analysis of longitudinal PRO data captured by a clinical registry for outpatients with atrial fibrillation (AF). METHODS: This expository paper describes the modelling approach and some methodological issues that require particular attention, including (a) determining the metric of time, (b) specifying the GMMs, and (c) including predictors of membership in the identified latent classes (groups or subtypes of patients with distinct trajectories). An example is provided of a longitudinal analysis of PRO data (patients' responses to the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire) collected between 2008 and 2016 for a population-based cardiac registry and deterministically linked with administrative health data. RESULTS: In determining the metric of time, multiple processes were required to ensure that "time" accounted for both the frequency and timing of the measurement occurrences in light of the variability in both the number of measures taken and the intervals between those measures. In specifying the GMM, convergence issues, a common problem that results in unreliable model estimates, required constrained parameter exploration techniques. For the identification of predictors of the latent classes, the 3-step (stepwise) approach was selected such that the addition of predictor variables did not change class membership itself. CONCLUSIONS: GMM can be a valuable tool for classifying multiple unique PRO trajectories that have previously been unobserved in real-world applications; however, their use requires substantial transparency regarding the processes underlying model building as they can directly affect the results and therefore their interpretation.

Patient-reported outcomes and the identification of subgroups of atrial fibrillation patients: a retrospective cohort study of linked clinical registry and administrative data.

PURPOSE: Previous research about the health and quality of life of people with atrial fibrillation has typically identified a single health trajectory. Our study aimed to examine variability in health trajectories and patient characteristics associated with such variability. METHODS: We conducted a retrospective analysis of data collected between 2008 and 2016 for a cardiac registry in British Columbia (Canada) linked with administrative health data. The Atrial Fibrillation Effect on Quality of Life Questionnaire was used to measure health status at up to 10 clinic visits. Growth mixture models were used and a three-step multinomial logistic regression was conducted to identify predictors of subgroups with different trajectories. RESULTS: The patients (N = 7439) were primarily men (61.1%) over 60 years of age (72.9%). Three subgroups of health status trajectories were identified: "poor but improving", "good and stable", and "excellent and stable" health. Compared with the other two groups, patients in the "poor but improving group" were more likely to (1) be less than 60 years of age; (2) be women; (3) have greater risk of stroke; (4) have had ablation therapy within 6 months to 1 year or more than 2 years after their initial consultation; and (5) have had anticoagulation therapy within 6 months. CONCLUSION: Using growth mixture models, we found that not all health trajectories are the same. These models can help to understand variability in trajectories with different patient characteristics that could inform tailored interventions and patient education strategies.

Response shift in results of patient-reported outcome measures: a commentary to The Response Shift-in Sync Working Group initiative.

PURPOSE: The Working Group undertook a critical, comprehensive synthesis of the response shift work to date. We aimed to (1) describe the rationale for this initiative; (2) outline how the Working Group operated; (3) summarize the papers that comprise this initiative; and (4) discuss the way forward. METHODS: Four interdisciplinary teams, consisting of response shift experts, external experts, and new investigators, prepared papers on (1) definitions and theoretical underpinnings, (2) operationalizations and response shift methods, (3) implications for healthcare decision-making, and (4) on the published magnitudes of response shift effects. Draft documents were discussed during a two-day meeting. Papers were reviewed by all members. RESULTS: Vanier and colleagues revised the formal definition and theory of response shift, and applied these in an amended, explanatory model of response shift. Sébille and colleagues conducted a critical examination of eleven response shift methods and concluded that for each method extra steps are required to make the response shift interpretation plausible. Sawatzky and colleagues created a framework for considering the impact of response shift on healthcare decision-making at the level of the individual patient (micro), the organization (meso), and policy (macro). Sajobi and colleagues are conducting a meta-analysis of published response shift effects. Preliminary findings indicate that the mean effect sizes are often small and variable across studies that measure different outcomes and use different methods. CONCLUSION: Future response shift research will benefit from collaboration among diverse people, formulating alternative hypotheses of response shift, and conducting the most conclusive studies aimed at testing these (falsification).