Interplay of disability, caregiver impact, and out-of-pocket expenditures in Duchenne muscular dystrophy: a cohort study.

BACKGROUND: Providing caregiving support to people with Duchenne muscular dystrophy (DMD) is challenging, beginning in early childhood, and continuing through the progression of multidimensional disability. This study addressed the interplay between caregiver impact, out-of-pocket expenditures, and DMD disability. To examine these interconnections, we investigated the association between caregiver impact domains and out-of-pocket expenditures; and the presence of clusters in caregivers on the basis of DMD-related disability domains in the patients for whom they provided caregiving support. METHODS: This web-based study recruited 566 DMD caregivers (140 males, 426 females; mean age 41.6 years, SD 8.8, range 21-72), examining caregiver impact using the DMD Caregiver Impact Measure, PROMIS-derived parent-proxy (PPP) measures of their child's disability, and items tapping out-of-pocket expenditures related to home and vehicle accommodations and assistive devices. T-tests compared caregiver impact scores by out-of-pocket expenditures incurred. Latent Profile Analyses (LPA) were conducted to generate impact profiles related to child's disability as reported by caregiver proxies. RESULTS: Higher out-of-pocket expenditures were generally associated with worse impact on the subscales, but several expenditures (e.g., kitchen, bathroom, scooter) were associated with lower impact. LPA indicated that the four-group solution provided the best relative fit and yielded good profile separation (entropy = 0.91). Caregivers with lowest impact reported the highest mobility, cognitive, and upper extremity functioning of their DMD care recipients, whereas the highest caregiver impact was driven by their care recipient's negative affect and fatigue. The upper-middle impact group showed great variability in proxy-disability domains, whereas the lower-middle group had similar levels of disability across domains. Profiles were represented across all child ages. CONCLUSION: Out-of-pocket expenditures were often associated with worse caregiver impact, but some associated with milder impact (i.e., bathroom or kitchen modification, investing in a ceiling lift or medical scooter). While their son's level of disability and age were related to impact on the DMD caregiver, the domains giving rise to highest caregiver impact were not the most visible aspects of disability, such as mobility, but rather negative affect and fatigue. Other contextual attributes are likely implicated, and will be addressed in the companion paper.

Drivers of caregiver impact in Duchenne muscular dystrophy: a cohort study.

BACKGROUND: In our companion paper, we addressed the interplay between caregiver impact, out-of-pocket expenditures, and Duchenne Muscular Dystrophy (DMD) disability. We found that DMD caregiver impact could be characterized by four Latent Profile Analysis impact profiles: lowest, lower middle, upper middle, and highest impact. The impact on caregivers was often but not always worse with greater out-of-pocket expenditures. Further, while the lowest-, lower-middle, and highest-impact profiles reflected low, moderate and high disability-related caregiver burden, respectively, the upper-middle profile group was quite variable in level of disability across domains. To better understand the four caregiver-impact profiles, we examine how a comprehensive set of psychosocial factors differentiate the four profile groups. METHODS: Psychosocial factors assessed included demographic characteristics, quality of life (QOL), stress, cognitive appraisal, reserve-building, and general and COVID-specific resilience. Linear modeling examined relationships between impact profiles and psychosocial factors. We used effect size rather than p-value as the criterion for determining relevance of the broad range of characteristics examined. RESULTS: Multivariate analyses implicated stress and environmental mastery, appraisal sampling of experience, COVID-specific variables, appraisal standards of comparison, appraisal goals, demographics, appraisal combinatory algorithm, reserve-building, and resilience, in order of prominence (average eta2 = 0.29, 0.29, 0.16, 0.15, 0.09, 0.07, 0.07, 0.06, 0.05, and 0.02, respectively). On the whole, comparisons of highest-versus-lowest impact profiles revealed more and larger differences than comparisons of upper-middle versus lower-middle impact profiles. Life stress, goals, and reserve-building activities had a smaller differentiating effect in the middle groups. CONCLUSION: A more comprehensive 'story' about DMD caregiver impact involves life stress, environmental mastery, COVID-specific variables, and cognitive and behavioral factors. Implications are discussed for coaching interventions to support DMD caregivers.

If it's information, it's not "bias": a scoping review and proposed nomenclature for future response-shift research.

BACKGROUND: The growth in response-shift methods has enabled a stronger empirical foundation to investigate response-shift phenomena in quality-of-life (QOL) research; but many of these methods utilize certain language in framing the research question(s) and interpreting results that treats response-shift effects as "bias," "noise," "nuisance," or otherwise warranting removal from the results rather than as information that matters. The present project will describe the various ways in which researchers have framed the questions for investigating response-shift issues and interpreted the findings, and will develop a nomenclature for such that highlights the important information about resilience reflected by response-shift findings. METHODS: A scoping review was done of the QOL and response-shift literature (n = 1100 articles) from 1963 to 2020. After culling only empirical response-shift articles, raters characterized how investigators framed and interpreted study research questions (n = 164 articles). RESULTS: Of 10 methods used, papers using four of them utilized terms like "bias" and aimed to remove response-shift effects to reveal "true change." Yet, the investigators' reflections on their own conclusions suggested that they do not truly believe that response shift is error to be removed. A structured nomenclature is proposed for discussing response-shift results in a range of research contexts and response-shift detection methods. CONCLUSIONS: It is time for a concerted and focused effort to change the nomenclature of those methods that demonstrated this misinterpretation. Only by framing and interpreting response shift as information, not bias, can we improve our understanding and methods to help to distill outcomes with and without response-shift effects.

Expanding the purview of wellness indicators: validating a new measure that includes attitudes, behaviors, and perspectives.

OBJECTIVE: The present study validated the DeltaQuest Wellness Measure (DQ Wellness), a new 15-item measure of wellness that spans relevant attitudes, behaviors, and perspectives. DESIGN: This cross-sectional web-based study recruited chronically-ill patients and/or caregivers (n = 3,961) and a nationally representative comparison group (n = 855). MAIN OUTCOME MEASURES: The DQ Wellness assesses: a way of being in the world that involves seeing and embracing the good and expressing kindness toward others; engagement in one's activities and self-care; downplaying negative thoughts that reduce one's energy; and an ability to feel joy. Six widely used measures of physical and mental health, cognition, and psychological well-being enabled construct-validity comparisons. Item-response theory (IRT) methods evaluated reliability, factor structure, and differential item functioning (DIF) by gender. RESULTS: The DQ Wellness showed strong cross-sectional reliability (marginal reliability = 0.89) and fit a bifactor model (RMSEA = 0.063, CFI = 0.982, TLI = 0.983). The DQ Wellness general score demonstrated construct validity, convergent and divergent validity, unique variance, and known-groups validity, and minimal gender DIF. The study is limited to addressing cross-sectional reliability and validity, and response rates are not known due to the recruitment source. CONCLUSION: The DQ Wellness is a relatively brief measure, taps novel content, and could be useful for observational or interventional studies.

Measuring Duchenne muscular dystrophy impact: development of a proxy-reported measure derived from PROMIS item banks.

BACKGROUND: Person-reported outcomes measurement development for rare diseases has lagged behind that of more common diseases. In studies of caregivers of patients with rare diseases, one relies on proxy report to characterize this disability. It is important to measure the child's disability accurately and comprehensively because it affects caregiver burden. We aimed to create a condition-specific caregiver proxy-report measure for Duchenne Muscular Dystrophy (DMD) in order to understand the impact of DMD on the caregiver. Drawing on relevant item banks from the Patient-Reported Outcome Measurement Information System (PROMIS), we sought to confirm their reliability and validity in the target sample of DMD caregivers. METHODS: This web-based study recruited DMD caregivers via Rare Patient Voice, patient-advocacy groups, and word of mouth. Recruitment was stratified by age of the caregiver's child with DMD, which broadly represents stages of DMD progression: 2-7, 8-12, 13-17, and > 18. Telephone interviews with DMD parent-caregivers pretested possible measures for content validity. The web-based study utilized an algorithm to categorize respondents' ambulatory status for tailored administration of PROMIS Parent-Proxy items as well as some new items developed based on caregiver interviews. Item response theory analyses were implemented. RESULTS: The study sample included 521 DMD caregivers representing equally the four age strata. The proxy-report measure included the following domains: fatigue impact, strength impact, cognitive function, upper extremity function, positive affect, negative affect, sleep-device symptoms, and mobility. The first five domains had strong psychometric characteristics (unidimensionality; acceptable model fit; strong standardized factor loadings; high marginal reliability). Negative Affect, covering anger, anxiety, depressive symptoms, and psychological stress, fit a bifactor model with good model fit, high marginal reliability, and strong factor loadings. The Sleep-device symptoms domain was not unidimensional, and the mobility domain did not have a simple structure due to residual correlations among items at opposite end of the mobility-disability continuum. These two domain scores were retained as clinimetric indices (i.e., uncalibrated scales), to achieve the overall goal of having a content-valid DMD-specific measure across all stages of disease severity. CONCLUSIONS: The present study derived a DMD-specific proxy-report measure from PROMIS item banks and supplemental items that could potentially be utilized in caregiver research across all stages of the care recipient's DMD. Future research will focus on assessing the responsiveness and validity of the measure over time and its comparison to DMD patient self-report.

Characterizing the quality-of-life impact of Duchenne muscular dystrophy on caregivers: a case-control investigation.

BACKGROUND: This study examined the impact of Duchenne muscular dystrophy (DMD) on family-member caregivers in terms of quality of life, life stress, and indirect costs, as compared to a stratified comparison group of parents of similar-age children without DMD. METHODS: A web-based survey included DMD caregivers and a nationally representative comparison group of parents of children without DMD stratified by Child Age Group. Outcomes included quality of life, resilience, caregiver impact, stressful life events, financial strain, out-of-pocket expenditures, work productivity and unrealized ambitions. General linear models assessed the main effect of Caregiver Group and the interaction of Caregiver Group with Child-Age-Group, after adjusting for demographic covariates. RESULTS: Compared to parents without a DMD child, DMD Caregivers reported better physical health but worse mental health, positive affect/well-being, environmental mastery, difficulty paying bills, and more hours missed from work. Providing caregiving support for DMD teenagers was the most challenging. DMD caregivers curtailed their educational and professional ambitions, and modified their homes to accommodate the disability associated with DMD. Their non-DMD children had to make sacrifices as well. Nonetheless, in resilience and life stress, DMD caregivers were comparable to the comparison group, and showed consistent levels of positive emotions across the age of their DMD child. CONCLUSION: DMD caregivers fared worse on most outcomes and faced more hurdles in work life. They face constraints and hidden costs that impact their health and financial well-being. Caregivers of teenagers with DMD reported higher impact. Nonetheless, parents of DMD children of all ages maintained notable resilience and positivity.

Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria.

AIMS: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening intravascular hematologic disorder with significant morbidity and premature mortality. Clinical trials (NCT02946463 and NCT03056040) comparing ravulizumab with eculizumab for PNH have supported the non-inferiority of the former and similar safety and tolerability. This secondary analysis compared PNH trial participants after 26 weeks on either treatment (n = 438) to a general-population sample (GenPop) (n = 15,386) and investigated response-shift effects. METHODS: Multivariate analysis of covariance (MANCOVA) investigated function and symptom scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 of people with PNH as compared to GenPop, after covariate adjustment. Risk-factor groups were created based on clinical indicators known to be associated with worse PNH outcomes, and separate MANCOVAs were computed for lower- and higher-risk-factor groups. Differential item functioning (DIF) analyses examined whether item response varied systematically (1) by treatment, (2) compared to GenPop, and (3) over time, the latter two suggesting and reflecting response-shift effects, respectively. DIF analyses examined 24 items from scales with at least two items. Recalibration response shift was operationalized as uniform DIF over time, reflecting the idea that, for a given group, the difficulty of endorsing an item changes over time, after adjusting for the total subscale score. Reprioritization response shift was operationalized as non-uniform DIF over time, i.e., the relative difficulty of endorsing an item over time changes across the total domain score. RESULTS: Across PNH risk-factor levels, people who had been on either treatment for 26 weeks reported better-than-expected functioning and lower symptom burden compared to GenPop. Ravulizumab generally showed larger effect sizes. Results were similar for lower and higher PNH risk factors, with slightly stronger effects in the former. DIF analyses revealed no treatment DIF, but did uncover group DIF (9 items with uniform DIF, and 11 with non-uniform) and DIF over time (7 items with uniform DIF, and 3 with non-uniform). CONCLUSIONS: This study revealed that people with PNH on ravulizumab or eculizumab for 26 weeks reported QOL levels better than those of the general population. Significant effects of DIF by group and DIF over time support recalibration and reprioritization response-shift effects. These findings suggest that the treatments enabled adaptive changes.

No impact of Asian ethnicity on EORTC QLQ-C30 scores: Group differences and differential item functioning in paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening terminal-complement-mediated disease resulting in intravascular hemolysis and thrombosis with significant morbidity and premature mortality. There exists no disease-specific quality-of-life (QOL) measure for PNH. Its QOL effects resemble those of hematologic cancers, which supports the use of cancer-specific QOL measures in PNH clinical trials. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 has published norms for many European and North American countries, but not for Asian countries. We investigated differences by Asian ethnicity in scores and item function on the EORTC QLQ-C30. METHODS: This secondary analysis focused on two non-inferiority PNH trials (301 and 302) comparing eculizumab and ravulizumab (n = 441). Analysis of covariance examined the main effect of Asian ethnicity on baseline EORTC QLQ-C30 scores, after adjusting for propensity scores encompassing trial, demographic and clinical factors. Mixed modeling of longitudinal data compared subscale scores in Asian vs. non-Asian patients, after propensity adjustment. Differential item function (DIF) was examined using ordinal regression models at baseline and longitudinally, to predict item score from total score, ethnicity, and their interaction to test for uniform DIF (significant main effect for Asian) and non-uniform DIF (significant Asian-by-total-score interaction). RESULTS: Of the 15 baseline domains, Asian patients scored slightly better on role and emotional functioning and slightly worse on constipation and diarrhea (0.22 < Cohen's d < 0.36). In longitudinal models, Asians reported slightly higher appetite loss, diarrhea, and financial difficulties than non-Asians (R2 increment < 0.0005). There was negligible uniform and non-uniform DIF, i.e., R2 0 to 0.018, far below Zumbo's (1999) criterion of 0.13. On average there were larger differences from norms for Asians (mean = 0.05, sd = 0.44) than non-Asians (mean = -0.07, sd = 0.36), but the size and direction of the differences varied considerably by domain, age, and gender. CONCLUSION: When compared to norms, Asian patients showed no systematic biases. DIF results supported this finding. We conclude that Asian ethnicity does not impact interpretation of EORTC QLQ-C30 scores.

Creating idiometric short-form measures of cognitive appraisal: balancing theory and pragmatics.

BACKGROUND: The Rapkin and Schwartz appraisal theory and measure provided a path toward documenting response-shift effects and describing individual differences in ways of thinking about quality of life (QOL) that distinguished people in different circumstances. Recent work developed and validated the QOL Appraisal Profileversion 2 (QOLAPv2), an 85-item measure that taps response-shift-detection domains of Frame of Reference, Standards of Comparison, Sampling of Experience, and Combinatory Algorithm. Recent theoretical work proposed that appraisal measurement constitutes a new class of measurement (idiometric), distinct from psychometric and clinimetric. To validate an idiometric measure, one would document that its items reflect different circumstances and population characteristics, and explain variance in QOL. The present work sought to develop idiometric short-forms of the QOLAPv2 item bank by examining which items were most informative, retaining the appraisal-domain structure. METHODS: This secondary analysis (n = 1481) included chronically-ill patients and their caregivers from a longitudinal web-based survey (mean follow-up 16.6 months). Data included the QOLAPv2, the Center for Disease Control Healthy Days Core Module, the PROMIS-10 Global Health, and demographic/medical variables. Appraisal items were measured at baseline (relevant to understanding cognitive appraisal processes); and with change scores (sensitive to response-shift effects). Multivariate analysis of covariance examined what demographic and health-status change variables were reflected by each of 85 appraisal items (in five sets), as dependent variables, and other demographic/medical variables. Multiple linear regression examined how appraisal items explained variance in global physical- and mental-health change, after covariate adjustment. A tally summarized item performance across all five sets of cross-sectional and longitudinal analyses. RESULTS: The vast majority (i.e., 80%) of the QOLAPv2 items performed well across the analyses presented. Using a relatively strict criterion of explaining meaningful variance across 60% of analyses, one would retain 68 items. A more lenient criterion (40%) would retain 71. CONCLUSIONS: The present study provides heuristics to support investigators' creating 'discretionary' QOLAPv2 short-forms to fit their study aim and amplifying individual differences in the cognitive processes underlying QOL. This approach enables adapting the measure to the study population, as per the expectation that respondent populations differ in the predominant cognitive processes used.

"Looking Under the Hood" of Anchor-Based Assessment of Clinically Important Change: A Machine Learning Approach.

OBJECTIVES: The Global Assessment of Change (GAC) item has facilitated the interpretation of change in patient-reported outcomes, providing an anchor for computing minimally important differences. Construct validity has been documented via disease-specific patient-reported outcomes change. We examined what domains, sociodemographic characteristics, attributions of change, and cognitive-appraisal processes are reflected in GAC ratings. METHODS: This secondary analysis examined data from 1,481 chronically ill patients and caregivers surveyed at baseline and 17 months. Items queried change since baseline in overall disease symptoms (GAC) and in physical, emotional, and social functioning. Candidate predictors included sociodemographic factors, health-related quality-of-life domains, change attributions, and quality-of-life appraisal processes. Least absolute shrinkage and selection operator and bootstrapping tested 77 predictors' effectiveness and stability. RESULTS: GAC worsening was notably associated with being disabled (ß = -0.24) and having difficulty paying bills (ß = -0.13). GAC was better explained by the physical domain than the emotional or social (ß = 0.67, 0.10, and 0.03, respectively; R2adj = 0.63) after sociodemographic-covariate adjustment. In a separate model (R2adj = 0.18), GAC variance was explained by attributions about changing health and changing response of one's health team, goals related to solving healthcare problems and maintaining activities, and appraisal about things getting better (ß = -0.14, 0.08, -0.07, 0.05, 0.21, respectively; prange ~0.0005-0.05) after adjustment. CONCLUSIONS: The GAC primarily reflects the physical domain, and the GAC reflects attributions, goals, and patterns of emphasis related to change in health and healthcare. Commonly unmeasured factors have some bearing on GAC scores and can facilitate the interpretation of change.

Moving toward better health: exercise practice is associated with improved outcomes after spine surgery in people with degenerative lumbar conditions.

Background: Recovery and rehabilitation following surgery can take many months. Understanding what patients can do to facilitate recovery would be beneficial for spinal surgeons. This study sought to evaluate the impact of exercise practice, before and after surgery, on long-term outcomes of spine surgery in a robust clinical sample. Methods: This prospective longitudinal cohort study included adult patients undergoing spinal surgery for degenerative spinal conditions. Patients were administered a survey that included preoperative and postoperative exercise practices and the following patient-reported outcome measures: the physical component score (PCS) and mental component score (MCS) of the Medical Outcomes Study 36-Item Short Form Survey (Rand-36), the Oswestry Disability Index (ODI) score, the Numeric Rating Scale (NRS) score for pain and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Short Form score. Random effects models investigated the relationship of exercise, follow-up time and their interaction in predicting each patient-reported outcome measure over time, with and without sociodemographic covariates. Results: There were 168 patients in the study sample with up to 12 months of follow-up data. Analysis revealed modest significant main effects of exercise on PCS, MCS, ODI and PROMIS scores and main effects of time on all outcomes. The exercise-by-time interaction was significant in predicting the trajectories of the ODI and MCS scores. When full models were adjusted for education and employment status, interaction effects were no longer significant, but exercise main effects remained significant for ODI score. Conclusion: Patients who engage in exercise before and after spine surgery have better mental health and spine-specific recovery trajectories than those who do not. All health care providers should encourage patients to exercise while they are waiting for surgery within preoperative limitations and as soon as they are able after surgery and to continue this over the long term.

Contexte: Le rétablissement et la réadaptation postopératoires s'échelonnent parfois sur plusieurs mois. Comprendre ce que les patients peuvent faire pour faciliter leur rétablissement serait utile aux spécialistes de la chirurgie de la colonne vertébrale. Cette étude a voulu évaluer l'impact de la pratique d'exercices avant et après une chirurgie de la colonne vertébrale sur son issue à long terme dans un solide échantillon clinique. Méthodes: Cette étude de cohorte longitudinale prospective a regroupé des patients adultes qui devaient subir une chirurgie de la colonne vertébrale pour des maladies dégénératives. Les patients ont été invités à répondre à un questionnaire qui portait entre autre sur la pratique d'exercices pré- et postopératoires et sur les paramètres autorapportés suivants : scores aux composantes physique (PCS) et mentale (MCS) du questionnaire SF-36 (Medical Outcomes Study 36-Item Short Form Survey [Rand-36]), à l'échelle d'incapacité d'Oswestry (ODI), à une échelle d'évaluation numérique (ÉÉN) de la douleur et au questionnaire court PROMIS (Patient-Reported Outcome Measurement Information System) sur l'interférence de la douleur. Des modèles à effets aléatoires ont permis d'analyser les liens entre l'exercice, la durée du suivi et leur interaction pour ce qui est de prédire chacun des paramètres autorapportés au fil du temps, avec et sans les covariables sociodémographiques. Résultats: L'étude a regroupé 168 patients et les données pour un suivi allant jusqu'à 12 mois. L'analyse a fait état d'effets majeurs significatifs modestes de l'exercice sur les paramètres PCS, MCS, ODI et PROMIS et d'effets majeurs du temps sur tous les paramètres. L'interaction entre exercices et durée du suivi a été significative pour prédire la trajectoire des scores ODI et MCS. Lorsque les modèles intégraux ont été ajustés pour tenir compte du niveau de scolarité et du statut professionnel, les effets de l'interaction n'étaient plus significatifs, mais les effets majeurs de l'exercice sont demeurés significatifs pour le score ODI. Conclusion: Les patients qui ont fait des exercices avant et après une chirurgie de la colonne vertébrale ont présenté des trajectoires plus favorables au plan de la santé mentale et du rétablissement de leur colonne vertébrale comparativement à ceux qui n'avaient pas fait d'exercices. Tous les professionnels de la santé devraient encourager les patients à faire des exercices pendant qu'ils attendent leur chirurgie en tenant compte de leurs limites préopératoires, à les reprendre le plus rapidement possible après la chirurgie et à les maintenir à long terme.

Patient factors that matter in predicting spine surgery outcomes: a machine learning approach.

OBJECTIVE: There is an increasing recognition of the importance of predictive analytics in spine surgery. This, along with the addition of personalized treatment, can optimize treatment outcomes. The goal of this study was to examine the value of clinical, demographic, expectation, and cognitive appraisal variables in predicting outcomes after surgery. METHODS: This prospective longitudinal cohort study followed adult patients undergoing spinal decompression and/or fusion surgery for degenerative spinal conditions. The authors focused on predicting the numeric rating scale (NRS) for pain, based on past research finding it to be the most responsive of the spine patient-reported outcomes. Clinical data included type of surgery, adverse events, comorbidities, and use of pain medications. Demographics included age, sex, employment status, education, and smoking status. Data on expectations related to pain relief, ability to do household and exercise/recreational activities without pain, preventing future disability, and sleeping comfort. Appraisal items addressed 22 cognitive processes related to quality of life (QOL). LASSO (least absolute shrinkage and selection operator) and bootstrapping tested predictors hierarchically to determine effective predictive subsets at approximately 10 months postsurgery, based on data either at baseline (model 1) or at approximately 3 months (model 2). RESULTS: The sample included 122 patients (mean age 61 years, with 53% being female). For model 1, analysis revealed better outcomes with patients expecting to be able to exercise or do recreational activities, focusing on recent events, and not focusing on how others see them (mean bootstrapped R2 [R2boot] = 0.12). For model 2, better outcomes were predicted by expecting symptom relief, focusing on the positive and on one's spinal condition (mean R2boot = 0.38). Bootstrapped analyses documented the stability of parameter estimates despite the small sample. CONCLUSIONS: Nearly 40% of the variance in spine outcomes was accounted for by cognitive factors, after adjusting for clinical and demographic factors. Different expectations and appraisal processes played a role in long- versus short-range predictions, suggesting that cognitive adaptation is important and relevant to pain relief outcomes after spine surgery. These results underscore the importance of addressing how people think about QOL and surgery outcomes to maximize the benefits of surgery.

Patient Factors That Matter in Predicting Hip Arthroplasty Outcomes: A Machine-Learning Approach.

BACKGROUND: Despite the success of total hip arthroplasty (THA), approximately 10%-15% of patients will be dissatisfied with their outcome. Identifying patients at risk of not achieving meaningful gains postoperatively is critical to pre-surgical counseling and clinical decision support. Machine learning has shown promise in creating predictive models. This study used a machine-learning model to identify patient-specific variables that predict the postoperative functional outcome in THA. METHODS: A prospective longitudinal cohort of 160 consecutive patients undergoing total hip replacement for the treatment of degenerative arthritis completed self-reported measures preoperatively and at 3 months postoperatively. Using four types of independent variables (patient demographics, patient-reported health, cognitive appraisal processes and surgical approach), a machine-learning model utilizing Least Absolute Shrinkage Selection Operator (LASSO) was constructed to predict postoperative Hip Disability and Osteoarthritis Outcome Score (HOOS) at 3 months. RESULTS: The most predictive independent variables of postoperative HOOS were cognitive appraisal processes. Variables that predicted a worse HOOS consisted of frequent thoughts of work (ß = -0.34), frequent comparison to healthier peers (ß = -0.26), increased body mass index (ß = -0.17), increased medical comorbidities (ß = -0.19), and the anterior surgical approach (ß = -0.15). Variables that predicted a better HOOS consisted of employment at the time of surgery (ß = 0.17), and thoughts related to family interaction (ß = 0.12), trying not to complain (ß = 0.13), and helping others (ß = 0.22). CONCLUSIONS: This clinical prediction model in THA revealed that the factors most predictive of outcome were cognitive appraisal processes, demonstrating their importance to outcome-based research. LEVEL OF EVIDENCE: Prognostic Level 1.

Response-shift effects in neuromyelitis optica spectrum disorder: estimating response-shift-adjusted scores using equating.

BACKGROUND: In our companion paper, random intercept models (RIMs) investigated response-shift effects in a clinical trial comparing Eculizumab to Placebo for people with neuromyelitis optica spectrum disorder (NMOSD). RIMs predicted Global Health using the EQ-5D Visual Analogue Scale item (VAS) to encompass broad criteria that people might consider. The SF36™v2 mental and physical component scores (MCS and PCS) helped us detect response shift in VAS. Here, we sought to "back-translate" the VAS into the MCS/PCS scores that would have been observed if response shift had not been present. METHODS: This secondary analysis utilized NMOSD clinical trial data evaluating the impact of Eculizumab in preventing relapses (n = 143). Analyses began by equating raw scores from the VAS, MCS, and PCS, and computing scores that removed response-shift effects. Correlation analysis and descriptive displays provided a more comprehensive examination of response-shift effects. RESULTS: MCS and PCS crosswalks with VAS equated the scores that include and exclude response-shift effects. These two sets of scores had low shared variance for MCS for both groups, suggesting that corresponding mental health constructs were substantially different. The shared variance contrast for physical health was distinct only for the Placebo group. The larger MCS response-shift effects were found at end of study for Placebo only and were more prominent at extremes of the MCS score distribution. CONCLUSIONS: Our results reveal notable treatment group differences in MCS but not PCS response shifts, which can explain null results detected in previous work. The method introduced herein provides a way to provide further information about response-shift effects in clinical trial data.

Response-shift effects in neuromyelitis optica spectrum disorder: a secondary analysis of clinical trial data.

BACKGROUND: Researchers have long posited that response-shift effects may obfuscate treatment effects. The present work investigated possible response-shift effects in a recent clinical trial testing a new treatment for Neuromyelitis Optica Spectrum Disorder (NMOSD). This pivotal trial provided impressive support for the drug Eculizumab in preventing relapse, but less strong or null results as the indicators became more subjective or evaluative. This pattern of results suggests that response-shift effects are present. METHODS: This secondary analysis utilized data from a randomized, double-blind trial evaluating the impact of Eculizumab in preventing relapses in 143 people with NMOSD. Treatment arm and then relapse status were hypothesized 'catalysts' of response shift in two series of analyses. We devised a "de-constructed" version of Oort structural-equation modeling using random-effects modeling for use in small samples. This method begins by testing an omnibus response-shift hypothesis and then, pending a positive result, implements a series of random-effects models to elucidate specific response-shift effects. RESULTS: In the omnibus test, the 'standard quality-of-life (QOL) model' captured substantially less well the experience of placebo as compared to Eculizumab group. Recalibration and reconceptualization response-shift effects were detected. Detected relapse-related response shifts included recalibration, reprioritization, and reconceptualization. CONCLUSIONS: Trial patients experienced response shifts related to treatment- and relapse-related experiences. Published trial results likely under-estimated Eculizumab vs. Placebo differences due to recalibration and reconceptualization, and relapse effects due to recalibration, reprioritization, and reconceptualization. This novel random-effects- model application builds on response-shift theory and provides a small-sample method for better estimating treatment effects in clinical trials.

Capturing patient experience: does quality-of-life appraisal entail a new class of measurement?

BACKGROUND: Two decades of research on quality-of-life (QOL) appraisal have demonstrated links between patient experience and health outcomes and have accounted for both intra-individual change and inter-individual differences in a wide range of research contexts. The present work investigates patterns across diagnostic and demographic groupings to demonstrate how population-specific circumstances drive the structure of QOL appraisal. METHODS: This secondary analysis (N = 6448) utilized data from six patient groups: spine surgery, multiple sclerosis, heterogeneous chronically ill, heterogeneous cancer, bladder cancer, and human immunodeficiency virus (HIV). We explored patterns of inter-item correlation across patient samples, using items from the Standards of Comparison and Sampling of Experience subsections of the QOL Appraisal Profile v1 and v2. Similar matrices were compared by demographic characteristics. RESULTS: Patterns of inter-item correlations for Standards of Comparison items varied sharply across disease groups and racial groups while being similar across age, gender, and education levels. Inter-item correlation matrices for Sampling of Experience items revealed marked differences among disease groups and educational and racial categories but were similar across age and gender groups. CONCLUSIONS: Appraisal parameters showed evidence of shared and unique aspects across samples and circumstances, findings which make sense in light of sample differences in health status and demographic influences. Tools to assess patient experience and meaning may be best understood as idiometric instruments. We discuss their distinctions from psychometric and clinimetric tools at theoretical, statistical, and applied levels.

Understanding haemophilia caregiver burden: does appraisal buffer the impact of haemophilia on caregivers over time?

Objective: The present work investigated haemophilia caregiver and patient characteristics associated with change in negative and positive aspects of caregiving. Design: Web-based survey data were collected from haemophilia A or B caregivers at baseline and two years later. Main Outcome Measures: Outcomes included Burden Summary and Positive Emotions change scores from the Haemophilia Caregiver Impact measure. Results: The sample included 323 caregivers (71% response rate; mean age 40, 90% female). Brief Appraisal Inventory Principal Components Analysis with varimax rotation yielded five scores: Awareness of Challenges, Fulfillment and Growth, Stay Positive, Social Comparison, and Interpersonal Problem-Solving. Regression analyses revealed that caregivers with more health conditions, who care for patients with increased bleeds and worse pain, and who focused more on Awareness of Challenges, Social Comparisons, and Interpersonal Problem-Solving reported worsened burden over follow-up (Adj. R2 = 0.37). Prioritisation of Stay[ing] Positive and reduced emphasis on Interpersonal Problem-Solving were associated with increased Positive Emotions (Adj. R2 = 0.32). Conclusion: Caregivers who focused less on a life unfettered by caregiving, comparing themselves to others, and interpersonal problem-solving and more on staying positive reported reductions in burden and improvements in positive emotions. These findings could translate to multicomponent psychoeducational interventions to help caregivers buffer haemophilia's impact.

Lung transplant referral practice patterns: a survey of cystic fibrosis physicians and general pulmonologists.

BACKGROUND: Many individuals with cystic fibrosis (CF) die from respiratory failure without referral for lung transplant. Physician practices that may expedite, delay, or preclude referral, are poorly understood. METHODS: Two parallel, web-based surveys focusing on lung transplant referral triggers and barriers, as well as pre-referral evaluation, were emailed to pulmonologists practicing in the New England region. One questionnaire was sent to CF providers (n = 61), and the second to general pulmonary providers practicing at the same institutions (n = 61). RESULTS: There were 43 (70%) responses to the CF provider survey, and 25 (41%) responses to the general pulmonary ('non-CF') provider survey. Primary reasons for CF providers to refer their patients included: rapidly declining lung function (91%) and a forced expiratory volume in 1 s (FEV1) below 30% predicted (74%). The greatest barriers to referral for both CF and non-CF providers included active tobacco use (65 and 96%, respectively, would not refer), and active alcohol or other substance use or dependence (63 and 80%). Furthermore, up to 42% of CF providers would potentially delay their referral if triple-combination therapy or other promising new, disease-specific therapy were anticipated. In general, non-CF providers perform a more robust pre-referral medical work-up, while CF providers complete a psychosocial evaluation in higher numbers. Across both groups, communication with lung transplant programs was reported to be inadequate. CONCLUSIONS: Physician-level barriers to timely lung transplant referral exist and need to be addressed. Enhanced communication between lung transplant programs and pulmonary providers may reduce these barriers.

Responsiveness of standard spine outcome tools: do they measure up?

OBJECTIVE: Over the past 2 decades, spine outcome research has become more standardized in response to recommendations from Deyo and others. By using the same generic and condition-specific patient-reported outcome (PRO) measures across studies, results are more easily compared. Given the challenges of maintaining high-quality data in clinical research studies, it would be important to evaluate the contribution of each PRO to confirm that it merits the respondent burden. This study aimed to examine the spine PROs' association with clinically important change and relative responsiveness in explaining variance in patients' global assessment of change (GAC). METHODS: This prospective longitudinal cohort study included adults recruited from 4 active spine surgery practices at a Toronto-based hospital. Patients were diagnosed with a degenerative lumbar spinal condition and underwent spinal decompression and/or fusion surgery. Participants completed the RAND-36 (to generate the physical component score [PCS] and mental component score [MCS]), Oswestry Disability Index (ODI), the numeric rating scale (NRS) for pain, Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference, and a GAC item. Random-effects models were used to investigate the sensitivity of PROs to the GAC and their responsiveness over time (i.e., PRO main effects and PRO-by-time interactions, respectively). RESULTS: The study sample included 168 patients (mean age 61 years, 50% female) with preoperative and up to 12 months of postoperative data. Random-effects models revealed significant main effects for all PROs. Significant time-by-PRO interactions were detected for the PCS, PROMIS, ODI, and NRS (p < 0.0005 in all cases), but not for the MCS. Further examination revealed different sensitivity of the PROs to the GAC at different times. The NRS, PROMIS, and PCS showed higher sensitivity early after surgery, and the PCS evinced a marked drop in sensitivity to the GAC at about 8 months postsurgery. CONCLUSIONS: All PROs currently included in the spine outcome core measures are associated with patients' subjective assessment of a clinically important change, and all but the MCS scores are responsive to such change. Based on these findings, the core spine PROs could be reduced to include fewer estimates of pain. The authors suggest replacing the less responsive measures with tools that help to characterize factors that are driving the patients' subjective assessment of change and that meaningfully address some of the higher levels in the hierarchy of quality-of-life outcomes.

Positive emotions despite substantial burden: The alchemy of haemophilia caregiving.

INTRODUCTION: Qualitative interviews when developing the haemophilia caregiver impact measure© (HCI) documented the importance of capturing the positive aspects of caregiving, not just the negative. AIM: The present study thus investigates the construct underlying the positive emotions HCI subscale and tests models proposing a more comprehensive way of thinking about this construct. METHODS: Secondary analysis was implemented on longitudinal web-based survey data (n = 323) from haemophilia A or haemophilia B caregivers. Person-reported outcomes (PROs) included the HCI, the PROMIS-10 and Ryff psychological well-being subscales. Predictors included caregiver demographics; patient haemophilia characteristics; exercise; adherence; and quality-of-life (QOL) appraisal processes as measured by the brief appraisal inventory (BAI) which yields composite scores assessing awareness of challenges, fulfillment and growth, stay positive, social comparison and interpersonal problem-solving. Second-order factor analysis, structural equation modelling and residual modelling were implemented. RESULTS: A structural equation model fit the data well that contained bifactor representation of well-being with a general factor comprised of environmental mastery, positive relations with others, physical functioning and emotional functioning. Positive emotions was modelled as a component of well-being, with a unique component ('Alchemy') characterized by its associations with stay positive, and awareness of challenges appraisals, and difficulty paying bills. Alchemy had positive linear relationships with the first two, and a positive quadratic relationship with difficulty paying bills. CONCLUSIONS: Adopting positive-focused ways of thinking about one's life limitations may transform the negatives of haemophilia caregiving into something positive. Such cognitive habits reflect an awareness and acceptance of the limitations imposed by haemophilia caregiving.