Impact of treatment of hyperkalaemia on quality of life: design of a prospective observational cohort study of long-term management of hyperkalaemia in patients with chronic kidney disease or chronic heart failure in Japan.

INTRODUCTION: Hyperkalaemia (HK) is a frequent complication in patients with chronic kidney disease (CKD) and/or chronic heart failure (CHF). HK must be managed, both to protect patients from its direct clinical adverse outcomes and to enable treatment with disease-modifying therapies including renin-angiotensin-aldosterone system inhibitors. However, the experiences of patients undergoing treatment of HK are not clearly understood. Optimising treatment decisions and improving long-term patient management requires a better understanding of patients' quality of life (QOL). Thus, the aims of this research are: (1) to describe treatment patterns and the impact of treatment on a patient's QOL, (2) to study the relationships between treatment patterns and the impact of treatment on a patient's QOL and (3) to study the relationships between the control of serum potassium (S-K) and the impact of treatment on a patient's QOL, in patients with HK. METHODS AND ANALYSIS: This is a prospective cohort study with 6 months of follow-up in 30-40 outpatient nephrology and cardiology clinics in Japan. The participants will be 350 patients with CKD or CHF who received their first potassium binders (PB) prescription to treat HK within the previous 6 months. Medical records will be used to obtain information on S-K, on treatment of HK with PBs and with diet, and on the patients' characteristics. To assess the impact of treatment on a patient's QOL, questionnaires will be used to obtain generic health-related QOL, CKD-specific and CHF-specific QOL, and PB-specific QOL. Multivariable regression models will be used to quantify how treatment patterns and S-K control are related to the impact of treatment on a patient's QOL. ETHICS AND DISSEMINATION: Institutional review boards at all participating facilities review the study protocol. Patient consent will be obtained. The results will be published in international journals. TRIAL REGISTRATION NUMBER: NCT05297409.

The effects of greater frequency of two most prevalent bothersome acute respiratory symptoms on health-related quality of life in the 2020 US general population.

PURPOSE: Upper respiratory tract infections (URTI) and related symptoms are widespread and a common reason for visiting primary care with cough and sore throat being most prevalent. Despite their impact on daily activities, no studies have explored the impact on health-related quality of life (HRQOL) in representative general populations. We aimed to understand the short-term impact of the two most prevalent URTI symptoms on HRQOL. METHODS: Online 2020 surveys including acute (≤ 4 weeks) respiratory symptoms (sore throat and cough) and SF-36® health survey (all with 4-week recall) were analysed using analysis of covariance (ANCOVA) in comparison with adult US population norms. Linear T-score transformation of SF-6D utility (ranging from 0 to 1) enabled direct comparisons with SF-36. RESULTS: In total, 7563 US adults responded (average age: 52 years; range: 18-100 years). Sore throat and cough lasting at least several days were experienced by 14% and 22% participants, respectively. Chronic respiratory conditions were reported by 22% of the sample. A clear and consistent pattern of group HRQOL means declining significantly (p < 0.001) for acute cough and sore throat symptom presence and severity. Declines were observed on SF-36 physical (PCS) and mental component (MCS) and health utility (SF-6D) scores controlling for covariates. Those reporting respiratory symptoms 'most days' declined ≥ 0.5 standard deviation (minimal important difference [MID]) worse with averages at the 19th and 34th centiles for cough on the PCS and MCS, and 21st to 26th centile for sore throat. CONCLUSION: Declines in HRQOL with acute cough and sore throat symptoms consistently exceeded MID standards and should not be ignored as self-limiting without intervention. Future studies on early self-care for symptom relief and its implications on HRQOL and health economics would be valuable to understand the benefits on healthcare burden and need for updating treatment guidelines.

Validation of a new instrument for measuring disease-specific quality of life: A pilot study among patients with chronic kidney disease and hyperkalemia.

BACKGROUND: To prepare for a longitudinal study of the effects of potassium-lowering treatment on quality of life (QOL), we quantified the validity of a new disease-specific instrument for measuring QOL, using data from patients who had hyperkalemia (HK) due to chronic kidney disease (CKD) or chronic heart failure, and were also being treated with potassium binders (PBs). METHODS: In this cross-sectional study, the participants were 98 patients at five outpatient clinics in Japan. The outcome measures were the Medical Outcomes Study 36-item short-form (SF-36), a widely used generic measure of QOL, and the Quality of Life Disease-specific Impact Scale (QDIS-7), a recently-developed disease-specific measure of QOL. Internal-consistency reliability was quantified, and factor analysis was done to confirm hypothesized QOL dimensions. Validation tests used two external criteria: CKD stage, and PB formulation. PB formulation was used because different formulations are associated with different degrees of patients' burden. Using a previously-described method, we computed the relative validity (RV) of the two measures. RESULTS: Two factor scoring of the SF-36 and one factor scoring of the QDIS-7, as standardized from previous studies, were confirmed. The RVs showed that the QDIS-7 was much more valid than the SF-36, for discriminating between groups defined clinically (by CKD stage), and also between groups defined by PB formulation. Reliability was satisfactory: 0.73-0.95 for the SF-36 and 0.86 for the QDIS-7. CONCLUSIONS: The QDIS-7 with CKD or PB attributions was more valid than the SF-36 for measuring the effects of CKD and of PB formulation on QOL.

Improving multimorbidity measurement using individualized disease-specific quality of life impact assessments: predictive validity of a new comorbidity index.

BACKGROUND: Interpretation of health-related quality of life (QOL) outcomes requires improved methods to control for the effects of multiple chronic conditions (MCC). This study systematically compared legacy and improved method effects of aggregating MCC on the accuracy of predictions of QOL outcomes. METHODS: Online surveys administered generic physical (PCS) and mental (MCS) QOL outcome measures, the Charlson Comorbidity Index (CCI), an expanded chronic condition checklist (CCC), and individualized QOL Disease-specific Impact Scale (QDIS) ratings in a developmental sample (N = 5490) of US adults. Controlling for sociodemographic variables, regression models compared 12- and 35-condition checklists, mortality vs. population QOL-weighting, and population vs. individualized QOL weighting methods. Analyses were cross-validated in an independent sample (N = 1220) representing the adult general population. Models compared estimates of variance explained (adjusted R2) and model fit (AIC) for generic PCS and MCS across aggregation methods at baseline and nine-month follow-up. RESULTS: In comparison with sociodemographic-only regression models (MCS R2 = 0.08, PCS = 0.09) and Charlson CCI models (MCS R2 = 0.12, PCS = 0.16), increased variance was accounted for using the 35-item CCC (MCS R2 = 0.22, PCS = 0.31), population MCS/PCS QOL weighting (R2 = 0.31-0.38, respectively) and individualized QDIS weighting (R2 = 0.33 & 0.42). Model R2 and fit were replicated upon cross-validation. CONCLUSIONS: Physical and mental outcomes were more accurately predicted using an expanded MCC checklist, population QOL rather than mortality CCI weighting, and individualized rather than population QOL weighting for each reported condition. The 3-min combination of CCC and QDIS ratings (QDIS-MCC) warrant further testing for purposes of predicting and interpreting QOL outcomes affected by MCC.

Quality of life in adults with autism spectrum disorder: influence of age, sex, and a controlled, randomized mindfulness-based stress reduction pilot intervention.

PURPOSE: Adults with autism spectrum disorder (ASD) consistently report worse functional health and well-being, compared to neurotypical (NT) peers. In a series of studies, we aimed to elucidated the effects of sex, age, and their interaction on health-related quality of life (HRQoL) and evaluated the effectiveness of mindfulness-based stress reduction (MBSR) for improving health-, disability-, and autism-related QoL, with possible sex and age outcome moderators, in adults with ASD. METHODS: Study 1 used the 36-Item Short Form Survey to compare mental and physical HRQoL composite scores in adults with ASD (n = 67) and matched NT adults (n = 66). Study 2 was a randomized pilot evaluation of the effect of MBSR, compared to an active control intervention with social support and relaxation education (support/education; n = 56), on the World Health Organization QoL BREF, Disability, and Autism-Specific scales in adults with ASD. RESULTS: In Study 1, we replicated findings that mental HRQoL is worse in both men and women with ASD, compared to NT counterparts, but physical HRQoL is only worse in women with ASD. We present novel findings that older age is associated with better mental HRQoL in women with ASD only. In Study 2, MBSR improved disability-related QoL in adults with ASD over and above the support/education intervention, but both interventions improved mental HRQoL. Lastly, both interventions were more effective for HRQoL improvements in women with ASD. CONCLUSION: Findings encourage precision medicine approaches tailored to age and sex groups for best HRQoL outcomes in adults with ASD. CLINICALTRIALS: gov Identifier: NCT04017793.

Predicting the 10-year risk of death from other causes in men with localized prostate cancer using patient-reported factors: Development of a tool.

OBJECTIVE: To develop a tool for estimating the 10-year risk of death from other causes in men with localized prostate cancer. SUBJECTS AND METHODS: We identified 2,425 patients from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, age <80, newly diagnosed with clinical stage T1-T3a prostate cancer from 1/1/1998-12/31/2009, with follow-up through 2/28/2013. We developed a Fine and Gray competing-risks model for 10-year other cause mortality considering age, patient-reported comorbid medical conditions, component scores and items of the SF-36 Health Survey, activities of daily living, and sociodemographic characteristics. Model discrimination and calibration were compared to predictions from Social Security life table mortality risk estimates. RESULTS: Over a median follow-up of 7.7 years, 76 men died of prostate-specific causes and 465 died of other causes. The strongest predictors of 10-year other cause mortality risk included increasing age at diagnosis, higher approximated Charlson Comorbidity Index score, worse patient-reported general health (fair or poor vs. excellent-good), smoking at diagnosis, and marital status (all other vs. married) (all p<0.05). Model discrimination improved over Social Security life tables (c-index of 0.70 vs. 0.59, respectively). Predictions were more accurate than predictions from the Social Security life tables, which overestimated risk in our population. CONCLUSIONS: We provide a tool for estimating the 10-year risk of dying from other causes when making decisions about treating prostate cancer using pre-treatment patient-reported characteristics.

Developing a New Version of the SF-6D Health State Classification System From the SF-36v2: SF-6Dv2.

OBJECTIVE: The objective of this study was to develop the classification system for version of the SF-6D (SF-6Dv2) from the SF-36v2. SF-6Dv2 is an improved version of SF-6D, one of the most widely used generic measures of health for the calculation of quality-adjusted life years. STUDY DESIGN AND SETTING: A 3-step process was undertaken to generate a new classification system: (1) factor analysis to establish dimensionality; (2) Rasch analysis to understand item performance; and (3) tests of differential item function. To evaluate robustness, Rasch analyses were performed in multiple subsets of 2 large cross-sectional datasets from recently discharged hospital patients and online patient samples. RESULTS: On the basis of factor analysis, other psychometric evidence, cross-cultural considerations, and amenability to valuation, the 6-dimension classification used in SF-6D was maintained. SF-6Dv2 resulted in the following modifications to SF-6D: a simpler classification of physical function with clearer separation between levels; a more detailed 5-level description of role limitations; using negative wording to describe vitality; and using pain severity rather than pain interference. CONCLUSIONS: The SF-6Dv2 classification system describes more distinct levels of health than SF-6D, changes the descriptions used for a number of dimensions and provides clearer wording for health state valuation. The second stage of the study has developed a utility value set using discrete choice methods so that the measure can be used in health technology assessment. Further work should investigate the psychometric characteristics of the new instrument.

Improving CKD-Specific Patient-Reported Measures of Health-Related Quality of Life.

BACKGROUND: Patient-reported outcome measures that are more practical and clinically useful are needed for patients with CKD. We compared a new CKD-specific quality-of-life impact scale (CKD-QOL) with currently used measures. METHODS: Patients (n=485) in different treatment groups (nondialysis stages 3-5, on dialysis, or post-transplant) completed the kidney-specific CKD-QOL and Kidney Disease Quality of Life-36 (KDQOL-36) forms and the generic SF-12 Health Survey at baseline and 3 months. New items summarizing quality of life (QOL) impact attributed to CKD across six QOL domains yielded single impact scores from a six-item static (fixed-length) form and from computerized adaptive tests (CATs) with three to six items. Validity tests compared the CKD-QOL, KDQOL-36 (Burden, Effects, and Symptoms/Problems subscales), and generic SF-12 measures across groups in four tests of clinical status and clinician assessment of change (CKD-specific tests), and number of comorbidities. ANOVA was used to test for group mean differences, variances in each measure explained by groups, and relative validity (RV) in comparison with the referent KDQOL-36 Burden subscale. RESULTS: KDQOL-36 and CKD-QOL measures generally discriminated better than generic SF-12v2 measures. The pattern of variances across CKD-specific tests comparing validity favored CKD-QOL two-fold over KDQOL-36. Two RV test results confirmed CKD-QOL improvements over the referent KDQOL scale. Results for static and CAT CKD-QOL forms were similar. SF-12 Physical and KDQOL-36 Symptoms scores worsened with increasing comorbid condition counts. CONCLUSIONS: Overall, compared with the KDQOL-36, the new approach to summarizing CKD-specific QOL impact performed better across multiple tests of validity. CAT surveys were more efficient than static surveys.

Varying the item format improved the range of measurement in patient-reported outcome measures assessing physical function.

BACKGROUND: Physical function (PF) is a core patient-reported outcome domain in clinical trials in rheumatic diseases. Frequently used PF measures have ceiling effects, leading to large sample size requirements and low sensitivity to change. In most of these instruments, the response category that indicates the highest PF level is the statement that one is able to perform a given physical activity without any limitations or difficulty. This study investigates whether using an item format with an extended response scale, allowing respondents to state that the performance of an activity is easy or very easy, increases the range of precise measurement of self-reported PF. METHODS: Three five-item PF short forms were constructed from the Patient-Reported Outcomes Measurement Information System (PROMIS®) wave 1 data. All forms included the same physical activities but varied in item stem and response scale: format A ("Are you able to …"; "without any difficulty"/"unable to do"); format B ("Does your health now limit you …"; "not at all"/"cannot do"); format C ("How difficult is it for you to …"; "very easy"/"impossible"). Each short-form item was answered by 2217-2835 subjects. We evaluated unidimensionality and estimated a graded response model for the 15 short-form items and remaining 119 items of the PROMIS PF bank to compare item and test information for the short forms along the PF continuum. We then used simulated data for five groups with different PF levels to illustrate differences in scoring precision between the short forms using different item formats. RESULTS: Sufficient unidimensionality of all short-form items and the original PF item bank was supported. Compared to formats A and B, format C increased the range of reliable measurement by about 0.5 standard deviations on the positive side of the PF continuum of the sample, provided more item information, and was more useful in distinguishing known groups with above-average functioning. CONCLUSIONS: Using an item format with an extended response scale is an efficient option to increase the measurement range of self-reported physical function without changing the content of the measure or affecting the latent construct of the instrument.

Validity and Responsiveness of the Knee Injury and Osteoarthritis Outcome Score: A Comparative Study Among Total Knee Replacement Patients.

OBJECTIVE: To evaluate validity and responsiveness of the Knee Injury and Osteoarthritis Outcome Score (KOOS) in relation to other patient-reported outcome measures before and after total knee replacement (TKR). METHODS: Pre-TKR and 6-month post-TKR data from 1,143 patients in a US joint replacement cohort were used to compare the KOOS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the SF-36 Health Survey (SF-36). Validity was evaluated with multiple methods, including correlations of pre-TKR scale scores and analysis of variance models that used pre-TKR data to compare the relative validity of scales in discriminating between groups differing in assistive walking device use and number of comorbid conditions. Validity was also evaluated by using post-TKR minus pre-TKR change scores to assess relative validity of scales in discriminating between groups rating themselves as better, same, or worse (BSW) in their capability to do activities at 6 months. Responsiveness also was described using effect sizes and standardized response means. RESULTS: In support of convergent and discriminant validity, KOOS scale scores were worse for patients using an assistive device but only declined weakly with increasing comorbid conditions. While all knee-specific scales discriminated between BSW groups, the KOOS quality of life (QOL) scale was significantly better (P < 0.05) than all measures except the SF-36 physical component summary. KOOS QOL also had the highest effect size, while SF-36 measures had lower effect sizes and standardized response means. KOOS pain and symptoms scales discriminated better than WOMAC pain and stiffness scales among BSW groups. CONCLUSION: KOOS scales were valid and responsive in this cohort of US TKR patients. KOOS QOL performed particularly well in capturing aggregate knee-specific outcomes.

Standardizing disease-specific quality of life measures across multiple chronic conditions: development and initial evaluation of the QOL Disease Impact Scale (QDIS®).

BACKGROUND: To document the development and evaluation of the Quality of life Disease Impact Scale (QDIS®), a measure that standardizes item content and scoring across chronic conditions and provides a summary, norm-based QOL impact score for each disease. METHODS: A bank of 49 disease impact items was constructed from previously-used descriptions of health impact to represent ten frequently-measured quality of life (QOL) content areas and operational definitions successfully utilized in generic QOL surveys. In contrast to health in general, all items were administered with attribution to a specific disease (osteoarthritis, rheumatoid arthritis, angina, myocardial infarction, congestive heart failure, chronic kidney disease (CKD), diabetes, asthma, or COPD). Responses from 5418 adults were analyzed as five disease groups: arthritis, cardiovascular, CKD, diabetes, and respiratory. Unidimensionality, item parameter and scale-level invariance, reliability, validity and responsiveness to change during 9-month follow-up were evaluated by disease group and for all groups combined using multi-group confirmatory factor analysis (MGCFA), item response theory (IRT) and analysis of variance methods. QDIS was normed in an independent chronically ill US population sample (N = 4120). RESULTS: MGCFA confirmed a 1-factor model, justifying a summary score estimated using equal parameters for each item across disease groups. In support of standardized IRT-based scoring, correlations were very high between disease-specific and standardized IRT item slopes (r = 0.88-0.96), thresholds (r = 0.93-0.99) and person-level scores (r ≥ 0.99). Internal consistency, test-retest and person-level IRT reliability were consistently satisfactory across groups. In support of interpreting QDIS as a disease-specific measure, in comparison with generic measures, QDIS consistently discriminated markedly better across disease severity levels, correlated higher with other disease-specific measures in cross-sectional tests, and was more responsive in comparisons of groups with better, same or worse evaluations of disease-specific outcomes at the 9-month follow-up. CONCLUSIONS: Standardization of content and scoring across diseases was shown to be justified psychometrically and enabled the first summary measure of disease-specific QOL impact normed in the chronically ill population. This disease-specific approach substantially improves discriminant validity and responsiveness over generic measures and provides a basis for better understanding the relative QOL impact of multiple chronic conditions in research and clinical practice.

The Validity of Disease-specific Quality of Life Attributions Among Adults with Multiple Chronic Conditions.

BACKGROUND: A crucial assumption underlying all disease-specific quality of life (QOL) measures, that patients can validly differentiate a specific disease in the presence of multiple chronic conditions, has not been tested using multiple methods. Our objective was to evaluate the convergent and discriminant validity of QOL attributions to specific diseases among adults with multiple chronic conditions (MCC). METHODS: Adults age 18 and older (N=4,480) sampled from eight pre-identified condition groups (asthma, COPD, angina/MI with angina, congestive heart failure, diabetes, chronic kidney disease, osteoarthritis, rheumatoid arthritis) completed an Internet survey. Comorbid conditions were determined using a 35-condition checklist. Product-moment correlations were analyzed separately by pre-identified condition group using the multitrait-multimethod of construct validation, where traits were defined by 9-26 conditions and each condition was measured by two methods: disease severity rating and Disease-specific Quality of Life Impact Scale (QDIS) global rating. A third method (symptom or clinical marker) was available for the eight pre-identified conditions. Convergent validity was supported when correlations among different methods of measuring the same condition (trait) were substantial (r≥0.40). Discriminant validity was supported when correlations between the same and different methods of measuring different conditions were significantly lower than corresponding convergent correlations. RESULTS: In support of convergent validity, 22 of 24 convergent correlations were substantial (r=0.38-0.84, median=0.53). In support of discriminant validity, 833 of 924 tests (90.2%) yielded significantly higher convergent than discriminant correlations across the eight pre-identified conditions. Exceptions to this pattern of results were most often observed for comorbid conditions within the same clinical area. CONCLUSIONS: Collectively, convergent and discriminant test results support the construct validity of disease-specific QOL impact attributions across MCC within the eight pre-identified conditions. Noteworthy exceptions should be considered when interpreting some specific QOL impact attributions and warrant further study. Pursuit of a summary disease-specific QOL impact score standardized across MCC is recommended.

Evaluation of smoking-specific and generic quality of life measures in current and former smokers in Germany and the United States.

BACKGROUND: Health-related quality of life (QOL) surveys include generic measures that enable comparisons across conditions and measures that focus more specifically on one disease or condition. We evaluated the psychometric properties of German- and English-language versions of survey scales representing both types of measures in samples of current and former smokers. METHODS: TQOLIT(™)v1 integrates new measures of smoking-specific symptoms and QOL impact attributed to smoking with generic SF-36 Health Survey measures. For purposes of evaluation, cross-sectional data were analyzed for two independent samples. Disease-free (otherwise healthy) adults ages 23-55 used a tablet to complete surveys in a clinical trial in Germany (125 current and 54 former smokers). Online general population surveys were completed in the US by otherwise healthy current and former smokers (N = 149 and 110, respectively). Evaluations included psychometric tests of assumptions underlying scale construction and scoring, score distributions, and reliability. Tests of validity included cross-sectional correlations and analyses of variance based on a conceptual framework and hypotheses for groups differing in self-reported smoking behavior (current versus former smoker, cigarettes per day (CPD)) and severity of smoking symptoms in both samples and, in the German trial only, clinical parameters of biomarkers of exposure. RESULTS: Tests of scaling assumptions and internal consistency reliability (alpha = 0.71-0.79) of the smoking-specific measures were satisfactory, although ceiling effects attenuated correlations for former smokers in both samples. Correlational evidence supporting validity of smoking-specific symptom and impact measures included their substantial inter-correlation and higher correlations (than generic measures) with smoking behavior (favoring former over current groups) and CPD in both samples. In the German trial, both smoking-specific measures correlated significantly (p < 0.05) with all four biomarkers. QOL impact attributed to smoking correlated with the SF-36 mental but not physical summary measures in both samples. CONCLUSIONS: German- and English-language TQOLITv1 surveys have comparable and satisfactory psychometric properties. Cross-sectional tests, including correlations with four biomarkers, support the validity of the new smoking-specific measures for use in studies of otherwise healthy smokers. Smoking-specific measures consistently performed better than generic QOL measures in all tests of validity.

Development of a Short Version of the Thyroid-Related Patient-Reported Outcome ThyPRO.

BACKGROUND: Thyroid diseases affect quality of life (QoL). The Thyroid-Related Patient-Reported Outcome (ThyPRO) is an international comprehensive well-validated patient-reported outcome, measuring thyroid-related QoL. The current version is rather long--85 items. The purpose of the present study was to develop an abbreviated version of the ThyPRO, with conserved good measurement properties. METHODS: A cross-sectional (N = 907) and a longitudinal sample (N = 435) of thyroid patients were analyzed. A graded item response theory (IRT) model was fitted to the cross-sectional data. Short-form scales with three items were aimed for, by selecting items with best fit according to the IRT model, avoiding cross-culturally noninvariant items. Seven scales measuring mental and social well-being and function as well as one overall QoL impact item were analyzed in a bifactor model, to develop a supplementary composite score. Short-form scales were linked to original scales with IRT-based summed-score-linking. Agreement between the short and long form was estimated by agreement plots, intraclass correlations, and mean score levels. Responsiveness was compared by relative validity indices, clinical validity by ability to detect clinically relevant differences, and test-retest reliability by intra-class correlation. RESULTS: One four-item scale was not abbreviated and one two-item scale was omitted from the short-form. For the 11 scales undergoing abbreviation, 10 with three and one with four items were developed. A bifactor model with good overall fit was fitted to the composite score, including the single QoL item. Responsiveness and clinical validity of the short-form scales were preserved, as were test-retest reliability (0.75-0.89). Short- versus long-form intraclass correlations were high (0.89-0.98), and the mean scale levels were similar. CONCLUSIONS: A 39-item version of the ThyPRO, with good measurement properties, was developed and is recommended for clinical use.

Preliminary Evaluation of a New German Translated Tobacco Quality of Life Impact Tool to Discriminate Between Healthy Current and Former Smokers and to Explore the Effect of Switching Smokers to a Reduced Toxicant Prototype Cigarette.

BACKGROUND: Assessment of health-related quality of life (HRQoL) is well established in clinical research, but ceiling effects in validated tools might prevent detection of changes in well respondents. Tobacco Quality of Life Impact Tool (TQOLITv1) uses conceptual and psychometric advances to enhance detection of HRQoL changes. METHODS: In a 6-month, forced-switch study, the German TQOLITv1 was assessed in healthy adult (age 23-55 years) current and matched former-smokers. At baseline, smokers were switched to reduced toxicant prototype (RTP) or conventional cigarette for 6 months. TQOLITv1 responses were collected at baseline, 3 and 6 months from current smokers whilst former smokers completed it at the latter two time points. TQOLITv1 includes SF-36v2 and new smoking-specific, physical and general-health measures. RESULTS: Reliability at baseline was good (Cronbach's coefficient alpha > 0.70) for all measures. The baseline percentage with the best possible score (ceiling effect) for former and current smokers was substantially better for the new physical function than SF-36 physical function measure (35% vs. 59% at ceiling, respectively). New smoking-specific measures discriminated current from former smokers better than general health measures. Smoking-specific symptoms (r = 0.73) were more stable from baseline to 6 months than other measures (r = 0.38-0.54) particularly more than the SF-36 mental component score (r = 0.24). Although both product smoking groups worsened in most HRQoL measures, changes in general and smoking-specific HRQoL impact measures favored RTP smokers. CONCLUSIONS: The German TQOLITv1 is sufficiently reliable and valid to assess HRQoL and may be more useful than SF-36v2 in evaluation of interventions in well smoking populations including those consuming RTPs.

Testing item response theory invariance of the standardized Quality-of-life Disease Impact Scale (QDIS(®)) in acute coronary syndrome patients: differential functioning of items and test.

PURPOSE: The Quality-of-life (QOL) Disease Impact Scale (QDIS(®)) standardizes the content and scoring of QOL impact attributed to different diseases using item response theory (IRT). This study examined the IRT invariance of the QDIS-standardized IRT parameters in an independent sample. METHOD: The differential functioning of items and test (DFIT) of a static short-form (QDIS-7) was examined across two independent sources: patients hospitalized for acute coronary syndrome (ACS) in the TRACE-CORE study (N = 1,544) and chronically ill US adults in the QDIS standardization sample. "ACS-specific" IRT item parameters were calibrated and linearly transformed to compare to "standardized" IRT item parameters. Differences in IRT model-expected item, scale and theta scores were examined. The DFIT results were also compared in a standard logistic regression differential item functioning analysis. RESULTS: Item parameters estimated in the ACS sample showed lower discrimination parameters than the standardized discrimination parameters, but only small differences were found for thresholds parameters. In DFIT, results on the non-compensatory differential item functioning index (range 0.005-0.074) were all below the threshold of 0.096. Item differences were further canceled out at the scale level. IRT-based theta scores for ACS patients using standardized and ACS-specific item parameters were highly correlated (r = 0.995, root-mean-square difference = 0.09). Using standardized item parameters, ACS patients scored one-half standard deviation higher (indicating greater QOL impact) compared to chronically ill adults in the standardization sample. CONCLUSION: The study showed sufficient IRT invariance to warrant the use of standardized IRT scoring of QDIS-7 for studies comparing the QOL impact attributed to acute coronary disease and other chronic conditions.

Energy, fatigue, or both? A bifactor modeling approach to the conceptualization and measurement of vitality.

PURPOSE: Vitality is an important domain reflecting both the physical and emotional components of health-related quality of life. Because of its complexity, it has been defined and measured both broadly and narrowly. We explored the dimensionality of a very comprehensive item bank hypothesized to measure vitality and its related concepts. METHODS: Secondary analyses were conducted using the responses of 1,343 adults representative of the US general population to Internet-based surveys including 42 items compiled from multiple scales (e.g., SF-36 Vitality, PROMIS-Fatigue), covering a broad range of vitality-related content areas (energy, fatigue, and their interference with physical, mental, social activities, and quality of life). Exploratory and confirmatory factor models were evaluated independently using split-half samples. Bifactor model was used to assess the essential unidimensionality of the items, in comparison with traditional unidimensional, multidimensional, and hierarchical models. Method effects of a common scale or phrase were modeled via correlating errors. RESULTS: The exploratory factor analysis identified one dominant factor. The confirmatory factor analysis identified a best-fitting (CFI = 0.964, RMSEA = 0.084) bifactor model with one general (vitality) and two group (energy and fatigue) factors, explaining 69, 3, and 4 % of total variance. Correlating errors accounting for the method effects were important in identifying the substantive dimensionality of the items. CONCLUSIONS: The bifactor model proved to be useful for evaluating the dimensionality of a complex construct. Results supported conceptualizing and measuring vitality as a unidimensional energy-fatigue construct. We encourage future studies comparing practical implications of measures based on the broader and narrower conceptualizations of vitality.

Assessing health-related quality of life in patients with benign non-toxic goitre.

Health-related quality of life (HRQoL) assessments are increasingly used to evaluate treatment effects and to shape the delivery of value based care. Valid generic and disease specific tools are available for quantifying HRQoL in patients with non-toxic goitre. However, few studies have applied these validated instruments to assess HRQoL in patients with benign non-toxic goitre. Limited evidence suggests that patients with non-toxic goitre have HRQoL impairments in multiple HRQoL domains. While the HRQoL-impact of non-toxic goitre may be small relative to other severely disabling medical conditions, treatment is almost exclusively elected for HRQoL indications. Thus better quantification of HRQoL, particularly at better (or more favorable) levels where many patients score, is essential. Web and mobile technologies have eased the ability to deliver surveys to patients. Routine consideration of HRQoL provides the opportunity to monitor the impact of treatment on the outcomes most meaningful for patients and the opportunity to help shape the delivery of value based health care.

Patient-reported functional health and well-being outcomes with drug therapy: a systematic review of randomized trials using the SF-36 health survey.

OBJECTIVES: To evaluate the responsiveness of the SF-36 Health Survey in drug trials and to determine how often clinically efficacious treatments produce meaningful functional health changes across medical conditions. RESEARCH DESIGN: We conducted a systematic review of randomized, double-blind, placebo-controlled drug trials published from 1995 to 2011 that documented results for primary clinical endpoints and SF-36 outcomes. PubMed and a database of SF-36 publications were searched. We evaluated responsiveness as concordance (both statistically significant or both nonsignificant) between primary clinical and SF-36 outcomes. To determine how often SF-36 physical and mental component summary (PCS, MCS) score changes were of meaningful magnitude, mean net of placebo changes with treatment were compared against the developer's recommended 3-point threshold for a minimal important difference (MID) across groups of medical conditions. RESULTS: Of 805 screened trials, 185 met eligibility criteria. Primary clinical and SF-36 outcomes were concordant in 151 trials (82%). Among clinically efficacious trials, 58% reported net mean SF-36 improvements ≥MID threshold; however, SF-36 changes were often modest (PCS IQR, 1.6-4.1; MCS IQR, 0.8-3.5). Variations in treatment impact were apparent across conditions. Clinically efficacious therapies for rheumatoid arthritis, psoriatic arthritis, and psoriasis consistently achieved the largest SF-36 improvements, with 87% exceeding MID, whereas no efficacious therapies for peripheral arterial disease or chronic obstructive pulmonary disease achieved MID threshold. CONCLUSIONS: The SF-36 responds to treatment impact, distinguishing drug therapies that, on average, produce meaningful functional health benefits. Overall, just over half of clinically efficacious trials report meaningful functional health improvements, and results vary widely by medical condition.