Ask1 and Akt act synergistically to promote ROS-dependent regeneration in Drosophila.

How cells communicate to initiate a regenerative response after damage has captivated scientists during the last few decades. It is known that one of the main signals emanating from injured cells is the Reactive Oxygen Species (ROS), which propagate to the surrounding tissue to trigger the replacement of the missing cells. However, the link between ROS production and the activation of regenerative signaling pathways is not yet fully understood. We describe here the non-autonomous ROS sensing mechanism by which living cells launch their regenerative program. To this aim, we used Drosophila imaginal discs as a model system due to its well-characterized regenerative ability after injury or cell death. We genetically-induced cell death and found that the Apoptosis signal-regulating kinase 1 (Ask1) is essential for regenerative growth. Ask1 senses ROS both in dying and living cells, but its activation is selectively attenuated in living cells by Akt1, the core kinase component of the insulin/insulin-like growth factor pathway. Akt1 phosphorylates Ask1 in a secondary site outside the kinase domain, which attenuates its activity. This modulation of Ask1 activity results in moderate levels of JNK signaling in the living tissue, as well as in activation of p38 signaling, both pathways required to turn on the regenerative response. Our findings demonstrate a non-autonomous activation of a ROS sensing mechanism by Ask1 and Akt1 to replace the missing tissue after damage. Collectively, these results provide the basis for understanding the molecular mechanism of communication between dying and living cells that triggers regeneration.

Psychometric properties of the EQ-5D-5L in patients with major depression: factor analysis and Rasch analysis.

BACKGROUND: The EQ-5D is one of the most recommended questionnaires for cost-effectiveness studies. AIMS: To study the psychometric properties of the EQ-5D-5L in patients with major depression. METHODS: This prospective observational study included 433 patients with major depression who completed the EQ-5D-5L and Patient Health Questionnaire-9 (PHQ-9) questionnaires at baseline, of whom 310 also did six months later. The structural validity was assessed by confirmatory factor analysis, the item functioning by item response analysis, and reliability by Cronbach's alpha. Convergent validity and known-groups validity was studied using the PHQ-9 and a general health question. To assess responsiveness effect sizes were calculated. RESULTS: The results supported the unidimensionality and showed adequate item functioning, with somewhat age-related item differential functioning for the mobility dimension. Cronbach's alpha was 0.77. The EQ-5D-5L showed a high correlation with the PHQ-9 and general health. The more severe the depression level and the poorer the general health, the lower the EQ-5D-5L scores (p < 0.001). Responsiveness parameters showed moderate changes among "improved" patients. CONCLUSIONS: These findings support the adequate psychometric properties of the EQ-5D-5L in patients with major depression. It could be very useful for clinicians and researchers as an outcome measure and for use in economic evaluation.

Health Related Quality of Life in Major Depressive Disorder: evolution in time and factors associated.

Major Depressive Disorder (MDD) is the most prevalent mental disorder. We aimed to analyze which factors were associated to their Health-Related Quality of Life (HRQoL) perception in patients diagnosed of MDD and how they evolved over six months.

Response Mapping Methods to Estimate the EQ-5D-5L From the Western Ontario McMaster Universities Osteoarthritis in Patients With Hip or Knee Osteoarthritis.

OBJECTIVES: The mapping technique can estimate generic preference-based measure scores through a specific measure that cannot be used in economic evaluations. This study compared 2 response mapping methods to estimate EQ-5D-5L scores using the Western Ontario McMaster Universities Osteoarthritis (WOMAC). METHODS: The sample consisted of 758 patients with the hip or knee osteoarthritis recruited in baseline. Bayesian networks (BN) and multinomial logistic regression (ML) were used as response mapping models. Predictions were obtained using the 6-month follow-up as a validation sample. The mean absolute error, mean squared error, deviation from the root mean squared error and intraclass correlation coefficient were calculated as precision measures. RESULTS: There was 5.5% of missing data, which was removed. The mean age was 69.6 years (standard deviation = 10.5), with 61.6% of women. The BN model presented lower mean absolute error, mean squared error, root mean squared error and higher intraclass correlation coefficient than the ML model. Only the WOMAC items pain and physical function items were related with the EQ-5D-5L dimensions. CONCLUSION: BN response mapping models are more robust methods, with better prediction results, than ML models. The BN model also provided a graphic representation of the dependency relationships between the EQ-5D-5L dimensions and the different WOMAC items that could be useful in the clinical investigation of patients with hip or knee osteoarthritis.

The Relationship Between Experiential Avoidance and Posttraumatic Stress Symptoms: A Moderated Mediation Model Involving Dissociation, Guilt, and Gender.

Experiential avoidance, dissociation, and guilt have been shown to be associated with trauma exposure and to play an important role in explaining the development and maintenance of posttraumatic stress symptoms. However, there is a lack of studies that simultaneously address the relationship between these variables, which has never been studied within the framework of emotional processing theory. Furthermore, gender differences in traumatic victimization, posttraumatic stress symptoms, experiential avoidance, dissociation, and guilt have also been reported. Therefore, this study had a double aim: a) to assess the mediating roles of dissociation and guilt in the relationship between experiential avoidance and posttraumatic stress symptoms; and b) to investigate whether gender moderates any such relationship. The final sample comprised 683 undergraduate students (150 men and 533 women) with a history of exposure to traumatic events and with posttraumatic stress symptoms. Mediation and moderated mediation analyses were conducted. Dissociation and guilt independently mediated the association between experiential avoidance and posttraumatic stress symptoms: however, this mediation effect was not moderated by gender. The findings suggest that interventions aimed at controlling psychological variables linked to PTSD (i.e. experiential avoidance, dissociation, and guilt) may be of help to both men and women.

Mapping WOMAC Onto the EQ-5D-5L Utility Index in Patients With Hip or Knee Osteoarthritis.

OBJECTIVES: To map the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) onto the EQ-5D-5L in patients with hip or knee osteoarthritis (OA). METHODS: A prospective observational study was conducted on 758 patients with hip or knee OA who completed the EQ-5D-5L and WOMAC questionnaires, of whom 644 completed them both again 6 months later. Baseline data were used to derive mapping functions. Generalized additive models were used to identify to which powers the WOMAC subscales should be raised to achieve a linear relationship with the response. For the modeling, general linear models (GLM), Tobit models, and beta regression models were used. Age, sex, and affected joints were also considered. Preferred models were selected based on Akaike and Bayesian information criteria, adjusted R2, mean absolute error (MAE), and root mean squared error (RMSE). The functions were validated with the follow-up data using MAE, RMSE, and the intraclass correlation coefficient. RESULTS: The preferred models were a GLM with Pain2+Pain3+Function+Pain·Function as covariates and a beta model with Pain3+Function+Function2+Function3 as covariates. The adjusted R2 were similar (0.6190 and 0.6136, respectively). The predictive performance of these models in the validation sample was similar and both models showed an overprediction for health states worse than death. CONCLUSION: To our knowledge, these are the first functions mapping the WOMAC onto the EQ-5D-5L in patients with hip or knee OA. They showed an acceptable fit and precision and could be very useful for clinicians and researchers when cost-effectiveness studies are needed and generic preference-based health-related quality of life instruments to derive utilities are not available.

Mapping analysis to predict EQ-5D-5 L utility values based on the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires in the Spanish population suffering from lower limb osteoarthritis.

BACKGROUND: The EQ-5D-5 L is a quality-of-life questionnaire based on individuals' preferences that is widely employed for cost-effectiveness analysis. Given the current demand for mapping algorithms to directly assign "utilities", this study aimed to generate different mapping models for predicting EQ-5D-5 L utility values based on scores of the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires provided by patients suffering from hip and knee osteoarthritis (OA), respectively, and to assess the predictive capability of these functions. METHODS: This was a prospective, observational study. Following the criteria of the American Rheumatism Association, 361 patients with hip OA and 397 with knee OA from three regions in Spain were included. Health-related quality of life (HRQoL) was assessed through the EQ-5D-5 L general questionnaire and the OHS and OKS specifically for lower limb OA. Based on the scores on the OHS and OKS questionnaires, EQ-5D-5 L utilities were estimated using 4 models: ordinary least squares (OLS), Tobit, generalized linear model (GLM), and beta regression (Breg). The models were validated on the same patients after 6 months: the mean absolute error (MAE) and mean squared error (MSE) with their 95% confidence intervals (CI), mean values of standard errors (SE), intraclass correlation coefficients (ICC), and Bland-Altman plots were obtained. RESULTS: The lowest MAEs were obtained using GLM and Breg models, with values of 0.1103 (0.0993-0.1214) and 0.1229 (0.1102-0.1335) for hip OA, and values of 0.1127 (0.1014-0.1239) and 0.1141 (0.1031-0.1251) for knee OA. MSE values were also lower using GLM and Breg. ICCs between predicted and observed values were around or over the 0.8 cut-off point. Bland-Altman plots showed an acceptable correlation, but precision was lower for subjects with worse HRQoL, which was also evident when comparing MAEs of the bottom and top halves of the utilities scale. Predictive equations for utilities based on OHS/OKS scores were proposed. CONCLUSIONS: The OHS and OKS scores allow for estimating EQ-5D-5 L utility indexes for patients with hip and knee OA, respectively, with adequate validity and precision. GLM and Breg produce the best predictions. The predictive power of proposed equations is more consistent for subjects in better health condition.

Interventions to improve medication adherence in mental health: the update of a systematic review of cost-effectiveness.

OBJECTIVE: Medication non-adherence in mental health problems has social and economic costs. The objective of the study was to review the cost-effectiveness of interventions to enhance medication adherence in patients with mental health problems. METHODS: The update of a previous systematic review was performed. Databases were searched in June 2019: MEDLINE, PSYCINFO, EMBASE, CINAHL, CRD, WOS. Cost-effectiveness studies comparing an intervention to improve the medication adherence with other interventions/usual care in adults with mental health problems were included. Data were extracted, methodological quality of the studies was assessed and a narrative synthesis was performed. RESULTS: Nine studies were included in the review. The interventions that showed medication adherence increase were: a financial incentive when depot injection was taken by patients with psychotic disorders, a value-based benefit design policy including copayment and counselling in a company setting, and a medication treatment decision supported by a pharmacogenetic test. The other studies (coaching by pharmacists; a psychological and educational intervention at health care centres) did not find differences between groups. No study found cost differences between alternatives. CONCLUSIONS: Interventions to improve medication adherence in adults with mental health problems could be cost-effective, especially those based on financial incentives, although more research is needed. KEYPOINTS There are several types of interventions designed to enhance medication adherence in patients with mental health problems. Few of them have demonstrated cost-effectiveness. Two studies found that a financial incentive per depot injection in patients with psychotic disorders improved the medication adherence. Two other studies found improvement in adherence due to two specific interventions: a value-based benefit design policy in a company setting and a pharmacogenetic test supporting the medication treatment decision. No study found differences in costs between the intervention and the comparator. More research is needed to implement cost-effective interventions.

EQ-5D-5L utilities per health states in Spanish population with knee or hip osteoarthritis.

BACKGROUND: The objective of this study was to obtain utilities by means of EQ-5D-5L for different health states in patients with knee osteoarthritis (KOA) or hip osteoarthritis (HOA) in Spain, and to compare these values with those used in foreign studies with the aim of discussing their transferability for their use in economic evaluations conducted in Spain. METHODS: Primary study: Observational prospective study of KOA or HOA patients in Spain. Sociodemographic and clinical characteristics were collected to characterize the sample. Utilities were elicited using the EQ-5D-5L questionnaire. ANOVA and bivariable analyses were conducted to identify differences between health states. LITERATURE REVIEW: Using the bibliographic databases NSH EED and CEA Registry, we conducted searches of model-based cost utilities analyses of technologies in KOA or HOA patients. Health states and utilities were extracted and compared with values obtained from the Spanish sample. RESULTS: Three hundred ninety-seven subjects with KOA and 361 subjects with HOA were included, with average utilities of 0.544 and 0.520, respectively. In both samples, differences were found in utilities according to level of pain, stiffness and physical function (WOMAC) and severity of symptoms (Oxford scales), so that the worst the symptoms, the lower the utilities. The utilities after surgery were higher than before surgery. Due to limitations from our study related to sample size and observational design, it was not possible to estimate utilities for approximately half the health states included in the published models because they were directly related to specific technologies. For almost 100% of health states of the selected studies we obtained very different utilities from those reported in the literature. CONCLUSIONS: To our knowledge this is the first article with detailed utilities estimated using the EQ-5D-5L in Spain for KOA and HOA patients. In both populations, utilities are lower for worse health states in terms of level of pain, stiffness and physical function according to WOMAC, and according to the Oxford scales. Most utilities obtained from the Spanish sample are lower than those reported in the international literature. Further studies estimating utilities from local populations are required to avoid the use of foreign sources in economic evaluations.

Ionic Polymerization in Cold Plasmas of Acetylene with Ar and He.

The ionic polymerization of acetylene in cold plasmas of C2H2/He and C2H2/Ar has been experimentally studied and modeled in radio frequency (rf) discharges with conditions selected to avoid particle formation. Steady-state distributions of positive and negative ions were measured with mass spectrometry. All the measured distributions are dominated by ions with an even number of carbon atoms, reflecting the characteristic polyyne structures typical for the polymerization of acetylene. The distributions show a monotonic decrease in intensity from ions with two carbon atoms until the highest number of atoms detected. For cations, the distributions extend until 12 carbon atoms. The anion distributions extend further, and negative ions with 20 C atoms are observed in the C2H2/Ar plasma. From the measured mass spectra it is not possible to decide on the possible presence of aromatic species in ions with more than six carbon atoms. A simple model assuming a homogeneous discharge was used to describe the plasma kinetics and could account for the measured ion distributions with reasonable values of charge density and electron temperature. The results of this work stress the important role of the vinylidene anion and indicate that Ar and He do not have much influence on the carbon chemistry.

Efficacy, Effectiveness, Safety, and Cost-effectiveness of Epidural Adhesiolysis for Treating Failed Back Surgery Syndrome. A Systematic Review.

BACKGROUND: Failed back surgery syndrome (FBSS) has a profound impact on patients' quality of life and represents a major clinical challenge and a significant economic burden for society. Adhesiolysis is used as a treatment to eliminate perineural/epidural adhesions in patients with chronic pain attributed to FBSS. OBJECTIVE: To evaluate the efficacy, effectiveness, safety, and cost-effectiveness of epidural adhesiolysis compared with other procedures for treating FBSS. METHOD: A systematic review was conducted. The electronic databases Medline/PreMedline, EMBASE, Cochrane Library Plus, Centre for Reviews and Dissemination databases, SCOPUS, Science Citation Index, and PEDRO were consulted through April 2017. Predefined criteria were used to determine inclusion of the studies and to assess their methodological quality. RESULTS: Ten reports were included. No randomized controlled trials (RCTs) on efficacy or cost-effectiveness were found. Three reports (corresponding to two RCTs, N = 212) suggested that adhesiolysis was effective, especially for pain and disability. However, both studies presented serious methodological flaws. In addition to RCTs, seven observational studies with high risk of bias reported data on effectiveness and safety. Fifty-eight adverse events were reported among 130 patients undergoing endoscopic adhesiolysis, and 19 among the 110 undergoing percutaneous adhesiolysis. CONCLUSIONS: The evidence on the efficacy and cost-effectiveness of adhesiolysis for treating FBSS is nonexistent, whereas evidence on its effectiveness and safety is insufficient. Incorporating data from observational studies did not improve the quality of the evidence on effectiveness.

Diagnostic Performance of Transvaginal Ultrasound for Detecting Cervical Invasion In Women With Endometrial Carcinoma: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the role of transvaginal ultrasound (TVUS) for diagnosing cervical invasion in the preoperative assessment of endometrial carcinoma. METHODS: A search for studies evaluating the role of TVUS for assessing cervical invasion in endometrial carcinoma from January 1990 to December 2016 was performed in the PubMed/MEDLINE, Web of Science, www.ClinicalTrials.gov, and www.who.int/trialsearchdatabases. The quality of the studies was evaluated by the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: We identified 211 citations. Ultimately, 17 studies comprising 1751 women were included. The mean prevalence of cervical invasion was 16.3%. The risk of bias was high in 7 studies for the domains "patient selection" and "index test," whereas it was considered low for the "reference test" domain. Overall, the pooled estimated sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of TVUS for detecting cervical invasion were 63% (95% confidence interval [CI], 51%-74%), 91% (95% CI, 87%-94%), 10.2 (95% CI, 5.7-18.3), and 0.38 (95% CI, 0.28-0.53), respectively. Heterogeneity was high for both sensitivity and specificity. CONCLUSIONS: Transvaginal ultrasound has acceptable diagnostic performance for detecting cervical invasion in women with endometrial carcinoma.

Psychometric properties of the EQ-5D-5L in patients with hip or knee osteoarthritis: reliability, validity and responsiveness.

PURPOSE: To study the psychometric properties, including reliability, validity and responsiveness, of the Spanish EQ-5D-5L questionnaire for patients with hip or knee osteoarthritis (OA). METHODS: We included 758 patients with hip or knee OA who completed the EQ-5D-5L and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, of whom 644 also did 6 months later. The EQ-5D-5L contains five questions from which a utility index is derived. The WOMAC covers three dimensions: pain, stiffness and physical function. Floor and ceiling effects were calculated. Reliability was assessed using Cronbach's alpha. Convergent validity was tested using the Spearman correlation coefficient between EQ-5D-5L and WOMAC. We examined known-groups validity by comparing the EQ-5D-5L between subgroups defined by WOMAC scores using ANOVA or the Kruskal-Wallis test. Effect sizes were calculated to assess responsiveness, and minimal clinically important difference (MCID) was estimated. RESULTS: The EQ-5D-5L showed minimal floor and ceiling effects (< 3%). Cronbach's alpha was 0.86. The EQ-5D-5L index was strongly correlated with WOMAC pain and function scores (- 0.688 and - 0.782). Patients with higher WOMAC scores had significantly (p < 0.0001) lower EQ-5D-5L index. The 20.19% had hip or knee replacement during the follow-up. Effect sizes were small among non-surgical patients, but > 0.80 among "improved" surgical patients, being the MCID for improvement 0.32 points. CONCLUSIONS: The results support the reliability, validity and responsiveness of the EQ-5D-5L, overcoming the limitations of the EQ-5D-3L in these patients. Therefore, the EQ-5D-5L could be very useful as an outcome measure, at least in patients with hip or knee OA.

ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration.

Upon apoptotic stimuli, epithelial cells compensate the gaps left by dead cells by activating proliferation. This has led to the proposal that dying cells signal to surrounding living cells to maintain homeostasis. Although the nature of these signals is not clear, reactive oxygen species (ROS) could act as a signaling mechanism as they can trigger pro-inflammatory responses to protect epithelia from environmental insults. Whether ROS emerge from dead cells and what is the genetic response triggered by ROS is pivotal to understand regeneration of Drosophila imaginal discs. We genetically induced cell death in wing imaginal discs, monitored the production of ROS and analyzed the signals required for repair. We found that cell death generates a burst of ROS that propagate to the nearby surviving cells. Propagated ROS activate p38 and induce tolerable levels of JNK. The activation of JNK and p38 results in the expression of the cytokines Unpaired (Upd), which triggers the JAK/STAT signaling pathway required for regeneration. Our findings demonstrate that this ROS/JNK/p38/Upd stress responsive module restores tissue homeostasis. This module is not only activated after cell death induction but also after physical damage and reveals one of the earliest responses for imaginal disc regeneration.

Validation of the Spanish version of the Oxford knee score and assessment of its utility to characterize quality of life of patients suffering from knee osteoarthritis: a multicentric study.

BACKGROUND: Knee osteoarthritis (OA) represents a heavy burden for patients and the society as a whole. The Oxford Knee Score (OKS) is a well known tool to assess the quality of life in patients with Knee OA. The purpose of this study was to analyze the psychometric properties of the Spanish version of the OKS, including its reliability, validity, and responsiveness. METHODS: Prospective observational study that included 397 patients diagnosed with knee OA according to the criterion of the American Rheumatism Association, which were recruited in 3 different Spanish regions. Their self-perceived health-related quality of life (HRQL) was assessed through 3 questionnaires: a generic one (the EQ-5D-5 L) and two specific ones adapted to Spanish (the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Oxford Knee Score (OKS). The follow-up period was 6 months, and the acceptability of the OKS was evaluated, together with its psychometric properties, presence of ceiling and floor effects, validity, reliability, and sensitivity to change. RESULTS: The OKS was fully answered in 99.5% of cases, with no evidence of ceiling or floor effects. Its factor structure can be explained in a single dimension. Its discriminating capacity was very good compared to the groups generated by the WOMAC and the EQ-5D-5 L. The correlation of the OKS with the dimensions of the latter questionnaires was around 0.7. The test-retest reliability was excellent (ICC 0.993; CI 95%: 0.990-0.995) and so was its internal consistency (Cronbach's α = 0.920). The effect size was 0.7 for moderate improvements in the HQRL, which is similar to that of the dimensions of the WOMAC and greater than for the EQ-5D-5 L. The minimum clinically significant difference that was detected by the questionnaire was 6.1 points, and the minimum detectable change was 4.4 points. CONCLUSIONS: The Spanish-adapted version of the OKS is a useful, valid tool for assessing the perceived HRQL in patients suffering from knee OA, with psychometric properties similar to the WOMAC, and that allows for discriminating the patient's condition at a particular moment as well as for appraising changes over time.

Cost-of-Illness in Rare Diseases.

Cost-of-illness (COI) studies quantify the economic burden of a disease, including direct healthcare and non-healthcare costs and productivity losses. Different approaches can be adopted to evaluate the resources associated to a disease and to calculate the total costs. Prevalence-based studies estimate the total costs of a disease during a given period, while incidence-based studies measure lifetime costs from onset until death. Data can be collected from individuals, using a bottom-up approach, or from population statistics, using a top-down approach. Different perspectives are possible, but the broadest and also mostly used is the societal one. Appropriate discounting should be applied for future costs and a sensitivity analyses of main parameters should be performed. The main limitation of COI studies is that they don't account the outcomes or benefits of possible treatments.There is a lack of COI studies in the field of rare diseases. A multinational COI study (BURQOL-RD) evaluated recently the burden of 10 rare diseases in Europe, using a prevalence-based method with a bottom-up approach to quantify resources from a societal perspective, which is the mostly used methodology for COI studies in rare diseases; however, several other studies illustrate different approaches to conduct COI analysis in this field, such as incidence-based methods or narrower perspectives.COI studies are useful to inform policy-makers about the magnitude of a disease. To support correctly the decision-making process, it is necessary to identify the cost-drivers through COI studies with robust design and standardized methodology.

METHODOLOGICAL QUALITY OF ECONOMIC EVALUATIONS ALONGSIDE TRIALS OF KNEE PHYSIOTHERAPY.

OBJECTIVES: The methodological quality of an economic evaluation performed alongside a clinical trial can be underestimated if the paper does not report key methodological features. This study discusses methodological assessment issues on the example of a systematic review on cost-effectiveness of physiotherapy for knee osteoarthritis. METHODS: Six economic evaluation studies included in the systematic review and related clinical trials were assessed using the 10-question check-list by Drummond and the Physiotherapy Evidence Database (PEDro) scale. RESULTS: All economic evaluations were performed alongside a clinical trial but the studied interventions were too heterogeneous to be synthesized. Methodological quality of the economic evaluations reported in the papers was not free of drawbacks, and in some cases, it improved when information from the related clinical trial was taken into account. CONCLUSIONS: Economic evaluation papers dedicate little space to methodological features of related clinical trials; therefore, the methodological quality can be underestimated if evaluated separately from the trials. Future economic evaluations should follow more strictly the recommendations about methodology and the authors should pay special attention to the quality of reporting.

Cross-cultural adaptation and validation of the Spanish version of the Oxford Hip Score in patients with hip osteoarthritis.

BACKGROUND: Osteoarthritis (OA) of the hip is a disease that entails a major burden for patients and the society as a whole. One way of measuring this burden for the patient is through impact on Health-related Quality of Life (HRQL). The Oxford Hip Score (OHS) is a well-known tool to measure HRQL in patients with OA of the hip. This study aims to assess the psychometric properties of the Spanish-adapted version of the OHS, including its reliability, validity, and sensitivity to change. METHODS: Prospective observational study that included 361 patients diagnosed with hip OA (according to the criterion of the American College of Rheumatology) from 3 different Spanish regions. Their HRQL was assessed using a generic questionnaire, the EQ-5D-5 L, and two specific ones (the Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC, and the OHS) adapted to Spanish. There was a follow-up period of 6 months, and the acceptability, psychometric properties, presence of ceiling and floor effects, validity, reliability, and sensitivity to changes of the OHS were measured. RESULTS: The OHS was fully answered in 99.4% of cases with no indication of ceiling or floor effects. Its factor structure can be explained in a single dimension. Its discriminative capacity was very good compared to the groups generated by the WOMAC and the EQ-5D-5 L. The correlation between the OHS and dimensions of the WOMAC or EQ-5D-5 L utilities was ≥0.7. Excellent test-retest reliability (ICC = 0.992; CI95%: 0.994-0.998) and internal consistency (Cronbach's α = 0.928) were observed. The minimal clinically important difference (MCID) was 7.0 points, and the minimum detectable change (MDC) was 5.5 points. The effect size for moderate improvement in perceived HRQL was 0.73, similar to that of WOMAC dimensions and higher than the EQ-5D-5 L. CONCLUSIONS: The Spanish-adapted version of the OHS is a useful, acceptable tool for the assessment of perceived HRQL in patients with hip OA, and has psychometric properties similar to those of the WOMAC that allow for discriminating both a patient's condition at a given moment and changes that can occur over time.

On the Estimation of the Cost-Effectiveness Threshold: Why, What, How?

BACKGROUND: Many health care systems claim to incorporate the cost-effectiveness criterion in their investment decisions. Information on the system's willingness to pay per effectiveness unit, normally measured as quality-adjusted life-years (QALYs), however, is not available in most countries. This is partly because of the controversy that remains around the use of a cost-effectiveness threshold, about what the threshold ought to represent, and about the appropriate methodology to arrive at a threshold value. OBJECTIVES: The aim of this article was to identify and critically appraise the conceptual perspectives and methodologies used to date to estimate the cost-effectiveness threshold. METHODS: We provided an in-depth discussion of different conceptual views and undertook a systematic review of empirical analyses. Identified studies were categorized into the two main conceptual perspectives that argue that the threshold should reflect 1) the value that society places on a QALY and 2) the opportunity cost of investment to the system given budget constraints. RESULTS: These studies showed different underpinning assumptions, strengths, and limitations, which are highlighted and discussed. Furthermore, this review allowed us to compare the cost-effectiveness threshold estimates derived from different types of studies. We found that thresholds based on society's valuation of a QALY are generally larger than thresholds resulting from estimating the opportunity cost to the health care system. CONCLUSIONS: This implies that some interventions with positive social net benefits, as informed by individuals' preferences, might not be an appropriate use of resources under fixed budget constraints.

The Minnesota living with heart failure questionnaire: comparison of different factor structures.

BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is one of the most widely used health-related quality of life questionnaires for patients with heart failure (HF). It provides scores for two dimensions, physical and emotional, and a total score. However, there are some concerns about its factor structure and alternatives have been proposed, some including a third factor representing a social dimension. The objectives of the present study were to analyze the internal structure of the MLHFQ and the unidimensionality of the total score, and to compare the different factor structures proposed. METHODS: The MLHFQ was given to 2565 patients with HF. The structural validity of the questionnaire was assessed by confirmatory factor analysis (CFA), and Rasch analysis. These two approaches were also applied to the alternative structures proposed. RESULTS: The CFA results for the hypothesized model of two latent factors and the Rasch analysis confirmed the adequacy of the physical and emotional scales. Rasch analysis for the total score showed only two problematic items. The results of the CFA for other two-factor structures proposed were not better than the results for the original structure. The Rasch analyses applied to the different social factors yielded the best results for Munyombwe's social dimension, composed of six items. CONCLUSIONS: Our results support the validity of using the MLHFQ physical, emotional and total scores in patients with HF, for clinical practice and research. In addition, they confirmed the existence of a third factor, and we recommend the use of Munyombwe's social factor.