Socioeconomic burden of schizophrenia: a targeted literature review of types of costs and associated drivers across 10 countries.

AIMS: Schizophrenia has the highest median societal cost per patient of all mental disorders. This review summarizes the different costs/cost drivers (cost components) associated with schizophrenia in 10 countries, including all cost types and stakeholder perspectives, and highlights aspects of disease associated with greatest costs. MATERIALS AND METHODS: Targeted literature review based on a search of published research from 2006 to 2021 in the United States (US), United Kingdom (UK), France, Germany, Italy, Spain, Canada, Japan, Brazil, and China. RESULTS: Sixty-four published articles (primary studies and literature reviews) were included. Comprehensive data were available on costs in schizophrenia overall, with very limited data for individual countries except the US. Most data is related to direct and not indirect costs, with extremely scarce data for several key cost components (adverse events, suicide, long-term care). Total schizophrenia-related per person per year (PPPY) costs were $2,004-94,229, with considerable variability among countries. Indirect costs were the main cost driver (50-90% of all costs), ranging from $1,852 to $62,431 PPPY. However, indirect costs are not collected systematically or incorporated in health technology assessments. Total schizophrenia-related PPPY direct costs were $4,394-31,798, with inpatient cost as the main cost driver (∼20-99% of direct costs). Intangible costs were not reported. Despite limited evidence, total schizophrenia-related costs were higher in patients with than without negative symptoms, largely due to increased costs of medication and medical visits. LIMITATIONS: As this was not a systematic review, prioritization of studies may have resulted in exclusion of potentially relevant data. All costs were converted to USD but not corrected for inflation or subjected to a gross domestic product deflator. CONCLUSIONS: Direct costs are most commonly reported in schizophrenia. The substantial underreporting of indirect and intangible costs undervalues the true economic burden of schizophrenia from a payer, patient, and societal perspective.

The true costs of diseases such as schizophrenia extend far beyond the obvious direct costs of hospital visits, outpatient appointments and medications to include indirect costs such as loss of productivity among patients and caregivers due to unemployment, early retirement and premature death. This review of literature published between 2006 and 2021 reveals that the indirect costs of schizophrenia actually account for between 50% and 90% of all costs, but are often not taken into account in healthcare planning. In addition, intangible costs, including the pain, suffering, stress, and anxiety experienced by patients and caregivers due to schizophrenia have not been reported in the literature. Costs were also higher for patients with negative symptoms of schizophrenia (where patients appear withdrawn and lacking in emotion, with few social relationships) compared with those with positive symptoms (including delusions or hallucinations). This is largely due to the greater costs for medications and medical visits among patients with negative symptoms. In summary, this review demonstrates that the true cost of schizophrenia, including direct, indirect, and intangible costs, is likely to be substantially higher than the values for the cost of disease currently reported.

Routine provision of feedback from patient-reported outcome measurements to healthcare providers and patients in clinical practice.

BACKGROUND: Patient-reported outcomes measures (PROMs) assess a patient's subjective appraisal of health outcomes from their own perspective. Despite hypothesised benefits that feedback  on PROMs can support decision-making in clinical practice and improve outcomes, there is uncertainty surrounding the effectiveness of PROMs feedback. OBJECTIVES: To assess the effects of PROMs feedback to patients, or healthcare workers, or both on patient-reported health outcomes and processes of care. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, two other databases and two clinical trial registries on 5 October 2020. We searched grey literature and consulted experts in the field. SELECTION CRITERIA: Two review authors independently screened and selected studies for inclusion. We included randomised trials directly comparing the effects on outcomes and processes of care of PROMs feedback to healthcare professionals and patients, or both with the impact of not providing such information. DATA COLLECTION AND ANALYSIS: Two groups of two authors independently extracted data from the included studies and evaluated study quality. We followed standard methodological procedures expected by Cochrane and EPOC. We used the GRADE approach to assess the certainty of the evidence. We conducted meta-analyses of the results where possible. MAIN RESULTS: We identified 116 randomised trials which assessed the effectiveness of PROMs feedback in improving processes or outcomes of care, or both in a broad range of disciplines including psychiatry, primary care, and oncology. Studies were conducted across diverse ambulatory primary and secondary care settings in North America, Europe and Australasia. A total of 49,785 patients were included across all the studies. The certainty of the evidence varied between very low and moderate. Many of the studies included in the review were at risk of performance and detection bias. The evidence suggests moderate certainty that PROMs feedback probably improves quality of life (standardised mean difference (SMD) 0.15, 95% confidence interval (CI) 0.05 to 0.26; 11 studies; 2687 participants), and leads to an increase in patient-physician communication (SMD 0.36, 95% CI 0.21 to 0.52; 5 studies; 658 participants), diagnosis and notation (risk ratio (RR) 1.73, 95% CI 1.44 to 2.08; 21 studies; 7223 participants), and disease control (RR 1.25, 95% CI 1.10 to 1.41; 14 studies; 2806 participants). The intervention probably makes little or no difference for general health perceptions (SMD 0.04, 95% CI -0.17 to 0.24; 2 studies, 552 participants; low-certainty evidence), social functioning (SMD 0.02, 95% CI -0.06 to 0.09; 15 studies; 2632 participants; moderate-certainty evidence), and pain (SMD 0.00, 95% CI -0.09 to 0.08; 9 studies; 2386 participants; moderate-certainty evidence). We are uncertain about the effect of PROMs feedback on physical functioning (14 studies; 2788 participants) and mental functioning (34 studies; 7782 participants), as well as fatigue (4 studies; 741 participants), as the certainty of the evidence was very low. We did not find studies reporting on adverse effects defined as distress following or related to PROM completion. AUTHORS' CONCLUSIONS: PROM feedback probably produces moderate improvements in communication between healthcare professionals and patients as well as in diagnosis and notation, and disease control, and small improvements to quality of life. Our confidence in the effects is limited by the risk of bias, heterogeneity and small number of trials conducted to assess outcomes of interest. It is unclear whether   many of these improvements are clinically meaningful or sustainable in the long term. There is a need for more high-quality studies in this area, particularly studies which employ cluster designs and utilise techniques to maintain allocation concealment.

Prognostic Factors and Treatment-Effect Modifiers in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years of age. Individuals with types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of types 1, 2, and 3 SMA. In untreated infants with type 1 SMA, absence of symptoms at birth, a later symptom onset, and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation, and, to a lesser extent, baseline function were identified as potential treatment-modifying factors for survival, emphasizing that early treatment with disease-modifying therapies (DMT) is essential in type 1 SMA. In patients with types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age, and ambulatory status. Individuals aged 6-15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment-effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching, or summarizing results from different studies on the treatments for SMA.

Most guideline organizations lack explicit guidance in how to incorporate cost considerations.

OBJECTIVES: Resource use and cost (RUC) evidence is one of the factors that can be considered when formulating recommendations in clinical practice guidelines (CPGs). However, it is unclear how CPG developers incorporate this information. The purpose of this study was to identify available guidance from guideline organizations on how to incorporate RUC in CPGs. STUDY DESIGN AND SETTING: This is a methodological survey. We searched MEDLINE, the G-I-N library, the Cochrane Methodology Register, and gray literature from inception to 2017. We included the most recent version of guidance documents. We excluded those that only reported methodology for adapting, endorsing, or updating CPGs, and documents reporting methods followed in the development of one or more specific CPGs. RESULTS: We included 77 documents from 67 organizations. Fifty-nine organizations (88.1%) include information regarding RUC during the CPG development process. Fifty-five (82.1%) organizations report taking RUC into account when developing recommendations: 44 (65.7%) do this explicitly, 5 (7.5%) implicitly, and 6 (9.0%) explicitly as optional. Twelve of the 44 organizations that explicitly consider RUC (27.3%) provide guidance to identify, assess and use the RUC evidence when developing recommendations. Twenty-three consider RUC when moving from the evidence to recommendations (52.3%). Seventeen of the 44 (38.6%) recommend making qualitative judgments about whether the desirable effects of interventions were worth the associated costs. CONCLUSION: More explicit guidance is needed alongside tools to help CPGs developers incorporate RUC evidence when formulating recommendations. Our results may be of use for guideline developers to improve this guidance.

mHealth Assessment: Conceptualization of a Global Framework.

BACKGROUND: The mass availability and use of mobile health (mHealth) technologies offers the potential for these technologies to support or substitute medical advice. However, it is worrisome that most assessment initiatives are still not able to successfully evaluate all aspects of mHealth solutions. As a result, multiple strategies to assess mHealth solutions are being proposed by medical regulatory bodies and similar organizations. OBJECTIVE: We aim to offer a collective description of a universally applicable description of mHealth assessment initiatives, given their current and, as we see it, potential impact. In doing so, we recommend a common foundation for the development or update of assessment initiatives by addressing the multistakeholder issues that mHealth technology adds to the traditional medical environment. METHODS: Organized by the Mobile World Capital Barcelona Foundation, we represent a workgroup consisting of patient associations, developers, and health authority representatives, including medical practitioners, within Europe. Contributions from each group's diverse competencies has allowed us to create an overview of the complex yet similar approaches to mHealth evaluation that are being developed today, including common gaps in concepts and perspectives. In response, we summarize commonalities of existing initiatives and exemplify additional characteristics that we believe will strengthen and unify these efforts. RESULTS: As opposed to a universal standard or protocol in evaluating mHealth solutions, assessment frameworks should respect the needs and capacity of each medical system or country. Therefore, we expect that the medical system will specify the content, resources, and workflow of assessment protocols in order to ensure a sustainable plan for mHealth solutions within their respective countries. CONCLUSIONS: A common framework for all mHealth initiatives around the world will be useful in order to assess whatever mHealth solution is desirable in different areas, adapting it to the specifics of each context, to bridge the gap between health authorities, patients, and mHealth developers. We aim to foster a more trusting and collaborative environment to safeguard the well-being of patients and citizens while encouraging innovation of technology and policy.

Ensuring Evidence-Based Safe and Effective mHealth Applications.

The Internet and the digitalization of information have brought big changes in healthcare, but the arrival of smartphones and tablets represent a true revolution and a new paradigm is opened which completely changes our lives. In order to validate the impact of these new technologies in health care, it is essential to have enough clinical studies that validate their impact in wellbeing and healthcare of the patient. Traditional regulatory organisations are still looking for their role in this area. If they follow the classical path of medical devices, we get to a technical, administration and economic collapse. This contribution first presents the main indicators showing the potential of mHealth adoption. It then proposes a classification of mobile health care apps, and presents frameworks for mHealth evaluation. Regulation of mHealth as part of the evaluation process is discussed. Finally, the necessary steps and challenges that have to be taken into account by the industry to prepare the entrance of these technologies into the EU market is analysed.

The validity of recommendations from clinical guidelines: a survival analysis.

BACKGROUND: Clinical guidelines should be updated to maintain their validity. Our aim was to estimate the length of time before recommendations become outdated. METHODS: We used a retrospective cohort design and included recommendations from clinical guidelines developed in the Spanish National Health System clinical guideline program since 2008. We performed a descriptive analysis of references, recommendations and resources used, and a survival analysis of recommendations using the Kaplan-Meier method. RESULTS: We included 113 recommendations from 4 clinical guidelines with a median of 4 years since the most recent search (range 3.9-4.4 yr). We retrieved 39 136 references (range 3343-14 787) using an exhaustive literature search, 668 of which were related to the recommendations in our sample. We identified 69 (10.3%) key references, corresponding to 25 (22.1%) recommendations that required updating. Ninety-two percent (95% confidence interval 86.9-97.0) of the recommendations were valid 1 year after their development. This probability decreased at 2 (85.7%), 3 (81.3%) and 4 years (77.8%). INTERPRETATION: Recommendations quickly become outdated, with 1 out of 5 recommendations being out of date after 3 years. Waiting more than 3 years to review a guideline is potentially too long.

Use of clinical practice guidelines and factors related to their uptake: a survey of health professionals in Spain.

RATIONALE, AIMS AND OBJECTIVE: This study aims to assess the use of clinical practice guidelines (CPGs) among health professionals and factors related to their uptake in clinical practice. METHODS: Cross-sectional study based on an online survey conducted among primary care (PC) and hospital-based care (HC) doctors in Spain in 2011. Questionnaire development included adaptation of similar surveys and contextualization through a qualitative study. After a pilot study and review, the final survey contained five domains: demographics, involvement in CPGs, consultation of CPGs, perceptions and attitudes regarding CPGs and Spanish NHS CPGs Programme. Professionals from selected health care centres in seven regions were contacted by email with an invitation and link to the Web-based questionnaire. We analysed between-group differences and explored potential predictors of CPGs use by means of a logistic regression. RESULTS: Six hundred seventy-six doctors responded to the survey (27.7% response rate). 47.1% were PC and 49.5% were HC doctors. 32.5% stated previous involvement in CPGs and 56.5% stated training in research methodology. 67.5% of the surveyed professionals reported using CPGs more than one time per week. The use of a system for classifying the quality of evidence (62.3%) and for grading the strength of the recommendations (58.6%), as well as the use of a rigorous methodology (49.6%), were the most frequently reported aspects related to CPG credibility. The lack of time (56.4%), especially in PC (65.3% versus 49.5% in HC; P < 0.001), and the absence of brief and easily accessible format (42.2%) were the main reported barriers to using CPGs. None of the studied factors showed statistically significant association in the logistic regression model. CONCLUSIONS: Study results suggest that, in general, Spanish doctors trust and use CPGs frequently. To improve uptake by health professionals and to overcome existing barriers, CPGs should be rigorously developed and made accessible at the point-of-care in user-friendly electronic formats. Due to the low response rate, findings should be extrapolated with caution.

Attitudes and perceptions about clinical guidelines: a qualitative study with Spanish physicians.

BACKGROUND: Clinical guidelines (CGs) are popular for healthcare decision making but their acceptability and use by healthcare providers is influenced by numerous factors. Some of these factors are professional-related, such as knowledge and perceptions of and attitudes toward CGs in general. The aim of our study was to evaluate attitudes and perceptions of Spanish physicians towards CGs. METHODS: We coordinated six discussion groups with a total of 46 physicians. The participants were drawn from 12 medical specialties from both specialized and primary care. We recorded the sessions and transcribed the content verbatim. We analyzed the data using an approach based on the grounded theory. RESULTS: We identified two main constructs that defined the physicians' perceptions towards guidelines: knowledge and usefulness. "Knowledge" defined the theoretical meanings of guidelines, while "Usefulness" referred to the pragmatic approach to guidelines. These constructs were interrelated through a series of categories such as confidence, usability, accessibility, dissemination and formats. CONCLUSIONS: In our study, the constructs that impacted most on physician's attitudes to clinical guidelines were knowledge and usefulness. The tension between the theoretical and the pragmatic constructs determined the attitudes and how physicians use guidelines. Groups developing guidelines should ask relevant clinical questions and develop implementable and context specific recommendations. Developers should be explicit and consistent in the development and presentation of recommendations.

Strategies to assess the validity of recommendations: a study protocol.

BACKGROUND: Clinical practice guidelines (CPGs) become quickly outdated and require a periodic reassessment of evidence research to maintain their validity. However, there is little research about this topic. Our project will provide evidence for some of the most pressing questions in this field: 1) what is the average time for recommendations to become out of date?; 2) what is the comparative performance of two restricted search strategies to evaluate the need to update recommendations?; and 3) what is the feasibility of a more regular monitoring and updating strategy compared to usual practice?. In this protocol we will focus on questions one and two. METHODS: The CPG Development Programme of the Spanish Ministry of Health developed 14 CPGs between 2008 and 2009. We will stratify guidelines by topic and by publication year, and include one CPG by strata.We will develop a strategy to assess the validity of CPG recommendations, which includes a baseline survey of clinical experts, an update of the original exhaustive literature searches, the identification of key references (reference that trigger a potential recommendation update), and the assessment of the potential changes in each recommendation.We will run two alternative search strategies to efficiently identify important new evidence: 1) PLUS search based in McMaster Premium LiteratUre Service (PLUS) database; and 2) a Restrictive Search (ReSe) based on the least number of MeSH terms and free text words needed to locate all the references of each original recommendation.We will perform a survival analysis of recommendations using the Kaplan-Meier method and we will use the log-rank test to analyse differences between survival curves according to the topic, the purpose, the strength of recommendations and the turnover. We will retrieve key references from the exhaustive search and evaluate their presence in the PLUS and ReSe search results. DISCUSSION: Our project, using a highly structured and transparent methodology, will provide guidance of when recommendations are likely to be at risk of being out of date. We will also assess two novel restrictive search strategies which could reduce the workload without compromising rigour when CPGs developers check for the need of updating.

Validation of the FRAX predictive model for major osteoporotic fracture in a historical cohort of Spanish women.

FRAX is a fracture risk assessment tool to estimate the 10-yr probability of a major osteoporotic fracture or a hip fracture. The aim of the study was to assess the predictive ability of FRAX for major osteoporotic fracture in a cohort of Spanish women. The study was based on a retrospective cohort of women aged 40-90 yr. Patients were followed from their first bone densitometry to the first major osteoporotic fracture event (forearm, proximal humerus, clinical spine, or hip fracture) or for 10 yr whichever comes first. A total of 1231 women were included. Bone mineral density data and self-reported data on risk factors for fracture were obtained. The predictive ability of FRAX was assessed by analyzing calibration and discrimination, with the calculation of observed-to-expected (O/E) fracture ratios and the receiver operating characteristic (ROC) curve, respectively. A total of 222 women (18.1%) reported at least 1 fracture after the first assessment. The incidence of fracture was 14 (95% confidence interval [CI]: 10-17), 19 (95% CI: 15-23), 28 (95% CI: 21-36), and 67 (95% CI: 8-125) cases per 1000 woman-years in women aged <55, 55-64, 65-74, and ≥75 yr, respectively. The O/E ratio was 3.9 (95% CI: 3.4-4.5; p<0.0001). The area under the ROC curve was 61% (95% CI: 57-65%). FRAX underestimated the risk of major osteoporotic fracture in this cohort of Spanish women, particularly in those with a low risk of fracture according to the clinical factors used in the FRAX tool. Our findings highlight the need for validation studies of FRAX in Spain.

Factores de riesgo de fracturas por fragilidad en una cohorte de mujeres españolas / Risk factors for fragility fractures in a cohort of Spanish women

Introducción Las fracturas por fragilidad constituyen un problema de salud pública. El objetivo fue analizar la asociación de los principales factores de riesgo de osteoporosis con la fracturas por fragilidad en una cohorte de mujeres con indicación de densitometría ósea. Métodos Cohorte retrospectiva con seguimiento hasta una fractura por fragilidad, de una población de mujeres de 40 a 90 años de edad con una primera visita para realizarse una densitometría entre enero de 1992 y febrero de 2008. Se calcularon la tasa de incidencia de fracturas por 1000 mujeres-año de seguimiento y la hazard ratio (HR) de fractura mediante un modelo de regresión de Cox. Resultados Se estudiaron 49.735 mujeres con una edad media de 57,8 años (desviación estándar: 8,5). De ellas, 3631 mujeres (7,1%) declararon al menos una fractura por fragilidad en las visitas posteriores a la basal. Los factores de riesgo con una mayor HR ajustada fueron la edad ≥75 años respecto a < 55 años (HR: 3,8; intervalo de confianza del 95% [IC95%]: 3,3-4,4) y tener un resultado de la densitometría valorable como osteoporosis respecto a normal (HR: 2; IC95%: 1,8-2,2). Los antecedentes de fracturas de húmero, cadera o vertebral tuvieron una HR ajustada de 1,2 (IC95%: 1,1-1,3).Conclusiones Los principales factores de riesgo de fracturas por fragilidad fueron la edad avanzada, el resultado de la densitometría y los antecedentes de fractura, aunque un 74% de las fracturas se produjeron con una densidad mineral ósea normal u osteopenia. Otros factores significativos fueron la artritis reumatoide y haber estado en tratamiento prolongado con corticosteroides(AU)

Introduction Fragility fractures are an important public health issue. The aim of this study was to analyze the association of the main osteoporotic risk factors related to fragility fracture in a cohort of women with an indication of bone densitometry (BD).Methods A retrospective cohort was followed-up until a fragile fracture occurred, in a population of women aged 40 to 90 years with a first visit for BD between January 1992 and February 2008. We calculated the incidence rate of fracture per 1000 women-years of follow-up, and the hazard ratio (HR) of fragile fracture using a Cox regression model. Results A total of 49,735 women were studied. The average age of participants was 57.8 years (SD: 8.5). Of these, 3631 women (7.1%) reported a new fragility fracture in post-baseline visits. Risk factors with higher adjusted HR were age ≥ 75 years compared with age < 55 years (HR: 3.8; 95% CI: 3.3-4.4) and having a BC result evaluated as osteoporosis compared to normal (HR: 2.0; 95% CI: 1.8-2.2). A personal history of humerus, hip or vertebral fractures had an adjusted HR of 1.2 (95% CI: 1.1-1.3).Conclusions The main risk factors for fragility fracture were advanced age, BD result and a personal history of fracture, although 74% of fractures were detected with a bone mineral density classified as normal or osteopenia. Other relevant factors were rheumatoid arthritis or having received prolonged corticosteroid therapy (AU)

[Risk factors for fragility fractures in a cohort of Spanish women]. / Factores de riesgo de fracturas por fragilidad en una cohorte de mujeres españolas.

INTRODUCTION: Fragility fractures are an important public health issue. The aim of this study was to analyze the association of the main osteoporotic risk factors related to fragility fracture in a cohort of women with an indication of bone densitometry (BD). METHODS: A retrospective cohort was followed-up until a fragile fracture occurred, in a population of women aged 40 to 90 years with a first visit for BD between January 1992 and February 2008. We calculated the incidence rate of fracture per 1000 women-years of follow-up, and the hazard ratio (HR) of fragile fracture using a Cox regression model. RESULTS: A total of 49,735 women were studied. The average age of participants was 57.8 years (SD: 8.5). Of these, 3631 women (7.1%) reported a new fragility fracture in post-baseline visits. Risk factors with higher adjusted HR were age ≥ 75 years compared with age < 55 years (HR: 3.8; 95% CI: 3.3-4.4) and having a BC result evaluated as osteoporosis compared to normal (HR: 2.0; 95% CI: 1.8-2.2). A personal history of humerus, hip or vertebral fractures had an adjusted HR of 1.2 (95% CI: 1.1-1.3). CONCLUSIONS: The main risk factors for fragility fracture were advanced age, BD result and a personal history of fracture, although 74% of fractures were detected with a bone mineral density classified as normal or osteopenia. Other relevant factors were rheumatoid arthritis or having received prolonged corticosteroid therapy.

Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems: a protocol for a qualitative study and a national survey.

BACKGROUND: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. METHODS/DESIGN: A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. DISCUSSION: Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere.

Disease-specific health-related quality of life questionnaires for heart failure: a systematic review with meta-analyses.

BACKGROUND: Heart failure (HF) is an increasingly common condition affecting patients' health-related quality of life (HRQL). However, there is little literature comparing HF-specific instruments. Our aim was to evaluate and compare data on the conceptual model and metric properties (reliability, validity and responsiveness) of HF-specific HRQL instruments, by performing a systematic review with meta-analyses. METHODS AND RESULTS: Of 2,541 articles initially identified, 421 were full-text reviewed. Ninety-four reported data on five questionnaires: Minnesota Living with Heart Failure Questionnaire (MLHFQ), Chronic Heart Failure Questionnaire (CHFQ), Quality of Life Questionnaire for Severe Heart Failure (QLQ-SHF), Kansas City Cardiomyopathy Questionnaire (KCCQ) and Left Ventricular Dysfunction (LVD-36) questionnaire. Metric properties (reliability, validity and responsiveness) were summarised using meta-analysis for pools above five estimates. Cronbach's alpha coefficients were generally high (0.83-0.95) for overall scores and scales measuring physical health. Associations with four validity criteria (New York Heart Association [NYHA] class, six-minute walk test [6MWT] and short form-36 [SF-36] 'Physical' and 'Social Functioning') were moderate to strong (0.41-0.84), except for those between two CHFQ domains (fatigue and dyspnoea) and the NYHA (0.19 and 0.22). Pooled estimates of change from eight meta-analyses showed the MLHFQ to be highly responsive, with changes in overall score ranging from -9.6 (95% confidence interval [CI]: -4.1; -15.2) for placebo to -17.7 (95% CI: -15.3; -20.2) for pacing devices. The CHFQ and KCCQ also showed good sensitivity to change. CONCLUSIONS: Most of the questionnaires studied met minimum psychometric criteria, though current evidence would primarily support the use of the MLHFQ, followed by the KCCQ and CHFQ.

New electrocardiographic diagnostic criteria for the pathologic R waves in leads V1 and V2 of anatomically lateral myocardial infarction.

AIMS: To study the different QRS patterns in leads V1 and V2 in first inferior, lateral, and combined inferolateral myocardial infarction (MI) to recognize which are the ECG criteria that best define the presence of lesions isolated to the anatomically lateral wall of the left ventricle. METHODS AND RESULTS: We studied consecutive patients with first inferior (15), lateral (9), or inferolateral (21) MI with reference to contrast enhanced cardiac magnetic resonance (CE-CRM). We measured the R-wave amplitude and duration, the R/S ratio, and the T-wave amplitude and polarity in leads V1 and V2. The specificity of the V1 criteria for lateral MI, that is, R/S amplitude ratio 1 or greater and R duration 40 milliseconds or longer, is very high but its sensitivity is low. We defined 2 new criteria, R/S of 0.5 or greater and R amplitude in V1 greater than 3 mm, with each achieving a sensitivity of 73.3% and specificity of 93.3% for lateral/inferolateral MI location. CONCLUSIONS: (1) New ECG criteria for lateral MI (R/S ratio in V1 > or =0.5 and R amplitude in V1 >3 mm) present very high specificity and lower but very acceptable sensitivity for lateral MI. (2) New criteria based on R waves in V2 or T waves in V1 to V2 do not discriminate between inferior and lateral MI. (3) The classical criteria (R/S amplitude ratio > or =1 and R duration > or =40 ms in V1) attain very high specificity but much lower sensitivity than the new criteria.

Relevancia de la muerte súbita cardíaca / Relevancy of sudden death of cardiac origin

Sudden death (SD) is of cardiac origin in approximately 80-90% of the cases and represents one of the most important challenges of the modern cardiology. Evaluation and understanding of its epidemiological, clinical and histopathological characteristics can lead to better results in its management. In Spain was carried a multicenter study MUSA with two arms: 1/ EULALIA: histopathological aspects of SD and 2/ MUSIC: SD in heart failure with focus on identification of population groups at risk, pathophysiological mechanisms of development and clinical prognostic markers. The preliminary conclusions of both studies are the following: 1/ EULALIA trial: From the total 121 sudden deaths, 109 (90%) were of cardiac origin and of these 45% presented characteristics of myocardial hypertrophy. The histopathological findings reveled that in only 48% of cases acute ischemic heart disease was present. In the other cases of ischemic heart disease the sudden death was probably by arrhythmic origin related with the presence of old myocardial infarction. This is the most striking difference compared with Anglo-Saxon studies. In the 29 cases of ACS, 18 had eroded and combination of eroded and ruptured plaques. In the cases of non-ACS plaques were stable in 20, and combination of stable and vulnerable plaques in 7 cases. Statistically significant results as independent predictors of sudden death gave the following markers: history of MI, cephalization of vessels in thorax X-ray, left atrium size > 45 mm, high levels of NT-proBNP and PIP, LBBB on ECG recording and body mass index.

Exploration of the value of health-related quality-of-life information from clinical research and into clinical practice.

Quality-of-life (QOL) instruments used in clinical research can provide important evidence to inform decisions about alternative treatments. This is particularly true when patients, such as those with cancer who are contemplating toxic chemotherapy, face tradeoffs between quantity of life and QOL or when the primary goal of therapy is to improve how patients feel. Surrogate measures (cardiac function, exercise capacity, bone density, tumor size) are inadequate substitutes for direct measurement of QOL. Quality-of-life measures will be most valuable when they comprehensively measure aspects of QOL that are both important to patients and likely to be influenced by therapy, when the QOL measurement instruments are valid (measuring what is intended) and responsive (able to detect all important changes, even if small), and when the results are readily interpretable (determining whether treatment-related changes are trivial, small but important, or large). Researchers are finding new, imaginative ways to help clinicians understand the magnitude of treatment impact on QOL. Additionally, QOL measures may be useful in clinical practice. Recent results from well-designed randomized controlled trials suggest that information on patient QOL provided to clinicians might, in some circumstances, result in benefits for these patients. Further investigation is warranted to confirm these observations and to define the particular combination of methods and settings most likely to yield important benefits.