Hospital Alto Deba

Discrete event simulation (DES) is a form of computer-based modeling that provides an intuitive and flexible approach to representing complex systems. It has been used in a wide range of health care applications. Most early applications involved analyses of systems with constrained resources, where the general aim was to improve the organization of delivered services. More recently, DES has increasingly been applied to evaluate specific technologies in the context of health technology assessment. The aim of this article is to provide consensus-based guidelines on the application of DES in a health care setting, covering the range of issues to which DES can be applied. The article works through the different stages of the modeling process: structural development, parameter estimation, model implementation, model analysis, and representation and reporting. For each stage, a brief description is provided, followed by consideration of issues that are of particular relevance to the application of DES in a health care setting. Each section contains a number of best practice recommendations that were iterated among the authors, as well as the wider modeling task force.

La evaluación económica de tecnologías sanitarias se ha convertido en los últimos años en Europa en una herramienta de primer orden para los gestores sanitarios en sus estrategias de asignación de recursos sanitarios y de adopción de nuevas tecnologías. España fue uno de los países pioneros en realizar propuestas de estandarización metodológica aplicable a estudios de evaluación económica. No obstante, la falta de decisión política y de apoyo de los gestores sanitarios a este tipo de herramientas hizo que las propuestas cayeran en desuso. Sin embargo, lo esperable es que a medio plazo sea cada vez más habitual que las nuevas tecnologías sanitarias financiadas por el Sistema Nacional de Salud deban aportar una adecuada evidencia de su valor terapéutico y social en comparación con su coste. Llegado ese momento, los actores del sistema requerirán una serie de reglas claras y consensuadas por parte de los agentes del sistema sobre las cuestiones técnicas o metodológicas que deben respetar los estudios de evaluación de tecnologías sanitarias. Por este motivo, las presentes recomendaciones orientan sobre cómo realizar y analizar los estudios de evaluación económica de calidad. Las recomendaciones aparecen bajo 17 encabezamientos o dominios, y bajo cada recomendación hay además un comentario, en el cual se justifican y discuten las propuestas en relación con otras opciones posibles. Over the last few years, economic evaluation of health technologies has become a major tool used by European health policy decision-makers to create strategies for prioritizing the allocation of health resources and the approval of new technologies. Spain was a pioneer in proposing the standardization of methodology applicable to economic evaluation studies. However, because health policy decision-makers refused to support the initiative, the methodology was never put into practice. In the medium term, evidence of the economic value of new health technologies financed by the national health system will probably be increasingly required. At that time, stakeholders and decision-makers will have to agree upon a clear and concise set of rules on the technical and methodological issues that must be followed by economic evaluations of health technologies. Consequently, we have provided guidelines and recommendations for producing first-rate economic evaluations. The recommendations appear under seventeen headings or sections. In each case, the recommended requirements to be satisfied by an economic evaluation of health technologies are provided and each recommendation is followed by a commentary, providing a justification and comparing and contrasting the proposal with other available alternatives.

The Trail Making Test (TMT) has been a useful assessment tool to investigate executive function. Several studies have recently improved the existing TMT norms by mean of large samples of healthy individuals stratified by a number of demographic variables from different populations. In contrast, criticisms have been raised about the utility of norms from healthy samples to detect changes across time in clinical samples where TMT performance used to be altered. In addition, few studies have compared groups of patients with deficits in TMT performance, making it difficult to decide whether a single set of norms is sufficient to assess different clinical populations. We provide normative data from three large samples of patients with traumatic brain injury (TBI) (n=90), schizophrenia spectrum disorders (n=127), and healthy Spanish speakers (n=223). Differences between healthy participants and patients in all TMT direct (TMT-A, TMT-B) and derived (B-A, B:A, B-A/A) scores were found. TMT performance was poorer in TBI patients than in schizophrenia patients except for the B:A and B-A/A scores, suggesting a similar underlying executive deficit. Normal ageing impaired both direct and derived TMT indices, as revealed by lower scores in the healthy elderly group (55-80 years old) as compared with young (16-24) and middle-aged (25-54) healthy participants. Three different sets of norms stratified by age, education, or both are presented for clinical use. Recommendations on TMT scores are made for future research.

BACKGROUND: Dignity therapy is psychotherapy to relieve psychological and existential distress in patients at the end of life. Little is known about its effect. AIM: To analyse the outcomes of dignity therapy in patients with advanced life-threatening diseases. DESIGN: Systematic review was conducted. Three authors extracted data of the articles and evaluated quality using Critical Appraisal Skills Programme. Data were synthesized, considering study objectives. DATA SOURCES: PubMed, CINAHL, Cochrane Library and PsycINFO. The years searched were 2002 (year of dignity therapy development) to January 2016. 'Dignity therapy' was used as search term. Studies with patients with advanced life-threatening diseases were included. RESULTS: Of 121 studies, 28 were included. Quality of studies is high. Results were grouped into effectiveness, satisfaction, suitability and feasibility, and adaptability to different diseases and cultures. Two of five randomized control trials applied dignity therapy to patients with high levels of baseline psychological distress. One showed statistically significant decrease on patients' anxiety and depression scores over time. The other showed statistical decrease on anxiety scores pre-post dignity therapy, not on depression. Nonrandomized studies suggested statistically significant improvements in existential and psychosocial measurements. Patients, relatives and professionals perceived it improved end-of-life experience. CONCLUSION: Evidence suggests that dignity therapy is beneficial. One randomized controlled trial with patients with high levels of psychological distress shows DT efficacy in anxiety and depression scores. Other design studies report beneficial outcomes in terms of end-of-life experience. Further research should understand how dignity therapy functions to establish a means for measuring its impact and assessing whether high level of distress patients can benefit most from this therapy.

The demand for diagnostic and therapeutic services for obstructive sleep apnoea syndrome (OSAS) showed marked growth during the 1990s. This paper analyses the long-term cost-effectiveness of nasal continuous positive airway pressure (nCPAP) treatment in comparison to conventional null treatment. A Markov model was used to represent the natural history of OSAS based upon published evidence. Utility values came from a survey of OSAS patients. Data on health costs were collected from hospitals in the Basque Country, Spain. The incremental cost-effectiveness ratio of nCPAP treatment is <6,000 Euros per quality-adjusted life year. On disaggregated analysis, nCPAP treatment accounts for 86% of incremental costs; 84% of incremental effectiveness is attributable to improved quality of life. Treatment of obstructive sleep apnoea syndrome with nasal continuous positive airway pressure has a cost-effectiveness that is in line with that of other commonly funded treatments such as antihypertensive drugs. The key clinical benefit of nasal continuous positive airway pressure treatment is improvement in the quality of life of patients with obstructive sleep apnoea syndrome. This benefit is also precisely the one for which the evidence base is strongest. The remaining uncertainties concerning the impact of nasal continuous positive airway pressure on long-term mortality have only a relatively small impact on the economics of treatment.

OBJECTIVES: Hypertensive patients are a heterogeneous population that can be distributed in groups showing different cardiovascular risk and benefit from treatment. This study examines the cost-effectiveness of arterial hypertension treatment by age, sex, arterial hypertension stage, type of drug used and level of treatment compliance. DESIGN: Markov models combining absolute risks for stroke, coronary heart disease and all causes of death with relative risks from clinical trials and observational studies. Data on health costs were collected from hospitals and primary care settings in the Basque Country (Spain). RESULTS: Cost-effectiveness ratios vary from 34,516 euros/quality adjusted life year (QALY) gained in 30-year-old women to 3,307 euros/QALY in 80-year-old men. A treatment compliance of 50% increases these values to 45,270 and 4,905 euros/QALY, respectively. Treatment of arterial hypertension stage II shows lower ratios (19,798 euros/QALY in 30-year-old women and 1,918 euros/QALY in 80-year-old persons). Cost-effectiveness ratios for arterial hypertension stage I vary from 645 euros/QALY in 80-year-old men for diuretics to 47,325 euros/QALY in 30-year-old women for inhibitors of the angiotensin converting enzyme. CONCLUSIONS: There are large variations in the cost-effectiveness of arterial hypertension treatment depending on age, sex, arterial hypertension stage, drug used and compliance. Improvement of treatment compliance yields the greatest gain both in effectiveness and efficiency.

BACKGROUND AND PURPOSE: The aim of this article was to analyze the likelihood of receiving informal care after a stroke and to study the burden and risk of burnout of primary caregivers in Spain. METHODS: The CONOCES study is an epidemiological, observational, prospective, multicenter study of patients diagnosed with stroke and admitted to a Stroke Unit in the Spanish healthcare system. At 3 and 12 months post-event, we estimated the time spent caring for the patient and the burden borne by primary caregivers. Several multivariate models were applied to estimate the likelihood of receiving informal caregiving, the burden, and the likelihood of caregivers being at a high risk of burnout. RESULTS: Eighty percent of those still alive at 3 and 12 months poststroke were receiving informal care. More than 40% of those receiving care needed a secondary caregiver at 3 months poststroke. The likelihood of receiving informal care was associated with stroke severity and the individual's health-related quality of life. When informal care was provided, both the burden borne by caregivers and the likelihood of caregivers being at a high risk of burnout was associated with (1) caregiving hours; (2) the patient's health-related quality of life; (3) the severity of the stroke measured at discharge; (4) the patient having atrial fibrillation; and (5) the degree of dependence. CONCLUSIONS: This study reveals the heavy burden borne by the caregivers of stroke survivors. Our analysis also identifies explanatory and predictive variables for the likelihood of receiving informal care, caregiver burden, and high risk of burnout.

BACKGROUND: Scoring scales such as the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS), and the Anticholinergic Cognitive Burden Scale (ACB) provide an estimation of total anticholinergic burden. Not all the lists include the same drugs, and the points given for certain drugs differ among them. Whether these discrepancies present important differences in the estimation of anticholinergic burden for an individual patient is unknown. Therefore, the aim of this study is to assess agreement among the three scales. METHOD: Anticholinergic burden was measured with the three scales in 83 patients aged ≥65 years in a medium- and long-stay psychiatric hospital. Subsequently, patients were categorized into three risk categories: low risk (0 points), medium risk (1-2 points) or high risk (3 or more points). The chance-corrected measures of agreement for the different scores were determined with the k-statistic (kappa). RESULTS: Values for kappa were: 0.19 for Anticholinergic Risk Scale-Anticholinergic Drug Scale, 0.21 for ACB-Anticholinergic Drug Scale and 0.25 for Anticholinergic Risk Scale-ACB. The mean anticholinergic burden measured with ACB was 3.28. CONCLUSIONS: There is poor agreement among the three scales. These lists cannot be directly applied to different settings in which drug availability differs substantially, and they require periodic updates. Anticholinergic burden in our setting (psychogeriatric inpatients) was particularly high.

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992–1996 and followed up for a mean (±SD) of 21.6 (±3.4) years. A total of 459 incident cases of dementia were ascertained through expert revision of medical records. Data on habitual diet was collected through a validated diet history method to assess adherence to the relative Mediterranean Diet (rMED) score. Hazard ratios (HR) of dementia by rMED levels (low, medium and high adherence levels: ≤6, 7–10 and ≥11 points, respectively) were estimated using multivariable Cox models, whereas time-dependent effects were evaluated using flexible parametric Royston-Parmar (RP) models. Results of the fully adjusted model showed that high versus low adherence to the categorical rMED score was associated with a 20% (HR = 0.80, 95%CI: 0.60–1.06) lower risk of dementia overall and HR of dementia was 8% (HR = 0.92, 0.85–0.99, p = 0.021) lower for each 2-point increment of the continuous rMED score. By sub-types, a favorable association was also found in women for non-AD (HR per 2-points = 0.74, 95%CI: 0.62–0.89), while not statistically significant in men for AD (HR per 2-points = 0.88, 0.76–1.01). The association was stronger in participants with lower education. In conclusion, in this large prospective cohort study MD was inversely associated with dementia incidence after accounting for major cardiovascular risk factors. The results differed by dementia sub-type, sex, and education but there was no significant evidence of effect modification.

BACKGROUND: Patients with acquired brain damage (ABD) have suffered a brain lesion that interrupts vital development in the physical, psychological and social spheres. Stroke and traumatic brain injury (TBI) are the two main causes. The objectives of this study were to estimate the incidence and prevalence of ABD in the population of the Basque Country and Navarre in 2008, to calculate the associated cost of the care required and finally to assess the loss in health-related quality of life. METHODS: On the one hand, a cross-sectional survey was carried out, in order to estimate the incidence of ABD and its consequences in terms of costs and loss in quality of life from the evolution of a sample of patients diagnosed with stroke and TBI. On the other hand, a discrete event simulation model was built that enabled the prevalence of ABD to be estimated. Finally, a calculation was made of the formal and informal costs of ABD in the population of the Basque Country and Navarre (2,750,000 people). RESULTS: The cross-sectional study showed that the incidences of ABD caused by stroke and TBI were 61.8 and 12.5 cases per 100,000 per year respectively, while the overall prevalence was 657 cases per 100,000 people. The SF-36 physical and mental component scores were 28.9 and 44.5 respectively. The total economic burden was calculated to be 382.14 million euro per year, distributed between 215.27 and 166.87 of formal and informal burden respectively. The average cost per individual was 21,040 € per year. CONCLUSIONS: The main conclusion of this study is that ABD has a high impact in both epidemiological and economic terms as well as loss in quality of life. The overall prevalence obtained is equivalent to 0.7% of the total population. The substantial economic burden is distributed nearly evenly between formal and informal costs. Specifically, it was found that the physical dimensions of quality of life are the most severely affected. The prevalence-based approach showed adequate to estimate the population impact of ABD and the resources needed to compensate the disability.

PURPOSE: Thrombolysis is used to treat stroke patients based on the National Institute of Neurological Disorders and Stroke study and meta-analysis results. We present a cost-effectiveness analysis based on a probabilistic model of the use of thrombolytic therapy in stroke treatment. METHODS: We surveyed patients who had had a stroke during their hospital stay and examined them again 1 year after release from the hospital to obtain data on costs and natural history. We then calculated utility weights using the European Quality of Life Questionnaire. When the model runs, 4,000 Monte Carlo simulations are undertaken in which each parameter value changes depending on its probability distribution. The results are expressed in terms of the cost-effectiveness plane and the cost-effectiveness acceptability curve. RESULTS: We studied 435 patients, of whom 304 had had an ischemic stroke. One year later, 216 were still alive. The mean utility values were 0.22 for disabled patients and 0.77 for autonomous patients. The incremental cost-effectiveness ratio (ICER) obtained by means of the parameters was -19,000 EUR/quality-adjusted life year, reflecting a saving of 6,000 EUR and a health benefit for patients. The cost-effectiveness plane showed that thrombolysis was a dominant variable in 96.1% of simulations. In the acceptability curves, only 0.4 of simulations obtained an ICER higher than the societal threshold. CONCLUSIONS: Thrombolytic therapy seems to be a useful intervention because it is inexpensive and cost-effective. The key factor is the decreased rate of disability, which results in a better quality of life of the patient and lower costs.

BACKGROUND: Patient's relatives usually care for patients with schizophrenia, and as informal caregivers they experience negative consequences. The aim of the EDUCA-III trial is to test the efficacy of a psychoeducational intervention program (PIP) versus standard care to reduce the caregiver burden at post-intervention (4 months), and at follow-up (8 months). METHOD: A two-arm, evaluator blind, multicentre, randomized controlled trial. The PIP group had 12 weekly group sessions. The control intervention group had the usual support and standard care. Primary outcomes were change scores since baseline on the Zarit Burden Interview (ZBI) and the Involvement Evaluation Questionnaire (IEQ). RESULTS: One hundred and nine caregivers were randomized to PIP and 114 to control condition from 23 research sites. The decrease of ZBI scores was significantly higher on the PIP arm at 4 months (mean difference [MD]=-4.33; 95% CI -7.96, -0.71), and at 8 months (MD=-4.46; 95% CI -7.79, -1.13). There were no significant decreases in the IEQ scores (MD at 4 months=-2.80; 95% CI -6.27, 0.67; MD at 8 months=-2.85; 95% CI -6.51, 0.81). CONCLUSIONS: The PIP condition seems to reduce caregiver burden. TRIAL REGISTRATION: ISRCTN32545295.

We conducted a multicenter, prospective, evaluator-blinded, 2-arm parallel randomized trial to compare the effectiveness of a group psychoeducational intervention (PIP) with that of standard care in dementia caregivers. The primary outcome was the burden experience evaluated by the Zarit Burden Interview. Secondary outcomes were psychological distress evaluated with the scaled General Health Questionnaire-28 items, and quality of life evaluated with the Short-Form Health Survey 12. Effectiveness endpoint was at 4 months since inception. Statistical analyses used complete case and intention-to-treat analysis (ITT). The trial recruited 238 caregivers from 22 research sites (115 randomized to PIP, 123 randomized to standard care). No differences were found in the Zarit Burden Interview scores (complete case analysis: mean difference=-1.02, 95% confidence interval=-4.41 to 2.37; ITT analysis: MD=-0.55, 95% confidence interval=-3.64 to 2.55), the Short-Form Health Survey 12 domain scores (all P>0.05), and total General Health Questionnaire-28 items scores and some of its subscales (all P>0.05) except the anxiety and insomnia subscale for the ITT analysis (P=0.03). In summary, PIP in modality of group intervention was not better than standard care to reduce caregiver burden and overall psychological distress or to improve quality-of-life domains. EDUCA-II trial registry: ISRCTN14411440.

The purpose of this study was to estimate the burden of osteoporotic fractures beyond the hospitalization period covering up to the first year after the fracture. This was a prospective, 12-month, observational study including patients aged ≥65 years hospitalized due to a first low-trauma hip fracture, in six Spanish regions. Health resource utilization (HRU), quality of life (QoL) and autonomy were collected and total costs calculated. Four hundred and eighty seven patients (mean ± SD age 83 ± 7 years, 77 % women) were included. Twenty-two percent of patients reported a prior non-hip low-trauma fracture, 16 % were receiving osteoporotic treatment at baseline, and 3 % had densitometry performed (1.8 % T-score ≤-2.5). Sixteen percent of patients died (women 14 %; men 25 %; p = 0.0011) during the first year. Mean hospital stay was 11.8 ± 7.9 days and 95.1 % of patients underwent surgery. Other relevant HRUs were: outpatient visits in 78 % of patients (mean 9.2 ± 9.7); walking aids, 58.7 %; rehabilitation facilities, 35.5 % (28.7 ± 41.2 sessions); and formal and informal home care, 22.2 % (49.6 ± 72.2 days) and 53.4 % (77.1 ± 101.0 h), respectively. Mean direct cost was €9690 (95 % confidence interval: 9184-10,197) in women and €9019 (8079-9958) in men. Main cost drivers were: first hospitalization episode (women €7067 [73 %]; men €7196 [80 %]); outpatient visits (€1323 [14 %]; €997 [11 %]); and home care (€905 [9 %]; €767 [9 %]). QoL and autonomy showed a marked decrease during hospitalization, not entirely recovered at 12 months (p < 0.05 vs. baseline for EQ-5D, Harris hip score and modified Barthel index). In a Spanish setting, osteoporotic hip fractures incur a high societal and economic cost, mainly due to the first hospitalization HRU, but also due to subsequent outpatient visits and home care.

We present a technique for the surgical correction of aphakia that allows intrascleral fixation of a posterior chamber intraocular lens (IOL) without sutures. The technique is useful in situations in which one haptic has to be fixated and capsule support is adequate for fixation of the second haptic. The haptic is externalized with a 25-gauge needle; no surgical instrumentation other than that needed for conventional cataract surgery is used. The technique is particularly appropriate for 3-piece IOLs with flexible haptics.

Among all contaminants of emerging interest, drugs are the ones that give rise to the greatest concern. Any of the multiple stages of the drug's life cycle (production, consumption and waste management) is a possible entry point to the different environmental matrices. Psychiatric drugs have received special attention because of two reasons. First, their use is increasing. Second, many of them act on phylogenetically highly conserved neuroendocrine systems, so they have the potential to affect many non-target organisms. Currently, wastewater is considered the most important source of drugs to the environment. Furthermore, the currently available wastewater treatment plants are not specifically prepared to remove drugs, so they reach practically all environmental matrices, even tap water. As drugs are designed to produce pharmacological effects at low concentrations, they are capable of producing ecotoxicological effects on microorganisms, flora and fauna, even on human health. It has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food chain. Drug pollution is a complicated and diffuse problem characterized by scientific uncertainties, a large number of stakeholders with different values and interests, and enormous complexity. Possible solutions consist on acting at source, using medicines more rationally, eco-prescribing or prescribing greener drugs, designing pharmaceuticals that are more readily biodegraded, educating both health professionals and citizens, and improving coordination and collaboration between environmental and healthcare sciences. Besides, end of pipe measures like improving or developing new purification systems (biological, physical, chemical, combination) that eliminate these residues efficiently and at a sustainable cost should be a priority. Here, we describe and discuss the main aspects of drug pollution, highlighting the specific issues of psychiatric drugs.

BACKGROUND: Reducing health inequalities on the basis of social factors has been a key driver in the development of Public Health policies. Health-related quality of life is a global indicator useful to assess health inequalities within a society. The objective of this study was to identify inequalities on health by analysing the interactive effects of gender, age, educational level, social class, body mass index and chronic diseases on health-related quality of life in a Spanish population sample. METHODS: We used data from the Spanish National Health Survey 2011-2012. Health-related quality of life was measured by the EQ-5D-5L instrument applying the Spanish value set. Probability of being in perfect health was ascertained by logistic regression models including gender, age, educational level, body mass index and social class and the corresponding terms of interaction. A two-part model combining logistic regression analysis and generalized linear models was applied to calculate the adjusted utility loss associated with chronic conditions (disutility values). RESULTS: The sample used for analysis contained 18,450 individuals. The mean age was 50 years, 51.3% were women, 55% were overweight or obese and 46.7% had low social status. The mean utility was 0.94 in men and 0.89 in women. Elderly women, obese people, those of low social class and those with chronic conditions had significant lower utility values. Within the regression analysis, interaction assessment revealed that the detrimental effect of obesity disappeared in higher social classes. Utility values for all chronic conditions considered were lower in women than in men and were on a gradient within social class, the lowest for individuals declaring stroke. The greatest decrease on health-related quality of life was determined by declaration of stroke (17.6%) or mental diseases (18.6%). CONCLUSIONS: The interactive effects of gender, age, educational level, social class, body mass index and chronic diseases on health-related quality of life in the Spanish population revealed important inequalities in health. Social class acted as a modulator of the stigma associated with obesity. Chronic conditions producing loss of autonomy had the greatest impact on reduction of health-related quality of life. This is the first study using the Spanish EQ-5D-5L value set to estimate utilities.

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

BACKGROUND: The use of cerebrospinal fluid (CSF) biomarkers could facilitate early detection of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) and the differential diagnosis between AD and non-AD dementias. OBJECTIVE: To determine the cost-effectiveness of the use of amyloid-β peptide (Aβ42), total tau and phosphorylated tau proteins in CSF to diagnose AD in MCI and dementia patients. METHODS: An economic evaluation was performed by means of cost-effectiveness analysis comparing two AD diagnostic alternatives: the combined determination of Aβ42 proteins, total tau and phosphorylated tau in CSF as biomarkers of AD, and the standard clinical diagnosis based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria. A decision analytic model was developed to synthesize the identified evidence and to compare the costs and effectiveness associated with each diagnostic strategy. A probabilistic sensitivity analysis using 2nd order Monte Carlo simulations was performed. Subsequently, acceptability curves were calculated and ANCOVA models were applied to the results of the Monte Carlo simulations in order to identify the parameters that led greater variability in the model outcomes. RESULTS: The use of CSF biomarkers as an early diagnostic strategy of AD in MCI patients is a dominant alternative (less costly and more effective strategy than standard clinical diagnostic criteria). In dementia patients, although there is a higher uncertainty, biomarkers in CSF seem a more cost-effective alternative than standard clinical diagnostic criteria. CONCLUSIONS: Detecting AD in MCI patients by determining Aβ42, total tau and phosphorylated tau proteins biomarkers in CSF is a cost-effective diagnostic alternative. No conclusive results were obtained on dementia patients.

BACKGROUND: A new scenario of therapy for chronic hepatitis C (CHC) is being established with the approval of sofosbuvir (SOF). OBJECTIVE: To estimate the cost-effectiveness of SOF-based regimens approved in the Summary of Product Characteristics (SmPC) versus the standard of care for different genotypes and patient populations (naive or pretreated). METHODS: A Markov model simulating CHC progression was used to estimate disease treatment costs and effects over patients' lifetimes, from the Spanish National Public Healthcare System perspective. Different therapeutic options were analysed for genotypes 1, 2 and 3 in naive population and for genotype 2 and 3 pretreated patients, according to data obtained from clinical trials. A one-way sensitivity analysis was performed to evaluate the uncertainty of certain parameters: treatment starting age, transition probabilities, drug costs and discount rate. A probabilistic sensitivity analysis was also carried out. RESULTS: For the naive population, the option SOF+pegylated-interferon-α (pIFN)+ribavirin (RBV) for 12 weeks recorded in SmPC for genotype 1 and 3 versus pIFN+RBV for 24 weeks estimated an incremental cost-effectiveness ratio (ICER) below the €40,000/quality-adjusted life-year (QALY) benchmark. For the pretreated population, SOF triple therapy reached an ICER on the threshold limit for genotype 3. Other options included in SmPC for different genotypes exceeded the accepted efficiency limit in our setting. CONCLUSIONS: The options that included SOF+RBV+pIFN in a 12-week course regimen fell below the efficiency threshold considered in our setting. IFN-free regimens administered for 24 weeks reached figures over the benchmark of €40,000/QALY.