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Diabetes mellitus (DM) is a complex, chronic, multifactorial, and costly health problem representing 8% of total public health expenditures in Spain. The objective of this study was to analyse the prevalence and costs of Anxiety (AX) and Depression (DP) in the Spanish working population with DM. Data were obtained from the National Health Survey of Spain 2017. A multivariate analysis was conducted to predict the use of resources and absenteeism/presenteeism. Direct and indirect costs were calculated. The final population analysed contained 15,822 subjects (18-65 years old). DM prevalence was 4.8%, and AX-DP 10.6% (50.5% were men). Self-diagnosed health was rated as regular, poor or very poor in 89% of DM subjects with DP-AX. The average costs estimated were €24,643.41 for DM subjects with AX-DP and €20,059.53 for those with only DM. The total estimated 2017 economic impact of DM was 2.4% of Spanish gross domestic product (13% directly related to DP-AX). Indirect costs represented 72.7% of total DP-AX costs. Spanish society is paying a considerable price for the incidence of DP-AX levels with DM in the working population. This global challenge has important repercussions for individuals' quality of life, health systems, and countries' development and economic growth.

BackgroundQuadrivalent Inactivated Vaccine (QIV) is expected to replace Trivalent Inactivated Vaccine (TIV) over time. In Portugal, TIV is free of charge for risk groups, which include older adults. In its turn, QIV – which provides broader protection as it includes an additional lineage B strain – was introduced in Portugal in October 2018, but only from the influenza season 2019/20 was provided free of charge for the risk groups. This study evaluates the cost-effectiveness of switching from TIV to QIV from the National Health Service perspective in the Portuguese elderly mainland population (≥ 65 years old).MethodsA decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the Incremental Cost-Effectiveness Ratio (ICER). In addition, a one-Way Sensitivity Analysis was performed to evaluate the impact of model parameters on the ICER; Probabilistic Sensitivity Analysis was also carried out to analyze the robustness of the base case results.ResultsThe high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of 5,283,047 €, and the resulting ICER would be 26,403,007€/QALY, mainly above the usual willingness-to-pay threshold.ConclusionsFrom the National Health Service perspective, our findings reveal that QIV is not cost-effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost-effective.

Leukemia is a heterogeneous group of hemopoietic cancers, which accounts for 2.6% of new cases per year of total cancer incidence worldwide. Grapes and grape-derived products, such as grape juice, are naturally rich in polyphenols, bioactive compounds with antioxidant properties. Certain polyphenols have been proved to alter oxidative balance, both in inducing apoptosis in cancer cells and in preventing cancer development via controlling oxidative stress. To assess the therapeutic potential of grape polyphenols in the treatment of leukemia, a systematic review and meta-analysis of the reported data on leukemia was carried out. Following the PRISMA guide, a literature review of published papers on leukemia and polyphenols from the last 50 years was conducted, and 17 scientific articles published from 2002 to 2017 were included in the study. Resveratrol 50 μM had the highest growth inhibition effect (67%) followed by quercetin (30%). The results also point to a differential effect of polyphenols based on cell lineage; monocytes- and myelocytic-derived cell lines are the most susceptible, with a mean of 85% and 64% proliferation inhibition, respectively. Moreover, results show that growth inhibition cannot be associated with a molecular effect of polyphenols on the cell cycle arrest., The authors would like to thank Universidad Francisco de Vitoria for awarding Daniel J García Martínez the research training scholarship to obtain his PhD. They would like to express additional gratitude to the company Mostos Españoles S.A. for the financial support that has allowed the development of this research project through a collaboration agreement with Universidad Francisco de Vitoria.

Summary Background Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting. Methods We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822. Findings Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62–11·73; seven trials) and serum ferritin (mean difference 49·66 μg/L, 13·63–85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51–16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions. Interpretation Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment. Funding None.

Objective Endoscopist-directed propofol (EDP) sedation is becoming more popular, with a reported safety and efficacy similar to anesthesiologist-administered propofol (AAP). The aim of this study is to compare the efficiency of EDP and AAP in patients of low-intermediate anesthetic risk. Methods A prospective cost-effectiveness comparison study was conducted. The costs of the endoscopic procedures in the EDP and AAP group were calculated using the full cost methodology after breaking down the endoscopic activity into relative value units to allocate costs in an equitable way. To determine the effectiveness, adverse events related to endoscopic sedation and the number of incomplete procedures were registered for the EDP group and compared with those published by anesthesiologists for AAP. Results A total of 1165 and 18 919 endoscopic procedures were, respectively, included in the EDP and AAP groups. The average costs of EDP vs. AAP for gastroscopy, colonoscopy and endoscopic ultrasound were O 182.81 vs. O 332.93, O 297.07 vs. O 459.76, and O 319.92 vs. O 485.12, respectively. No significant differences were detected regarding the rate of overall adverse events (4.43 vs. 4.46%) or serious adverse events (0 vs. 0.17%); the rate of arterial hypotension was significantly lower in the EDP group: 0.34 vs. 1.78% [odds ratio (OR), 0.19; 95% confidence interval (CI), 0.08-0.46] and the desaturation rate was significantly lower in the AAP group: 3.26 vs. 1.29% (OR, 2.58; 95% CI, 1.85-3.60). No significant differences were found in terms of incomplete examinations (0.17 vs. 0.14%). Conclusion In patients with low-intermediate anesthetic risk referred for an endoscopic examination, EDP appears to be more efficient than AAP.

Objective To evaluate the cost-effectiveness of the inclusion of trigger point-dry needling (TrP-DN) into an exercise program for the management of subacromial pain syndrome. Methods Fifty patients with unilateral subacromial pain syndrome were randomized with concealed allocation to exercise alone or exercise plus TrP-DN. Both groups were asked to perform an exercise program targeting the rotator cuff musculature twice daily for five weeks. Patients allocated to the exercise plus TrP-DN group also received dry needling during the second and fourth sessions. Societal costs and health-related quality of life (estimated by EuroQol-5D-5L) over a one-year follow-up were used to generate incremental cost per quality-adjusted life-year (QALY) ratios for each intervention. Results Intention-to-treat analysis was possible for 48 (96%) of the participants. Those in the exercise group made more visits to medical doctors and received a greater number of other treatments (P

[Background]: The genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population., [Methods]: Genotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the “optimal” polygenic profile has been quantified using the genotype score (GS)., [Results]: Statistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213–4.760 (p = 0.002)) in the polymorphisms studied., [Conclusions]: Genotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity., The present study has been funded by the Spanish Higher Council of Sports (CSD), through the project “Study and validation of genetic polymorphisms that predict a better performance in endurance sports” (15/UPB10/08).

Background: Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury. Objectives: To assess the effects of indomethacin for adults with severe traumatic brain injury. Search methods: We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field. Selection criteria: Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery. Data collection and analysis: Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods. Main results: We identified no eligible studies for this review, either completed or ongoing. Authors' conclusions: We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review. Fil: Martín Saborido, Carlos. Universidad Nebrija; España Fil: López Alcalde, Jesús. No especifíca; Fil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Sánchez Martín, Carlos Enrique. No especifíca; Fil: Garcia Garcia, Elena. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; Argentina Fil: Escobar Aguilar, Gema. Universidad Nebrija; España Fil: Palermo, Maria Carolina. Universidad de Buenos Aires; Argentina Fil: Baccaro, Fernando G. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina

The authors would like to thank Carlos González Rodríguez for his support in the literature review., Objective: In this study we conducted an economic evaluation of a surveillance programme to prevent hip dislocation in children with cerebral palsy. Method: We developed a model that compared costs and health outcomes of children with cerebral palsy with and without a surveillance programme. Information from a number of sources was combined into a decision analytical model, primarily based on data from a comparative study with a 20-year follow-up. Effectiveness was measured using Quality-Adjusted Life Years (QALYs). The analysis took the perspective of the Spanish National Health Service. We undertook extensive sensitivity analyses including a probabilistic sensitivity analysis. Results: The surveillance programme led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of 12,282D . The results were robust to model assumptions. The probability that the programme was cost-effective was estimated to be over 80% at the threshold of 25.000D /QALY recommended in Spain. Conclusion: This study indicates that surveillance programmes to prevent hip dislocation in children with cerebral palsy are likely to be cost-effective., Objetivo: En este estudio se realiza una evaluación económica de un programa de vigilancia para prevenir la luxación de cadera en ninos ˜ y ninas ˜ con parálisis cerebral. Método: Se desarrolló un modelo que comparó los costes y los resultados en salud de ninos ˜ y ninas ˜ con parálisis cerebral incluidas y no incluidas en un programa de vigilancia. Se combinó la información proveniente de diversas fuentes en un modelo analítico de decisión, principalmente basado en datos de un estudio comparativo con 20 anos ˜ de seguimiento. La efectividad se midió empleando los anos ˜ de vida ajustados por calidad (AVAC). El análisis tomó la perspectiva del Sistema Nacional de Salud de Espana. ˜ Se realizó un extenso análisis de sensibilidad, incluyendo un análisis de sensibilidad probabilístico. Resultados: El programa de vigilancia estuvo asociado a más AVAC y mayores costes sanitarios, con un coste incremental por AVAC ganado estimado en 12.282 D . Los resultados fueron robustos a los supuestos del modelo. La probabilidad de que el programa fuera coste-efectivo se estimó en un valor por encima del 80% para el umbral de 25.000 D por AVAC recomendado en Espana. ˜ Conclusión: Este estudio indica que es probable que los programas de vigilancia para prevenir la luxación de cadera en ninos ˜ y ninas ˜ con parálisis cerebral sean coste-efectivos., Ministry of Health, Social Services and Equality in Spain

Postpartum hemorrhage is one of the main causes of maternal death. Oxytocin has traditionally been used to prevent postpartum hemorrhage. Aim: To compare oxytocin with carbetocin, a long-acting analog of oxytocin, for prevention of uterine hemorrhage after cesarean delivery. Materials & methods: Clinical data were retrieved from the 2012 Cochrane meta-analysis “Carbetocin for preventing postpartum hemorrhage” . A decision tree was constructed. The direct costs were those of medications from the Peruvian official price list (DIGEMID). Costs associated with additional oxytocic drugs, blood transfusions, postpartum hemorrhage kits and hysterectomy were obtained from Hospital Nacional Edgardo Rebagliati Martins. The perspective of the study was that of the payer. The time horizon for calculating quality-adjusted life years (QALYs) was 1 year (2015). Results: Patients who received carbetocin required fewer additional uterotonic agents, had fewer hemorrhages and received fewer blood transfusions. Therefore, the costs associated with these interventions were lower. The incremental cost–effectiveness ratio was S/. 49,918 per QALY gained, which is lower than the threshold we estimated for Peru. Conclusion: Carbetocin is more cost-effective than oxytocin for prevention of uterine hemorrhage after cesarean delivery.

Background: Late state colorectal cancer treatments have important side effects that should be avoided in patients where drug effectiveness is not adequate. PrediCTC is a new biomarkers blood test developed to determinate the chemotherapy response in unresectable metastatic colorectal cancer patients that could allow to obviate unnecessary treatments. Aim: To assess from the Spanish Societal Perspective the cost-utility of the test PrediCTC compared to the computed tomography in aim to evaluate chemotherapy treatment response in late stage colorectal cancer patients. Methods: Based on the results of Barbazán et al., a Markov model has been developed, in which the different lines and cycles that the colorectal patient can receive and how they can move between them according to the computed tomography or PrediCTC have been represented. The effectiveness has been expressed in quality adjusted life years (QALYs), avoiding adverse events. Results: Base case analysis shows savings in different types of costs for PrediCTC (per patient): €14.30 in those arise from adverse events, €22,345.73 in chemotherapy costs, €4849.61 in other direct costs, and €306.21 in indirect costs. Although computed tomography 12-week assessed patients gain 0.17 QALYs compared with PrediCTC. Conclusions: From the Spanish Societal Perspective, PrediCTC is not a cost-utility option but allows to identify earlier patients who are not benefiting from first-line chemotherapy avoiding unnecessary side effects and costs.

Resumen Introduccion y objetivos En la ultima decada, la telemedicina aplicada a la monitorizacion de marcapasos cardiacos ha experimentado un extraordinario crecimiento. Se desconoce si esta tecnologia tiene una eficiencia diferente de la convencional. El objetivo del estudio es realizar una revision sistematica analizando la evidencia disponible con respecto al consumo de recursos y los resultados en salud en ambas modalidades de seguimiento. Metodos La busqueda se realizo en 11 bases de datos y se incluyeron estudios publicados hasta noviembre de 2014. Los criterios de inclusion fueron: a) diseno experimental u observacional; b) estudios basados en evaluaciones economicas completas; c) pacientes con marcapasos, y d) telemonitorizacion comparada con la modalidad hospitalaria. Resultados Siete estudios cumplian los criterios de inclusion, con informacion sobre 2.852 pacientes con una media de edad de 81 anos; el bloqueo auriculoventricular era la principal indicacion. En la telemonitorizacion, los eventos cardiovasculares se detectan y tratan 2 meses antes, con lo que se reduce en un 34% el numero de hospitalizaciones, asi como las visitas rutinarias y de urgencias al hospital. No hubo diferencias intergrupales significativas en calidad de vida percibida o numero de eventos adversos. El coste de la telemonitorizacion es un 60% menor que el de la monitorizacion hospitalaria. Conclusiones En la telemonitorizacion de marcapasos, los eventos cardiovasculares se detectan antes y disminuyen las hospitalizaciones y el numero de visitas al hospital. Ademas, con la telemonitorizacion se reducen los costes asociados al seguimiento.

[ES] Objetivo: Evaluar la eficacia de las manipulaciones espinales en pacientes con «síndrome del latigazo cervical» (whiplash) (SLC). Diseño: Revisión sistemática. Fuentes de datos: Búsqueda sistemática desde enero de 2000 hasta mayo de 2006 en: CINAHL, The Cochrane Library, EMBASE, MEDLINE, Centre for Reviews and Dissemination Index Medicus, PEDro y libros de ponencias de congresos de fisioterapia desde 2000 hasta 2005. Selección de estudios: Criterios de inclusión: estudios de pacientes con SLC y tratamiento basado en manipulaciones espinales exclusivas o combinadas con otras técnicas. Los resultados debían expresarse en al menos uno de los siguientes términos: dolor, efecto general percibido o amplitud de movimientos. Extracción de datos: Los artículos fueron seleccionados por 2 revisores de forma independiente. El análisis de la calidad metodológica se realizó siguiendo las recomendaciones de la Agencia de Evaluación de Tecnologías Sanitarias. La escasez y variedad de los datos encontrados imposibilitaron su análisis estadístico. Resultados: De 290 documentos encontrados se analizaron 9: 7 eran revisiones y 2, estudios primarios. En general, ninguna de las revisiones mostraba pruebas de que las técnicas manipulativas fueran más efectivas que otros tratamientos. La exposición de los resultados era en muchos casos vaga y defectuosa. Conclusiones: No se han encontrado pruebas suficiente de que las manipulaciones espinales sean un tratamiento efectivo del SLC. Aunque parece que a corto plazo produce una mejoría del dolor, no se puede confirmar su evolución a largo plazo, ni sus ventajas clínicas o económicas frente a los tratamientos convencionales. [EN] To assess the efficacy of spinal manipulation treatments in patients with whiplash injuries. Systematic review. A systematic search was conducted between January 2000 and May 2006 in CINAHL, the Cochrane Library, EMBASE, MEDLINE, CRD (Center for Reviews and Dissemination), Spanish Index Medicus, and PEDro. Reports of Physiotherapy congresses between 2000 and 2005 were reviewed. studies of patients with whiplash injuries who were treated with spinal manipulations, either exclusively or combined with other therapies. Outcomes were expressed in at least one of the following: pain, global perceived effect or range of movement (ROM). Only 9 of the first screening (290) were analyzed. The studies were independently selected by 2 reviewers. Methodological quality was assessed on the basis of the recommendations of the Agency for Health Technology Evaluation. The lack of data and their heterogeneity made any statistical analysis impossible. Of the 9 studies analyzed, 7 were systematic reviews and 2 were primary studies. No review showed evidence of the efficacy of spinal manipulations versus other therapies. The results were often explained vaguely and inadequately. There is not enough evidence to suggest that spinal manipulation is an effective treatment for whiplash. Though in the short term it seems to improve pain, any long-term benefit or clinical or economic advantages versus conventional therapies could not be determined. Sí

Introduction and objectives Over the last decade, telemedicine applied to pacemaker monitoring has undergone extraordinary growth. It is not known if telemonitoring is more or less efficient than conventional monitoring. The aim of this study was to carry out a systematic review analyzing the available evidence on resource use and health outcomes in both follow-up modalities. Methods We searched 11 databases and included studies published up until November 2014. The inclusion criteria were: a) experimental or observational design; b) studies based on complete economic evaluations; c) patients with pacemakers, and d) telemonitoring compared with conventional hospital monitoring. Results Seven studies met the inclusion criteria, providing information on 2852 patients, with a mean age of 81 years. The main indication for device implantation was atrioventricular block. With telemonitoring, cardiovascular events were detected and treated 2 months earlier than with conventional monitoring, thus reducing length of hospital stay by 34% and reducing routine and emergency hospital visits as well. There were no significant intergroup differences in perceived quality of life or number of adverse events. The cost of telemonitoring was 60% lower than that of conventional hospital monitoring. Conclusions Compared with conventional monitoring, cardiovascular events were detected earlier and the number or hospitalizations and hospital visits was reduced with pacemaker telemonitoring. In addition, the costs associated with follow-up were lower with telemonitoring.

The aim of this economic evaluation was to estimate the cost-effectiveness of fluticasone propionate/formoterol (FP/FORM; Flutiform®) and compare it to those of fluticasone/salmeterol (FS) and budesonide/formoterol (BF) when used in the treatment of adult patients with moderate-to-severe asthma. A Markov model was developed with five asthma health states: successful control, suboptimal control, outpatient-managed exacerbation, inpatient-managed exacerbation, and death. The time horizon was set at 12 months. Transition probabilities and indirect resource utilization were derived from previous international and Spanish publications. Univariate and probabilistic sensitivity analyses (SAs) were applied. FP/FORM was less expensive to acquire than FS or BF (20% lower than FS and 30% lower than BF), while the quality-adjusted life years (QALYs) of the three options compared were very similar. Cost per patient in the FP/FORM cohort was 9326€/year, making it the cheapest option, 1.5% cheaper than FS and 2.6% cheaper than BF. The suboptimal control health state dominated the costs (80% of the total cost) in each of the analyzed options and scenarios. The results of the SAs verified the data obtained from the base case scenario. From a Spanish societal perspective, in 2014, FP/FORM produced a similar gain in QALYs but at a lower cost when compared to FS and BF in a highly meaningful number of replications and scenarios. FP/FORM can therefore be considered a cost-effective option in the treatment of moderate-to-severe asthma in Spain. The cost savings were mainly due to the significantly lower acquisition cost of FP/FORM than the other two options. Mundipharma Pharmaceuticals, S.L., Madrid, Spain.