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Background: We recently demonstrated that late functional improvement between 3-12 months post-stroke occurs in about one-fourth of patients with ischaemic stroke. It is unknown whether this improvement is associated with better long-term clinical or health-economic outcomes. Methods: In a prospective, population-based cohort of 1-year ischaemic stroke survivors (Oxford Vascular Study;2002-2014), we determined changes in functional status (modified Rankin Scale[mRS], Rivermead Mobility Index[RMI], Barthel Index[BI]) from 3-12 months post-stroke. We examined the association of late improvement (by ≥1 mRS grades, ≥1 RMI points, and/or ≥2 BI points) with 5-year mortality, institutionalization (Cox regressions), and health/social-care costs (generalized linear models), adjusted for age/sex/3-month disability/stroke subtype. Results: Among 1,288 1-year survivors, 1,135 had 3-month mRS>0, with 319(28.1%) demonstrating late improvement. 1-year survivors with late mRS improvement had lower 5-year mortality (aHR:0.68,95%CI 0.51-0.91,p=0.009), institutionalization (aHR:0.48,0.33-0.72,p<0.001), and costs (margin -$17,369,-25,271 to -9,469,p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (e.g. 5-year death/institutionalization aHR:0.59,0.44-0.79,p<0.001) and on examining late improvement per RMI and/or BI (e.g. 5-year death/institutionalization aHR:0.67,0.53-0.84,p=0.001). Conclusions: Late functional improvement post-stroke is associated with lower 5-year mortality, institutionalization, and costs. These findings should motivate patients and clinicians to maximize late recovery and encourage payers to consider access to rehabilitative services for at least 1-year post-stroke.
We define a Grothendieck ring of varieties with actions of finite groups and show that the orbifold Euler characteristic and the Euler characteristics of higher orders can be defined as homomorphisms from this ring to the ring of integers. We describe two natural λ-structures on the ring and the corresponding power structures over it and show that one of these power structures is effective. We define a Grothendieck ring of varieties with equivariant vector bundles and show that the generalized (‘motivic’) Euler characteristics of higher orders can be defined as homomorphisms from this ring to the Grothendieck ring of varieties extended by powers of the class of the complex affine line. We give an analogue of the Macdonald type formula for the generating series of the generalized higher-order Euler characteristics of wreath products.
The hypoglossal nerve stimulation (HNS) produces a tongue protrusion for the treatment of mod-severe obstructive sleep apnea (OSA). It is one of the emerging health technologies prioritized to assess its possible inclusion on the Spanish National Health System. The objective of this study is to evaluate the efficacy and safety of this system in the treatment of OSA.
An early assessment (horizon scanning) was performed. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies of OSA patients treated with HNS published until 01 March 2017 were reviewed. Outcomes considered were: AHI (Apnea Hypopnea Index) ODI (Oxygen Desaturation Index) ESS (Epworth sleepiness scale) and AE (adverse events).
Four devices of HNS were founded: Inspire™, HGNS®, Aura6000™, and Nixoah™. We found two randomized controlled trials (RCT). The Inspire™ RCT showed significant results on mean differences on AHI (−16.9, 95% CI −24.7 to −9.0); ODI (−15.1, 95% CI −22.7 to −7.5) and ESS (−4.5, 95% CI −7.5 to −1.4) in 46 patients, after one week of follow-up. The HGNS® RCT showed non-significant differences on AHI (device active 22.1 ± 5.2 vs control 29.7 ± 6.2), ODI (11.4 ± 4.1 vs 19.5 ± 5.2) and ESS (9.8 ± 1.0 vs 14.1 ± 2.5) in 21 patients at 6 months. A systematic review that included 6 cases series (3 with HGNS®, 2 with Inspire™ and 1 with Aura6000™) without device subgroup analysis and 7 cohorts studies (6 with Inspire™ and one with Aura6000™) showed significant differences comparing AHI, ODI and ESS results to before treatment values. Major AE reported from the studies varied from 4 to 4.5%. No study with Nixoah™ was found.
Inspire™ seems to be an effective option for OSA patients although the evidence is scarce and of low quality for all HNS devices. It would be necessary further well-designed studies.
Minimally invasive capsulorhexis is an incision in the anterior capsule in the peripheral zone for cataract extraction. It allows reduction of the size of the lesion, ensuring a better transparency of the visual axis, preserving the capsule almost intact and a layer of lenticular epithelial cells. The procedure could have a potential regenerative effect of the lens in a natural way. The objective of this study is to assess the efficacy and safety of minimally invasive capsulorhexis to promote lens regeneration in children's cataracts.
This technology was identified by the early Awareness and Alert System, “SINTESIS-new technologies” of Agencia de Evaluación de Tecnologías Sanitarias (AETS) Instituto de Salud Carlos III (ISCIII). An early assessment was conducted. The searched databases were: PubMed, Centre for Reviews and Dissemination (CRD), and Cochrane Library. Clinical studies using the procedure published in any language until 29 September 2017 were reviewed.
An open-label, randomized trial in pediatric cataract patients (age: 0–2 years) was retrieved. Twelve patients underwent minimally invasive capsulorhexis, while twenty-five patients received the standard treatment. Regarding efficacy, a transparent regenerated biconvex lens was found in 100 percent of eyes three months after surgery, but wasn't found in the control group. 100 percent of capsular openings healed within one month after surgery in the experimental group, but not in the control group. Both groups increased their visual acuity parameters without significant differences. Regarding safety, children receiving the standard technique had a higher incidence of corneal edema (eight percent in the intervention vs thirty percent in the control group), anterior chamber inflammation (seventeen percent vs seventy-four percent), additional laser capsulotomy (zero percent vs eighty-four percent) and increased visual axis opacification (four percent vs eighty-four percent).
Minimally invasive capsulorhexis in children's cataracts seems to be a promising new procedure. Preliminary efficacy results were good and safety profile was better than standard treatment. However, it would be necessary to continue further studies to confirm these results.
Ovarian cancer (OC) has the highest mortality rate of all gynecologic malignancies. Completeness of cytoreductive surgery is a key prognostic factor for survival. To differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is difficult and can lead to incomplete tumour removal. OTL38 is a folate analogue conjugated to a near-infrared fluorescent dye which has high specificity and affinity for folate receptor alpha (FRα) expressed in OC. OTL38 together with a specific imaging system can help the surgeon to visualize diseased tissue. The objective of this work is to know the effectiveness and safety of OTL38 in of OC surgery.
Early assessment of OTL38 identified through the early-awareness and alert-system, “SINTESIS-new technologies”, of AETS-ISCIII. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies using the OTL38 in cytoreductive surgery in OC published until September 2017 were reviewed.
Only one publication, supported by industry, was retrieved. The study assesses the pharmacokinetics and tolerability of OLT38 in 30 healthy people randomized into 4 groups with different doses and a control group. The study also analyses the percentage of cytoreduction in 12 OC patients. Infusion of 0.025, 0.05, and 0.1 mg/kg OTL38 doses was associated with mild adverse events which did not require intervention. The 0.2 mg/kg dose was associated to adverse events of moderate severity. In OC patients, 0.0125 mg/kg dose was considered the optimal dose with mild adverse events. OTL38 accumulated in FRα-positive tumours and metastases allowed the surgeon to resect an additional 29 percent of malignant lesions which were not detected using standard inspection and palpation methods.
The OTL38 is an emergent health technology, which could help in cytoreductive surgery for ovarian cancer. However, the evidence is scarce and it would be necessary to continue further studies.
Modern Spain has remained largely absent from the debates and narratives of global history. In sharp contrast to the early modern period, the case of Spain in the nineteenth century has been overwhelmingly studied from regional and national perspectives. Fortunately, valuable efforts to integrate this country into wider frames of analysis have emerged in the last decade. Building on these writings, this article will argue that connections and entanglements represent two valuable perspectives, which allow the insertion of the Spanish experience into contemporary narratives of global history. The article has two aims. First, it seeks to ‘decentre’ modern Spain, by moving beyond its territorial borders within the Iberian Peninsula, and by examining its global dimensions, through connections with territories, colonies, and nations on several continents. Second, it aims to reveal valuable insights for current debates on global history, which arise from a focus on a country that is usually considered to have been both marginal and peripheral.
Conventional gastric balloons for weight loss require endoscopy for placement and removal. The ELIPSETM is a new gastric balloon designed for weight loss that is swallowed and does not require endoscopy or anesthesia. The device is designed to remain in the stomach and be expelled after a predetermined time of 4 months. The objective of this work is to assess the efficacy and safety of the ELIPSETM procedureless gastric balloon for weight loss.
The ELIPSETM procedureless gastric balloon was identified by the early Awareness and Alert System, “SINTESIS-new technologies,” of The Instituto De Salud Carlos III (AETS-ISCIII). An early assessment of the technology was conducted. The searched databases were: MEDLINE (PubMed), Centre for Reviews and Dissemination, and the Cochrane Library. Clinical studies using the device published in any language until 10 January 2017 were reviewed.
A prospective, non-randomized, open label study supported by industry was retrieved. Thirty-four patients were enrolled. Six patients treated with an experimental device were excluded. Twenty-eight patients successfully swallowed the device. No endoscopy or anesthesia was required. All devices were excreted safely. Of the twenty-five patients finally studied, the mean percent total body weight loss was 10 percent (95 percent Confidence Interval, CI 7.3–12.7) and the mean waist circumference was reduced by 8.4cm (95 percent CI 5.7-11.8) at 4 months. Improvements were also seen in metabolic parameters (HbA1c, Low density lipoprotein, triglycerides and blood pressure). All aspects of quality of life measured by the Impact of Weight on Quality of Life (IWQoL) questionnaire demonstrated significant improvements. About safety, there were no serious adverse events or serious adverse device effects, however 64 percent of patients had vomiting, 54 percent experienced nausea, 25 percent had abdominal pain and 2 patients were excluded because of symptoms.
The ELIPSETM gastric balloon for weight loss seems to be an effective therapy with an acceptable safety profile. However it would be necessary to continue further studies to confirm these results, including comparative studies with current treatments.
Sleep problems are pervasive in people with schizophrenia, but there are no clinical guidelines for their treatment. The Better Sleep Trial (BEST) concluded that suitably adapted cognitive–behavioural therapy (CBT) is likely to be highly effective, although its cost-effectiveness is unknown.
To assess the potential cost-effectiveness of CBT for sleep disorders in patients with schizophrenia.
An economic evaluation of the BEST study with a 6-month time horizon was used to establish the cost-effectiveness of CBT plus usual care in terms of costs per quality-adjusted life year (QALY) gained. Uncertainty was displayed on cost-effectiveness planes and acceptability curves. Value of information analysis was performed to estimate the benefits of obtaining further evidence.
On average, the treatment led to a 0.035 QALY gain (95% CI −0.016 to 0.084), and £1524 (95% CI −10 529 to 4736) and £1227 (95% CI −10 395 to 5361) lower costs from National Health Service and societal perspectives, respectively. The estimated value of collecting more information about the effects of the CBT on costs and QALYs was approximately £87 million.
CBT for insomnia in people with schizophrenia is effective and potentially cost-effective. A larger trial is needed to provide clear evidence about its cost-effectiveness.
Patients with schizophrenia have multiple complex health needs, as well as very high rates of depression, suicidal ideation and poor physical health. The results of this study showed that treating pervasive sleep problems in this patient group with cognitive–behavioural therapy (CBT) is very likely to improve patient quality of life in the short term. Clinicians most commonly use hypnotic medication to treat sleeping disorders. This study indicates that CBT may be an effective and cost-effective intervention in this patient group. This alternative would also be aligned with patient preferences for psychological and behavioural-type therapy.
Early awareness and alert systems (EAAS) try to anticipate the impact of new technologies in the healthcare systems. Spain, which has a decentralized health system with public provision and universal health coverage, has been a pioneer in establishing EAAS activities. From 2006 a network of regional agencies coordinated EAAS activities. Taking into account the individual agencies scarce resources and in order to improve efficiency, this collaboration decided to distribute tasks when identifying and early assessment of new and emerging health technologies. The aim was to inform the common benefit package of the Spanish public health system.
Four out of eight Spanish Health Technology Assessment (HTA) agencies had EAAS in Spain (AETS-Carlos III Institute; AETSA-Andalusia; Avalia-t-Galicia; Osteba-Basque Country). Each agency has taken care of different sources for the identification of new and emerging non-drug health technologies: industry and innovator contacts, health expert networks, mass media and EAAS databases. Members of the network used the same filtration criteria to reach the final list. The system will run in parallel to a biannual identification process in major databases.
In 2016, the network identified and filtered sixty-three technologies: ten by mass media; five by health experts; thirty-five other EAAS and thirteen by direct contact with industry and innovators. Main represented specialties were: endocrinology (seven); gynecology and obstetrics (six); cardiology and cardiac surgery (five); emergency medicine (four); dermatology (three) and pneumology (three). Technologies were grouped by specialty in order to inform the different commissions that discuss inclusion in the Spanish Benefit Package. Specialty monographs will be published to inform stakeholders.
The approach is feasible, and increases the capacity of individual agencies to address the needs of the national and regional systems by improving their efficiency. There is a need to previously define the methods and the criteria that will be used for the identification and filtration.
Alzheimer's disease (AD) is the most common type of dementia. Plasmapheresis is a procedure consisting of removing the plasma, or specific elements which are considered to be involved in pathological processes. Plasmapheresis could reduce the A beta peptides load in the brain. The objective is to study the safety and efficacy of plasmapheresis for AD.
Systematic review, with all studies published before April 2016 reviewed. Selected studies included patients with AD treated with plasmapheresis. GRADE was used to assess quality. Efficacy outcomes include: (i) Cognitive, functional and behavior status, through Mini Mental State Examination, and Alzheimer Disease Assessment Scale-Cognitive test; (ii) Plasma and cerebrospinal fluid A beta levels; (iii) Brain-imaging and functional neuroimaging studies. Safety outcomes included side effects related to the treatment.
Two papers reporting results from three studies were selected: (i) pilot study (n = 10), (ii) its extended study (12 months more of follow-up) (n = 7), and (iii) clinical trial (n = 39). The quality of evidence was very low. About efficacy, the studies didn't report quantitative results and were inconclusive. The pilot study and its extended study reported (1): a tendency towards stabilization in cognitive status; the plasma levels of A beta peptides didn't show a clear pattern; and the brain-imaging assessment suggested a progressive volume increase in the hippocampus. The clinical trial reported in the experimental group vs control (2): a better score for the cognitive status; an increase of plasma A beta peptides; and did not find significant differences between groups for cerebrospinal fluid A beta peptides. The brain-imaging assessment showed a progressive loss of hippocampus volume in both groups. Regarding safety, the studies didn't report quantitative data. We didn't find economic evaluation studies.
The included studies had very high risk of bias and very low quality. We found no evidence on efficacy and safety of plasmapheresis treating AD. Plasmapheresis isn't a priority line in research of AD treatment.
Ischaemic heart disease is the leading cause of death worldwide. Magmaris™ is a new drug-eluting resorbable stent used for coronary reperfusion during a balloon angioplasty. Magmaris™ is composed of absorbable magnesium scaffold and its surface is coated with bioresorbable poly-L-lactide, which incorporates Sirolimus. Magmaris™ has theoretical advantages as the stent body disappears after vascular constrictive remodeling. It would provide the stability and elasticity of non-resorbable metal stents, but without long-term problems such as endothelial dysfunction, delay in endothelialization, risk of thrombosis and complications due to long-term antiplatelet medication. The objective of this work is to assess efficacy and safety of Magmaris ™ in patients with angina or silent ischaemia.
Early assessment of Magmaris™ identified through the Early-Awareness and Alert-System, “SINTESIS-new technologies”, of The Instituto De Salud Carlos III (AETS-ISCIII). The searched databases were: MEDLINE (PubMed), EMBASE, WOS, Clinical Trials and Cochrane Library. Clinical studies using Magmaris™ published in any language until December 2016 were reviewed.
One prospective, non-randomized, non-controlled, multicenter, clinical trial with two publications was retrieved. The first publication (123 patients) showed mainly imaging outcomes of angiography, intravascular ultrasound and tomography at 6 months of follow up. The second publication (118 patients) with data from 12 months of follow up also reported: Target lesion failure in four patients (3.4 percent; 95 percent Confidence Interval, CI:0.9–8.4); one target-vessel myocardial infarction (0.8 percent; one myocardial infarction (0.8 percent); two clinically driven target lesion revascularisation (1.7 percent) and two clinically driven target-vessel revascularisation (1.7 percent). No definite scaffold thrombosis was observed. No procedural complications were reported. This trial is expected to continue up to 36 months of follow up.
Clinical data show that Magmaris™ seems to be an effective and safe treatment in patients with angina or silent ischaemia undergoing balloon angioplasty. More research specially randomized controlled trials are necessary to confirm these results.
The Spanish National Network (REDETS) is a group of eight agencies, units and services, depending on National and Regional Governments that coordinate their work within a common methodological framework, guided by the principles of mutual recognition and cooperation. The necessity of considering a Quality Management System has been detected and, consequently, a common tool for all the members needs to be developed. We describe in this study the process to achieve that goal.
Based on both a review of previous literature and the proposal for a self-evaluating tool, a group of experts from each agency through consensus have developed a tool for self-evaluation in Health Technology Assessment (HTA) agencies. Through the structure described in the handbook of the Andalusian Agency for Healthcare Quality (ACSA), each standard should have a statement or proposal that needs to also include evidence or good practices, and the corresponding evaluation questions. In separate workgroups, the definition of these proposals, evidence and evaluation questions were developed. One face-to-face meeting and two meetings via teleconference were necessary to achieve a final document with all the quality standards.
From a proposed structure of sixty-six standards, the titles, definitions, statements and evidence as well as good practices and evaluation questions were established in workgroups with consensus among all of the members (1 - 3). The final version of the self-assessment tool was composed of sixty-eight standards, grouped in twelve quality criteria structured in four dimensions: I Responsibility, II Clients and Stakeholders, III Production Process, and IV Resources.
Quality management requires an evaluation tool and this version, based on a systematic review and consensus, is a useful and practical instrument for developing a handbook by each member of REDETS. An online version of the tool is in process of development.
The Union of the Iberian Crowns (1580–1640) promoted a wider cultural exchange between Portuguese and Spanish Asian settlements in Asia. This paper identifies the remarkable circulation of artisans and patrons and the development of new building techniques during this period, which allowed for a shared cultural dialogue that may be best described as forms of mestizage. So, it tries to address the mobility of patrons and architects, which helps explain the diffusion of techniques and models. The first case shows how cultural dialogue promoted new techniques from local traditions and materials, which were later used in neighbouring settlements. The second demonstrates the role these mixed solutions played in the creation of the image of a pure state, in the form of public palaces, a mestizo society, mainly in urban houses, and a local cultural resistance, keeping traditional housing forms in the native quarters. Thanks to this approach, the currently preserved built heritage can be seen not only as a European cultural transfer but also as the result of a fruitful global dialogue.
Aims were to assess the efficacy of metacognitive training (MCT) in people with a recent onset of psychosis in terms of symptoms as a primary outcome and metacognitive variables as a secondary outcome.
A multicenter, randomized, controlled clinical trial was performed. A total of 126 patients were randomized to an MCT or a psycho-educational intervention with cognitive-behavioral elements. The sample was composed of people with a recent onset of psychosis, recruited from nine public centers in Spain. The treatment consisted of eight weekly sessions for both groups. Patients were assessed at three time-points: baseline, post-treatment, and at 6 months follow-up. The evaluator was blinded to the condition of the patient. Symptoms were assessed with the PANSS and metacognition was assessed with a battery of questionnaires of cognitive biases and social cognition.
Both MCT and psycho-educational groups had improved symptoms post-treatment and at follow-up, with greater improvements in the MCT group. The MCT group was superior to the psycho-educational group on the Beck Cognitive Insight Scale (BCIS) total (p = 0.026) and self-certainty (p = 0.035) and dependence self-subscale of irrational beliefs, comparing baseline and post-treatment. Moreover, comparing baseline and follow-up, the MCT group was better than the psycho-educational group in self-reflectiveness on the BCIS (p = 0.047), total BCIS (p = 0.045), and intolerance to frustration (p = 0.014). Jumping to Conclusions (JTC) improved more in the MCT group than the psycho-educational group (p = 0.021). Regarding the comparison within each group, Theory of Mind (ToM), Personalizing Bias, and other subscales of irrational beliefs improved in the MCT group but not the psycho-educational group (p < 0.001–0.032).
MCT could be an effective psychological intervention for people with recent onset of psychosis in order to improve cognitive insight, JTC, and tolerance to frustration. It seems that MCT could be useful to improve symptoms, ToM, and personalizing bias.
Durante la última década se ha producido un número importante de estudios sobre la efectividad de las sanciones judiciales para reintegrar a delincuentes juveniles y los efectos de las prácticas correccionales en su reincidencia delictiva. El hallazgo común en la mayoría de aquellas investigaciones es que las medidas judiciales (generalmente denominadas medidas socioeducativas en el caso de menores infractores) aplicadas en ámbitos comunitarios son más efectivas que aquellas que se ejecutan en contextos de privación de la libertad. Aunque reconozcamos la importancia de favorecer el uso de sanciones judiciales en ámbitos comunitarios antes que el encarcelamiento -y por tanto estos hallazgos contribuyan a tal posición- estos estudios aparentemente no han tomado en cuenta los efectos de sesgo metodológico condicionados por la Administración de Justicia Criminal. En los ensayos aleatorios controlados, los sujetos son asignados al azar en los tratamientos a los que son sometidos. En la Justicia Criminal, existe un sesgo de selección atribuido al juez al momento de sancionar a un convicto con un tipo de sanción (de encarcelamiento o no), según el tipo de delito cometido o según las características de riesgo criminogénico de éste. Por tanto, concluir sobre la efectividad de una intervención sin tales controles metodológicos restringe la validez de sus resultados. Por otro lado, la efectividad de los programas de reintegración incorporados en las sanciones judiciales ha sido generalmente medida a través de las tasas de reincidencia de tales programas. Sin embargo, en la composición de la varianza de reincidencia explicada subyacen tanto los efectos atribuidos a los programas como a otras variables intervinientes que generalmente no son controladas dadas las limitaciones metodológicas de los diseños de investigación posibles de ejecutar en contextos judiciales. Tomando en cuenta los resultados de las revisiones sistemáticas y los meta-análisis desarrollados fundamentalmente por el Grupo Campbell, este artículo analiza el estado del arte reportado en la literatura internacional sobre la efectividad correccional y discute las discrepancias metodológicas de los estudios previos ante los nuevos hallazgos.