Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease

The occurrence of depression in patients with coronary heart disease (CHD) substantially increases the likelihood of a poorer cardiovascular prognosis. Although antidepressants are generally effective in decreasing depression, their use in patients with CHD is controversial. We carried out a meta-analysis to evaluate the health effects of selective serotonin reuptake inhibitors (SSRIs) versus placebo or no antidepressants in patients with CHD and depression. Observational studies and randomized controlled trials (RCTs) were searched in MEDLINE, EMBASE, PsycINFO, Cochrane Controlled Clinical Trial Register and other trial registries, and references of relevant articles. Primary outcomes were readmission for CHD (including myocardial infarction, unstable angina, and stroke) and all-cause mortality; the secondary outcome was severity of depression symptoms. Seven articles on 6 RCTs involving 2,461 participants were included. One study incorrectly randomized participants, and another was a reanalysis of RCT data. These were considered observational and analyzed separately. When only properly randomized trials were considered (n = 734 patients), patients on SSRIs showed no significant differences in mortality (risk ratio 0.39, 95% confidence interval 0.08 to 2.01) or CHD readmission rates (0.74, 0.44 to 1.23) compared to controls. Conversely, when all studies were included, SSRI use was associated with a significant decrease in CHD readmission (0.63, 0.46 to 0.86) and mortality rates (0.56, 0.35 to 0.88). A significantly greater improvement in depression symptoms was always apparent in patients on SSRIs with all selected indicators. In conclusion, in patients with CHD and depression, SSRI medication decreases depression symptoms and may improve CHD prognosis.

Guided tissue regeneration/deproteinized bovine bone mineral or papilla preservation flaps alone for treatment of intrabony defects. II: radiographic predictors and outcomes

OBJECTIVES: This study reports the secondary analysis of a randomized-controlled clinical trial designed to assess the efficacy of deproteinized bovine mineral and a collagen membrane in the treatment of intrabony defects. The specific aims of this report are (1) to analyse the radiographic bone changes 1 year after therapy and (2) to assess the association between radiographic defect angle and treatment outcomes. MATERIALS AND METHODS: Baseline and 12-month radiographs were collected from 120 patients with advanced chronic periodontitis from 10 centres in seven countries as part of a multi-centre clinical trial. All patients had at least one intrabony defect > or =3 mm in depth. The treatment consisted of simplified or modified papilla preservation flaps to access the defect. After debridement of the area, a deproteinized bovine mineral and a collagen membrane were applied in the test subjects, and omitted in the controls. Main outcome measures were radiographic bone fill and defect resolution 1 year after surgery. RESULTS: One hundred and twenty pairs of radiographs were obtained, of which 110 pairs were measurable (57 tests and 53 controls). One year after treatment, radiographic resolution of the intrabony component was significantly higher in the test group (3.2+/-1.7 mm) when compared with the controls (1.7+/-1.9 mm). Multivariate analysis indicated that the treatment and the baseline radiographic depth of the intrabony defect significantly influenced the radiographic bone fill of the intrabony defect 1 year following treatment. The percentage of resolution of the defect was influenced by the treatment provided and the baseline plaque score. The baseline radiographic defect angle did not show a significant impact on the clinical and radiographic outcomes. CONCLUSIONS: Regenerative periodontal surgery with a deproteinized bovine bone mineral and a collagen membrane offered additional benefits in terms of radiographic resolution of the intrabony defect and predictability of outcomes with respect to papilla preservation flaps alone.

Effects of adjunct electroacupuncture on severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease

OBJECTIVE: To compare severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease treated with a combination of conventional analgesics and electroacupuncture (EAP) or with conventional analgesics alone. DESIGN: Controlled clinical trial. ANIMALS: 15 dogs undergoing surgery because of acute thoracolumbar disk disease. PROCEDURES: Dogs were alternately assigned to treatment (conventional analgesics and adjunct EAP) and control (conventional analgesics alone) groups. Analgesic treatment was adjusted as necessary by the attending clinician, who was not aware of group assignment. Pain scores were assigned 1, 3, and 12 hours after surgery and every 12 hours thereafter for 72 hours by the same individual who performed acupuncture treatments. RESULTS: Total dose of fentanyl administered during the first 12 hours after surgery was significantly lower in the treatment group than in the control group, but dosages of analgesics administered from 12 through 72 hours after surgery did not differ between groups. Pain score was significantly lower in the treatment group than in the control group 36 hours after surgery, but did not differ significantly between groups at any other time. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided equivocal evidence that adjunct EAP might provide some mild benefit in regard to severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease.

Curing lights for orthodontic bonding: a systematic review and meta-analysis

INTRODUCTION Light cure of resin-based adhesives is the mainstay of orthodontic bonding. In recent years, alternatives to conventional halogen lights offering reduced curing time and the potential for lower attachment failure rates have emerged. The relative merits of curing lights in current use, including halogen-based lamps, light-emitting diodes (LEDs), and plasma arc lights, have not been analyzed systematically. In this study, we reviewed randomized controlled trials and controlled clinical trials to assess the risks of attachment failure and bonding time in orthodontic patients in whom brackets were cured with halogen lights, LEDs, or plasma arc systems. METHODS Multiple electronic database searches were undertaken, including MEDLINE, EMBASE, and the Cochrane Oral Health Group's Trials Register, CENTRAL. Language restrictions were not applied. Unpublished literature was searched on ClinicalTrials.gov, the National Research Register, Pro-Quest Dissertation Abstracts, and Thesis database. Search terms included randomized controlled trial, controlled clinical trial, random allocation, double blind method, single blind method, orthodontics, LED, halogen, bond, and bracket. Authors of primary studies were contacted as required, and reference lists of the included studies were screened. RESULTS Randomized controlled trials and clinical controlled trials directly comparing conventional halogen lights, LEDs, or plasma arc systems involving patients with full arch, fixed, or bonded orthodontic appliances (not banded) with follow-up periods of a minimum of 6 months were included. Using predefined forms, 2 authors undertook independent extraction of articles; disagreements were resolved by discussion. The assessment of the risk of bias of the randomized controlled trials was based on the Cochrane Risk of Bias tool. Ten studies met the inclusion criteria; 2 were excluded because of high risk of bias. In the comparison of bond failure risk with halogen lights and plasma arc lights, 1851 brackets were included in both groups. Little statistical heterogeneity was observed in this analysis (I(2) = 4.8%; P = 0.379). There was no statistical difference in bond failure risk between the groups (OR, 0.92; 95% CI, 0.68-1.23; prediction intervals, 0.54, 1.56). Similarly, no statistical difference in bond failure risk was observed in the meta-analysis comparing halogen lights and LEDs (OR, 0.96; 95% CI, 0.64-1.44; prediction intervals, 0.07, 13.32). The pooled estimates from both comparisons were OR, 0.93; 95% CI, 0.74-1.17; and prediction intervals, 0.69, 1.17. CONCLUSIONS There is no evidence to support the use of 1 light cure type over another based on risk of attachment failure.

The effectiveness of laceback ligatures during initial orthodontic alignment: a systematic review and meta-analysis

Lacebacks may be used to limit unwanted incisor proclination during initial orthodontic alignment; however, their use has not met with universal approval. This systematic review aims to appraise the evidence in relation to the effectiveness of lacebacks in controlling incisor position during initial alignment. Electronic database searches of published literature (MEDLINE via Ovid, Cochrane Central Register of Controlled Trials, LILACS, and IBECS) and unpublished literature were performed. Search terms used included randomized controlled trial, controlled clinical trial, random allocation, double blind method, orthodontics, and laceback. Data were extracted using custom forms. Risk of bias assessment was made using the Cochrane Collaboration risk of bias tool. The quality of the evidence was also assessed using GRADE. Mean differences in incisor inclination and antero-posterior changes in incisor and molar position during alignment were calculated. Two studies involving 97 participants were found to be at low risk of bias and were included in the quantitative synthesis. The random effects meta-analysis demonstrated that the use of lacebacks was associated with 0.5 mm greater posterior movement of the incisors during alignment; this finding was of limited clinical importance and statistically non-significant [95 per cent confidence interval (CI): -1.25, 0.25, P = 0.19]. Little difference (0.46 mm) was also found between laceback and non-laceback groups with regards to mesial molar movement (95 per cent CI: -0.33, 1.24, P = 0.26). According to the GRADE assessment, the overall quality of evidence relating to the use of lacebacks was high. There is no evidence to support the use of lacebacks for the control of the sagittal position of the incisors during initial orthodontic alignment.

Oral prophylaxis and its effects on halitosis-associated and inflammatory parameters in patients with chronic periodontitis

OBJECTIVE A controlled clinical trial was conducted to evaluate the effects of oral prophylaxis on halitosis-associated, immunological and microbiological parameters. METHODS Thirty subjects were included in this controlled clinical trial (patients with generalized chronic periodontitis and controls without clinical attachment loss; each n = 15). Before oral prophylaxis and 14 days after (including tongue cleaning) volatile sulphur compounds (VSC), organoleptic scores and a tongue coating index were evaluated. The levels of IL-1β, IL-8, IL-10 and MMP-8 were measured in GCF, and also major periodontal pathogens were detected. Data were statistically analysed using anova and paired t-test. RESULTS Supragingival plaque and calculus removal with combined tongue cleaning was able to reduce significantly (P < 0.05) the VSC values in both groups (no significant differences between both groups). Two weeks after periodontal debridement, the VSC values were observed in the periodontitis group, but not in the control group, similar to the baseline values. The difference between the groups was statistically significant (P < 0.05). Only a repeated prophylaxis session in the periodontitis group was able to reduce VSC values significantly in comparison with baseline (P < 0.05). Organoleptic scores (10 and 30 cm) were significantly different (P < 0.05) between both groups before and after the treatment. Periodontal pathogens and host-derived markers were not significantly affected by a single prophylaxis session. CONCLUSIONS Oral prophylaxis may result in a significant decrease in VSC values. However, in periodontal diseases, a more complex treatment seems to be necessary.

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis

BACKGROUND For patients with acute iliofemoral deep vein thrombosis, it remains unclear whether the addition of intravascular high-frequency, low-power ultrasound energy facilitates the resolution of thrombosis during catheter-directed thrombolysis. METHODS AND RESULTS In a controlled clinical trial, 48 patients (mean age 50±21 years, 52% women) with acute iliofemoral deep vein thrombosis were randomized to receive ultrasound-assisted catheter-directed thrombolysis (N=24) or conventional catheter-directed thrombolysis (N=24). Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients. The primary efficacy end point was the percentage of thrombus load reduction from baseline to 15 hours according to the length-adjusted thrombus score, obtained from standardized venograms and evaluated by a core laboratory blinded to group assignment. The percentage of thrombus load reduction was 55%±27% in the ultrasound-assisted catheter-directed thrombolysis group and 54%±27% in the conventional catheter-directed thrombolysis group (P=0.91). Adjunctive angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%) patients, respectively (P>0.99). Treatment-related complications occurred in 3 (12%) and 2 (8%) patients, respectively (P>0.99). At 3-month follow-up, primary venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis group and 96% in the conventional catheter-directed thrombolysis group (P=0.33), and there was no difference in the severity of the post-thrombotic syndrome (mean Villalta score: 3.0±3.9 [range 0-15] versus 1.9±1.9 [range 0-7]; P=0.21), respectively. CONCLUSIONS In this randomized controlled clinical trial of patients with acute iliofemoral deep vein thrombosis treated with a fixed-dose catheter thrombolysis regimen, the addition of intravascular ultrasound did not facilitate thrombus resolution. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01482273.

Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease

OBJECTIVE This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. METHODS AND RESULTS Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. CONCLUSION Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.

How do Swiss family physicians treat subclinical hypothyroidism?

Subclinical hypothyroidism is a common condition, and its prevalence increases with age. Currently, guidelines regarding the screening and treatment of subclinical hypothyroidism are controversial. An international survey of general practitioners (GPs), to which Swiss GPs also contributed, showed large inter-country variations in treatment strategies for subclinical hypothyroidism. These differences are mainly explained by the lack of strong evidence for the management of this condition. The European randomized-controlled clinical trial TRUST should help clarify recommendations for screening and thyroxin replacement for the elderly with subclinical hypothyroidism. Working in close collaboration with GPs in Switzerland for the recruitment of patients will ensure that the findings from this study will be applicable to primary care settings.

Oral Health Education Program on Dental Caries Incidence for School Children.

OBJECTIVE This 3-year retrospective controlled clinical trial assessed the effect of a school-based oral health education program on caries incidence in children. STUDY DESIGN A total of 240 students, aged 5 to 7 years, from two public schools in Monte Sião, Brazil, were included in this study. A school-based oral health education program was developed in one of the schools (experimental group), including 120 students, while the 120 students from the other school did not participate in the program (control group). All children were initially examined for dental caries (dmf-t), and after 3 years, 98 children from the experimental group and 96 from the control group were again examined and answered a questionnaire on oral health issues. The between-groups difference in caries incidence on permanent teeth was calculated using Poisson regression analyses. Logistic regression was used to observe the association between caries incidence and other variables. RESULTS More students from the experimental group stated knowing what was dental caries and declared that they use dental floss daily, but no significant differences in caries incidence was observed between the experimental and control groups. CONCLUSION The school-based oral health education program is not adequately efficient to decrease caries incidence after three years, but some issues about oral health knowledge could be slightly improved.

Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.

Blood loss and bleeding complications may often be observed in critically ill patients on renal replacement therapies (RRT). Here we investigate procedural (i.e. RRT-related) and non-procedural blood loss as well as transfusion requirements in regard to the chosen mode of dialysis (i.e. intermittent haemodialysis [IHD] versus continuous veno-venous haemofiltration [CVVH]). Two hundred and fifty-two patients (122 CVVH, 159 male; aged 61.5±13.9 years) with dialysis-dependent acute renal failure were analysed in a sub-analysis of the prospective randomised controlled clinical trial-CONVINT-comparing IHD and CVVH. Bleeding complications including severity of bleeding and RRT-related blood loss were assessed. We observed that 3.6% of patients died related to severe bleeding episodes (between group P=0.94). Major all-cause bleeding complications were observed in 23% IHD versus 26% of CVVH group patients (P=0.95). Under CVVH, the rate of RRT-related blood loss events (57.4% versus 30.4%, P=0.01) and mean total blood volume lost was increased (222.3±291.9 versus 112.5±222.7 ml per patient, P <0.001). Overall, transfusion rates did not differ between the study groups. In patients with sepsis, transfusion rates of all blood products were significantly higher when compared to cardiogenic shock (all P <0.01) or other conditions. In conclusion, procedural and non-procedural blood loss may often be observed in critically ill patients on RRT. In CVVH-treated patients, procedural blood loss was increased but overall transfusion rates remained unchanged. Our data show that IHD and CVVH may be regarded as equivalent approaches in critically ill patients with dialysis-dependent acute renal failure in this regard.

The impact of a brief foot care intervention for persons with diabetes

Purpose of the study. The purpose of this randomized controlled clinical trial was to determine if a brief intervention would improve foot self-care behaviors in adult patients with Type 2 diabetes who presented to the emergency department for non-emergent care in a predominantly Hispanic southwestern border community. ^ Methods. A pre-post-test, three-group design was used to compare the foot self-care behaviors of patients who received usual care to those who received lower extremity amputation (LEA) risk assessment and to those who received LEA risk assessment plus a brief foot self-care intervention. After being randomized into 3 groups (N = 167), baseline assessments of demographics, diabetes history, acculturation, and the Summary of Diabetes Self Care Activities (SDSCA) questionnaire and Modified Insulin Management Diabetes Self Efficacy Scale (MIMDSES) were completed in English or Spanish. At one-month, 144 (84%) participants were available for follow-up by the research assistant masked to group assignment. ^ Results. At baseline, significant differences in foot self-care behaviors and self monitoring blood glucose were noted based on ethnicity and gender. Men had significantly lower confidence in their ability to manage their diabetes overall. There was a significant difference between baseline and follow up self reported foot self-care behaviors within the intervention group (t (47) = −4.32, p < .01) and the control group (t (46) = −2.06, p < .05). There were no significant differences between groups for self-reported foot self-care behaviors. There was a significant difference in observed foot self-care behaviors between groups (F(2,135) = 2.99, p < .05). Self-efficacy scores were positively correlated with self-reported self-care behaviors. ^ Conclusions. This predominantly Hispanic population with type 2 diabetes reported performing diabetes self-care behaviors less than five days a week. There were within group changes, but no significant between group changes in reported self-care behaviors. However, at the one month follow up, there were significant differences between groups in observed foot self-care behaviors with the intervention group demonstrating the most accurate behaviors. Differences based on gender and ethnicity emphasize the need to individualize diabetes education. Priorities for culturally competent diabetes education, approaches to increasing self-efficacy and future research directions are suggested. ^

A model to develop a platform for personalised health applications

Antecedentes Europa vive una situación insostenible. Desde el 2008 se han reducido los recursos de los gobiernos a raíz de la crisis económica. El continente Europeo envejece con ritmo constante al punto que se prevé que en 2050 habrá sólo dos trabajadores por jubilado [54]. A esta situación se le añade el aumento de la incidencia de las enfermedades crónicas, relacionadas con el envejecimiento, cuyo coste puede alcanzar el 7% del PIB de un país [51]. Es necesario un cambio de paradigma. Una nueva manera de cuidar de la salud de las personas: sustentable, eficaz y preventiva más que curativa. Algunos estudios abogan por el cuidado personalizado de la salud (pHealth). En este modelo las prácticas médicas son adaptadas e individualizadas al paciente, desde la detección de los factores de riesgo hasta la personalización de los tratamientos basada en la respuesta del individuo [81]. El cuidado personalizado de la salud está asociado a menudo al uso de las tecnologías de la información y comunicación (TICs) que, con su desarrollo exponencial, ofrecen oportunidades interesantes para la mejora de la salud. El cambio de paradigma hacia el pHealth está lentamente ocurriendo, tanto en el ámbito de la investigación como en la industria, pero todavía no de manera significativa. Existen todavía muchas barreras relacionadas a la economía, a la política y la cultura. También existen barreras puramente tecnológicas, como la falta de sistemas de información interoperables [199]. A pesar de que los aspectos de interoperabilidad están evolucionando, todavía hace falta un diseño de referencia especialmente direccionado a la implementación y el despliegue en gran escala de sistemas basados en pHealth. La presente Tesis representa un intento de organizar la disciplina de la aplicación de las TICs al cuidado personalizado de la salud en un modelo de referencia, que permita la creación de plataformas de desarrollo de software para simplificar tareas comunes de desarrollo en este dominio. Preguntas de investigación RQ1 >Es posible definir un modelo, basado en técnicas de ingeniería del software, que represente el dominio del cuidado personalizado de la salud de una forma abstracta y representativa? RQ2 >Es posible construir una plataforma de desarrollo basada en este modelo? RQ3 >Esta plataforma ayuda a los desarrolladores a crear sistemas pHealth complejos e integrados? Métodos Para la descripción del modelo se adoptó el estándar ISO/IEC/IEEE 42010por ser lo suficientemente general y abstracto para el amplio enfoque de esta tesis [25]. El modelo está definido en varias partes: un modelo conceptual, expresado a través de mapas conceptuales que representan las partes interesadas (stakeholders), los artefactos y la información compartida; y escenarios y casos de uso para la descripción de sus funcionalidades. El modelo fue desarrollado de acuerdo a la información obtenida del análisis de la literatura, incluyendo 7 informes industriales y científicos, 9 estándares, 10 artículos en conferencias, 37 artículos en revistas, 25 páginas web y 5 libros. Basándose en el modelo se definieron los requisitos para la creación de la plataforma de desarrollo, enriquecidos por otros requisitos recolectados a través de una encuesta realizada a 11 ingenieros con experiencia en la rama. Para el desarrollo de la plataforma, se adoptó la metodología de integración continua [74] que permitió ejecutar tests automáticos en un servidor y también desplegar aplicaciones en una página web. En cuanto a la metodología utilizada para la validación se adoptó un marco para la formulación de teorías en la ingeniería del software [181]. Esto requiere el desarrollo de modelos y proposiciones que han de ser validados dentro de un ámbito de investigación definido, y que sirvan para guiar al investigador en la búsqueda de la evidencia necesaria para justificarla. La validación del modelo fue desarrollada mediante una encuesta online en tres rondas con un número creciente de invitados. El cuestionario fue enviado a 134 contactos y distribuido en algunos canales públicos como listas de correo y redes sociales. El objetivo era evaluar la legibilidad del modelo, su nivel de cobertura del dominio y su potencial utilidad en el diseño de sistemas derivados. El cuestionario incluía preguntas cuantitativas de tipo Likert y campos para recolección de comentarios. La plataforma de desarrollo fue validada en dos etapas. En la primera etapa se utilizó la plataforma en un experimento a pequeña escala, que consistió en una sesión de entrenamiento de 12 horas en la que 4 desarrolladores tuvieron que desarrollar algunos casos de uso y reunirse en un grupo focal para discutir su uso. La segunda etapa se realizó durante los tests de un proyecto en gran escala llamado HeartCycle [160]. En este proyecto un equipo de diseñadores y programadores desarrollaron tres aplicaciones en el campo de las enfermedades cardio-vasculares. Una de estas aplicaciones fue testeada en un ensayo clínico con pacientes reales. Al analizar el proyecto, el equipo de desarrollo se reunió en un grupo focal para identificar las ventajas y desventajas de la plataforma y su utilidad. Resultados Por lo que concierne el modelo que describe el dominio del pHealth, la parte conceptual incluye una descripción de los roles principales y las preocupaciones de los participantes, un modelo de los artefactos TIC que se usan comúnmente y un modelo para representar los datos típicos que son necesarios formalizar e intercambiar entre sistemas basados en pHealth. El modelo funcional incluye un conjunto de 18 escenarios, repartidos en: punto de vista de la persona asistida, punto de vista del cuidador, punto de vista del desarrollador, punto de vista de los proveedores de tecnologías y punto de vista de las autoridades; y un conjunto de 52 casos de uso repartidos en 6 categorías: actividades de la persona asistida, reacciones del sistema, actividades del cuidador, \engagement" del usuario, actividades del desarrollador y actividades de despliegue. Como resultado del cuestionario de validación del modelo, un total de 65 personas revisó el modelo proporcionando su nivel de acuerdo con las dimensiones evaluadas y un total de 248 comentarios sobre cómo mejorar el modelo. Los conocimientos de los participantes variaban desde la ingeniería del software (70%) hasta las especialidades médicas (15%), con declarado interés en eHealth (24%), mHealth (16%), Ambient Assisted Living (21%), medicina personalizada (5%), sistemas basados en pHealth (15%), informática médica (10%) e ingeniería biomédica (8%) con una media de 7.25_4.99 años de experiencia en estas áreas. Los resultados de la encuesta muestran que los expertos contactados consideran el modelo fácil de leer (media de 1.89_0.79 siendo 1 el valor más favorable y 5 el peor), suficientemente abstracto (1.99_0.88) y formal (2.13_0.77), con una cobertura suficiente del dominio (2.26_0.95), útil para describir el dominio (2.02_0.7) y para generar sistemas más específicos (2_0.75). Los expertos también reportan un interés parcial en utilizar el modelo en su trabajo (2.48_0.91). Gracias a sus comentarios, el modelo fue mejorado y enriquecido con conceptos que faltaban, aunque no se pudo demonstrar su mejora en las dimensiones evaluadas, dada la composición diferente de personas en las tres rondas de evaluación. Desde el modelo, se generó una plataforma de desarrollo llamada \pHealth Patient Platform (pHPP)". La plataforma desarrollada incluye librerías, herramientas de programación y desarrollo, un tutorial y una aplicación de ejemplo. Se definieron cuatro módulos principales de la arquitectura: el Data Collection Engine, que permite abstraer las fuentes de datos como sensores o servicios externos, mapeando los datos a bases de datos u ontologías, y permitiendo interacción basada en eventos; el GUI Engine, que abstrae la interfaz de usuario en un modelo de interacción basado en mensajes; y el Rule Engine, que proporciona a los desarrolladores un medio simple para programar la lógica de la aplicación en forma de reglas \if-then". Después de que la plataforma pHPP fue utilizada durante 5 años en el proyecto HeartCycle, 5 desarrolladores fueron reunidos en un grupo de discusión para analizar y evaluar la plataforma. De estas evaluaciones se concluye que la plataforma fue diseñada para encajar las necesidades de los ingenieros que trabajan en la rama, permitiendo la separación de problemas entre las distintas especialidades, y simplificando algunas tareas de desarrollo como el manejo de datos y la interacción asíncrona. A pesar de ello, se encontraron algunos defectos a causa de la inmadurez de algunas tecnologías empleadas, y la ausencia de algunas herramientas específicas para el dominio como el procesado de datos o algunos protocolos de comunicación relacionados con la salud. Dentro del proyecto HeartCycle la plataforma fue utilizada para el desarrollo de la aplicación \Guided Exercise", un sistema TIC para la rehabilitación de pacientes que han sufrido un infarto del miocardio. El sistema fue testeado en un ensayo clínico randomizado en el cual a 55 pacientes se les dio el sistema para su uso por 21 semanas. De los resultados técnicos del ensayo se puede concluir que, a pesar de algunos errores menores prontamente corregidos durante el estudio, la plataforma es estable y fiable. Conclusiones La investigación llevada a cabo en esta Tesis y los resultados obtenidos proporcionan las respuestas a las tres preguntas de investigación que motivaron este trabajo: RQ1 Se ha desarrollado un modelo para representar el dominio de los sistemas personalizados de salud. La evaluación hecha por los expertos de la rama concluye que el modelo representa el dominio con precisión y con un balance apropiado entre abstracción y detalle. RQ2 Se ha desarrollado, con éxito, una plataforma de desarrollo basada en el modelo. RQ3 Se ha demostrado que la plataforma es capaz de ayudar a los desarrolladores en la creación de software pHealth complejos. Las ventajas de la plataforma han sido demostradas en el ámbito de un proyecto de gran escala, aunque el enfoque genérico adoptado indica que la plataforma podría ofrecer beneficios también en otros contextos. Los resultados de estas evaluaciones ofrecen indicios de que, ambos, el modelo y la plataforma serán buenos candidatos para poderse convertir en una referencia para futuros desarrollos de sistemas pHealth. ABSTRACT Background Europe is living in an unsustainable situation. The economic crisis has been reducing governments' economic resources since 2008 and threatening social and health systems, while the proportion of older people in the European population continues to increase so that it is foreseen that in 2050 there will be only two workers per retiree [54]. To this situation it should be added the rise, strongly related to age, of chronic diseases the burden of which has been estimated to be up to the 7% of a country's gross domestic product [51]. There is a need for a paradigm shift, the need for a new way of caring for people's health, shifting the focus from curing conditions that have arisen to a sustainable and effective approach with the emphasis on prevention. Some advocate the adoption of personalised health care (pHealth), a model where medical practices are tailored to the patient's unique life, from the detection of risk factors to the customization of treatments based on each individual's response [81]. Personalised health is often associated to the use of Information and Communications Technology (ICT), that, with its exponential development, offers interesting opportunities for improving healthcare. The shift towards pHealth is slowly taking place, both in research and in industry, but the change is not significant yet. Many barriers still exist related to economy, politics and culture, while others are purely technological, like the lack of interoperable information systems [199]. Though interoperability aspects are evolving, there is still the need of a reference design, especially tackling implementation and large scale deployment of pHealth systems. This thesis contributes to organizing the subject of ICT systems for personalised health into a reference model that allows for the creation of software development platforms to ease common development issues in the domain. Research questions RQ1 Is it possible to define a model, based on software engineering techniques, for representing the personalised health domain in an abstract and representative way? RQ2 Is it possible to build a development platform based on this model? RQ3 Does the development platform help developers create complex integrated pHealth systems? Methods As method for describing the model, the ISO/IEC/IEEE 42010 framework [25] is adopted for its generality and high level of abstraction. The model is specified in different parts: a conceptual model, which makes use of concept maps, for representing stakeholders, artefacts and shared information, and in scenarios and use cases for the representation of the functionalities of pHealth systems. The model was derived from literature analysis, including 7 industrial and scientific reports, 9 electronic standards, 10 conference proceedings papers, 37 journal papers, 25 websites and 5 books. Based on the reference model, requirements were drawn for building the development platform enriched with a set of requirements gathered in a survey run among 11 experienced engineers. For developing the platform, the continuous integration methodology [74] was adopted which allowed to perform automatic tests on a server and also to deploy packaged releases on a web site. As a validation methodology, a theory building framework for SW engineering was adopted from [181]. The framework, chosen as a guide to find evidence for justifying the research questions, imposed the creation of theories based on models and propositions to be validated within a scope. The validation of the model was conducted as an on-line survey in three validation rounds, encompassing a growing number of participants. The survey was submitted to 134 experts of the field and on some public channels like relevant mailing lists and social networks. Its objective was to assess the model's readability, its level of coverage of the domain and its potential usefulness in the design of actual, derived systems. The questionnaires included quantitative Likert scale questions and free text inputs for comments. The development platform was validated in two scopes. As a small-scale experiment, the platform was used in a 12 hours training session where 4 developers had to perform an exercise consisting in developing a set of typical pHealth use cases At the end of the session, a focus group was held to identify benefits and drawbacks of the platform. The second validation was held as a test-case study in a large scale research project called HeartCycle the aim of which was to develop a closed-loop disease management system for heart failure and coronary heart disease patients [160]. During this project three applications were developed by a team of programmers and designers. One of these applications was tested in a clinical trial with actual patients. At the end of the project, the team was interviewed in a focus group to assess the role the platform had within the project. Results For what regards the model that describes the pHealth domain, its conceptual part includes a description of the main roles and concerns of pHealth stakeholders, a model of the ICT artefacts that are commonly adopted and a model representing the typical data that need to be formalized among pHealth systems. The functional model includes a set of 18 scenarios, divided into assisted person's view, caregiver's view, developer's view, technology and services providers' view and authority's view, and a set of 52 Use Cases grouped in 6 categories: assisted person's activities, system reactions, caregiver's activities, user engagement, developer's activities and deployer's activities. For what concerns the validation of the model, a total of 65 people participated in the online survey providing their level of agreement in all the assessed dimensions and a total of 248 comments on how to improve and complete the model. Participants' background spanned from engineering and software development (70%) to medical specialities (15%), with declared interest in the fields of eHealth (24%), mHealth (16%), Ambient Assisted Living (21%), Personalized Medicine (5%), Personal Health Systems (15%), Medical Informatics (10%) and Biomedical Engineering (8%) with an average of 7.25_4.99 years of experience in these fields. From the analysis of the answers it is possible to observe that the contacted experts considered the model easily readable (average of 1.89_0.79 being 1 the most favourable scoring and 5 the worst), sufficiently abstract (1.99_0.88) and formal (2.13_0.77) for its purpose, with a sufficient coverage of the domain (2.26_0.95), useful for describing the domain (2.02_0.7) and for generating more specific systems (2_0.75) and they reported a partial interest in using the model in their job (2.48_0.91). Thanks to their comments, the model was improved and enriched with concepts that were missing at the beginning, nonetheless it was not possible to prove an improvement among the iterations, due to the diversity of the participants in the three rounds. From the model, a development platform for the pHealth domain was generated called pHealth Patient Platform (pHPP). The platform includes a set of libraries, programming and deployment tools, a tutorial and a sample application. The main four modules of the architecture are: the Data Collection Engine, which allows abstracting sources of information like sensors or external services, mapping data to databases and ontologies, and allowing event-based interaction and filtering, the GUI Engine, which abstracts the user interface in a message-like interaction model, the Workow Engine, which allows programming the application's user interaction ows with graphical workows, and the Rule Engine, which gives developers a simple means for programming the application's logic in the form of \if-then" rules. After the 5 years experience of HeartCycle, partially programmed with pHPP, 5 developers were joined in a focus group to discuss the advantages and drawbacks of the platform. The view that emerged from the training course and the focus group was that the platform is well-suited to the needs of the engineers working in the field, it allowed the separation of concerns among the different specialities and it simplified some common development tasks like data management and asynchronous interaction. Nevertheless, some deficiencies were pointed out in terms of a lack of maturity of some technological choices, and for the absence of some domain-specific tools, e.g. for data processing or for health-related communication protocols. Within HeartCycle, the platform was used to develop part of the Guided Exercise system, a composition of ICT tools for the physical rehabilitation of patients who suffered from myocardial infarction. The system developed using the platform was tested in a randomized controlled clinical trial, in which 55 patients used the system for 21 weeks. The technical results of this trial showed that the system was stable and reliable. Some minor bugs were detected, but these were promptly corrected using the platform. This shows that the platform, as well as facilitating the development task, can be successfully used to produce reliable software. Conclusions The research work carried out in developing this thesis provides responses to the three three research questions that were the motivation for the work. RQ1 A model was developed representing the domain of personalised health systems, and the assessment of experts in the field was that it represents the domain accurately, with an appropriate balance between abstraction and detail. RQ2 A development platform based on the model was successfully developed. RQ3 The platform has been shown to assist developers create complex pHealth software. This was demonstrated within the scope of one large-scale project, but the generic approach adopted provides indications that it would offer benefits more widely. The results of these evaluations provide indications that both the model and the platform are good candidates for being a reference for future pHealth developments.

Análise comparativa de enxertos de gordura em refinamentos de reconstrução mamária com e sem suplementação de células-tronco

INTRODUÇÃO: Os enxertos de gordura tem se mostrado como uma poderosa técnica cirúrgica em reconstrução mamaria secundária e os enxertos enriquecidos com células-tronco, além de suas ações parácrinas, vem apresentando resultados encorajadores no que tange a persistência volumétrica. OBJETIVO: Este estudo clínico teve como objetivo analisar comparativamente quantitativa e qualitativamente enxertos de gordura enriquecidos com células da fração vásculoestromal em reconstrução mamária secundária e a incidência de complicações. MÉTODO: Nós desenvolvemos um método que produz enxertos de gordura, na sala de cirurgia, em uma taxa de enriquecimento maior que os já publicados (2:1). Este estudo clínico prospectivo e controlado analisou qualitativa e quantitativamente enxertos de gordura com (GT - grupo tronco) e sem (GC - grupo controle) adição das células da fração vásculo-estromal fresca em reconstrução mamária secundária; através de volumetria mamária por RNM de mamas, imunofenotipagem e contagem celular. Também foram estudados os resultados estéticos, a satisfação das pacientes e as complicações. RESULTADOS: A persistência volumétrica no GT foi 78,9% e 51,4% no GC, entretanto não houve diferença estatisticamente significativa entre os grupos. CD90 foi o marcador mais expresso e que alcançou diferença significante e ao mesmo tempo apresentou correlação positiva entre a sua expressão e a persistência volumétrica (r=0.651, p=0.03). Necrose gordurosa ocorreu, isoladamente em 4 pacientes do GT submetidas à radioterapia e nenhuma paciente do GC apresentou este evento. Desta forma, pacientes do GC mostraram tendência de estar mais satisfeitas com o enxerto de gordura. Nos dois grupos, os resultados estéticos foram iguais e não foram observadas recidivas loco-regionais. CONCLUSÃO: Os resultados do enriquecimento em uma taxa maior que as já publicadas são encorajadores, apesar de a persistência volumétrica não ter alcançado diferença estatisticamente significante entre os grupos. Enxertos de gordura enriquecidos na proporção 2:1 podem não ser indicados para pacientes submetidas à radioterapia apesar de terem se mostrados seguros num tempo de seguimento de 3 anos

Investigação da eficácia da teleconsulta na programação do implante coclear

A demanda crescente de usuários de implante coclear (IC) e a distribuição irregular de profissionais especializados no país, tornam necessário o deslocamento de pacientes por longas distâncias para os atendimentos, com consequente aumento dos custos diretos e indiretos do tratamento. A teleconsulta pode ser vista como uma alternativa em potencial para o acesso desta população a estes serviços. O presente ensaio clínico, randomizado, controlado, avaliou a eficácia da teleconsulta síncrona na programação dos sistemas de IC em usuários acompanhados em um Programa de Implante Coclear credenciado pelo Sistema Único de Saúde. Participaram do estudo 79 indivíduos com idades entre nove e 68 anos (média de 21,6), 41 do sexo masculino e 38 do sexo feminino, usuários de IC por um período de 0,58 a 24,75 anos. Estes indivíduos foram divididos em dois grupos, de acordo com o modo de programação do IC: controle (n=40), que realizou o procedimento face a face e experimental (n=39) que realizou a teleconsulta síncrona. Treze fonoaudiólogos sem experiência na programação do dispositivo atuaram como facilitadores das teleconsultas. Os procedimentos de programação do IC englobaram a telemetria de impedância, definição dos níveis de estimulação elétrica, varredura e balanceamento dos eletrodos e ajuste fino da programação. Como medidas de avaliação de resultados foram utilizados o tempo dispendido na consulta, a audiometria em campo livre, o percentual de reconhecimento de sentenças no silêncio e no ruído, o limiar de reconhecimento de sentenças no silêncio e ruído (HINT-Brasil), a avaliação da satisfação com a consulta (escala MISS-21) e de aspectos pertinentes à teleconsulta. Os facilitadores responderam as questões abertas referentes à suas impressões dos atendimentos. Os dados foram analisados por meio de estatística inferencial (testes t de Student, Wilcoxon, Mann-Whitney e correlação de Spearman). Os resultados mostraram que após a programação do IC, em média, os participantes apresentaram limiares audiométricos abaixo de 30 dB NA. O reconhecimento da fala pós atendimento, respectivamente para os grupos experimental e controle, foram de 81,3% e 83,8% (silêncio) e 57,9% e 58,1% (ruído). No HINT-Brasil os resultados foram, respectivamente, para os grupos experimental e controle 61,4 dB NA e 61,8 dB NA (silêncio) e relação S/R de 9,5 dB NA e 10,4 dB NA (ruído). Os participantes estiveram satisfeitos com a consulta. Não houve diferença estatisticamente significativa entre os grupos em nenhuma das medidas de resultado. Todos os participantes relataram que teleconsulta pode ser vista como uma alternativa viável ao atendimento face a face e sua aplicação clínica facilitaria a rotina de pacientes usuários de IC. Os facilitadores destacaram a sua importância para o aprendizado e como ferramenta de formação continuada. A teleconsulta síncrona foi eficaz na programação dos sistemas de IC e amplamente aceita pelos usuários e profissionais.