Comparison of traveling-subject and ComBat harmonization methods for assessing structural brain characteristics.

Multisite magnetic resonance imaging (MRI) is increasingly used in clinical research and development. Measurement biases-caused by site differences in scanner/image-acquisition protocols-negatively influence the reliability and reproducibility of image-analysis methods. Harmonization can reduce bias and improve the reproducibility of multisite datasets. Herein, a traveling-subject (TS) dataset including 56 T1-weighted MRI scans of 20 healthy participants in three different MRI procedures-20, 19, and 17 subjects in Procedures 1, 2, and 3, respectively-was considered to compare the reproducibility of TS-GLM, ComBat, and TS-ComBat harmonization methods. The minimum participant count required for harmonization was determined, and the Cohen's d between different MRI procedures was evaluated as a measurement-bias indicator. The measurement-bias reduction realized with different methods was evaluated by comparing test-retest scans for 20 healthy participants. Moreover, the minimum subject count for harmonization was determined by comparing test-retest datasets. The results revealed that TS-GLM and TS-ComBat reduced measurement bias by up to 85 and 81.3%, respectively. Meanwhile, ComBat showed a reduction of only 59.0%. At least 6 TSs were required to harmonize data obtained from different MRI scanners, complying with the imaging protocol predetermined for multisite investigations and operated with similar scan parameters. The results indicate that TS-based harmonization outperforms ComBat for measurement-bias reduction and is optimal for MRI data in well-prepared multisite investigations. One drawback is the small sample size used, potentially limiting the applicability of ComBat. Investigation on the number of subjects needed for a large-scale study is an interesting future problem.

The Marburg-Münster Affective Disorders Cohort Study (MACS): A quality assurance protocol for MR neuroimaging data.

Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses. We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data. We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.

Harmonization of cortical thickness measurements across scanners and sites.

With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such unwanted sources of variation, which we refer to as "scanner effects", can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements across a total of 11 scanners. We propose a set of tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.

Technical Note: A safe, cheap, and easy-to-use isotropic diffusion MRI phantom for clinical and multicenter studies.

PURPOSE: Since Diffusion Weighted Imaging (DWI) data acquisition and processing are not standardized, substantial differences in DWI derived measures such as Apparent Diffusion Coefficient (ADC) may arise which are related to the acquisition or MRI processing method, but not to the sample under study. Quality assurance using a standardized test object, or phantom, is a key factor in standardizing DWI across scanners. METHODS: Current diffusion phantoms are either complex to use, not available in larger quantities, contain substances unwanted in a clinical environment, or are expensive. A diffusion phantom based on a polyvinylpyrrolidone (PVP) solution, together with a phantom holder, is presented and compared to existing diffusion phantoms for use in clinical DWI scans. An ADC vs. temperature calibration curve was obtained. RESULTS: ADC of the phantom (808 to 857 ± 0.2 mm2 /s) is in the same range as ADC values found in brain tissue. ADC measurements are highly reproducible across time with an intra-class correlation coefficient of > 0.8. ADC as function of temperature (in Kelvin) can be estimated as ADCm(T)=[exp(-7.09)·exp-2903.81T-1293.55] with a total uncertainty (95% confidence limit) of ± 1.7%. CONCLUSION: We present an isotropic diffusion MRI phantom, together with its temperature calibration curve, that is easy-to-use in a clinical environment, cost-effective, reproducible to produce, and that contains no harmful substances.

Relación de la inteligencia emocional y la calidad de vida profesional con la consecución de objetivos laborales en el distrito de atención primaria Costa del Sol / Relationship between perceived emotional intelligence and professional quality of life with the achievement of occupational objectives in the costa del sol primary health care district

OBJETIVO: Explorar la relación existente entre «calidad de vida profesional» e «inteligencia emocional percibida», y la relación de ambas con el grado de consecución de objetivos laborales en el Distrito de Atención Primaria Costa del Sol. DISEÑO: Estudio observacional descriptivo transversal multicéntrico. Emplazamiento: Distrito Sanitario Costa del Sol en la Provincia de Málaga. PARTICIPANTES: Muestra de profesionales de todas las categorías, fijos y contratados, de las Unidades de Gestión del Distrito Costa del Sol (n = 303). Respondieron 247 (81,5%). MEDICIONES PRINCIPALES: Se recogieron los datos de porcentaje de consecución de objetivos del año 2010 y los datos sociodemográficos de los participantes; para ello se utilizaron cuestionarios autoadministrados diseñados ad hoc. Para medir la «inteligencia emocional percibida» y «calidad de vida profesional percibida», se utilizaron los cuestionarios TMMS-24 que mide las dimensiones: percepción, comprensión y regulación emocional y CVP-35 que mide las dimensiones: apoyo directivo, demanda de trabajo y motivación intrínseca. RESULTADOS: Se observaron correlaciones significativas entre calidad de vida profesional e inteligencia emocional en las categorías de regulación (p < 0,01) y comprensión (p < 0,05). También existían correlaciones significativas entre la profesión y tipo de contrato con la consecución de objetivos, (p < 0,005) y entre calidad de vida profesional y tipo de contrato (p < 0,05). CONCLUSIONES: La calidad de vida profesional percibida se relaciona con la percepción y la regulación como dimensiones de la inteligencia emocional. Desde los órganos de gestión se debe promover el conocimiento de métodos del manejo de las emociones en todos sus profesional

OBJECTIVE: To examine the relationship between "Quality of Professional Life" and "Perceived Emotional Intelligence" and the relationship of both of these with the level of achievement of occupational objectives in the Costa del Sol Primary Health Care District. DESIGN: Multicentre descriptive cross-sectional observational study. LOCATION: The Costa del Sol Primary Health Care District in the province of Málaga. PARTICIPANTS: Sample of Employees of all categories in fixed and contracted employment in the Management Units of the Costa del Sol District. (N = 303). Respondents 247 (81.5%). Principal Measurements: The data collected was that of the percentage of achievement of objectives in 2010 and the socio-demographic data of the participants, using ad hoc designed self-report questionnaires. The TMMS -24 questionnaire was used to measure the "Perceived Emotional Intelligence", with the following dimensions: Perception, comprehension, and emotional control, and the CVP-35 measuring: management support, work demands, and intrinsic motivation. RESULTS: Significant correlationas were observed between Quality of Professional Life and Emotional Intelligence in the Regulation (p< .01) and Comprehension categories (p < 0.05). There were also significant correlations between the profession and the type of contract in the achievement of objectives (p< .005), and quality of professional life and type of contract (p< .05). CONCLUSIONS: The perceived quality of professional life is related to perception and regulation dimensions of Emotional Intelligence. Knowledge of emotion management methods should be promoted by management organisations for all employees

Evolución de la sintomatología autista de los 2 a los 4 años: un estudio de seguimiento / Evolution of autistic symptoms from two to four years: a follow-up study / Evolució de la simptomatologiaautistadels dos als quatre anys: un estudi de seguiment

La detección e intervención temprana en el trastorno del espectro autista (TEA) es de gran relevancia para su pronóstico y su evolución. El principal objetivo de este estudio es analizar y detectar qué síntomas destacan como más significativos y cuáles son los que se mantienen en el tiempo. Se ha realizado un estudio longitudinal de tres años con una muestra clínica de 15 niños, de 24 a 47 meses de edad. Los síntomas han sido evaluados mediante los instrumentos ATA y ADI-R. Los resultados indican que las dimensiones detectadas en la escala ATA manipulación del ambiente, lenguaje y comunicación, hiper e hipoactividad, son las que presentan mayor estabilidad temporal. Las dimensiones restantes presentan menor estabilidad

Early detection and intervention in autism spectrum disorder (ASD) is of great importance for prognosis and evolution. The article aims to highlight the importance of detection and early intervention. Specifically in children with autism spectrum disorders (ASD), difficulty in detection involves a delay in the onset of therapeutic intervention, and therefore affects their prognosis and devolution. The aim of the study to analyze and detect the symptoms that stand out as especially significant and determine which are maintained over time. We performed a three-year longitudinal study with a clinical sample of 15 children, aged from 24 to 47 months. ATA-scales and ADI-R were used to evaluate symptoms. The results indicate that of the dimensions measured on the ATA scale, the manipulation of the environment, difficulties in language and communication and hyper and hypoactivity are those that display the greatest degree of stability over time. The other symptoms show lesser stability

La detecció i interven­ció primerenca en el trastorn de l’espectre autista (TEA) és de gran rellevància pel seu pronòstic i evolució. El principal objectiu d’aquest estudi és analitzar i detectar quins símptomes destaquen com a més significatius i quins són els que es mantenen en el temps. S’ha realitzat un estudi longitudinal de tres anys amb una mostra clínica de 15 nens, de 24 a 47 mesos d’edat. Els símptomes han estat avaluats mitjançant els instruments ATA i ADI-R. Els resultats indiquen que les dimensions detectades a l’escala ATA manipulació de l’ambient, llenguatge i comunicació, hiper i hipoactivitat són les que presenten més estabilitat temporal. La resta de dimensions presenten menys estabilitat

Estudio actitudes sobre vacunación antigripal en profesionales sanitarios de atención primaria de Cataluña / Primary health care professionals attitudes towards influenza immunzation in Catalonia

OBJETIVO: Los trabajadores sanitarios tienen riesgo de adquirir la gripe y actuar como vectores para la transmisión nosocomial. El objetivo del estudio fue la valoración de los conocimientos y actitudes de los profesionales sobre la vacunación antigripal, y determinar los factores asociados a ella por parte de profesionales de atención primaria en Cataluña. DISEÑO: Estudio transversal mediante una encuesta anónima vía web. Emplazamiento: Profesionales sanitarios de atención primaria del Instituto Catalán de la Salud. PARTICIPANTES: Se incluyó a 1.212 profesionales de atención primaria. Se excluyó a los profesionales con contraindicación para recibir la vacuna o indicación de vacunación por condición médica de riesgo y aquellos que hubieran participado en la red centinela de vigilancia de la gripe Pla d'Informació Diària d'Infeccions Respiratòries Agudes de Catalunya (PIDIRAC). RESULTADOS: Se consideraron 423 respuestas válidas, con una cobertura vacunal global del 46,6%. Se vacunaron más los que tenían de 45 a 54 años, los pediatras, los vacunados en las 3 temporadas anteriores o en alguna de ellas y los que convivían con enfermos crónicos. Se observó asociación entre estar vacunado y considerar que la vacunación es la mejor medida preventiva, preocupación por contraer la gripe y considerar importante la vacunación del personal sanitario. CONCLUSIONES: Las actividades dirigidas a aumentar la cobertura de vacunación en profesionales sanitarios deberían dirigirse fundamentalmente a corregir concepciones erróneas sobre la vacunación de la gripe en profesionales sanitarios

OBJECTIVE: Health personnel are at risk of acquiring influenza infection and of nosocomial influenza transmission. The objective of this study was to assess the relationship between the knowledge and attitudes of primary care health personnel in Catalonia as regards influenza vaccine and the factors related to the uptake of this vaccine. DESIGN: A cross-sectional study using a web survey. SETTING: Primary care health personnel of the Catalan Health Institute. PARTICIPANTS: A total of 1212 primary health care personnel were included in the survey. Those who had medical reasons for being or not being vaccinated were excluded. RESULTS: A total of 423 replies were valid, with a 46.6% overall vaccination coverage. Vaccination rate was higher among 45 to 54 year-olds, paediatricians, those vaccinated in preceding seasons, and those living with chronic patients. There was an association between having received the vaccine and considering vaccination the best preventive action, advocating vaccination to at risk population, concern about acquiring influenza, and considering health personnel vaccination important. CONCLUSIONS: Actions taken to increase vaccination rate among health personnel should aim at correcting lack of knowledge and misconceptions about influenza vaccination of health personnel

Bloqueos centrales en pediatría: una revisión de la literatura actual / Central blockades in pediatrics: a review of current literature

La anestesia neuroaxial pediátrica es una herramienta efectiva que puede ser usada como complemento o alternativa a la anestesia general. Sin embargo, siempre ha generado dudas en cuanto a su utilidad y relación riesgo-beneficio. El propósito de esta revisión es describir el papel actual de los bloqueos centrales en la población pediátrica, actualizar aspectos prácticos y de seguridad, así como repasar los últimos avances tecnológicos aplicados a este procedimiento (AU)

Pediatric neuraxial anesthesia is an effective tool that can be used as a supplement or alternative to general anesthesia. However, there have always been doubts about its usefulness and risk-benefit ratio. The purpose of this review is to describe the current role of central blockades in pediatric patients, upgrade practical and safety aspects, and review the latest technological advances applied to this procedure (AU)

Estudio de prevalencia de posible trastorno por déficit de atención e hiperactividad en niños preescolares / Prevalence study of possible attention deficit disorder and hyperactivity in preschool children / Estudi de prevalença de possible trastorn per dèficit d’atenció i hiperactivitat en nens preescolars

Nuestro objetivo es realizar un estudio piloto clínico-epidemiológico de trastorno por déficit de atención e hiperactividad (TDAH) en población preescolar. El método utilizado ha sido un estudio poblacional multicéntrico. Evaluamos 1.171 preescolares, el 4,1% de los cuales correspondían a un posible caso de TDAH. Los posibles factores asociados a una presencia de sospecha de TDAH han sido antecedentes familiares de TDAH, consumo de tabaco en el embarazo y antecedentes de dificultades en el desarrollo psicomotor. Es importante realizar una detección precoz del TDAH en la época preescolar para iniciar de forma temprana intervenciones efectivas

Our objective is to conduct a clinical-epidemiological pilot study of Attention deficit hyperactivity disorder (ADHD) in the preschool population. The method used was a multicenter demographic study. We evaluated 1,171 preschool children, 4.1 % of whom could be possible cases of ADHD. The possible factors associated with suspected ADHD were a family history of ADHD, smoking during pregnancy and psychomotor developmental difficulties. An early detection of ADHD at preschool age is important in order to start effective intervention

El nostre ob­jectiu és realitzar un estudi pilot clínic i epidemiològic de trastorn per dèficit d’atenció i hiperactivitat (TDAH) en la població escolar. El mètode emprat ha estat un estudi poblacional multicèntric. Vam avaluar 1.171 preescolars, el 4,1% dels quals corresponien a un possible cas de TDAH. Els possibles factors associats a una presència de sospita de TDAH han estat an­tecedents familiars de TDAH, consum de tabac en l’embaràs i antecedents de dificultats en el desenvolupament psicomotor. És important realitzar una detecció precoç del TDAH en l’època preescolar per iniciar de manera primerenca intervencions efectives

Managing personal health information in distributed research network environments.

BACKGROUND: Studying rare outcomes, new interventions and diverse populations often requires collaborations across multiple health research partners. However, transferring healthcare research data from one institution to another can increase the risk of data privacy and security breaches. METHODS: A working group of multi-site research programmers evaluated the need for tools to support data security and data privacy. The group determined that data privacy support tools should: 1) allow for a range of allowable Protected Health Information (PHI); 2) clearly identify what type of data should be protected under the Health Insurance Portability and Accountability Act (HIPAA); and 3) help analysts identify which protected health information data elements are allowable in a given project and how they should be protected during data transfer. Based on these requirements we developed two performance support tools to support data programmers and site analysts in exchanging research data. RESULTS: The first tool, a workplan template, guides the lead programmer through effectively communicating the details of multi-site programming, including how to run the program, what output the program will create, and whether the output is expected to contain protected health information. The second performance support tool is a checklist that site analysts can use to ensure that multi-site program output conforms to expectations and does not contain protected health information beyond what is allowed under the multi-site research agreements. CONCLUSIONS: Together the two tools create a formal multi-site programming workflow designed to reduce the chance of accidental PHI disclosure.

Calibration standards for multicenter clinical trials of fluorescence spectroscopy for in vivo diagnosis.

In the context of clinical trials, calibration protocols for optical instruments that ensure measurement accuracy and the ability to carry out meaningful comparisons of data acquired from multiple instruments are required. A series of calibration standards and procedures are presented to assess technical feasibility of optical devices for cervical precancer detection. Measurements of positive and negative standards, and tissue are made with two generations of research grade spectrometers. Calibration accuracy, ability of standards to correct and account for changes in experimental conditions, and device components are analyzed. The relative frequency of measured calibration standards is investigated retrospectively using statistical analysis of trends in instrument performance. Fluorescence measurements of standards and tissue made with completely different spectrometers show good agreement in intensity and lineshape. Frequency of wavelength calibration standards is increased to every 2 h to compensate for thermal drifts in grating mount. Variations in illumination energy detected between standards and patient measurements require probe redesign to allow for simultaneous acquisition of illumination power with every patient measurement. The use of frequent and well-characterized standards enables meaningful comparison of data from multiple devices and unambiguous interpretation of experiments among the biomedical optics community.

Rationale and design of HOMED-BP Study: hypertension objective treatment based on measurement by electrical devices of blood pressure study.

BACKGROUND: How far should blood pressure (BP) be lowered to achieve the greatest reduction in the risk of cardiovascular disease? Although a few trials have tried to answer this question, they failed to convincingly establish an optimal target BP level, in part because of poor reproducibility and the wide variability of conventional casual BP measurement they used. At the same time, in Japan, calcium antagonist (Ca-A) and angiotensin-converting enzyme inhibitor (ACE-I) have been two major medications in initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also now used widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medications can give the greatest benefit in reducing the risk of cardiovascular disease in the Japanese hypertensive patient. OBJECTIVE: The objectives of the study are, first, to determine an optimal target BP level, based on BP values self-measured at home (home BP). This way of measurement provides more reproducible and less variable BP values than conventional casual measurements. Secondly, we seek to determine the optimal initial antihypertensive medication for the Japanese hypertensive population. METHOD: The study is a 2 x 3 factorial randomized controlled trial conducted with a prospective randomized open-blinded endpoint design. The study will include a total of 9000 untreated essential hypertensive patients aged 40 to 78 years with home BP values > or = 135/85 mmHg. Eligible patients are randomized to one of the two home BP target groups (systolic/diastolic home BP within the range of 134-125/84-80 mmHg, or > or = 125/80 mmHg), and to regimens based on one of three initial antihypertensive drugs (Ca-A or ACE-I or ARB). These randomizations, performed by our host computer, are transmitted to terminals at the outpatient clinic through the Internet. The patient measures BP at home with newly developed equipment (HEM-7471C-N; Omron, Japan) that records BP values, the date, and the time of each measurement. The data are downloaded to the outpatient terminal at every clinic visit then transmitted to the host computer via the Internet. Based on these home BP values, the host computer determines the necessity of additional therapy or dose increments in four further steps to reach the randomized target BP, and then transmits the information to the terminal at the outpatient clinic. The primary study outcome is a composite of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death. The scheduled average post-randomization duration of follow-up is 7 years. CONCLUSION: This is the first large-scale home BP-based and Internet-connected intervention trial on antihypertensive treatment. The HOMED-BP study (Hypertension Objective treatment based on Measurement by Electrical Devices of BP) will improve the recruitment of general practitioners and participants and will supply unbiased BP data, providing reliable information on optimal target BP levels and the optimal initial antihypertensive medication.

Concordancia entre observadores en la evaluación de protocolos de investigación clínica / The agreement between observators in evaluation of clinical research protocols

Objetivo: Determinar el nivel de concordancia entre los integrantes de la Unidad de Epidemiología Clínica en la evaluación de aspectos metodológicos de los protocolos de investigación clínica. Material y métodos: Se seleccionaron aleatoriamente 15 protocolos de investigación registrados durante 1992 en el Hospital General de México, y fueron evaluados por ocho observadores de la Unidad de Epidemiología Clínica siguiéndose un formato diseñado para el estudio. Cada protocolo fue calificado en tres escalas: 1) aprobado/rechazado, 2) escala ordinal de cuatro categorías de la calidad metodológica y 3) puntaje detallado que calificaba cada uno de los aspectos del estudio: Cada protocolo fue independientemente evaluado por todos los observadores. Análisis: Se calcularon coeficientes Kappa y Kappa ponderada entre las parejas de observadores y el coeficiente de correlación intraclase en las calificaciones de los protocolos. Resultados: Se observó una concordancia regular en las parejas de observadores al aprobar o rechazar un protocolo. Las concordancias en la escala de cuatro puntos fueron diversas: buena en cinco parejas y moderada a baja en 11. La concordancia del puntaje total fue excelente. Conclusiones: Los resultados preliminares sugieren que la evaluación objetiva y estandarizada de los protocolos de investigación, utilizando criterios de rigidez científica disminuiría sesgos del evaluador y mejorarían la calidad de presentación de los mismos

MS COSTAR: a computerized patient record adapted for clinical research purposes.

Standardized and computerized neurological data will be a requirement for clinical studies in the future. MS COSTAR is a system that has been designed for multiple sclerosis clinical research. Adoption of standards and a computer method for recording and storing these data should be a high priority for the design and future of multi-center studies on multiple sclerosis.