Multimodal non-rigid image registration methods for therapy and surgery planning

La planificación pre-operatoria se ha convertido en una tarea esencial en cirugías y terapias de marcada complejidad, especialmente aquellas relacionadas con órgano blando. Un ejemplo donde la planificación preoperatoria tiene gran interés es la cirugía hepática. Dicha planificación comprende la detección e identificación precisa de las lesiones individuales y vasos así como la correcta segmentación y estimación volumétrica del hígado funcional. Este proceso es muy importante porque determina tanto si el paciente es un candidato adecuado para terapia quirúrgica como la definición del abordaje a seguir en el procedimiento. La radioterapia de órgano blando es un segundo ejemplo donde la planificación se requiere tanto para la radioterapia externa convencional como para la radioterapia intraoperatoria. La planificación comprende la segmentación de tumor y órganos vulnerables y la estimación de la dosimetría. La segmentación de hígado funcional y la estimación volumétrica para planificación de la cirugía se estiman habitualmente a partir de imágenes de tomografía computarizada (TC). De igual modo, en la planificación de radioterapia, los objetivos de la radiación se delinean normalmente sobre TC. Sin embargo, los avances en las tecnologías de imagen de resonancia magnética (RM) están ofreciendo progresivamente ventajas adicionales. Por ejemplo, se ha visto que el ratio de detección de metástasis hepáticas es significativamente superior en RM con contraste Gd–EOB–DTPA que en TC. Por tanto, recientes estudios han destacado la importancia de combinar la información de TC y RM para conseguir el mayor nivel posible de precisión en radioterapia y para facilitar una descripción precisa de las lesiones del hígado. Con el objetivo de mejorar la planificación preoperatoria en ambos escenarios se precisa claramente de un algoritmo de registro no rígido de imagen. Sin embargo, la gran mayoría de sistemas comerciales solo proporcionan métodos de registro rígido. Las medidas de intensidad de voxel han demostrado ser criterios de similitud de imágenes robustos, y, entre ellas, la Información Mutua (IM) es siempre la primera elegida en registros multimodales. Sin embargo, uno de los principales problemas de la IM es la ausencia de información espacial y la asunción de que las relaciones estadísticas entre las imágenes son homogéneas a lo largo de su domino completo. La hipótesis de esta tesis es que la incorporación de información espacial de órganos al proceso de registro puede mejorar la robustez y calidad del mismo, beneficiándose de la disponibilidad de las segmentaciones clínicas. En este trabajo, se propone y valida un esquema de registro multimodal no rígido 3D usando una nueva métrica llamada Información Mutua Centrada en el Órgano (Organ-Focused Mutual Information metric (OF-MI)) y se compara con la formulación clásica de la Información Mutua. Esto permite mejorar los resultados del registro en áreas problemáticas incorporando información regional al criterio de similitud, beneficiándose de la disponibilidad real de segmentaciones en protocolos estándares clínicos, y permitiendo que la dependencia estadística entre las dos modalidades de imagen difiera entre órganos o regiones. El método propuesto se ha aplicado al registro de TC y RM con contraste Gd–EOB–DTPA así como al registro de imágenes de TC y MR para planificación de radioterapia intraoperatoria rectal. Adicionalmente, se ha desarrollado un algoritmo de apoyo de segmentación 3D basado en Level-Sets para la incorporación de la información de órgano en el registro. El algoritmo de segmentación se ha diseñado específicamente para la estimación volumétrica de hígado sano funcional y ha demostrado un buen funcionamiento en un conjunto de imágenes de TC abdominales. Los resultados muestran una mejora estadísticamente significativa de OF-MI comparada con la Información Mutua clásica en las medidas de calidad de los registros; tanto con datos simulados (p<0.001) como con datos reales en registro hepático de TC y RM con contraste Gd– EOB–DTPA y en registro para planificación de radioterapia rectal usando OF-MI multi-órgano (p<0.05). Adicionalmente, OF-MI presenta resultados más estables con menor dispersión que la Información Mutua y un comportamiento más robusto con respecto a cambios en la relación señal-ruido y a la variación de parámetros. La métrica OF-MI propuesta en esta tesis presenta siempre igual o mayor precisión que la clásica Información Mutua y consecuentemente puede ser una muy buena alternativa en aplicaciones donde la robustez del método y la facilidad en la elección de parámetros sean particularmente importantes. Abstract Pre-operative planning has become an essential task in complex surgeries and therapies, especially for those affecting soft tissue. One example where soft tissue preoperative planning is of high interest is liver surgery. It involves the accurate detection and identification of individual liver lesions and vessels as well as the proper functional liver segmentation and volume estimation. This process is very important because it determines whether the patient is a suitable candidate for surgical therapy and the type of procedure. Soft tissue radiation therapy is a second example where planning is required for both conventional external and intraoperative radiotherapy. It involves the segmentation of the tumor target and vulnerable organs and the estimation of the planned dose. Functional liver segmentations and volume estimations for surgery planning are commonly estimated from computed tomography (CT) images. Similarly, in radiation therapy planning, targets to be irradiated and healthy and vulnerable tissues to be protected from irradiation are commonly delineated on CT scans. However, developments in magnetic resonance imaging (MRI) technology are progressively offering advantages. For instance, the hepatic metastasis detection rate has been found to be significantly higher in Gd–EOB–DTPAenhanced MRI than in CT. Therefore, recent studies highlight the importance of combining the information from CT and MRI to achieve the highest level of accuracy in radiotherapy and to facilitate accurate liver lesion description. In order to improve those two soft tissue pre operative planning scenarios, an accurate nonrigid image registration algorithm is clearly required. However, the vast majority of commercial systems only provide rigid registration. Voxel intensity measures have been shown to be robust measures of image similarity, and among them, Mutual Information (MI) is always the first candidate in multimodal registrations. However, one of the main drawbacks of Mutual Information is the absence of spatial information and the assumption that statistical relationships between images are the same over the whole domain of the image. The hypothesis of the present thesis is that incorporating spatial organ information into the registration process may improve the registration robustness and quality, taking advantage of the clinical segmentations availability. In this work, a multimodal nonrigid 3D registration framework using a new Organ- Focused Mutual Information metric (OF-MI) is proposed, validated and compared to the classical formulation of the Mutual Information (MI). It allows improving registration results in problematic areas by adding regional information into the similitude criterion taking advantage of actual segmentations availability in standard clinical protocols and allowing the statistical dependence between the two modalities differ among organs or regions. The proposed method is applied to CT and T1 weighted delayed Gd–EOB–DTPA-enhanced MRI registration as well as to register CT and MRI images in rectal intraoperative radiotherapy planning. Additionally, a 3D support segmentation algorithm based on Level-Sets has been developed for the incorporation of the organ information into the registration. The segmentation algorithm has been specifically designed for the healthy and functional liver volume estimation demonstrating good performance in a set of abdominal CT studies. Results show a statistical significant improvement of registration quality measures with OF-MI compared to MI with both simulated data (p<0.001) and real data in liver applications registering CT and Gd–EOB–DTPA-enhanced MRI and in registration for rectal radiotherapy planning using multi-organ OF-MI (p<0.05). Additionally, OF-MI presents more stable results with smaller dispersion than MI and a more robust behavior with respect to SNR changes and parameters variation. The proposed OF-MI always presents equal or better accuracy than the classical MI and consequently can be a very convenient alternative within applications where the robustness of the method and the facility to choose the parameters are particularly important.

Organ-focused mutual information for nonrigid multimodal registration of liver CT and Gd–EOB–DTPA-enhanced MRI

Accurate detection of liver lesions is of great importance in hepatic surgery planning. Recent studies have shown that the detection rate of liver lesions is significantly higher in gadoxetic acid-enhanced magnetic resonance imaging (Gd–EOB–DTPA-enhanced MRI) than in contrast-enhanced portal-phase computed tomography (CT); however, the latter remains essential because of its high specificity, good performance in estimating liver volumes and better vessel visibility. To characterize liver lesions using both the above image modalities, we propose a multimodal nonrigid registration framework using organ-focused mutual information (OF-MI). This proposal tries to improve mutual information (MI) based registration by adding spatial information, benefiting from the availability of expert liver segmentation in clinical protocols. The incorporation of an additional information channel containing liver segmentation information was studied. A dataset of real clinical images and simulated images was used in the validation process. A Gd–EOB–DTPA-enhanced MRI simulation framework is presented. To evaluate results, warping index errors were calculated for the simulated data, and landmark-based and surface-based errors were calculated for the real data. An improvement of the registration accuracy for OF-MI as compared with MI was found for both simulated and real datasets. Statistical significance of the difference was tested and confirmed in the simulated dataset (p < 0.01).

High-efficiency retroviral-mediated gene transfer into human and nonhuman primate peripheral blood lymphocytes.

Peripheral blood lymphocytes (PBLs) are primary targets for gene therapy of inherited and acquired disorders of the immune system. We describe the development of an optimized transduction system that provides for high-efficiency retrovirus-mediated gene transfer into primary PBLs. This optimized transduction protocol combines centrifugation of the lymphocytes (1000 x g) at the inception of transduction with phosphate depletion, low-temperature incubation (32 degrees C), and the use of the packaging cell line PG13. Gene marking studies of human and primate PBLs using these optimized transduction conditions demonstrated that the transduction efficiency exceeded 50% of the total lymphocyte population. The optimized transduction efficiency of PBLs with amphotropic retroviral vectors was in excess of 25%. The transduction procedure does not alter phenotype, viability, or expansion of the transduced cells. Our data indicate that this optimized transduction system leads to high-efficiency gene transfer into primary human lymphocytes, which obviates the requirement for selection of transduced cells prior to gene-therapy procedures. Thus, large quantities of healthy retrovirally transduced lymphocytes containing a broad immunological repertoire can be generated for use in clinical protocols. Our results represent a significant improvement in the methodology for the transduction of lymphocytes for gene therapy.

Estimativa de dose nos pulmões para procedimentos de tomografia computadorizada

Desde o seu desenvolvimento na década de 1970 a tomografia computadorizada (TC) passou por grandes mudanças tecnológicas, tornando-se uma importante ferramenta diagnóstica para a medicina. Consequentemente o papel da TC em diagnóstico por imagem expandiu-se rapidamente, principalmente devido a melhorias na qualidade da imagem e tempo de aquisição. A dose de radiação recebida por pacientes devido a tais procedimentos vem ganhando atenção, levando a comunidade científica e os fabricantes a trabalharem juntos em direção a determinação e otimização de doses. Nas últimas décadas muitas metodologias para dosimetria em pacientes têm sido propostas, baseadas especialmente em cálculos utilizando a técnica Monte Carlo ou medições experimentais com objetos simuladores e dosímetros. A possibilidade de medições in vivo também está sendo investigada. Atualmente as principais técnicas para a otimização da dose incluem redução e/ou modulação da corrente anódica. O presente trabalho propõe uma metodologia experimental para estimativa de doses absorvidas pelos pulmões devido a protocolos clínicos de TC, usando um objeto simulador antropomórfico adulto e dosímetros termoluminescentes de Fluoreto de Lítio (LiF). Sete protocolos clínicos diferentes foram selecionados, com base em sua relevância com respeito à otimização de dose e frequência na rotina clínica de dois hospitais de grande porte: Instituto de Radiologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InRad) e Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira (ICESP). Quatro protocolos de otimização de dose foram analisados: Auto mA, Auto + Smart mA, Baixa Dose (BD) e Ultra Baixa Dose (UBD). Os dois primeiros protocolos supracitados buscam redução de dose por meio de modulação da corrente anódica, enquanto os protocolos BD e UBD propõem a redução do valor da corrente anódica, mantendo-a constante. Os protocolos BD e UBD proporcionaram redução de dose de 72,7(8) % e 91(1) %, respectivamente; 16,8(1,3) % e 35,0(1,2) % de redução de dose foram obtidas com os protocolos Auto mA e Auto + Smart mA, respectivamente. As estimativas de dose para os protocolos analisados neste estudo são compatíveis com estudos similares publicados na literatura, demonstrando a eficiência da metodologia para o cálculo de doses absorvidas no pulmão. Sua aplicabilidade pode ser estendida a diferentes órgãos, diferentes protocolos de CT e diferentes tipos de objetos simuladores antropomórficos (pediátricos, por exemplo). Por fim, a comparação entre os valores de doses estimadas para os pulmões e valores de estimativas de doses dependentes do tamanho (Size Specific Dose Estimates SSDE) demonstrou dependência linear entre as duas grandezas. Resultados de estudos similares exibiram comportamentos similares para doses no reto, sugerindo que doses absorvidas pelos uma órgãos podem ser linearmente dependente dos valores de SSDE, com coeficientes lineares específicos para cada órgão. Uma investigação mais aprofundada sobre doses em órgãos é necessária para avaliar essa hipótese.

Validação do protocolo de avaliação do frênulo da língua em bebês

Este estudo teve por objetivo validar o Protocolo de avaliação do frênulo da língua em bebês. Para isso, a partir do cálculo amostral, foi aplicado o protocolo em 100 bebês saudáveis, nascidos a termo, com 30 dias de vida, em amamentação exclusiva. O processo de validação consistiu da análise da validade de conteúdo, de critério e de construto, bem como da confiabilidade, sensibilidade, especificidade, valor preditivo positivo e negativo. A validade de conteúdo foi realizada por três examinadores, por meio da classificação de cada item quanto à clareza e posterior aplicação do Índice de Validação do Conteúdo. As avaliadoras sugeriram modificações no protocolo, por consenso, possibilitando obter a versão final. Para a validade de critério, comparou-se o Protocolo de avaliação do frênulo da língua em bebês com o instrumento Bristol Tongue Assessment Tool (BTAT). A validade de construto foi analisada a partir da comparação dos escores do protocolo aplicado nos bebês com 30 e 75 dias. As avaliações foram realizadas por duas fonoaudiólogas especialistas em Motricidade Orofacial (denominadas A1 e A2), devidamente treinadas e calibradas, por meio da análise das filmagens realizadas durante a aplicação do protocolo, para verificação da concordância entre examinadores, bem como definição dos valores de sensibilidade, especificidade e valores preditivos. Para a análise da concordância intra-avaliador foi realizado o teste/reteste de 20% da amostra pela A2. Quanto ao tratamento estatístico, para a análise de concordância intra e entre avaliadores, foram utilizados o Coeficiente de Correlação Intraclasse e o cálculo do erro do método. Para análise da validade de construto foram aplicados os testes de Wilcoxon e Mann-Whitney. O nível de significância adotado em todos os testes foi de 5%. Houve 100% de concordância na validação do conteúdo. A validade de critério apresentou correlações fortes dos itens correspondentes do Protocolo de avaliação do frênulo da língua em bebês e do instrumento BTAT, sendo o valor do coeficiente de correlação de Spearman igual a -0,997. Os resultados obtidos evidenciaram uma concordância muito boa intra e entre avaliadores, com valores baixos de erro casual e valores de p>0,05 (evidenciando que não há diferença entre a análise dos avaliadores) e Coeficiente de Correlação Intraclasse maior que 0,75; mostrando ainda, uma capacidade significativa do protocolo em mensurar as mudanças resultantes da frenotomia lingual, pela história clínica, avaliação anatomofuncional e avaliação da sucção não nutritiva e nutritiva (p<0,05). Quando comparados os resultados dos bebês com alteração do frênulo lingual (grupo experimental) e sem alteração (grupo controle), com 30 e 75 dias, houve diferença nos escores parciais e no escore total do exame clínico e do protocolo completo. Os índices de sensibilidade, especificidade e valores preditivos positivo e negativo foram 100%. A ocorrência das alterações do frênulo lingual nesse estudo foi de 21%. Concluiu-se, com este estudo, que o Protocolo de avaliação do frênulo da língua em bebês mostrou ser um instrumento válido e confiável de avaliação, assegurando acurácia em diagnosticar as alterações do frênulo lingual dentro dos parâmetros investigados, podendo ser aplicado por diferentes avaliadores, desde que os mesmos sejam capacitados e treinados para sua aplicação.

After hours medical ward duties in a teaching hospital

In many Australian hospitals a medical officer is available for urgent review of in-patients outside normal working hours. Current practice in nurse-initiated requests for medical officer involvement out of hours may adversely affect patient outcome as well as medical and nursing resource use at these times. Of 10 523 nurse-initiated requests for out-of-hours review recorded by medical officers at our hospital in 2002-2003, the most frequent reasons for the requests were medication review, IV fluid orders, IV resite, venesection and pathology review, none of which are related to acute changes in clinical condition. Requests for routine review of medication and fluid orders were found to be rarely essential and often inappropriate. Medical officer activity was highest before midnight and least after midnight, suggesting most requests are fulfilled in the evening. Several strategies to reduce inappropriate out-of-hours requests were identified. Routine tasks could be completed by primary treating unit staff before going off-duty. IV cannulation and venesection may be performed by appropriately trained phlebotomists or skilled advanced practice nursing staff. Meticulous ordering of 'as required' analgesia and night sedation would reduce unnecessary requests. Clinical protocols for nurse-initiated adjustment of drugs with variable dosing may also decrease inefficiencies. This would leave the ward cover medical officers more available for their primary function of urgent patient review.

Avaliação clínica e da qualidade de vida utilizando dois protocolos para recuperação miofuncional em pacientes que se submeteram à cirurgia ortognática: resultados preliminares

The objective of this randomized, blind and prospective clinical trial was to compare the pain, the edema, the mandibular movements, the masticatory efficiency and life quality, in the first 60 days after surgery using 2 different clinical protocols for myofunctional recovery, in patients who underwent orthognathic surgery. A sample of 19 patients was used and divided into 2 groups. The control group (CG) consisted of 10 patients who had postoperative rehabilitation guided by a standard protocol, conducted by the Service of Surgery and Traumatology Oral and Maxillofacial. In other hand, the experimental group (EC) totaled 9 patients who received the speech therapy rehabilitation protocol specialized, by professionals in the area. The variables pain, edema and mandibular movements were analyzed during 48h, 96h, 7 days, 14 days, 30 and 60 days post-surgery. The masticatory efficiency and the quality of life were classified with 60 days after surgery . The data were submitted an analysis of variance, Student's t-test and Fisher's independence, at the level of 5% probability. It was identified that patients of GE have benefited in the first 14 days(p<0,001), as they have had reported less pain than those in the CG. Significant statistics differences between groups for pain parameters (after 14 days) (p=0,065), edema(p=0,063), mandibular movements(p=0,068), masticatory efficiency(p=0,630) and the impact on quality of life (p=0,813) were not observed on this study. The speech therapy protocol for myofunctional recovery (EG), although it has not obtained statistical results superiors than the CG in the general context, presents itself as a viable alternative to conventional therapy assumed by many maxillofacial surgeons, allowing the surgeon to optimize time with patients in the period postoperatively.

Ambulance Treatment Space Ergonomic Layout

This is the first time a multidisciplinary team has employed an iterative co-design method to determine the ergonomic layout of an emergency ambulance treatment space. This process allowed the research team to understand how treatment protocols were performed and developed analytical tools to reach an optimum configuration towards ambulance design standardisation. Fusari conducted participatory observations during 12-hour shifts with front-line ambulance clinicians, hospital staff and patients to understand the details of their working environments whilst on response to urgent and emergency calls. A simple yet accurate 1:1 mock-up of the existing ambulance was built for detailed analysis of these procedures through simulations. Paramedics were called in to participate in interviews and role-playing inside the model to recreate tasks, how they are performed, the equipment used and to understand the limitations of the current ambulance. The use of Link Analysis distilled 5 modes of use. In parallel, an exhaustive audit of all equipment and consumables used in ambulances was performed (logging and photography) to define space use. These developed 12 layout options for refinement and CAD modelling and presented back to paramedics. The preferred options and features were then developed into a full size test rig and appearance model. Two key studies informed the process. The 2005 National Patient Safety Agency funded study “Future Ambulances” outlined 9 design challenges for future standardisation of emergency vehicles and equipment. Secondly, the 2007 EPSRC funded “Smart Pods” project investigated a new system of mobile urgent and emergency medicine to treat patients in the community. A full-size mobile demonstrator unit featuring the evidence-based ergonomic layout was built for clinical tests through simulated emergency scenarios. Results from clinical trials clearly show that the new layout improves infection control, speeds up treatment, and makes it easier for ambulance crews to follow correct clinical protocols.

Hyaluronic acid as neuropathic ulcer treatment: a case report

The prevalence of diabetic polyneuropathy in Spain is 22% increasing with age, standing at less than 5% in patients between 15 and 19 years and reaching 29.8% in those aged 70 to 74 years age. Infection is an important complication in Diabetic Foot, frequently associated with minor amputation and even lower extremity amputation. The study presents a clinical case of a 68-year-old man who consulted for a diabetic foot ulcer in the metatarseal area of the right foot, diagnosed two years ago and without healing success. An exploration protocol of the diabetic food was made. Afterwards, a surgical debridement was done and a cure procedure with pure hyaluronic acid, a bandage and foot unloading was followed. After 69 days of treatment, a complete ulcer healing was achieved. After the injure healing, a biomechanical exploration was made and a plantar support was produced to avoid the reappearance of the injury because of local hyperpressure.

Best practice principles for management of children with developmental coordination disorder (DCD) : results of a scoping review

Background. Developmental coordination disorder (DCD) is a prevalent health condition that is frequently unrecognized despite the substantial evidence that has accumulated regarding how it affects children’s health, education and skills.Most literature focuses on measurement of impairment and description of intervention approaches for individual children; little is known about the principles that should guide best practice and service delivery for children with DCD as a population. The purpose of this study was to identify these principles. Methods. A scoping review was used to ‘map’ the information available to inform intervention and service delivery. Scholarly and grey literature written in English was identified in six databases, using a combination of keywords (e.g. guidelines, management, models and DCD); a ‘snow-balling’ technique was also used in Canada and the UK to access clinical protocols used in publicly funded health care systems. Over 500 documents were screened: 31 met inclusion criteria as they outlined practice principles for children with DCD as a population. Data regarding best practices were independently extracted by two reviewers and then compared with achieve consistency and consensus. Results. Two over-arching themes emerged, with five principles: (1) Organizing services to efficiently meet the comprehensive needs of children (e.g. Increasing awareness of DCD and coordination; Implementing clearly defined pathways; Using a graduated/staged approach); (2) Working collaboratively to offer evidence-based services (e.g. Integration of child and family views; Evidence-based interventions fostering function, participation and prevention). Conclusion Numerous documents support each of the principles, reflecting agreement across studies about recommended organization of services.While these principles may apply to many populations of children with disabilities, this review highlights how essential these principles are in DCD. Researchers, managers, clinicians, community partners and families are encouraged to work together in designing, implementing and evaluating interventions that reflect these principles.

Desenlaces de la escala Omaha+ en los pacientes en cuidado intensivo en la fundación santa fe de Bogotá

Introducción La ventilación mecánica es fundamental en el manejo de la falla respiratoria aguda, actualmente no existe consenso sobre el momento exacto de extubación. Este estudio describe el comportamiento de la escala OMAHA+ en nuestra institución. Objetivo Principal Describir los desenlaces clínicos relacionados con la escala OMAHA+ durante la extubación de los pacientes de las unidades de cuidado intensivo del hospital universitario. Métodos Estudio descriptivo, retrospectivo, basado en el registro de la escala OMAHA+ de 68 pacientes durante el proceso de extubación en las Unidades de cuidado intensivo adulto de la Fundación Santa Fe de Bogotá durante Agosto de 2014 a Mayo de 2015. Resultados Se encontraron valores gasométricos cercanos a la normalidad, con una PaO2/FiO2 media de 261 (DS 60,6), SaO2 media de 96% (DS 2%), media de lactato sérico de 1.5 mmol/L (DS 1,2 mmol/L), con signos vitales normales. La causa más común de ingreso a UCI fue Neumonía, seguida por cirugía cardiaca y abdominal. Las medias de parámetros ventilatorios al momento de extubación fueron; PEEP de 6 (DS 0,8), volumen corriente de 8ml/Kg (DS 1,4 ml/Kg), índice de Tobín de 34 (DS 11,9), test de fuga positivo 94%, y sólo una extubación fallida. Conclusiones La escala OMAHA+ puede ser una herramienta útil, aplicable y fácilmente reproducible en los pacientes con soporte ventilatorio mecánico invasivo previo al proceso de extubación, con baja proporción de fallo. Estos resultados deben ser evaluados en estudios prospectivos.

Caracterización sociodemográfica de las enfermedades huérfanas en Colombia

Las enfermedades huérfanas en Colombia, se definen como aquellas crónicamente debilitantes, que amenazan la vida, de baja prevalencia (menor 1/5000) y alta complejidad. Se estima que a nivel mundial existen entre 6000 a 8000 enfermedades raras diferentes(1). Varios países a nivel mundial individual o colectivamente, en los últimos años han creado políticas e incentivos para la investigación y protección de los pacientes con enfermedades raras. Sin embargo, a pesar del creciente número de publicaciones; la información sobre su etiología, fisiología, historia natural y datos epidemiológicos persiste escasa o ausente. Los registros de pacientes, son una valiosa herramienta para la caracterización de las enfermedades, su manejo y desenlaces con o sin tratamiento. Permiten mejorar políticas de salud pública y cuidado del paciente, contribuyendo a mejorar desenlaces sociales, económicos y de calidad de vida. En Colombia, bajo el decreto 1954 de 2012 y las resoluciones 3681 de 2013 y 0430 de 2013 se creó el fundamento legal para la creación de un registro nacional de enfermedades huérfanas. El presente estudio busca determinar la caracterización socio-demográfica y la prevalencia de las enfermedades huérfanas en Colombia en el periodo 2013. Métodos: Se realizó un estudio observacional de corte transversal de fuente secundaria sobre pacientes con enfermedades huérfanas en el territorio nacional; basándose en el registro nacional de enfermedades huérfanas obtenido por el Ministerio de Salud y Protección Social en el periodo 2013 bajo la normativa del decreto 1954 de 2012 y las resoluciones 3681 de 2013 y 0430 de 2013. Las bases de datos obtenidas fueron re-categorizadas en Excel versión 15.17 para la extracción de datos y su análisis estadístico posterior, fue realizado en el paquete estadístico para las ciencias sociales (SPSS v.20, Chicago, IL). Resultados: Se encontraron un total de 13173 pacientes con enfermedades huérfanas para el 2013. De estos, el 53.96% (7132) eran de género femenino y el 46.03% (6083) masculino; la mediana de la edad fue de 28 años con un rango inter-cuartil de 39 años, el 9% de los pacientes presentaron discapacidad. El registro contenía un total de 653 enfermedades huérfanas; el 34% del total de las enfermedades listadas en nuestro país (2). Las patologías más frecuentes fueron el Déficit Congénito del Factor VIII, Miastenia Grave, Enfermedad de Von Willebrand, Estatura Baja por Anomalía de Hormona de Crecimiento y Displasia Broncopulmonar. Discusión: Se estimó que aproximadamente 3.3 millones de colombianos debían tener una enfermedad huérfana para el 2013. El registro nacional logró recolectar datos de 13173 (0.4%). Este bajo número de pacientes, marca un importante sub-registro que se debe al uso de los códigos CIE-10, desconocimiento del personal de salud frente a las enfermedades huérfanas y clasificación errónea de los pacientes. Se encontraron un total de 653 enfermedades, un 34% de las enfermedades reportadas en el listado nacional de enfermedades huérfanas (2) y un 7% del total de enfermedades reportadas en ORPHANET para el periodo 2013 (3). Conclusiones: La recolección de datos y la sensibilización sobre las enfermedades huérfanas al personal de salud, es una estrategia de vital importancia para el diagnóstico temprano, medidas específicas de control e intervenciones de los pacientes. El identificar apropiadamente a los pacientes con este tipo de patologías, permite su ingreso en el registro y por ende mejora el sub-registro de datos. Sin embargo, cabe aclarar que el panorama ideal sería, el uso de un sistema de recolección diferente al CIE-10 y que abarque en mayor medida la totalidad de las enfermedades huérfanas.

Fate of clinical research studies after ethical approval--follow-up of study protocols until publication.

BACKGROUND: Many clinical studies are ultimately not fully published in peer-reviewed journals. Underreporting of clinical research is wasteful and can result in biased estimates of treatment effect or harm, leading to recommendations that are inappropriate or even dangerous. METHODS: We assembled a cohort of clinical studies approved 2000-2002 by the Research Ethics Committee of the University of Freiburg, Germany. Published full articles were searched in electronic databases and investigators contacted. Data on study characteristics were extracted from protocols and corresponding publications. We characterized the cohort, quantified its publication outcome and compared protocols and publications for selected aspects. RESULTS: Of 917 approved studies, 807 were started and 110 were not, either locally or as a whole. Of the started studies, 576 (71%) were completed according to protocol, 128 (16%) discontinued and 42 (5%) are still ongoing; for 61 (8%) there was no information about their course. We identified 782 full publications corresponding to 419 of the 807 initiated studies; the publication proportion was 52% (95% CI: 0.48-0.55). Study design was not significantly associated with subsequent publication. Multicentre status, international collaboration, large sample size and commercial or non-commercial funding were positively associated with subsequent publication. Commercial funding was mentioned in 203 (48%) protocols and in 205 (49%) of the publications. In most published studies (339; 81%) this information corresponded between protocol and publication. Most studies were published in English (367; 88%); some in German (25; 6%) or both languages (27; 6%). The local investigators were listed as (co-)authors in the publications corresponding to 259 (62%) studies. CONCLUSION: Half of the clinical research conducted at a large German university medical centre remains unpublished; future research is built on an incomplete database. Research resources are likely wasted as neither health care professionals nor patients nor policy makers can use the results when making decisions.

Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

BACKGROUND: Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. PARTICIPANTS AND METHODS: Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. RESULTS: Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. CONCLUSION: No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

Clinical and radiographic changes around dental implants inserted in different levels in relation to the crestal bone, under different restoration protocols, in the dog model

Background: The aim of the present study was to evaluate clinical and radiographic changes that occur around dental implants inserted in different levels in relation to crestal bone under different restoration protocols.Methods: Thirty-six implants were inserted in the edentulous mandible of six mongrel dogs. Each implant was assigned to an experimental group according to the distance from the top of the implant to the crestal bone: Bone Level (at crestal bone level), Minus 1 (1 mm below crestal bone), or Minus 2 (2 mm below crestal bone). Each hemimandible was submitted to a restoration protocol: conventional (prosthesis was installed 120 days after implant placement, including 30 days with healing cap) or immediate (prosthesis was installed 24 hours after implant placement). Fixed partial prostheses were installed bilaterally in the same day. After 90 days, clinical and radiographic parameters were evaluated.Results: As long as the implants were inserted in more apical positions, the first bone-to-implant contact (fBIC) was positioned more apically (P<0.05). However, the apical positioning of the implants did not influence the ridge loss or the position of the soft tissue margin (PSTM) (P>0.05). In addition, in immediately restored sites, the PSTM was located significantly more coronally than that in conventionally restored sites (P=0.02).Conclusions: Despite the more apical positioning of the fBIC, the height of the peri-implant soft tissues and ridge was not jeopardized. Moreover, the immediate restoration protocol was beneficial to the maintenance of the PSTM. Further studies are suggested to evaluate the significance of these results in longer healing periods.