Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto es evaluar el desempeño de las pruebas diagnósticas convencionales y moleculares, para la detección de TB latente y activa pacientes con VIH, en dos hospitales públicos de Bogotá. Para TB latente se evaluó la concordancia entre las pruebas QuantiFERON-TB (QTF) y Tuberculina (PPD), sugiriendo superioridad del QTF sobre la PPD. Se evaluaron tres pruebas diagnósticas por su sensibilidad y especificidad, baciloscopia (BK), GenoType®MTBDR plus (Genotype) y PCR IS6110 teniendo como estándar de oro el cultivo. Los resultados de sensibilidad (S) y especificidad (E) de cada prueba con una prevalencia del 19,4 % de TB pulmonar y extrapulmonar en los pacientes que participaron del estudio fue: BK S: 64% E: 99,1%; Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 73% E: 95,5%, de la misma forma se determinaron los valores predictivos positivos y negativos (VPP y VPN) BK: 88,9% y 94,8%, Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 90% y 95,7%. Se concluyó bajo análisis de curva ROC que las pruebas muestran un rendimiento diagnóstico similar por separado en el diagnóstico de TB en pacientes con VIH, aumentando su rendimiento diagnostico cuando se combinan

Seguridad del monitoreo hemodinámico invasivo versus mínimamente invasivo en pacientes con choque cardiogénico en cuidado intensivo adultos. Revisión sistemática

Introducción: El monitoreo hemodinámico es una herramienta para diagnosticar el choque cardiogénico y monitorear la respuesta al tratamiento; puede ser invasivo, mínimamente invasivo o no invasivo. Se realiza rutinariamente con catéter de arteria pulmonar (CAP) o catéter de Swan Ganz; nuevas técnicas de monitoreo hemodinámico mínimamente invasivo tienen menor tasa de complicaciones. Actualmente se desconoce cuál técnica de monitoreo cuenta con mayor seguridad en el paciente con choque cardiogénico. Objetivo: Evaluar la seguridad del monitoreo hemodinámico invasivo comparado con el mínimamente invasivo en pacientes con choque cardiogénico en cuidado intensivo adultos. Diseño: Revisión sistemática de la literatura. Búsqueda en Pubmed, EMBASE, OVID - Cochrane Library, Lilacs, Scielo, registros de ensayos clínicos, actas de conferencias, repositorios, búsqueda de literatura gris en Google Scholar, Teseo y Open Grey hasta agosto de 2016, publicados en inglés y español. Resultados: Se identificó un único estudio con 331 pacientes críticamente enfermos que comparó el monitoreo hemodinámico con CAP versus PiCCO que concluyó que después de la corrección de los factores de confusión, la elección del tipo de monitoreo no influyó en los resultados clínicos más importantes en términos de complicaciones y mortalidad. Dado que se incluyeron otros diagnósticos, no es posible extrapolar los resultados sólo a choque cardiogénico. Conclusión: En la literatura disponible no hay evidencia de que el monitoreo hemodinámico invasivo comparado con el mínimamente invasivo, en pacientes adultos críticamente enfermos con choque cardiogénico, tenga diferencias en cuanto a complicaciones y mortalidad.

Validation of the interRAI Cognitive Performance Scale against independent clinical diagnosis and the Mini-Mental State Examination in older hospitalized patients

Objective To compare the diagnostic accuracy of the interRAI Acute Care (AC) Cognitive Performance Scale (CPS2) and the Mini-Mental State Examination (MMSE), against independent clinical diagnosis for detecting dementia in older hospitalized patients. Design, Setting, and Participants The study was part of a prospective observational cohort study of patients aged ≥70 years admitted to four acute hospitals in Queensland, Australia, between 2008 and 2010. Recruitment was consecutive and patients expected to remain in hospital for ≥48 hours were eligible to participate. Data for 462 patients were available for this study. Measurements Trained research nurses completed comprehensive geriatric assessments and administered the interRAI AC and MMSE to patients. Two physicians independently reviewed patients’ medical records and assessments to establish the diagnosis of dementia. Indicators of diagnostic accuracy included sensitivity, specificity, predictive values, likelihood ratios and areas under receiver (AUC) operating characteristic curves. Results 85 patients (18.4%) were considered to have dementia according to independent clinical diagnosis. The sensitivity of the CPS2 [0.68 (95%CI: 0.58–0.77)] was not statistically different to the MMSE [0.75 (0.64–0.83)] in predicting physician diagnosed dementia. The AUCs for the 2 instruments were also not statistically different: CPS2 AUC = 0.83 (95%CI: 0.78–0.89) and MMSE AUC = 0.87 (95%CI: 0.83–0.91), while the CPS2 demonstrated higher specificity [0.92 95%CI: 0.89–0.95)] than the MMSE [0.82 (0.77–0.85)]. Agreement between the CPS2 and clinical diagnosis was substantial (87.4%; κ=0.61). Conclusion The CPS2 appears to be a reliable screening tool for assessing cognitive impairment in acutely unwell older hospitalized patients. These findings add to the growing body of evidence supporting the utility of the interRAI AC, within which the CPS2 is embedded. The interRAI AC offers the advantage of being able to accurately screen for both dementia and delirium without the need to use additional assessments, thus increasing assessment efficiency.

Validação e aplicação clínica de uma escala de cognição social na esquizofrenia = Validation and clinical use of a measure of social cognition in schizophrenia

RESUMO: A cognição social encontra-se frequentemente alterada na esquizofrenia. Esta alteração relaciona-se com a diminuição do funcionamento social,caracterizando-se quer por défices quer por vieses cognitivos sociais. No entanto, existem poucos instrumentos fiáveis e válidos para avaliar a cognição social na esquizofrenia, nomeadamente capazes de medir os vieses cognitivos sociais e a cognição social auto-relevante. Adicionalmente, as bases biológicas da disfunção social não estão totalmente esclarecidas. Evidências recentes sugerem que o peptídeo oxitocina (OXT) influencia o funcionamento social, e que esta relação poderá ser mediada pela cognição social. Este Trabalho de Projecto descreve a contribuição do autor para o desenvolvimento e avaliação psicométrica inicial de um novo instrumento de avaliação da cognição social, e a utilidade desta escala na investigação das associações entre a OXT e a capacidade e vieses cognitivos sociais. A Waiting Room Task (WRT), uma escala constituída por 26 vídeos sequenciais que simulam a experiência de observar outra pessoa numa sala de espera, foi administrada num estudo transversal com 61 doentes com esquizofrenia e 20 controlos saudáveis. Observou-se uma menor capacidade cognitiva social e um aumento dos vieses cognitivos sociais nos doentes com esquizofrenia, comparativamente aos controlos. Nos controlos e doentes com delírios, o desempenho na WRT correlacionou-se significativamente com os níveis de OXT. Esta correlação não se observou nos doentes sem delírios, sugerindo que o papel da OXT na cognição social poderá encontrar-se atenuado neste grupo. Estes achados fornecem suporte inicial para a adequação da WRT como instrumento de avaliação da cognição social na esquizofrenia, podendo ainda ser útil na investigação da sua base biológica. ------------ ABSTRACT: Social cognition is often impaired in schizophrenia. This impairment is related to poor social functioning and is characterized by both social cognitive deficits and biases. However, there are few reliable and valid measures of social cognition in schizophrenia, particularly measures of social cognitive bias and of self-relevant social cognition. Also, the biological bases of social dysfunction are not well understood. Emerging evidence suggests that the peptide oxytocin (OXT) influences social functioning, and that this relationship may be mediated by social cognition. This Research Project describes the author’s contribution to the development and initial psychometric testing of a new measure of social cognition, and the utility of this instrument to examine associations between OXT and social cognitive capacity and bias. The Waiting Room Task WRT), a video-based test comprising 26 sequential videos simulating the experience of facing another person in a waiting room, was administered in a cross-sectional study involving 61 patients with schizophrenia and 20 healthy controls. Social cognitive capacity was lower and social cognitive bias was increased in patients with schizophrenia compared with controls. Among controls and patients with delusions, performance on the WRT was significantly correlated with OXT level. This correlation was not found in patients without delusions suggesting that OXT’s role in social cognition may be blunted in this group. These findings provide initial support for the adequacy of the WRT as a measure for assessing social cognition in schizophrenia that may also be useful in understanding its biological underpinnings.

Feasibility and clinical outcomes when using practice guidelines for evaluation of fever in returning travelers and migrants : a validation study.

BACKGROUND: Practice guidelines for examining febrile patients presenting upon returning from the tropics were developed to assist primary care physicians in decision making. Because of the low level of evidence available in this field, there was a need to validate them and assess their feasibility in the context they have been designed for. OBJECTIVES: The objectives of the study were to (1) evaluate physicians' adherence to recommendations; (2) investigate reasons for non-adherence; and (3) ensure good clinical outcome of patients, the ultimate goal being to improve the quality of the guidelines, in particular to tailor them for the needs of the target audience and population. METHODS: Physicians consulting the guidelines on the Internet (www.fevertravel.ch) were invited to participate in the study. Navigation through the decision chart was automatically recorded, including diagnostic tests performed, initial and final diagnoses, and clinical outcomes. The reasons for non-adherence were investigated and qualitative feedback was collected. RESULTS: A total of 539 physician/patient pairs were included in this study. Full adherence to guidelines was observed in 29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for non-adherence were as follows: no repetition of malaria tests (111/352) and no presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain without leukocytosis (46/101). Overall, 20% of diversions from guidelines were considered reasonable because there was an alternative presumptive diagnosis or the symptoms were mild, which means that the corrected adherence rate per case was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and all complications could be attributed to the underlying illness rather than to adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible, useful, and leading to good clinical outcomes. Almost one third of physicians strictly adhered to the guidelines. Other physicians used the guidelines not to forget specific diagnoses but finally diverged from the proposed attitudes. These diversions should be scrutinized for further refinement of the guidelines to better fit to physician and patient needs.

The Development, Validation and Implementation of a Broad-Based ADME Genotyping Assay into Research and Clinical Trials

Afin d’adresser la variabilité interindividuelle observée dans la réponse pharmacocinétique à de nombreux médicaments, nous avons créé un panel de génotypage personnalisée en utilisant des méthodes de conception et d’élaboration d’essais uniques. Celles-ci ont pour but premier de capturer les variations génétiques présentent dans les gènes clés impliqués dans les processus d'absorption, de distribution, de métabolisme et d’excrétion (ADME) de nombreux agents thérapeutiques. Bien que ces gènes et voies de signalement sont impliqués dans plusieurs mécanismes pharmacocinétiques qui sont bien connues, il y a eu jusqu’à présent peu d'efforts envers l’évaluation simultanée d’un grand nombre de ces gènes moyennant un seul outil expérimental. La recherche pharmacogénomique peut être réalisée en utilisant deux approches: 1) les marqueurs fonctionnels peuvent être utilisés pour présélectionner ou stratifier les populations de patients en se basant sur des états métaboliques connus; 2) les marqueurs Tag peuvent être utilisés pour découvrir de nouvelles corrélations génotype-phénotype. Présentement, il existe un besoin pour un outil de recherche qui englobe un grand nombre de gènes ADME et variantes et dont le contenu est applicable à ces deux modèles d'étude. Dans le cadre de cette thèse, nous avons développé un panel d’essais de génotypage de 3,000 marqueurs génétiques ADME qui peuvent satisfaire ce besoin. Dans le cadre de ce projet, les gènes et marqueurs associés avec la famille ADME ont été sélectionnés en collaboration avec plusieurs groupes du milieu universitaire et de l'industrie pharmaceutique. Pendant trois phases de développement de cet essai de génotypage, le taux de conversion pour 3,000 marqueurs a été amélioré de 83% à 97,4% grâce à l'incorporation de nouvelles stratégies ayant pour but de surmonter les zones d'interférence génomiques comprenant entre autres les régions homologues et les polymorphismes sous-jacent les régions d’intérêt. La précision du panel de génotypage a été validée par l’évaluation de plus de 200 échantillons pour lesquelles les génotypes sont connus pour lesquels nous avons obtenu une concordance > 98%. De plus, une comparaison croisée entre nos données provenant de cet essai et des données obtenues par différentes plateformes technologiques déjà disponibles sur le marché a révélé une concordance globale de > 99,5%. L'efficacité de notre stratégie de conception ont été démontrées par l'utilisation réussie de cet essai dans le cadre de plusieurs projets de recherche où plus de 1,000 échantillons ont été testés. Nous avons entre autre évalué avec succès 150 échantillons hépatiques qui ont été largement caractérisés pour plusieurs phénotypes. Dans ces échantillons, nous avons pu valider 13 gènes ADME avec cis-eQTL précédemment rapportés et de découvrir et de 13 autres gènes ADME avec cis eQTLs qui n'avaient pas été observés en utilisant des méthodes standard. Enfin, à l'appui de ce travail, un outil logiciel a été développé, Opitimus Primer, pour aider pour aider au développement du test. Le logiciel a également été utilisé pour aider à l'enrichissement de cibles génomiques pour d'expériences séquençage. Le contenu ainsi que la conception, l’optimisation et la validation de notre panel le distingue largement de l’ensemble des essais commerciaux couramment disponibles sur le marché qui comprennent soit des marqueurs fonctionnels pour seulement un petit nombre de gènes, ou alors n’offre pas une couverture adéquate pour les gènes connus d’ADME. Nous pouvons ainsi conclure que l’essai que nous avons développé est et continuera certainement d’être un outil d’une grande utilité pour les futures études et essais cliniques dans le domaine de la pharmacocinétique, qui bénéficieraient de l'évaluation d'une longue liste complète de gènes d’ADME.

Isolated greater tuberosity fractures of the proximal humerus : validation and clinical implications for a new radiologic measurement method and classification

Pre-publication drafts are reproduced with permission and copyright © 2013 of the Journal of Orthopaedic Trauma [Mutch J, Rouleau DM, Laflamme GY, Hagemeister N. Accurate Measurement of Greater Tuberosity Displacement without Computed Tomography: Validation of a method on Plain Radiography to guide Surgical Treatment. J Orthop Trauma. 2013 Nov 21: Epub ahead of print.] and copyright © 2014 of the British Editorial Society of Bone and Joint Surgery [Mutch JAJ, Laflamme GY, Hagemeister N, Cikes A, Rouleau DM. A new morphologic classification for greater tuberosity fractures of the proximal humerus: validation and clinical Implications. Bone Joint J 2014;96-B:In press.]

Generic and diabetes-specific well-being in the AT.LANTUS follow-on study : further psychometric validation of the W-BQ28 indicates its utility in research and clinical practice in type 2 diabetes in the UK

Aims  To undertake further psychometric validation of the W-BQ28 to determine its suitability for use in adults with Type 2 diabetes in the UK using data from the AT.LANTUS follow-on study.

Methods  A total of 353 people with Type 2 diabetes participated in the AT.LANTUS Follow-on study, completing measures of well-being (W-BQ28), treatment satisfaction (DTSQ) and self-care (SCI-R). Confirmatory factor analyses was used to confirm the W-BQ28 structure and internal consistency reliability was assessed. Additional statistical tests were conducted to explore convergent, divergent and known-groups validity. Minimal important differences were calculated using distribution and anchor-based techniques.

Results  Structure of the W-BQ28 (seven four-item subscales plus 16-item generic and 12-item diabetes-specific scales) was confirmed (comparative fit index = 0.917, root mean square error of approximation (RMSEA) = 0.057). Internal consistency reliability was satisfactory (four-item subscales: alpha = 0.73–0.90; 12/16-item scales: α = 0.84–0.90). Convergent validity was supported by expected moderate to high correlations (rs = 0.35–0.67) between all W-BQ28 subscales (except Energy); divergent validity was supported by expected low to moderate correlations with treatment satisfaction (rs = −0.03–0.52) and self-care (rs = 0.02–0.22). Known-groups validity was supported with statistically significant differences by sex, age and HbA1c for expected subscales. Minimal important differences were established (range 0.14–2.90).

Conclusions  The W-BQ28 is a valid and reliable measure of generic and diabetes-specific well-being in Type 2 diabetes in the UK. Confirmation of the utility of W-BQ28 (including establishment of minimal important differences) means that its use is indicated in research and clinical practice.

Validation and development of a clinical prediction rule in clinically suspected community-acquired pneumonia

To develop a mathematical model to predict the probability of having community-acquired pneumonia and to evaluate an already developed prediction rule that has not been validated in a clinical scenario.

Validation of the Italian version of the Yale-Brown Obsessive Compulsive Scale-Second Edition (Y-BOCS-II) in a clinical sample

OBJECTIVE: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most widely accepted measure of obsessive-compulsive disorder (OCD) symptom severity. Recently, the scale has been revised into a second edition (Y-BOCS-II) in order to improve its measurement properties. The present study aimed to evaluate the psychometric properties of the Italian version of the Y-BOCS-II Severity Scale (SS) in a large clinical sample. METHOD: The original version of the Y-BOCS-II was translated into Italian, which involved forward and back-translation procedures. The Italian Y-BOCS-II-SS was administered to one hundred twenty-five treatment-seeking adults with OCD, together with the original Y-BOCS-SS and a battery of self-report measures assessing OCD symptom severity and depressive and anxious symptomology. The factor structure, internal consistency, temporal stability, and construct validity were investigated on the whole sample, while inter-rater and test-retest reliability were assessed on a subsample of participants. RESULTS: Factor analyses revealed a two-factor structure different from those of the original scale, comprising (1) symptom severity; and (2) interference from symptoms. Internal consistency, test-retest reliability over a 2-week period and inter-rater reliability were satisfactory. The Y-BOCS-II-SS also showed excellent construct validity (and better than the Y-BOCS-SS), with good convergent and discriminant validity when assessed against other OCD symptom measures and measures of depression, anxiety and worry. CONCLUSIONS: These findings suggest that the Italian version of the Y-BOCS-II-SS retains the adequate psychometric properties of the original and that it can be confidently used as an assessment tool of OCD symptoms in both clinical and research settings.

Development and Validation of a Clinical Scale for the Evaluation of Forearm Skin Photoaging

Background: Despite the focus on facial photoaging ratings, there are few classifications developed for forearm skin aging assessment.Objective: To develop and validate a clinical scale for the evaluation of forearm skin aging.Methods: Three clinical dermatology faculty members selected, discussed, and appraised the main signs of forearm photoaging. The validation of the resulting scale was performed by 5 assessors who were previously trained to classify 102 photographs of forearms with different degrees of aging. Retests were performed in 15 days.Results: There was significant correlation between the selected variables and the subjective global aging scale. The developed scale showed high internal consistency (Cronbach's alpha = 0.87) and high correlation with the global photoaging scale (rho = 0.92). Inter- and intraobserver final scores showed high agreement.Conclusion: A validated clinical photoaging scale for forearms with internal consistency, reliability, and validity was developed.

Sleep quality, the neglected outcome variable in clinical studies focusing on locomotor system; a construct validation study

In addition to general health and pain, sleep is highly relevant to judging the well-being of an individual. Of these three important outcome variables, however, sleep is neglected in most outcome studies.Sleep is a very important resource for recovery from daily stresses and strains, and any alteration of sleep will likely affect mental and physical health, especially during disease. Sleep assessment therefore should be standard in all population-based or clinical studies focusing on the locomotor system. Yet current sleep assessment tools are either too long or too specific for general use.

Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules

Background The loose and stringent Asthma Predictive Indices (API), developed in Tucson, are popular rules to predict asthma in preschool children. To be clinically useful, they require validation in different settings. Objective To assess the predictive performance of the API in an independent population and compare it with simpler rules based only on preschool wheeze. Methods We studied 1954 children of the population-based Leicester Respiratory Cohort, followed up from age 1 to 10 years. The API and frequency of wheeze were assessed at age 3 years, and we determined their association with asthma at ages 7 and 10 years by using logistic regression. We computed test characteristics and measures of predictive performance to validate the API and compare it with simpler rules. Results The ability of the API to predict asthma in Leicester was comparable to Tucson: for the loose API, odds ratios for asthma at age 7 years were 5.2 in Leicester (5.5 in Tucson), and positive predictive values were 26% (26%). For the stringent API, these values were 8.2 (9.8) and 40% (48%). For the simpler rule early wheeze, corresponding values were 5.4 and 21%; for early frequent wheeze, 6.7 and 36%. The discriminative ability of all prediction rules was moderate (c statistic ≤ 0.7) and overall predictive performance low (scaled Brier score < 20%). Conclusion Predictive performance of the API in Leicester, although comparable to the original study, was modest and similar to prediction based only on preschool wheeze. This highlights the need for better prediction rules.