Évaluation du statut de phosphorylation de STAT1 par cytométrie en flux / Evaluation of STAT1 Phosphorylation Status by Flow Cytometry

INTRODUCTION: Une demande d'introduction d'une nouvelle analyse au Répertoire québécois et système de mesure des procédures de biologie médicale (ci-après nommé Répertoire) a été transmise à l'Institut national d'excellence en santé et en services sociaux (INESSS) à travers le mécanisme d'évaluation des nouvelles analyses de biologie médicale. Le mandat vise à évaluer la pertinence d'introduire le statut de phosphorylation de la protéine STAT1 par cytométrie en flux au Répertoire. MÉTHODOLOGIE: L'évaluation a été réalisée selon l'approche basée sur l'appréciation globale de la valeur que l'Institut préconise dans son Énoncé de principes et fondements éthiques, et qui stipule qu'une intervention apporte de la valeur dans la mesure où son usage ou sa mise en place contribue à la triple finalité du système de santé et de services sociaux dans le contexte québécois. La démarche d'évaluation comprend une revue de la documentation scientifique, une recherche de la littérature grise et une consultation ad hoc menée auprès de cliniciens spécialisés en immunologie-allergologie pédiatrique et adulte. Une revue de la littérature économique a été réalisée concernant l'efficience du statut de phosphorylation de STAT1 (pSTAT1). Une analyse d'impact budgétaire considérant les coûts liés à l'ajout au Répertoire de ce test a également été réalisée. Les coûts ont été projetés sur un horizon de trois ans selon la perspective du système de soins de santé québécois. L'ensemble des données scientifiques, contextuelles et expérientielles a été interprété et apprécié à l'aide d'une approche basée sur l'appréciation globale de la valeur définie selon cinq dimensions : socioculturelle, populationnelle, clinique, organisationnelle et économique. Les constats issus de cette démarche évaluative ont servi à guider les discussions et le processus d'analyse de la Direction de l'évaluation des médicaments et des technologies à des fins de remboursement. CONTEXTE DE L'ÉVALUATION: Les erreurs innées de l'immunité (EII), précédemment appelées déficits immunitaires primaires (DIP), sont un groupe de maladies génétiques qui se manifestent entre autres par une susceptibilité accrue aux infections récurrentes, atypiques, sévères ou chroniques, aux réactions allergiques, inflammatoires ou auto-immunes, aux insuffisances médullaires et à certains cancers. Ces maladies sont monogéniques et causées par des variants germinaux pathogènes qui entraînent la perte ou le gain de fonction d'un des gènes impliqués dans les EII. Plusieurs protéines sont impliquées dans les EII, telles que celles de la voie de signalisation JAK/STAT. La famille des STAT comprend sept membres : STAT1, 2, 3, 4, 5A, 5B et 6. Une perte de fonction de STAT1 peut être responsable d'une susceptibilité accrue aux infections mycobactériennes. Les mutations activatrices de STAT1 provoquent un défaut de déphosphorylation qui se manifeste cliniquement par de la candidose mucocutanée chronique et des manifestations auto-immunes systémiques. DIMENSION SOCIOCULTURELLE: Plusieurs des sociétés savantes consultées s'étant positionnées sur le sujet recommandent le test du statut de pSTAT1 dans le diagnostic de certaines EII. Les cliniciens consultés sont aussi de cet avis. L'ajout éventuel d'un test fonctionnel comme celui de pSTAT1 est en concordance avec la Politique québécoise pour les maladies rares, Pour une meilleure reconnaissance et prise en charge des personnes atteintes de maladies rares, qui a été publiée en 2023. Cette politique vise à « optimiser l'accès à des soins et à des services de santé de qualité, sécuritaires, équitables, inclusifs et adaptés aux besoins particuliers des patients atteints de maladies rares, et culturellement sensibles ¼. Dimension populationnelle: Les trois types de dysfonctions associés à la phosphorylation de la protéine STAT1 (le gain ou la perte de fonction et la présence d'autoanticorps anti-IFN-γ neutralisants) peuvent être détectés par le test de cytométrie en flux (CMF). Le traitement des dysfonctions de STAT1 inclut principalement des combinaisons d'antifongiques ou d'antibiotiques souvent à long terme, des greffes de cellules souches hématopoïétiques (GCSH) et des inhibiteurs de la voie JAK/STAT. L'ajout du test de pSTAT1 au Répertoire contribuerait à la prise en charge rapide des patients et aiderait au choix de traitement, limitant ainsi l'errance médicale de ces patients. De plus, il permettrait de promouvoir la disponibilité du test et de standardiser les résultats obtenus. DIMENSION CLINIQUE: Afin de documenter la validité et l'utilité clinique du test, huit articles ont été retenus, soit six documents sur les pertes et les gains de fonction de STAT1 et deux articles sur la présence d'autoanticorps anti-IFN-γ. Les données montrent que l'évaluation du statut de pSTAT1 contribue à détecter les défauts de la boucle d'amplification IL-12/IFN-γ, à valider les anomalies fonctionnelles de STAT1 et à identifier la présence d'autoanticorps neutralisants anti-IFN-γ chez les patients cliniquement suspectés de certaines EII. Il sert également à évaluer la fonctionnalité des variants de signification incertaine (VSI) obtenus après des analyses génétiques et aide à cibler les investigations génétiques. Enfin, certaines données montrent que le test pSTAT1 améliore la prise en charge des patients, notamment en ce qui concerne le recours à l'antibioprophylaxie, à l'immunomodulation ou à la GCSH. DIMENSIONS ORGANISATIONNELLE ET ÉCONOMIQUE: Le test de pSTAT1 est offert par la grappe Montréal-CHU Sainte-Justine depuis 2014. Il a été effectué entre 2014 et 2023 sous un code générique qui regroupe tous les tests de CMF associés à une valeur pondérée inférieure à celle estimée du test pSTAT1. Le laboratoire demandeur mentionne avoir la capacité d'effectuer la totalité des analyses pour couvrir les besoins de toute la province et de faire face à une augmentation de la volumétrie, le cas échéant. Selon les cliniciens consultés, la réalisation du test localement apporterait un gain de temps et un soutien pour l'interprétation des résultats. L'accès à d'autres tests comme celui du dosage de l'IL-12 devrait demeurer disponible via les envois hors Québec pour couvrir des besoins exceptionnels. Une réponse sera obtenue en 24 à 36 heures; ce délai est jugé adéquat par les cliniciens consultés. L'efficience de l'analyse proposée ne peut être évaluée justement compte tenu du fait que les issues cliniques et les coûts ne peuvent être adéquatement mesurés ou approximés. Toutefois, l'introduction de l'analyse proposée au Répertoire devrait engendrer des économies d'environ 132 000 $ au cours des trois premières années. Bien que le coût de cette analyse ne puisse être justifié par des écrits scientifiques ou une évaluation robuste, aucun signal n'indique que son utilisation, spécifique au contexte de certaines EII, pourrait constituer une utilisation non responsable des ressources. Le risque économique de son introduction est considéré comme très faible. CONCLUSIONS: À la lumière des constats formulés ci-dessus, l'INESSS recommande l'introduction de l'analyse portant sur l'évaluation du statut de phosphorylation de STAT1 par cytométrie en flux au Répertoire, étant donné que: cette analyse est recommandée par les sociétés savantes et les cliniciens spécialisés dans le diagnostic de certaines erreurs innées de l'immunité; la littérature scientifique montre que le test permet la détection des dysfonctions de STAT1 et la vérification de la fonctionnalité des VSI. Il aide à la prise en charge adéquate des patients, afin de diminuer l'errance diagnostique souvent observée avec les maladies rares et d'offrir un traitement approprié rapidement; l'analyse est disponible depuis plus de dix années dans le réseau québécois de la santé et des services sociaux; le recours à l'analyse dans le contexte des EII constituerait une utilisation responsable des ressources; e risque économique de l'inscription de l'analyse au Répertoire est considéré comme étant très faible. Le ou les laboratoires désignés devront satisfaire aux exigences de la norme ISO 15189.

INTRODUCTION: The Institut national d'excellence en santé et en services sociaux (INESSS) has received a request to introduce a new assay to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire), through the evaluation mechanism for new medical biology assays. The mandate is to evaluate the relevance of introducing the phosphorylation status of the STAT1 protein by flow cytometry into the Répertoire. METHODOLOGY: The evaluation was conducted according to the overall value assessment approach advocated by the Institute in its Statement of Ethical Principles and Foundations, which stipulates that an intervention brings value insofar as its use or implementation contributes to the triple aim of the health and social services system in Quebec. The evaluation process included a review of the scientific literature, a grey literature search and an ad hoc consultation with clinicians specializing in pediatric and adult immunologyallergology. A review of the economic literature was conducted on the efficiency of STAT1 phosphorylation status (pSTAT1). A budget impact analysis was also conducted, considering the costs associated with adding this test to the Répertoire. Costs were projected over a three-year horizon from the perspective of the Quebec healthcare system. All scientific, contextual, and experiential data were interpreted and assessed using an approach based on an overall value assessment defined according to five dimensions: sociocultural, population-based, clinical, organizational, and economic. The findings of this evaluative approach were used to guide the discussions and analysis process of the Direction de l'évaluation des médicaments et des technologies à fins de remboursement. EVALUATION CONTEXT: Inborn errors of immunity (IEIs), previously known as primary immune deficiencies (PIDs), are a group of genetic diseases manifested by, among other things, increased susceptibility to recurrent, atypical, severe, or chronic infections, allergic, inflammatory, or autoimmune reactions, bone marrow failure and certain cancers. These diseases are monogenic and caused by pathogenic germline variants that result in the loss or gain of function of one of the genes involved in IEIs. Several proteins are involved in IEIs, such as those of the JAK/STAT signaling pathway. The STAT family comprises seven members: STAT1, 2, 3, 4, 5A, 5B and 6. Loss of STAT1 function may be responsible for increased susceptibility to mycobacterial infections. Activating mutations in STAT1 cause a dephosphorylation defect that manifests clinically as chronic mucocutaneous candidiasis and systemic autoimmune manifestations. Socio-Cultural Dimension: Several of the learned societies consulted on this subject recommend testing for pSTAT1 status in the diagnosis of certain IEIs. The clinicians consulted also share this opinion. The possible addition of a functional test such as pSTAT1 is in line with the Politique québécoise pour les maladies rares, Pour une meilleure reconnaissance et prise en charge des personnes atteintes de maladies rares, published in 2023. This policy aims to "optimize access to quality health care and services that are safe, equitable, inclusive, and adapted to the specific needs of culturally sensitive patients with rare diseases." Population Dimension: The three types of dysfunctions associated with phosphorylation of the STAT1 protein (gain or loss of function and the presence of neutralizing anti-IFN-γ autoantibodies) can be detected by flow cytometry testing. Treatment of STAT1 dysfunction mainly includes often long-term combinations of antifungals or antibiotics, hematopoietic stem cell transplantation (HSCT), and inhibitors of the JAK/STAT pathway. The addition of the pSTAT1 test to the Répertoire would contribute to the rapid management of patients and help in the choice of treatment, thus limiting medical wandering for these patients. It would also promote the availability of the test and standardize the results obtained. Clinical Dimension: In order to document the validity and clinical utility of the test, eight papers were selected: six papers on loss and gain of function of STAT1 and two papers on the presence of antiIFN-γ autoantibodies. The data show that evaluation of pSTAT1 status helps to detect defects in the IL-12/IFN-γ amplification loop, validate STAT1 functional abnormalities and identify the presence of neutralizing anti-IFN-γ autoantibodies in patients clinically suspected of certain IEIs. It is also used to assess the functionality of variants of uncertain significance (VUSs) obtained after genetic analysis and helps target genetic investigations. Finally, there is some evidence that pSTAT1 improves patient management, particularly regarding the use of antibiotic prophylaxis, immunomodulation, or HSCT. Organizational and Economic Dimensions: The pSTAT1 test has been offered by the Montreal-CHU Sainte-Justine laboratories since 2014. It was performed between 2014 and 2023 under a generic code that groups together all flow cytometry tests associated with a weighted value lower than that estimated for the pSTAT1 test. The applicant laboratory states that it has the capacity to perform all the tests to cover the needs of the entire province, and to cope with any increase in volume. According to the clinicians consulted, performing the test locally would save time and provide support in interpreting results. Access to other tests, such as the IL-12 assay, should remain available via shipments outside Quebec to cover exceptional needs. A response will be obtained within 24 to 36 hours; this timeframe is deemed adequate by the clinicians consulted. The efficiency of the proposed analysis cannot be accurately evaluated, as clinical outcomes and costs cannot be adequately measured or approximated. However, the introduction of the proposed analysis to the Répertoire is expected to generate savings of approximately $132,000 over the first three years. Although the cost of this analysis cannot be justified by scientific literature or robust evaluation, there are no indications that its use, specific to the context of certain IEIs, might constitute an unaccountable use of resources. The economic risk of its introduction is considered very low. CONCLUSIONS: Considering the above findings, the INESSS recommends the introduction of the analysis of STAT1 phosphorylation status by flow cytometry to the Répertoire, given that: This analysis is recommended by learned societies and clinicians specializing in the diagnosis of certain innate immune errors; the scientific literature shows that the test enables detection of STAT1 dysfunction and verification of VUS functionality. It helps to ensure that patients are properly managed, so as to reduce the diagnostic wandering often observed with rare diseases, and to offer appropriate treatment rapidly; analysis has been available for over ten years in the Quebec health and social services network; the use of analysis in the context of IEIs would be a responsible use of resources; the economic risk of listing the analysis in the Répertoire is considered to be very low. The designated laboratory(ies) must meet ISO 15189 requirements.

Directrices de la OMS sobre gestión de la sangre y los componentes sanguíneos como medicamentos esenciales. Anexo 3 del sexagésimo sétimo informe del Comité de Expertos de la OMS en Patrones Biológicos

La OMS define los medicamentos esenciales como aquellos productos medicinales que satisfacen las necesidades sanitarias de la mayoría de la población. Por consiguiente, deben estar disponibles en todo momento, en cantidad suficiente y en las formulaciones adecuadas, y con calidad y asequibilidad garantizadas. Estas directrices de la OMS tienen por objeto proporcionar un marco de referencia para establecer la supervisión reguladora de la sangre y los componentes sanguíneos destinados a transfusión como medicamentos esenciales. El concepto subyacente es que tales sangre y componentes sanguíneos son productos terapéuticos biológicos de origen humano, cuya preparación debe estar sujeta a normalización y supervisión reguladoras para garantizar su calidad, seguridad y eficacia. El marco proporcionado en estas directrices es parecido al que se aplica ampliamente para la regulación de los medicamentos producidos bajo las buenas prácticas de preparación actuales, pero adaptado para abordar los atributos específicos de la sangre y los componentes sanguíneos para transfusión, que los distinguen de los productos medicinales derivados del plasma y de los medicamentos (o productos farmacéuticos) en general. En las jurisdicciones donde los marcos jurídicos en vigor para los medicamentos fabricados con arreglo a las buenas prácticas de preparación actuales de las preparaciones farmacéuticas no se apliquen a la sangre y los componentes sanguíneos, la regulación paralela basada en el modelo proporcionado por las presentes directrices incluiría la aplicación de las buenas prácticas de preparación análogas para tales productos.

Plasma de convaleciente para el tratamiento de la COVID-19: Protocolo para el acceso y uso en Venezuela / Convalescent Plasma for the Treatment of COVID-19: Protocol for access and use in Venezuela

En diciembre 2019, en Wuhan, China, se registró un aumento inusual de casos de infección respiratoria aguda de rápida progresión y alta letalidad. Al poco tiempo es identificado el agente causal, un coronavirus denominado SARS-CoV-2 y se caracteriza una nueva enfermedad, COVID-19. En ausencia hasta el momento de tratamientos específicos, eficaces y seguros, se justifica explorar alternativas científicamente fundamentadas a nuestro alcance como el uso de Plasma de Convaleciente (PC-CoV19) como coadyuvante para el tratamiento de la COVID-19. El plasma de pacientes recuperados de una enfermedad infecciosa, Plasma de Convaleciente, ha sido utilizado en el tratamiento de patologías infecciosas. Hay antecedentes inmediatos de su uso en enfermedades producidas por otro tipo de coronavirus y se registran experiencias y estudios clínicos con resultados preliminares durante esta pandemia. Quimbiotec, empresa productora de hemoderivados y fármacos recombinantes del Estado venezolano, y el Banco Municipal de Sangre, definen un protocolo para promover condiciones para la aféresis, procesamiento, conservación, almacenamiento, distribución, transfusión y evaluación de la seguridad y eficacia del PC-CoV19 como alternativa en el tratamiento de la COVID-19 en Venezuela. Se incluye la identificación de capacidades y de talento, la estructura física, equipos y especialistas necesarios, así como la definición de procesos para establecer rutinas controladas y auditables para sentar bases del acceso y uso del PC-CoV19 en el Sistema Nacional de Salud de Venezuela y preparar el diseño y ejecución de estudios clínicos. Se presenta el Protocolo y algunos nudos críticos en su ejecución a la fecha, herramientas y estrategias utilizadas para su solución(AU)

On December 2019, in Wuhan, China, there was an unusual increase in cases of a fast-progressing acute respiratory infection with high fatality rate. Soon after, the causing agent is identiied, a coronavirus called SARS-CoV-2, and a new disease, COVID-19 is characterized. Currently, in the absence of specific, effective and safe treatments, it is justified to explore all scientifically based alternatives available to us, such as the use of Convalescent Plasma (PC-CoV19) as acoadjutant treatment of COVID-19.Plasma from patients who have recovered from an infectious disease, Convalescent Plasma, has been used in the treatment of other infectious disease. There is recent history of its use in diseases caused by another type of coronavirus, and clinical experiences and studies have already been published with preliminary results during this pandemic. Quimbiotec, a Venezuelan State public company that produces blood products and recombinant drugs, and Banco Municipal de Sangre, deined a protocol to promote conditions for aphaeresis, processing, conservation, storage, distribution, transfusion, and evaluation of safety and eficacy of PC-CoV19 as an alternative for the treatment of COVID-19 in Venezuela. This protocol includes identification of capacities, physical structure, equipment and skills, talent, professionals needed, as well as a definition of processes to establish controlled and auditable routines to lay the foundations for access and use of PC-CoV19 in the Venezuela Health System, and prepare the design and implementation of clinical studies. The protocol and currently critical points in its implementation, as well as tools and strategies used for its solution, are presented(AU)

Diagnostic performance of a commercial ELISA used as a complementary test for bovine tuberculosis in two bovine herds with different disease status / Desempenho diagnóstico de um ELISA comercial usado como teste complementar para tuberculose bovina em dois rebanhos bovinos com diferentes estágios de controle da doença

Bovine tuberculosis is a worldwide spread zoonotic disease. Intradermal tuberculinizations are the most used diagnostic tests in the world. Serological tests can be an ancillary diagnosis for bovine tuberculosis. The objective of this study was to evaluate the diagnostic performance of the ELISA Mycobacterium Bovis Antibody Test Kit IDEXX ™ in infected herds, which were in different disease control stages. One hundred and twenty animals from two dairy herds of Minas Gerais state, Brazil, were subjected to the ELISA serological test and the comparative cervical tuberculin test (CCT). Diagnostic test parameters were estimated using Bayesian latent class models and concordance between tests estimated by the frequentist approach. The ELISA test presented lower sensitivity than CCT in both herds. Its sensitivity was higher in the herd in sanitation process. Specificity estimates were above 95% in both herds. Kappa index indicated low concordance or even disagreement between tests. According to the results, the ELISA IDEXX should not be used as substitution for CCT. The tests must not be associated in series. Parallel association increased diagnostic sensitivity in the herd which was in the process of sanitation.(AU)

A tuberculose bovina é uma zoonose de distribuição mundial cujos testes mais utilizados para o diagnóstico são as tuberculinizações intradérmicas, simples e compartivas. Contudo, testes sorológicos podem constituir diagnósticos auxiliares. O objetivo deste estudo foi avaliar o desempenho diagnóstico do teste ELISA Mycobacterium Bovis Antibody Test Kit IDEXX ® em rebanhos bovinos infectados, que se encontravam em diferentes estágios de controle da doença. Cento e vinte animais de dois rebanhos leiteiros provenientes do estado de Minas Geais-Brasil foram submetidos ao ELISA e à tuberculinização cervical compartiva (TCC). Avaliou-se o desempenho dos testes por meio de modelos Bayesianos de classe latente e a concordância entre os eles, por meio de estatística frequentista. Uma maior sensibilidade do teste foi observada no rebanho previamente tuberculinizado. Em ambos os rebanhos o TCC foi mais sensível que o ELISA. Especificidade acima de 95% foi encontrada em ambos os rebanhos. Foram observadas baixa concordância ou mesmo discordância entre os testes. De acordo com os resultados obtidos, o teste ELISA-IDEXX não deve ser utilizado em substituição à TCC, tampouco devem ser associados em série. Houve aumento da sensibilidade quando os testes foram associados em paralelo no rebanho que já se encontrava em processo de saneamento.(AU)

Diagnostic performance of a commercial ELISA used as a complementary test for bovine tuberculosis in two bovine herds with different disease status / Desempenho diagnóstico de um ELISA comercial usado como teste complementar para tuberculose bovina em dois rebanhos bovinos com diferentes estágios de controle da doença

Bovine tuberculosis is a worldwide spread zoonotic disease. Intradermal tuberculinizations are the most used diagnostic tests in the world. Serological tests can be an ancillary diagnosis for bovine tuberculosis. The objective of this study was to evaluate the diagnostic performance of the ELISA Mycobacterium Bovis Antibody Test Kit IDEXX ™ in infected herds, which were in different disease control stages. One hundred and twenty animals from two dairy herds of Minas Gerais state, Brazil, were subjected to the ELISA serological test and the comparative cervical tuberculin test (CCT). Diagnostic test parameters were estimated using Bayesian latent class models and concordance between tests estimated by the frequentist approach. The ELISA test presented lower sensitivity than CCT in both herds. Its sensitivity was higher in the herd in sanitation process. Specificity estimates were above 95% in both herds. Kappa index indicated low concordance or even disagreement between tests. According to the results, the ELISA IDEXX should not be used as substitution for CCT. The tests must not be associated in series. Parallel association increased diagnostic sensitivity in the herd which was in the process of sanitation.(AU)

A tuberculose bovina é uma zoonose de distribuição mundial cujos testes mais utilizados para o diagnóstico são as tuberculinizações intradérmicas, simples e compartivas. Contudo, testes sorológicos podem constituir diagnósticos auxiliares. O objetivo deste estudo foi avaliar o desempenho diagnóstico do teste ELISA Mycobacterium Bovis Antibody Test Kit IDEXX ® em rebanhos bovinos infectados, que se encontravam em diferentes estágios de controle da doença. Cento e vinte animais de dois rebanhos leiteiros provenientes do estado de Minas Geais-Brasil foram submetidos ao ELISA e à tuberculinização cervical compartiva (TCC). Avaliou-se o desempenho dos testes por meio de modelos Bayesianos de classe latente e a concordância entre os eles, por meio de estatística frequentista. Uma maior sensibilidade do teste foi observada no rebanho previamente tuberculinizado. Em ambos os rebanhos o TCC foi mais sensível que o ELISA. Especificidade acima de 95% foi encontrada em ambos os rebanhos. Foram observadas baixa concordância ou mesmo discordância entre os testes. De acordo com os resultados obtidos, o teste ELISA-IDEXX não deve ser utilizado em substituição à TCC, tampouco devem ser associados em série. Houve aumento da sensibilidade quando os testes foram associados em paralelo no rebanho que já se encontrava em processo de saneamento.(AU)

Caution Is Required When Using Non-Food and Drug Administration-Cleared Assays to Diagnose Sexually Transmitted Infections in Children.

Nucleic acid amplification testing is the gold-standard for Chlamydia trachomatis and Neisseria gonorrhoeae testing in adults. We present 3 pediatric cases in which testing resulted in probable false-positive results. Clinicians should avoid tests without clearance from a regulatory agency and should maintain consistent communication with laboratories.

Validez y fiabilidad de prueba diagnóstica en entrenamiento sobre procedimientos laparoscópicos básicos / Validity and reliability of diagnostic testing in training on basic laparoscopic procedures

Introducción: la falta de uniformidad en las competencias de cirugía mínimamente invasiva motivó la utilización de la evaluación diagnóstica para determinar los conocimientos previos que poseen los educandos de posgrado sobre este tema.Objetivo: constatar la validez y fiabilidad de los resultados que se obtuvieron con la prueba diagnóstica del entrenamiento "Intensivo en procedimientos laparoscópicos básicos". Métodos: se exploraron los niveles cognoscitivos de las dimensiones: sutura laparoscópica, disección del Triangulo de Calot en la colecistectomía laparoscópica, tratamiento de la litiasis coledociana y Apendicectomía Laparoscópica. Se aplicó un test de Verdadero o Falso a especialistas en Cirugía General, Pediátrica y Coloproctología. Se utilizó la consulta a expertos como fuente de evidencia de validez de contenido de la prueba y la fórmula de Kuder-Richardson 20 para determinar su coeficiente de fiabilidad. Resultados: se consideró apropiada la validez en la definición precisa del universo de contenido que se deseaba medir. El 75 por ciento de los ítems no se diseñaron apropiadamente por lo que no se acreditó la validez en el grado de suficiencia del ámbito que se deseaba evaluar. Conclusiones: no se constató la validez y fiabilidad de los resultados que se obtuvieron con la prueba diagnóstica del entrenamiento "Intensivo en procedimientos laparoscópicos básicos". Se perfeccionó el instrumento de evaluación diagnóstica de dicho entrenamiento a partir del análisis de la validez y fiabilidad de los resultados obtenidos(AU)

Introduction: the lack of uniformity in basic skills of laparoscopic surgery led to the use of diagnostic assessment to determine prior knowledge level by graduate students. Objective: to prove the validity and reliability of the results obtained with the diagnostic test for students of "Basic laparoscopic procedures intensive training". Methods: there were explored the following cognitive dimensions: Laparoscopic suturing, dissection of Calot triangle in laparoscopic cholecystectomy, Treatment of cholelithiasis and Laparoscopic appendectomy. A True or False Test was applied to specialists in General Surgery, Pediatric and Coloproctology. Consulting experts was considered as a source of evidence for content validity of the test and the Kuder-Richardson formula 20 was used to determine the reliability coefficient. Results: it was considered appropriated the validity in the definition of content, which was intended to measure. 75 percent of items were not appropriated designed, that's why validity in sufficiency's grade was not accredited. Conclusions: the diagnosed test for "Basic laparoscopic procedures intensive training" was improved like consequence of validity and fidelity's analysis from the obtained results(AU)

Diagnosis of Helicobacter pylori infection by invasive and noninvasive tests

Although several invasive and noninvasive tests have been developed for the diagnosis of Helicobacter pylori infection, all of the tests have their limitations. We conducted a study to investigate and compare the suitability of rapid urease test (RUT), serology, histopathology and stool antigen tests with polymerase chain reaction (PCR) for detection of H. pylori, and correlate the diagnostic methods with PCR. Eighty nine patients (61 adults, 28 children) referred to the Firoozgar Hospital and Children Medical Center Hospital for diagnostic upper gastrointestinal endoscopy entered to the study and noninvasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in feces were measured. The biopsies were utilized for histological examination, RUT and PCR. The H. pylori statuses were evaluated by the positivity of ureC PCR in biopsy specimens and 53 subjects had H. pylori positive result. Histopathology showed high overall performance in adults and children with sensitivity and specificity 100% and 90%, respectively. Sensitivity, specificity, and accuracy for stool antigen test were 87.8%, 75% and 82%, respectively. Correlation of RUT, serology (IgG), histopathology and stool antigen tests with PCR were 0.82, 0.32, 0.91 and 0.63, respectively. In conclusion, the RUT and histopathology are as accurate as the PCR of biopsy and stool antigen test can consider as appropriate noninvasive test for detection of H. pylori infection.(AU)

Utilização da escala de dificuldade percebida na produção da fala na avaliação aeróbia em cicloergometro (Talk Test) / Use the scale of perceived difficulty in production of speech in the assessment aerobic cycle ergometer (Talk Test)

O Talk Test (TT) é uma ferramenta que avalia subjetivamente a intensidade ótima para a prática de exercício com base na capacidade de manter uma conversa confortável durante o esforço. O objetivo do presente estudo foi obter evidências de validade (concorrente e de constructo) do TT. Quatorze sujeitos, 7 mulheres e 7 homens (22 ± 8 anos, 69 ± 15 Kg, 169 ± 10 cm, 21 ± 12 %G) foram submetidos a um teste progressivo em cicloergmetro, carga inicial de 25 watts e incremento de 25 watts a cada 2 minutos (60-70 RPM) até a exaustão. Ao final dos estágios o avaliado recitava três vezes uma frase conhecida, indicando a sua Dificuldade Percebida na Produção da Fala (DPPF) de acordo com a escala proposta por Rotstein et al. (2004). A carga com valor 7, correspondente à “difícil” (L7DPPF) foi utilizada como indicadora do segundo limiar fisiológico, assim como o do Ponto de Deflexão da Freqüência Cardíaca (PDFC), identificado pelo Dmáx positivo da diferença entre um ajuste polinomial de terceira ordem e ajuste linear de todos os pontos da relação FC / Carga. Para as análises foram empregados os testes Kolmogorov-Smirnov, Kruskall-Wallis, post-hoc de Dunn’s, e o método de Bland- Altman, além da correlação de Spearman (p<0,05). Não foram identificadas iferenças significativas entre L7DPPF e PDFC (p=0,03), além de serem associados à carga máxima atingida no teste (r=0,90 e r=0,81). As duas técnicas de identificação do LTF2 – PDFC e o L7DPPF – se mostraram semelhante pelo método Bland-Altman, (IC 95% = 0,41 – 1,46). Sendo o TT um indicador de aptidão aeróbia, o L7DPPF pode ser considerado um método para predizer LTF2.

Talk Test is a tool used to to evaluate by a subjective manner the optimal exercise intensity. It is based on individual capacity to maintain a confortable speech during the effort. The aim of the study was to verify evidence of validitiy (concurrent and constructo) of the Talk Test. Fourteen subjects (7 males and 7 females) volunteered to a cicle ergometer progressive test with intial load of 25 Watts and increments of 25 Watts each 2 minutes until exhaustion. Subjects should recite a known sentence for three times at the end of each stage and indicate their Perceived Speech Production Difficult (DPPF) accoding to the scale of Rotstein et al., (2004) where the load at the level 7 which is “difficult” was taken as a physiological threshold indicator. The Second Physiological Threshold (LT2) was considered the Heart Rate Deflection Point (PDFC) identified by the positive Dmax method. For analyzes were employed olmogorov-Smirnov test, Kruskal-Wallis post hoc Dunn's, and Bland- Altman, beyond the Spearman correlation (p <0.05). No significant differences were identified between L7DPPF and PDFC (p = 0.03), and are associated with the maximum load reached in the test (r = 0.90 and r = 0.81). Both techniques of identification of LTF2 - PDFC and L7DPPF - were similar by Bland- Altman method (95% CI = 0.41 to 1.46). TT being an indicator of aerobic fitness, the L7DPPF could be considered a method to predict LTF2.