Remarkable progress has been made in the development of effective treatments for patients with rheumatoid arthritis (RA). To ensure that a patient is optimally responding to treatment, consistent monitoring of disease activity is recommended. Established composite and individual disease activity measures often cannot be computed due to missing laboratory values. Simplified measures that can be calculated without a lab value have been developed and previous studies have validated these new measures, yet differences in their performance compared with established measures remain. Therefore, the goal of my doctoral research was to examine and evaluate disease activity and composite measures to facilitate monitoring of response in clinical care settings and inclusion of patients with missing laboratory values in epidemiological research. In the first study, the validity of two composite measures, the Clinical Disease Activity Index (CDAI) and the Disease Activity Score with 28 joint count (DAS28) was examined and both were significantly associated with a rheumatologist’s decision to change therapy (CDAI OR=1.58; 95% CI: 1.42, 1.76) (DAS28 OR=1.34; 95% CI 1.27,1.56). However, further evaluation using receiver operating characteristic (ROC) analysis found that they were not strong predictors of physician decisions to change therapy (AUC=0.75, 0.76, respectively). Thus, they should not be used to guide treatment decisions in the clinic. Two measures of disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are often not measured and impede the computation of composite measures of disease activity. In the second study, significant factors which may predict the measurement of the ESR and CRP were identified and included physician and clinical variables but no quantitative disease activity measures. Thus the suitability of the ESR and CRP as measures of disease activity is suspect. In the final study, I created a new composite measure, the modified disease activity score with 28 joint count (mDAS28), by replacing the laboratory value in the DAS28. The mDAS28 was then validated by comparing its performance with the DAS28. The measures were strongly correlated (r=0.87), and strong agreement was found between the two measures when categorizing patients to levels of disease activity (ĸ=0.77) and treatment response (ĸ=0.73). Therefore, the mDAS28 could be used in place of the DAS28 when laboratory values needed to compute the DAS28 are missing. In summary, I found that the CDAI and DAS28 were not strong predictors of the rheumatologist’s decision to change therapy. I also found that the variability in the measurement of ESR and CRP was not associated with disease activity. I was able to modify the DAS28 by replacing the laboratory measure and create a new simplified measure, the mDAS28. I also validated the mDAS28 for use in the clinic and in epidemiological research when the DAS28 is unavailable.

Utilizing multiple biomarkers in medical research is crucial for the diagnostic accuracy of detecting diseases. An optimal method for combining these biomarkers is essential to maximize the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC). The optimality of the likelihood ratio has been proven but the challenges persist in estimating the likelihood ratio, primarily on the estimation of multivariate density functions. In this study, we propose a non-parametric approach for estimating multivariate density functions by utilizing Smoothing Spline density estimation to approximate the full likelihood function for both diseased and non-diseased groups, which compose the likelihood ratio. Simulation results demonstrate the efficiency of our method compared to other biomarker combination techniques under various settings for generated biomarker values. Additionally, we apply the proposed method to a real-world study aimed at detecting childhood autism spectrum disorder (ASD), showcasing its practical relevance and potential for future applications in medical research. Change point detection for functional time series has attracted considerable attention from researchers. Existing methods either rely on FPCA, which may perform poorly with complex data, or use bootstrap approaches in forms that fall short in effectively detecting diverse change functions. In our study, we propose a novel self-normalized test for functional time series implemented via a non-overlapping block bootstrap to circumvent reliance on FPCA. The SN factor ensures both monotonic power and adaptability for detecting diverse change functions on complex data. We also demonstrate our test's robustness in detecting changes in the autocovariance operator. Simulation studies confirm the superior performance of our test across various settings, and real-world applications further illustrate its practical utility. / Doctor of Philosophy / In medical research, it is crucial to accurately detect diseases and predict patient outcomes using multiple health indicators, also known as biomarkers. Combining these biomarkers effectively can significantly improve our ability to diagnose and treat various health conditions. However, finding the best way to combine these biomarkers has been a long-standing challenge. In this study, we propose a new, easy-to-understand method for combining multiple biomarkers using advanced estimation techniques. Our method takes into account various factors and provides a more accurate way to evaluate the combined information from different biomarkers. Through simulations, we demonstrated that our method performs better than other existing methods under a variety of scenarios. Furthermore, we applied our new method to a real-world study focusing on detecting childhood autism spectrum disorder (ASD), highlighting its practical value and potential for future applications in medical research. Detecting changes in patterns over time, especially shifts in averages, has become an important focus in data analysis. Existing methods often rely on techniques that may not perform well with more complex data or are limited in the types of changes they can detect. In this study, we introduce a new approach that improves the accuracy of detecting changes in complex data patterns. Our method is flexible and can identify changes in both the mean and variation of the data over time. Through simulations, we demonstrate that this approach is more accurate than current methods. Furthermore, we applied our method to real-world climate research data, illustrating its practical value.

Objectif : Déterminer la fiabilité et la précision d’un prototype d’appareil non invasif de mesure de glucose dans le tissu interstitiel, le PGS (Photonic Glucose Sensor), en utilisant des clamps glycémiques multi-étagés. Méthodes : Le PGS a été évalué chez 13 sujets avec diabète de type 1. Deux PGS étaient testés par sujet, un sur chacun des triceps, pour évaluer la sensibilité, la spécificité, la reproductibilité et la précision comparativement à la technique de référence (le Beckman®). Chaque sujet était soumis à un clamp de glucose multi-étagé de 8 heures aux concentrations de 3, 5, 8 et 12 mmol/L, de 2 heures chacun. Résultats : La corrélation entre le PGS et le Beckman® était de 0,70. Pour la détection des hypoglycémies, la sensibilité était de 63,4%, la spécificité de 91,6%, la valeur prédictive positive (VPP) 71,8% et la valeur prédictive négative (VPN) 88,2%. Pour la détection de l’hyperglycémie, la sensibilité était de 64,7% et la spécificité de 92%, la VPP 70,8% et la VPN : 89,7%. La courbe ROC (Receiver Operating Characteristics) démontrait une précision de 0,86 pour l’hypoglycémie et de 0,87 pour l’hyperglycémie. La reproductibilité selon la « Clark Error Grid » était de 88% (A+B). Conclusion : La performance du PGS était comparable, sinon meilleure que les autres appareils sur le marché(Freestyle® Navigator, Medtronic Guardian® RT, Dexcom® STS-7) avec l’avantage qu’il n’y a pas d’aiguille. Il s’agit donc d’un appareil avec beaucoup de potentiel comme outil pour faciliter le monitoring au cours du traitement intensif du diabète. Mot clés : Diabète, diabète de type 1, PGS (Photonic Glucose Sensor), mesure continue de glucose, courbe ROC, « Clark Error Grid». / Objective: To determine the reliability and precision of a prototype of a non-invasive device for continuous measurement of interstitial glucose, the PGS (Photonic Glucose Sensor), using multi-level glycaemic clamp. Methods: The PGS was evaluated in 13 subjects with type 1 diabetes. Two PGS were tested with each subject, one on each triceps, to evaluate the sensitivity, specificity, reproducibility and accuracy compared to the reference technique, the glucose analyzer Beckman®. Each subject was submitted to a multi-level 8 hour glucose clamp at 3, 5, 8 and 12 mmol / L, 2 hours each. Results: The correlation between the PGS and the Beckman® was 0.70. For the detection of hypoglycaemia, the sensitivity was 63.4%, the specificity 91.6%, the positive predictive value (PPV) 71.8% and the negative predictive value (NPV) 88.2%. For the detection of hyperglycaemia, the sensitivity was 64.7% the specificity 92%, the PPV 70.8% and the NPV: 89.7%. The ROC (Receiver Operating Characteristics) curve showed an accuracy of 0.86 and 0.87 for hypoglycaemia and hyperglycaemia respectively. Reproducibility according to the Clark Error Grid was 88% in the A and B zone. Conclusion: The performance of the PGS was comparable or better than other continuous glucose monitoring devices on the market (Freestyle® Navigator, Medtronic Guardian® RT, Dexcom® STS-7) with the advantage that it has no needle. It is therefore an interesting device and hopefully, which could facilitate the monitoring in the intensive treatment of diabetes. Key words: Diabetes, type 1 diabetes, PGS (Photonic Glucose Sensor), ROC curve, Clark Error Grid, continuous glucose monitoring, CGMS.

Huit instruments d’évaluation du risque ont été appliqués sur 580 délinquants sexuels. Il s’agit du VRAG, du SORAG, du RRASOR, de la Statique-99, de la Statique-2002, du RM-2000, du MnSORT-R et du SVR-20. De plus, les sujets ont été cotés sur la PCL-R, qui vise la mesure de la psychopathie, mais qui a fait ses preuves en matière de prédiction de la récidive (Gendreau, Little, et Goggin, 1996). En vue de mesurer l’efficacité de ces instruments et de la PCL-R, une période de suivi de 25 ans a été observée. Aussi, une division de l’échantillon a été faite par rapport à l’âge au moment de la libération, afin de mesurer les différences entre les délinquants âgés de 34 ans et moins et ceux de 35 ans et plus. Le présent travail vise à répondre à trois objectifs de recherche, soit 1) Décrire l’évolution du risque en fonction de l’âge, 2) Étudier le lien entre l’âge, le type de délinquant et la récidive et 3) Comparer l’efficacité de neuf instruments structurés à prédire quatre types de récidive en fonction de l’âge. Les résultats de l’étude suggèrent que l’âge influence le niveau de risque représenté par les délinquants. Par ailleurs, les analyses des différents types de récidive indiquent que le type de victime privilégié par les délinquants influence également ce niveau de risque. Les implications théoriques et pratiques seront discutées. / Eight evaluation techniques demonstrating high risk sexual offenders has been taken upon 580 individual sexual offenders. They are among the VRAG, the SORAG, the RRASOR, the Static-99, the Static-2002, the RM-2000, the MnSORT-R ans the SVR-20. Also, the subjects have been quoted according to the PCL-R, which focuses on their mental health, however supporting the quotes by prediction and relaps (Gendreau, Little, et Goggin, 1996). With the ongoing measuring of the suitability of these instruments as well as the PCL-R, it will take a period of 25 years for the observance. As well, a group of subjects have been studied from the age they were let out of prison, to come up with conclusions differentiating the offenders aging 34 and less with the offenders aging 35 and older. The present work on this subject matter hopes to focus on three research objectives: 1) Describe the evolution of risk according to the age, 2) To study the common point between age, they type of offender, and their relaps, and 3) To compare the suitability of 9 instruments the predict 4 types of relaps according to their age. The study results suggest that age affects the level of risk posed by offenders. Furthermore, analyses of different types of recidivism indicate that the preferred type of victim offender also influences the level of risk. The theoretical and practical implications are discussed.

INTRODUÇÃO: O Hipotireoidismo congênito (HC) é uma das endocrinopatias mais frequentes em pediatria e pode causar retardo mental e do crescimento, se não for tratado precocemente. A determinação do nível do hormônio estimulador da tireoide em sangue total após o nascimento (TSHneo) constitui uma estratégia efetiva para o rastreamento de HC, embora não exista consenso em relação aos níveis considerados seguros para essa detecção. Muitos serviços utilizam os valores de corte do TSH neonatal de 10,0 e 15,0 ?UI/mL, por ensaios imunofluorimétricos. OBJETIVO: Analisar a capacidade de detecção dos casos de hipotireoidismo congênito por diferentes níveis de corte do TSH neonatal e os efeitos destes sobre o sistema de triagem neonatal para essa doença, em nascidos vivos avaliados pelo Programa de Triagem Neonatal (PTN) da rede pública do Estado de Mato Grosso (MT), de 01 de janeiro de 2010 a 31 de dezembro de 2012. MÉTODOS: Estudo de coorte, de corte transversal, com coleta retrospectiva de dados obtidos a partir do banco de dados do Serviço de Referência em Triagem Neonatal do Estado de Mato Grosso, de nascidos vivos no período 01/01/2010 a 31/12/2012 e avaliados pelo PTN-MT. Estes foram divididos em dois grupos: I. Controle: Crianças com exame de triagem neonatal normal; II. Estudo: Crianças com HC. Análise estatística incluiu o uso do teste qui-quadrado ou exato de Fischer para análise das características dos recém-nascidos entre os grupos e o teste t de Student ou não paramétrico de Mann-Whitney para análise dos níveis de TSH em sangue total de ambos os grupos e, avaliação das concentrações de TSH e T4 livre no soro, em crianças com HC. Construiu-se uma curva ROC (Receiver Operating Characteristic), para a avaliação dos pontos de corte do TSHneo. O nível de significância foi p<0,05. RESULTADOS: Entre as 111.705 crianças triadas pelo Programa, 50 tiveram o diagnóstico de HC, sob o ponto de corte do TSHneo de 5,0 ?UI/mL. A prevalência da doença foi de 1:2.234 nascidos vivos. A cobertura do Programa estadual foi de 73,9%. Para o Grupo II, os níveis do TSHneo foram superiores a 20,0 ?UI/mL em 61,4% das crianças e, os níveis de TSH no soro excederam este valor em 83,7%. A curva ROC identificou o ponto de corte do TSHneo de 5,03 ?UI/mL, como o correspondente à sensibilidade de 100% e a maior especificidade associada (93,7%). A área observada sob a curva foi de 0,9898 (p<0,0001). CONCLUSÕES: Observou-se uma cobertura inadequada do PTN-MT. O ponto de corte do TSH neonatal de 5,0 ?UI/mL, adotado pelo PTN-MT, foi confirmado pela curva ROC como o mais seguro para detectar HC e determinou a elevada prevalência da doença no Estado de Mato Grosso / INTRODUCTION: Congenital hypothyroidism (CH) is a very common pediatric endocrine disorder and can cause mental and growth retardation without early treatment. Measuring the total blood thyroid-stimulating hormone level after birth (TSHneo) is an effective screening strategy for CH, although there is not yet a consensus on the appropriate diagnostic levels. Many services use the neonatal TSH cut-off points of 10.0 and 15.0 uIU/mL per imunofluorimetric assay. OBJECTIVE: The aim of the present study was to analyze the ability of various TSHneo cutoff values to detect CH and their effects on the Newborn Screening Program (NSP) of the State of Mato Grosso (MT) from January 1, 2010, to december 31, 2012. METHODS: Cohort study, cross-sectional, based on retrospective data collection obtained from the database of the Reference Service for Neonatal Screening of the State of Mato Grosso, for all live births from January 1, 2010, to December 31, 2012, reviewed by NSP-MT. The infants were divided into two groups: I-Control: infants with normal newborn screening tests and II-Study: infants with CH. Statistical analysis included the chi-square or Fisher\'s exact test to compare the characteristics of the newborns from both groups and Student\'s t-test or the non-parametric Mann-Whitney test to analyse the total blood TSH level from both groups of infants and evaluate the serum TSH and free thyroxine (T4) concentrations in infants with CH. A Receiver Operating Characteristic (ROC) curve was constructed to assess the TSHneo cutoff values. The significance level was p < 0.05. RESULTS: Using a TSHneo cutoff value 5.0 uIU/mL, 50 out of 111,705 screened infants were diagnosed with CH. The prevalence of CH was 1:2,234 live births. The state program coverage was 73.9%. For Group II, the TSHneo levels were higher than 20.0 uIU/mL in 61.4% of infants, and the serum TSH levels exceeded that level in 83.7%. The ROC curve showed that a TSHneo cutoff value of 5.03 uIU/mL had 100% sensitivity and the greatest associated specificity (93.7%). The area under the curve was 0.9898 (p < 0.0001). CONCLUSIONS: An inadequate coverage of the NSP-MT was observed. The ROC curve confirmed that the TSHneo cutoff value of 5.0 ?IU/mL adopted by the NSP-MT was the safest for detecting CH and determined the high prevalence of disease that was found in the State of Mato Grosso

INTRODUÇÃO: O câncer de ovário é o mais letal de todos os cânceres ginecológicos e requer ser tratado por ginecologistas especializados em centros terciários para se obter melhor prognóstico. Este trabalho tem como objetivo analisar e comparar quatro estratégias diferentes para predizer a benignidade ou malignidade de tumores pélvicos supostamente de origem ovariana utilizando para este fim, marcadores tumorais CA 125 e HE4, índice de risco de malignidade (IRM) e algoritmo ROMA. MÉTODOS: Neste estudo prospectivo foram avaliadas 128 pacientes com diagnóstico de tumores pélvicos supostamente de origem ovariana atendidas na Divisão de Clínica Ginecológica do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo e Instituto do Câncer do Estado de São Paulo entre julho de 2008 e janeiro 2011. Foram calculadas a sensibilidade e a especificidade e construídas curvas ROC para comparar os quatro parâmetros (CA 125, HE4, ROMA e IRM) na eficácia de diferenciar tumores ovarianos. RESULTADOS: A sensibilidade obtida para CA 125, HE4, ROMA e IRM foi de, respectivamente, 70,4%, 79,7%, 74,1% e 63,0%. A especificidade para CA 125, HE4, ROMA e IRM foi de, respectivamente, 74,2%, 66,7%, 75,8% e 92,4%. Não houve diferença na comparação das áreas abaixo da curva ROC entre os quatro parâmetros. CONCLUSÕES: Nenhum dos quatro métodos estudados é o ideal na diferenciação de tumores ovarianos. Entre os quatro parâmetros analisados o HE4 foi o parâmetro com melhor sensibilidade na diferenciação de tumores ovarianos. A acurácia dos quatro métodos é equivalente e podem ser utilizados indistintamente para referenciar pacientes para serviços especializados no tratamento de câncer de ovário / BACKGROUND: Ovarian cancer is the most lethal of all gynecological cancers and requires to be treated by gynecologic oncologists in tertiary centers accustomed to treating this disease to achieve the best prognosis. This study aims to compare four different strategies to predict the benignity or malignancy of pelvic tumors presumably of ovarian origin using, for this purpose, tumor markers CA 125 and HE4, risk malignancy index (RMI) and algorithm ROMA. METHODS: This prospective study evaluated 128 patients supposedly with ovarian tumors treated at the Divisão de Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Instituto do Câncer do Estado de São Paulo between July 2008 and January 2011. We calculated sensitivity, specificity and ROC curves to compare the four parameters (CA 125, HE4, ROMA and RMI) ability to differentiate the ovarian tumors. RESULTS: The sensitivity obtained for CA 125, HE4, ROMA and RMI was, respectively, 70.4%, 79.7%, 74.1% and 63.0%. The specificity obtained for CA 125, HE4, ROMA and RMI was, respectively, 74.2%, 66.7%, 75.8% and 92.4%. There was no difference the areas under the ROC curve among the four parameters. CONCLUSIONS: None of the four studied methods is best in the differentiation of ovarian tumors. Among the four parameters analyzed, HE4 was the parameter with highest sensitivity in the differentiation of ovarian tumors. The accuracy of the four methods is equivalent and can be used interchangeably to refer patients for specialized services in the treatment of ovarian cancer

INTRODUÇÃO: O câncer de ovário é o mais letal de todos os cânceres ginecológicos e requer ser tratado por ginecologistas especializados em centros terciários para se obter melhor prognóstico. Este trabalho tem como objetivo analisar e comparar quatro estratégias diferentes para predizer a benignidade ou malignidade de tumores pélvicos supostamente de origem ovariana utilizando para este fim, marcadores tumorais CA 125 e HE4, índice de risco de malignidade (IRM) e algoritmo ROMA. MÉTODOS: Neste estudo prospectivo foram avaliadas 128 pacientes com diagnóstico de tumores pélvicos supostamente de origem ovariana atendidas na Divisão de Clínica Ginecológica do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo e Instituto do Câncer do Estado de São Paulo entre julho de 2008 e janeiro 2011. Foram calculadas a sensibilidade e a especificidade e construídas curvas ROC para comparar os quatro parâmetros (CA 125, HE4, ROMA e IRM) na eficácia de diferenciar tumores ovarianos. RESULTADOS: A sensibilidade obtida para CA 125, HE4, ROMA e IRM foi de, respectivamente, 70,4%, 79,7%, 74,1% e 63,0%. A especificidade para CA 125, HE4, ROMA e IRM foi de, respectivamente, 74,2%, 66,7%, 75,8% e 92,4%. Não houve diferença na comparação das áreas abaixo da curva ROC entre os quatro parâmetros. CONCLUSÕES: Nenhum dos quatro métodos estudados é o ideal na diferenciação de tumores ovarianos. Entre os quatro parâmetros analisados o HE4 foi o parâmetro com melhor sensibilidade na diferenciação de tumores ovarianos. A acurácia dos quatro métodos é equivalente e podem ser utilizados indistintamente para referenciar pacientes para serviços especializados no tratamento de câncer de ovário / BACKGROUND: Ovarian cancer is the most lethal of all gynecological cancers and requires to be treated by gynecologic oncologists in tertiary centers accustomed to treating this disease to achieve the best prognosis. This study aims to compare four different strategies to predict the benignity or malignancy of pelvic tumors presumably of ovarian origin using, for this purpose, tumor markers CA 125 and HE4, risk malignancy index (RMI) and algorithm ROMA. METHODS: This prospective study evaluated 128 patients supposedly with ovarian tumors treated at the Divisão de Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Instituto do Câncer do Estado de São Paulo between July 2008 and January 2011. We calculated sensitivity, specificity and ROC curves to compare the four parameters (CA 125, HE4, ROMA and RMI) ability to differentiate the ovarian tumors. RESULTS: The sensitivity obtained for CA 125, HE4, ROMA and RMI was, respectively, 70.4%, 79.7%, 74.1% and 63.0%. The specificity obtained for CA 125, HE4, ROMA and RMI was, respectively, 74.2%, 66.7%, 75.8% and 92.4%. There was no difference the areas under the ROC curve among the four parameters. CONCLUSIONS: None of the four studied methods is best in the differentiation of ovarian tumors. Among the four parameters analyzed, HE4 was the parameter with highest sensitivity in the differentiation of ovarian tumors. The accuracy of the four methods is equivalent and can be used interchangeably to refer patients for specialized services in the treatment of ovarian cancer

Predictive power of classification models can be evaluated by various measures. The most popular measures in data mining (DM) are Gini coefficient, Kolmogorov-Smirnov statistic and lift. These measures are each based on a completely different way of calculation. If an analyst is used to one of these measures it can be difficult for him to asses the predictive power of a model evaluated by another measure. The aim of this thesis is to develop a method how to convert one performance measure into another. Even though this thesis focuses mainly on the above-mentioned measures, it deals also with other measures like sensitivity, specificity, total accuracy and area under ROC curve. During development of DM models you may need to work with a sample that is stratified by values of the target variable Y instead of working with the whole population containing millions of observations. If you evaluate a model developed on a stratified data you may need to convert these measures to the whole population. This thesis describes a way, how to carry out this conversion. A software application (CPM) enabling all these conversions makes part of this thesis. With this application you can not only convert one performance measure to another, but you can also convert measures calculated on a stratified sample to the whole population. Besides the above mentioned performance measures (sensitivity, specificity, total accuracy, Gini coefficient, Kolmogorov-Smirnov statistic), CPM will also generate confusion matrix and performance charts (lift chart, gains chart, ROC chart and KS chart). This thesis comprises the user manual to this application as well as the web address where the application can be downloaded. The theory described in this thesis was verified on the real data.

INTRODUÇÃO: O Hipotireoidismo congênito (HC) é uma das endocrinopatias mais frequentes em pediatria e pode causar retardo mental e do crescimento, se não for tratado precocemente. A determinação do nível do hormônio estimulador da tireoide em sangue total após o nascimento (TSHneo) constitui uma estratégia efetiva para o rastreamento de HC, embora não exista consenso em relação aos níveis considerados seguros para essa detecção. Muitos serviços utilizam os valores de corte do TSH neonatal de 10,0 e 15,0 ?UI/mL, por ensaios imunofluorimétricos. OBJETIVO: Analisar a capacidade de detecção dos casos de hipotireoidismo congênito por diferentes níveis de corte do TSH neonatal e os efeitos destes sobre o sistema de triagem neonatal para essa doença, em nascidos vivos avaliados pelo Programa de Triagem Neonatal (PTN) da rede pública do Estado de Mato Grosso (MT), de 01 de janeiro de 2010 a 31 de dezembro de 2012. MÉTODOS: Estudo de coorte, de corte transversal, com coleta retrospectiva de dados obtidos a partir do banco de dados do Serviço de Referência em Triagem Neonatal do Estado de Mato Grosso, de nascidos vivos no período 01/01/2010 a 31/12/2012 e avaliados pelo PTN-MT. Estes foram divididos em dois grupos: I. Controle: Crianças com exame de triagem neonatal normal; II. Estudo: Crianças com HC. Análise estatística incluiu o uso do teste qui-quadrado ou exato de Fischer para análise das características dos recém-nascidos entre os grupos e o teste t de Student ou não paramétrico de Mann-Whitney para análise dos níveis de TSH em sangue total de ambos os grupos e, avaliação das concentrações de TSH e T4 livre no soro, em crianças com HC. Construiu-se uma curva ROC (Receiver Operating Characteristic), para a avaliação dos pontos de corte do TSHneo. O nível de significância foi p<0,05. RESULTADOS: Entre as 111.705 crianças triadas pelo Programa, 50 tiveram o diagnóstico de HC, sob o ponto de corte do TSHneo de 5,0 ?UI/mL. A prevalência da doença foi de 1:2.234 nascidos vivos. A cobertura do Programa estadual foi de 73,9%. Para o Grupo II, os níveis do TSHneo foram superiores a 20,0 ?UI/mL em 61,4% das crianças e, os níveis de TSH no soro excederam este valor em 83,7%. A curva ROC identificou o ponto de corte do TSHneo de 5,03 ?UI/mL, como o correspondente à sensibilidade de 100% e a maior especificidade associada (93,7%). A área observada sob a curva foi de 0,9898 (p<0,0001). CONCLUSÕES: Observou-se uma cobertura inadequada do PTN-MT. O ponto de corte do TSH neonatal de 5,0 ?UI/mL, adotado pelo PTN-MT, foi confirmado pela curva ROC como o mais seguro para detectar HC e determinou a elevada prevalência da doença no Estado de Mato Grosso / INTRODUCTION: Congenital hypothyroidism (CH) is a very common pediatric endocrine disorder and can cause mental and growth retardation without early treatment. Measuring the total blood thyroid-stimulating hormone level after birth (TSHneo) is an effective screening strategy for CH, although there is not yet a consensus on the appropriate diagnostic levels. Many services use the neonatal TSH cut-off points of 10.0 and 15.0 uIU/mL per imunofluorimetric assay. OBJECTIVE: The aim of the present study was to analyze the ability of various TSHneo cutoff values to detect CH and their effects on the Newborn Screening Program (NSP) of the State of Mato Grosso (MT) from January 1, 2010, to december 31, 2012. METHODS: Cohort study, cross-sectional, based on retrospective data collection obtained from the database of the Reference Service for Neonatal Screening of the State of Mato Grosso, for all live births from January 1, 2010, to December 31, 2012, reviewed by NSP-MT. The infants were divided into two groups: I-Control: infants with normal newborn screening tests and II-Study: infants with CH. Statistical analysis included the chi-square or Fisher\'s exact test to compare the characteristics of the newborns from both groups and Student\'s t-test or the non-parametric Mann-Whitney test to analyse the total blood TSH level from both groups of infants and evaluate the serum TSH and free thyroxine (T4) concentrations in infants with CH. A Receiver Operating Characteristic (ROC) curve was constructed to assess the TSHneo cutoff values. The significance level was p < 0.05. RESULTS: Using a TSHneo cutoff value 5.0 uIU/mL, 50 out of 111,705 screened infants were diagnosed with CH. The prevalence of CH was 1:2,234 live births. The state program coverage was 73.9%. For Group II, the TSHneo levels were higher than 20.0 uIU/mL in 61.4% of infants, and the serum TSH levels exceeded that level in 83.7%. The ROC curve showed that a TSHneo cutoff value of 5.03 uIU/mL had 100% sensitivity and the greatest associated specificity (93.7%). The area under the curve was 0.9898 (p < 0.0001). CONCLUSIONS: An inadequate coverage of the NSP-MT was observed. The ROC curve confirmed that the TSHneo cutoff value of 5.0 ?IU/mL adopted by the NSP-MT was the safest for detecting CH and determined the high prevalence of disease that was found in the State of Mato Grosso

<p>Akutni pankreatitis predstavlja zbirni pojam dinamičkih, lokalnih i sistemskih patofiziolo&scaron;kih procesa nastalih iznenadnim prodorom aktivnih litičkih pankreasnih enzima u žlezdani parenhim. Cilj istraživanja je da se Utvrditi senzitivnost difuzione sekvence magnetne rezonance (DWI) radi utvrđivanja morfolo&scaron;kih promena parenhima kod akutnog pankreatitisa. Poređenje difuzione mape i difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kod pacijenata sa morfolo&scaron;ki urednim parenhimom pankreasa na magnetnoj rezonanci. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na pol. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na godine. Odrediti prelomnu tačku difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom. Studija je bila prospektivnog karaktera i obuhvatilo je 30 ispitanika sa morfolo&scaron;ki urednim parenhimom pankreasa i 30 sa dijagnozom akutnog pankreatitisa unutar 72 sata od početka simptoma. Svi pacijenti su pregledani magnetnom rezonancom u Centru za radiologiju, Kliničkog Centra Vojvodine. Rezultati ukazuju da postoje razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kontrolne grupe. Takođe smo dokazali da difuzioni koeficijent zavisi od pola i starosti i utvrdili smo prelomnu tačku difuzije za rano dijagnostikovanje akutnog pankreatitisa.</p> / <p>Acute pancreatitis is defined as cumulative term of dynamic local and general pathophysiological processes caused by sudden penetration of active lithic pancreatic enzymes in the glandular parenchyma. Goal of this research is to note the changes (sensitivity) in values of diffusion weighted images (DWI) in acute pancreatitis and to determine morphological changes in glandular parenchyma of pancreas. Comparation of DWI between patients with acute pancreatitis and patients with normal pancreatic parenchyma based on magnetic resonance (MRI). We also want to determine whether there were statistically significant differences of DWI in patients with acute pancreatitis in relation to sex and age. One of our goals also was to determine breakpoint of DWI as a sure sign of acute pancreatitis. This was prospective study and included 30 patients with morphologically healthy parenchyma of the pancreas (control group) and 30 with the diagnosis of acute pancreatitis &ndash; in first 72 hours of the onset of symptoms. All patients were examined on MRI in department of Radiology of Clinical Center of Vojvodina. Our results indicate that was a big difference of DWI between patients with acute pancreatitis and control group. We prove that DWI depends on the sex and age. 1,77x10-6mm/s2 was breakpoint which indicates acute pancreatitis.</p>