Implementation of an integrated care strategy for child contacts of tuberculosis patients: a quasi-experimental study protocol.

BACKGROUND: Childhood tuberculosis continues to be a major public health problem. Although the visibility of the epidemic in this population group has increased, further research is needed. OBJECTIVE: To design, implement and evaluate an integrated care strategy for children under five years old who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients in Medellín and the Metropolitan Area. METHODS: A quasi-experimental study in which approximately 300 children who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients from Medellín and the Metropolitan Area will be evaluated and recruited over one year. A subgroup of these children, estimated at 85, who require treatment for latent tuberculosis, will receive an integrated care strategy that includes: some modifications of the current standardized scheme in Colombia, with rifampicin treatment daily for four months, follow-up under the project scheme with nursing personnel, general practitioners, specialists, professionals from other disciplines such as social work, psychology, and nutritionist. Additionally, transportation and food assistance will be provided to encourage treatment compliance. This strategy will be compared with isoniazid treatment received by a cohort of children between 2015 and 2018 following the standardized scheme in the country. The study was approved by the CIB Research Ethics Committee and UPB. CLINICALTRIALS: gov identifier NCT04331262. DISCUSSION: This study is expected to contribute to the development of integrated care strategies for the treatment of latent tuberculosis in children. The results will have a direct impact on the management of childhood tuberculosis contributing to achieving the goals proposed by the World Health Organization's End TB Strategy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04331262 . Implementation of an Integrated Care Strategy for Children Contacts of Patients with Tuberculosis. Registered 2 April 2020.

Reproducibility of a protocol for standardized reading of chest X-rays of children household contact of patients with tuberculosis.

BACKGROUND: The interpretation of the chest radiograph may vary because it depends on the reader and due to the non-specificity of findings in tuberculosis (TB). We aim to assess the reproducibility of a standardized chest radiograph reading protocol in contacts of patients with pulmonary TB under the 5 years of age. METHODS: Descriptive, cross-sectional study with children under the age of five, household contacts of patients with confirmed pulmonary TB from Medellín, Bello and Itagüí (Colombia) between Jan-01-2015 and May-31-2016. Standardized reading protocol: two radiologists, blinded independent reading, use of template (Dr. Andronikou design) in case of disagreement a third reading was performed. Kappa coefficient for intra and inter observer agreement, and prevalence ratio were estimated of sociodemographic characteristics, TB exposure and interpretation of chest X-ray. RESULTS: From 278 children, standardized reading found 255 (91.7%) normal X-rays, 10 (3.6%) consistent with TB, and 13 (4.7%) other alterations. Global agreement was 91.3% (Kappa = 0.51). Inter-observer agreement between readers 1-2 was 90.0% (Kappa = 0.59) and 1-3 93.2% (Kappa = 0.59). Intra-observer agreement for reader 1 was 95.5% (Kappa = 0.86), 2 84.0% (Kappa = 0.51), and 3 94.7% (Kappa = 0.68). Greater inter-observer disagreement was between readers 1-2 for soft tissue density suggestive of adenopathy (4.6%), airspace opacification (1.17%) and pleural effusion (0.58%); between readers 1-3 for soft tissue density suggestive of adenopathy (4.2%), opacification of airspace (2.5%) and cavities (0.8%). CONCLUSIONS: Chest radiographs are an affordable tool that contributes to the diagnosis of TB, so having a standardized reading protocol showed good agreement and improves the reproducibility of radiograph interpretation.

Prevalence of soil transmitted helminths in school-aged children, Colombia, 2012-2013.

BACKGROUND: This study aims to establish the prevalence of soil-transmitted helminth (STH) intestinal infections, nutritional status, and anemia in school children aged 7 to 10 years old in the biogeographic provinces of Colombia in 2012-2013. STH prevalence in the country has not been described within the last 30 years and it is needed in order to establish policies its control in the country. METHODOLOGY: National Survey of STH in school-aged children with a multistage stratified probability sampling was conducted. The overall prevalence and intensity of STH infection, as well as for each parasite, (A. lumbricoides, T. trichiura and hookworms) were calculated for the country and for each of the nine biogeographic provinces. PRINCIPAL FINDINGS: Stool samples were collected from 6045 children in eight out of nine biogeographic provinces. The combined prevalence of STH in the country was 29.6%. T. trichiura was the most prevalent helminth (18.4%), followed by A. lumbricoides (11.3%), and hookworms (6.4%). For A. lumbricoides and hookworms, the highest prevalence values were found in the Amazonía province (58.0% and 35.7%, respectively). Regarding STH intensity, most cases showed moderate intensity (41.3%) for A. lumbricoides, and light intensity, for T. trichiura and hookworms. The national prevalence of anemia in school-aged children was 14.2%, lowest in the Nor-Andina province (3.5%), and highest in the Territorios Insulares oceánicos del Caribe province (45.1%). SIGNIFICANCE: Colombia has a moderate risk of STH infection in school-aged populations, with considerable variation in the prevalence values among the biogeographic provinces. Like any public health issue, this problem should be handled with a comprehensive approach that involves deworming programs and strategies for STH control according to the specific epidemiological and socioeconomic conditions and sanitation service coverage in each biogeographic province. The program should be further supported by intersectoral action to improve living conditions, particularly the excreta disposal, promoted at municipality levels.

Tuberculosis: una ventana de análisis de las políticas públicas en salud / Tuberculosis, a window of analysis of public health policies

Las políticas públicas están orientadas a resolver problemas que políticamente se identifican como colectivos y que demandan un conjunto de decisiones y acciones por diferentes actores generalmente públicos, para evitar en la población los efectos negativos que estos problemas generan (1). La tuberculosis ­TB­ como problema de salud pública ha sido objeto de formulación de políticas públicas desde hace muchos años, las cuales cubre desde un ámbito global, hasta los ámbitos locales para su prevención y control en los diferentes países del mundo. De hecho, enmarcados en las metas de desarrollo sostenible post-2015 (MDS) se ha definido por la Organización Mundial de la Salud ­OMS­ como meta, disminuir la incidencia de TB en un 90% y su mortalidad en un 95% para el año 2035 con respecto al año 2015 (2). La política global comprende la atención y prevención integral de la TB centrada en el paciente, con el compromiso político de destinar recursos suficientes para su prevención y control, incluyendo la investigación y la innovación. Los principios en los que se basa la política son el de la dirección de los gobiernos, la alianza con las organizaciones de la sociedad civil y de la comunidad y la promoción de los derechos humanos, la ética y la equidad. Política suscrita y adaptada por Colombia. La TB afecta principalmente población vulnerada en sus condiciones de vida como el hacinamiento en la vivienda, carencia de seguridad alimentaria, limitado acceso a los servicios de salud y a un diagnóstico oportuno. Igualmente afecta a la población infantil, indígena, población privada de la libertad, habitantes de calle y con presencia de morbilidades concomitantes como la infección del virus de la Inmunodeficiencia Humana ­VIH­ la diabetes y el cáncer y la exposición ocupacional y la presencia de formas multirresistentes a los antibióticos ­MDR­. En Colombia, según las estadísticas de la OMS, se notificaron 13.467 nuevos casos de TB en el año 2016, con un número estimado de casos de 16 mil para una tasa de incidencia de 32 por cien mil habitantes, con una cobertura de tratamiento del 80% y una proporción de co-infección con el Virus de la Inmunodeficiencia Humana ­VIH­ del 14% (3). Si bien se cuenta con un tratamiento eficaz para su control, requiere de su administración de forma estrictamente supervisada, por un periodo de tiempo no menor a seis meses, el seguimiento de la respuesta y efectos secundarios del mismo, el acompañamiento a las familias y acciones de salud pública como la vacunación, la búsqueda de los sintomáticos respiratorios, la aplicación de pruebas diagnósticas, educación en salud y el compromiso político tanto del sector salud como de diferentes sectores sociales. Es por ello, que el control de la enfermedad es un trazador no sólo de las condiciones de vida de la población sino también del desempeño de los sistemas de salud. El objetivo del presente artículo es mostrar cómo a partir del resultado de diferentes investigaciones realizadas por integrantes del Centro Colombiano de Investigación en TB ­CCITB­ se puede evaluar el impacto de diferentes decisiones y acciones de política pública para el sector de la salud en Colombia.

Public policies are aimed at solving problems that are politically identified as collective and that demand a set of decisions and actions by different public actors, to avoid the negative effects that these problems generate in the population. Tuberculosis -TB- as a public health problem, has been the subject of public policy formulation for many years, which covers from a global scope to local areas for its prevention and control in different countries. In fact, framed within the goals of sustainable development post-2015 (MDS), it has been defined by the World Health Organization - WHO- as a goal to reduce the incidence of TB by 90% and its mortality by 95% for the year 2035 with respect to the year 2015. This global policy includes comprehensive care and prevention of TB centered on the patient, with the political commitment to allocate sufficient resources for prevention and control, including research and innovation. The principles on which the policy is based are the direction of governments, the alliance with civil society and community organizations and the promotion of human rights, ethics and equity. This policy has been subscribed and adapted by Colombia. TB mainly affects the population by their living conditions, such as overcrowded housing, lack of food security, limited access to health services and timely diagnosis. It also affects the child population, indigenous, population deprived of freedom, homeless and those with concomitant morbidities such as human immunodeficiency virus infection - HIV - diabetes and cancer and occupational exposure and the presence of forms multiresistant to antibiotics (MDR). In Colombia, according to WHO statistics, 13,467 new cases of TB were reported in 2016, with an estimated number of cases of 16,000 for an incidence rate of 32 per 100,000 inhabitants, with 80 treatment coverage. % and a proportion of co-infection with the human immunodeficiency virus - HIV- of 14%. Although there is an effective treatment for its control, it requires administration in a strictly supervised manner, for a period of time not less than six months, the follow-up of response and side effects thereof, the accompaniment of families and actions of public health such as vaccination, search for respiratory symptoms, application of diagnostic tests, health education and the political commitment of the health and social sectors as well. That is why the control of the disease is a tracer not only of the living conditions of the population but also of the performance of the health systems. The objective of this article is to show how, based on the results of different investigations carried out by members of the Colombian Center for Research in TB - CCITB - the impact of different decisions and public policy actions for the health sector in Colombia can be evaluated.

Gender Differences in the Interpretation of Experiences of Patients with Tuberculosis in Medellín, Colombia.

OBJECTIVE: This study sought to determine gender differences in the interpretation of tuberculosis (TB) in a group of patients from the city of Medellín. METHODOLOGY: This was a qualitative study, with the grounded theory method. Twelve semistructured interviews were applied to patients from both genders who were cured of TB. The sample was selected through convenience and for analysis the information was categorized through the Atlas Ti tool. RESULTS: Regarding the symptoms, the most reported is cough, but men manifest expectoration more frequently. Men overstated the symptoms, while women tend to minimize them. Women report mental impairment and emotional-type manifestations produced by the disease. Men and women expressed ignorance about the disease upon diagnosis. Both manifested fear of infection, work incapacity, loss of employment, rejection by others, and death. Also highlighted is the importance of family support and of the healthcare personnel. Women expressed shame in that others knew of their disease and mentioned greater intolerance with taking the medications. CONCLUSION: The gender role constructed culturally constitutes the central axis that explains how men and women interpret TB and can be modified by educational and accompaniment processes. Family support plays an important role in the healing process. Although common aspects exist, delving into the gender differences against the interpretation of TB may permit a different approach of the disease and better control of it.

Gender differences in the interpretation of experiences of patients with tuberculosis in Medellín, Colombia / Diferencias de género en la interpretación de las vivencias de pacientes con tuberculosis. Medellín, Colombia / Diferenças de gênero na interpretação das vivências de pacientes com tuberculoses. Medellín, Colômbia

Objective. This study sought to determine gender differences in the interpretation of tuberculosis (TB) in a group of patients from the city of Medellín. Methodology. This was a qualitative study, with the grounded theory method. Twelve semistructured interviews were applied to patients from both genders who were cured of TB. The sample was selected through convenience and for analysis the information was categorized through the Atlas Ti tool. Results. Regarding the symptoms, the most reported is cough, but men manifest expectoration more frequently. Men overstated the symptoms, while women tend to minimize them. Women report mental impairment and emotional-type manifestations produced by the disease. Men and women expressed ignorance about the disease upon diagnosis. Both manifested fear of infection, work incapacity, loss of employment, rejection by others, and death. Also highlighted is the importance of family support and of the healthcare personnel. Women expressed shame in that others knew of their disease and mentioned greater intolerance with taking the medications. Conclusion. The gender role constructed culturally constitutes the central axis that explains how men and women interpret TB and can be modified by educational and accompaniment processes. Family support plays an important role in the healing process. Although common aspects exist, delving into the gender differences against the interpretation of TB may permit a different approach of the disease and better control of it.

Objetivo. Determinar las distintas interpretaciones con respecto a la tuberculosis (TB) a partir de las diferencias de género en un grupo de pacientes de la ciudad de Medellín. Metodología. Estudio cualitativo, con el método de la teoría fundamentada. Se aplicaron 12 entrevistas semiestructuradas a pacientes de ambos géneros curados de TB. La muestra se seleccionó por conveniencia y para el análisis se categorizó la información mediante la herramienta Atlas Ti. Resultados. Con relación a los síntomas el más expresado es la tos, pero los hombres manifiestan con más frecuencia la expectoración. Ellos sobredimensionan los síntomas, mientras las mujeres tienden a minimizarlos. Estas, a su vez, refieren deterioro mental y manifestaciones de tipo emocional producidas por la enfermedad. Tanto hombres como mujeres expresaron desconocimiento sobre la enfermedad en el momento del diagnóstico. Ambos manifestaron miedo al contagio, incapacidad laboral, pérdida del empleo, rechazo de los otros y a la muerte. También resaltaron la importancia del apoyo familiar y del personal de salud. Las mujeres expresaron vergüenza de que otros supieran de su enfermedad y mencionaron mayores intolerancias con la ingesta de los medicamentos. Conclusión. El rol de género, construido culturalmente, constituye el eje central que explica la manera como hombres y mujeres interpretan la TB, lo que puede ser modificado por procesos educativos y de acompañamiento. El apoyo familiar juega un papel importante en el proceso de curación. Aunque hay aspectos comunes, la profundización en las diferencias de género frente a la interpretación de la TB, puede permitir un abordaje diferente de la enfermedad y un mejor control de la misma.

Objetivo. Determinar as diferenças de gênero na interpretação da tuberculose (TB) num grupo de pacientes da cidade de Medellín. Metodologia. Estudo qualitativo, com o método da teoria fundamentada. Aplicaram-se 12 entrevistas semiestruturadas, a pacientes curados de TB de ambos gêneros. A mostra se selecionou por conveniência e para a análise se categorizou a informação mediante a ferramenta Atlas Ti. Resultados. Com relação aos sintomas o mais expressado é a tosse, mas os homens manifestam com mais frequência a expectoração. Os homens sobre-dimensionam os sintomas, enquanto as mulheres tendem a minimizá-los. As mulheres referem deterioração mental e manifestações de tipo emocional produzidas pela doença. Homens e mulheres expressaram desconhecimento sobre a doença no momento do diagnóstico. Ambos manifestaram medo ao contágio, incapacidade trabalhista, perda do emprego, rejeição dos outros e morte. Também ressaltaram a importância do apoio familiar e do pessoal de saúde. As mulheres expressaram vergonha de que outros soubessem da doença e mencionaram maiores intolerâncias com a tomada dos medicamentos Conclusão. O papel de gênero construído culturalmente constitui o eixo central que explica a maneira como homens e mulheres interpretam a TB e pode ser modificado por processos educativos e de acompanhamento. O apoio familiar joga um papel importante no processo de cura. Ainda que há aspectos comuns, o aprofundamento nas diferenças de gênero frente à interpretação da TB, pode permitir uma abordagem diferente da doença e um melhor controle da mesma.

Estudio y manejo clínico de menores que conviven con pacientes de tuberculosis pulmonar, Medellín 2010-2011 / Study and clinical management of child household contacts of tuberculosis patients, Medellin 2010-2011 / Estudo e manejo clínico de menores conviventes com pacientes de tuberculose pulmonar, Medellín 2010-2011

Introducción: el tratamiento para tuberculosis latente disminuye el riesgo de infección de los niños que conviven con pacientes de dicha enfermedad. Objetivo: describir el estudio y manejo clínico de los menores de 5 años que convivían en Medellín con pacientes de tuberculosis pulmonar en el período 2010-1011. Materiales y métodos: estudio observacional de corte. Se exploró la relación entre las características sociodemográficas, clínicas y de manejo de los niños y los casos índice. Resultados: 28,6% fueron estudiados al menos con radiografía de tórax y prueba de tuberculina. De los evaluados clínicamente, 7,9% tenían tuberculosis activa; de los demás, 19,4% recibieron tratamiento para tuberculosis latente. Hubo mayor oportunidad de ser estudiado si el conviviente tenía régimen de salud contributivo o subsidiado (OR ajustado: 6,7; IC 95%: 1,5-30,5). La oportunidad de recibir tratamiento para tuberculosis latente se relacionó con la prueba de tuberculina (OR ajustado: 40,2; IC 95%: 2,59-623,6). Conclusión: los menores no estaban siendo adecuadamente estudiados ni recibían el tratamiento apropiado, por lo que su prevalencia de tuberculosis activa no disminuyó. Se requiere crear un protocolo estandarizado para el manejo de los menores en similares condiciones y supervisar su aplicación.

Introduction: Treatment for latent tuberculosis decreases the risk of this infection in children who are household contacts of patients with such disease. Objective: To describe the study and clinical management of children under 5 years of age who were household contacts of pulmonary tuberculosis patients in Medellin, Colombia during the period 2010-2011. Materials and methods: Cross-sectional study. The relationship between socio-demographic and clinical characteristics, and the management of children and index cases was explored. Results: 28.6% were studied with at least chest X rays and tuberculin skin test. Of those who attended clinical evaluation, 7.9% had active tuberculosis; out of the remaining, 19.4% received treatment for latent tuberculosis. The probability of being studied was higher if the household contact had contributory or subsidized health coverage (adjusted OR: 6.7; 95% CI: 1.5-30.5). The opportunity to receive treatment for latent tuberculosis was related to the tuberculin skin test (adjusted OR: 40.2; 95% CI: 2.59-623.6). Conclusion: The household contacts had not been adequately studied, and did not receive the right treatment, so the prevalence of active tuberculosis among them did not decrease. It is necessary to establish a standardized protocol for the management of children living under similar conditions, and to monitor its implementation.

Introdução: o tratamento para tuberculose latente diminui o risco de infecção dos meninos que convivem com pacientes de dita doença. Objetivo: descrever o estudo e manejo clínico dos menores de 5 anos que conviviam em Medellín com pacientes de tuberculose pulmonar no período 2010- 1011. Materiais e métodos: estudo observacional de corte. Explorou-se a relação entre as características sóciodemográficas, clínicas e de manejo das crianças e os casos índice. Resultados: 28,6% foram estudados ao menos com radiografia de tórax e prova de tuberculina. Dos avaliados clinicamente, 7,9% tinham tuberculose ativa; dos demais, 19,4% receberam tratamento para tuberculose latente. Teve maior oportunidade de ser estudado se o convivente tinha regime de saúde tributável ou subsidiado (OR ajustado: 6,7; IC 95%: 1,5-30,5). A oportunidade de receber tratamento para tuberculose latente se relacionou com a prova de tuberculina (OR ajustado: 40,2; IC 95%: 2,59-623,6). Conclusão: os menores estudados não estavam sendo adequadamente estudados nem recebiam o tratamento apropriado, pelo que sua prevalência de tuberculose ativa não diminuiu. Requer-se criar um protocolo padronizado para o manejo dos menores em similares condições e supervisionar sua aplicação.

Actividad antibacteriana y clínica de la moxifloxacina comparada con otros antibióticos para el manejo de infecciones bucales / Clinical antibacterial activity and moxifloxacin compared with other antibiotics for oral infections handling

La cavidad bucal constituye uno de los principales nichos ecológicos para bacterias aerobias y principalmente anaerobias. Estos microorganismos juegan un papel importante en la patogénesis de las infecciones bucales y en las infecciones focales de origen oral. Las infecciones bucales más frecuentes incluyen caries, periodontitis, absceso periapical, absceso periodontal, pericoronitis, pulpitis, osteítis e infección de los espacios aponeuróticos. Algunos estudios indican un aumento en la prevalencia de microorganismos presentes en la cavidad bucal que son resistentes a algunos de los antibióticos usualmente empleados para combatir este tipo de infecciones, por lo cual es necesario tener presente antibióticos alternativos para uso terapéutico o profiláctico. Moxifloxacina (MXF) es una 8-methoxiquinolona de amplio espectro, eficaz contra patógenos respiratorios intracelulares típicos y atípicos, bacterias gram negativas y muchas bacterias anaeróbicas obligadas. MXF es también muy activo contra cepas que son resistentes a la penicilina, macrólidos, tetraciclinas, thrimethoprim/sulfa y algunas fluroquinolonas. Cuando se compara con la amoxicilina/clavulánico (AMX-CLA), el esquema de dosificación de la MXF (400 mg/diarios), podría garantizar un mayor cumplimiento con las prescripciones. Además, su mecanismo de acción también puede proporcionar un alivio más rápido de los síntomas de la infección odontogénica, convirtiéndose en una posible alternativa antimicrobiana contra anaerobios obligados residentes en la cavidad bucal

The oral cavity constitutes one of the principal ecological niches for obligate anaerobic bacteria. These microorganisms play an important role in the pathogenesis of oral infections and focal infections of oral origin. Most of these infections are odontogenics, being the most frequent decays, periodontitis, periapical abscess, periodontal abscess, pericoronitis, pulpitis, osteitis and infection of the aponeurotic spaces. Some published studies highlight the growing prevalence of obligate anaerobes in oral origin that are resistant to some of these antibiotics, giving rise to the need to investigate alternative antibiotics for therapeutic or prophylactic use. Moxifloxacin (MXF) is an 8-methoxyquinolone with a broad spectrum of activity, including activity against typical, atypical and intracellular respiratory pathogens, gram negative pathogens and many obligate anaerobic bacteria. MXF is also highly active against strains that are resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. The dosing schedule of the MXF (400 mg / day) could ensure greater compliance with the requirements and its mechanism of action may also provide a faster relief of symptoms of infection odontogenic, when compared with amoxicillin / clavulanate (AMX-CLA). In addition, may represent a possible alternative antimicrobial against oral anaerobes

Factores asociados con el resultado virológico de la terapia antirretroviral altamente activa (HAART) en 340 pacientes Naive, Medellín - Colombia, 1997 - 2000 / Associated factors to virologic result on highly active antiretroviral theraphy (HAART) in 340 Naive patients: Medellín - Colombia, 1997 – 2000

Contexto: La mayoría de los estudios que soportan las guías actuales de manejo de la enfermedad VIH-SIDA han sido realizados en países desarrollados. Sin embargo, su aplicabilidad y efectividad de las terapias en países en vía de desarrollo puede variar, dado que al tener diferentes características socioeconómicas pueden modificarel resultado de la terapia. Objetivo: Medir la efectividad de la terapia HAART y los factores asociados con eléxito virológico al sexto mes de tratamiento. Diseño: Cohorte histórica.Sitio: Clínica pública ambulatoria para pacientes con VIH-SIDA en un paíssubdesarrollado (Medellín-Colombia). Mayo 1997 a mayo 2000. Pacientes: 340 pacientes naive, mayores de 13 años, todos iniciaron TerapiaAntirretroviral Altamente Activa (HAART). Medición: La variable dependiente fue la carga viral al sexto mes, categorizada mayor o menor de 500 copias/ml. El análisis univariado se realizó con la medición de la razón de disparidades (OR) para las variables categóricas y la t de student para las variables cuantitativas. La regresión logística se utilizó para identificar losfactores asociados ajustando por variables de confusión...

Context: Most studies supporting guidelines on HIV/AIDS have been conducted in developed countries. Nevertheless, their applicability on effectiveness of therapies may vary in developing countries, because of different socioeconomic characteristicswhich can affect therapy responses.Objective: To measure HAART effectiveness and factors associated with favorable virologic responses after six months of treatment. Study design: Historical Cohort. Place: Public Hospital with ambulatory service for HIV/AIDS patients in a developing country (Medellín, Colombia). May 1997 trough May 2000. Patients: 340 naive patients, over 13 years of age, which began HAART theraphy. Measurements: The dependent variable was the viral load after six months of therapy, classified as a result either over or below 500 copies/ml. Univariate analysiswas conducted using odds ratios for categorical variables and student – t test for quantitative ones. Logistic regression was used in order to identify adjusted risk factors of confounding factors...