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Abstract Background A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed. Aims The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation. Methods In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process. Results In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location. Conclusions The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease.

Objective To measure agreement between nine structured approaches for diagnosing childhood tuberculosis; to quantify differences in the number of tuberculosis cases diagnosed with the different approaches, and to determine the distribution of cases in different categories of diagnostic certainty. Methods We investigated 1445 children aged < 2 years during a vaccine trial (2001-2006) in a rural South African community. Clinical, radiological and microbiological data were collected prospectively. Tuberculosis case status was determined using each of the nine diagnostic approaches. We calculated differences in case frequency and categorical agreement for binary (tuberculosis/not tuberculosis) outcomes using McNemar's test (with 95% confidence intervals, CIs) and Cohen's kappa coefficient (K). Findings Tuberculosis case frequency ranged from 6.9% to 89.2% (median: 41.7). Significant differences in case frequency (P < 0.05) occurred in 34 of the 36 pair-wise comparisons between structured diagnostic approaches (range of absolute differences: 1.5-82.3%). Kappa ranged from 0.02 to 0.71 (median: 0.18). The two systems that yielded the highest case frequencies (89.2% and 70.0%) showed fair agreement (K: 0.33); the two that yielded the lowest case frequencies (6.9% and 10.0%) showed slight agreement (K: 0.18). Conclusion There is only slight agreement between structured approaches for the screening and diagnosis of childhood tuberculosis and high variability between them in terms of case yield. Diagnostic systems that yield similarly low case frequencies may be identifying different subpopulations of children. The study findings do not support the routine clinical use of structured approaches for the definitive diagnosis of childhood tuberculosis, although high-yielding systems may be useful screening tools. Objectif Mesurer le degre d'accord entre neuf approches structurees pour le diagnostic de la tuberculose chez l'enfant; quantifier les differences en termes de nombres de cas de tuberculose diagnostiques entre ces neuf approches ; et determiner la repartition des cas dans les differentes categories de certitude diagnostique. Methodes Nous avons etudie 1445 enfants de moins de 2 ans appartenant a une communaute rurale d'Afrique du Sud, dans le cadre d'un essai vaccinal (2001-2006). Des donnees cliniques, radiologiques et microbiologiques ont ete collectees prospectivement. Nous avons determine quel statut diagnostique (tuberculeux/non tuberculeux) etait affecte par chacune des approches aux cas potentiels de tuberculose. Nous avons calcule les differences en termes de frequence des cas et l'accord concernant la categorie de certitude pour les resultats binaires (tuberculose/absence de tuberculose) en utilisant le test de McNemar (avec les intervalles de confiance a 95 %, IC) et le coefficient kappa de Cohen (K). Resultats La frequence des cas de tuberculose se situait entre 6,9 et 89,2 % (mediane : 41,7 %). Des differences significatives sont apparues dans la frequence des cas (p < 0,05) dans 34 des 36 comparaisons par paire entre les approches diagnostiques structurees (plage de differences absolues : 1,5-82,3 %). Le coefficient kappa variait de 0,02 a 0,71 (mediane : 0,18). Les deux systemes donnant les plus fortes frequences de cas (89,2 % et 70,0 % respectivement) presentaient un accord satisfaisant (K : 0,33) ; les deux autres systemes, qui avaient fourni les plus faibles frequences (6,9 % et 10,0 %, respectivement), n'etaient que faiblement en accord (K : 0,18). Conclusion Il n'existe qu'un faible accord entre les approches structurees du depistage et du diagnostic de la tuberculose chez l'enfant et il apparait entre elles une forte variabilite du rendement en cas. Les systemes diagnostiques ayant fourni de maniere similaire des frequences de cas peu elevees pourraient identifier des sous-populations d'enfants differentes. Les resultats de cette etude ne sont pas en faveur d'un usage clinique systematique de ces approches structurees pour le diagnostic definitif des enfants tuberculeux, mais les systemes fournissant un rendement eleve en cas pourraient constituer des outils de depistage utiles. Objetivo Medir la concordancia entre nueve sistemas estructurados de diagnostico de la tuberculosis infantil; cuantificar las diferencias en cuanto al numero de casos de tuberculosis diagnosticados con los diferentes sistemas, y determinar la distribucion de casos en distintas categorias de certeza diagnostica. Metodos Se estudio a 1445 ninos menores de 2 anos durante un ensayo de vacunas (2001-2006) Ilevado a cabo en una comunidad rural de Sudafrica. Se reunieron de forma prospectiva datos clinicos, radiologicos y microbiologicos, y se determino si los ninos sufrian o no tuberculosis usando cada una de las nueve modalidades de diagnostico. Para calcular las diferencias en la frecuencia de casos y la concordancia de categorias para resultados binarios (tuberculosis/no tuberculosis), aplicamos la prueba de McNemar (con intervalos de confianza del 95%) y el coeficiente kappa de Cohen (K). Resultados La frecuencia de casos de tuberculosis se situo entre 6,9% y 89,2% (mediana: 41,7). Se observaron diferencias significativas en la frecuencia de casos (P < 0,05) en 34 de las 36 comparaciones emparejadas entre los sistemas de diagnostico estructurado (intervalo de diferencias absolutas: 1,5-82,3%). Kappa oscilo entre 0,02 y 0,71 (mediana: 0,18). Los dos sistemas que hallaron las frecuencias de casos mas altas (89,2% y 70,0%), mostraron una concordancia aceptable (K: 0,33); y los dos que hallaron las frecuencias de casos mas bajas (6,9% y 10,0%) mostraron una concordancia baja (K: 0,18). Conclusion Se observa solo una baja concordancia entre los sistemas estructurados en lo relativo al cribado y diagnostico de la tuberculosis infantil, y una alta variabilidad entre ellos en terminos de deteccion de casos. Sistemas de diagnostico que arrojan frecuencias de casos similarmente bajas podrian estar detectando subpoblaciones de ninos diferentes. Los resultados del estudio no respaldan el uso clinico sistematico de criterios estructurados para el diagnostico definitivo de la tuberculosis infantil, pero los sistemas que consiguen valores altos de deteccion pueden ser un valioso instrumento de cribado., Introduction Despite the scale of the worldwide tuberculosis epidemic, the disease remains very difficult to diagnose in children, especially in regions with limited resources. (1) Childhood tuberculosis is often paucibacillary [...]

Objectives. Researchers examined physicians' treatment strategies for tuberculosis to determine whether they would follow recommendations of the Centers for Disease Control and Prevention and the American Thoracic Society. Methods. A national survey sampled 1772 physicians. Analyses tested correlates of recommended treatment regimens. Results. Among respondents, 59.4% described a recommended regimen. Specialists; physicians aware of professional publications, treatment recommendations, and reporting requirements; and those having more than 50% of patients in nursing homes were more likely to describe recommended regimens. Physicians who had been in practice longer, relied on personal experience, or had more than 50% of patients receiving Medicaid were less likely to describe recommended regimens. Conclusions. Physicians who treat tuberculosis require training and support. Policymakers should consider who should treat tuberculosis and how recommended practice should be ensured. (Am J Public Health. 1997;87:2008-2011)

AFTER YEARS OF STEADY DECLINE, there has been an unprecedented resurgence since 1985 in the number of cases of tuberculosis (TB) in the United States. More recently, drug-resistant TB has […]

Background: A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed. Aims: The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation. Methods: In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process. Results: In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location. Conclusions: The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease. [ABSTRACT FROM AUTHOR]

Problem New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. Approach We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization -- Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Local setting Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Relevant changes Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Lessons learnt Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional researchcapacity strengthening. Such capacity-building approaches pr [ABSTRACT FROM AUTHOR]

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease. Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments. Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB. This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.