Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Person-centered strategies for delivering TB diagnostic services in Lima, Peru.

SETTING: Lima, Peru. OBJECTIVE: To close the gap in TB diagnosis, TB diagnostic services must match care-seeking preferences. We sought to identify preferred strategies for delivering TB diagnostic services and to determine whether preferences differ among demographic groups. DESIGN: During May 2022-January 2023, we recruited adults who recently initiated treatment for pulmonary TB. We used an object-case best-worst scaling instrument to assess the desirability of nine hypothetical strategies for delivering TB diagnostic services. A t-test was used to assess differences in preference scores between groups. RESULTS: Among 150 participants, the strategies with the highest preference scores were an integrated mobile unit offering screening for multiple conditions, expedited attention at the health center, and home-based screening. These were strongly preferred by 42%, 25%, and 27% of participants, respectively, and 80% of participants strongly preferred at least one of the three. Expedited attention at the health center scored more highly among people who experienced >2 months delay in TB diagnosis compared to those who experienced a more rapid diagnosis (0.37 ± 0.06 vs. 0.17 ± 0.06; P = 0.031). CONCLUSION: Providing person-centered TB diagnostic services at diverse access points could help reach different populations, which could promote early diagnosis and help close the diagnosis gap.

CONTEXTE: Lima, Pérou. OBJECTIF: Pour combler les lacunes dans le diagnostic de la TB, les services de diagnostic de la TB doivent correspondre aux préférences en matière de recherche de soins. Nous avons cherché à identifier les stratégies préférées pour la prestation de services de diagnostic de la TB et à déterminer si les préférences diffèrent entre les groupes démographiques. MÉTHODE: De mai 2022 à janvier 2023, nous avons recruté des adultes ayant récemment commencé un traitement contre la TB pulmonaire. Nous avons utilisé un instrument d'évaluation du meilleur et du pire pour évaluer la désirabilité de neuf stratégies hypothétiques de prestation de services de diagnostic de la TB. Un test-t a été utilisé pour évaluer les différences dans les scores de préférence entre les groupes. RÉSULTATS: Parmi les 150 participants, les stratégies ayant les scores de préférence les plus élevés étaient une unité mobile intégrée offrant un dépistage pour des conditions multiples, une attention accélérée au centre de santé et un dépistage à domicile. Ces stratégies ont été fortement préférées par 42%, 25% et 27% des participants, respectivement, et 80% des participants ont fortement préféré au moins l'une des trois. L'attention accélérée au centre de santé a obtenu un score plus élevé chez les personnes ayant subi un retard de diagnostic de la TB de plus de 2 mois que chez celles ayant subi un diagnostic plus rapide (0,37 ± 0,06 contre 0,17 ± 0,06 ; P = 0,031). CONCLUSION: La fourniture de services de diagnostic de la TB centrés sur la personne à divers points d'accès pourrait permettre d'atteindre différentes populations, ce qui pourrait favoriser un diagnostic précoce et contribuer à combler le fossé en matière de diagnostic.

Adaptation and validation of a TB stigma scale for adolescents in Lima, Peru.

BACKGROUND: TB-related stigma contributes to poor clinical outcomes and reduced wellbeing for affected individuals. Adolescents may be particularly susceptible to TB-related stigma due to their heightened sensitivity to peer acceptance, yet few studies have evaluated TB-related stigma in this group. Without a validated scale, it remains challenging to measure TB-related stigma in adolescents.METHODS: We adapted and validated the Van Rie TB Stigma Scale (VTSS) for adolescents on treatment for rifampicin-susceptible TB in Lima, Peru. The modified stigma scale was administered within a larger survey, which measured other psychosocial factors, including depression, adverse childhood experiences (ACEs), and social support. Data analysis included factor analysis, internal consistency, and convergent validity.RESULTS: From October 2020 to September 2021, 249 adolescents (individuals aged 10-19 years) completed the survey. Preliminary confirmatory factor analysis led to removal of two items. The final 10-item scale demonstrated good internal consistency (Cronbach's α = 0.82) and adequate model fit (χ²/df = 2.0; root mean square error of approximation: 0.06; comparative fit index: 0.94; Tucker-Lewis Index: 0.92: standardized root mean square residual: 0.05). Stigma was positively correlated with ACEs (γ = 0.13), depression (γ = 0.39), and suicidal ideation (γ = 0.27), and negatively correlated with social support (γ = -0.19).CONCLUSION: This adolescent TB stigma scale may serve as a practical tool to measure TB-related stigma and evaluate the impact of stigma-reduction interventions in adolescents.

Latent TB and depressive symptoms in household contacts of persons with active TB.

BACKGROUND: Depression is common among persons with TB and is associated with poor clinical outcomes. However, little is known about the relationship between latent TB infection (LTBI) and depression. We assessed the association between LTBI and depressive symptoms among household contacts (HHCs) of patients receiving TB treatment.METHODS: We enrolled 1,009 HHCs of 307 patients receiving TB treatment in Lima, Peru, during 2016-2018. At enrollment, HHC LTBI status was assessed using the interferon-gamma release assay (IGRA). Depressive symptoms were assessed at baseline and 12 months later using the Patient Health Questionnaire-9 (PHQ-9) with a cut-off of ≥5. We used logistic regression to estimate the odds ratio (OR) for PHQ-9 ≥5, comparing HHCs with and without baseline LTBI.RESULTS: Among 921 HHCs, 374 (41.0%) had LTBI at baseline, and 69 (12.4%) of 567 HHCs had PHQ-9 ≥5. Compared to HHCs without LTBI at enrollment, those with LTBI had almost two times the odds of PHQ-9 ≥5 at follow-up after controlling for potential confounders (adjusted OR 1.93, 95% CI 1.09-3.39); this association was driven by greater severities of depressive symptoms.CONCLUSION: HHCs with LTBI had increased odds of depressive symptoms 1 year later. This population may benefit from mental health screening and interventions integrated into TB programs.

Culture-negative TB: clinical characteristics, risk factors and treatment outcomes.

BACKGROUND: Although culture remains the standard for TB diagnosis, 15-20% of patients diagnosed and treated for TB are culture-negative. We explored clinical characteristics, risk factors and treatment outcomes for culture-negative TB in a Peruvian cohort.METHODS: We recruited 4,500 index TB patients and 10,160 household contacts in Lima, Peru, and enrolled 692 secondary patients diagnosed with TB during follow-up of household contacts. We analyzed smear and culture status, sociodemographic factors, clinical characteristics and TB treatment outcomes to compare culture-negative and positive patients.RESULTS: Of the 4,880 adult patients, 915 (18.8%) were culture-negative. Culture-negative patients were less likely to report symptoms of TB disease and disease of longer duration. A multivariate analysis showed no statistically significant difference in loss to follow-up, treatment failure or recurrence between the culture-negative and -positive groups but a higher rate of death among culture-negative patients with an adjusted OR of 1.65 (95% CI 1.05-2.60). In a multivariate analysis of determinants of culture negativity, older age, substance use and being a secondary case were associated with culture status.CONCLUSIONS: More recognition and awareness of culture-negative TB is key for early and correct diagnosis to reduce transmission and improve treatment outcomes.

Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications.

BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015-2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0-82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.

Using digital chatbots to close gaps in healthcare access during the COVID-19 pandemic.

INTRODUCTION: Chatbots have emerged as a first link to care in recent years. The COVID-19 pandemic, and consequent health system disruptions, expanded their use. Socios En Salud (SES) introduced chatbots in Peru, which experienced one of the highest excess COVID mortalities in the world. METHODS: SES and the government identified unmet population health needs, which could be amenable to virtual interventions. Chatbots were developed to screen individuals for these conditions; we describe the period of deployment, number of screenings, and number of people who received services. RESULTS: Between April 2020 and May 2021, SES deployed nine ChatBots: four for mental health, two for maternal and child health, and three for chronic diseases: breast cancer, hypertension, diabetes mellitus, and obesity. Mental health services were provided to 42,932 people, 99.99% of those offered services. The other ChatBots reached fewer people. Overall, more than 50% of eligible people accepted chatbot-based services. DISCUSSION: ChatBot use was highest for mental health. Chatbots may increase connections between a vulnerable population and health services; this is likely dependent on several factors, including condition, population, and penetration of smart phones. Future research will be critical to understand user experience and preferences and to ensure that chatbots link vulnerable populations to appropriate, high-quality care.

INTRODUCTION: Les chatbots se sont imposés comme un premier lien aux soins ces dernières années. La pandémie de COVID-19, et les perturbations du système de santé qui en ont résultées, ont élargi leur champ d'application. Socios En Salud (SES) a introduit les chatbots au Pérou, qui a connu l'une des surmortalités dues au COVID les plus élevées au monde. MÉTHODES: SES et le gouvernement ont identifié des besoins non satisfaits en matière de santé de la population, qui pourraient faire l'objet d'interventions virtuelles. Des chatbots ont été développés pour dépister des individus pour ces conditions ; nous décrivons la période de leur déploiement, le nombre de dépistages et le nombre de personnes qui ont reçu ces services. RÉSULTATS: Entre avril 2020 et mai 2021, SES a déployé neuf ChatBots : quatre pour la santé mentale, deux pour la santé maternelle et infantile et trois pour les maladies chroniques, comme le cancer du sein, l'hypertension, le diabète et l'obésité. Des services de santé mentale ont été fournis à 42 932 personnes, soit 99,99% des personnes proposées. Les autres ChatBots ont touché moins de personnes. Dans l'ensemble, plus de 50% des personnes éligibles ont accepté les services proposés par les chatbots. DISCUSSION: L'utilisation des ChatBots était la plus élevée pour la santé mentale. Les chatbots peuvent augmenter les connexions entre une population vulnérable et les services de santé, mais cela dépende de plusieurs facteurs, dont la condition, la type de population et la pénétration des smartphones. Les recherches futures seront essentielles pour comprendre l'expérience et les préférences des utilisateurs et pour s'assurer que les chatbots relient les populations vulnérables vulnérables aux soins appropriés et de qualité.

Effectiveness of multimodal exercises integrated with cognitive-behavioral therapy in working patients with chronic neck pain: protocol of a randomized controlled trial with 1-year follow-up.

BACKGROUND: The etiology of neck pain is multifactorial and includes personal and work-related factors such as age, sex, wrong postures, and repeated strains. Studies based on bio-psychosocial model also link chronic neck pain to psychological factors. Over time, the use of multidisciplinary interventions for chronic neck pain has grown in order to improve disability, pain, and adaptive cognitions and behaviors towards patients' problems. The objective is to evaluate the effectiveness of an individual-based multidisciplinary rehabilitation program that integrates cognitive-behavioral therapy focused on kinesiophobia with specific exercises in the treatment of patients with chronic neck pain, employed in different working activities. METHODS: A randomized, parallel-group superiority-controlled trial will be conducted with 1-year follow-up. One hundred seventy patients engaged in several working activities (blue collar and white collar workers) will be randomly allocated to either the experimental (receiving a multidisciplinary rehabilitation program combining multimodal exercises with psychologist-lead cognitive-behavioral therapy sessions) or the control group (receiving general care physiotherapy). Both groups will follow individual-based programs once a week for 10 weeks. The main outcome measures will be the Neck Disability Index, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, a pain numerical rating scale, the Short-Form Health Survey, and the Work Ability Index. Participants will be evaluated before, after training, and after 12 months. DISCUSSION: Findings may provide empirical evidence on the effectiveness of an individual-based multidisciplinary rehabilitation program on inducing clinically significant and long-term improvements in the disability, pain, psychological factors, and quality of life of workers with chronic neck pain and that these would be maintained in the long term. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities' recommendations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04768790 . Registered on 24 February 2021.

A structured community engagement strategy to support uptake of TB active case-finding.

BACKGROUND: In Lima, Peru, a mobile TB screening program ("TB Móvil") was implemented in high TB prevalence districts to increase TB screening. Community engagement activities to promote TB Móvil were simultaneously conducted. OBJECTIVE: To describe a structured, theory-driven community engagement strategy to support the uptake of TB Móvil. METHODS: We adapted Popular Opinion Leader (POL), an evidence-based social networking intervention previously used in Peru to promote HIV testing, for TB Móvil. Community health workers, women who run soup kitchens, and motorcycle taxi drivers served as "popular opinion leaders" who disseminated information about TB Móvil in everyday conversations, aided by a multi-media campaign. Performance indicators of POL included the number/characteristics of persons screened; number of multimedia elements; and proportion of persons with abnormal radiographs hearing about TB Móvil before attending. RESULTS: Between February 2019 and January 2020, 63,899 people attended the TB Móvil program at 210 sites; 60.1% were female. The multimedia campaign included 36 videos, 16 audio vignettes, flyers, posters, community murals and "jingles." Among attendees receiving an abnormal chest X-ray suggestive of TB, 48% (6,935/14,563) reported hearing about TB Móvil before attending. CONCLUSIONS: POL promotes the uptake of TB Móvil and should be considered as a strategy for increasing TB screening uptake.

CONTEXTE: À Lima, Pérou, un programme mobile de dépistage de la TB (« TB Móvil ¼) a été mis en place dans les quartiers à forte prévalence de TB afin d'accroître le dépistage de la maladie. Des activités de mobilisation communautaire visant à promouvoir TB Móvil ont été menées en parallèle. L'objectif de ce rapport est de décrire une stratégie structurée de mobilisation communautaire, fondée sur des principes théoriques, afin de soutenir le recours au programme TB Móvil. MÉTHODES: Nous avons adapté à TB Móvil l'intervention factuelle de réseautage social appelée « Popular Opinion Leader (POL; leader d'opinion) ¼, précédemment utilisée au Pérou pour promouvoir le dépistage du VIH. Les agents de santé communautaires, les femmes responsables de la soupe populaire et les chauffeurs de mototaxis étaient des leaders d'opinion. Ils communiquaient des informations sur TB Móvil lors de leurs conversations quotidiennes, qui étaient étayées par une campagne multimédia. Les indicateurs de performance des POL comprenaient le nombre/les caractéristiques des personnes dépistées, le nombre d'éléments multimédias et le pourcentage de personnes avec cliché radiographique anormal qui avaient entendu parler de TB Móvil avant de se faire dépister. RÉSULTATS: Entre février 2019 et janvier 2020, 63 899 personnes ont pris part au programme TB Móvil dans 210 sites ; 60,1% étaient des femmes. La campagne multimédia reposait sur 36 vidéos, 16 vignettes audio, des prospectus, des posters, des peintures murales dans la communauté et des « jingles ¼. Parmi les personnes dont la radiographie pulmonaire était anormale et évocatrice de TB, 48% (6 935/14 563) ont rapporté avoir entendu parler de TB Móvil avant de venir consulter. CONCLUSIONS: L'intervention POL, qui semblait renforcer le recours au programme TB Móvil, peut donc servir d'une stratégie de promotion du dépistage de la TB.

Integrated screening and testing for TB and COVID-19 in Peru.

We describe the experience of integrating COVID-19 screening and testing into a mobile TB screening unit in Lima, Peru. All attendees received chest radiographs, which were analysed using CAD4TB and CAD4COVID; Xpert MTB/RIF Ultra was used to test for TB, and antibody and polymerase chain reaction (PCR) for SARS-CoV-2. One Xpert-positive TB case was diagnosed per 168 people screened, one person with SARS-CoV-2 antibodies per 3 people screened, and one PCR-confirmed SARS-CoV-2 infection per 8 people screened. Integrated screening can help to avoid delays in the diagnosis of both TB and COVID-19.

Nous décrivons l'expérience de l'intégration du dépistage et du test COVID-19 dans une unité mobile de dépistage de la TB à Lima, au Pérou. Toutes les personnes présentes ont reçu des radiographies pulmonaires, qui ont été analysées à l'aide de CAD4TB et CAD4COVID ; Xpert® MTB/RIF Ultra a été utilisé pour le dépistage de la TB, et les anticorps et la réaction en chaîne par polymérase (PCR) pour le SARS-CoV-2. Un cas de TB Xpert-positif a été diagnostiqué pour 168 personnes dépistées, une personne présentant des anticorps du SARS-CoV-2 pour 3 personnes dépistées et une infection du SARS-CoV-2 confirmée par PCR pour 8 personnes dépistées. Le dépistage intégré peut contribuer à éviter les retards dans le diagnostic de la TB et du COVID-19.

Characterization of hand forces exerted during non-powered hospital bed pushing and pulling tasks.

Accurate assessment of biomechanical risk associated with pushing/pulling tasks represents a challenging issue, especially in the health system where personnel are often required to maneuver beds and carts. Most studies in this field have been carried out in the laboratory, while few data have been collected under actual working conditions. This study aims to characterize the forces exerted during non-powered hospital bed maneuvering. Twenty participants were required to move a bed (equipped with a customized handlebar to measure exerted forces) along an actual hospital path including straight, turn and maneuver phases. The results show that higher forces are associated with the initial phase (peak and mean values 222 and 68 N) while the straight, turn and maneuvering phases required similar (lower) efforts. The combined effect of left, right and transversal forces suggests that the trunk of the operator might experience axial rotation, thus calling for further investigations of this aspect.

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial.

BACKGROUND: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. METHODS: endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. DISCUSSION: The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

Uncovering reasons for treatment initiation delays among children with TB in Lima, Peru.

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0-14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7-117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

Introducing new and repurposed TB drugs: the endTB experience.

In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015-2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.

Occupational low-level exposure to hard metals: cobalt and tungsten biomonitoring as an effective tool to evaluate the effectiveness of industrial hygiene interventions for risk management.

Purpose: The aim of the study was to assess the exposure to Cobalt (Co) and Tungsten (W) in a group of hard metal tool sharpeners through a combined approach of air and biological monitoring, and to evaluate the effectiveness of a control and improvement intervention carried out in collaboration with the medical officers of the local Health Protection Agency, by biomonitoring.Methods: We enrolled 132 workers from 17 companies of the province of Brescia, northern Italy. The study was performed in two phases: (1) an environmental and biomonitoring survey to assess the workers' exposure to Co and W at their usual working conditions; (2) a further biomonitoring survey 3 months after the enforcement of a control and improvement intervention, to assess its effectiveness.Results: Workers were found to be exposed to low concentration of airborne dust containing Co and W but after the intervention we recorded a significant decrease of the urinary concentrations of both Co and W. The extent of the decrease was correlated to the number of preventive industrial hygiene interventions that were carried out.Conclusions: Biological monitoring of Co and W in the hard metal tools manufacturing industry is a sensitive and effective method to evaluate the effectiveness of prevention practices.

Performance of a household tuberculosis exposure survey among children in a Latin American setting.

OBJECTIVE: To evaluate the performance of a survey that quantifies the intensity of household tuberculosis (TB) exposure among children.METHODS: Children aged 0-14 years in Lima, Peru, with ≥1 signs and/or symptoms of TB and a history of contact with an adult TB patient were included. The 10-question survey was administered to caregivers and addressed sleep proximity, frequency of exposure, and infectiousness of the contact. Infection status was determined using tuberculin skin tests (TSTs). The exposure scale was evaluated for association with TST positivity using mixed-effects regression analyses.RESULTS: The exposure score was significantly associated with TST positivity (age-adjusted odds ratio [aOR] 1.14, 95%CI 1.02-1.28). We observed a stronger association with TST positivity in children aged ≤5 years; (aOR 1.23, 95%CI 1.07-1.41) and no association in children 6-14 years of age (aOR 0.99, 95%CI 0.82-1.20).CONCLUSION: This survey was easy to use and modestly successful in predicting TST positivity in children aged ≤5 years. It may be a useful resource for clinicians for diagnosing TB in children, and for national TB programs aiming to scale up preventive therapy initiatives.

Feasibility and yield of screening for non-communicable diseases among treated tuberculosis patients in Peru.

INTRODUCTION: The increasing prevalence of non-communicable diseases (NCDs) poses a major challenge to low- and middle-income countries. Patients' engagement with health services for anti-tuberculosis treatment provides an opportunity for screening for NCDs and for linkage to care. METHODS: We explored the feasibility and yield of screening for NCDs in patients treated for tuberculosis (TB) in Lima, Peru, as part of a study focused on chronic respiratory sequelae. A representative sample of community controls was recruited from the same geographical area. Screening entailed taking a medical history and performing ambulatory blood pressure measurement and urinalysis. RESULTS: A total of 177 participants with previous TB (33 with multidrug-resistant TB) and 161 community controls were evaluated. There was an almost four-fold increased prevalence of self-reported diabetes mellitus (DM) in the TB group (adjusted prevalence ratio 3.66, 95%CI 1.68-8.01). Among those without self-reported DM, 3.3% had glycosuria, with a number needed to screen (NNS) of 31. The NNS to find one (new) case of hypertension or proteinuria in the TB group was respectively 24 and 5. CONCLUSION: Patient-centred care that includes pragmatic NCD screening is feasible in TB patients, and the treatment period provides a good opportunity to link patients to ongoing care.

Mental disorders and drug/alcohol use in patients commencing extensively drug-resistant tuberculosis treatment.

Mental disorders and alcohol/drug use worsen treatment outcomes for multidrug-resistant tuberculosis (TB), but data are lacking for extensively drug-resistant (XDR) TB. We investigated the association of baseline mental disorders and alcohol/drug use on XDR-TB treatment outcomes in a retrospective study of 53 XDR-TB Peruvian patients during 2010-2012. Logistic regression estimated the odds ratios for unfavourable XDR-TB treatment outcomes. Overall treatment success was 25%. Mental disorders and drug/alcohol use were found in respectively 22.4% and 20.4% of patients; neither were associated with unfavourable treatment outcomes. Future research should explore the relationship between mental health and drug/alcohol use in XDR-TB treatment outcomes.

Les troubles mentaux et la consommation d'alcool/de drogue entravent le résultat du traitement de la tuberculose multirésistante (TB-MDR), mais on manque de données pour la TB ultrarésistante (TB-XDR). Nous avons examiné l'association de troubles mentaux préexistants et de consommation d'alcool/de drogue sur le résultat du traitement de la TB-XDR dans une étude rétrospective de 53 patients péruviens atteints de TB-XDR en 2010­2012. Une régression logistique a estimé les odds ratios de résultat défavorable du traitement de la TB-XDR. Le taux d'ensemble de succès du traitement a été de 25%. Des troubles mentaux et une consommation d'alcool/de drogue ont été constatés chez respectivement 22,4% et 20,4% des patients ; aucun n'a été associé à un résultat défavorable du traitement. Des recherches ultérieures devraient explorer la relation entre santé mentale et consommation de drogue/alcool et leur impact sur le traitement de la TB-XDR.

Los trastornos mentales y el consumo de alcohol y de drogas agravan los desenlaces terapéuticos de la tuberculosis multidrogorresistente (TB-MDR), pero no existen datos en cuanto a la TB extremadamente resistente (TB-XDR). En un estudio retrospectivo en 53 pacientes peruianos que padecieron TB-XDR del 2010 al 2012, se investigó la asociación de la presencia inicial de trastornos mentales y consumo de alcohol o drogas con los desenlaces del tratamiento de la TB-XDR. Mediante un modelo de regresión logística se calcularon los cocientes de posibilidades de desenlaces terapéuticos desfavorables. La tasa global de éxito terapéutico fue de 25%. Se encontró que el 22,4% de los pacientes sufría trastornos mentales y el 20,4% consumía alcohol o drogas; ninguna de estas características se asoció con desenlaces desfavorables del tratamiento. Nuevas investigaciones tendrán que explorar la correlación que existe entre la salud mental y el consumo de alcohol o drogas y los desenlaces terapéuticos de la TB-XDR.