Tuberculosis-Associated Respiratory Disability in Children, Adolescents, and Adults: Protocol for a Systematic Review and Individual Participant Data Meta-Analysis.

Background: Approximately 2% of the global population has survived tuberculosis (TB). Increasing evidence indicates that a significant proportion of pulmonary TB survivors develop TB-associated respiratory disability, commonly referred to as post-TB lung disease (PLTD) and marked by impaired respiratory function, persistent symptoms, and activity limitations. However, the prevalence, risk factors, and progression of TB-associated respiratory disability throughout the life course are not well understood. To address these gaps, we will undertake a systematic review and individual participant-level data meta-analysis (IPD-MA) focusing on TB-associated respiratory disability in children, adolescents, and adults successfully treated for pulmonary TB. Methods and analysis: We will systematically search MEDLINE, Embase, CENTRAL, Global Index Medicus, and medRxiv for original studies investigating TB-associated respiratory disability in people of all ages who have completed treatment for microbiologically confirmed or clinically diagnosed pulmonary TB. Authors of eligible studies will be invited to contribute de-identified data and form a collaborative group. Primary outcomes will be (1) abnormal lung function based on spirometry parameters and (2) chronic respiratory symptoms. We will estimate the overall and subgroup-specific prevalence of each outcome through IPD meta-analysis. Next, we will develop clinical prediction tools assessing the risk of future TB-associated respiratory disability at (i) the start of TB treatment and (ii) end of TB treatment for those without existing signs of disability. Finally, we will use stepwise hierarchical modelling to identify epidemiological determinants of respiratory disability. Ethics and dissemination: This study has been approved by the ethics review boards at the Rhode Island Hospital (2138217-2) and the Research Institute of the McGill University Health Centre (2024-10345). Individual study authors will be required to obtain institutional approval prior to sharing data. Results will be disseminated through open-access, peer-reviewed publications and conference presentations. Prospero registration number: CRD42024529906.

Assessing the Impact of the Metal Artifact Reduction Tool on Detecting Furcation Lesions in Maxillary Molars with Different Intracanal Posts: An Ex Vivo Cone-beam Computed Tomography Study.

INTRODUCTION: Considering the potential image compromise and diagnostic challenges posed by metals, this study aimed to assess the efficacy of the metal artifact reduction (MAR) tool in cone-beam computed tomography examinations for detecting furcation lesions in upper molars treated endodontically and restored with different intracanal posts. METHODS: This ex vivo study used 45 endodontically treated maxillary first molars, categorized into the following3 groups (n = 15): control (without intracanal post), metal post, and fiberglass post. Simulations were conducted in the laboratory to replicate alveolar bone, periodontal ligament, and grade I, II, and III furcation lesions. Cone-beam computed tomography scans were obtained with and without the MAR tool, and the furcation lesions were evaluated considering a 5-point Likert scale. Data were analyzed at 5%. RESULTS: In the control group, there was no influence of MAR (P > .05); grade II lesions were not diagnosed, and grade III lesions were the most detected (P < .05). In the metal post group with MAR, grade III lesions were diagnosed more frequently than I and II (P < .05) and grade III without MAR (P < .05). In the fiberglass post group, the diagnosis of grade I lesions decreased with MAR (P < .05), and without MAR, grade III was most diagnosed (P < .05); grade III lesions were the most diagnosed (P < .05). CONCLUSIONS: The MAR tool was only effective for diagnosing grade III furcation lesions, regardless of the intracanal material. Its application for grade I and II lesions did not contribute to improved diagnosis. Furthermore, in the fiberglass post group with grade I lesions, the MAR tool negatively affected the detection of the lesions.

Long-Term Protective Effect of Tuberculosis Preventive Therapy in a Medium/High Tuberculosis Incidence Setting.

BACKGROUND: The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings. METHODS: We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated. RESULTS: The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01- 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3-5.6] vs 1.1 [.4-2.3] per 1000 PY; IR ratio, 2.7 [1.0-7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6-6.6] vs 1.1 [.5-2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2-8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1-9.7]). CONCLUSIONS: In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis.

Interleukin-6 and -27 as potential novel biomarkers for human pleural tuberculosis regardless of the immunological status.

Tuberculosis (TB) is the leading cause of pleural exudative effusions. Inflammatory markers, such as IFNγ and ADA, have been used as proxies for its diagnosis. We evaluated ex vivo levels of several cytokines in 83 pleural effusion specimens from patients with TB (including 10 with HIV co-infection) and 26 patients with other pleuritis using multiplex and ELISA assays. IL-6 and IL-27 levels were higher (p ≤ 0.04) in TB patients, regardless of the HIV status and the approach. IL-2, IL-4, IL-8, IFNγ, TNF and G-CSF showed variable results depending on the assay. This warranty these markers to be further validated.

Association of indicators of extensive disease and rifampin-resistant tuberculosis treatment outcomes: an individual participant data meta-analysis.

BACKGROUND: Indicators of extensive disease-acid fast bacilli (AFB) smear positivity and lung cavitation-have been inconsistently associated with clinical rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) outcomes. We evaluated the association of these indicators with end-of-treatment outcomes. METHODS: We did an individual participant data meta-analysis of people treated for RR/MDR-TB with longer regimens with documented AFB smear and chest radiography findings. We compared people AFB smear-negative without cavities to people: (1) smear-negative with lung cavities; (2) smear-positive without lung cavities and (3) AFB smear-positive with lung cavities. Using multivariable logistic regression accounting for demographic, treatment and clinical factors, we calculated adjusted ORs (aOR) for any unfavourable outcome (death, lost to follow-up, failure/recurrence), and mortality and treatment failure/recurrence alone. RESULTS: We included 5596 participants; included participants significantly differed from excluded participants. Overall, 774 (13.8%) were AFB smear-negative without cavities, 647 (11.6%) only had cavities, 1424 (25.4%) were AFB smear-positive alone and 2751 (49.2%) were AFB smear-positive with cavities. The median age was 37 years (IQR: 28-47), 3580 (64%) were male and 686 (12.5%) had HIV. Compared with participants AFB smear-negative without cavities, aOR (95% CI) for any unfavourable outcome was 1.0 (0.8 to 1.4) for participants smear-negative with lung cavities, 1.2 (0.9 to 1.5) if smear-positive without cavities and 1.6 (1.3 to 2.0) if AFB smear-positive with lung cavities. Odds were only significantly increased for mortality (1.5, 95% CI 1.1 to 2.1) and failure/recurrence (2.2, 95% CI 1.5 to 3.3) among participants AFB smear-positive with lung cavities. CONCLUSION: Only the combination of AFB smear-positivity and lung cavitation was associated with unfavourable outcomes, suggesting they may benefit from stronger regimens.

A Systematic Review and Meta-Analysis of Tuberculous Preventative Therapy Adverse Events.

BACKGROUND: Tuberculosis preventative therapy (TPT) is a key part of the World Health Organization's (WHO) end tuberculosis (TB) strategy. However, the occurrence of potentially serious adverse events (AE) is a limitation of TPT regimens. We conducted a systemic review and meta-analysis to estimate the incidence of AE and hepatotoxicity with various TPT regimens to help inform clinical decision making. METHODS: We searched MEDLINE, Cochrane, Health Star, and EMBASE from 1952 to April 2021 for studies reporting AE associated with TPT. Included studies reported AE stratified by regimen and provided the number of participants receiving each regimen. We used a random-effect model to meta-analyze the cumulative incidence of AE. RESULTS: We included 175 publications describing TPT-related AE in 277 cohorts. Among adults, the incidence of any AE, and hepatotoxicity leading to drug discontinuation was 3.7% and 1.1%, respectively, compared to 0.4% and 0.02%, respectively, in children. The highest incidence of any AE, and AE leading to drug discontinuation was with 3 months isoniazid and rifapentine (3HP), and the lowest was with 4 months rifampin (4R). 4R also had the lowest incidence of hepato-toxic AE and drug discontinuation due to hepato-toxic AE. 3HP also had a low incidence of hepato-toxic AE. CONCLUSIONS: Although our study was limited by variability in methods and quality of AE reporting in the studies reviewed, pediatric populations had a very low incidence of AE with all TPT regimens reviewed. In adults, compared to mono-H regimens all rifamycin-based regimens were safer, although 4R had the lowest incidence of TPT-related AE of all types and of hepatotoxicity.

Residual respiratory disability after successful treatment of pulmonary tuberculosis: a systematic review and meta-analysis.

Background: Pulmonary tuberculosis (PTB) can result in long-term health consequences, even after successful treatment. We conducted a systematic review and meta-analysis to estimate the occurrence of respiratory impairment, other disability states, and respiratory complications following successful PTB treatment. Methods: We identified studies from January 1, 1960, to December 6, 2022, describing populations of all ages that successfully completed treatment for active PTB and had been assessed for at least one of the following outcomes: occurrence of respiratory impairment, other disability states, or respiratory complications following PTB treatment. Studies were excluded if they reported on participants with self-reported TB, extra-pulmonary TB, inactive TB, latent TB, or if participants had been selected on the basis of having more advanced disease. Study characteristics and outcome-related data were abstracted. Meta-analysis was performed using a random effects model. We adapted the Newcastle Ottawa Scale to evaluate the methodological quality of the included studies. Heterogeneity was assessed using the I2 statistic and prediction intervals. Publication bias was assessed using Doi plots and LFK indices. This study is registered with PROSPERO (CRD42021276327). Findings: 61 studies with 41,014 participants with PTB were included. In 42 studies reporting post-treatment lung function measurements, 59.1% (I2 = 98.3%) of participants with PTB had abnormal spirometry compared to 5.4% (I2 = 97.4%) of controls. Specifically, 17.8% (I2 = 96.6%) had obstruction, 21.3% (I2 = 95.4%) restriction, and 12.7% (I2 = 93.2%) a mixed pattern. Among 13 studies with 3179 participants with PTB, 72.6% (I2 = 92.8%) of participants with PTB had a Medical Research Council dyspnoea score of 1-2 and 24.7% (I2 = 92.2%) a score of 3-5. Mean 6-min walk distance in 13 studies was 440.5 m (I2 = 99.0%) in all participants (78.9% predicted, I2 = 98.9%) and 403.0 m (I2 = 95.1%) among MDR-TB participants in 3 studies (70.5% predicted, I2 = 97.6%). Four studies reported data on incidence of lung cancer, with an incidence rate ratio of 4.0 (95% CI 2.1-7.6) and incidence rate difference of 2.7 per 1000 person-years (95% CI 1.2-4.2) when compared to controls. Quality assessment indicated overall low-quality evidence in this field, heterogeneity was high for pooled estimates of nearly all outcomes of interest, and publication bias was considered likely for almost all outcomes. Interpretation: The occurrence of post-PTB respiratory impairment, other disability states, and respiratory complications is high, adding to the potential benefits of disease prevention, and highlighting the need for optimised management after successful treatment. Funding: Canadian Institutes of Health Research Foundation Grant.

GeneXpert or chest-X-ray or tuberculin skin testing for household contact assessment (GXT): protocol for a cluster-randomized trial.

BACKGROUND: The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5. METHODS: This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0-50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the "Comité Local d'Éthique Pour la Recherche Biomédicale (CLERB) de l'Université de Parakou," Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries. DISCUSSION: This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04528823.

Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis.

BACKGROUND: The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes. METHODS: We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (BMI <18.5 kg/m2) and not underweight. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by human immunodeficiency virus (HIV) status and other variables using likelihood ratio tests. We also estimated cumulative incidence of mortality during treatment stratified by HIV. RESULTS: Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (interquartile range) age was 37 years (29 to 47), and 455 (9%) had HIV. Compared with nonunderweight patients, the aOR among underweight patients was 1.7 (95% CI, 1.4-1.9) for any unfavorable outcome, 3.1 (2.4-3.9) for death, and 1.6 (1.2-2.0) for failure/recurrence. Significant effect modification was found for World Health Organization region of treatment. Among HIV-negative patients, 24-month mortality was 14.8% (95% CI, 12.7%-17.3%) for underweight and 5.6% (4.5%-7.0%) for not underweight patients. Among patients with HIV, corresponding values were 33.0% (25.6%-42.6%) and 20.9% (14.1%-27.6%). CONCLUSIONS: Low BMI at treatment initiation for RR-TB is associated with increased odds of unfavorable treatment outcome, particularly mortality.

Scaling up investigation and treatment of household contacts of tuberculosis patients in Brazil: a cost-effectiveness and budget impact analysis.

Background: In Brazil, investigation and treatment of tuberculosis infection (TBI) in households contacts (HHC) of TB patients is not a priority. We estimated the cost-effectiveness and budget-impact of scaling-up an enhanced HHC management in Brazil. Methods: We conceptualized a cascade-of-care that captures how HHC of tuberculosis patients are investigated in Brazil (status quo) and two enhanced strategies for management of HHC focusing on: (1) only tuberculosis disease (TBD) detection and, (2) TBD and TBI detection and treatment. Effectiveness was the number of HHC diagnosed with TBD and completing TBI treatment. Proportions in the cascades-of-care were derived from a meta-analysis. Health-system costs (2019 US$) were based on literature and official data from Brazil. The impact of enhanced strategies was extrapolated using reported data from 2019. Findings: With the status quo, 0 (95% uncertainty interval: 0-1) HHC are diagnosed with TBD and 2 (0-16) complete TBI treatment. With strategy(1), an additional 15 (3-45) HHC would be diagnosed with TBD at a cost of US$346 each. With strategy(2), 81 (19-226) additional HHC would complete TBI treatment at a cost of US$84 each. A combined strategy, implemented nationally to enhance TBD detection and TBI treatment would result in an additional 9,711 (845-28,693) TBD being detected, and 51,277 (12,028-143,495) more HHC completing TBI treatment each year, utilizing 10.9% and 11.6% of the annual national tuberculosis program budget, respectively. Interpretation: Enhanced detection and treatment of TBD and TBI among HHC in Brazil can be achieved at a national level using current tools at reasonable cost. Funding: None.

Crianças com necessidades de saúde especiais em um serviço de pronto atendimento pediátrico: estudo transversal / Children with special health care needs in a pediatric emergency service: a cross-sectional study / Niños con necesidades especiales de salud en un servicio de urgencias pediátricas: estudio transversal

Objetivos: rastrear crianças com necessidades de saúde especiais em um serviço de pronto atendimento pediátrico e analisar suas demandas de cuidado. Método: estudo transversal, desenvolvido de março a junho de 2019, em serviço hospitalar de emergência infantil, no município de Rio das Ostras, Rio de Janeiro, Brasil. Aplicaram-se a versão brasileira do Children with Special Health Care Needs Screener (CSHCN Screener®) e o instrumento caracterizador de demandas com familiares cuidadores de crianças. Utilizou-se a estatística descritiva. Resultados: crianças com necessidades de saúde especiais corresponderam a 5,1%, dentre 235 famílias rastreadas. Os principais domínios de necessidades de saúde foram maior utilização de serviços e dependência de medicamentos. Dentre as demandas de cuidados, destacaram-se os cuidados habituais modificados. Conclusão: as seis demandas de cuidados foram identificadas entre as crianças rastreadas. Recomenda-se a adoção do CSHCN Screener® para ampliar a visibilidade e indicar estratégias assistenciais a esse grupo populacional.

Objectives: to screen children with special health needs in a pediatric emergency service and analyze their care demands. Method: a cross-sectional study, carried out from March to June 2019, in a children's emergency hospital service, in the municipality of Rio das Ostras, Rio de Janeiro, Brazil. The Brazilian version of the Children with Special Health Care Needs Screener (CSHCN Screener®) and the instrument characterizing demands with family caregivers of children were applied. Descriptive statistics were used. Results: children with special health needs corresponded to 5.1% of the 235 families screened. The main domains of health needs were greater use of services and dependence on medicines. Among the care demands, the modified usual care stood out. Bottom line: the six care demands were identified among the screened children. The adoption of the CSHCN Screener® is recommended to increase visibility and indicate assistance strategies for this population group.

Objetivos: buscar los niños con necesidades especiales de salud en un servicio de urgencias pediátricas y analizar sus demandas de cuidado. Método: estudio transversal, conducido de marzo a junio de 2019, en un servicio de emergencia hospitalaria infantil, en el ayuntamiento de Rio das Ostras, Rio de Janeiro, Brasil. Se aplicó la versión brasileña del Children with Special Health Care Needs Screener (CSHCN Screener®) y el instrumento de caracterización de demandas con parientes que cuidan a sus niños. Se utilizó estadística descriptiva. Resultados: los niños con necesidades especiales de salud correspondieron al 5,1% de las 235 familias procuradas. Los principales dominios de las necesidades de salud fueron el mayor uso de los servicios y la dependencia de medicamentos. Entre las demandas de cuidado, se destacaron los cuidados habituales alterados. Conclusión: las seis demandas de cuidado fueron identificadas entre los niños evaluados. Se recomienda la adopción del CSHCN Screener® para aumentar la visibilidad e indicar estrategias de atención a este grupo poblacional.

Habilidades de autorregulação emocional e resolução de problemas interpessoais em pré-escolares: relato de experiência / Emotional self-regulation skills and interpersonal problem-solving skills in preschoolers: experience report / Habilidades de autorregulación emocional y resolución de problemas interpersonales en niños en edad preescolar: relato de experiencia

Este trabalho relata a experiência de um grupo de graduandas, vinculadas ao Programa de Educação Tutorial do Ministério da Educação, sobre a imple-mentação de um projeto de promoção das habilidades de autorregulação emocional e resolução de problemas interpessoais em uma escola de educação infantil. Considera-se a idade pré-escolar como estratégica para intervenções de prevenção e promoção em saúde mental e a escola como o contexto mais propício para intervenções proativas. Participaram aproximadamente 80 alunos, com média de 5 anos de idade, de quatro turmas do segundo período de uma escola municipal de educação infantil da cidade de Juiz de Fora/MG. A intervenção subdividiu-se em dois eixos de trabalho: autorregulação emocional e resolução de problemas interpessoais, realizada mediante seis encontros semanais para cada eixo, com a utilização de recursos lúdicos e audiovisuais. A atividade foi avaliada de forma bastante positiva pelas docentes, que rela-taram a apropriação e utilização dos conteúdos pelas crianças, bem como a sua transposição para a sala de aula. Conclui-se que projetos dessa natureza devem ser estimulados com maior frequência na escola, considerando seu potencial de prevenção de comportamentos agressivos e promoção de desenvolvimento socioemocional na infância.

This paper reports on the experience of a group of students, associated with the Tutorial Education Program of the Ministry of Education in Brazil, with a project to promote emotional self-regulation skills and interpersonal problem--solving skills in a preschool. Pre school is known as a strategic period for prevention and promotion actions in mental health and schools are the most proper environment for proactive actions. About 80 students participated, with an average age of 5 years old, from four second period classes of a public city preschool in the city of Juiz de Fora, state of Minas Gerais. The intervention was subdivided into two axes: emotional self-regulation and interpersonal problem-solving. Each axis was developed through six weekly meetings, using playful and audiovisual resources. The intervention was assessed positively by the teachers, who reported that the children learned and used the concepts, applying them in the classroom. In conclusion, projects like this should be stimulated more often in schools, given their potential for preventing aggressive behaviors and promoting socio-emotional development in early childhood.

Este trabajo relata la experiencia de un grupo de estudiantes de pregrado vinculados al Programa de Educación Tutorial del Ministerio de Educación, en Brasil, acerca de la implementación de un proyecto para promover las habili-dades de autorregulación emocional y resolución de problemas interpersonales en una escuela de educación infantil. La edad preescolar es estratégica para intervenciones de prevención y promoción en salud mental y la escuela es el contexto más propicio para intervenciones proactivas. Participaron aproxi-madamente 80 alumnos, con una edad promedio de 5 años, de cuatro clases del segundo período de una escuela municipal de Educación Infantil de la ciudad de Juiz de Fora, estado de Minas Gerais. La intervención se subdividió en dos ejes de trabajo: autorregulación emocional y resolución de problemas interpersonales, realizada a través de seis encuentros semanales para cada eje, con el uso de recursos lúdicos y audiovisuales. La actividad fue evaluada de manera muy positiva por las profesoras, quienes informaron la apropia-ción y uso del contenido por parte de los niños, así como su transposición a la clase. Se concluye que proyectos de esta naturaleza deben ser estimulados con mayor frecuencia en la escuela, considerando su potencial para prevenir conductas agresivas y promover el desarrollo socioemocional en la infancia.

A simple protocol for tuberculin skin test reading certification.

Although tuberculosis preventive therapy is one of the cornerstones for eliminating the disease, many barriers exist in the cascade of care for latent tuberculosis infection, including the need to certify healthcare professionals for reading tuberculin skin tests (TST). This paper proposes and evaluates a simple protocol for TST reading training. Primary care workers from different backgrounds received a 2-hour theoretical course, followed by a practical course on bleb reading. Blebs were obtained by injecting saline into sausages and then in volunteers. A certified trainer then evaluated the effectiveness of this protocol by analyzing the trainees' ability to read TST induration in clinical routine, blinded to each other's readings. Interobserver agreement was analyzed using the Bland-Altman test. The trainees' reading accuracy was calculated using two cut-off points - 5 and 10mm - and the effect of the number of readings was analyzed using a linear mixed model. Eleven healthcare workers read 53 saline blebs and 88 TST indurations, with high agreement for TST reading (0.07mm average bias). Sensitivity was 100% (94.6; 100.0) at 5mm cut-off and 87.3% (75.5; 94.7) at 10mm cut-off. The regression model found no effect of the number of readings [coefficient: -0.007 (-0.055; 0.040)]. A simple training protocol for reading TST with saline blebs simulations in sausages and volunteers was sufficient to achieve accurate TST induration readings, with no effect observed for the number of readings. Training with saline blebs injected into voluntary individuals is safer and easier than the traditional method.

The latent tuberculosis cascade-of-care among people living with HIV: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence. METHODS AND FINDINGS: We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle-Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade. A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts. CONCLUSIONS: Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT.

Effects of programmatic interventions to improve the management of latent tuberculosis: a follow up study up to five months after implementation.

BACKGROUND: Less than 19% of those needing tuberculosis (TB) preventive treatment complete it, due to losses in several steps of the cascade of care for latent TB infection. A cluster randomized trial of a programmatic public health intervention to improve management of latent TB infection in household contacts was conducted in Rio de Janeiro. Interventions included contact registry, initial and in-service training, and a TB booklet. We conducted a follow-up study starting one month after the conclusion of this trial, to measure the effect of interventions implemented, and to identify remaining barriers and facilitators to latent TB infection treatment, from different perspectives. METHODS: In two health clinics in Rio de Janeiro that received the interventions in the trial, data for the latent TB infection cascade of care for household contacts was collected over a five-month period. The number of household contacts initiating treatment per 100 index-TB patients was compared with the cascade of care data obtained before and during the intervention trial. Semi-structured open-ended questionnaires were administered to healthcare workers, household contacts and index-TB patients regarding knowledge and perceptions about TB and study interventions. RESULTS: In this follow-up study, 184 household contacts per 100 index-TB patients were identified. When compared to the intervention period, there were 65 fewer household contacts per 100 index-TB patients, (95% CI -115, - 15) but the number starting latent TB infection treatment was sustained (difference -2, 95% CI -8,5). A total of 31 index-TB patients, 22 household contacts and 19 health care workers were interviewed. Among index-TB patients, 61% said all their household contacts had been tested for latent TB infection. All health care workers said it was very important to test household contacts, and 95% mentioned that possessing correct knowledge on the benefits of latent TB infection treatment was the main facilitator to enable them to recommend this treatment. CONCLUSION: In this follow-up study, we observed a sustained effect of interventions to strengthen the latent TB infection cascade of care on increasing the number of household contacts starting latent TB infection treatment.

The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs : A Systematic Review and Meta-analysis.

BACKGROUND: Nasopharyngeal swabs are the primary sampling method used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but they require a trained health care professional and extensive personal protective equipment. PURPOSE: To determine the difference in sensitivity for SARS-CoV-2 detection between nasopharyngeal swabs and saliva and estimate the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs. DATA SOURCES: Embase, Medline, medRxiv, and bioRxiv were searched from 1 January to 1 November 2020. Cost inputs were from nationally representative sources in Canada and were converted to 2020 U.S. dollars. STUDY SELECTION: Studies including at least 5 paired nasopharyngeal swab and saliva samples and reporting diagnostic accuracy for SARS-CoV-2 detection. DATA EXTRACTION: Data were independently extracted using standardized forms, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). DATA SYNTHESIS: Thirty-seven studies with 7332 paired samples were included. Against a reference standard of a positive result on either sample, the sensitivity of saliva was 3.4 percentage points lower (95% CI, 9.9 percentage points lower to 3.1 percentage points higher) than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva's sensitivity was 1.5 percentage points higher (CI, 7.3 percentage points lower to 10.3 percentage points higher) than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less (CI, 14.7 percentage points less to 0.8 percentage point more) sensitive. In this subgroup, if testing 100 000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more (95% uncertainty interval, 5 fewer to 166 more) persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8093. LIMITATION: The reference standard was imperfect, and saliva collection procedures varied. CONCLUSION: Saliva sampling seems to be a similarly sensitive and less costly alternative that could replace nasopharyngeal swabs for collection of clinical samples for SARS-CoV-2 testing. PRIMARY FUNDING SOURCE: McGill Interdisciplinary Initiative in Infection and Immunity. (PROSPERO: CRD42020203415).

Comparing the Diagnostic Performance of QuantiFERON-TB Gold Plus to Other Tests of Latent Tuberculosis Infection: A Systematic Review and Meta-analysis.

BACKGROUND: We conducted a review to compare the sensitivity, specificity, reproducibility, and predictive ability of QuantiFERON-TB Gold Plus (QFT-Plus) with that of QuantiFERON-TB Gold In-Tube (QFT-GIT; QIAGEN, Hilden, Germany) and other latent tuberculosis infection (LTBI) tests. METHODS: We searched MEDLINE, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from January 2013 through May 2020. We included studies comparing QFT-Plus with at least one other LTBI test. We estimated sensitivity from studies of patients with active tuberculosis, and specificity from studies of healthy individuals with low risk of LTBI. Three independent reviewers evaluated eligibility, extracted data, and assessed risk of bias. RESULTS: Compared with QFT-GIT, the sensitivity of QFT-Plus in patients with active TB was 1.3% higher (95% confidence interval [CI], -0.3% to 2.9%); in 2 studies of patients with very low probability of LTBI, the specificity was 0.9% lower (95% CI, -2.4% to 0.6%). These differences were not statistically significant. The agreement between QFT-Plus and QFT-GIT was high, with a pooled Cohen's kappa statistic of 0.83 (95% CI, 0.79 to 0.88). The reproducibility of QFT-GIT and QFT-Plus was similarly poor. All participants in the studies to estimate sensitivity were aged ≥15 years, and only 6 were people living with human immunodeficiency virus. We found no studies to assess predictive ability. CONCLUSIONS: QFT-Plus has diagnostic performance that is very similar to that of QFT-GIT. Further studies are needed to assess the sensitivity of QFT-Plus in immunocompromised patients and younger children before concluding if this new version offers advantages.

Preparo de alta de famílias na promoção dos cuidados domiciliares do recém-nascido: revisão integrativa / Preparation of discharge of families in the promotion of the home care of the newborn: integrative review

Objetivo: Analisar evidências científicas da enfermagem acerca das melhores práticas relacionadas ao preparo de alta de famílias na promoção dos cuidados domiciliares do recém-nascido. Métodos: revisão integrativa da literatura realizada nos recursos informacionais LILACS, MEDLINE, BDENF, CINAHL e SCIELO, com utilização dos descritores controlados em português: "recém-nascido", "cuidado do lactente", "alta do paciente" e "enfermagem neonatal", e suas versões em inglês e espanhol, no recorte temporal de 2008 a 2018. Resultados: foram selecionados 14 estudos completos para análise interpretativa que permitiu a identificação de duas categorias: melhores práticas relacionadas ao preparo de alta de famílias de recém-nascidos e limitações no preparo de alta de famílias de recém-nascidos. Conclusão: evidenciaram-se distintas estratégias pedagógicas que podem ser desenvolvidas pela enfermagem junto aos familiares no processo de alta hospitalar, bem como a necessidade de sua efetiva aplicabilidade para a promoção dos cuidados domiciliares do recém-nascido com segurança e qualidade

Objetivo:Analizarla evidencia científica de enfermería sobre las mejores prácticas relacionadas con la preparación de las familias para recibir el alta en la promoción de la atención domiciliaria del recién nacido.Métodos: revisión integradora de la literatura realizada en los recursos de información LILACS, MEDLINE, BDENF, CINAHL y SciELO, usando descriptores controlados en portugués: "recién nacido", "cuidado del lactante", "alta del paciente" y "enfermería neonatal", y sus versiones en inglés y español, en el recorte temporal de 2008 a 2018. Resultados: se seleccionaron 14 estudios completos para análisis interpretativo que permitió la identificación de dos categorías: mejores prácticas relacionadas con la preparación de alta de familias de recién nacidos y limitaciones en la preparación de alta de familias de recién nacidos. Conclusión: se evidenció distintas estrategias pedagógicas que pueden ser desarrolladas por la enfermería junto a los familiares en el proceso de alta hospitalaria, así como la necesidad de su efectiva aplicabilidad para la promoción de los cuidados domiciliarios del recién nacido con seguridad y calidad

Objective: To analyzescientific evidence of nursing about the best practices related to preparing families to be discharged in the promotion of home care for the newborn.Methods: an integrative review of the literature on the information resources LILACS, MEDLINE, BDENF, CINAHL and SCIELO, using the descriptors controlled in Portuguese: "newborn", "infant care", "patient discharge" and "neonatal nursing" , and its versions in English and Spanish, in the time cut from 2008 to 2018. Results: 14 complete studies were selected for interpretative analysis that allowed the identification of two categories: best practices related to the preparation of discharge of newborn families and limitations in the preparation of discharge of newborn families. Conclusion: different pedagogical strategies that could be developed by nursing with family members in the hospital discharge process were evidenced, as well as the need for their effective applicability to the promotion of home care of the newborn with safety and quality

Boas práticas no cuidado ao recém-nascido com boa vitalidade na sala de parto: revisão integrativa / Good practices in caring for a newborn with good vitality in the delivery room: integrative review / Buenas prácticas en el cuidado de un recién nacido con buena vitalidad en la sala de entrega: revisión integrativa

Objetivo: analisar a produção científica brasileira sobre boas práticas relacionadas ao cuidado do recém-nascido com boa vitalidade na sala de parto. Métodos: revisão integrativa realizada em cinco recursos informacionais, mediante associação dos descritores: recém-nascido; assistência perinatal; e, parto humanizado, em português, inglês e espanhol. Resultados: 12 publicações compuseram a análise interpretativa, nas quais contato pele a pele imediato mãe-bebê, aleitamento materno precoce e clampeamento oportuno do cordão umbilical são reconhecidos como boas práticas ao recém-nascido na sala de parto. A adesão ou não a essas condutas associam-se a fatores como tipo de parto, presença de acompanhante, vínculo com a equipe de saúde, infraestrutura, disponibilidade de recursos e hospital intitulado Amigo da Criança. Conclusão: é necessária uma mudança de paradigma vislumbrando o fortalecimento do vínculo entre mãe e bebê, logo, são necessários profissionais capacitados e sensibilizados para a humanização das condutas na sala de parto

Objective: to analyze the Brazilian scientific production on good practices related to the care of newborns with good vitality in the delivery room. Method: integrative review carried out on five information resources, using the association of descriptors: newborn; perinatal care; and humanized birth, in Portuguese, English and Spanish. Results: 12 publications comprised the interpretative analysis, in which mother-infant immediate skin-to-skin contact, early breastfeeding, and timely umbilical cord clamping are recognized as good practices for the newborn in the delivery room. Adherence or not to these behaviors is associated with factors such as type of delivery, presence of companion, bond with the health team, infrastructure, availability of resources and hospital called Child Friendly

Objetivo: analizar la producción científica brasileña sobre buenas prácticas relacionadas con el cuidado de recién nacidos con buena vitalidad en la sala de partos. Método: revisión integradora en cinco recursos de información, utilizando la asociación de descriptores: recién nacido; cuidado perinatal; y nacimiento humanizado, en portugués, inglés y español. Resultados: 12 publicaciones comprendieron el análisis interpretativo, en el cual el contacto inmediato piel a piel de la madre y el bebé, la lactancia temprana y el pinzamiento oportuno del cordón umbilical se reconocen como buenas prácticas. El cumplimiento de estas se asocia a tipo de parto, presencia de acompañante, vínculo con equipo de salud, infraestructura, disponibilidad de recursos y hospital llamado Child Friendly. Conclusión: se necesita un cambio de paradigma para prever el fortalecimiento del vínculo entre la madre y el bebé, por lo tanto, se necesitan profesionales capacitados y sensibilizados para humanizar la conducta en la sala de partos

A simple protocol for tuberculin skin test reading certification / Um protocolo simples para a certificação da leitura da prova tuberculínica / Un protocolo simple para la certificación de la lectura de la prueba cutánea de tuberculina

Although tuberculosis preventive therapy is one of the cornerstones for eliminating the disease, many barriers exist in the cascade of care for latent tuberculosis infection, including the need to certify healthcare professionals for reading tuberculin skin tests (TST). This paper proposes and evaluates a simple protocol for TST reading training. Primary care workers from different backgrounds received a 2-hour theoretical course, followed by a practical course on bleb reading. Blebs were obtained by injecting saline into sausages and then in volunteers. A certified trainer then evaluated the effectiveness of this protocol by analyzing the trainees' ability to read TST induration in clinical routine, blinded to each other's readings. Interobserver agreement was analyzed using the Bland-Altman test. The trainees' reading accuracy was calculated using two cut-off points - 5 and 10mm - and the effect of the number of readings was analyzed using a linear mixed model. Eleven healthcare workers read 53 saline blebs and 88 TST indurations, with high agreement for TST reading (0.07mm average bias). Sensitivity was 100% (94.6; 100.0) at 5mm cut-off and 87.3% (75.5; 94.7) at 10mm cut-off. The regression model found no effect of the number of readings [coefficient: -0.007 (-0.055; 0.040)]. A simple training protocol for reading TST with saline blebs simulations in sausages and volunteers was sufficient to achieve accurate TST induration readings, with no effect observed for the number of readings. Training with saline blebs injected into voluntary individuals is safer and easier than the traditional method.

A terapia preventiva da tuberculose é uma das bases para a eliminação da tuberculose. Entretanto, existem muitas barreiras na cascata de cuidados da infecção latente de tuberculose, incluindo a necessidade de certificação dos profissionais de saúde para a leitura da prova tuberculínica (PPD). Aqui, propomos e avaliamos um protocolo simples para capacitação na leitura do PPD. Profissionais na atenção primária com diferentes formações receberam um curso teórico de duas horas, seguido por um curso prático sobre a leitura da enduração. Nas sessões práticas, as pápulas foram obtidas pela injeção de solução salina em salsichas, e depois em voluntários. Depois, a eficácia do protocolo foi avaliada por um instrutor credenciado, com base na capacidade do aluno de ler a enduração do PPD na rotina clínica (em formato duplo-cego em relação às respectivas leituras). A concordância inter-observador foi analisada com o teste de Bland-Altman. A acurácia das leituras dos alunos foi calculada com dois pontos de corte: 5 e 10mm. O efeito do número de leituras foi analisado com um modelo linear misto. Onze profissionais de saúde leram 53 pápulas de solução salina e 88 endurações de PPD. A concordância na leitura dos PPDs foi alta (média de 0,07mm de viés). A sensibilidade foi 100% (94,6; 100,0) com o ponto de corte de 5mm e 87,3% (75,5; 94,7) com o ponto de corte de 10mm. No modelo de regressão, não houve efeito do número de leituras [coeficiente: -0,007 (-0,055; 0,040)]. Um protocolo simples de treinamento em leitura da prova tuberculínica com simulações usando pápulas criadas com solução salina em salsichas e em voluntários foi suficiente para alcançar leituras acuradas da enduração da prova, sem efeito observado pelo número de leituras. O treinamento com pápulas criadas com solução salina em voluntários é mais seguro e mais fácil, comparado com o treinamento tradicional.

La terapia preventiva de la tuberculosis es una de las piedras angulares para la erradicación de la tuberculosis. No obstante, existen muchas barreras en la cascada de cuidado de una infección latente de tuberculosis, incluyendo la necesidad de certificación, en el caso de los profesionales de atención en salud, para la lectura de la prueba cutánea de tuberculina (TST). Aquí proponemos y evaluamos un protocolo simple para el entrenamiento en la lectura de TST. Trabajadores de salud de atención primaria de diferentes contextos recibieron un curso de 2 horas teórico, seguido de una práctica en la lectura de la ampolla. Las ampollas se obtienen inyectado una solución salina en salchichas y luego en voluntarios. Posteriormente, la eficacia de este protocolo fue evaluada mediante un formador certificado a través de la habilidad del personal en formación para la lectura de induración del TST en la rutina clínica, con lecturas cegadas entre ellos. Se analizó la concordancia entre los observadores usando el test Bland-Altman. La precisión de la lectura por parte del personal en formación se calculó usando dos puntos de corte: 5 y 10mm. El efecto del número de lecturas fue analizado usando un modelo lineal mixto. Once trabajadores de salud leyeron 53 soluciones salinas en ampollas y 88 induraciones TST. La concordancia en la lectura del TST fue alta (0,07mm promedio de sesgo). La sensibilidad fue de un 100% (94,6; 100,0) usando los 5mm de corte y 87,3% (75,5; 94,7) usando los 10mm de corte. En el modelo de regresión, no hubo efecto del número de lecturas [coeficiente: -0,007 (-0,055; 0,040)]. Un simple protocolo de entrenamiento para la lectura TST con simulaciones, usando solución salina en ampollas en salchichas y voluntarios fue suficiente para alcanzar lecturas precisas de induración TST, sin efectos observados por el número de lecturas. El entrenamiento con ampollas salinas en personas voluntarias es más seguro y más fácil que el entrenamiento tradicional.