Efficacy and Safety of Anti-Osteoporotic Agents across CKD Stages: A Meta-Analysis of Randomized Clinical Trials.

INTRODUCTION: Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in stages 4 and 5. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic. RESULTS: We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (teriparatide, denosumab, romosozumab, raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22-0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in stages 4 and 5. Teriparatide, denosumab, and romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (denosumab, raloxifene, risedronate, alendronate, teriparatide) and placebo. However, romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1-5 across the trials. CONCLUSIONS: Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in stages 1-3. However, this benefit is not apparent in stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.

Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up.

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

PASS to End TB in Europe: Accelerated efforts on prevention and systematic screening to end tuberculosis in the WHO European Region by 2030.

OBJECTIVES: Outline the objectives, methods, and initial stages of the Prevention and Systematic Screening (PASS) initiative, a complimentary element of the innovative new approach of technical assistance mechanisms of WHO and its partners to countries aligned to the Regional TB Action Plan to End TB in the European Region by 2030. DESIGN: To provide an objective and critical overview of the existing landscape on TB epidemic in the WHO European Region (the European Region) and ii) identify the strategic significance of proactive measures aimed at approaching TB pre-elimination in the Region. RESULTS: Interventions primarily include systematic screening for TB disease and treatment for TB infection (TBI). CONCLUSIONS: PASS to End TB is an exemplary initiative of how technical and funding partners are joining hands to support national health programmes to work towards global commitments to curb major public health challenges like TB.

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease.

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

Effectiveness and safety of modified fully oral 9-month treatment regimens for rifampicin-resistant tuberculosis: a prospective cohort study.

BACKGROUND: In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide, ethambutol, high-dose isoniazid, pyrazinamide, and clofazimine for the management of rifampicin-resistant tuberculosis. A high prevalence of resistance to constituent drugs precluded its widespread use by countries in the WHO European region. We evaluated three 9-month fully oral modified STRs (mSTRs) in which ethionamide, ethambutol, isoniazid, and pyrazinamide were replaced by linezolid, cycloserine, or delamanid (or a combination). METHODS: This multicountry, prospective, single-arm, cohort study examined the effectiveness and safety of mSTRs for fluoroquinolone-susceptible, rifampicin-resistant pulmonary tuberculosis in 13 countries in the WHO European region during 2020-23. We enrolled adults and children of all ages with bacteriologically confirmed rifampicin-resistant, fluoroquinolone-susceptible pulmonary tuberculosis, and children (aged 0-18 years) with clinically diagnosed disease and a confirmed contact with rifampicin-resistant, fluoroquinolone-susceptible tuberculosis. Participants aged 6 years or older received one of two regimens: bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine; or bedaquiline, linezolid, levofloxacin, clofazimine, and delamanid. Children younger than 6 years received delamanid, linezolid, levofloxacin, and clofazimine. Participants were followed up for 12 months after successful treatment completion to detect recurrence and death. The primary outcome was the cumulative probability of not having an unsuccessful study outcome (defined as treatment failure, on-treatment loss to follow-up, death, or recurrence) before 22 months of study follow-up. The primary safety outcome was the incidence of each adverse event of interest (peripheral neuropathy, optic neuritis, myelosuppression, hepatitis, prolonged QT interval, hypokalaemia, and acute kidney injury) of grade 3 or higher severity during the treatment course. FINDINGS: Between Aug 28, 2020 and May 26, 2021, 7272 patients were screened and 2636 were included in the treatment cohort. 1966 (74·6%) were male, 670 (25·4%) were female, and median age was 43 years (IQR 33-53). Treatment success was recorded for 2181 (82·7%) participants. The cumulative probability of not having an unsuccessful study outcome 22 months after treatment initiation was 79% (95% CI 78-81). Increasing age (adjusted hazard ratio 2·61 [95% CI 1·70-4·04] for people aged >64 years vs 35-44 years), HIV-positive status (1·53 [1·16-2·01]), presence of bilateral cavities (1·68 [1·29-2·19]), smoking history (1·34 [1·05-1·71]), baseline anaemia (1·46 [1·15-1·86]), unemployment (1·37 [1·04-1·80]), elevated baseline liver enzymes (1·40 [1·13-1·73]), and excessive alcohol use (1·47 [1·14-1·89]) were positively associated with unsuccessful study outcomes. In the safety cohort of 2813 participants who received at least one dose, 301 adverse events of interest were recorded in 252 (9·0%) participants with the most frequent being myelosuppression (139 [4·9%] participants, 157 [52·2%] events). INTERPRETATION: The high treatment success and good safety results indicate considerable potential for the use of mSTRs in programmatic conditions, especially for individuals not eligible for the current WHO-recommended 6-month regimen and in settings with a need for alternative options. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria; United States Agency for International Development; Government of Germany; and WHO. TRANSLATION: For the Russian translation of the abstract see Supplementary Materials section.

Migration and medical screening for tuberculosis / Imigração e triagem médica para tuberculose

ABSTRACT Vulnerable populations, such as migrants and refugees, have an increased risk of tuberculosis disease, especially in the first years after arrival in the host country. The presence of migrants and refugees in Brazil exponentially grew over the period between 2011 and 2020, and approximately 1.3 million migrants from the Global South were estimated to be residing in Brazil, most of whom from Venezuela and Haiti. Tuberculosis control programs for migrants can be divided into pre- and post-migration screening strategies. Pre-migration screening aims to identify cases of tuberculosis infection (TBI) and can be carried out in the country of origin (pre-entry) or in the destination country (at entry). Pre-migration screening can also detect migrants at an increased risk of developing tuberculosis in the future. High-risk migrants are then followed up in post-migration screening. In Brazil, migrants are considered a priority group for the active search for tuberculosis cases. However, there is no recommendation or plan regarding screening for TBI in migrants and refugees. Ensuring prevention, diagnosis, and treatment for TBI and tuberculosis disease in migrant populations is an important aspect of tuberculosis control and elimination. In this review article, we address epidemiological aspects and access to health care for migrants in Brazil. In addition, the migration medical screening for tuberculosis was reviewed.

RESUMO Populações vulneráveis, como imigrantes e refugiados, apresentam maior risco de tuberculose doença, especialmente nos primeiros anos após a chegada ao país de acolhimento. A presença de imigrantes e refugiados no Brasil cresceu exponencialmente no período entre 2011 e 2020, sendo estimado que aproximadamente 1,3 milhão de imigrantes do Sul Global residiam no Brasil, a maioria proveniente da Venezuela e do Haiti. Os programas de controle da tuberculose para imigrantes podem ser divididos em estratégias de triagem pré- e pós-migração. A triagem pré-migração visa identificar casos de tuberculose infecção (TBI) e pode ser realizada no país de origem (pré-entrada) ou no país de destino (no momento da entrada). A triagem pré-migração também pode detectar imigrantes com maior risco de desenvolver tuberculose no futuro. Os imigrantes de alto risco são então acompanhados na triagem pós-migração. No Brasil, os imigrantes são considerados um grupo prioritário para a busca ativa de casos de tuberculose. No entanto, não há recomendação ou plano sobre triagem para TBI em imigrantes e refugiados. Garantir a prevenção, o diagnóstico e o tratamento da TBI e da tuberculose doença em populações imigrantes é um aspecto importante do controle e eliminação da tuberculose. Neste artigo de revisão, abordamos aspectos epidemiológicos e acesso à saúde para imigrantes no Brasil. Além disso, revisou-se a triagem médica de imigrantes para tuberculose.

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease / Recomendações da Sociedade Brasileira de Pneumologia e Tisiologia para o manejo da doença pulmonar pós-tuberculose

ABSTRACT Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

RESUMO Historicamente, todos os esforços contra a tuberculose concentraram-se no diagnóstico rápido e no tratamento efetivo para quebrar a cadeia de transmissão do Mycobacterium tuberculosis. No entanto, nos últimos anos, têm sido encontradas mais e mais evidências sobre as dramáticas consequências da condição definida como doença pulmonar pós-tuberculose (DPPT). Aproximadamente um terço dos pacientes que sobrevivem à tuberculose pulmonar enfrenta morbidades consideráveis e persistentes, incluindo comprometimento respiratório, desafios psicossociais e redução da qualidade de vida relacionada à saúde após o término do tratamento. Diante da importante carga global e local da tuberculose, bem como da carga estimada da DPPT, considerou-se urgente o desenvolvimento de um documento de consenso por uma sociedade científica brasileira - a Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) - para a prevenção e manejo dessa condição, a fim de alocar recursos de forma adequada para e nos serviços de tuberculose e servir de guia para os profissionais de saúde. Uma equipe de onze pneumologistas e um metodologista foi criada pela SBPT para revisar as evidências atuais sobre a DPPT e desenvolver recomendações adaptadas ao contexto brasileiro. O painel de especialistas selecionou os temas com base nas evidências atuais e diretrizes internacionais. Durante a primeira fase, três membros do painel redigiram as recomendações, que foram divididas em três seções: definição e prevalência de DPPT, avaliação da DPPT e manejo da DPPT. Na segunda fase, todos os membros do painel analisaram, discutiram e revisaram as recomendações até chegar a um consenso. O documento foi aprovado formalmente pela SBPT em sessão especial organizada durante o Congresso Anual da SBPT de 2023.

Bedaquiline-containing regimens and multidrug-resistant tuberculosis: a systematic review and meta-analysis / Esquemas terapêuticos com bedaquilina e tuberculose multirresistente: revisão sistemática e meta-análise

ABSTRACT Objective: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time. The present study sought to evaluate the treatment success rate of bedaquiline-based regimens in MDR-TB patients. Methods: This was a systematic review and meta-analysis of studies published up to March 15, 2021. The pooled treatment success rates and 95% CIs were assessed with the fixed-effect model or the random-effects model. Values of p < 0.05 were considered significant for publication bias. Results: A total of 2,679 articles were retrieved by database searching. Of those, 29 met the inclusion criteria. Of those, 25 were observational studies (including a total of 3,536 patients) and 4 were experimental studies (including a total of 440 patients). The pooled treatment success rate was 74.7% (95% CI, 69.8-79.0) in the observational studies and 86.1% (95% CI, 76.8-92.1; p = 0.00; I2 = 75%) in the experimental studies. There was no evidence of publication bias (p > 0.05). Conclusions: In patients with MDR-TB receiving bedaquiline, culture conversion and treatment success rates are high even in cases of extensive resistance.

RESUMO Objetivo: A tuberculose multirresistente (MDR-TB, do inglês multidrug-resistant tuberculosis) é uma doença infecciosa potencialmente fatal. O tratamento exige múltiplos agentes antimicrobianos usados durante longos períodos. O presente estudo buscou avaliar a taxa de sucesso de esquemas terapêuticos com bedaquilina em pacientes com MDR-TB. Métodos: Trata-se de uma revisão sistemática e meta-análise de estudos publicados até 15 de março de 2021. As taxas combinadas de sucesso do tratamento e os IC95% foram avaliados por meio do modelo de efeito fixo ou do modelo de efeitos aleatórios. Valores de p < 0,05 foram considerados significativos para viés de publicação. Resultados: Por meio de buscas eletrônicas em bancos de dados, foram recuperados 2.679 artigos. Destes, 29 preencheram os critérios de inclusão. Destes, 25 eram estudos observacionais (com um total de 3.536 pacientes) e 4 eram estudos experimentais (com um total de 440 pacientes). A taxa combinada de sucesso do tratamento foi de 74,7% (IC95%: 69,8-79,0) nos estudos observacionais e de 86,1% (IC95%: 76,8-92,1; p = 0,00; I2 = 75%) nos estudos experimentais. Não foram encontradas evidências de viés de publicação (p > 0,05). Conclusões: Em pacientes com MDR-TB tratados com bedaquilina, as taxas de conversão da cultura e sucesso do tratamento são altas mesmo em casos de resistência extensa.

Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts / Sequelas pulmonares da tuberculose: comparação de coortes do Brasil, Itália e México

ABSTRACT Objective: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

RESUMO Objetivo: Avaliar a função pulmonar em uma coorte de pacientes com história de tuberculose pulmonar no Brasil, bem como avaliar o declínio da função pulmonar ao longo do tempo e compará-lo com o observado em coortes semelhantes no México e Itália. Métodos: As três coortes foram comparadas quanto à idade, tabagismo, testes de função pulmonar, teste de caminhada de seis minutos e gasometria arterial. Na coorte brasileira, os resultados dos testes de função pulmonar, do teste de caminhada de seis minutos e da gasometria arterial logo após o término do tratamento da tuberculose foram comparados com os obtidos no fim do período de acompanhamento. Resultados: As três coortes foram muito diferentes quanto aos resultados dos testes de função pulmonar. Os padrões ventilatórios mais comuns nas coortes brasileira, italiana e mexicana foram o padrão obstrutivo, o padrão misto e o padrão normal [em 58 pacientes (50,9%), em 18 pacientes (41,9%) e em 26 pacientes (44,1%), respectivamente]. Apenas 2 casos de tuberculose multirresistente foram incluídos na coorte brasileira, ao passo que na coorte mexicana foram incluídos 27 casos (45,8%). As médias da PaO2 e SaO2 foram mais baixas na coorte mexicana do que na brasileira (p < 0,0001 e p < 0,002 para PaO2 e SaO2, respectivamente). Na coorte brasileira, quase todos os parâmetros funcionais se deterioraram ao longo do tempo. Conclusões: Este estudo reforça a importância do tratamento precoce e eficaz de pacientes com tuberculose sensível, pois a tuberculose multirresistente aumenta o dano pulmonar. Quando o tratamento da tuberculose é concluído, os pacientes devem ser avaliados o quanto antes e, caso se estabeleça o diagnóstico de sequelas pulmonares da tuberculose, é preciso tratá-los e oferecer-lhes reabilitação pulmonar, pois há evidências de que ela é eficaz nesses pacientes.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study / Medidas de confinamento específicas de cada país em resposta à pandemia de COVID-19 e seu impacto no controle da tuberculose: um estudo global

ABSTRACT The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

RESUMO O objetivo deste estudo foi descrever as medidas de confinamento específicas de cada país e os indicadores de tuberculose coletados durante o primeiro ano da pandemia de COVID-19. Dados referentes a confinamento/restrições sociais (uso obrigatório de máscaras faciais e higiene obrigatória das mãos; restrições a viagens internacionais e locais; restrições a visitas familiares e fechamento das escolas) foram coletados de 24 países em cinco continentes. A maioria dos países implantou múltiplos confinamentos, com reabertura parcial ou total. Houve uma redução geral dos casos de tuberculose ativa, tuberculose resistente e tuberculose latente. Embora os confinamentos nacionais tenham sido eficazes na contenção dos casos de COVID-19, vários indicadores de tuberculose foram afetados durante a pandemia.

Tuberculosis and COVID-19, the new cursed duet: what differs between Brazil and Europe? / Tuberculose e COVID-19, o novo dueto maldito: quais as diferenças entre Brasil e Europa?

ABSTRACT On April 1st, 2020, COVID-19 surpassed tuberculosis regarding the number of deaths per day worldwide. The combination of tuberculosis and COVID-19 has great potential for morbidity and mortality. In addition, the COVID-19 pandemic has had a significant impact on the diagnosis and treatment of tuberculosis. In this review article, we address concurrent tuberculosis and COVID-19, with particular regard to the differences between Brazil and Europe. In addition, we discuss priorities in clinical care, public health, and research.

RESUMO Em 1º de abril de 2020, a COVID-19 ultrapassou a tuberculose em número de óbitos por dia no mundo. A associação da tuberculose com a COVID-19 apresenta grande potencial de morbidade e mortalidade. Além disso, a pandemia de COVID-19 tem tido um impacto significativo no diagnóstico e tratamento da tuberculose. Neste artigo de revisão, abordamos tuberculose e COVID-19 concomitantes, com particular atenção às diferenças entre Brasil e Europa. Além disso, discutimos as prioridades em atendimento clínico, saúde pública e pesquisa.

Time course of exercise capacity in patients recovering from COVID-19-associated pneumonia / Evolução temporal da capacidade de exercício em pacientes em recuperação de pneumonia associada à COVID-19

ABSTRACT Objective: High prevalences of muscle weakness and impaired physical performance in hospitalized patients recovering from COVID-19-associated pneumonia have been reported. Our objective was to determine whether the level of exercise capacity after discharge would affect long-term functional outcomes in these patients. Methods: From three to five weeks after discharge from acute care hospitals (T0), patients underwent a six-minute walk test (6MWT) and were divided into two groups according to the distance walked in percentage of predicted values: <75% group and ≥75% group. At T0 and three months later (T1), patients completed the Short Physical Performance Battery and the Euro Quality of Life Visual Analogue Scale, and pulmonary function and respiratory muscle function were assessed. In addition, a repeat 6MWT was also performed at T1. Results: At T0, 6MWD values and Short Physical Performance Battery scores were lower in the <75% group than in the ≥75% group. No differences were found in the Euro Quality of Life Visual Analogue Scale scores, pulmonary function variables, respiratory muscle function variables, length of hospital stay, or previous treatment. At T1, both groups improved their exercise capacity, but only the subjects in the <75% group showed significant improvements in dyspnea and lower extremity function. Exercise capacity and functional status values returned to predicted values in all of the patients in both groups. Conclusions: Four weeks after discharge, COVID-19 survivors with exercise limitation showed no significant differences in physiological or clinical characteristics or in perceived health status when compared with patients without exercise limitation. Three months later, those patients recovered their exercise capacity.

RESUMO Objetivo: Há relatos de altas prevalências de fraqueza muscular e de comprometimento do desempenho físico em pacientes hospitalizados em recuperação de pneumonia associada à COVID-19. Nosso objetivo foi determinar se o nível de capacidade de exercício após a alta altera os desfechos funcionais em longo prazo nesses pacientes. Métodos: Três a cinco semanas após a alta dos cuidados agudos (T0), os pacientes foram submetidos ao teste de caminhada de seis minutos (TC6) e divididos em dois grupos de acordo com a distância percorrida no TC6 (DTC6) em percentual do previsto: grupo <75% e grupo ≥75%. Em T0 e três meses depois (T1), os pacientes responderam à Short Physical Performance Battery e à Euro Quality of Life Visual Analogue Scale, e foram avaliadas a função pulmonar e a função muscular respiratória. Além disso, o TC6 foi repetido em T1. Resultados: Em T0, a DTC6 e as pontuações na Short Physical Performance Battery foram menores no grupo <75% do que no grupo ≥75%. Não foram encontradas diferenças nas pontuações na Euro Quality of Life Visual Analogue Scale, nas variáveis de função pulmonar e função muscular respiratória, no tempo de internação hospitalar ou no tratamento anterior. Em T1, ambos os grupos melhoraram a capacidade de exercício, mas apenas os indivíduos do grupo <75% apresentaram melhoras significativas na dispneia e na função dos membros inferiores. Os valores de capacidade de exercício e estado funcional retornaram aos valores previstos em todos os pacientes de ambos os grupos. Conclusões: Quatro semanas após a alta, os sobreviventes da COVID-19 com limitação ao exercício não apresentaram diferenças significativas nas características fisiológicas e clínicas ou na percepção do estado de saúde em comparação aos pacientes sem limitação ao exercício. Três meses depois, esses pacientes recuperaram sua capacidade de exercício.

Shortened tuberculosis treatment regimens: what is new? / Esquemas mais curtos de tratamento da tuberculose: o que há de novo?

ABSTRACT Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.

RESUMO Em virtude da carga global da tuberculose, esquemas mais curtos de tratamento com medicamentos já existentes ou reaproveitados são necessários para contribuir para o controle da doença. A longa duração do tratamento da tuberculose sensível (TBS) está relacionada com não adesão e perda de seguimento, e a taxa de sucesso do tratamento da tuberculose multirresistente (TBMR) é baixa (de aproximadamente 50%) com esquemas mais longos. Neste artigo de revisão, relatamos avanços recentes e ensaios clínicos em andamento cujo objetivo é encurtar os esquemas de tratamento de TBS e TBMR. Discutimos o papel da rifampicina em altas doses, assim como o da clofazimina e linezolida em esquemas de tratamento de TBS. Relatamos também os resultados de estudos observacionais e ensaios clínicos de avaliação de um esquema padronizado de nove meses à base de moxifloxacina para o tratamento de TBMR. Mais estudos, especialmente ensaios clínicos randomizados, são necessários para avaliar esquemas que incluam medicamentos mais novos, medicamentos comprovadamente ou provavelmente eficazes e medicamentos exclusivamente orais na tentativa de dispensar o uso de medicamentos injetáveis.

International collaboration among medical societies is an effective way to boost Latin American production of articles on tuberculosis / A colaboração internacional entre sociedades médicas é uma forma eficaz de aumentar a produção de artigos sobre tuberculose na América Latina

ABSTRACT Objective: Most studies of tuberculosis originate from high-income countries with a low incidence of tuberculosis. A review of the scientific production on tuberculosis in Latin American countries, most of which are low- or middle-income countries (some with high or intermediate tuberculosis incidence rates), would improve the understanding of public health challenges, clinical needs, and research priorities. The aims of this systematic review were to determine what has been published recently in Latin America, to identify the leading authors involved, and to quantify the impact of international collaborations. Methods: We used PubMed to identify relevant manuscripts on pulmonary tuberculosis (PTB), drug-resistant tuberculosis (DR-TB), or multidrug-resistant tuberculosis (MDR-TB), published between 2013 and 2018. We selected only studies conducted in countries with an annual tuberculosis incidence of ≥ 10,000 reported cases and an annual MDR-TB incidence of ≥ 300 estimated cases, including Brazil, Peru, Mexico, Colombia, and Argentina. Articles were stratified by country, type, and topic. Results: We identified as eligible 395 studies on PTB and 188 studies on DR/MDR-TB-of which 96.4% and 96.8%, respectively, were original studies; 35.5% and 32.4%, respectively, had an epidemiological focus; and 52.7% and 36.2%, respectively, were conducted in Brazil. The recent Latin American Thoracic Association/European Respiratory Society/Brazilian Thoracic Association collaborative project boosted the production of high-quality articles on PTB and DR/MDR-TB in Latin America. Conclusions: Most of the recent Latin American studies on tuberculosis were conducted in Brazil, Mexico, or Peru. Collaboration among medical societies facilitates the production of scientific papers on tuberculosis. Such initiatives are in support of the World Health Organization call for intensified research and innovation in tuberculosis.

RESUMO Objetivo: A maioria dos estudos sobre tuberculose é proveniente de países de alta renda com baixa incidência de tuberculose. Uma revisão da produção científica sobre tuberculose na América Latina, região onde a maioria dos países é de baixa ou média renda, alguns com alta ou média incidência de tuberculose, seria útil para entender as necessidades clínicas e de saúde pública, bem como as prioridades de pesquisa. O objetivo desta revisão sistemática foi identificar o que foi publicado recentemente na América Latina, os principais autores envolvidos e o impacto das colaborações internacionais. Métodos: O PubMed foi usado para identificar manuscritos relevantes sobre tuberculose pulmonar (TBP) e tuberculose resistente ou multirresistente publicados entre 2013 e 2018. Foram selecionados apenas os estudos realizados em países com incidência anual de tuberculose ≥ 10.000 casos notificados e incidência anual de tuberculose multirresistente ≥ 300 casos estimados, incluindo Brasil, Peru, México, Colômbia e Argentina. Os artigos foram estratificados por país, tipo e tópico. Resultados: Foram identificados 395 estudos sobre TBP e 188 sobre tuberculose resistente/multirresistente, dos quais 96,4% e 96,8%, respectivamente, eram estudos originais; 35,5% e 32,4%, respectivamente, concentravam-se em epidemiologia; 52,7% e 36,2%, respectivamente, haviam sido realizados no Brasil. O recente projeto colaborativo da Asociación Latinoamericana de Tórax/European Respiratory Society/Sociedade Brasileira de Pneumologia e Tisiologia impulsionou a produção de artigos de alta qualidade sobre TBP e tuberculose resistente/multirresistente na América Latina. Conclusões: A maioria dos estudos recentes sobre tuberculose na América Latina foi realizada no Brasil, México ou Peru. A colaboração entre sociedades médicas facilita a produção de artigos científicos sobre tuberculose. Iniciativas assim atendem ao pedido da Organização Mundial da Saúde de intensificação das pesquisas e inovações na área de tuberculose.

Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation / Tratamento da tuberculose grave e suas sequelas: da terapia intensiva à cirurgia e reabilitação

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

RESUMO A tuberculose multirresistente e a tuberculose extensivamente resistente ainda são um desafio para médicos e especialistas em saúde pública. Os desfechos globais do tratamento ainda são insatisfatórios; apenas 54% dos pacientes têm um desfecho positivo. Os desfechos globais são ainda piores em pacientes infectados por cepas altamente resistentes. O tratamento da tuberculose multirresistente/extensivamente resistente é difícil em virtude dos eventos adversos frequentes, da longa duração dos esquemas terapêuticos, do alto custo dos medicamentos de segunda linha, das sequelas pós-infecciosas crônicas e da perda da função orgânica. Esforços de pesquisa (estudos e ensaios) estão em andamento e têm diversos objetivos: aumentar as taxas de sucesso do tratamento; compreender o potencial de medicamentos novos e reaproveitados; encurtar o tratamento e reduzir as taxas de eventos adversos. Espera-se que melhor acesso ao diagnóstico rápido, maior conhecimento e terapias mais eficazes reduzam as complicações e o comprometimento da função pulmonar. O objetivo deste artigo é discutir o tratamento da tuberculose grave (potencialmente fatal, que necessita de níveis maiores de atenção) e suas sequelas, desde a terapia intensiva até o pós-operatório, reabilitação e recuperação. São também discutidas as intervenções não farmacológicas disponíveis para tratar sequelas crônicas e melhorar a qualidade de vida dos pacientes. Como a maioria dos casos de tuberculose multirresistente/extensivamente resistente resulta em comprometimento da função pulmonar (obstrução principalmente, mas às vezes restrição), qualidade de vida prejudicada e desempenho reduzido (medido por meio de testes de caminhada ou outros), são necessárias outras intervenções (cessação do tabagismo, reabilitação pulmonar, vacinação e prevenção de infecções bacterianas secundárias/exacerbações, por exemplo, complementadas por apoio psicológico e nutricional).