Effect modification of greenness on PM2.5 associated all-cause mortality in a multidrug-resistant tuberculosis cohort

RationaleEvidence for the association between fine particulate matter (PM2.5) and mortality among patients with tuberculosis (TB) is limited. Whether greenness protects air pollution-related mortality among patients with multidrug-resistant tuberculosis (MDR-TB) is completely unknown.Methods2305 patients reported in Zhejiang and Ningxia were followed up from MDR-TB diagnosis until death, loss to follow-up or end of the study (31 December 2019), with an average follow-up of 1724 days per patient. 16-day averages of contemporaneous Normalised Difference Vegetation Index (NDVI) in the 500 m buffer of patient’s residence, annual average PM2.5 and estimated oxidant capacity Ox were assigned to patients regarding their geocoded home addresses. Cox proportional hazards regression models were used to estimate HRs per 10 μg/m3 exposure to PM2.5 and all-cause mortality among the cohort and individuals across the three tertiles, adjusting for potential covariates.ResultsHRs of 1.702 (95% CI 1.680 to 1.725) and 1.169 (1.162 to 1.175) were observed for PM2.5 associated with mortality for the full cohort and individuals with the greatest tertile of NDVI. Exposures to PM2.5 were stronger in association with mortality for younger patients (HR 2.434 (2.432 to 2.435)), female (2.209 (1.874 to 2.845)), patients in rural (1.780 (1.731 to 1.829)) and from Ningxia (1.221 (1.078 to 1.385)). Cumulative exposures increased the HRs of PM2.5-related mortality, while greater greenness flattened the risk with HRs reduced in 0.188–0.194 on average.ConclusionsIndividuals with MDR-TB could benefit from greenness by having attenuated associations between PM2.5 and mortality. Improving greener space and air quality may contribute to lower the risk of mortality from TB/MDR-TB and other diseases.

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Active surveillance for adverse events in patients on longer treatment regimens for multidrug-resistant tuberculosis in Viet Nam

PLoS ONE ◽

10.1371/journal.pone.0255357 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0255357

Author(s):

Nguyen Bao Ngoc ◽

Hoa Vu Dinh ◽

Nguyen Thi Thuy ◽

Duong Van Quang ◽

Cao Thi Thu Huyen ◽

...

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Bayesian Model Averaging ◽

Multidrug Resistant ◽

Treatment Regimens ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Objective Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. Method We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. Results Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91–37.42]), renal dysfunction (HR = 8.46 [1.91–37.42]), alcoholism (HR = 13.28 [5.04–34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14–1.43]). Conclusion While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.

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Predictors of mortality among multidrug-resistant tuberculosis patients in central Ethiopia: a retrospective follow-up study

Epidemiology and Infection ◽

10.1017/s0950268820002514 ◽

2020 ◽

Vol 148 ◽

Author(s):

Getahun Molla Kassa ◽

Abilo Tadesse ◽

Yalemzewod Assefa Gelaw ◽

Temesgen Tadesse Alemayehu ◽

Adino Tesfahun Tsegaye ◽

...

Keyword(s):

The Elderly ◽

Multidrug Resistant ◽

Central Ethiopia ◽

Predictors Of Mortality ◽

Follow Up Study ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Co Morbidity ◽

Mdr Tb

Abstract The burden of multidrug-resistant tuberculosis (MDR-TB) related to mortality in resource-poor countries remains high. This study aimed to estimate the incidence and predictors of death among MDR-TB patients in central Ethiopia. A retrospective follow-up study was conducted at three hospitals in the Amhara region on 451 patients receiving treatment for MDR-TB from September 2010 to January 2017. Data were collected from patient registration books, charts and computer databases. Data were fitted to a parametric frailty model and survival was expressed as an adjusted hazard ratio (AHR) with a 95% confidence interval (CI). The median follow-up time of participants was 20 months (interquartile range: 12, 22) and 46 (10.20%) of patients died during this period. The incidence rate of mortality was 7.42 (95% CI 5.56–9.91)/100 person-years. Older age (AHR = 1.04, 95% CI 1.01–1.08), inability to self-care (AHR = 13.71, 95% CI 5.46–34.40), co-morbidity (AHR = 5.74, 95% CI 2.19–15.08), low body mass index (AHR = 4.13, 95% CI 1.02–16.64), acute lung complications (AHR = 4.22, 95% CI 1.66–10.70) and lung consolidation at baseline (AHR = 5.27, 95% CI 1.06–26.18) were independent predictors of mortality. Most of the identified predictor factors of death in this study were considered to be avoidable if the TB programme had provided nutritional support for malnourished patients and ensured a close follow-up of the elderly, and patients with co-morbidities.

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Survival of patients with multidrug-resistant tuberculosis in Central China: a retrospective cohort study

Epidemiology and Infection ◽

10.1017/s0950268820000485 ◽

2020 ◽

Vol 148 ◽

Author(s):

Jianjie Wang ◽

Meilan Zhou ◽

Zi Chen ◽

Cong Chen ◽

Gang Wu ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Patient Survival ◽

Multidrug Resistant ◽

Central China ◽

Risk Of Death ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01–2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30–2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.

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Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Biomédica ◽

10.7705/biomedica.5072 ◽

2020 ◽

Vol 40 (4) ◽

pp. 616-625

Author(s):

Ángela Tobón ◽

Johana Rueda ◽

Diego H. Cáceres ◽

Gloria I. Mejía ◽

Elsa M. Zapata ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

Chronic Obstructive ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Poor Outcomes ◽

Lost To Follow Up

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

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Efficacy and safety of regimen containing bedaquiline in children with drug-resistant tuberculosis

Medical Council ◽

10.21518/2079-701x-2021-16-138-146 ◽

2021 ◽

pp. 138-146

Author(s):

V. A. Aksenova ◽

N. I. Klevno ◽

A. V. Kazakov ◽

D. A. Kudlay ◽

A. D. Pakhlavonova ◽

...

Keyword(s):

Multidrug Resistant ◽

Drug Resistant ◽

Efficacy And Safety ◽

Duration Of Treatment ◽

Drug Resistant Tuberculosis ◽

Children And Adolescent ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Introduction. The treatment of children with multidrug-resistant and extensively drug-resistant tuberculosis (MDR / XDR-TB) is a difficult task due to many factors: the duration of treatment, the lack of drugs with children’s dosages, age restrictions (according to the drug instructions).Purpose of the study. To assess the efficacy and safety of regimen with the inclusion of bedaquiline in children and adolescent with respiratory tuberculosis with drug-resistant tuberculosis.Materials and methods. The study is prospective, cohort, non-comparative from the period 2017–2019. We included 24 patients aged 5 to 17 years with MDR-TB (established or suspected) began regimen containing bedaquiline for 24 weeks. The duration of observation of patients included in the study was 24 months.Results. We can state a sufficient level of safety of using the latter for 24 weeks: adverse events presumably associated directly with the intake of bedaquiline were noted in only 1 patient out of 24 (4.2%; 95% CI 0.7-20.3). The efficacy of a regimen containing bedaquiline in combination with other anti-tuberculosis reserve drugs is beyond doubt: positive clinical and radiological dynamics and cessation of bacterial excretion by the end of the 24-week course of treatment were noted in all patients included in the study. In the course of 2-year follow-up, no exacerbation of the tuberculous process was observed in any case. All patients achieved clinical cure of tuberculosis.Conclusion. Regimen containing bedaquiline for children aged 5–17 years with multidrug-resistant tuberculosis is effective and safe.

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Multidrug-resistant tuberculosis in Lisbon: unfavourable treatment and associated factors, 2000–2014

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.18.0596 ◽

2019 ◽

Vol 23 (10) ◽

pp. 1075-1081

Author(s):

M. Bhering ◽

A. Kritski ◽

C. Nunes ◽

R. Duarte

Keyword(s):

Multidrug Resistant ◽

Foreign Born ◽

Loss To Follow Up ◽

Factors Associated ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Immunodeficiency Virus ◽

Mdr Tb ◽

The City

SETTING: The incidence of tuberculosis (TB) has been decreasing in Portugal. Lisbon concentrates the largest number of cases of multidrug-resistant (MDR) TB in the country. This study aims at identifying clinical and demographic factors associated with unfavourable treatment results of patients with MDR-TB in the city.METHOD: The data on 265 MDR-TB cases, notified from 2000 to 2014 in the District of Lisbon, were collected from the Tuberculosis Surveillance System. Unfavourable cases were classified as failure, loss to follow-up (LTFU) and death. Bivariate and multivariate logistic regressions were undertaken to estimate the factors associated with unfavourable outcomes, LTFU and death.RESULTS: The proportion of unfavourable outcomes was 30.5%. These were associated mostly with being male, foreign-born and resistant to kanamycin. Death was associated with being human immunodeficiency virus-positive and resistant to kanamycin. Being foreign-born had a 4.46-fold higher odds of a LTFU outcome than did being Portuguese-born. The foreign-born patients were mostly African immigrants.CONCLUSION: The main finding in this study is that foreign-born patients are associated with a higher probability of unfavourable outcomes than Portuguese-born patients. Therefore, foreign-born patients need more careful monitoring in the control of MDR-TB.

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Survival Status and Predictors of Mortality among Multidrug-Resistant Tuberculosis Patients in Saint Peter’s Specialized Hospital, Addis Ababa, Ethiopia

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2021/6696199 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Mikyas Arega Muluneh ◽

Abayneh Birlie Zeru ◽

Behailu Tariku Derseh ◽

Abebaw Molla Kebede

Keyword(s):

Addis Ababa ◽

Multidrug Resistant ◽

Survival Status ◽

Clinical Complications ◽

Resistant Tuberculosis ◽

Cox Proportional Hazard ◽

Multidrug Resistant Tuberculosis ◽

Specialized Hospital ◽

Mdr Tb

Background. Multidrug-Resistant Tuberculosis (MDR-TB) is tuberculosis that is resistant to at least both rifampicin and isoniazid. The World Health Organization as reported in 2019 revealed that Ethiopia is among the 20 countries with the highest estimated numbers of incident MDR-TB cases. However, supporting evidence is limited in the study area after the Ethiopian national strategic plan for tuberculosis prevention and control is started. Objective. To determine survival status and predictors of mortality among multidrug-resistant tuberculosis patients treated in Saint Peter’s Specialized Hospital at Addis Ababa, Ethiopia, 2020. Methods. An institutional retrospective cohort study was conducted using all MDR-TB patients who were enrolled in Saint. Peter’s Specialized Hospital from January 01, 2015, to December 31, 2017. A pretested data extraction form that had 5 items for sociodemographic and 15 items for the measurement of clinical characteristics of 484 MDR-TB patients was used. STATA software version 14.2 was used for data cleaning and analysis. A variable that fitted in the bivariable Cox proportional hazard model at p value <0.25 was used in the final multivariable Cox proportional hazard model, and independent predictors of time to event were determined at a p value of 0.05. Result. A total of 484 patients were followed up for 5,078 person-months. Among the total patients, nearly half, 238 (48.8%), were males. The median age of patients was 30 years (interquartile range (IQR), 24–39), and 56 (11.6%) were aged between 1 and 19 years. During the follow-up period, 315 (65.1%) patients were cured, 125 (25.8%) completed treatment, 24 (5%) died, and 20 (4.1%) were lost to follow-up. The overall cumulative probability survival of the patients at the end of treatment was 94.85% (95% confidence interval (CI): 92.38%–96.53%). The independent predictors of time to death were being anemic (AHR = 3.65; 95% CI: 1.36, 9.79), having clinical complication (AHR = 3; 95% CI: 1.2, 7.5), and being HIV infected (AHR = 5.8; 95% CI: 2.2, 15.7). Conclusions. MDR-TB patients’ survival rate was high in St Peter’s Specialized Hospital. MDR-TB patients with anemia, HIV coinfection, and clinical complications had higher risk of mortality. So, prevention and controlling of anemia, HIV/AIDS, and clinical complications will reduce the mortality of MDR-TB patients.

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Clinical Profile and Treatment Evaluation of Rifampicin-Resistant and Multidrug-Resistant Tuberculosis Patients at Dr. Kanujoso Djatiwibowo Public Hospital, Balikpapan

Jurnal Respirologi Indonesia ◽

10.36497/jri.v38i3.2 ◽

2018 ◽

Vol 38 (3) ◽

pp. 135-142

Author(s):

Randy Adiwinata ◽

Josephine Rasidi ◽

Maurits Marpaung

Keyword(s):

Success Rate ◽

Public Hospital ◽

Multidrug Resistant ◽

Clinical Profile ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Lost To Follow Up

Background: Rifampicin-resistant (RR-TB) and multidrug-resistant tuberculosis (MDR-TB) remains a major health problem worldwide and in Indonesia also become a challenge in total eradication of tuberculosis. Dr. Kanujoso Djatiwibowo Public Hospital (RSKD) Balikpapan is one of the two referral hospitals in East Kalimantan for evaluation and initiation of MDR-TB treatment. The objective of this study is to evaluate clinical profile and treatment of RR-TB and MDR-TB patients at RSKD. Methods: A retrospective cross-sectional study was conducted using data from eTB manager database and medical record of RR-TB and MDR-TB at RSKD from January 2013 to October 2016. Results: Twenty eight RR-TB and MDR-TB patients, most of them were female (53.6%), belong to 35-44 age group (28.6%), housewife (25%), graduated from senior high school (42,9%), malnutrition (28.6%), and relapse cases (50%). Diabetes mellitus and anemia were found in 42,9% and 44.4% of the patients, respectively. The most resistant pattern is rifampicin-resistant TB (57,1%) followed by rifampicin and isoniazid resistant. The most common side effect of TB treatment was gastrointestinal complaints (44.4%). The success rate of MDRTB treatment at RSKD was 20%, followed by 20% mortality, 50% of lost to follow up, 10% of treatment failure, and there are 8 patients still ongoing therapy. Conclusion: Most of the RR-TB and MDR-TB cases were relapse cases. Counseling, education, and support for the patients undergoing MDR-TB treatment are strongly needed to increase success rate and decreasing number of lost to follow up.

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Long term follow-up of multidrug resistant tuberculosis in a pubertal child

Paediatrica Indonesiana ◽

10.14238/pi58.4.2018.198-204 ◽

2018 ◽

Vol 58 (4) ◽

pp. 198-204

Author(s):

Andri Kurnia Wahyudhi ◽

Retno Asih Setyoningrum ◽

Ahmad Suryawan

Keyword(s):

Side Effects ◽

Multidrug Resistant ◽

Long Term Results ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Long Term Follow Up

Increasing awareness of the rising global rates of multidrug-resistant tuberculosis (MDR-TB) has led to a concerted international effort to confront this disease. Nonetheless, despite cure rates >80% in some programs, MDR-TB patients tend to have chronic disease and require prolonged therapy.1-3 Little is known about the long-term results and follow-up of patients with MDR-TB, include the recurrence rate and chronic disability in patients who have recovered from TB.4 There are many side effects and adverse reactions to drugs can occur during MDR-TB treatment. These could be physical and or psychological, as well as reversible or irreversible. Treatment of MDR-TB requires a combination regimen, consists of second and third-line anti-tuberculosis drugs which more toxic than first-line drugs. Additionally, MDR-TB treatment requires a long duration of treatment (18-24 months) and causes discomfort in the patient.5 In a cohort of 60 patients treated for MDR-TB, the most common side effects included gastritis (100%), dermatological disorders (43%), and peripheral neuropathy (16.7).6 While in a cohort of 75 patients, the incidence of depression, anxiety, and psychosis for MDR-TB treatments was 13.3%, 12.0%, and 12.0%, respectively.7 Aggressive and effective management are needed so the patient can tolerate the treatment and remain adhere the treatment.8 Long-term follow-up is required for the rehabilitation of disorders due to psychosocial sequelae. As such, psychosocial support can be benefit pediatric MDR-TB patients. Here, we present a case report on a two-year follow-up of a pubertal child with MDR-TB, focusing on medical aspects and her development.

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Effectiveness and safety of clofazimine in multidrug-resistant tuberculosis: a nationwide report from Brazil

European Respiratory Journal ◽

10.1183/13993003.02445-2016 ◽

2017 ◽

Vol 49 (3) ◽

pp. 1602445 ◽

Cited By ~ 40

Author(s):

Margareth Dalcolmo ◽

Regina Gayoso ◽

Giovanni Sotgiu ◽

Lia D'Ambrosio ◽

Jorge L. Rocha ◽

...

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

Success Rates ◽

Loss To Follow Up ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Daily Dose ◽

Mdr Tb

Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day−1 (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used).All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed. The effectiveness of clofazimine was assessed by comparing the treatment outcomes of patients undergoing clofazimine-containing regimens against those undergoing clofazimine-free regimens and its safety by describing clofazimine-attributed adverse events. A total of 1446 patients were treated with clofazimine-containing regimens and 1096 with pyrazinamide-containing regimens.Although success rates were similar in patients treated with clofazimine versus those treated with pyrazinamide (880 out of 1446, 60.9%, versus 708 out of 1096, 64.6%; p=0.054), clofazimine-treated cases exhibited higher death rates due to tuberculosis than pyrazinamide-treated ones (314 out of 1446, 21.7%, versus 120 out of 1096, 10.9%) but fewer failures (78 out of 1446, 5.4%, versus 95 out of 1096, 8.7%) and less loss to follow-up (144 out of 1446, 10.0%, versus 151 out of 1096, 13.8%). No relevant differences were detected when comparing adverse events in patients treated with clofazimine-containing regimens to those treated with clofazimine-free regimens. However, the incidence of side-effects was less than previously reported (gastro-intestinal complaints: 10.5%; hyper-pigmentation: 50.2%; neurological disturbances: 9–13%).

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