Pharmacokinetics and pharmacodynamics of high-dose isoniazid for the treatment of rifampicin- or multidrug-resistant tuberculosis in Indonesia.

BACKGROUND: Pharmacokinetic data on high-dose isoniazid for the treatment of rifampicin-/multidrug-resistant tuberculosis (RR/MDR-TB) are limited. We aimed to describe the pharmacokinetics of high-dose isoniazid, estimate exposure target attainment, identify predictors of exposures, and explore exposure-response relationships in RR/MDR-TB patients. METHODS: We performed an observational pharmacokinetic study, with exploratory pharmacokinetic/pharmacodynamic analyses, in Indonesian adults aged 18-65 years treated for pulmonary RR/MDR-TB with standardized regimens containing high-dose isoniazid (10-15 mg/kg/day) for 9-11 months. Intensive pharmacokinetic sampling was performed after ≥2 weeks of treatment. Total plasma drug exposure (AUC0-24) and peak concentration (Cmax) were assessed using non-compartmental analyses. AUC0-24/MIC ratio of 85 and Cmax/MIC ratio of 17.5 were used as exposure targets. Multivariable linear and logistic regression analyses were used to identify predictors of drug exposures and responses, respectively. RESULTS: We consecutively enrolled 40 patients (median age 37.5 years). The geometric mean isoniazid AUC0-24 and Cmax were 35.4 h·mg/L and 8.5 mg/L, respectively. Lower AUC0-24 and Cmax values were associated (P < 0.05) with non-slow acetylator phenotype, and lower Cmax values were associated with male sex. Of the 26 patients with MIC data, less than 25% achieved the proposed targets for isoniazid AUC0-24/MIC (n = 6/26) and Cmax/MIC (n = 5/26). Lower isoniazid AUC0-24 values were associated with delayed sputum culture conversion (>2 months of treatment) [adjusted OR 0.18 (95% CI 0.04-0.89)]. CONCLUSIONS: Isoniazid exposures below targets were observed in most patients, and certain risk groups for low isoniazid exposures may require dose adjustment. The effect of low isoniazid exposures on delayed culture conversion deserves attention.

Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis.

Background: In Indonesia, drug resistance testing for TB largely relies on Xpert MTB/RIF, and it is unknown what proportion of drug-resistant (DR) TB is adequately diagnosed and treated. Methods: We conducted a cascade of care analysis on a cohort of presumptive rifampicin-resistant (RR) TB patients registered in 2015-2018 in a tertiary hospital in Indonesia. Estimated incidences of (presumptive) DR-TB cases were assumption-based using global reports. Data on diagnosis and consecutive cascades steps, including their timing were collected from national electronic registers, and medical records. We described a secondary cascade for patients receiving treatment not supported by phenotypic drug susceptibility testing (pDST). Factors associated with delay and loss between diagnosis and treatment were identified using logistic regression. Findings: Less than a third of estimated incident TB cases at risk of DR-TB were identified as presumptive DR-TB case and tested, and 9.8% (982/10,065) of estimated true DR-TB cases was diagnosed. Of those diagnosed, only 45.1% (443/982) had treatment regimens supported by pDST results, but this did not significantly influence treatment outcomes. Only 25.5% (250/982) of diagnosed patients completed all steps of the cascade including successful treatment. Delays between diagnosis and treatment were substantial, and more common among those referred from a primary healthcare facility, and among those who were employed, living outside of Bandung, and reporting engagement with the private sector. Interpretation: The DR-TB care cascade in this urban setting in Indonesia is characterized by substantial attrition and delays. Strategies to increase access to DR-TB diagnosis accompanied by optimisation of clinical care could substantially improve outcomes and reduce onward transmission. Funding: Radboud university medical center and University of Otago.

The Kynurenine/Tryptophan Ratio as a Promising Metabolomic Biomarker for Diagnosing the Spectrum of Tuberculosis Infection and Disease.

The metabolic system and immunology used to be seen as distinct fields of study. Recent developments in our understanding of how the immune system operates in health and disease have connected these fields to complex systems. An effective technique for identifying probable abnormalities of metabolic homeostasis brought on by disease is metabolomics, which is defined as the thorough study of small molecule metabolic intermediates within a biological system that collectively make up the metabolome. A prognostic metabolic biomarker with adequate prognostic accuracy for tuberculosis progression has recently been created. The rate-limiting host enzyme for the conversion of tryptophan to kynurenine, indoleamine 2,3-dioxygenase (IDO), is greatly elevated in the lungs of tuberculosis disease patients. Targeted study on tryptophan in tuberculosis disease indicates that such decreases may also resembled this upregulation. Although tuberculosis diagnosis has improved with the use of interferon release assay and tuberculosis nucleic acid amplification, tuberculosis control is made difficult by the lack of a biomarker to diagnose active tuberculosis disease. We hope that the reader of this work can develop an understanding of the advantages of metabolomics testing, particularly as a sort of testing that can be used for both diagnosing and monitoring a patient's response to treatment for tuberculosis.

Analytical and Clinical Validation of Assays for Volumetric Absorptive Microsampling (VAMS) of Drugs in Different Blood Matrices: A Literature Review.

Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10-50 µL) within a few seconds (2-4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS). After optimization and validation of an analytical method of a drug taken by VAMS, a clinical validation study is needed to show that the results by VAMS can substitute what is gained from CVS and to justify implementation in routine practice. This narrative review aimed to assess and present studies about optimization and analytical validation of assays for drugs taken by VAMS, considering their physicochemical drug properties, extraction conditions, validation results, and studies on clinical validation of VAMS compared to CVS. The review revealed that the bio-analysis of many drugs taken with the VAMS technique was optimized and validated. However, only a few clinical validation studies have been performed so far. All drugs that underwent a clinical validation study demonstrated good agreement between the two techniques (VAMS and CVS), but only by Bland-Altman analysis. Only for tacrolimus and mycophenolic acid were three measurements of agreement evaluated. Therefore, VAMS can be considered an alternative to CVS in routine practice, especially for tacrolimus and mycophenolic acid. Still, more extensive clinical validation studies need to be performed for other drugs.

Anemia with elevation of growth differentiation factor-15 level in linezolid treated multidrug-resistant tuberculosis: Case series of three patients.

Linezolid is now recommended as a first line drug for Multidrug Resistant Tuberculosis (MDR-TB). Previous studies reported hematologic toxicity as one of the main side effects. The mechanism of this toxicity is mitochondrial dysfunction, for which a biomarker is Growth differentiation factor-15 (GDF-15). There is no previous report about GDF-15 and its association with hematologic toxicity from Linezolid in the treatment of MDR-TB. We present three cases of MDR-TB involving severe anemia associated with linezolid who had GDF-15 elevation. These cases highlight the need for more research into the relationship between GDF-15 and hematologic toxicity in MDR-TB patients treated with linezolid.

MDR Pathogens Organisms as Risk Factor of Mortality in Secondary Pulmonary Bacterial Infections Among COVID-19 Patients: Observational Studies in Two Referral Hospitals in West Java, Indonesia.

Purpose: The coronavirus disease (COVID-19) outbreak has created a global health crisis. Secondary pulmonary bacterial infection is a COVID-19 complication, increasing morbidity and mortality. This study aimed to determine the pathogens, antibiotic susceptibility patterns, and risk factors for mortality in hospitalized COVID-19 patients. Patients and Methods: This retrospective study used secondary data from patients' electronic medical records at Hasan Sadikin General Hospital and Santo Borromeus Hospital between March 2020 and March 2021. Overall, 2230 hospitalized COVID-19 patients were screened, and 182 of them who were hospitalized ≥48 hours with a procalcitonin level of ≥0.25 ng/mL were enrolled. Culture examination was performed on sputum samples to determine pathogen and antibiotic susceptibilities. Univariate and multivariate analyses were used to determine mortality-related risk factors in hospitalized COVID-19 patients. Results: The prevalence of secondary pulmonary bacterial infections in COVID-19 patients was 8.2%, with 161/182 pathogen growth from sputum samples. Mainly gram-negative bacteria (64.8%) were present, including Acinetobacter baumannii (31.9%), Klebsiella pneumoniae (19.8%), and Pseudomonas aeruginosa (8.8%). High rate of multidrug-resistant (MDR) pathogens was found among isolate (45.9%), ie carbapenem-resistance A. baumannii (CR-Ab) was 84.2%, extended-spectrum ß-lactamase (ESBL) among K. pneumoniae was 61.1%. Secondary infection of MDR pathogens was associated with a higher risk of mortality (AOR 5.63, p = 0.001). Other associated factors were age ≥60 years, ventilator use, and female gender. Conclusion: Gram-negative bacteria are the predominant pathogens causing secondary pulmonary bacterial infection in COVID-19 patients, implying nosocomial infection. High resistance to first-line antimicrobial drugs was observed in Gram-negative bacteria and Gram-positive bacteria. High rate of MDR pathogens was found among isolate and was associated with a significant risk of mortality.

Barriers to Optimal Tuberculosis Treatment Services at Community Health Centers: A Qualitative Study From a High Prevalent Tuberculosis Country.

Background: Community health centers (CHCs) are a backbone healthcare facility for tuberculosis (TB) services. Identifying barriers amongst TB service providers at the CHC level is required to help them deliver successful TB treatment. Aims: The current study aimed to analyze barriers to successful TB treatment from the perspective of TB service providers at the CHC level in a high prevalent TB country. Methods: A qualitative study was conducted using in-depth interviews and focus group discussions in a province of Indonesia with a high TB prevalence. Two districts representing rural and urban areas were selected to obtain information from TB service providers (i.e., physicians and nurses) at the CHC level. In addition, key informant interviews with TB patients, hospital TB specialists, pharmacists, and activists were conducted. The trustworthiness and credibility of the information were established using information saturation, participant validation, and triangulation approaches. The interviews were also transcribed for the inductive analysis using Atlas.ti 8.4 software. Results: We identified 210 meaning units from 48 participants and classified them into two main themes: organizational capacity and TB program activities. We identified the inadequacy of human resources, facility, and external coordination as the main barriers to organizational capacity. Furthermore, the barriers were identified regarding TB program activities, that is, inadequate TB case finding, diagnosis, drug supply chain and dispensing management, treatment and monitoring, case recording and reporting, and public-private collaboration. Conclusion: Strengthening CHCs in the management of TB is critical to reaching the national and global goals of TB eradication by 2035. These findings can be considered to develop evaluation strategies to improve the successful TB treatment in high prevalent TB countries, especially Indonesia.

Risk factors of latent tuberculosis among chronic kidney disease with routine haemodialysis patients.

INTRODUCTION: Since immune system alteration occurs, chronic kidney disease (CKD) on routine haemodialysis (HD) patients have a greater risk for latent tuberculosis (LTB). LTB needs special attention so that it does not develop into an active form, because infection in CKD patients increases the mortality. This study aims to determine the risk factors that associated with LTB among CKD on routine HD patients. METHODS: This was a cross-sectional study conducted in Haemodialysis Unit, Hasan Sadikin General Hospital, Bandung. The subjects were recruited from March-May 2020. Subjects aged > 18 years at least have undergoing HD in 3 months and twice a week HD were included in this study. Patients with active tuberculosis (TB) suspected, malignancy, or immunocompromised were excluded. LTB was diagnosed using interferon-γ release assays (IGRA). All data including age, sex, CKD etiologies, smoking status, HD adequacy that assessed using KT/V and urea reduction ratio (URR), and contact status with TB patients were obtained and recorded in case report form. RESULTS: A total of 120 subjects were involved. LTB based on IGRA was occurred in 39.2% subjects, while 56.7% and 4.1% subjects had negative and indeterminate IGRA, respectively. Adequacy of HD based on KT/V value was not significantly different between positive and negative IGRA subjects. Positive IGRA subjects had lower URR (p = 0.042). Smoking status had significant association with LTB (OR = 2.5[95%CI 1.2-5.4, p = 0.017). Furthermore, URR < 73% also had significant association with LTB (OR = 2.6[1.2-5.6, p = 0.013). CONCLUSION: Smoking status and HD adequacy based on URR < 73% are associated factors that contribute to LTB among CKD on HD patients.

The role of 99mTc-ethambutol scintigraphy to diagnose pulmonary tuberculosis.

Tuberculosis is a significant health problem in many parts of the world. According to the Global Tuberculosis Report 2020, 10 million new tuberculosis cases were reported worldwide in 2019, with only 57% of these cases being bacteriologically confirmed. Current tuberculosis diagnostic tests depend on the quality of the sputum, leaving many diagnostic uncertainties. Diagnostic delays result in ongoing transmission and more severe, progressive disease in the affected person. This shows that current diagnostic tests are not sufficient to establish all tuberculosis cases accurately, and there is a need for a new diagnostic technique. 99mTc-ethambutol scintigraphy was recently reported as a new diagnostic test for tuberculosis, with a sensitivity and specificity of 93.9% and 85.7%, respectively. Here, we report a case of the importance of this new technique for diagnosing tuberculosis when the existing bacteriological and molecular tests failed to confirm the diagnosis.

Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria.

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

Factors associated with treatment outcome of MDR/RR-TB patients treated with shorter injectable based regimen in West Java Indonesia.

BACKGROUND AND AIMS: Multi drug or rifampicin resistant tuberculosis (MDR/RR-TB) is a major burden to TB prevention and eradication globally. Since 2016, WHO guidelines have included options for treating MDR/RR-TB with a standard regimen of 9 to 11 months duration (the 'shorter regimen') rather than an individual regimen of at least 20 months. This regimen has been introduced in Indonesia since September 2017. Therefore, we aimed to determine the success rate and factors associated with the treatment outcome of shorter injectable based regimen in West Java province, Indonesia. METHODS: This was a retrospective cohort study of MDR/RR-TB patients aged over 18 years old who received the shorter injectable based regimen between September 2017 and December 2020. We defined successful outcomes as the combined proportion of patients who were cured or had complete treatment. While, unsuccessful outcomes were defined as the combined proportion of patients who died from any causes, failure, and loss to follow-up (LTFU). RESULTS: A total of 315 patients were included in this study. The success rate was 64.5%. Multivariate analysis showed male gender (aRR = 1.18, 95% CI 1.04 to 1.34) increased the chance of successful outcome, while malnutrition (aRR = 0.78, 95% CI 0.68 to 0.89), history of previous TB treatment (aRR = 0.80%CI 0.68 to 0.94), and time of culture conversion >2 months (aRR = 0.72 (95% CI 0.59 to 0.87) decreased the chance of successful outcome. CONCLUSION: History of previous TB treatment, time of culture conversion >2 months, and malnutrition were independent factors that decrease the chance for success rate, while male gender increase the likelihood for success rate of patients treated by the shorter injectable based regimen.

A Case of Complex Pulmonary Hypertension: the Importance of Diagnostic Investigation.

Pulmonary hypertension (PH) encompasses several heterogeneous groups of multiple diseases characterized by abnormal pulmonary arterial blood pressure elevation. Unrepaired atrial septal defect (ASD) may be associated with pulmonary arterial hypertension (PAH), indicating pulmonary vascular remodeling. Furthermore, unrepaired ASD could also be associated with other conditions, such as left heart disease or thromboembolism, contributing to the disease progression. We present a case of a 61-years-old woman with complex PH comprising several etiologies, which are PAH due to unrepaired Secundum ASD, mitral regurgitation caused by mitral valve prolapse as a group 2 PH, pulmonary embolism (PE) which progress to chronic thromboembolism PH (CTEPH) and post-acute sequelae of SARS Cov-2. We highlighted the importance of diagnostic investigation in PH, which is crucial to avoid misdiagnosis and inappropriate treatment that could be detrimental for the patient.

Transporter and metabolizer gene polymorphisms affect fluoroquinolone pharmacokinetic parameters.

Tuberculosis (TB) is an infectious disease that occurs globally. Treatment of TB has been hindered by problems with multidrug-resistant strains (MDR-TB). Fluoroquinolones are one of the main drugs used for the treatment of MDR-TB. The success of therapy can be influenced by genetic factors and their impact on pharmacokinetic parameters. This review was conducted by searching the PubMed database with keywords polymorphism and fluoroquinolones. The presence of gene polymorphisms, including UGT1A1, UGT1A9, SLCO1B1, and ABCB1, can affect fluoroquinolones pharmacokinetic parameters such as area under the curve (AUC), creatinine clearance (CCr), maximum plasma concentration (Cmax), half-life (t1/2) and peak time (tmax) of fluoroquinolones.

Polymorphisms of SLCO1B1 Gene in Sundanese Ethnic Population of Tuberculosis Patients in Indonesia.

BACKGROUND: The blood level of rifampicin, one of the tuberculosis (TB) drugs, depends on the organic anion transporting polypeptide 1B1 (OATP1B1) in hepatocytes. This protein is encoded by the solute carrier organic anion 1B1 (SLCO1B1) gene. Its genetic variation has been reported to have an impact on clinical outcomes and drug efficacy. However, the polymorphism in the SLCO1B1 gene has not been examined in Indonesia yet. We aimed to identify the frequency of polymorphism in SLCO1B1 gene among pulmonary TB patients in Bandung, Indonesia. METHODS: Cross-sectional study was conducted in West Java. 145 pulmonary TB patients who were treated with first-line drugs treatment (including rifampicin 450 mg daily) were analyzed for polymorphism in SLCO1B1 gene. Patients aged between 18-64 years old and mainly came from Sundanese ethnic group (92.4%). Genetic variants were detected using Polymerase Chain Reaction (PCR) and Sanger sequencing. RESULTS: Polymorphism of c.463C>A(rs11045819) was not identified, while heterozygous and homozygous polymorphism of c.85-7793C>T(rs4149032) were identified in 74 (51.0%) and 56 (38.6%) patients, respectively. The minor allele frequency (MAF) of T (mutant) allele of c.85-7793C>T(rs4149032) was 64.13% (186/209), higher than in the general population, which the MAF of rs4149032 is 53.6% based on 1000 genome database. CONCLUSION: This study highlights the presence of different allele frequencies of polymorphisms within the population, which might affect treatment outcomes.

Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy.

Drug-resistant tuberculosis (DR-TB) requires prolonged and complex therapy which is associated with several adverse drug reactions (ADR). The burden of ADR can affect the quality of life (QoL) of patients that consists of physical, mental, and social well-being, and influences the beliefs and behaviors of patient related to treatment. This article reviews the burden of ADR and its association with QoL and adherence. We used PubMed to retrieve the relevant original research articles written in English from 2011 to 2021. We combined the following keywords: "tuberculosis," "Drug-resistant tuberculosis," "Side Effect," "Adverse Drug Reactions," "Adverse Event," "Quality of Life," "Adherence," "Non-adherence," "Default," and "Loss to follow-up." Article selection process was unsystematic. We included 12 relevant main articles and summarized into two main topics, namely, 1) ADR and QoL (3 articles), and 2) ADR and therapy adherence (9 articles). The result showed that patients with ADR tend to have low QoL, even in the end of treatment. Although it was torturing, the presence of ADR does not always result in non-adherence. It is probably because the perception about the benefit of the treatment dominates the perceived barrier. In conclusion, burden of ADR generally tends to degrade QoL of patients and potentially influence the adherence. A comprehensive support from family, community, and healthcare provider is required to help patients in coping with the burden of ADR. Nevertheless, the regimen safety and efficacy improvement are highly needed.

Association Between Vitamin D Levels and FEV1, Number of Exacerbations, and CAT Score in Stable COPD Patients in Indonesia.

PURPOSE: This study aimed to assess the association between vitamin D levels and forced expiratory volume in one second (FEV1), number of exacerbations, and symptoms based on COPD assessment test (CAT) scores in stable COPD patients in Indonesia. PATIENTS AND METHODS: An observational cross-sectional study was conducted. Subjects were stable COPD patients who were treated at a pulmonary clinic in a tertiary referral hospital in West Java from March to June 2018. RESULTS: Thirty subjects were recruited this study with an average age 62±8 years. The mean vitamin D level was 20.17±8.91 ng/mL. Half of the patients had low vitamin D level (<20ng/mL) (50%). The mean FEV1 (%) predicted value was 37.2±14. The median exacerbation per year was 1 (0-5) and symptoms based on CAT score was 14 (3-34). No correlation was found between vitamin D levels and FEV1 (%) predicted value (r=0.126, p=0.253). Vitamin D level was inversely correlated with number of exacerbations (r=-0.639, p<0.001) and CAT (r= -0.802, p<0.001). CONCLUSION: Low level of vitamin D was associated with more frequent exacerbation and higher CAT scores but was not associated with FEV1 (%) predicted.

The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial.

AIMS: Diabetes mellitus (DM) is associated with worse tuberculosis (TB) treatment outcomes, especially among those with poor glycemic control. We examined whether a structured clinical algorithm could improve glycemic control in TB patients with DM. METHODS: In an open label randomized trial, TB-DM patients were randomized to scheduled counselling, glucose monitoring, and adjustment of medication using a structured clinical algorithm (intervention arm) or routine DM management (control arm), with glycated hemoglobin (HbA1c) at month 6 as the primary end point. RESULTS: We randomized 150 pulmonary TB-DM patients (92% culture positive, 51.3% male, mean age 53 years). Baseline mean HbA1c was 11.0% in the intervention arm (n = 76) and 11.6% in the control arm (n = 74). At 6 months, HbA1c had decreased more in the intervention arm compared with the control arm (a difference of 1.82% HbA1c, 95% CI 0.82-2.83, p < 0.001). Five patients were hospitalized in the intervention arm and seven in the control arm. There was more hypoglycemia (35.0% vs 11.8%; p = 0.002) in the intervention arm. Two deaths occurred in the intervention arm, one due to cardiorespiratory failure and one because of suspected septic shock and multiorgan failure. CONCLUSION: Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control.

Factors affecting outcome of longer regimen multidrug-resistant tuberculosis treatment in West Java Indonesia: A retrospective cohort study.

BACKGROUND: Multidrug-resistant tuberculosis had high treatment failure and mortality. Success rate of treatment currently 56% at global level, 48% in Indonesia and 36% in West Java province, the most populated province and surround Jakarta, the capitol of Indonesia. OBJECTIVE: This study aimed to evaluate factors affecting success of multidrug-resistant tuberculosis treatment in patients using longer treatment regimen in West Java Indonesia. METHODS: This was a retrospective cohort study of multidrug-resistant tuberculosis patients treated with longer regimen at Hasan Sadikin General Hospital from January 2015 to December 2017. Potential risk factors associated with the treatment outcome were analyzed using multiple logistic regression. RESULTS: A total of 492 patients were enrolled during the study period. Fifty percents multidrug-resistant tuberculosis patients had successful treatment outcome. Age ≤45 years, male, normal body mass index, no previous tuberculosis treatment, culture conversion ≤2 months, acid fast bacilli sputum smear ≤+1 were independent factors associated with increased treatment success. Sputum culture conversion ≤2 months was the major factor affecting successful outcome (RR 2.79; 95% CI: 1.61-4.84; p-value<0.001). Human Immunodeficiency Virus infection, chronic kidney disease, and cavitary lesion were independent risk factors for unfavourable outcome. CONCLUSION: Age, gender, body mass index, tuberculosis treatment history, time of sputum conversion, acid fast bacilli sputum smear, HIV infection, chronic kidney disease, and cavitary lesion can be used as predictors for longer multidrug-resistant tuberculosis treatment regimen outcome.

Effect of increased BMI and obesity on the outcome of COVID-19 adult patients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Corona virus diseases 2019 (COVID-19) pandemic spread rapidly. Growing evidences that overweight and obesity which extent nearly a third of the world population were associated with severe COVID-19. This study aimed to explore the association and risk of increased BMI and obesity with composite poor outcome in COVID-19 adult patients. METHODS: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles in COVID-19 adult patients and obesity based on classification of Body Mass Index (BMI) and composite poor outcome which consist of ICU admission, ARDS, severe COVID-19, use of mechanical ventilation, hospital admission, and mortality. RESULTS: Sixteen studies were included in meta-analysis with 9 studies presented BMI as continuous outcome and 10 studies presented BMI as dichotomous outcome (cut-off ≥30 kg/m2). COVID-19 patients with composite poor outcome had higher BMI with mean difference 1.12 (95% CI, 0.67-1.57, P < 0.001). Meanwhile, obesity was associated with composite poor outcome with odds ratio (OR) = 1.78 (95% CI, 1.25-2.54, P < 0.001) Multivariate meta-regression showed the association between BMI and obesity on composite poor outcome were affected by age, gender, DM type 2, and hypertension. CONCLUSION: Obesity is a risk factor of composite poor outcome of COVID-19. On the other hand, COVID-19 patients with composite poor outcome have higher BMI. BMI is an important routine procedure that should always be assessed in the management of COVID-19 patients and special attention should be given to patients with obesity.

Diabetes Mellitus Among Pulmonary Tuberculosis Patients From 4 Tuberculosis-endemic Countries: The TANDEM Study.

BACKGROUND: Diabetes mellitus (DM) increases active tuberculosis (TB) risk and worsens TB outcomes, jeopardizing TB control especially in TB-endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania, and South Africa. METHODS: Age-adjusted DM prevalence was estimated using laboratory glycated hemoglobin (HbA1c) or fasting plasma glucose in TB patients. Detailed and standardized sociodemographic, anthropometric, and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multilevel mixed-effect regression models with robust standard errors. RESULTS: Of 2185 TB patients (median age 36.6 years, 61.2% male, 3.8% human immunodeficiency virus-infected), 12.5% (267/2128) had DM, one third of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB-DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB-DM patients were older and had a higher body mass index (BMI) (P value < .05). Compared to those with newly diagnosed DM, TB patients with diagnosed DM had higher BMI and HbA1c, less severe TB, and more frequent comorbidities, DM complications, and hypertension (P value < .05). CONCLUSIONS: We show that DM prevalence and clinical characteristics of TB-DM vary across settings. Diabetes is primarily known but untreated, hyperglycemia is often severe, and many patients with TB-DM have significant cardiovascular disease risk and severe TB. This underlines the need to improve strategies for better clinical management of combined TB and DM.