Treatment Strategy for Rifampin-Susceptible Tuberculosis.

BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.).

Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Histoplasma antigen detection in unconfirmed pulmonary tuberculosis and cross-reactivity with Aspergillus antigen in patients and in food in Jakarta, Indonesia.

PURPOSE: H. capsulatum is endemic in Indonesia, but the value of Histoplasma antigen detection has not been studied. PATIENTS AND METHODS: Histoplasma galactomannan (GM) ELISA was applied to sera of patients with unproven pulmonary tuberculosis (TB) and patients with a positive Aspergillus GM. Both Histoplasma and Aspergillus GM tests were performed to determine any possible cross-reaction with certain foods. RESULTS: Fourteen of 122 (11.5%) sera of patients with newly diagnosed clinical TB were positive for Histoplasma GM. The positivity rate in the serum of patients 5-6 and 12 months after TB diagnosis was 3.8% and 3.5%, respectively. Of 88 positive Aspergillus GM sera, 63 (71.6%) were also positive for Histoplasma GM. All tested foods were positive for Aspergillus GM, while 65% of foods were positive for Histoplasma GM. CONCLUSION: Galactomannan is widespread in sera and food in Jakarta, possibly related to food consumption. Histoplasma and Aspergillus antigen detection for the diagnosis will require additional means of confirming the diagnosis; negative tests may be more helpful for ruling out invasive histoplasmosis and aspergillosis.

Factors affecting time to treatment initiation after diagnosis for multidrug-resistant/rifampicin-resistant tuberculosis patients: A mixed-methods study in Jakarta, Indonesia.

OBJECTIVE: To investigate the time to treatment initiation (TTI) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients after diagnosis in Indonesia and biological, psychological and social factors associated with the time interval. METHODS: This study was conducted in Persahabatan Hospital, Jakarta using a mixed-methods approach. Registry data and medical records of MDR/RR-TB patients were collected and matched (hospital dataset), and linked with psychosocial assessment results (linked dataset). Descriptive analysis was conducted to understand patient characteristics and the distribution of TTI after RR-TB diagnosis by GeneXpert. Generalised linear regression was used to analyse factors associated with delay duration, and logistic regression to explore factors associated with the delay longer than the median duration for both datasets (basic vs. extended model). In-depth interviews were conducted with patients and healthcare workers to understand the procedure of treatment initiation and how different factors led to delay. RESULTS: The hospital dataset included 275 patient-matched cases, and 188 were further linked with psychosocial assessment results. The median time interval was 24 days [interquartile range (IQR) 23.5] and 26 days (IQR 21.25), respectively. Regression analysis showed that in the extended model, comorbidities (exp [coefficient]= 1.93), unemployment (exp [coefficient] = 1.80) and poor knowledge of MDR/RR-TB (exp (coefficient) = 1.67) seemed to have the strongest effects on prolonging the time interval (p < 0.05). Unsuccessful TB treatment history was the only factor that significantly increased the risk of delay longer than the median duration (p < 0.05) in the basic model, while none of the factors were significant in the extended model. The qualitative study identified provider-side factors (centralised service provision and insufficient human resources) and patient-side factors (physical weakness, psychological stress and financial concern) associated with treatment delay. CONCLUSION: MDR/RR-TB patients in Persahabatan Hospital, Jakarta, Indonesia waited around 25 days for treatment initiation after RR-TB diagnosis. Health system solutions are needed to address challenges facing both MDR/RR-TB patients and healthcare providers to reduce delay in treatment initiation.

A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL).

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB. METHODS: In this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible. RESULTS: Of the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA. CONCLUSION: CPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Cost of seeking care for tuberculosis since the implementation of universal health coverage in Indonesia.

BACKGROUND: Although tuberculosis (TB) patients often incur high costs to access TB-related services, it was unclear beforehand whether the implementation of universal health coverage (UHC) in Indonesia in 2014 would reduce direct costs and change the pattern of care-seeking behaviour. After its introduction, we therefore assessed TB patients' care-seeking behaviour and the costs they incurred for diagnosis, and the determinants of both. METHODS: In this cross sectional study, we interviewed adult TB patients in urban, suburban, and rural districts of Indonesia in July-September 2016. We selected consecutively patients who had been treated for TB in primary health centers for at least 1 month until we reached at least 90 patients in each district. After establishing which direct and indirect costs they had incurred during the pre-diagnostic phase, we calculated the total costs (in US Dollars). To identify the determinants of these costs, we applied a general linear mixed model to adjust for our cluster-sampling design. RESULTS: Ninety-three patients of the 282 included in our analysis (33%) first sought care at a private clinic. The preference for such clinics was higher among those living in the rural district (aOR 1.88, 95% CI 0.85-4.15, P = 0.119) and among those with a low educational level (aOR 1.69, 95% CI 0.92-3.10, P = 0.090). Visiting a private clinic as the first contact also led to more visits (ß 0.90, 95% CI 0.57-1.24, P < 0.001) and higher costs than first visiting a Primary Health Centre, both in terms of direct costs (ß = 16.87, 95%CI 10.54-23.20, P < 0.001) and total costs (ß = 18.41, 95%CI 10.35-26.47, P < 0.001). CONCLUSION: Despite UHC, high costs of TB seeking care remain, with direct medical costs contributing most to the total costs. First seeking care from private providers tends to lead to more pre-diagnostic visits and higher costs. To reduce diagnostic delays and minimize patients' costs, it is essential to strengthen the public-private mix and reduce the fragmented system between the national health insurance scheme and the National TB Programme.

The Role of TB-LAMP Method in Detecting Mycobacterium tuberculosis from Sputum of Patients Suspected of Having Pulmonary Tuberculosis.

BACKGROUND: Indonesia is one of the countries with the highest incidence of tuberculosis (TB) in the world. Appropriate diagnosis is an effort to control TB. The World Health Organization has recommended loop-mediated isothermal amplification (LAMP). In order to be applied routinely, it is necessary to do research to evaluate the LAMP method. METHODS: the research was a cross-sectional study and was carried out at the Clinical Microbiology Laboratory of the Faculty of Medicine, Universitas Indonesia, for 100 patients suspected of having pulmonary TB. Each patient handed over two direct sputum specimens. For each direct sputum specimen, an acid-fast bacilli (AFB) smear was carried out. Two direct sputum specimens from each patient were combined to produce mixed sputum. For each mixed sputum specimen, an AFB smear, Lowenstein-Jensen culture, and TB-LAMP were carried out. RESULTS: the percentage of LAMP (+) cells in mixed sputum that was AFB (-) was 32.78%. The TB-LAMP showed a sensitivity of 100% (95% CI 89.56-100%), a specificity of 69.64% (95% CI 55.74-80.84%), positive predictive value of 71.19% (95% CI 57.73-81.86%), and negative predictive value of 100% (95% CI 88.83-100%). CONCLUSION: TB-LAMP has both high sensitivity and negative predictive value.

Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan.

Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.

Discordance Between Clinical Status and Chest X-Ray (CXR) in COVID-19 Patient with Asymptomatic Transmission in Jakarta.

Coronavirus Disease 2019 (COVID-19) symptoms are highly various in each patient. CXR are routinely used to monitor the disease progression. However, it is not known whether chest X-Ray (CXR) is a good modality to assess COVID-19 pneumonia.Male, 55 years-old, with pneumonia caused by COVID-19. Discordance was found between patient's clinical status and CXR lesion. On the 7th day of symptoms, patient was clinically well despite severe lesion shown on CXR. On the following day, patient clinically deteriorated despite the improvement on CXR lesion.Improvement of CXR does not always correlate well with patient's clinical status. Clinician have to be careful when using CXR to monitor patient with COVID-19 pneumonia.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients.

Numerous studies have reported low concentrations of antituberculosis drugs in tuberculosis (TB) patients, but few studies have examined whether low drug concentrations affect TB treatment response. We examined steady-state plasma concentrations of isoniazid, rifampin, and pyrazinamide at 2 h after the administration of drugs (C(2 h)) among 181 patients with pulmonary tuberculosis in Indonesia and related these to bacteriological response during treatment. C(2 h) values below reference values for either isoniazid, rifampin, or pyrazinamide were found in 91% of patients; 60% had at least two low C(2 h) concentrations. The isoniazid C2 h was noticeably lower in fast versus slow acetylators (0.9 mg/liter versus 2.2 mg/liter, P < 0.001). At the end of treatment, 82% of the patients were cured, whereas 30 patients (17%) had dropped out during the study, and 2 patients (1%) failed treatment. No association was found between C(2 h) concentrations and sputum culture results at 8 weeks of treatment. Post hoc analysis showed that patients with low pyrazinamide C2 h (P = 0.01) and patients with large extensive lung lesions (P = 0.01) were at risk of at least one positive culture at week 4, 8, or 24/32. Antituberculosis drug concentrations were often low, but treatment response was nevertheless good. No association was found between drug concentrations and 8 weeks culture conversion, but low pyrazinamide drug concentrations may be associated with a less favorable bacteriological response. The use of higher doses of pyrazinamide may warrant further investigation.

The role of high dose vitamin d and glutathione supplementation in COVID-19 treatment: A case series.

COVID-19 has been affecting millions of people worldwide and becoming a global public health burden. Therefore, exploring treatment options is essential to help flatten the curve and reduce hospitalization time. This is a case series of ten COVID-19 patients in Jakarta and Tangerang, Indonesia, who received a high dose of vitamin D and glutathione supplementation daily. Within 5-7 days of treatment, all patients were confirmed COVID-19 negative. To date, this is the first report from Indonesia describing the potential benefit of supplementing vitamin D and glutathione concurrently in improving clinical conditions and expediting the recovery time of COVID-19 patients.

Association between cardiovascular diseases and COVID-19 pneumonia outcome in Indonesia: a multi-center cohort study.

Background: COVID-19 is a pandemic affecting 185 countries, including Indonesia. Cardiovascular diseases (CVD) in COVID-19 patients were linked to worse clinical outcomes. However, the association remained inconclusive due to limited data in Indonesia. This study aimed to determine the association between CVD in COVID-19 pneumonia patients with its clinical outcomes. Methods: This retrospective cohort study was conducted in four Indonesian hospitals, enrolling 584 adult COVID-19 pneumonia patients from September 2020 to July 2021. Patients were categorized into two groups: non-CVD and CVD [hypertension, coronary artery disease (CAD), chronic heart failure (CHF), hypertensive heart disease (HHD), arrhythmia, cardiomegaly, left ventricular hypertrophy (LVH), mitral regurgitation (MR), and myocardial injury (MI)]. Clinical outcomes include in-hospital mortality, intensive care unit admission, ventilator use, earlier death, and prolonged hospital stay. Mann-Whitney test was used for analysis. Results: The most common CVD was hypertension (48.1%), followed by MI (10.6%), CAD (9.2%), CHF (6.8%), HHD (3.1%), arrhythmia (1.7%), and others (0.7%). The in-hospital mortality rate was 24%, and patients were hospitalized for a median of 12 days. MI was the only CVD that increased in-hospital mortality (RR 2.105). It was also significantly increased in patients with diabetes mellitus (RR 1.475) and chronic kidney disease (RR 2.079). Meanwhile, prolonged hospital stay was associated with any CVD (RR 1.553), hypertension (RR 1.511), MI (RR 1.969), CHF (RR 1.595), diabetes mellitus (RR 1.359), and cerebrovascular disease (RR 2.203). Conclusion: COVID-19 pneumonia in patients with CVD, specifically MI and hypertension, worsens the COVID-19 clinical outcomes.

Correlation expression Toll-like receptor 4 with multidrugs resistant tuberculosis in diabetes mellitus condition.

BACKGROUND: Toll-like receptor (TLR) are ligand homologous protein in the APC cell membrane that has functions as a receptor to triger leukocytes and innate immune responses. When there is a Microbacterium tuberculosis (MTB) infection enters from droplets to the lungs, the alveolar macrophages perform a phagocytic function. The interaction between M. tuberculosis and the TLR macrophage receptors produces chemokines which induce migration of monocytes and dendrite cells for destruction. Diabetes militus (DM) has become risk factor for developing tuberculosis. DM condition will reduce immunity and the ability of immune cell phagocytes bactery and triger severe infections. The consequences of more severe infection and metabolic disorders that occur make a person more likely to experience Multidrugs resistant MTB. Not much data that reports on the expression of TLR4 as a ligand that triggers an immune response in conditions of MDR and DM. We try to find out correlation between TLR-4 in MDR MTB, diabetes and level of MTB bacteria in experimental animals. METHODS: We conducted an experimental study on 30 experimental mice weighing 25 grams consisting of negative control grub, infected with MTB, infected with MDR MTB, negative control diabetes, MTB DM, MDR MTB DM. DM animals were induced by streptozosin to experience DM, then in the treatment of infection, intraperitoneal MTB and MDR MTB bacterial injections were given. Termination was carried out on day 14. We count number of bacteria level in the lungs and perform evaluation TLR4 from blood sampel. RESULTS: The negative control group had mean TLR value of 1.47 (± 0.46) while the MTB group showed an increase in TLR 9.22 (± 0.39) followed by MDR MTB 9.50 (± 0.29), DM negative control 9, 21 (± 0.24) and more increasing in conditions of DM MTB 13.36 (± 0.32) and DM MDR MTB 13.35 (± 0.34). ANOVA analysis showed a significant difference (P = 0.00). pearson correlation analysis find strong correlation TLR4 in MTB and MDR MTB with diabetes. CONCLUSION: there were a significant difference level TLR4 between MTB and MDR TB infection with diabetes. higher TLR4 level higher in DM MTB, DM MDR MTB. TLR 4 strong correlates with an increase in the number of MTB bacteria.

Evaluation of safety and effectiveness of remdesivir in treating COVID-19 patients after emergency use authorization study.

Background: This study aimed to determine the real-world safety and effectiveness of remdesivir in hospitalized adult COVID-19 patients with moderate-to-critical disease in Indonesia. Methods: A multicenter, retrospective cohort study was conducted at four COVID-19 referral hospitals in Jakarta. A total of 587 patients were included, of whom 243 received remdesivir within 72 h of admission. The safety endpoints were the proportions of patients with any adverse event (AE), any grade 3 AE, and AE of each system organ class. The effectiveness endpoints were ICU admission >24 h from baseline, live discharge and mortality at day 14, live discharge and mortality at day 28, and virologic conversion. Patients who received remdesivir within 72 h of admission were considered the treatment group, and those who did not were the control group. Multivariate adjustments were performed using a modified Poisson regression. Results: The study found no significant differences in safety endpoints between the two groups. However, the effectiveness endpoints showed that remdesivir was associated with a decreased risk of ICU admission >24 h from baseline (RR 0.71, 95% CI 0.52-0.96), an increased probability of live discharge at day 14 (RR 1.37, 95% CI 1.08-1.74), and an increased probability of live discharge at day 28 (RR 1.28, 95% CI 1.05-1.57). The rate of virologic conversion was not significantly different between the two groups. Conclusion: The study concludes that remdesivir is safe and effective in the treatment of moderate-to-critical COVID-19 in a real-world setting in Indonesia.

Clinical utility and diagnostic value of tumor-educated platelets in lung cancer: a systematic review and meta-analysis.

Background: The review addresses the knowledge gap concerning the diagnostic value and clinical utility of tumor-educated platelets (TEPs) in adult patients with lung cancer. Methods: We searched twelve databases: PubMed, CENTRAL, EMBASE, CINAHL, MEDLINE, Scopus, ProQuest, MedRxiv, BioRxiv, SSRN, Clinicaltrials.gov, and CNKI up to 24 March 2023, to include any diagnostic study regarding TEPs and LC. TEPs diagnostic value was evaluated from pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC). QUADAS 2 was used to assess the risk of bias. Heterogeneity analysis was assessed using the receiver operating characteristic (ROC) plane, Galbraith plot, bivariate boxplot, sensitivity analysis, and meta-regression. TEPs clinical utility was evaluated from Fagan's nomogram. Results: 44 reports from 10 studies, including 7,858 events and 6,632 controls, were analyzed. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.80 (95% CI 0.79-0.80), 0.69 (95% CI 0.69-0.70), 2.92 (95% CI 2.50-3.41), 0.26 (95% CI 0.21-0.32), and 12.1 (95% CI 8.61-16.76), respectively. In addition, the AUC of the Summary ROC curve was 0.85 (95% CI: 0.81-0.88). The overall risk of bias was low. Heterogeneity may result from cancer stage, cancer control, measuring equipment, and RNA types across studies. There was no apparent publication bias (p=0.29) with significant positive (79%) and negative (22%) post-test probability, according to Deeks funnel plot asymmetry test and Fagan's nomogram. Conclusion: TEPs could be a moderately effective candidate biomarker for LC diagnosis.

Expert review of global real-world data on COVID-19 vaccine booster effectiveness and safety during the omicron-dominant phase of the pandemic.

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies. AREAS COVERED: Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines. EXPERT OPINION: Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

The seroprevalence of anti-Histoplasma capsulatum IgG antibody among pulmonary tuberculosis patients in seven referral tuberculosis hospitals in Indonesia.

BACKGROUND: Histoplasma capsulatum exposure is rarely suspected in Indonesia. Pulmonary histoplasmosis can occur simultaneously with pulmonary tuberculosis (TB) or as an alternative diagnosis in clinically-diagnosed TB patients with no microbiological evidence of TB. This study aimed to determine the seroprevalence of anti-H. capsulatum IgG antibody among pulmonary TB patients. METHODOLOGY: This was a sub-study of 306 participants from a prospective cohort pulmonary TB study conducted at seven TB referral hospitals in Indonesia. The study population was presumptive pulmonary TB adult patients who underwent microbiological TB examinations and were categorized as drug-sensitive (DS), drug-resistant (DR), and clinically-diagnosed TB. Anti-H. capsulatum IgG antibody levels at baseline were measured using MVista Histoplasma Ab enzyme immunoassays. Data were summarized using descriptive statistics. Bivariate and multivariate logistic regression analysis were performed to assess factors associated with anti-H. capsulatum IgG antibody positive result. RESULTS: 12.7% (39/306) of pulmonary TB patients were positive for anti-H. capsulatum IgG antibodies (DR-TB patients (15.9%, 18/114), DS-TB (13.0%, 15/115), and clinically-diagnosed TB (7.8%, 6/77)). The median unit value of anti-H. capsulatum IgG antibody for all positive samples was 15.7 (IQR 10.2-28.9) EU. This median unit value was higher in clinically-diagnosed TB patients compared to DS-TB or DR-TB patients (38.1 (IQR 25.6-46.6) EU, 19.7 (IQR 12.3-28.9) EU, and 10.9 (IQR 9.2-15.4), respectively). There were 10 patients (3.3%) with anti-H. capsulatum IgG antibody levels above 30 EU. Factors associated with the anti-H. capsulatum IgG antibody positive result were malignancies (OR 4.88, 95% CI 1.09-21.69, p = 0.037) and cavitary lesions (OR 2.27, 95% CI 1.09-4.70, p = 0.028). CONCLUSIONS: Our results provide evidence of exposure to H. capsulatum among pulmonary TB patients in Indonesia. Further studies are needed to provide a comprehensive picture of this fungal disease in other populations and regions to enhance awareness among clinicians and public health officials.

Characteristics and outcomes of patients with severe COVID-19 in Indonesia: Lessons from the first wave.

BACKGROUND: Indonesia's national response to COVID-19 evolved rapidly throughout 2020. Understanding pandemic response and outcomes is crucial for better mitigation strategies ahead. This study describes the characteristics and outcomes of patients admitted to ICU during the early stages of the pandemic. METHODS: This is a multi-centre prospective observational study including patients from twelve collaborating hospitals in Indonesia. All patients were clinically suspected or laboratory-confirmed COVID-19 cases admitted to ICU between January 2020 and March 2021. The primary outcome was monthly ICU mortality. Descriptive statistics of patient characteristics and treatment were generated as secondary outcomes. RESULTS: From 559 subjects, the overall mortality was 68% and decreased over the study period, while the mortality of patients that received mechanical ventilation was 92%, consistently high over the study period. Fatal cases showed 2- and 4-day delays from symptoms onset to hospital admissions and ICU admissions, respectively. Evidence-backed approaches which could influence patient outcome, such as extracorporeal membrane oxygenation, prone positioning, renal replacement therapy, and neuromuscular blockade were scarcely administered. CONCLUSIONS: The mortality rate of COVID-19 patients in Indonesia was extremely high during the first major outbreak of disease, particularly in those mechanically ventilated. Delayed admission and unavailability of evidence-based approaches due to high burden on health facility during COVID-19 crisis could be addressed by efficient public health measures and enhancing health infrastructure to improve the future pandemic response.