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All Journal Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research
Rohani Lasmaria
Medical Staff Group/Department of Pulmonology and Respiratory Medicine, Arifin Achmad Regional General Hospital/Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Neuroscience

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Efficacy and Safety of Adjunctive Corticosteroids in Non-HIV Pneumocystis jirovecii Pneumonia with Respiratory Failure: A Systematic Review and Meta-Analysis of Randomized and Observational Studies Reza Rahmadinata; Rohani Lasmaria
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i2.1508

Abstract

Background: Pneumocystis jirovecii pneumonia in HIV-negative immunocompromised patients carries a mortality rate significantly higher than in the HIV-positive population. While adjunctive corticosteroids are the standard of care for HIV-associated pneumonia to prevent Immune Reconstitution Inflammatory Syndrome, their efficacy in non-HIV patients remains controversial due to differing immunopathogenesis. This study evaluated the efficacy and safety of adjunctive corticosteroids in non-HIV patients with respiratory failure, specifically addressing the discordance between historical observational data and recent randomized evidence. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching databases from January 2014 to July 2025. We included randomized controlled trials and observational studies of non-HIV adults with pneumonia receiving adjunctive corticosteroids. To address methodological heterogeneity, we performed stratified analyses separating randomized trial data from observational cohorts and conducted sensitivity analyses to account for outliers. Risk of bias was assessed using Cochrane RoB-2 and the Newcastle-Ottawa Scale. Results: Ten studies comprising 2,900 patients were analyzed. The randomized trial demonstrated no statistically significant reduction in 28-day mortality with corticosteroids (21.5% vs 32.4%, p=0.069). In the observational arm, initial pooled analysis suggested benefit, but sensitivity analysis removing a large administrative database study shifted the result to null. Crucially, higher cumulative steroid doses were associated with increased 90-day mortality (Hazard Ratio 1.01 per 100mg equivalent; p<0.05) and a significantly increased risk of secondary infections and hyperglycemia. Subgroup analysis revealed no benefit for pulse-dose regimens over standard dosing. Conclusion: Unlike in HIV, adjunctive corticosteroids do not confer a consistent survival benefit in non-HIV Pneumocystis pneumonia and are associated with dose-dependent toxicity. The routine use of corticosteroids should be abandoned in favor of a cautious approach restricted to severe, early hypoxemia using standard rather than pulse doses.
The Hepatotoxicity and Adherence Advantage of Short-Course Rifapentine/Isoniazid (3HP) over Stratified Isoniazid Monotherapy (6H/9H): A Systematic Review and Meta-Analysis Agus Subhan; Rohani Lasmaria
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i2.1520

Abstract

Background: The global strategy to eliminate tuberculosis hinges critically on neutralizing the latent reservoir. For decades, the standard of care has been daily Isoniazid monotherapy for 6 or 9 months. However, the effectiveness of this regimen is historically compromised by poor adherence due to its duration and significant rates of hepatotoxicity, particularly in older adults. The 3-month once-weekly regimen of Rifapentine plus Isoniazid offers a promising alternative, yet a consolidated high-level analysis comparing it specifically against stratified Isoniazid monotherapy across diverse high-risk groups was necessary to justify global policy shifts. Methods: We conducted a systematic review and meta-analysis of eight pivotal studies, including large-scale randomized controlled trials and programmatic surveillance studies. Outcomes included prevention of active tuberculosis, Grade 3/4 hepatotoxicity, and treatment completion. Data were pooled using a random effects model to account for clinical heterogeneity. Subgroup analyses stratified comparators by duration and administration method. Results: The analysis of over 10,000 participants revealed that the short-course regimen was non-inferior to isoniazid monotherapy for tuberculosis prevention (Pooled Risk Ratio 0.54; 95% CI 0.30–0.97). Crucially, the Rifapentine-based regimen demonstrated a profound reduction in grade 3/4 hepatotoxicity compared to Isoniazid monotherapy (Pooled Risk Ratio 0.16; 95% CI 0.08–0.32), with the benefit most pronounced in elderly populations. Treatment completion was significantly higher in the short-course group (Pooled Risk Ratio 1.25; 95% CI 1.15–1.36), with programmatic data confirming adherence exceeding 85% even under self-administration. Conclusion: The 3-month Rifapentine/Isoniazid regimen offers a superior safety profile and significantly higher treatment completion rates compared to Isoniazid monotherapy while maintaining equivalent efficacy. The regimen’s ability to minimize liver injury while maximizing adherence supports its adoption as a preferred standard of care, particularly for older adults.
Efficacy and Safety of Adjunctive Corticosteroids in Non-HIV Pneumocystis jirovecii Pneumonia with Respiratory Failure: A Systematic Review and Meta-Analysis of Randomized and Observational Studies Reza Rahmadinata; Rohani Lasmaria
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i2.1508

Abstract

Background: Pneumocystis jirovecii pneumonia in HIV-negative immunocompromised patients carries a mortality rate significantly higher than in the HIV-positive population. While adjunctive corticosteroids are the standard of care for HIV-associated pneumonia to prevent Immune Reconstitution Inflammatory Syndrome, their efficacy in non-HIV patients remains controversial due to differing immunopathogenesis. This study evaluated the efficacy and safety of adjunctive corticosteroids in non-HIV patients with respiratory failure, specifically addressing the discordance between historical observational data and recent randomized evidence. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching databases from January 2014 to July 2025. We included randomized controlled trials and observational studies of non-HIV adults with pneumonia receiving adjunctive corticosteroids. To address methodological heterogeneity, we performed stratified analyses separating randomized trial data from observational cohorts and conducted sensitivity analyses to account for outliers. Risk of bias was assessed using Cochrane RoB-2 and the Newcastle-Ottawa Scale. Results: Ten studies comprising 2,900 patients were analyzed. The randomized trial demonstrated no statistically significant reduction in 28-day mortality with corticosteroids (21.5% vs 32.4%, p=0.069). In the observational arm, initial pooled analysis suggested benefit, but sensitivity analysis removing a large administrative database study shifted the result to null. Crucially, higher cumulative steroid doses were associated with increased 90-day mortality (Hazard Ratio 1.01 per 100mg equivalent; p<0.05) and a significantly increased risk of secondary infections and hyperglycemia. Subgroup analysis revealed no benefit for pulse-dose regimens over standard dosing. Conclusion: Unlike in HIV, adjunctive corticosteroids do not confer a consistent survival benefit in non-HIV Pneumocystis pneumonia and are associated with dose-dependent toxicity. The routine use of corticosteroids should be abandoned in favor of a cautious approach restricted to severe, early hypoxemia using standard rather than pulse doses.
The Hepatotoxicity and Adherence Advantage of Short-Course Rifapentine/Isoniazid (3HP) over Stratified Isoniazid Monotherapy (6H/9H): A Systematic Review and Meta-Analysis Agus Subhan; Rohani Lasmaria
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i2.1520

Abstract

Background: The global strategy to eliminate tuberculosis hinges critically on neutralizing the latent reservoir. For decades, the standard of care has been daily Isoniazid monotherapy for 6 or 9 months. However, the effectiveness of this regimen is historically compromised by poor adherence due to its duration and significant rates of hepatotoxicity, particularly in older adults. The 3-month once-weekly regimen of Rifapentine plus Isoniazid offers a promising alternative, yet a consolidated high-level analysis comparing it specifically against stratified Isoniazid monotherapy across diverse high-risk groups was necessary to justify global policy shifts. Methods: We conducted a systematic review and meta-analysis of eight pivotal studies, including large-scale randomized controlled trials and programmatic surveillance studies. Outcomes included prevention of active tuberculosis, Grade 3/4 hepatotoxicity, and treatment completion. Data were pooled using a random effects model to account for clinical heterogeneity. Subgroup analyses stratified comparators by duration and administration method. Results: The analysis of over 10,000 participants revealed that the short-course regimen was non-inferior to isoniazid monotherapy for tuberculosis prevention (Pooled Risk Ratio 0.54; 95% CI 0.30–0.97). Crucially, the Rifapentine-based regimen demonstrated a profound reduction in grade 3/4 hepatotoxicity compared to Isoniazid monotherapy (Pooled Risk Ratio 0.16; 95% CI 0.08–0.32), with the benefit most pronounced in elderly populations. Treatment completion was significantly higher in the short-course group (Pooled Risk Ratio 1.25; 95% CI 1.15–1.36), with programmatic data confirming adherence exceeding 85% even under self-administration. Conclusion: The 3-month Rifapentine/Isoniazid regimen offers a superior safety profile and significantly higher treatment completion rates compared to Isoniazid monotherapy while maintaining equivalent efficacy. The regimen’s ability to minimize liver injury while maximizing adherence supports its adoption as a preferred standard of care, particularly for older adults.
Co-Authors Agus Subhan Reza Rahmadinata