Comparative Effectiveness of Tuberculosis Treatment Daily versus Intermittent Regimen in Indonesian TB-DM Patients: Real World Patient Database Study

Background: diabetes mellitus (DM) increases the risk of active TB by three times; there is no specific treatment strategy for tuberculosis-DM (TB-DM) patients. The 2017 WHO guidelines no longer recommended an intermittent regimen in the advanced phase of TB treatment due to higher risk of failure, relapse, and drug resistance compared to the daily regimen. This study aims to compare the effectiveness of treatment, in terms of clinical response and sputum conversion, of TB-DM patients in the advanced phase between the two-treatment delivery schedules. Methods: a retrospective cohort study from the medical records of patients from 1 January 2015 to 31 December 2018 at Persahabatan Hospital, Jakarta. The inclusion criteria are TB-DM patients aged >18 years with non-reactive HIV test, who have entered the advanced phase of category 1 TB treatment with smear positive at the time of diagnosis. Results: a total of 72 patients met the inclusion criteria. (75% male and 88.8% had at least 1+ smear results at the time of diagnosis). Thirty subjects still have positive smear at the beginning of the advance phase of treatment. After the advanced phase, 44.2% in the intermittent and 41.4% in the daily group were curedhaving sputum conversion. Seven subjects had side effects; but there were lots of dropouts and it is unclear whether they dropped because of side effects or not. Conclusion:there is no difference between sputum conversion profile and treatment success in advanced phase TB-DM treatment category 1 between the daily and intermittent regimen.ly for diabetic patients.

Efavirenz Plasma Concentrations and HIV Viral Load in HIV/AIDS-tuberculosis Infection Patients Treated with Rifampicin

Aim:to determine the effect of a rifampicin-containing tuberculosis regimen on efavirenz plasma concentrations and viral load in HIV/AIDS-Tuberculosis infection patients who received efavirenz-based antiretroviral therapy. Methods:plasma efavirenz concentrations and HIV viral load were measured in HIV/AIDS patients treated with 600 mg efavirenz-based antiretroviral for 3 to 6 months and in HIV/AIDS-Tuberculosis infection patients treated with similar antiretroviral regimen plus rifampicin-containing antituberculosis in Sulianti Saroso Infectious disease Hospital, Jakarta. Plasma efavirenz concentration in both groups were compared using Mann-Whitney test, while proportion of patients with viral load >40 copy/mL were analyzed with chi-square test. Results:forty five patients (27 with HIV/AIDS and 18 with HIV/AIDS-Tuberculosis infections) were recruited during the period of February to May 2015. The median efavirenz plasma concentration obtained from HIV/AIDS group was 0,680 mg/L(range 0,24 to 5,67 mg/L and that obtained from HIV/AIDS-Tuberculosis group was 0.685 mg/L (0.12 -2.23 mg/L) which was not significantly different statistically. The proportion of patients with viral load ≥40 copies/mL after 3-6 months of ARV treatment in the HIV/AIDS group was 51.9%, and in the HIV/AIDS-Tuberculosis group was 72.2%, which was not significantly different statistically (Chi Square test, p=0.291). Conclusion:plasma efavirenz concentration in HIV/AIDS-tuberculosis patients receiving antiretroviral and rifampicin is not significantly different from that on HIV/AIDS patients without tuberculosis. Proportion of patients with viral load of >40 copy/mL is higher in HIV/AIDS-tuberculosis patients receiving rifampicin compared to HIV/AIDS patients that not receive rifampicin. However, this difference did not reach statistical significance. Confirmatory studies with bigger sample size are needed to clarify the influence of rifampicin on plasma level ofefavirenzand and on viral load

A PROSPECTIVE SURVEY OF APPROPRIATENESS OF PAIN PHARMACOTHERAPY MANAGEMENT IN POST-CESAREAN SECTION PATIENTS IN CIPTO MANGUNKUSUMO HOSPITAL

Objective: In this study, we sought to assess the pattern of analgesic usage, adequacy of pain management, side effects, and analgesic drug interactionsin the post-emergency cesarean surgery setting.Methods: This was a prospective observational study of 80 patients who underwent emergency cesarean surgery at the Obstetrics and GynecologyDepartment of the Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSUPN-CM) between July 2015 and January 2016. Adequacy of painmanagement during the first 3 post-operative days was assessed using Pain Management Index. Relation between pain intensity during activities andrest with patient characteristic was assessed using Chi-squared test and Fischer’s exact test.Results: Nineteen patients (8.7%) were prescribed two types of nonsteroid anti-inflammatory drugs concomitantly, and 41.8% received inappropriateanalgesics at a lower frequency. Most patients experienced pain with numerical rating scale score >3 in the first 24 h post-surgery: 59 patients(73.75%) experienced pain during activities and 7 patients (8.75%) during rest.Conclusion: Post-emergency cesarean surgery pain management at RSUPN-CM was not optimal. Most patients did not receive adequate painmanagement in the first 24 h post-surgery

Evaluasi Elektrokardiogram Interval QTc dan JTc pada Penderita Malaria Vivaks yang Diberikan Dihidroartemisinin-Piperakuin dan Primakuin

Dihidroartemisinin-piperakuin (DHA-PPQ) telah digunakan secara global sebagai terapi malaria vivaks. Salah satu efek samping DHA-PPQ adalah pemanjangan repolarisasi ventrikel yang dapat menimbulkanaritmia ventrikuler yaitu Torsade de Pointes (TdP). Studi before-after ini bertujuan untuk mengetahuiperbedaan rerata interval QTc dan JTc penderita malaria vivaks sebelum dan sesudah pemberian DHA-PPQdan primakuin (PQ). Penelitian dilakukan di Lembaga Biologi Molekuler Eijkman, Jakarta pada bulan Mei-Juli2015. Sumber data adalah data sekunder hasil rekaman EKG pada penelitian utama “Safety, tolerability, andefficacy of artesunat-pyonaridine or dihydroartemisinin-piperaquine in combination with primaquine as radicalcure for P.vivax in Indonesian soldiers” tahun 2010. Subyek yang masuk kriteria seleksi pada pemberianDHA-PPQ dan PQ, masing-masing berjumlah 24 subyek dan 14 subyek. Interval QT dan JT dalam penelitianini menggunakan dua formula yang sudah dikoreksi terhadap frekuensi denyut jantung yaitu formula Bazett(QTcB, JTcB) dan Fridericia (QTcF, JTcF). Pemberian DHA-PPQ menunjukkan pemanjangan rerata intervalQTcF secara bermakna dibandingkan baseline yaitu sebesar 14,42 milidetik terjadi di D3 predose dan 20,53milidetik di D3 postdose. Rerata pemanjangan interval JTcF setelah pemberian DHA-PPQ adalah 13,43milidetik di D3 postdose. Pada pemberian PQ terdapat perbedaan nilai rerata interval QTcB dibandingkanbaseline sebesar 19,42 milidetik. Rerata pemanjangan interval JTcF dibandingkan baseline 16,50 milidetik diD42 postdose dan secara statistik bermakna. Kata kunci: dihidroartemisinin-piperakuin, primakuin, malaria vivaks, Torsade de Pointes, interval QTc, interval JTc.   Electrocardiogram Evaluation of QTc and JTc Interval of DihydroartemisininPiperaquine and Primaquine Therapies Given to The Vivax Malaria Patient

FIXED-DOSE COMBINATION VERSUS SEPARATE ANTITUBERCULOSIS FORMULATIONS IN PULMONARY TUBERCULOSIS PATIENTS: EVALUATION OF EFFECTIVENESS AND SAFETY

Objective: This study aimed to compare the effectiveness and safety of fixed dose combination (FDC) versus separate (separate formulation [SF])antituberculosis (TB) formulations in patients with bacteriologically confirmed pulmonary TB.Methods: Data were collected retrospectively from patient records, which included all newly diagnosed bacteriologically confirmed pulmonaryTB patients treated with first category FDC or SF between January 2014 and January 2017 at the Dr. Esnawan Antariksa Hospital. The efficacy ofthe formulations was determined according to acid-fast bacilli (AFB) sputum smear conversion at the end of the intensive phase (month 2), after6 months of therapy, and after the extended treatment phase (month 3). Adverse drug reactions (ADRs) during treatments were recorded as safetyoutcomes. Chi-square tests were used to analyze the differences between the groups.Results: On comparing patients treated with FDC (n=33) and SF (n=30), rates of sputum conversions did not differ significantly after 2 months(83.3% vs. 78.7%, p=0.693) and the intensive phase was extended by 1 month for patients with conversion failures at this time point. One of sevenpatients in the FDC group did not achieve sputum conversion during the extended phase and was recorded as a medication failure. At the end ofcontinuation phase, all other subjects achieved sputum conversion. The overall frequencies of ADRs were not significantly higher in the FDC groupthan that in the SF group (36.4% vs. 23.3%, p=0.260).Conclusion: No differences in effectiveness and safety profiles were identified between first category FDC and separate anti TB formulations

QUALITATIVE REVIEW OF ANTIBIOTIC USE FOR NEONATAL SEPSIS

Objective: The aim of this study is to evaluate the antibiotic use in neonates with sepsis.Methods: An observational retrospective study was conducted using medical records of neonates diagnosed with early-/late-onset sepsis who wereprescribed antibiotics and who were treated in the neonatal intensive care unit (NICU) at the Dr. Cipto Mangunkusumo Hospital between January 1 andDecember 31, 2015. Patient records were screened for antibiotic use; qualitative analyses were performed using the Gyssens algorithm. Concordanceof empirical antibiotic prescriptions with subsequent blood culture and sensitivity tests was evaluated.Results: A total of 176 sepsis cases included 80 and 96 neonates with normal and low birth weights (LBWs), respectively. Ampicillinsulbactam+gentamycin, which is indicated in local guidelines as the first-line antibiotic combination for neonatal sepsis, was most frequentlyprescribed. In the normal birth weight group, appropriate antibiotic use (Gyssens Category I) was found in 89.7% of cases, whereas Gyssens Category V(no indication) was found in 4.54% of cases. In the LBW group, 88.1% and 6.2% of cases were included in Gyssens Categories I and V, respectively.Only 17.5% and 13.5% cultured blood specimens from normal and LBW groups, respectively, yielded positive results; the most commonly identifiedbacteria were Acinetobacter baumannii and Klebsiella pneumonia. All isolates were resistant to ampicillin-sulbactam; only 7.4% were sensitive togentamicin.Conclusion: Antibiotic use for neonatal sepsis in NICU in this study can be considered appropriate, suggesting proper implementation of antimicrobialguidelines. However, high rates of resistance to the first-line antibiotics for neonatal sepsis are concerning

KIDNEY INJURY MOLECULE-1 AS AN EARLY AMIKACIN-INDUCED NEPHROTOXICITY MARKER IN PATIENTS WITH SEPSIS HOSPITALIZED IN THE INTENSIVE CARE UNIT

Objective: This study sought to determine the correlation between trough plasma amikacin concentrations and urinary normalized kidney injurymolecule-1 (KIM-1) concentrations as an early biomarker of nephrotoxicity in patients with sepsis who are hospitalized in an intensive care unit.Methods: In this pilot study, 12 patients with sepsis were treated with amikacin 1000 mg/day between May 2015 and September 2015. The correlationbetween trough plasma amikacin concentrations measured after the third dose and the elevation of urinary normalized KIM-1 concentrations afterthe third amikacin dose relative to the first/second dose was evaluated.Results: In total, three patients had trough plasma amikacin concentrations exceeding the safe level (>10 μg/ml). Furthermore, eight patientsdisplayed higher normalized KIM-1 concentrations after third dose than after the first/second dose; however, there was no correlation betweentrough amikacin concentrations and the elevation of urinary normalized KIM-1 concentrations (r=0.3, p=0.3).Conclusion: The study results illustrated that short-term treatment with an amikacin dose of 1000 mg/day was generally safe in patients with sepsis

Outcomes of Daily Dose versus Part-daily Dose Treatment for Lung Tuberculosis: A Real-World Database Study in an Indonesian Hospital

Background: a meta-analysis of randomized control trials (RCTs) on category I pulmonary tuberculosis (PTB) treatments showed that either part-daily (2RHZE/4R3H3) or daily dose (2RHZE/4RH) had the same failure and recurrence rates. However, the World Health Organization (WHO) concluded that the part-daily dose had higher failure and recurrence rates. Therefore, this study was conducted to compare the treatment outcomes between both regimens, whether daily dose regimen has a better treatment outcome than part-daily dose regimen, and the adverse effects between both regimens. Methods: this was an analytic cross-sectional study of patients at the Persahabatan General Hospital, over the period of January 2015-June 2018. Data were taken from medical records and supported by telephone interviews, each regimen group had 175 patients. Results: there were no significant differences for success rates (p=0.470), lost to follow up rates (p=0.659), failure rates (p=1.000), death rates (p=1.000), and adverse effects in the continuation phase (p=0.324) between the groups. There were, however, significant differences in cure rates (p < 0.001) and complete treatment rates (p<0.001) between the groups. Conclusion: the cure rate and complete treatment rate were found to be better for the part-daily than the daily doses. The success rate of both regimens were the same as Indonesia’s target (90%). In the continuation phase, there were no significant difference of adverse effects between both regimens

Evaluasi Elektrokardiogram Interval QTc dan JTc pada Penderita Malaria Vivaks yang Diberikan Dihidroartemisinin-Piperakuin dan Primakuin

Dihidroartemisinin-piperakuin (DHA-PPQ) telah digunakan secara global sebagai terapi malaria vivaks. Salah satu efek samping DHA-PPQ adalah pemanjangan repolarisasi ventrikel yang dapat menimbulkanaritmia ventrikuler yaitu Torsade de Pointes (TdP). Studi before-after ini bertujuan untuk mengetahuiperbedaan rerata interval QTc dan JTc penderita malaria vivaks sebelum dan sesudah pemberian DHA-PPQdan primakuin (PQ). Penelitian dilakukan di Lembaga Biologi Molekuler Eijkman, Jakarta pada bulan Mei-Juli2015. Sumber data adalah data sekunder hasil rekaman EKG pada penelitian utama &ldquo;Safety, tolerability, andefficacy of artesunat-pyonaridine or dihydroartemisinin-piperaquine in combination with primaquine as radicalcure for P.vivax in Indonesian soldiers&rdquo; tahun 2010. Subyek yang masuk kriteria seleksi pada pemberianDHA-PPQ dan PQ, masing-masing berjumlah 24 subyek dan 14 subyek. Interval QT dan JT dalam penelitianini menggunakan dua formula yang sudah dikoreksi terhadap frekuensi denyut jantung yaitu formula Bazett(QTcB, JTcB) dan Fridericia (QTcF, JTcF). Pemberian DHA-PPQ menunjukkan pemanjangan rerata intervalQTcF secara bermakna dibandingkan baseline yaitu sebesar 14,42 milidetik terjadi di D3 predose dan 20,53milidetik di D3 postdose. Rerata pemanjangan interval JTcF setelah pemberian DHA-PPQ adalah 13,43milidetik di D3 postdose. Pada pemberian PQ terdapat perbedaan nilai rerata interval QTcB dibandingkanbaseline sebesar 19,42 milidetik. Rerata pemanjangan interval JTcF dibandingkan baseline 16,50 milidetik diD42 postdose dan secara statistik bermakna. Kata kunci: dihidroartemisinin-piperakuin, primakuin, malaria vivaks, Torsade de Pointes, interval QTc, interval JTc. &nbsp; Electrocardiogram Evaluation of QTc and JTc Interval of DihydroartemisininPiperaquine and Primaquine Therapies Given to The Vivax Malaria Patients Abstract Dihydroartemisinin-piperaquin (DHA-PPQ) has been used globally as standard combination therapies for vivax malaria treatment. One of the side effects that must be put into caution is the prolongation ofventricular repolarization, which can lead to the development of ventricular arrhythmia known as Torsadede Pointes (TdP). This study used&nbsp; &lsquo;before and after&rsquo; design and was aimed to find out whether there was asignificant difference of QTc and JTc interval of vivax malaria patients pre and post DHA-PPQ and Primaquin(PQ) dose. The ECG record of DHA-PPQ and PQ, respectively, 24 and 14 subjects. QT and JT intervalsare affected by heart rate, thus, both of them have to be corrected according to the heart rate using twoformulas, i.e.: Bazett (QTcB, JTcB) and Fridericia (QTcF, JTcF) formulas. The results showed significant QTcFprolongations of 14.42 ms predose and 20.53 ms postdose on D3 DHA-PPQ treatment compared to thebaseline value, whereas prolongations of JT interval were 13.43 ms found on D3 postdose. The results aftergiven PQ showed mean difference of QTcB compared to the baseline value was 19.42 ms. The result for JTcFinterval after given PQ, showed mean difference of prolongations compared to the baseline value was 16.50ms, which was statistically significant. Key words: dihydroartemisinin-piperaquine, primaquine vivax malaria, Torsade de Pointes, QTcinterval,JTc interva

A cost-effectiveness and safety analysis of dual antiplatelet therapy comparing aspirin–clopidogrel to aspirin–ticagrelor in patients with acute coronary syndrome

Background: Dual antiplatelet therapy (DAPT) using either an aspirin–clopidogrel (A–C) combination or aspirin–ticagrelor (A–T) combination has become the standard therapy for acute coronary syndrome (ACS). Ticagrelor shows better pharmacokinetic profiles but is more expensive. This study aimed to compare cost-effectiveness and safety profiles of A–C versus A–T in patients with ACS. Methods: This was a retrospective cohort study of ACS patient at the Cipto Mangunkusumo Hospital between 2014 and 2016. ACS patients treated for the first time with A–T or A–C were included. Occurrence of major adverse cardiovascular events (MACE) within 3, 6, 9, and 12 months were used as effectiveness outcomes, while safety outcomes were measured based on the incidence of adverse drug reactions (major and minor bleeding, dyspnea, and hyperuricemia). Cost-effectiveness analysis was presented as incremental cost-effectiveness ratio (ICER). Results: Data records obtained from 123 ACS patients treated with A–C and 57 ACS patients treated with A–T were evaluated. Within the first three months, the MACE rate was 15.8% in the A–T group and 31.7% in the A–C group (RR: 0.498, 95% CI: 0.259–0.957, p=0.039). There was no statistically significant difference observed in the number of MACE between groups after 6, 9, and 12 months. The A–T group had a higher incidence of major bleeding (melena) than the A–C group (5.3% vs 1.62%, p=0.681), especially in geriatric patients. Minor bleeding was observed in three patients of the A–C group, but in none of the patients in the A–T group. The cost of ICER was IDR 279,438, indicating the additional cost needed for avoiding MACE within 3 months, if A–T was used. Conclusion: The aspirin–ticagrelor combination is a clinically superior and cost-effective option for MACE prevention among ACS patients, especially during the first three months of DAPT, with a slight but not significantly higher major bleeding risk when compared to the aspirin–clopidogrel combination