Safety and Efficacy of NC120 for Improving Lipid Profile: A Double Blind Randomized Controlled Trial

Background: the use of statin to lower blood cholesterol is often associated with bothersome adverse effects such as myopathy and liver dysfunction. NC120 is herbal lipid lowering drug containing red yeast rice (RYR) extract, guggulipid, and chromium picolinate, and expected to have better safety profile. The aim of this study was to evaluate the efficacy and safety profiles of NC120 in lowering blood lipid. Methods: this was a double blind randomized clinical trial comparing NC120 with placebo in subjects with hypercholesterolemia. Two capsules of NC120 or placebo were administered twice a day for 28 days. Blood total-cholesterol, LDL-cholesterol, and triglyceride were measured on day-0, day-7, and day-28. Unpaired t-test was used to compare study parameter between groups, and one-way ANOVA was used to compare within group. Results: 25 subjects received NC120 and 24 subjects received placebo. Significant decrease of total cholesterol and LDL-cholesterol were observed since day-7 in NC120 group, while the changes in placebo group were not significant at all time of observation. No significant decrease of triglyceride was observed in NC120 group and in placebo group. Side effects were minor and comparable between the two groups. Conclusion: NC120 is effective in reducing total cholesterol and LDL-cholesterol, but not triglyceride. This drug shows a good safety profile, and thus can be considered for patients who can not tolerate statin drugs

An Observational Study to Evaluate the Safety and Efficacy of Telbivudine in Adults with Chronic Hepatitis B

Aim: to assess the safety and efficacy of telbivudine therapy in adult patients with CHB in Indonesia. Methods: the study design was prospective cohort study. Multicenter study of adult CHB patients requiring oral antiviral therapy in daily practice setting. All patients received 600 mg of telbivudine daily for one year. Recruitment and decision to start telbivudine therapy was based on clinical indication as assessed by the participating physicians. The primary end-point was patient safety (adverse event or serious adverse events); while the secondary end-points were HBeAg seroconversion, changes of serum HBV DNA levels and serum ALT normalization. Patients were assessed at week-24 and week-52 of treatment. Results: a total of 176 cases were eligible for analysis, comprising 104 (59.8%) HBeAg-positive and 70 (40.2%) HBeAg-negative patients. Adverse events were reported in 7 (4.0%) patients, most of them were mild. HBeAg loss and seroconversion rate was 28.8% and 14.14% at week-52 respectively. Undetectable HBV DNA (PCR negativity) was 51.8% at week-24 and 62.7% at week-52. Median HBV DNA levels were significantly reduced from baseline to week-24 and week-52 treatment (both p<0.001; Wilcoxon’s signed-rank test). Normalization of serum ALT activity occurred in 85 (73.28%) patients at week-52. Conclusion: Telbivudine therapy is generally safe and well tolerated among adult Indonesian patients with chronic hepatitis B. Treatment efficacy in terms of HBeAg loss and seroconversion, changes of HBV DNA levels and serum ALT normalization were similar to previous reported studies. Key words: Alanine aminotransferase, chronic hepatitis B, HBV DNA, oral antiviral treatment, telbivudine therapy

QT Interval Prolongation Associated with Amiodarone Use in Cipto Mangunkusumo Hospital, Jakarta

Aim: to evaluate the incidence of QTc interval prolongation associated with the use of amiodarone, as well as factors that influence its occurrence. Methods: this was a descriptive retrospective study conducted from November 2010 until December 2011 using medical record of patients at ICCU Cipto Mangunkusumo Hospital from 2004-2011. Four groups of patients were included: (1) patients receiving amiodarone and other drugs causing which can cause QTc prolongation, (2) patients receiving amiodarone and other drug not causing QTc prolongation, (3) patients receiving drugs which can cause causing QTc prolongation, (4) patients not receiving amiodarone, nor other drugs which can cause causing QTc prolongation (served as control group). Difference of QTc interval within the same group was analyzed with paired t-test or Wilcoxon matched-pairs test. Between groups comparison were performed with Kruskal Wallis test. The influence of other factors (sex, age, heart failure, liver disorder, electrolyte imbalance) on QTc prolongation was analyzed using multiple regression. Results: QTc interval prolongation in groups 1, 2, and 3 were respectively 65.5%, 63.3%, 56.6%, which were significantly different from control group (24.4%); Hypernatremia and hypertension were revealed as significant risk factor for QTc prolongation. Mortality occurred in 3, 4, and 4 patients in group 1, 2, and 3 respectively, and none in group 4. Conclusion: QTc interval prolongation occurred in association with amiodarone and other drugs known to prolong QTc interval. Hypernatremia and hypertension were shown as significant influencing factor of QTc interval prolongation. Key words: amiodarone, antiarrhythmia, QTc interva

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 &gt;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

Effect of Metformin on Handgrip Strength, Gait Speed, Myostatin Serum Level, and Health-related Quality of Life: A Double Blind Randomized Controlled Trial among Non-diabetic Pre-frail Elderly Patients

Background: sarcopenia contributes to the development of frailty syndrome. Frailty syndrome is potentially improved by modifying insulin resistance, inflammation, and myostatin level. This study is aimed to investigate the effect of metformin on handgrip strength, gait speed, myostatin serum level, and health-related quality of life (HR-QoL) among non-diabetic pre-frail elderly patients. Methods: a double blind randomized controlled trial study was conducted on non-diabetic elderly outpatients aged ≥ 60 years with pre-frail status based on phenotype and/ or index criteria (Cardiovascular Health Study and/ or Frailty Index 40 items) consecutively recruited from March 2015 to June 2016 at Cipto Mangunkusumo Hospital. One-hundred-twenty subjects who met the research criteria were randomized and equally assigned into 3 x 500 mg metformin or placebo group. The study outcomes were measured at baseline and after 16 weeks of intervention. Results: out of 120 subjects, 43 subjects in metformin group and 48 subjects in placebo group who completed the intervention. There was a significant improvement on the mean gait speed of metformin group by 0.39 (0.77) second or 0.13 (0.24) meter/second that remained significant after adjusting for important prognostic factors (p = 0.024). There was no significant difference on handgrip strength, myostatin serum level, and HR-QoL between both groups. Conclusion: 3 x 500 mg metformin for 16 weeks was statistically significant and clinically important in improving usual gait speed as one of the HR-QoL dimensions, but did not significantly improve the EQ-5D index score, handgrip strength, nor myostatin serum level

A Clinical Trial on Biological Half Life of Bioactive Protein from Lumbricus rubellus, DLBS1033 in Healthy Volunteers

Background: DLBS1033 is a bioactive protein fraction extracted from Lumbricus rubellus, with fibrinogenolytic, fibrinolytic and anti-aggregation activities reported in an in vitro study. Plasma half-life is an important parameter to calculate its dose. This study was conducted to evaluate the biological half-life of DLBS1033 by measuring serial plasmin-antiplasmin (PAP) complex. PAP complex is a stable and inactive compound as a result of fibrinolysis process. Methods: this was an open-label clinical trial in healthy adult subjects. Subjects were divided into two groups to receive single dose drugs (received 3 x 490 mg) or repeated administration until steady state conditions (3 x 490 mg/day for 3 days). Blood samples for PAP complex measurement were collected at time 0 (before drug administration for single dose group), then at 0.5, 1, 1.5, 2, 3, 6, 8, 10, 12, and 24 hours after drug administration. Safety parameters used in this study were creatinine, prothrombin time (PT), activated partial thromboplastin time (aPTT), SGOT, and SGPT. Results: the biological half-life of DLBS1033 was calculated based on the mean of PAP complex concentration on each time sampling. In single dose group, the highest mean of PAP complex concentration was reached before drug administration. Our result showed that the activity of DLBS1033 could not be determined after single dose administration. In steady state condition, the PAP complex concentration increase in 2 hours after last drug administration. The biological half-life of DLBS1033 was 8.6 hours. There were no significant safety findings on all laboratory parameters and no serious adverse events. Conclusion: it is concluded that the fibrinolytic effects of DLBS1033 can be measured in steady state condition. The biological half-life of DLBS1033 in steady state condition was 8.6 hours. There were no serious adverse events on two groups of subjects

The Role of Hepatitis C Virus NS5A Region Mutation and SNP IL-28B of Host to Support Successful Pegylated Interferon and Ribavirin Treatment in Patients with HCV-HIV Coinfection: A Prospective Cohort Study

Background: HIV infection in HCV-infected patients accelerates disease progression and reduces the success rate of Peg-IFN/RBV treatment. HCV mutation in NS5A-ISDR/PKR-BD region improved the outcome in HCV monoinfection treated with Peg-IFN/RBV. SNP-IL28B polymorphism is predicted to have an effect on HCV quasispecies evolution. However, the role of NS5A mutation and SNP IL-28B in HIV-HCV coinfection is still unclear. The aim of the study is to determine the role of HCV NS5A-ISDR/PKR-BD mutation and SNP IL-28 polymorphism on the successfulness of Peg-IFN/RBV therapy in HCV-HIV coinfection. Methods: prospective cohort was performed in this study. Plasma sample were obtained from 30 and 8 patients with HCV-HIV coinfection and HCV monoinfection, respectively. PCR nucleotide sequencing was performed after RNA virus extraction and cDNA synthesis. Protein secondary structure and prediction of mutation function were analyzed using PredictProtein (PP) program. Results: sixteen HCV-HIV coinfected patients and none from eight HCV patients achieved sustained virological response (SVR). ≥1 non-neutral mutation was found in 24/30 HCV-HIV coinfection and more frequent in SVR group (14 patients). ≥1 non-neutral mutation were found statistically significant for overall SVR achievement (p<0.05) in all patients regardless of coinfection or monoinfection status. Of the 27 HCV-HIV coinfected patients with CC-gene, 21 subjects had non-neutral mutation. The structure which was expected as NS5A binding site structure was different from consensus (wild type) in SVR group, while the structure was similar to consensus in non-SVR group. Conclusion: having ≥1 non-neutral mutation was associated with SVR achievement in Peg-IFN/RBV therapy, regardless of monoinfection and coinfection status

The Effect of Mangiferin Against Brain Damage Caused by Oxidative Stress and Inflammation Induced by Doxorubicin

Doxorubicin (DOX) is an anthracycline antibiotic used for anticancer therapy. However, this agent can cause various systemic side effects including cognitive impairments in chronic use. Brain damage due to DOX is caused by an increase of tumor necrosis factor-alpha (TNF-α) level in the brain. Increased TNF-α can further lead to chronic inflammation which can lead to neuronal deaths or neurodegenerative diseases. Mangiferin (MAG), a compound extracted from Mangifera indica, has been found neuroprotective activities, but its effect on DOX-induced brain damage is unknown. This study aims to determine the effect of MAG on brain damage induced by DOX. Male Sprague-Dawley rats were induced by DOX intraperitoneally. MAG was given orally at the doses of 30 and 60 mg/kg bw for 7 consecutive weeks. The parameters measured were inflammatory and oxidative stress markers in brain tissue. Coadministration of MAG with DOX reduced inflammation which was marked by the reduction of TNF-α mRNA expression, decreased TNF-α level and reduction of oxidative stress marked by increase of superoxide dismutase level and decrease of malondialdehyde level. In conclusion, MAG was shown to have a neuroprotective effect on brain damage induced by DOX, partly due to inhibition of inflammation and oxidative stress

Medical Journal of Indonesia, under managerial transition

[no abstract available