Volume 30, Issue 6 - Conference Special Issue: 2nd International Graduate Student Conference on Pharmaceutical Sciences (IGSCPS) & 2019 International Joint Symposium of the 8th Asia Pacific Pharmacy Education Network and the 2nd Halal Pharmaceuticals and Cosmetics (APPEN-HPC) / Guest Editors: Elida Zairina & Chrismawan Ardianto

Background The growing burden of diabetes mellitus (DM) in Southeast Asia puts pharmacists in the ideal position to provide management of DM. This narrative review aims to describe the evidence of pharmacist contribution in improving DM in Southeast Asia. Content A literature search was conducted to identify relevant research articles published from 2010 to 2018 in four databases (Scopus, Pubmed, MEDLINE, and Springerlink) describing pharmacist roles and activities intended to improve management of DM in Southeast Asian countries. Results were synthesized narratively and divided into three main sections: (1) the role of pharmacist in DM management, (2) the impact of pharmacist role, and (3) the barriers to the implementation of services in DM management. A total of 16 studies were identified, of which ten studies mentioned services that were conducted exclusively by a pharmacist and the remaining collaborated with other health professionals. A number of pharmacist services were reported including prevention, dispensing, medication review, drug information services, patient counselling and education, monitoring, follow-up, and referral. Barriers related to individual, organizational, and public recognition were described. Summary and outlook The Pharmacist can contribute to improve DM management in a variety of settings. Action research on pharmacist intervention in DM is recommended.

Background The Chronic Disease Management Program or Program Pengelolaan Penyakit Kronis (Prolanis) is a program initiated by the Social Insurance Administration Organization or Badan Penyelenggara Jaminan Social (BPJS) in Indonesia. Prolanis aim to provide a proactive healthcare service approach for patients with chronic diseases particularly those with diabetes mellitus and hypertension. Prolanis also aims to achieve the optimal quality of life in patients with chronic disease through effective and efficient healthcare services including cost. All primary healthcare centers and a few of the private clinics in Indonesia have implemented Prolanis, however, the impact of the program has not been reviewed. This review aimed to see the implementation of Prolanis in healthcare facilities in Indonesia. Methods A literature review was conducted by searching articles through Google Scholar and PubMed databases up to August 2019. The following keywords or terms were used: Prolanis, BPJS indexed with terms related to blood pressure or hypertension in Indonesia. The references, citations and similar articles from the identified articles were used to identify additional sources. Results Twenty-four articles were identified through the first search using the key terms although only eight articles met the inclusion criteria. This review showed that the implementation of Prolanis in the healthcare facilities in Indonesia was varied in terms of the activities and services provided. The healthcare professional involved in the implementation of Prolanis were also varied. There were some barriers faced by the healthcare facilities including the availability of funding, the healthcare facilities and infrastructures, the unavailability of standard operating orocedures (SOPs) as well as the limitation of human resources involved in Prolanis. Conclusions The implementation of Prolanis in Indonesia has not been optimized, as there were some barriers during its implementation in the healthcare facilities.

Background Oxidative stress plays a pivotal role in the pathophysiology and pathogenesis of mental diseases, such as depression or anxiety. Psychological stress induced by predatory stimulus is one of the models that explain how induced affective behavior is manifested as a depression-like state. Quercetin is a flavonoid that exhibits potential pharmacological activity on mental diseases. Thus, the present study was designed to investigate the effect of quercetin on innate fear and affective behavior induced by repeated predator stress exposure on mice. Materials and methods ICR mice were exposed to predatory stress for 3 days. Quercetin at a dose of 50 mg/kg was given intraperitoneally along with stress induction. The freezing behavior during the stress induction was analyzed. The anxiety-like and depressive-like behaviors and cognitive and motor functions were examined on the last day of induction. Results Predatory stress increased the affective behaviors (anxiety-like and depressive-like behaviors) and produced freezing behavior without alterations in the cognitive function and exploratory behavior. Treatment with quercetin 50 mg/kg attenuated the freezing, anxiety-like and depressive-like behaviors. Conclusions Repeated predator stress exposure causes both innate fear and depression-like state for the prey animals. Quercetin may have a protective effect against depression and alleviates the fear of traumatic events.

Background Myalgia in patients can be associated with a large array of conditions, including injuries, infections and inflammations. Treatment for myalgia may include the use of oral, topical and injectable medicines (IM). However, the use of IM has been restricted by the World Health Organization due to the common hazards associated with inappropriate medicine use, risks of disease transmission and more expensive spending for using IM. Accordingly, the Ministry of Health of Indonesia (MoH) has limited the use at the level of ≤1% in every primary care center (Puskesmas) across the nation. The aim of this study was to report and evaluate rational drug use injection in myalgia in a Puskesmas in Pamekasan, Indonesia. Methods This study reviewed official documents, such as rational drug use report, medicine use databases and drug request report. The documents were obtained from the district health office or public domain from 2014 to 2018. Data were then collated, extracted and presented as frequencies. Results The average rate of use of IM for myalgia in Pamekasan was 36.15%. All 20 Puskesmas in Pamekasan conducted injection practice above the recommended level, thus reflecting a major gap between practice and policy implementation. This study implies that a substantial effort is needed to enforce the policy. Conclusions The use of IM for myalgia treatment in Pamekasan from 2014 to 2018 was significantly higher than the recommended level, thus reflecting a major problem in the practice. This is an alarming call for the local healthcare stakeholders to improve such a situation.

Background Social media (SM) is everywhere, and it affects all aspects of life, including health care. This study aimed to identify pharmacist activity in SM and explore the potential for pharmacist contributions using SM. Methods Focus group discussions (FGDs) were conducted in four cities in Indonesia. The investigators collaborated with a local pharmacist association to select a wide range of pharmacists as participants. The discussions were audiotaped, transcribed, and thematically analyzed. Results Forty-one pharmacists participated in the FGDs. Four broad themes were identified: pharmacist use of SM, current initiatives using SM, public acceptance, and opportunities for role expansion. WhatsApp was the most used SM and had meaningful contribution to spread information and change a patient’s behavior. Participants used SM mainly for personal purposes, but when it came to pharmacy and health issues, they were among the first to be contacted by patients or to counter misleading information in SM. A number of participants actively used SM for health promotion in form of sharing health information, promoting use of medicines, providing drug reminders, and encouraging compliance to medication. The public had a high trust to information provided by pharmacists in SM. Although participants believed pharmacists can play a role in educating patients and influencing the health of the communities, they considered being active in SM as burdensome, time consuming, and potential for lawsuit. Conclusions SM has become a venue for pharmacists to improve the health of the people. Several unique features in SM may facilitate pharmacist contributions; however, whether pharmacists continue to undertake such initiative cannot be guaranteed.

Background The Government of Indonesia has put in place many interventions for rationalizing drug use at all levels of the health services including in primary care centers (puskesmas). One of the programs for the rational use of drugs at the puskesmas is the monitoring and evaluation of drug use conducted by pharmacists. The purpose of this research was to evaluate the rationality of drug use in Pamekasan puskesmas that use World Health Organization (WHO) prescribing indicators and to find the difference in the percentage of rationality of drug use between puskesmas in Pamekasan. Methods This study reviewed official documents considering reporting of rational drug use. The documents were obtained from the district health office or from the public domain from 2014 to 2018. Data were then collated, extracted, and presented as frequencies. Results The percentage prescribed for antibiotics for acute respiratory infection (ARI) non-pneumonia was 47.27% and percentage prescribing antibiotic drugs in a non-specific diarrhea was 59.85%. The percentage prescribed for injection was 36.15%. The average number of drugs prescribed per treatment was 2.61. Conclusions The majority of WHO guidelines stated that prescribing indicators were not met by the puskesmas in Pamekasan, except for the parameters for the average number of drugs prescribed per consultation. This shows an alarming clarion call for the local healthcare stakeholders to improve such situations.

Background Schizophrenia is a chronic disorder that requires long-term treatment to achieve symptom remission and quality of life improvement. Antipsychotic medications are primary treatments for schizophrenia patients. Second-generation antipsychotics (SGAs) have been recognized as first-line drugs in the treatment of schizophrenia. This study aimed at determining the prescription patterns of SGAs in schizophrenia outpatients in the National Mental Hospital in Indonesia. Methods A retrospective study with descriptive analysis was conducted between October and December 2018, exclusive to data of the patients with schizophrenia only. Data were collected from the prescription records of schizophrenia outpatients. This study performed a descriptive analysis of patient characteristics, percentage of SGAs prescribed, regimen doses of SGAs, average number of SGAs prescribed per patient, and pattern of antipsychotics prescribed. Results The most commonly used SGAs were risperidone 55%, followed by clozapine 38%, aripiprazole 3%, quetiapine 3%, and olanzapine 1%. Antipsychotics were generally prescribed in their recommended doses. Almost all SGAs were prescribed as polypharmacy, and the most common combination of SGAs were risperidone and clozapine. Conclusions This study highlighted that risperidone was the major choice for treatment in the outpatient setting. Polypharmacy is the most common pattern prescription of SGAs in the National Mental Hospital in Indonesia. New studies should focus on the analyses of polypharmacy prospectively, and the role of pharmacist in collaboration with other health professionals in the managing of schizophrenia therapy.

Background Pharmacists are known as health care professionals who are responsible for the safety and efficacy of medicine to achieve optimal therapeutic results. Community pharmacists have an opportunity to provide direct services including giving an active medication information service in women during pregnancy and breastfeeding. This study aimed to determine the factors associated with the practice of community pharmacists for actively giving the drug information service for women with chronic diseases during pregnancy and breastfeeding based on the Health Belief Model. Methods About 300 community pharmacists were randomly chosen to participate in the study. All participants were asked to complete questionnaires that were designed based on the theory of the Health Belief Models. The questionnaires measured the community pharmacists’ knowledge, beliefs, cues to action, and practice for actively giving medication information services. Results About 267 pharmacists in the community agreed to participate in this study. Nearly 80% of the participants were female pharmacists (n = 213). The results show that pharmacists’ knowledge had significant influences towards perceived threat (p = 0.009), perceived benefit (p = 0.011), and pharmacists’ self-efficacy (p < 0.001). The self-efficacy factor was the most influential factor in the practice of pharmacists to give medication information service actively (p < 0.001). Conclusions The findings of the study indicate that self-efficacy is the most important factor for pharmacist to be able to provide the medication information services successfully particularly in women during pregnancy and breastfeeding. Providing continuous learning programs through seminars and training related to medication use during pregnancy and breastfeeding to pharmacists is needed to optimise the confidence and the ability of pharmacists in providing the services.

Background Previous studies suggest a highly variable response of antiepileptic drugs (AEDs). This may be because the response to AEDs has been changed to sustained period of freedom from seizures. This study was conducted to determine whether therapeutic changes of AEDs in the treatment of seizure would be observable in an Indonesian population. Methods The study was conducted at the outpatient neurology polyclinic at the Universitas Airlangga Hospital, Surabaya, Indonesia. This was an observational retrospective cohort study, examining the outcomes of 41 cases of switching AEDs (increase or decrease of the dose, switch to branded or generic, or added or reduced type of AEDs). Results After treatment with the switched AED, seizure did not show any significant improvement. However, the incidence of seizure during and after the therapeutic change showed a downward trend (from 44% to 32%). Conclusions According to the present study, mere optimization of antiepileptic therapy may not result in a steep decrease in seizure events, particularly in polytherapy with AEDs. On the other hand, monotherapy with AEDs evidences to decreasing tendency of seizures.

Background Understanding job satisfaction among community pharmacists is important as it may affect roles and performance. Several barriers in practice may affect job satisfaction. Objectives To explore barriers affecting job satisfaction among Indonesian community pharmacists. Methods This study reported data from the Nationwide Community Pharmacy Survey 2018. The results specific to participants in the East Java region were used for this study. Community pharmacists (507) participated in the survey between September 2018 and March 2019. The survey used questionnaire that asked 22 factors, which may act as barriers affecting job satisfaction. Data were analyzed using descriptive statistics. Results The majority of respondents were female (83.43%), and most respondents were aged 31–40 years (41.63%). Most respondents perceived nine barriers such as lack of time for interaction and lack of recognition that were dominant affecting job satisfaction. On the other hand, respondents were not in major agreement perceiving the remaining barriers as dominant affecting job satisfaction. More than half of the respondents disagreed that the remaining barriers were significant affecting job satisfaction. Conclusions This study identified some significant barriers affecting job satisfaction among community pharmacists. In general, barriers can arise from individual, management, and environmental issues suggesting a specific approach to reduce these barriers.

Background The prevalence of type 2 diabetes mellitus (DMT2) in Indonesia increased significantly from 6.9% (2013) to 8.5% (2018), putting Indonesia in top six countries in the world with maximum DMT2 patients. Patients with uncontrolled DMT2 are at risk for complications. As such, insulin is often administered to keep the levels under control. Unfortunately, poor adherence to insulin therapy is common, reflecting some factors that may affect the therapy. The aim of this study was to identify and analyze the characteristics of patients contributing to adherence to insulin therapy among DMT2 outpatients using the Health Belief Model (HBM) approach. Methods A cross-sectional survey was conducted on a sample of 84 DMT2 outpatients in a private hospital in Surabaya between April and May 2019. Respondents were selected using the accidental sampling technique. Data were analyzed using descriptive analysis and chi-square. Results The level of respondents’ adherence was high (73.8%). There was no significant relationship between sex, age, level of education, occupation, and duration of use and patient adherence. Using the HBM approach, this study showed a significant relationship between the five components of HBM (perceived susceptibility, perceived severity, perceived benefit, perceived barrier and perceived self-efficacy) and patient adherence. Conclusions Patient adherence was influenced primarily by patient belief to the therapy of insulin. The characteristics of patients had no effect on adherence, yet further research is recommended to examine such adherence to a different population.

Background Nasopharyngeal cancer (NPC) is the most common neck/head cancer occurring in Indonesia and is the fourth most malignant after breast cancer, cervical cancer, and lung cancer. It is known that the cost of chemotherapy may not be separated from quality of life (QoL) to reflect the success of therapy, especially in cancer patients. Thus, studies on the correlation between chemotherapy cost and the QoL in NPC patients are needed. Methods The participants were recruited by a consecutive sampling method. All patients diagnosed with NPC using a paclitaxel-cisplatin chemotherapy regimen in August–March 2019 for first until the third chemotherapy cycle were assessed for their the chemotherapy cost and QoL before the first chemotherapy cycle and after the third cycle using the EORTC QLQ-C30 questionnaire. Chemotherapy cost and QoL were analyzed using SPSS version 20 to find out the correlation. Results Data from 26 patients showed a notable increase in the QoL after the third chemotherapy cycle. Thus, there was a relationship between chemotherapy cost and QoL in NPC patients. The total cost of chemotherapy increased with the increase in cycles of chemotherapy. We further analyzed the correlation between QoL and the cost of chemotherapy. We found that there was a correlation between the cost and the aspects of global health status, the QoL. Conclusions It is concluded that chemotherapy that is followed by the increase in cost in chemotherapy improves the QoL.

Background Postpartum bleeding and pregnancy induced hypertension – including preeclampsia – remain to be a great cause of maternal mortality. The use of aspirin for preventing preeclampsia has been practiced recently by fetomaternal specialists in Indonesia. This study aimed to analyze the impact of education using an aspirin booklet provided by pharmacists on knowledge and adherence in taking aspirin among pregnant women with high risk for preeclampsia. Methods This was one group of pretest-posttest study. We enrolled all pregnant women with high risk for preeclampsia screened at 11 +0 –13 +6 weeks’ gestation at Fetomaternal Clinic, Dr. Ramelan Naval Hospital, Surabaya. All subjects prescribed with low-dose aspirin (100 mg) for preeclampsia prevention received oral and written education using the aspirin booklet and had been followed up for 2 months. Knowledge about aspirin for preeclampsia prevention was measured by a validated questionnaire developed for this study. Adherence to aspirin was measured by pill count method. Results A total of 12 pregnant women with high risk for preeclampsia were included during the study period. This study showed a statistically significant difference on knowledge of preeclampsia prevention before and after receiving oral and written education using aspirin booklet (p-value = 0.020), as well as aspirin adherence (p-value = 0.011). Conclusion The use of oral education and written aspirin booklet provided by pharmacists had impact on knowledge of preeclampsia prevention and adherence in taking aspirin among pregnant women with high risk for preeclampsia. We recommend to conduct randomized control study of adequate number of subjects.

Background The quality of well being self-administered (QWB-SA) questionnaire is one of the generic instruments which can be used to measure the utility score to assess the quality-adjusted life years (QALYs) as an outcome parameter in pharmacoeconomics study. This research aimed to study the translation, cultural adaptation, and validation of the QWB-SA questionnaire in Indonesian language. Methods This research was conducted among the general population of 459 people in Yogyakarta city. The translation was done using the forward-backward method by independent linguists, and then reviewed by a team consisting of linguists, methodologists, and pharmacists. The psychometric evaluations included face validity, internal-construct validity, convergent validity, and known-group validity tests, while the reliability test was the test-retest of reliability with the Spearman’s rank correlation and Pearson test. Results The translation results and cultural adaptations were modified from the aspect of idiomatic, semantic and conceptual equivalence of the items on the QWB-SA questionnaire. The internal-construct validity showed a very strong and moderate correlation among dimensions and the QWB utility index. The convergent validity showed moderate-to-weak correlation compared to the Euro-quality of life-5 dimension questionnaire. The reliability test showed the Cronbach alpha coefficient of 0.626, and the test-retest of reliability showed a strong and moderate correlation. Conclusions The QWB-SA questionnaire is valid and reliable, and can be used as an alternative to measure utility as a QALY’s parameter in the health-economic evaluation.

Background Hypertension is one of the major health problems of the world and one of the most important causes of death in Indonesia. Complication due to hypertension leads to myocardial infarction, stroke, and renal failure. Pharmacist in primary care centers (Puskesmas) plays an important role in the management of hypertension. The purpose of this study was to assess the knowledge, attitude, and practice (KAP) of pharmacists working in Puskesmas in Surabaya, Indonesia, towards the management of hypertension. Methods A cross-sectional survey was conducted from March to July 2019 in 63 Puskesmas in Surabaya. A questionnaire was developed from the literature to assess KAP and administered to the pharmacists. Data was analyzed using SPSS version-17 and presented in terms of descriptive variables. The mean age of the participants was 34.6 ± 4.9 years (24–45 years old), and 82.5% were females. Majority of the respondents (74.6%) had more than 5 years of experience in Puskesmas. Results Overall, pharmacists had moderate knowledge, and the majority had good attitude and showed satisfactory practice in the management of hypertension. Conclusions There is still a need for continuing education, workshops, and seminars for pharmacists in order to maintain their performance.

Background The prevalence of diabetes mellitus continues to increase every year, including in Indonesia. To prevent complications of diabetes mellitus, patients need to adhere to therapy. The aim of this study was to assess patient adherence to diabetes mellitus drug therapy at Tanjung Karang Primary Health Care Center, Mataram. Methods A total of 60 participants were recruited in April–May 2019. The inclusion criteria of respondents were patients who were diagnosed with diabetes mellitus, treated at Tanjung Karang Primary Health Care Center for more than 1 month, and aged at least 18 years. Assessment of adherence to therapy was carried out using a validated questionnaire, which was the Adherence to Refill Medication Scale (ARMS) questionnaire. The scale used was the Likert scale (1–4) with a score range of 12–48. The higher the total score, the lower the compliance. Results The average age of the respondents was 54.97 years. The average ARMS score was 19.52 ± 5.688 with the lowest score of 12 and the highest score of 33. Among all respondents, only 8.3% had good adherence (total score of 12). Based on the subscales, the average score for refilling medicine and intentional nonadherence in taking medicine was 7.18 ± 2.383, the unintentional nonadherence in taking medicine was 8.13 ± 2.764, and the persistence in refilling medicine was 4.12 ± 1.738. Conclusions Patient medication adherence to the treatment of diabetes mellitus needs to be improved. An approach through healthcare professionals can be achieved so that the therapeutic outcome will be achieved.

Background Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H 2 O 2 . On the other hand, lipoprotein-associated phospholipase (Lp-PLA 2 ) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H 2 O 2 and Lp-PLA 2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis. Methods True laboratory experiment with randomized post-test control of group design using 25 wistar rats ( Rattus norvegicus ) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW. Results ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H 2 0 2 (p = 0.003). The amount of Lp-PLA 2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis. Conclusions PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.

Background Antiplatelet agents used in coronary heart disease (CHD) cause gastrointestinal side effects. Omeprazole can prevent and cure these antiplatelet side effects. Clopidogrel combined with aspirin increases the risk of gastrointestinal tract ulcers and bleeding. This research studied the effect of omeprazole on the antiplatelet effect of clopidogrel. Methods CHD patients using clopidogrel and aspirin receive omeprazole 20 mg in a single dose for 10 days. Platelet antiaggregation point for clopidogrel was measured using VerifyNow P2Y12. The cutoff points used were: low on treatment platelet reactivity (LPR) <85 P2Y12 reaction unit (PRU), normal on treatment platelet reactivity (NPR) 85–208 PRU, and high on treatment platelet reactivity (HPR) >208 PRU. Results Using the paired t-test PRU points pre- and post-omeprazole were 154 ± 85.89 PRU and 169.4 ± 56.15 PRU, respectively. The PRU points were consistent or decreased from the previous PRU points below the HPR cutoff (p: 0.215; >0.05). Before omeprazole use, five patients were categorized as NPR, two patients as LPR, and three patients as HPR. After omeprazole use, two patients, each from HPR and NPR category had a PRU point >208; the rest showed results below the HPR point. Conclusions In this study the PRU points of clopidogrel after omeprazole use showed a PRU <208. The hypothesis that omeprazole may reduce the antiaggregation effect of clopidogrel as shown by the increase in PRU above the cutoff points >208 PRU (HPR) was not proven.

Background Hypertension is a cardiovascular disease which has become a major health problem in Indonesia. Left ventricle hypertrophy is one of the cardiac complications of hypertension that is characterized by thickening of the left ventricle and increasing the mass of cardiac muscle. Methods This study was an experimental study with a posttest group design. Twenty-four mice were divided into four groups. The normal group was given distilled water, the negative control group was given L-NAME 1.75 mg/25 g BW/day, the positive control group was given L-NAME 1.75 mg/25 g BW/day + captopril 0.04875 mg/30 g BW/day, and the adjuvant captopril group was given L-NAME 1.75 mg/25 g BW/day + captopril 0.04875 mg/30 g BW/day + curcuma extract 31.25 mg/30 g BW for 30 days. Results The results of one-way analysis of variance (ANOVA) test analysis on the adjuvant treatment of the captopril group revealed no significant effect on cardiac muscle mass (p > 0.05), while the thickness of the left ventricle was significant (p < 0.05). Conclusions Captopril-Curcuma group resulted in a decrease of cardiac muscle and the thickness of the left ventricle in male mice with hypertension.

Background Coenzyme Q10 is a fat-soluble antioxidant that can help to prevent collagen and elastin damage and avoid wrinkles. Coenzyme Q10 has several disadvantages to be formulated in topical dosage forms, such as low water solubility and large molecular weight. These make coenzyme Q10 retained in the stratum corneum and cause low skin penetration, so proper formulation is required to get products that can penetrate the skin layer. A nanostructured lipid carrier (NLC) consists of a matrix of solid lipids and liquid lipids in a certain amount with nanoparticle size; it may help increase the penetration of active ingredients. Methods For the antiaging activity test, mice were grouped into four treatment groups and killed on the 14th day; then the back of the skin was stained with Masson trichrome staining. For the irritation test, the mice were grouped into three groups and killed after 24 h; then the back of the mice was stained with hematoxylin-eosin staining. Results The number of fibroblasts in mice with NLC coenzyme Q10 is highest from all test groups. The irritation test results after 24 h of application preparation showed that NLC coenzyme Q10 did not irritate the skin of the back of male mice. Conclusions One percent coenzyme Q10 loaded in NLC induced the number of fibroblast cells in the mice model and showed no irritability effect in histopathology preparations.

Background It was reported that hemodialysis (HD) with either a new or reused dialyzer raises medical problems that require therapeutic regimens. This study aimed to investigate the medical problems and their management in patients undergoing HD. Methods This study was conducted by prospectively observing patients with chronic kidney disease undergoing HD. The incidence of medical problems and the treatment given were recorded. Results Among 351 cases of HD, medical problems occurred in 15.7% of cases, including hypotension as the most dominant, followed by muscle cramps, shivering, headache, asphyxia, fever, chest pain, and pruritus. Hypotension was ameliorated with intravenous 40% dextrose and normal saline. Muscle cramps were overcome with 40% dextrose, normal saline, methampyrone, and calcium gluconate. Shivering was managed by warming the patients followed by intravenous methampyrone, 40% dextrose, and normal saline. Meanwhile, headache was reduced by paracetamol or intravenous methampyrone and 40% dextrose. Fever was treated by intravenous methampyrone or oral paracetamol. Pruritus was managed by intravenous dexamethasone and diphenhydramine. Conclusions Medical problems occurring during HD are prevalent and need immediate therapy. Pharmacists and clinicians should work in collaboration to improve the patients’ quality of life.

Background Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET) from a compound is essential, especially for modified novel compounds. Previous research has successfully designed several modified compounds of 5- O -benzoyl derivatives from pinostrobin, a flavanone that has cytotoxic activity. This study aims to describe the properties of ADMET from the 5- O -benzoylpinostrobin derivative. Methods Prediction of the properties of ADMET was carried out using three web servers consisting of SwissADME, pkCSM, and ProTox-II. The observed parameters are divided into ADMET parameters. Results In general, absorption parameters indicate that the 5- O -benzoylpinostrobin derivative has lower water solubility than the parent pinostrobin. Distribution parameters show mixed results for distribution through the blood-brain barrier. Metabolism parameters showed different results with generally inhibitory activity shown in CYP2C19, CYP2C9, and CYP3A4. The excretion parameters showed a higher total clearance than pinostrobin except in the trifluoromethyl derivative. The toxicity parameters showed both pinostrobin and the 5- O -benzoylpinostrobin derivatives, including the class IV toxicity category with the lowest LD 50 value indicated by the nitro derivative of 1500, with the possible target of the androgen receptor and prostaglandin G/H synthase 1. Conclusions Overall, the 5- O -benzoylpinostrobin derivative has the predicted ADMET profile that is relatively similar to pinostrobin, with the most noticeable difference being shown in the absorption parameters where all 5- O -benzoylpinostrobin derivatives have lower water solubility than pinostrobin.

Background Nonalcoholic fatty liver disease (NAFLD) is indicated by liver steatosis without excessive alcohol use or other liver disease. Several studies have reported that metabolic syndromes such as obesity, type 2 diabetes mellitus, and dyslipidemia have a linear correlation associated with NAFLD pathophysiology. One of the characteristics of dyslipidemia in NAFLD is increase in serum triglycerides. This study aimed to develop a model of NAFLD characterized by an increase in serum triglyceride levels and histological profile of liver steatosis by high-fat diet in rats. Methods Twelve Wistar rats were fed with pellets enriched with 60% fat. They were housed individually, and the remaining pellets were weighted every day for intake evaluation. Blood samples were collected at day 0 and at the end of each trial period at days 7, 14, 21, and 28 for the measurement of triglyceride levels. Every animal from each group was also sacrificed for liver histopathological examination. Results This study has established developing the NAFLD animal model by induction of a high-fat diet. The levels of serum triglycerides were increased from baseline 80.41 ± 12.82 to 1152.00 ± 73.62, 493.66 ± 159.98, 556.00 ± 120.79, and 489.00 ± 156.75 mg/dL at days 7, 14, 21, and 28, respectively. Liver histology also showed liver steatosis development, inflammation, and hepatocellular ballooning, which were associated with the NAFLD state. Conclusions High-fat diet in rats induced hypertriglyceridemia along with NAFLD-like liver histopathology.

Background Previous studies have shown that 5- O -benzoylpinostrobin derivatives is a potential anti-breast cancer, with the highest potential being the HER2 inhibitors, is a protein’s member of the epidermal growth factor receptor (EGFR) family. Overexpression of EGFR itself is known to be one of the causes of other cancer, including non-small cell lung cancer (NSCLC). Thus, it is possible that 5- O -benzoylpinostrobin derivatives can also inhibit the overexpression of EGFR in NSCLC. In the case of NSCLC, mutations of EGFR are often found in several amino acids, such as L858R, T790M, and V948R. This study aimed to determine the potential of 5-O-benzoylpinostrobin derivatives as an inhibitor of wild type and L858R/T790M/V948R-mutant EGFR. Methods Docking was performed using AutoDock Vina 1.1.2 on both wild type and L858R/T790M/V948R-mutant EGFR. Parameters observed, consisted of free energy of binding (ΔG) and amino acid interactions of each ligand. Results Docking results showed that all 5- O -benzoylpinostrobin derivatives showed a lower ΔG for both wild type and L858R/T790M/V948R-mutant EGFR, with the lowest ΔG shown by 4-methyl-5- O -benzoylpinostrobin and 4-trifluoromethyl-5- O -benzoylpinostrobin. Both the ligands have the similarity of interacting amino acids compared to reference ligands between 76.47 and 88.24%. Specifically, the ΔG of all test ligands was lower in mutant EGFR than in the wild type, which indicates the potential of the ligand as EGFR inhibitors where a mutation to EGFR occurs. Conclusions These results confirm that 5- O -benzoylpinostrobin derivatives have the potential to inhibit EGFR in both wild type and L858R/T790M/V948R-mutant.

Background Insulin therapy is a major part of diabetes treatment. The insulin injection technique must be done accurately and needs a professional process for diabetes mellitus (DM) patients. The aim of this research is to evaluate the relationship of education level pertaining to the accuracy of insulin injection techniques through HbA 1c values. Methods We used a cross-sectional study with sampling using a purposive technique according to the inclusion criteria: diagnosed with DM and using insulin therapy with/without a combination of oral antidiabetic drugs, having HbA 1c levels of data ± 3 months from the time of study, willing to become research respondents by signing informed consent. The study was conducted by filling out the questionnaire Forum for Injection Technique and Therapy Expert Recommendation (FITTER) and interviews. Results Fifty subjects with primary education were able to perform insulin injection techniques with 20% accuracy while subjects with secondary education level showed 14% accuracy, and higher education 2%. All of these results had HbA 1c values > 6.5%. 100 % of the subjects were provided with educational resources and 78% had a care-giver at home. Statistical analysis of correlation between levels of education with the accuracy of the insulin injection technique was carried out through the Somers’ correlation test (p = 0.81, r = −0.03). This study shows there is no relationship between the level of education and the accuracy of insulin injection techniques through HbA 1c values. This might occur due to several factors such as information sources and caregiver’s practice.

Background One of the therapies used to treat type 2 diabetes mellitus (T2DM) disease is combination insulin which consists of rapid-acting insulin and intermediate-acting insulin (premixed). This study aimed to examine the profile of premixed insulin related to blood glucose concentration and to identify the drug interactions due to the combination of premixed insulin with other drugs taken by T2DM patients. Methods This study was a prospective observational study with cross-sectional data that were analyzed descriptively. The respondents invited were T2DM patients with or without complication or comorbid disease who received premixed insulin with or without a combination of oral antidiabetic therapy in the Outpatient Unit of Universitas Airlangga Hospital, Surabaya. The research instruments used are data sheet, patient medical record, and fasting and postprandial blood glucose concentration. Results A total of 118 patients received premixed insulin therapy, but only 80 patients were included in the inclusion criteria. Based on types of insulin, the combination of 30% aspart and 70% protamine aspart was used by 91.25% T2DM patients, and a combination of 25% insulin lispro and 75% protamine lispro was used by 8.75% T2DM patients. There were 30.3% of patients who could achieve the target of 80–130 mg/dL in fasting blood glucose concentrations, and 35.1% of patients achieved the target of ≤180 mg/dL in postprandial blood glucose concentration. Drug interactions may occur in patients who use premixed insulin with glimepiride, lisinopril, fenofibrate, candesartan, irbesartan, and gemfibrozil. Conclusions In this study, premixed insulin have not reached the target of fasting and postprandial blood glucose concentrations in most patients.

Background Hyperglycemic crisis is one of the complications of diabetes mellitus, which is common in hospitalized diabetic patient with intercurrent illness, requiring immediate action to control blood glucose. As an effort to attain rapid, gradually and more definite blood glucose, insulin is given intravenously. This study aimed to explore the patterns of blood glucose in hyperglycemic crisis and intercurrent illness, precipitating conditions, insulin regimen and blood glucose (BG) level results. Methods It was a cross-sectional study conducted on type 2 diabetic patients. The inclusion criteria were as follows: hospitalized in the general/internal medicine ward with or without any complication or comorbidity receiving intravenous insulin therapy; have pre- and post-BG data after insulin intervention. Results In 3 months of the study period, 22 patients fulfilled the inclusion criteria with 28 cases of intravenous insulin therapy, and 1 patient could get more than one intervention. The major condition toward a hyperglycemic crisis condition was infection. The patient’s BG before interventions was 243 mg/dL to more than 600 mg/dL. The dosage of insulin varied from 4 to 10 units per hour, intravenously with a frequency of 1–4 times. The dosage consideration was not only based on BG levels but also on the patient’s condition. The reduction in BG level varied greatly between 0.2 and 28.1 mg/dL per unit of insulin. The BG level of three patients did not decrease. On the other hand, one patient experienced mild hypoglycemia. Conclusions Infection conditions were the most common factor for the hyperglycemia crisis. Moreover, intravenous insulin dosing was done individually, and there was a large variation in the results of the decrease in BG levels.

Background Adherence to medication has an important role in the long-term management of diabetes. The Indonesian Endocrinologist Association found that of the 50% of the entire population who have been diagnosed with diabetes, two-thirds are undergoing therapy and only one-third have been achieving the intended outcomes of the drug therapy. This study aimed to identify patients’ adherence behavior and the root causes of non-adherence. Methods This study used a non-experimental mixed-methods approach. A total of 40 patients with type 2 diabetes mellitus (T2DM), who were part of the referral program of the National Health Care Security System (BPJS Kesehatan) were recruited by purposive sampling from 17 primary health care centers in Surabaya, Indonesia. Results The adherence behavior assessment revealed non-adherence among 80% of the patients. The highest instances of non-adherence based on the percentage scores involved the following: patients forgot to take the medications (38.23%), patients preferred not to take the medications (20.59%) and the drug products were not available for the patient (14.71%). The factors influencing non-adherence included the complex instructions for taking medication, the absence of a reminder, the unwanted side effects of the drug, the feeling of repetition, the feeling that drugs were ineffective and the concern for the drug’s effects on the kidney. Conclusions The high rates of non-adherence identified in this study encourage pharmacists to implement better medication therapy management for chronic diseases. The patients’ understanding of drug therapy indications and regimens is very important in increasing the expectations of achieving effective treatment, awareness and concern for medication safety and treatment compliance.

Background Non-Hodgkin lymphoma (NHL) is a large group of primary malignancies of solid lymphoid tissue. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL. DLBCL has an aggressive natural history but responds well to chemotherapy. The objective of this study was to review the use of chemotherapy, identify its side effects, and examine the response to chemotherapy in patients with NHL at Dr. Soetomo General Hospital. Methods This study was a retrospective observational study using secondary data obtained from patients’ medical records from 2016 to 2018. Demographic data (age, sex), clinical characteristics, chemotherapy regimens, side effects of chemotherapy, and response to chemotherapy were recorded. Results Results revealed that of the 43 patients (age ranged from 21 to 80 years) who were included in this study, the prevalence of DLBCL was higher in male patients (74%) and about 44% patients were at stage III. R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine/oncovin, prednisone) (53%) was the most used chemotherapy regimen in this study. A total of 65% of patients showed good responses and 35% showed no response to the therapy. The most common side effect was myelosuppression, including 25% and 8% of the patients having anemia and leukopenia, respectively. Conclusions R-CHOP is the most used regimen. Most of patients with NHL have a complete response and the predominant side effect is anemia.

Background Stress ulcer is a superficial and asymptomatic lesion and causes bleeding. As many as 50% of death cases are reported as the result of stress ulcer bleeding. Stress ulcer prophylaxis (SUP) is a drug used to prevent gastrointestinal tract injuries due to stress ulcers. The inappropriate use of SUP drugs can cause adverse drug reactions, and thus SUP drugs are only given to patients in accordance with guidelines in order to avoid the overuse of SUP drugs. The aim of this present study is to analyse the suitability of SUP drug usage based on the criteria from the American Society of Health-System Pharmacists (ASHP) and the drug costs of SUP overuse. Methods An observational descriptive study was conducted from April 24, 2019, to May 17, 2019, in the inpatient surgical ward of Dr. Soetomo General Hospital. Data were obtained from patient medical health records. Results One hundred fifty-two patients used 1404 SUP drugs. Approximately 48% of usage did not suit the ASHP criteria and was considered as medication overuse. The cost of excessive SUP usage during the study period was more than US $65, which is 30.08% of the total drug cost of prescribed stress ulcer drugs. Conclusions The present study suggests that the relatively high excessive drug costs for SUP show a need for monitoring of the application of SUP therapy guidelines.

Background Neuroinflammation is one of the main causes of neurodegenerative events. Phytoestrogen is a group compounds that have an estrogen-like structure or function. Phytoestrogen has a high potential to overcome neuroinflammation caused by estrogen deficiency in postmenopausal women. Marsilea crenata Presl. is a plant known to contain phytoestrogens. This research aimed to analyze the activity of an n-butanol fraction of M. crenata leaves in inhibiting the classical pathway activation of microglia HMC3 cell line to M 1 polarity, which has proinflammatory characteristics. Methods Microglia HMC3 cell line was cultured in Eagle’s minimum essential medium and induced with IFN-γ for 24 h to activate the cell to M 1 polarity in 24-well microplates. The n-butanol fraction was added with various doses of 62.5, 125, and 250 ppm and genistein 50 μM as a positive control. The expression of major histocompatibility complex II (MHC II) as a marker was tested using a confocal laser scanning microscope. Results The result of MHC II measurement shows a significant difference in the MHC II expression in the microglia HMC3 cell line between the negative control and all treatment groups at p<0.05, indicating a non-monotonic dose-response profile. Conclusions The best dosage to inhibit MHC II expression was 250 ppm with the value of 200.983 AU. It is then concluded that n-butanol fraction of M. crenata leaves has antineuroinflammation activity due to its phytoestrogens.

Background Phytoestrogens have a high potential to overcome the neuroinflammation caused by estrogen deficiency. Marsilea crenata Presl. is a plant known to contain phytoestrogens. This research aimed to report the activity of a 96% ethanol extract of M. crenata leaves in inducing activation of microglia HMC3 cell to M 2 polarity, which has anti-inflammatory characteristics. Methods The study was done by culturing microglia HMC3 cell in 24-well microplate and inducing it with IFN-γ for 24 h to activate the cell to M 1 polarity, which has proinflammatory characteristics. The 96% ethanol extract was added with various doses of 62.5, 125, and 250 ppm. Genistein, 50 μM, was used as a positive control. The analysis of the immunofluorescence of Arginase-1 (Arg1) and ERβ as markers was done using a convocal laser scanning microscope. Results The result of Arg1 shows a significant difference in Arg1 expression in the microglia HMC3 cell line between the negative control and all treatment groups at p < 0.05, with the best result at 250 ppm, whereas for ERβ, the results show, at doses of 125 and 250 ppm, that the 96% ethanol extract of M. crenata leaves decrease the activated ERβ expression at p < 0.05, with the best result at 250 ppm. The Arg1 and activated ERβ expression have a weak negative relationship with the Pearson correlation test. Conclusions The 96% ethanol extract of M. crenata leaves has an antineuroinflammation activity through the induction of Arg1 and activated ERβ expression in microglia HMC3 cell, with the best dose at 250 ppm.

Background Meloxicam (MLX) is a potent non-steroidal anti-inflammatory drug with poor solubility. Solid dispersion (SD) is an effective formulation strategy to improve the dissolution rate of poorly water-soluble compounds. Hydroxy propyl methyl cellulose (HPMC) as an inert polymer carrier and nicotinic acid (NA) as disturbance can be used as a matrix of SD. The aim of this study was to determine the effect of MLX-HPMC-NA SD on the solubility and dissolution of MLX. Methods SD was prepared by the solvent evaporation technique with methanol being used as a solvent. Methanol was evaporated at room temperature. SD of MLX was prepared involving various matrix compositions at MLX:HPMC:NA ratios of 1:1:1 (SD1), 1:1:2 (SD2), 1:2:1 (SD3), and 1:2:2 (SD4). Results The solubility profile of MLX in SD3 (64.34 ppm) showed a higher improvement than the physical mixture (15.99 ppm) and pure MLX (6.89 ppm). This increase might be due to the formation of molecular dispersion of MLX in the polymer as hydrophilic matrix and NA have both donor-acceptor sites for hydrogen bonding interactions. The dissolution profile of SD3 also showed the highest improvement. The melting endotherm of SD3 was detected at 219.5 °C, in which case it originated from NA rather than from MLX, showing that MLX was molecularly dispersed and amorphous. Conclusions MLX solubility and dissolution profile could be improved by the SD technique with a matrix of HPMC and NA. The best result was given by SD3 with an MLX:HPMC:NA ratio of 1:2:1. Based on the characterization study, it is predicted that hydrophilic polymer and hydrogen bonding interactions play important roles in MLX solubility or dissolution rate improvement.

Background Solid dispersion (SD) represents a good method for enhancing the solubility of poorly water-soluble drugs. Meloxicam (MLX), a nonsteroidal anti-inflammatory drug has poor solubility in water. Hydroxypropyl methylcellulose (HPMC) 2910 3 cps, a hydrophilic carrier and nicotinamide (NC), a hydrotropic agent can be used as matrix of SD. The aim of this study is to investigate the effect of HPMC 2910 3 cps and NC as SD matrix on the solubility and dissolution rate of MLX. Methods The SD of MLX was prepared by solvent evaporation method using methanol as solvent. The SD formulations composed of HPMC and NC in different ratios (1:1:1, 1:1:2, 1:2:1, 1:2:2). The physical state of MLX SD were characterized by Differential Thermal Analyzer (DTA), Fourier Transform Infrared Spectroscopy, powder X-ray diffractometer (PXRD), Scanning Electron Microscopy (SEM). The solubility and dissolution of the MLX SD were also evaluated. Results The results of differential thermal analysis (DTA) showed that the melting point of MLX SD was lower than MLX further the X-ray diffractogram showed a decrease of the crystallinity of MLX in SD. Those indicated that MLX was dispersed molecularly in SD. The SD showed a widening transmission peak at 3000–3500 cm −1 which resembled the peak of pure MLX transmission. It indicated that intermolecular hydrogen bonds were formed between MLX, HPMC, and NC. The solubility and the dissolution efficiency (ED 60 ) of SD with MLX-HPMC 2910 3 cps-NC = 1:2:1 increased 3.59 times and 1.50 times higher then MLX substance. Conclusions MLX-HPMC-NC SD system increased the solubility and dissolution of MLX. The SD with MLX-HPMC 2910 3 cps-NC ratio of 1:2:1 had the highest solubility and ED 60 compared to the other SD formulas.

Background The high prevalence of thrombotic abnormalities has become a major concern in the health sector. This is triggered by uncontrolled platelet aggregation, which causes complications and death. The problem becomes more complicated because of the undesirable side effects of the drugs currently in use, some of which have reportedly become resistant. This study aims to evaluate the potency of o -hydroxycinnamic acid derivatives (OCA1a–22a) and their pharmacokinetic properties and toxicity for them to be developed as new antiplatelet candidates. Methods In silico analysis of pharmacokinetics was carried out using pKCSM. Molecular docking of the compounds OCA 1a–22a was performed using the Molegro Virtual Docker. In silico evaluation of the potency of biological activity was done by measuring the bonding energy of each tested compound to the target receptor i.e. COX-1 and P2Y 12 , as the Moldock score (MDS). Results pKCSM analyses showed that more than 90% of OCA 1a–22a are absorbed through the intestine and distributed in plasma. Most tested compounds are not hepatotoxic, and none is mutagenic. An evaluation of the COX-1 receptor showed that OCA 2a–22a have lower binding energy compared to aspirin, which is the COX-1 inhibitor used today. So, it can be predicted that OCA 2–22a have stronger activity. Interactions with P2Y 12 show lower MDS than aspirin, but slightly higher than ibuprofen, which is the standard ligand. Conclusions ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile prediction shows that OCA 1a–22a have the potential to be developed as oral preparations. OCA 1a–22a have strong potential to interact with COX-1 and P2Y 12 receptors, so they are prospective anti-platelet candidates.

Background Osteoarthritis (OA) is a chronic disease in the joints. One of the proinflammatory cytokines that is thought to have a major role in the inflammatory process, the emergence of pain, and cartilage damage in OA is tumor necrosis factor α (TNF-α). Meloxicam is a nonsteroidal anti-inflammatory drug class of drugs that is relatively selective in inhibiting the activity of cyclooxygenase 2 (COX-2) formation. This study is conducted to prove the change in TNF-α level in the use of meloxicam with model in animals suffering from OA. Methods The OA rat model was induced with sodium monoiodoacetate intra-articularly. Rats were divided into 5 groups: negative control group, positive control group, and treatment groups with various doses of meloxicam. Hyperalgesia effect was evaluated using a warm plate test, and TNF-α level was determined using enzyme-linked immunosorbent assay. Results The treatment groups that received meloxicam at a dose of 1.0, 3.0, or 10.0 mg/kg body weight (BW) did not show significant differences in rat knee joint diameter (p = 0.99), but showed a significant difference in sensitivity to heat stimulation (p = 0.02) compared to the control group. Osteoarthritis rats experienced a significant reduction in TNF-α level after being given meloxicam at a dose of 10 mg/kg BW compared with the control group. This shows that the 10 mg/kg BW of meloxicam is a potential dose in reducing the TNF-α level in OA rat models. Conclusions Based on these data, it can be concluded that the inhibition of pain and the development of OA by meloxicam in animal models may be assigned to a decreased level of TNF-α.

Background Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA. Methods The OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection. Results MIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01). Conclusions Taken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.

Background Osteoarthritis (OA) is a chronic degenerative joint disease, characterized by physiological disorders, such as cartilage degradation, bone remodeling, osteophyte formation, and joint inflammation, which results in pain. Several studies have reported problems with the use of pain medications in OA, such as the use of a combination of many drugs and their long-term use. Therefore, this study was designed to evaluate the use of pain medications in OA patients. The study focused on the analysis of effectiveness and drug related problems (DRPs) with the category of drug interactions and adverse drug events (ADEs) in knee OA patients in Orthopedic and Traumatology Clinic, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia. Methods The study used a retrospective approach through tracking and recording of the medical data from the period of 1st January to 30th June, 2018. The potential of drug interactions was determined by analyzing data based on literature. The actual side effects of the drug were identified based on the patient’s medical record through clinical data, laboratory data, and therapeutic data received by the patient. The study involved 143 subjects who met the inclusion criteria of 871 visits to the hospital. Results The results showed that women as much as 80.42% with an age distribution of at most 46–65 years are the most affected by OA cases. The predominant history of illness and comorbidities in OA patients was hypertension in 58.74% of patients. The use of analgesic meloxicam had a percentage of 26.06%, sodium diclofenac 20.21%, mefenamic acid 4.36% and paracetamol 4.25%. The effectiveness of the use of pain reliever was characterized by a decrease in VAS in each patient at the beginning and at the end of the study, where a decrease in pain intensity occurred in 79.72% of patients who received pain medications. Based on drug interactions, we were able to identify pharmacodynamic interactions of 43 events (4.94%) and onine events of pharmacokinetic interactions (1.03%), with a minor severity of 7 events (0.80%),44 moderate events (5.05%), and one major event (0.11%). Mostly identified side effects of the drugs were those due to the use of non-steroid anti inflammatory drugs, which occurred in 42 events (4.82%). Conclusions It can be concluded that OA therapy with a number of pain relievers shows an adequate therapeutic response with some side effects and interactions both pharmacokinetically and pharmacodynamically.

Background Inappropriate antibiotic therapy is accelerating the development of antimicrobial resistance (AMR). Upper respiratory tract infections (URTIs) are predominantly caused by viruses, resulting in the prescription of antibiotics to a few selected patients. Previous studies in primary health care centers (PHCCs) in Indonesia have shown a high percentage of antibiotic therapy for URTIs. This study tries to analyze the difference in profiles of antibiotic prescription in the treatment of children and adults with URTI in Bangka Tengah, Indonesia. Methods Random prescriptions from patients diagnosed with URTIs (sinusitis, bronchitis, common cold, and pharyngitis) from all PHCCs in Bangka Tengah were collected from January to February 2018. Prescriptions from patients with overlapping diagnoses, such as URTI with diarrhea or typhoid, were excluded. Results During the two months of data collection, 1348 prescriptions for adults and children with URTIs were studied. Children were 1.30 (95% CI, 1.03–1.58) times more likely to be treated with antibiotics compared to adults. Amoxicillin was the most commonly prescribed antibiotic both in children (92.3%) and adults (78.6%). Ciprofloxacin was commonly prescribed in adults (14.6%) but not in children (0.3%). Conclusions This study confirms the major antibiotic overuse in patients with URTI, especially in children. Owing to the fact that children are more likely to get URTI of viral origin, they receive high percentage of antibiotic therapy. These findings support the need for collaborated intervention to decrease unnecessary prescription of antibiotics in Bangka Tengah.

Background The profile of patients with HIV/AIDS is required to develop appropriate HIV/AIDS prevention and treatment programs in Indonesia. Turen is one of the four sub-districts with the highest number of patients with HIV/AIDS in Malang District, Indonesia. The purpose of this study is to determine the sociodemographic profile, sources of infection, use of antiretrovirals and CD4 counts on HIV/AIDS outpatients in Turen Primary Health Centre (PHC). Methods The sociodemographic data, antiretroviral use, and CD4 counts were obtained from medical records on HIV/AIDS outpatients in Turen PHC. A qualitative approach using in-depth interviews was used to explore the source of infection. Descriptive analysis was used to summarise the quantitative data, while thematic analysis was used to analyse the qualitative data derived from interviews. Results A total of 45 HIV/AIDS outpatient medical records were reviewed. Of those, the majority were females (57.8%), ages 26–35 years (51.1%), married (55.6%) and having income less than 2 million rupiah (73.3%). All of them used a combination of antiretroviral therapy from two classes of antiretrovirals, i.e. nucleotide analog reverse transcriptase inhibitor and non-nucleotide analog reverse transcriptase inhibitor; the majority were treated with fixed-dose combination of tenofovir-lamifudin-efavirenz. The CD4 counts data were obtained from 31 patients with an average number of 282 cells/mm 3 . The qualitative data from interviews with 15 patients revealed that the source of infection was from husband, unsafe/unprotected sex and blood donor. Conclusions The high prevalence of HIV/AIDS among young married women and poor control of the disease in Indonesia warrants further considerations. The government should work together with all related stakeholders in raising awareness of HIV/AIDS, particularly among women, as well as improving treatment and support for people living with HIV/AIDS.

Background Medicinal plants are known to perform many pharmacological actions due to their chemical metabolites, which include antiviral effects. Previously, the extract of Ruta angustifolia was shown to have potential anti-hepatitis C virus (HCV) activity without any cytotoxicity, with a 50% inhibitory concentration of 3.0 μg/mL and a 50% cytotoxicity concentration of >100 μg/mL. Furthermore, the combination of medicinal plants and current anti-HCV agents, such as a direct-acting antiviral agent, was shown to potentiate their overall effectiveness. In the course of this study, the ethanolic extract of R. angustifolia was evaluated for its anti-HCV effects; specifically, the mechanism of action on HCV NS3 and NS5A protease was investigated. Methods Analysis of the use of this extract in conjunction with current NS3 inhibitor drugs, simeprevir (SMV) and telaprevir (TVR), was performed. Anti-HCV activity was performed by in vitro culture of hepatocyte cells. The cells were infected and treated with various concentrations of the sample. HCV inhibition was calculated and CompuSyn software analysis was used to determine the synergistic effect of the combination. Results Results demonstrated that R. angustifolia extract inhibited the post-entry step and decreased the protein levels of HCV NS3 and NS5A. The combination of extract and SMV and TVR mediated a synergistic effect. Conclusions These findings suggest that combining R. angustifolia extract with current anti-HCV drugs should be considered when developing alternative and complementary anti-HCV medicines.

Background Indonesian Ministry of Health advocate doctors, especially in government-owned healthcare facility, to prescribe generic drugs including amoxicillin. Although BPOM (the National Agency of Drug and Food Control) already guarantees that the generic amoxicillin and the branded one were interchangeable, lack of confidence in generic drugs still remains among patients, pharmacists, and doctors. This issue supported by lack of publication confirmed the therapeutic equivalence of branded and generic drugs. This study aims to evaluate and compare the in vitro microbiological assay of different generic and branded amoxicillin that are available in Indonesian market, especially those used in government-owned healthcare facilities. Methods Microbiological assays for five samples of amoxicillin tablet containing 500 mg amoxicillin available in Indonesia were determined using a method from Indonesia Pharmacopeia. Samples were coded as Products A to E. The assay was carried out by measuring the diameter of the inhibition zones in the plate agar incubated with Escherichia coli and Staphylococcus aureus . The obtained data were evaluated to determine the sample potency and compared with the amoxicillin reference standard. Results Minor and insignificant differences (p > 0.05) were found in the diameters of the inhibition zones. Potency ratio measured both in E. coli and S. aureus were all between 95% and 105%. The lowest of the tested samples were from Product C, which resulted to ratio potencies of 96.3% and 95.5% in E. coli and S. aureus , respectively. Conclusions All five samples were in the range of the acceptance criteria. Therefore, from the view of the microbiological assay, these products are in equivalence in quality and are interchangeable.

Background With the development of infectious diseases, the use of antibiotics is increasing. Amoxicillin is a penicillin class of antibiotics that are widely used today. Compliance with amoxicillin can reduce the risk of microbial resistance. Two fundamental factors that determine patient compliance in antibiotic therapy are the patient's knowledge and attitude towards the antibiotic. In this study, we want to know the effect of knowledge and attitudes of patients on their compliance in using amoxicillin antibiotics. Methods This study was an observational study with a cross section approach, a purposive sampling method by giving questionnaires to 100 respondents who received amoxicillin in Arjuno Primary Health Care, Klojen District in April 2019. Research variables include knowledge, attitudes, and patient compliance in using amoxicillin antibiotics. Data analysis was performed to determine the effect of knowledge and attitudes of patients on compliance with amoxicillin antibiotic therapy. Results The results showed that knowledge significantly influences the complience (sig = 0.00), while attitude does not significantly influence compliance in using amoxicillin antibiotics(sig = 0,136). Knowledge and attitude were known to have a significant effect on compliance with amoxicillin antibiotic therapy (sig = 0.00), the magnitude of the influence of the two variables (R 2 = 16.7%). Conclusions It can be concluded that the patient's knowledge and attitude influences his compliance to antibiotic therapy.

Background PBP2a is a type of penicillin-binding proteins (PBPs) that cause resistivity in methicillin-resistant Staphylococcus aureus (MRSA) from β-lactam antibiotics. MRSA susceptible with cefttobiprole (fifth generation of cephalosporin as an anti-MRSA agent) which inhibits PBP2a and stops its growth. Contrary to its efficacy, ceftobiprole causes taste disturbance more than any other cephalosporins; furthermore, its mechanism is unknown. This study aims to explore an in silico study of a natural compound, which serves as a potential alternative to overcome MRSA with minimum adverse side effects. Methods A molecular docking study was performed using Molegro Virtual Docker version 5.5. Brazilin and proto-sappanins A–E are phytochemical compounds contained in sappan wood extract and are docked into the binding site of PBP2a (Protein Data Bank: ID 4DKI). Results Brazilin and proto-sappanins A–E have some interaction with Ser 403 amino acid residue which is an important interaction to inhibit PBP2a protein. The result of the molecular docking study showed that the MolDock score of proto-sappanins D and E is lower than that of methicillin but higher than that of its native ligand (ceftobiprole). Conclusions The results of this study suggest that proto-sappanins D and E have an excellent potential activity as an alternative to ceftobiprole in limiting MRSA growth through PBP2A enzyme inhibition.

The active component in cullilawan oil can be synthesized into curcumin analogue product, which has pharmacological activity. The synthesis process by using conventional and microwave methods can produce different isomer products. Different synthesis products and models of animal are used to provide different hepatoprotective effects. The aim of this study was to use the curcumin analogue synthetic products (AKS-k and AKS-m) from cullilawan oil in male mice ( Mus musculus L.) liver damage treatment induced by carbon tetrachloride (CCl 4 ). The in vivo method was employed using biochemical of blood and histopathological images of liver cells as indicators. The results showed that the curcumin analogue synthetic product using microwave methods had better pharmacological effects than the conventional method product in terms of the results of blood biochemical analysis and microscopic images of liver cells.

Background In the post-vaccination era, as it is today, generalized tetanus is a rare diagnosis, although mortality and morbidity continue to increase significantly throughout the world. Infection occurs when the Clostridium tetani spores are introduced into wounds, skin lesions and infections. The symptoms often begin with stiffness or spasms in the jaw muscles; they are called trismus or “lockjaw” and/or then spread to the neck and abdominal muscles. Case presentation This is a report of a 42-year-old man who was referred to the hospital with dysphagia, rigidity and trismus. He was diagnosed with generalized tetanus with a Philips score of 15. The patient was admitted to the isolation unit, received treatment that included procaine penicillin, metronidazole, diazepam, human tetanus immunoglobulin (TIG) and anti-tetanus serum (ATS). Treatment was considered according to the guidelines of the World Health Organization, and also, the drug dose has no adverse event reaction during the treatment. Conclusion The therapeutic response is related to the identification and appropriate treatment, especially in hospitalized patients with inadequate immunization so that patients recover soon.