Synthesis and in vitro Activity of Eugenyl Benzoate Derivatives as BCL-2 Inhibitor in Colorectal Cancer with QSAR and Molecular Docking Approach.

OBJECTIVE: This study is aimed to acquiring new compounds of Eugenyl benzoate (2-methoxy-4-(prop-2-en-1-yl)phenyl benzoate) derivatives that can inhibit HT29 colorectal cancer cells. METHODS: In this research, we used several chemical reactions to synthesize novel compounds, such as Esterification, Demethylation, Halohydrin, and Sharpless reaction. Cytotoxicity assays were performed to test the inhibitory activity of compounds against HT29 colon cancer cells. QSAR analysis were carried out to analyse the relationship of chemical structure of the novel compounds with their cytotoxic activity. RESULT: Ten novel compounds were successfully synthesized and tested in vitro against the HT29 cell. The IC50 of the novel compounds were between 26.56 µmol/ml - 286.81 µmol/ml which compound 4-[(2S)-2,3-dihydroxypropyl]-2-methoxyphenyl 2-hydroxybenzoate (9) showed as best active compound as BCL-2 inhibitors better than other synthesized compounds and Eugenol as well. QSAR analysis of the in vitro results gave a Log equation: 1/IC50 = -0.865-0.210 (LogP)2 + 1,264 (logP)-0.994 CMR (n = 10; r = 0.706; SE: 0.21; F = 0.497, sig = 7.86). The equation shows the log variable P and CMR affect IC50. The properties of hydrophobicity (log P) are more instrumental than the ones of steric (CMR). CONCLUSION: The active compound (9) given best activities as BCL-2 inhibitors than other eugenol derivatives. QSAR indicates the logP and CMR have effect on its colorectal cytotoxic activity which the hydrophobicity parameter (logP) plays more role than the steric parameter (CMR).

The Translation Process of Pharmaceutical Care Network Europe v9.00 to Bahasa Indonesia: An Instrument to Detect Drug-Related Problem.

Background: Drug-related problems (DRPs) remain a major health challenge in tertiary health services such as hospitals in Indonesia. These problems are detected and solved using classification systems such as Pharmaceutical Care Network Europe (PCNE). Therefore, this study aims to obtain a valid and reliable Bahasa Indonesia version of the PCNE. Methods: A draft of the Bahasa Indonesia version of the PCNE v9.00 was discussed by four experts from May to August 2020 using the Delphi method. Furthermore, the instrument was assessed for its readability, clarity and comprehensiveness by 46 hospital pharmacists throughout Indonesia. In October 2020, two pharmacists from Haji General Hospital, Makassar, Indonesia carried out the inter-rater agreement to assess 20 cases where the proportion of coding matches between both raters were observed. Results: The instrument was found to be valid after passing the face and content validity, and the Scale Content Validity Index (S-CVI) value for each PCNE domain was 0.91, 0.89, 0.93, 0.97 and 0.93, respectively. Moreover, there was a fair agreement between the two raters that ranged between 40%-90%. Also, kappa statistics showed a substantial agreement on the 'Problems' and 'Causes' domains. Conclusion: The Bahasa Indonesia version of the PCNE v9.00 instrument passed face and content validity as well as inter-agreement to be used in hospital settings.

Effective Clinical Pathway Improves Interprofessional Collaboration and Reduces Antibiotics Prophylaxis Use in Orthopedic Surgery in Hospitals in Indonesia.

Clinical pathways can improve the quality of health services. The effectiveness and impact of implementing clinical pathways are controversial. The preparation of clinical pathways not only enacts therapeutic guidelines but requires mutual agreement in accordance with the roles, duties, and contributions of each profession in the team. This study aimed to investigate the perception of interprofessional collaboration practices and the impact of clinical pathway implementation on collaborative and Defined Daily Dose (DDD) prophylactic antibiotics per 100 bed-days in orthopedic surgery. The Collaborative Practice Assessment Tool (CPAT) questionnaire was used as a tool to measure healthcare' perceptions of collaborative practice. The clinical pathway (CP) in this study was adapted from existing CPs published by the Indonesian Orthopaedic Association (Perhimpunan Dokter Spesialis Orthopaedi dan Traumatologi Indonesia, PABOI) and was commended by local domestic surgeons and orthopedic bodies. We then compared post-implementation results with pre-implementation clinical pathway data using ANCOVA to explore our categorical data and its influence towards CPAT response. ANOVA was then employed for aggregated DDD per 100 bed-days to compare pre and post intervention. The results showed that the relationships among members were associated with the working length. Six to ten years of working had a significantly better relationship among members than those who have worked one to five years. Interestingly, pharmacists' leadership score was significantly lower than other professions. The clinical pathway implementation reduced barriers in team collaboration, improved team coordination and organization, and reduced third-generation cephalosporin use for prophylaxis in surgery (pre: 59 DDD per 100 bed-days; post: 28 DDD per 100 bed-days). This shows that the clinical pathway could benefit antibiotic stewardship in improving antibiotic prescription, therefore reducing the incidence of resistant bacteria.

Discordance to ASHP Therapeutic Guidelines Increases the Risk of Surgical Site Infection.

Clean surgery without contamination does not require prophylactic antibiotics, but there are high-risk surgical procedures that may cause infection and/or involve vital organs such as the heart, brain, and lungs, and these indeed require the use of antibiotics. This study aimed to determine the quantity of antibiotic use based on the defined daily dose (DDD) per 100 bed days and the quality of antibiotic use based on the percentage of concordance with The American Society of Health-System Pharmacists (ASHP) therapeutic guidelines (i.e., route of administration, time of administration, selection, dose, and duration). This includes the profiles of surgical site infection (SSI) in surgical patients from January through June 2019. The study subjects were 487 surgical patients from two hospitals who met the inclusion criteria. There were 322 patients out of 487 patients who had a clean surgical procedure. Ceftriaxone (J01DD04) was the most used antibiotic, with a total DDD/100 bed days value in hospitals A and B, respectively: pre-surgery: 14.71, 77.65, during surgery: 22.57, 87.31, and postsurgery: 38.34, 93.65. In addition, 35% of antibiotics were given more than 120 min before incision. The lowest concordance to ASHP therapeutic guideline in hospital A (17.6%) and B (1.9%) was antibiotic selection. Two patients experienced SSI with bacterial growths of Proteus spp., Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli. The usage of prophylactic antibiotics for surgical procedures was high and varied between hospitals. Hospital B had significantly lower concordance to antibiotic therapeutic guidelines, resulting to a higher infection rate, compared with hospital A. ASHP adherence components were then further investigated, after which antibiotic dosing interval and injection time was found to be a significant predictor for positive bacterial growth based on logit-logistic regression. Further interventions and strategies to implement antibiotic stewardship is needed to improve antibiotic prescriptions and their use.

Oral anti-tuberculosis drugs: An urgent medication reconciliation at hospitals in Indonesia.

BACKGROUND: Four oral anti-tuberculosis drugs are conceived to be the most effective ones to eradicate Mycobacterium tuberculosis bacteria and to obviate the resistant organisms. However, the patients' adherence and medication discrepancies are obstacles to achieving the goal. This study aimed to define the anti-tuberculosis drugs used in the hospitals and to detect the discrepancies in the continuity of the tuberculosis treatment. DESIGN AND METHODS: This retrospective cross-sectional study was based on medical records of adult patients, and was conducted in two district tertiary care hospitals. Only 35 out of 136 patient records from Hospital A and 33 out of 85 records from Hospital B met the inclusion criteria. RESULTS: The most common systemic anti-infective drugs in the study were ceftriaxone (51.80 DDD/100 patient-days) used in Hospital A and isoniazid (59.53 DDD/100 patient-days) used in Hospital B. The number of rifampicin prescriptions was less than that of isoniazid. Each patient received an average of two DDD/100 patient-days, which is an under dosage for an effective treatment. CONCLUSION: This study showed a medication discrepancy of Tuberculosis therapy. Tuberculosis patients' medical histories are not under the full attention of treating physicians wherever they are admitted. Thus, medication reconciliation is needed to accomplish the goal of a Tuberculosis-free world in 2050.

Antibiotic stewardship knowledge and belief differences among healthcare professionals in hospitals: A survey study.

BACKGROUND: Collaborative practice in healthcare has been recommended to improve the quality of antimicrobial stewardship interventions, a behavioral change in antimicrobial use. Insufficient knowledge regarding antibiotic resistance, the fear of complications from infections, and how providers perceive antibiotic use and resistance are likely to influence prescribing behavior. This study's objective was to identify the knowledge and belief healthcare professionals' differences about antibiotic stewardship. METHODS: This cross-sectional survey study of three hospitals in the East Java province, Indonesia utilized a 43-item questionnaire to assess antimicrobial stewardship knowledge and belief. There were 12 knowledge questions (total possible score: 12) and 31 belief questions (total possible score: 155). The Kuder Richardson 20 (KR-20) and Cronbach alpha values of the questionnaire were 0.54 and 0.92, respectively. RESULTS: Out of the 257 respondents, 19% (48/257) had a low scores of knowledge, and 39% (101/257) had low scores on belief about antibiotic stewardship (101/257). Most midwives had a low scores on knowledge (25/61) and low scores on belief (46/61). Respondents with high scores on belief were 17% (10/59) physicians, 15% (4/27) pharmacists, 8% (5/65) nurses, and 3% (2/61) midwives. CONCLUSION: Among healthcare professionals, knowledge and belief differences concerning antibiotic stewardship vary widely. These differences will affect their capability, behavior, and contribution to the healthcare team collaboration and performance. Further studies are needed to evaluate the correlation between the level of inter-professional collaboration and the quality of the antibiotic stewardship implementation.

Educational Video Improves Knowledge about Outpatients' Usage of Antibiotics in Two Public Hospitals in Indonesia.

The inappropriate use or misuse of antibiotics, particularly by outpatients, increases antibiotic resistance. A lack of public knowledge about "Responsible use of antibiotics" and "How to obtain antibiotics" is a major cause of this. This study aimed to assess the effectiveness of an educational video about antibiotics and antibiotic use to increase outpatients' knowledge shown in two public hospitals in East Java, Indonesia. A quasi-experimental research setting was used with a one-group pre-test-post-test design, carried out from November 2018 to January 2019. The study population consisted of outpatients to whom antibiotics were prescribed. Participants were selected using a purposive sampling technique; 98 outpatients at MZ General Hospital in the S regency and 96 at SG General Hospital in the L regency were included. A questionnaire was used to measure the respondents' knowledge, and consisted of five domains, i.e., the definition of infections and antibiotics, obtaining the antibiotics, directions for use, storage instructions, and antibiotic resistance. The knowledge test score was the total score of the Guttman scale (a dichotomous "yes" or "no" answer). To determine the significance of the difference in knowledge before and after providing the educational video and in the knowledge score between hospitals, the (paired) Student's t-test was applied. The educational videos significantly improved outpatients' knowledge, which increased by 41% in MZ General Hospital, and by 42% in SG General Hospital. It was concluded that an educational video provides a useful method to improve the knowledge of the outpatients regarding antibiotics.

The Effect of Javanese Language Videos with a Community Based Interactive Approach Method as an Educational Instrument for Knowledge, Perception, and Adherence amongst Tuberculosis Patients.

The long period of tuberculosis treatment causes patients to have a high risk of forgetting or stopping the medication altogether, which increases the risk of oral anti-tuberculosis drug resistance. The patient's knowledge and perception of the disease affect the patient's adherence to treatment. This research objective was to determine the impact of educational videos in the local language on the level of knowledge, perception, and adherence of tuberculosis patients in the Regional General Hospital (RSUD) Bangil. This quasi-experimental study design with a one-month follow-up allocated 62 respondents in the intervention group and 60 in the control group. The pre- and post-experiment levels of knowledge and perception were measured with a validated set of questions. Adherence was measured by pill counts. The results showed that the intervention increases the level of knowledge of the intervention group higher than that of the control group (p-value < 0.05) and remained high after one month of follow-up. The perceptions domains that changed after education using Javanese (Ngoko) language videos with the Community Based Interactive Approach (CBIA) method were the timeline, personal control, illness coherence, and emotional representations (p-value < 0.05). More than 95% of respondents in the intervention group take 95% of their pill compared to 58% of respondents in the control group (p-value < 0.05). Utilization of the local languages for design a community-based interactive approach to educate and communicate is important and effective.

Adaptation and Validation of the Screening Tool of Older People's Prescriptions Instrument for the Indonesian Population.

OBJECTIVE: In this study, we aimed to prepare and validate an Indonesian version for the Screening Tool of Older People's Prescriptions (STOPP), which is an instrument to identify inappropriate medications for elderly patients. METHODS: The Indonesian version of STOPP (STOPP_INA) was developed using modified transcultural adaptation guidelines from the American Academy of Orthopedic Surgeons. Our method consisted of translating original STOPP into Indonesian (forwardly translation), synthesis of forward translation, translation into English and synthesis of back translation, a review by the copyright holder of STOPP, a review by the expert team, pretest, revision of STOPP_INA, field test, and psychometric analysis of the final version of the questionnaire. The study design for this part was quasi-experimental with purposive sampling for members of the translator's team, expert's team, and respondents in the pretest, but they were different from field testing that used purposive and postsurvey sampling for respondents. Content validity and face validity were used to construct the validity of STOPP_INA by assessing item-level content validity and correlation between items and total values. Internal consistency was measured with Cronbach's alpha coefficient. FINDINGS: The expert panel agreed on a list of 81 criteria. Five (62.50%) of expert team members agreed and could be continued to the field test without revision of STOPP_INA and 3 (37.50%) agreed with a revision. The research subjects in the psychometric test had 230 respondents, 5 (2.17%) resigned, with an average of item-level content validity index of 0.99. The construct validity analysis showed that 5-item criteria are "not valid," namely in A1, A3, B7, B10, and C3. Reliability analysis showed the Cronbach's Alpha and Cronbach's Alpha Based on Standardized Items were 0.978 and 0.979. CONCLUSION: The expert team was be agreed on 81 criteria (100%) of adaptation of STOPP version 2 criteria. There were 5 criteria that not valid statistically, they could not be removed from the instrument because they can influence content and construct of the instrument. The STOPP_INA has been developed for the Indonesian population, currently being tested in clinical practice against elderly patients undergoing hospitalization.

Drug-related Problems in Hypertensive Patients: A Cross-sectional Study from Indonesia.

OBJECTIVE: The treatment of hypertension requires special attention because of comorbidities and polypharmacy. In a previous study, polypharmacy has been associated with a high risk of drug-related problems (DRPs). This study aimed to analyze DRPs in Indonesian hypertensive patients focusing on drug therapy effectiveness and adverse drug reactions. METHODS: A cross-sectional study was conducted using medical records' data, prescriptions, and nursing records to observe DRPs that occurred in outpatients with hypertension from February to April 2019. A total of 114 outpatients aged ≥23 years with a primary diagnosis of primary hypertension were included in this study. DRPs were reviewed based on literature, recent guidelines, and drug interaction software. Classification DRPs were done using Indonesian-translated Pharmaceutical Care Network Europe V6.02. The data obtained were analyzed using univariate descriptive analysis. FINDINGS: Of all participants, 65 (57%) outpatients were found to have DRPs related to treatment effectiveness (54 cases) and adverse drug reactions (36 cases). The primary cause of the problems was an inappropriate drug (94.14%) and dose selection (2.86%). Potential drug interactions were found high (62.14%) in the combination of an antihypertensive agent with other drugs among patients. Overprescribing drugs without clear indications, untreated indications, and subtherapeutic dosage were also reported in this study. CONCLUSION: A significant percentage of outpatients being treated for hypertension experienced DRPs. The role of clinical pharmacists and physicians in monitoring drug therapy needs to be prioritized to prevent and resolve DRPs in outpatients with hypertension.

Evaluation of a Clinical Pharmacist Intervention on Clinical and Drug-Related Problems Among Coronary Heart Disease Inpatients: A pre-experimental prospective study at a general hospital in Indonesia.

OBJECTIVES: This study aimed to evaluate the role of a clinical pharmacist intervention in decreasing subsequent clinical and drug-related problems (DRPs) among coronary heart disease (CHD) inpatients with at least one previous DRP. METHODS: This pre-experimental study with a pre-post design was carried out from January to April 2017 among inpatients with at least one previous DRP at a general hospital in Tangerang District, Banten, Indonesia. Clinical and DRPs were documented prospectively by a clinical pharmacist, with DRPs classified using Version 6.2 of the DRP classification scheme of the Pharmaceutical Care Network Europe Foundation. The intervention consisted of a discussion of identified DRPs with physicians, patients, pharmaceutical logistics clerks, nurses and nutritionists. Following this, any subsequent clinical and DRPs were re-identified and further interventions were conducted as necessary. RESULTS: A total of 75 inpatients were included in the study. Pre-intervention, there were 443 DRPs and 202 clinical problems. The most frequent DRPs were adverse drug reactions (52.6%), followed by drug effects (41.8%). Most DRPs were of moderate severity and would have resulted in moderate consequences had the pharmacist not intervened. The interventions resulted in a significant reduction in the number of DRPs, type of DRPs and number of clinical problems (P <0.05 each). Patients with complications were 26.047 times more likely to have no reduction or an increased number of clinical problems compared to patients without complications (P <0.05). CONCLUSION: Clinical pharmacist interventions were found to reduce subsequent DRPs and clinical problems among CHD patients with at least one previous DRP.

Factors related to rational antibiotic prescriptions in community health centers in Depok City, Indonesia.

Irrational antibiotic prescription is common in developing countries, including in Indonesia. The aims of this study were to evaluate antibiotic prescription patterns and the factors related to the rationale for antibiotic prescriptions in community health centers in Depok City, Indonesia. The study employed a cross-sectional design in eleven primary health centers in Depok City, Indonesia. The sample consisted of 28 physicians and 788 oral antibiotic prescriptions, 392 of which were evaluated for rationality according to local guidelines issued by the Ministry of Health Republic of Indonesia from October to December 2012. Data were analyzed with chi-square tests and logistic regression analysis. The most widely prescribed antibiotics were amoxicillin (73.5%) and co-trimoxazole (17.4%). The most frequent diseases were acute pharyngitis (40.2%) and non-specific respiratory infection (25.4%). Approximately 220 of the 392 prescriptions did not meet the criteria for rational antibiotic prescriptions with regard to antibiotic selection (22.7%), duration of administration (72.3%), frequency of administration (3.2%), or duration and frequency of administration (1.8%). Physicians who had attended training for rational drug use were 2.01 times more rational than physicians who had never attended training. Physicians with a short working period (i.e., <7 years) were 3.95 times more rational in prescribing antibiotics than physicians who had been working for longer periods (i.e., >7 years). Most antibiotics were prescribed irrationally. Training for rational drug use and length of practice were factors related to the rationality of antibiotic prescriptions. Suitable interventions are urgently required to encourage the rational prescription of antibiotics in the PHCs.

Incidence of cisplatin-induced nephrotoxicity and associated factors among cancer patients in Indonesia.

BACKGROUND: Cisplatin is still used as a first-line medication for solid tumors. Nephrotoxicity is a serious side effect that can decrease renal function and restrict applicable doses. This research aimed to obtain the profile of cisplatin-induced nephrotoxicity and its associated factors in adult cancer patients at Dharmais National Cancer Hospital (DNCH). MATERIALS AND METHODS: The design was cross-sectional with data obtained from patient medical records. We retrospectively reviewed adult cancer patients treated with cisplatin ≥60mg/m2 for at least four consecutive chemotherapy cycles from August 2011 to November 2013. The nephrotoxicity criterion was renal function decline characterized by creatinine clearance <60 ml/min using the Cockroft-Gault (CG) equation. RESULTS: Eighty-eight subjects received at least four chemotherapy cycles of cisplatin. The prevalence of cisplatin nephrotoxicity was 34.1%. Symptoms could be observed after the first cycle of chemotherapy, and the degree of renal impairment was higher with increased numbers of cycles (r=-0.946, r2=89.5%). Factors that affected the decline of renal function were patient age (p=0.008, OR=3.433, 95%CI= 1.363-8.645) and hypertension (p=0.026, OR=2.931, 95%CI=1.120-7.670). CONCLUSIONS: Cisplatin nephrotoxicity occurred in more than one-third of patients after the fourth cycle of chemotherapy and worsened after each cycle despite preventive strategies such as hydration. The decline of renal function induced by cisplatin ≥60 mg/m2 was affected by age and hypertension.

A comparative study between prescribed and over-the-counter antibiotics.

OBJECTIVE: To examine the influence of pharmacists` demographic characteristics on dispensing antibiotics purchased with and without a prescription in the community pharmacies. METHODS: This cross-sectional study was conducted in 24 randomly-selected community pharmacies located in Abu Dhabi, United Arab Emirates between March and September 2009. Data were collected through a closed-structured questionnaire and analyzed using the Statistical Package for Social Sciences Version 17. Descriptive statistics, odds ratios, significance and 95% CI and logistic regression analyses were then used to analyze the resulting data. RESULTS: Participating pharmacists conducted a total of 1645 antibiotic transactions (1211 [73.6%] dispensed with prescriptions versus and 434 [26.4%] without). Gender and socioeconomic status of the patients had a significant effect in acquiring antibiotics without prescription (p=0.012, p=0.001). Clarithromycin (91.5%), cefuroxime (91.3%), and co-amoxiclav (66.4%) were dispensed with prescription. Ceftriaxone (53.3%), amoxicillin (47.8%) and co-amoxiclav (33.6%) were dispensed without prescription. Dispensing of antibiotics with prescription were frequently given a 5, 7, or 10 day regimen, while those without prescription were frequently given 3-7 days duration. Co-amoxiclav for sore throat was commonly dispensed without prescription. Ceftriaxone for sexually transmitted diseases was dispensed at a similar rate, both with and without prescription. CONCLUSION: Dispensing antibiotic without prescription is illegal and alarming. Patient interviews and interventions to improve the current prescribing pattern for both prescribers and pharmacists are highly warranted.

Self-medication with antimicrobial drugs in Europe.

We surveyed the populations of 19 European countries to compare the prevalence of antimicrobial drug self-medication in the previous 12 months and intended self-medication and storage and to identify the associated demographic characteristics. By using a multistage sampling design, 1,000-3,000 adults in each country were randomly selected. The prevalence of actual self-medication varied from 1 to 210 per 1,000 and intended self-medication from 73 to 449 per 1,000; both rates were high in eastern and southern Europe and low in northern and western Europe. The most common reasons for self-medication were throat symptoms (e.g., dry, inflamed, red, or sore throat, inflamed tonsils, tonsil pain). The main medication sources were pharmacies and medication leftover from previous prescriptions. Younger age, higher education, and presence of a chronic disease were associated with higher rates of self-medication. Attempts to reduce inappropriate self-medication should target prescribers, pharmacists, and the general public.

Survey of surgical antimicrobial prophylaxis in czech republic.

OBJECTIVE: To characterize the pattern of surgical antimicrobial prophylaxis in the Czech Republic. METHOD: Cross sectional survey with a self-administered postal questionnaire. Data collected included use of antimicrobial prophylaxis, surgical site infection rate, pathogens causing surgical site infection and demographics of the institution. Descriptive and multivariate analyses were performed. SETTING: Hospital, surgical departments in the Czech Republic. MAIN OUTCOME MEASURE: Prevalence of surgical antimicrobial use, factors associated with use, the profile of antimicrobial use, timing, route, dosage regimen and duration of initiated prophylaxis. RESULT: The response rate was 55.5%. Surgical antimicrobial prophylaxis was used in 97.5% of departments, and 85% departments justified prophylaxis based on guideline. The timing of the first dosage was within 2 h of operation in 95.0% of departments and 36.7% of all departments administered more than 2 doses of SAP in operations that lasted less than 4 h of all respondents. The three most common prophylactic antimicrobial agent used were cefazolin, co-amoxiclav and cefuroxime amongst the 26 single antimicrobial agents and 16 antimicrobial combinations. Penicillins and enzyme inhibitor was the most frequent class used. Surgical antimicrobial prophylaxis was administered intravenously in 82.5% of all cases. The regimen used varied markedly in dose and duration prescribed. The surgical site infection rate occurred. 1-5% in 71.7% of departments. Most departments identified the causative pathogen at all times. Staphylococcus aureus was the most frequent pathogen of surgical site infection and was detected in 90.8% of all departments. There was significant association between Pseudomonas aeruginosa with cefuroxime use and Bacteriodes fragilis with co amoxiclav use. CONCLUSION: This survey has identified several areas for improvement in surgical antimicrobial prophylaxis in the Czech Republic. Particular areas of concern include route of administration, duration and timing of first dosage of SAP, and the inappropriate use of broad-spectrum antimicrobials.