Potential drug-drug interactions and their associated factors in hospitalized COVID-19 patients with comorbidities.

Background: Hospitalized COVID-19 patients with comorbidities receive more complex drug therapy. This increases the probability of potential drug-drug interactions (pDDIs). Studies on pDDIs in hospitalized patients with COVID-19 in countries with limited resources like Indonesia during the later period of the disease are still limited. This study aims to identify the pattern of pDDIs in hospitalized COVID-19 patients with comorbidities and their associated factors, especially in the second wave of the disease in Indonesia. Methods: This study was a longitudinal-retrospective study observing hospitalized COVID-19 patients with comorbidities using medical record data in June-August 2021 at a public hospital in a region in Indonesia. pDDIs were identified using the Lexicomp® database. Data were descriptively analyzed. Factors associated with important pDDIs were analyzed in multivariate logistic regression model. Results: A total of 258 patients with a mean age of 56.99 ± 11.94 years met the inclusion criteria. Diabetes mellitus was the most common comorbidity experienced by 58.14% of the patients. More than 70% of the patients had one comorbidity and the average number of administered drugs was 9.55 ± 2.71 items per patient. Type D pDDIs, which required modification of therapeutic regimens, amounted to 21.55% of the total interactions. Only the number of drugs was significantly and independently associated with type D pDDIs (adjusted odds ratio 1.47 [1.23-1.75], p < 0.01). Conclusion: The drugs involved in the pDDIs of hospitalized COVID-19 patients with comorbidities may differ depending on the disease periods, hospital settings, or countries. This study was small, single center, and of short duration. However, it may give a glimpse of important pDDIs during the delta variant of COVID-19 in a similar limited-resource setting. Further studies are needed to confirm the clinical significance of these pDDIs.

Potential roles of community-based pharmacists in assisting home-quarantined patients with COVID-19 in a resource-challenged setting.

OBJECTIVES: To present the experiences of community-based drug information centre (DIC) pharmacists assisting home-quarantined patients with COVID-19 in Indonesia. METHODS: A prospective case study included home-quarantined patients with suspected/confirmed COVID-19 contacting pharmacists at a DIC in Indonesia in July 2021. Patient characteristics, pharmacist interventions and outcomes were reported. KEY FINDINGS: Fifteen home-quarantined patients were screened for COVID-19 and were provided with follow-up services (i.e. medication review and monitoring). Worsening symptoms and/or reduction in oxygen saturation were reported in seven patients where a referral to medical services was made for them. Most patients recovered at follow-up (4-14 days). CONCLUSIONS: Community-based DIC pharmacists potentially contributed to the frontline emergency response, as observed during the COVID-19 crisis in Indonesia.

Sex disparities in the effect of statins on lipid parameters: The PharmLines Initiative.

ABSTRACT: Real-world evidence on a potential statin effect modification by sex is inconclusive, especially for the primary prevention of cardiovascular disease (CVD). We aimed to quantify the differences in the effect of statins on lipid parameters between men and women.The PharmLines Initiative linked the Lifelines Cohort Study and the IADB.nl prescription database. This database covers a representative population from the Netherlands. We selected participants aged ≥40 years at the index date: the date of the first prescription of any statin monotherapy in the study period 2006 to 2017. Multivariate regression modeling was used to compare the difference of the mean percentage change of lipid parameters (% mean difference [MD]) from baseline to follow-up measurement between the sexes.Out of 5366 statin users from approximately 50,000 participants available in the final linked database, 685 were statin initiators. At baseline, women had significantly higher levels of mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) than men (all P values <.01). At follow-up, women had a significantly higher mean percentage change of HDL-C compared to men (adjusted % MD 5.59, 95% confidence interval [CI] 2.42-8.75, P < .01). There was no significant sex difference in other parameters, nor in the proportion of men and women who achieved LDL-C ≤2.5 mmol/L.Statins appear to have a greater effect on increasing HDL-C levels in women than men while showing similar effect on other lipid parameters in both sexes. Men should not be treated differently than women.

Association between adherence to statin therapy and low-density lipoprotein cholesterol (LDL-c) response in first-time users of standard-dose and low-dose statins: the PharmLines initiative.

OBJECTIVE: To investigate whether statin adherence (defined as proportion days covered, PDC) is associated with LDL-c response in statin initiators on standard and low starting doses of statins, and to detect a possible interaction with sex. METHODS: An inception cohort study was conducted using the PharmLines Initiative, a linkage between the Lifelines Cohort Study and the University of Groningen's IADB.nl (prescription database). First-time statin users were followed from baseline to follow-up measurement. We matched participants (1:1) between the standard-dose and the low-dose group of statin users on the duration of follow-up. Multiple linear regression analysis was used to model the association. RESULTS: In univariate analysis, PDC was significantly associated with LDL-c response similarly (slope = -0.021), in both the standard-dose group (N = 115, p < .001) and the low-dose group (N = 115, p = .003). In the standard-dose group, the same level of PDC appeared to be significantly associated with a greater LDL-c level reduction in women (slope = -0.027, N = 48, p < .001) than in men (slope = -0.017, N = 67, p < .001). Meanwhile, in the low-dose group, the reduction of LDL-c level from baseline seemed to be greater in men (slope = -0.023, N = 56, p < .001) than in women (slope = -0.020, N = 59, p < .001) for the same level of PDC. In multiple regression analysis, the significant association between PDC and LDL-c with a similar pattern to the univariate result was maintained only in the standard-dose group. CONCLUSIONS: Adherence is significantly associated with LDL-c response to statins at follow-up. Sex appears to significantly modify this association. At a similar adherence level, women seem to experience a better LDL-c response to standard-dose statins compared to men in a real-world setting.

Association between Adherence to Guideline-Recommended Preventive Medications and In-Hospital Mortality among Non-Reperfused ST-Elevation Myocardial Infarction Patients Admitted to a Tertiary Care Academic Center in a Developing Country.

Background and aims: Acute ST-elevation myocardial infarction (STEMI) is a potentially fatal presentation of coronary artery disease (CAD). Evidence of the impact of acute pharmacological interventions in non-reperfused STEMI patients on subsequent events is limited. We aimed to assess the association between adherence to guideline-recommended preventive medications and in-hospital mortality among this high-risk patient population. Methods: We conducted a cohort study using data obtained from the Jakarta Acute Coronary Syndrome (JAC) Registry database from a tertiary care academic hospital in Indonesia. We included 1132 of 2694 patients with STEMI recorded between 1 January 2014 and 31 December 2016 who did not undergo acute reperfusion therapy. Adherence to guideline-recommended preventive medications was defined as the combined administration of aspirin, clopidogrel, anticoagulants and statins after hospital admission. The main outcome measure was in-hospital mortality. Results: Overall, 778 of 1132 patients (69%) received the combination of preventive medications. The guideline non-adherent group had significantly more patients with earlier onset of STEMI, higher Killip class and thrombolysis in myocardial infarction (TIMI) score. After adjustments for measured characteristics using logistic regression modeling, exposure to the combination of preventive therapies was associated with a statistically significant lower risk for in-hospital mortality (adjusted odds ratio: 0.46, 95% confidence interval: 0.30-0.70). Conclusions: Adherence to guideline-recommended preventive medications was associated with lower risk of in-hospital mortality in non-reperfused STEMI patients. The predictors of not receiving these medications need to be confirmed in future research.

Key factors influencing the prescribing of statins: a qualitative study among physicians working in primary healthcare facilities in Indonesia.

OBJECTIVES: To elicit key factors influencing physicians' decision to prescribe statins. DESIGN: A qualitative study using a phenomenological approach within a pragmatism interpretive framework. A combination of purposive and snowball sampling was used to recruit physicians. Data were collected through face-to-face, semistructured interviews with physicians working in primary healthcare facilities in a capital of a province in Indonesia. We recorded and verbatim transcribed the interviews. Coding was done independently by two researchers and data were analysed using phenomenological data analyses. Key factors influencing physicians' decision to prescribe statins were classified into factors at the microlevels, mesolevels and macrolevels according to the structural model by Scoggins et al. PARTICIPANTS AND SETTING: Physicians working in primary healthcare facilities in a capital of a province in Indonesia. RESULTS: Ten physicians were included in the study. Key factors at the microlevel were that physicians knew guidelines in general, but there was uncertainty how to take into account the level of total cholesterol in combination with other cardiovascular risk factors such as diabetes and hypertension. At the macrolevel, the new National Health Insurance System (NHIS) that appeared to facilitate the prescription of statins though more clinical information should be integrated in the system's platform to support appropriate prescribing. CONCLUSIONS: The findings indicate lack of awareness of specific details in current guideline recommendations. Appropriate prescribing of statins should be enhanced using the new NHIS.

Use of medicine pricing and reimbursement policies for universal health coverage in Indonesia.

OBJECTIVES: This study aimed to define the problems of the current use of the e-Catalogue and the national formulary (NF)-two elements of medicine pricing and reimbursement policies in Indonesia for achieving universal health coverage (UHC)-by examining the knowledge and attitudes of stakeholders. Specifically, to investigate (1) the perceived challenges involved in the further implementation of the e-Catalogue and the NF, (2) reasons of prescribing medicines not listed in the NF, and (3) possible improvements in the acceptance and use of the e-Catalogue and the NF. METHODS: Semi-structured interviews were conducted with stakeholders (policymakers, healthcare providers, a pharmaceutical industry representative, and experienced patients) to collect the qualitative data. The data was analysed using directed content analysis, following the guidelines of the COnsolidated criteria for REporting Qualitative studies (COREQ) in reporting the findings. RESULTS: Interestingly, 20 of 45 participants decided to withdraw from the interview due to their lack of knowledge of the e-Catalogue and the NF. All 25 stakeholders who fully participated in this research were in favor of the e-Catalogue and the NF. However, interviewees identified a range of challenges. A major challenge was the lack of harmonization between the lists of medicines in the e-Catalogue and the NF. Several system and personal reasons for prescribing medicines not listed in the NF were identified. Important reasons were a lack of incentives for physicians as well as a lack of transparent and evidence-based methods of selection for the medicines to be listed in the NF. CONCLUSIONS: The e-Catalogue and the NF have not been fully utilized for achieving UHC in Indonesia. Some possible improvements suggested were harmonization of medicines listed in the e-Catalogue and the NF, restructuring incentive programs for prescribing NF medicines, and increasing the transparency and evidence-based approach for selection of medicines listed in the e-Catalogue and the NF.

The implementation of HTA in medicine pricing and reimbursement policies in Indonesia: Insights from multiple stakeholders.

OBJECTIVES: This study aimed to identify the barriers and facilitators to improve the use of health technology assessment (HTA) for the selection of medicines listed in the e-Catalogue and the national formulary in Indonesia. METHODS: Semi-structured interviews were conducted to collect qualitative data. Purposive sampling was used to recruit the stakeholders consisting of policymakers, a pharmaceutical industry representative, healthcare providers, and patients. The data were analyzed using directed content analysis and following the COnsolidated criteria for REporting Qualitative studies (COREQ). RESULTS: The twenty-five participants interviewed agreed with the use of HTA for supporting the e-Catalogue and the national formulary and perceived the advantages of HTA implementation outweighed the disadvantages. Barriers mentioned were a lack of capability of local human resources, financial incentives, a clear framework and insufficient data. Strategies suggested to overcome the barriers were establishing (inter)national networks to build up capacity, setting up departments of HTA in several universities in Indonesia, and introducing a clear HTA framework. Facilitators mentioned were the ambition to achieve universal health coverage, the presence of legal frameworks to implement HTA in the e-Catalogue and the national formulary, and the demands for appropriate medicine policies. CONCLUSIONS: Several barriers are currently hampering broad implementation of HTA in medicine pricing and reimbursement policy in Indonesia. Solutions to these issues appear feasible and important facilitators exist.

Long-term incidence and risk factors of cardiovascular events in Asian populations: systematic review and meta-analysis of population-based cohort studies.

BACKGROUND: Scientific studies on cardiovascular disease (CVD) burden and risk factors are predominantly based on short-term risk in Westerner populations, and such information may not be applicable to Asian populations, especially over the longer term. This review aims to estimate the long-term (>10 years) CVD burden, including coronary heart disease (CHD) and stroke, as well as associated risk factors in Asian populations. METHODS: PubMed, Embase and Web of Science were systematically searched, and hits screened on: Asian adults, free of CVD at baseline; cohort study design (follow-up >10 years). Primary outcomes were fatal and non-fatal CVD events. Pooled estimates and between-study heterogeneity were calculated using random effects models, Q and I2 statistics. RESULTS: Overall, 32 studies were eligible for inclusion (follow-up: 11-29 years). The average long-term rate of fatal CVD is 3.68 per 1000 person-years (95% CI 2.84-4.53), the long-term cumulative risk 6.35% (95% CI 4.69%-8.01%, mean 20.13 years) and the cumulative fatal stroke/CHD risk ratio 1.5:1. Important risk factors for long-term fatal CVD (RR, 95% CI) were male gender (1.49, 1.36-1.64), age over 60/65 years (7.55, 5.59-10.19) and current smoking (1.68, 1.26-2.24). High non-HDL-c, and ß- and γ-tocopherol serum were associated only with CHD (HR 2.46 [95% CI 1.29-4.71] and 2.47 [1.10-5.61] respectively), while stage 1 and 2 hypertensions were associated only with fatal stroke (2.02 [1.19-3.44] and 2.89 [1.68-4.96] respectively). CONCLUSIONS: Over a 10 year + follow-up period Asian subjects had a higher risk of stroke than CHD. Contrary to CVD prevention in Western countries, strategies should also consider stroke instead of CHD only.

Indonesian pharmacists' and pharmacy students' attitudes towards collaboration with physicians.

BACKGROUND: Recent implementation of national health coverage and the increasing health burden in Indonesia require health professionals, including pharmacists, to work more collaboratively to improve access and quality of health care. Nevertheless, relatively little is known about Indonesian pharmacists' attitude towards collaboration. OBJECTIVE: To assess and compare the attitude of Indonesian pharmacy students and pharmacists towards collaboration with physicians. METHODS: A survey of 95 pharmacy students (Universitas Surabaya) and 114 pharmacists (public health facilities in East Java) in Indonesia was conducted using the validated questionnaire, Scale of Attitudes Toward Physician-Pharmacist Collaboration (SATP2C), which was translated in Bahasa Indonesia. The questionnaire contained 16 items which were based on a 4-point Likert scale. Descriptive statistics were used to summarise the responses, (i.e., individual scores, factor scores and total scores). RESULTS: Response rates of 97.9% and 65.8% were reported for students and pharmacists, respectively. The mean total score of SATP2C among Indonesian students and pharmacists were 56.53 versus 56.77, respectively; indicating positive attitudes toward collaboration. Further analysis of each item of SATP2C confirmed the positive attitudes in which mean and median scores of ≥3 were reported for most items in both groups. Significant differences between students and pharmacists were found regarding the following items: (i) 'there are many overlapping areas of responsibility between pharmacists and physicians' (3.28 versus 2.89, respectively; p<0.001), (ii) 'pharmacist should clarify a physician's order' (3.54 versus 3.71, respectively; p=0.046); and (iii) 'physicians should consult with pharmacists about adverse reactions or refractory to drug treatment' (3.60 versus 3.44, respectively; p=0.022). CONCLUSIONS: Indonesian pharmacists reported positive attitudes toward collaboration with physicians. Further research is needed to understand other factors contributing in translating those positive attitudes into actual practice, and thus, providing a good foundation for policy makers, researchers and practitioners to support pharmacist-physician collaboration in Indonesia.

Indonesian pharmacists' and pharmacy students' attitudes towar ds collaboration with physicians

Background: Recent implementation of national health coverage and the increasing health burden in Indonesia require health professionals, including pharmacists, to work more collaboratively to improve access and quality of health care. Nevertheless, relatively little is known about Indonesian pharmacists’ attitude towards collaboration. Objective: To assess and compare the attitude of Indonesian pharmacy students and pharmacists towards collaboration with physicians. Methods: A survey of 95 pharmacy students (Universitas Surabaya) and 114 pharmacists (public health facilities in East Java) in Indonesia was conducted using the validated questionnaire, Scale of Attitudes Toward Physician-Pharmacist Collaboration (SATP2C), which was translated in Bahasa Indonesia. The questionnaire contained 16 items which were based on a 4-point Likert scale. Descriptive statistics were used to summarise the responses, (i.e., individual scores, factor scores and total scores). Results: Response rates of 97.9% and 65.8% were reported for students and pharmacists, respectively. The mean total score of SATP2C among Indonesian students and pharmacists were 56.53 versus 56.77, respectively; indicating positive attitudes toward collaboration. Further analysis of each item of SATP2C confirmed the positive attitudes in which mean and median scores of ≥3 were reported for most items in both groups. Significant differences between students and pharmacists were found regarding the following items: I) 'there are many overlapping areas of responsibility between pharmacists and physicians’ (3.28 versus 2.89, respectively; p<0.001), (II) 'pharmacist should clarify a physician's order' (3.54 versus 3.71, respectively; p=0.046); and (III) ‘physicians should consult with pharmacists about adverse reactions or refractory to drug treatment’ (3.60 versus 3.44, respectively; p=0.022). Conclusions: Indonesian pharmacists reported positive attitudes toward collaboration with physicians. Further research is needed to understand other factors contributing in translating those positive attitudes into actual practice, and thus, providing a good foundation for policy makers, researchers and practitioners to support pharmacist-physician collaboration in Indonesia (AU)

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