Multidisciplinary tuberculosis care: leveraging the role of hospital pharmacists.

INTRODUCTION: Optimal pharmacological treatment of tuberculosis (TB) requires a multidisciplinary team, yet the hospital pharmacist's role is unclear. We aimed to analyse hospital pharmacist-provided clinical pharmacy services (CPS) implementation in TB care. METHOD: A nationwide survey-based online cross-sectional study was conducted on hospital pharmacists in Indonesia from 1 November 2022 to 22 November 2022. Outcomes were the extent of pharmacists' involvement in multidisciplinary TB care, TB-related CPS provided and views on TB-related CPS. The probability of pharmacists' involvement in multidisciplinary TB teams was assessed using logistic regression. RESULTS: In total, 439 pharmacists (mean age 31.2±6.22 years, 78% female) completed the survey. Thirty-six per cent were part of multidisciplinary TB care, and 23% had TB-related tasks. Adherence monitoring (90%) and drug use evaluation (86%) were the most conducted TB-related CPS. Pharmacists' views on TB-related CPS implementation were generally positive, except for financial incentives. Work experience (OR 1.99, 95% CI 1.09 to 3.61), ever received TB-related training (OR 3.51, 95% CI 2.03 to 6.14) and specific assignments to provide TB-related CPS (OR 8.42, 95% CI 4.99 to 14.59) significantly increased pharmacist involvement in multidisciplinary TB care. CONCLUSION: Around one-third of hospital pharmacists are part of multidisciplinary TB care, with medication adherence and drug use monitoring as primary tasks. Pharmacists' experience, training, assignment to provide TB-related CPS and financial incentives are key elements for further implementation in multidisciplinary TB care. Pharmacists should proactively support current TB care and conduct operational research, sharing data with healthcare peers and fostering a collaborative multidisciplinary TB care team.

Knowledge, perception, and willingness to provide telepharmacy services among pharmacy students: a multicenter cross-sectional study in Indonesia.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic accelerated the provision of telepharmacy services. However, little is known about the knowledge, perception, and willingness of pharmacy students as future key players in telepharmacy adoption to provide such a service, particularly in a setting without well-established telepharmacy services before the COVID-19 pandemic. OBJECTIVE: With this survey we aimed to assess the level of knowledge, perception, and willingness to provide telepharmacy services and to identify associated factors among pharmacy students in Indonesia. METHODS: We applied a multicenter cross-sectional study design with convenience sampling technique among pharmacy students in three public universities in Bandung City, Surabaya City, and Special Region of Yogyakarta, Indonesia. The knowledge, perception, and willingness to provide telepharmacy services were assessed using an online questionnaire. Ordinal regression analysis was performed to determine factors associated with a high knowledge level, whereas binary logistic regression analyses were performed to determine factors associated with a positive perception of telepharmacy services. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. RESULTS: Among 313 respondents, 83.4% were female, and the mean age was 20 years. Although only 13.2% showed a high knowledge level, 66.5% showed a positive perception of telepharmacy services and 97.4% were willing to provide telepharmacy services in the future. An increase in age (OR 1.33; 95% CI 1.14-1.54) and being advance in smartphone usage (OR 5.21; 95% CI 2.03-13.42) are associated with an increased likelihood of having a high knowledge level about telepharmacy services. Male students had a lower likelihood of having a positive perception of telepharmacy services than females (OR 0.46; 95% CI 0.24-0.85). CONCLUSION: Despite limited knowledge of telepharmacy, the majority of pharmacy students reported a positive perception and willingness to provide telepharmacy services in their future careers. Therefore, telepharmacy practice models must be included as a subject course in the curriculum, better preparing future pharmacists to perform their roles effectively. Furthermore, student-specific factors such as age and expertise in smartphone usage that associated with knowledge and gender that associated with perception should be considered to facilitate telepharmacy adoption in Indonesia.

Clinical and economic burden of drug-susceptible tuberculosis in Indonesia: national trends 2017-19.

BACKGROUND: The global incidence of tuberculosis is decreasing, yet it remains high in Indonesia. The Indonesian National Tuberculosis Program facilitates mandatory notification, which enables early detection and treatment, minimises complications, prevents transmission, and decreases deaths. This study aimed to assess the characteristics, trends, and economic burden of notified drug-susceptible tuberculosis cases registered in this system from 2017 to 2019. METHODS: We performed a multiyear cross-sectional study focusing on drug-susceptible tuberculosis notified cases, incidence, geographical tuberculosis case distribution, treatment outcomes, and costs in Indonesia using data from Sistem Informasi Tuberkulosis (2017-19). The settings were Indonesian health-care facilities that provide tuberculosis control programmes and services. Eligible patients were those who were diagnosed with drug-susceptible tuberculosis and notified to Sistem Informasi Tuberkulosis. FINDINGS: Between 2017 and 2019, notified cases increased from 429 219 to 523 614 individuals, corresponding to an increase in incidence from 167 cases per 100 000 to 196 cases per 100 000. In 2019, more than 250 cases per 100 000 inhabitants were notified in Jakarta, North Sulawesi, Gorontalo, and Papua. Treatment success rate increased from 363 098 (84·60%) of 429 219 in 2017 to 452 966 (86·51%) of 523 614 in 2019, with a relatively stable mortality, changing from 3·15% to 3·05%. HIV status was increasingly confirmed, with unknown status decreasing from 66·21% to 43·68%. The costs of visits and monitoring and drug regimens were relatively stable, with total direct medical costs slightly increasing from US$39·40 to $40·40 per case. INTERPRETATION: Progress was made on drug-susceptible tuberculosis management in Indonesia. However, further intensified efforts, including case-finding, optimising diagnosis, and cost-effective tuberculosis management are required if Indonesia is to achieve the 2025 WHO End Tuberculosis Strategy target incidence of fewer than 55 cases per 100 000 people. These data are an important starting point for understanding drug-susceptible tuberculosis dynamics in Indonesia and optimising its management. FUNDING: Directorate General of Higher Education; Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia.

Barriers to Optimal Tuberculosis Treatment Services at Community Health Centers: A Qualitative Study From a High Prevalent Tuberculosis Country.

Background: Community health centers (CHCs) are a backbone healthcare facility for tuberculosis (TB) services. Identifying barriers amongst TB service providers at the CHC level is required to help them deliver successful TB treatment. Aims: The current study aimed to analyze barriers to successful TB treatment from the perspective of TB service providers at the CHC level in a high prevalent TB country. Methods: A qualitative study was conducted using in-depth interviews and focus group discussions in a province of Indonesia with a high TB prevalence. Two districts representing rural and urban areas were selected to obtain information from TB service providers (i.e., physicians and nurses) at the CHC level. In addition, key informant interviews with TB patients, hospital TB specialists, pharmacists, and activists were conducted. The trustworthiness and credibility of the information were established using information saturation, participant validation, and triangulation approaches. The interviews were also transcribed for the inductive analysis using Atlas.ti 8.4 software. Results: We identified 210 meaning units from 48 participants and classified them into two main themes: organizational capacity and TB program activities. We identified the inadequacy of human resources, facility, and external coordination as the main barriers to organizational capacity. Furthermore, the barriers were identified regarding TB program activities, that is, inadequate TB case finding, diagnosis, drug supply chain and dispensing management, treatment and monitoring, case recording and reporting, and public-private collaboration. Conclusion: Strengthening CHCs in the management of TB is critical to reaching the national and global goals of TB eradication by 2035. These findings can be considered to develop evaluation strategies to improve the successful TB treatment in high prevalent TB countries, especially Indonesia.

Digital Health Technologies to Improve Medication Adherence and Treatment Outcomes in Patients With Tuberculosis: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems of nonadherence to medication and improving treatment outcomes. OBJECTIVE: This paper systematically reviews the effect of DHT in improving medication adherence and treatment outcomes in patients with TB. METHODS: A literature search in PubMed and Cochrane databases was conducted. Randomized controlled trials (RCTs) that analyzed the effect of DHT interventions on medication adherence outcomes (treatment completion, treatment adherence, missed doses, and noncompleted rate) and treatment outcomes (cure rate and smear conversion) were included. Adult patients with either active or latent TB infection were included. The Jadad score was used for evaluating the study quality. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed to report study findings. RESULTS: In all, 16 RCTs were selected from 552 studies found, and 6 types of DHT interventions for TB were identified: 3 RCTs examined video directly observed therapy (VDOT), 1 examined video-observed therapy (VOT), 1 examined an ingestible sensor, 1 examined phone call reminders, 2 examined medication monitor boxes, and 8 examined SMS text message reminders. The outcomes used were treatment adherence, including treatment completion, treatment adherence, missed dose, and noncompleted rate, as well as clinical outcomes, including cure rate and smear conversion. In treatment completion, 4 RCTs (VDOT, VOT, ingestible sensor, SMS reminder) found significant effects, with odds ratios and relative risks (RRs) ranging from 1.10 to 7.69. Treatment adherence was increased in 1 study by SMS reminders (RR 1.05; 95% CI 1.04-1.06), and missed dose was reduced in 1 study by a medication monitor box (mean ratio 0.58; 95% CI 0.42-0.79). In contrast, 3 RCTs of VDOT and 3 RCTs of SMS reminders did not find significant effects for treatment completion. Moreover, no improvement was found in treatment adherence in 1 RCT of VDOT, missed dose in 1 RCT of SMS reminder, and noncompleted rate in 1 RCT of a monitor box, and 2 RCTs of SMS reminders. For clinical outcomes such as cure rate, 2 RCTs reported that phone calls (RR 1.30; 95% CI 1.07-1.59) and SMS reminders (OR 2.47; 95% CI 1.13-5.43) significantly affected cure rates. However, 3 RCTs found that SMS reminders did not have a significant impact on cure rate or smear conversion. CONCLUSIONS: It was found that DHT interventions can be a promising approach. However, the interventions exhibited variable effects regarding effect direction and the extent of improving TB medication adherence and clinical outcomes. Developing DHT interventions with personalized feedback is required to have a consistent and beneficial effect on medication adherence and outcomes among patients with TB.

Barriers and strategies to successful tuberculosis treatment in a high-burden tuberculosis setting: a qualitative study from the patient's perspective.

BACKGROUND: Previously treated tuberculosis (TB) patients are a widely reported risk factor for multidrug-resistant tuberculosis. Identifying patients' problems during treatment is necessary to control TB, especially in a high-burden setting. We therefore explored barriers to successful TB treatment from the patients' perspective, aiming to identify potential patient-centred care strategies to improve TB treatment outcome in Indonesia. METHODS: A qualitative study was conducted in a province of Indonesia with high TB prevalence. Participants from various backgrounds (i.e., TB patients, physicians, nurses, pharmacists, TB activist, TB programmers at the district and primary care levels) were subject to in-depth interviews and focus group discussions (FGDs). All interviews and FGDs were transcribed verbatim from audio and visual recordings and the respective transcriptions were used for data analysis. Barriers were constructed by interpreting the codes' pattern and co-occurrence. The information's trustworthiness and credibility were established using information saturation, participant validation and triangulation approaches. Data were inductively analysed using the Atlas.ti 8.4 software and reported following the COREQ 32-items. RESULTS: We interviewed 63 of the 66 pre-defined participants and identified 15 barriers. The barriers were classified into three themes, i.e., socio-demography and economy; knowledge and perception and TB treatment. Since the barriers can be interrelated, we determined five main barriers across all barrier themes, i.e., lack of TB knowledge, stigmatisation, long distance to the health facility, adverse drug reaction and loss of household income. CONCLUSION: The main treatment barriers can be considered to strengthen patient-centred care for TB patients in Indonesia. A multi-component approach including TB patients, healthcare providers, broad community and policy makers is required to improve TB treatment success.

Interventions to improve medication adherence in tuberculosis patients: a systematic review of randomized controlled studies.

Non-adherence to anti-tuberculosis (anti-TB) medication is a major risk factor for poor treatment outcomes. We therefore assessed the effectiveness of medication adherence enhancing interventions in TB patients. We report a systematic review of randomized controlled trials that included either latent tuberculosis infection (LTBI) or active TB patients. Outcomes of interest included adherence rate, completed treatment, defaulted treatment and treatment outcomes. We identified four LTBI and ten active TB studies. In active TB patients, directly observed treatment (DOT) by trained community workers, short messaging service combined with education, counselling, monthly TB vouchers, drug box reminders and combinations of those were found effective. In LTBI patients, shorter regimens and DOT effectively improved treatment completion. Interestingly, DOT showed variable effectiveness, highlighting that implementation, population and setting may play important roles. Since non-adherence factors are patient-specific, personalized interventions are required to enhance the impact of a programme to improve medication adherence in TB patients.

Treatment outcomes of drug-resistant tuberculosis in the Netherlands, 2005-2015.

Background: Since in low incidence TB countries population migration and complex treatment of drug-resistant tuberculosis (DR-TB) patients are major issues, we aimed to analyse patient risk factors associated with the incidence of poor outcome of TB treatment among DR-TB patients in the Netherlands. Methods: This retrospective cohort study included adult patients with confirmed DR-TB treated from 2005 to 2015. We obtained data from a nationwide exhaustive registry of tuberculosis patients in the Netherlands. Predictors for unsuccessful TB treatment (defaulted and failed treatment) and TB-associated mortality were analysed using multivariate logistic regression. Results: Among 10,303 registered TB patients, 545 patients with DR-TB were analysed. Six types of DR-TB were identified from the included patients, i.e. isoniazid mono- or poly-resistance (68%); rifampicin mono- or poly-resistance (3.1%); pyrazinamide mono-resistance (8.3%); ethambutol mono-resistance (0.1%); multidrug-resistance (18.9%); and extensively drug-resistance (0.7%). The majority of patients were foreign-born (86%) and newly diagnosed TB (89%) patients. The cumulative incidence of unsuccessful treatment and mortality were 5 and 1%, respectively. Among all DR-TB cases, patients with Multi Drug-Resistant Tuberculosis (MDR-TB) (OR 4.43; 95%CI 1.70-11.60) were more likely to have unsuccessful treatment, while miliary and central nervous system TB (OR 15.60; 95%CI 2.18-111.52) may also be predictors for TB mortality. Additionally, patients with substance abuse and homelessness tend to have unsuccessful treatment. Conclusions: In recent years, we identified a low incidence of DR-TB as well as the poor outcome of DR-TB treatment. The majority of cases were primary drug-resistant and foreign-born. To further improve treatment outcome, special attention should be given to the high-risk DR-TB patients.

A systematic review finds inconsistency in the measures used to estimate adherence and persistence to multiple cardiometabolic medications.

OBJECTIVES: We reviewed measures used to estimate adherence and persistence to multiple cardiometabolic medications from prescription data, particularly for blood pressure-lowering, lipid-lowering, and/or glucose-lowering medication, and give guidance on which measures to choose. STUDY DESIGN AND SETTING: A literature search of Medline, Embase, and PsycINFO databases was conducted to identify studies assessing medication adherence and/or persistence for patients using multiple cardiometabolic medications. Two reviewers performed the study selection process independently. RESULTS: From the 54 studies assessing adherence, only 36 (67%) clearly described the measures used. Five measures for adherence were identified, including adherence to "all," to "any," to "both" medication, "average adherence," and "highest/lowest adherence". From the 22 studies assessing persistence, only six (27%) clearly described the measures used. Three measures for persistence were identified, including persistence with "all," with "both," and with "any" medication. Less than half of the studies explicitly considered medication switches when relevant. CONCLUSION: From the identified measures, the "any medication" measure is most suitable for identifying patients in need of an intervention, whereas the "all medication" measure is useful for assessing the effect of interventions. More attention is needed for adequate measurement definitions when reporting on and interpreting adherence or persistence estimates to multiple medications.

DNA methyltransferase 3A gene polymorphism contributes to daily life stress susceptibility.

Daily life stress markedly affects the response toward stressful stimuli. DNA methy-lation is one of the factors that regulate this response, and is a normal mechanism of somatic cell growth, but its regulatory gene variations may cause alterations in the stress response. The aim of the present study was to investigate genotypic variants of the DNA methyltransferase 3A (DNMT3A) gene in 129 healthy subjects and evaluate its association with daily life stress. Blood samples were collected, and genomic DNA was isolated. DNA was amplified using specific tetra primers for DNMT3A (C/T) rs11683424 and visualized following 2% agarose gel electrophoresis. The association of DNMT3A genetic variants with daily life stress was analyzed using the Kessler Psychological Distress Scale (K10). We observed that the distribution of subjects with genotype CC (wild type), CT (heteromutant), and TT (homomutant) was 13.95%, 81.4%, and 4.65%, respectively. Genetic variations significantly affected the daily life stress condition (p=0.04) in Indonesian healthy subjects, but most of the subjects with the CT phenotype were classified in a stress condition.

Three years of antibacterial consumption in Indonesian Community Health Centers: The application of anatomical therapeutic chemical/defined daily doses and drug utilization 90% method to monitor antibacterial use.

CONTEXT: Irrational use of antibacterial drugs in Community Health-Care Centers (CHCs) may lead to increased resistance, morbidity, and mortality. AIMS: The aim of this study was to determine patterns of antibacterial use at CHCs in a district of Indonesia and use this as data for an antibiotic policy. SETTINGS AND DESIGN: The observational-descriptive study was conducted in a district of Indonesia to obtain antibacterial use from 2008 to 2010. SUBJECTS AND METHODS: The data obtained from the report on the use of medicines were classified and processed using the anatomical therapeutic chemical (ATC) and defined daily doses (DDD) method, with DDD/1000 patients as a unit measurement. The number of patients was obtained from attending patients in that research period. The most abundant antibacterial drugs use segment was identified by the drug utilization 90% (DU90%) method. STATISTICAL ANALYSIS USED: Descriptive analysis were performed in this study. RESULTS: Fourteen kinds of antibacterial drugs were used in 61 CHCs. The total of antibacterial drug use during the period 2008-2010 was 871.36 DDD/1000 patients/day. Declining antibacterial use was observed between 2008 and 2010. Six kinds of antibacterial drugs were the most commonly used. The data show that the average use per visit was as high as 24.41 DDD. CONCLUSIONS: Amoxicillin, sulfamethoxazole and trimethoprim are antibacterials that have to be reconsidered by physicians for use in the Bandung CHC. The high use of antibacterial drugs, as described in the study, can be used as reference to develop an antimicrobial stewardship program and increase awareness of resistance, adverse drug reaction and drug interaction of antibacterial drugs.

Induction of caspase cascade pathway by kaempferol-3-O-rhamnoside in LNCaP prostate cancer cell lines.

Prostate cancer has become a leading cause of mortality in humans. Previous studies have shown the potential anticancer properties of kaempferol-3-O-rhamnoside in breast cancer cell lines. In the present study, the anticancer potential of kaempferol-3-O-rhamnoside was investigated in LNCaP human prostate cancer cell lines. The inhibition of cell proliferation was investigated using MTT assays, whereas its ability to induce the caspase-cascade pathway was investigated by western blotting. The results showed that kaempferol-3-O-rhamnoside inhibits the proliferation of LNCaP cells in a dose-dependent manner by upregulating the expression of caspase-8, caspase-9, caspase-3 and poly (ADP-ribose) polymerase proteins. Although further studies are required, the results of the present study indicate the potential application of kaempferol-3-O-rhamnoside in cancer treatment.

Assessment of patient care indicators at community pharmacies in Bandung City, Indonesia.

Community pharmacies supply medications; therefore are involved in the patient care process. The objective of this study was to study the quality of patient care given by these pharmacies. We conducted a cross sectional study of 13 community pharmacies in Bandung City, Indonesia. Data collected were patient care indicators whose standard is defined by the World Health Organization (WHO). These were assessed by observing 1961 subjects who presented to the studied pharmacies to receive their medication. The average dispensing time was 62 seconds. Ninety-six percent of the prescribed medicine was dispensed correctly and 99% of the prescribed medication was sufficiently labeled. Only 88% of patients were able to repeat the correct dosage regimen of their prescribed medicines. Although the average dispensing time was greater than the recommended 60 seconds, the dispensing time ranged from 3 to 435 seconds. Greater attention should be focused on making sure the patient understands the dosage regimen correctly to ensure patient compliance with the correct regimen.