Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. METHODS AND FINDINGS: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. INTERPRETATION: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.

Characteristics, knowledge, attitude, and practice of pharmacy personnel in supporting tuberculosis treatment: A multicenter cross-sectional study in a high-burden tuberculosis country.

BACKGROUND: Positive roles of community pharmacy in tuberculosis (TB) care have been widely reported. However, the actual practice of supporting TB treatment is not optimal yet. OBJECTIVES: We analyzed the current practice of community pharmacy personnel and its factors in supporting the successful treatment of TB patients in Indonesia, aiming to develop strategies for effective and sustainable TB practice models for the community pharmacy. METHODS: We performed a cross-sectional survey in 3 areas representing Indonesia's eastern, central, and western parts. Development and validation of the questionnaire were conducted to assess 4 domains, that is, characteristics, knowledge, attitudes, and practice of community pharmacy personnel in supporting the successful treatment of TB patients. Data were collected with purposive convenience sampling using online and offline questionnaires. Descriptive analyses were used to summarize factors in each domain, while binary logistic regression was used to analyze the associated factors of the practice. RESULTS: Thirty-five questionnaire items indicated a valid instrument, and the study successfully included 844 participants who comprised pharmacists (n = 473, 56%) and pharmacy assistants (n = 371, 44%). Although most of the knowledge items were correctly answered by more than 60% of the participants, items related to TB signs, risk groups, drug regimens, and medicine uses were still less than 60%. This was in line with exposure to updated TB training in only 51% of the participants (n = 426). Most of the participants had a positive attitude toward their professional role (n = 736, 87%), capability (n = 646, 77%), and consequences (n = 655, 78%) in supporting TB treatment. However, this was not aligned with the actual practice of supporting TB treatment, intensively performed by only 1.3% of participants (n = 11). We identified several factors associated with the practice, that is, a pharmacy assistant background (P < 0.05), short working time (P < 0.05), experience in TB training (P < 0.001), and a positive attitude (P < 0.001). CONCLUSION: This study highlighted a limited number of community pharmacy personnel intensively practicing as TB treatment supporters in Indonesia. An interventional package considering the identified factors is needed to develop effective and sustainable practices in the real world.

HIV/AIDS in Indonesia: current treatment landscape, future therapeutic horizons, and herbal approaches.

HIV/AIDS is still a major worldwide health concern, and Indonesia is making efforts to mitigate its effects. Antiretroviral therapy (ARV), which aims to decrease viral replication, boost immunological function, and lengthen the lifespans of persons living with HIV/AIDS, is the cornerstone of Indonesia's strategy. The availability of ARV has significantly increased, yet problems including stigma and the requirement for regular medication adherence still exist. To address the broader needs of those affected by HIV/AIDS, Indonesia lays a major focus on comprehensive care, which includes mental health and social support, in addition to ARV. Data show that, despite progress, there is still a stigma surrounding HIV/AIDS, which affects patient outcomes and access to care. With vigorous research into cutting-edge antiretroviral medications and treatment techniques, Indonesia has a thriving future therapeutic landscape. The goals of these programs are to increase treatment effectiveness, decrease side effects, and increase access to cutting-edge treatments. Preventive methods, such as PrEP (pre-exposure prophylaxis), are making progress, and efforts to find a cure are gaining prominence. Notably, HIV/AIDS management plan of Indonesia heavily relies on natural remedies. Patient care incorporates traditional Indonesian medicine, such as jamu and several herbal medicines. Although there is little scientific proof to support the effectiveness of these herbal remedies, complementary and alternative therapies frequently employ them to manage symptoms and promote general wellness. In terms of the 95-95-95 targets, Indonesia is making an effort to comply with these international goals by seeking to diagnose 95% of HIV-positive individuals, provide sustained ARV to 95% of those diagnosed, and achieve viral suppression in 95% of ARV recipients. Although there are gaps in reaching these aims, progress is being made, in part because of the aforementioned challenges. In summary, Indonesia employs a multimodal approach to HIV/AIDS management, including traditional herbal cures, continuous research into cutting-edge treatments, and conventional ARV. In order to enhance overall health outcomes and create a healthier society, the future of HIV/AIDS treatment in Indonesia is concentrated on expanding therapeutic alternatives, reaching the 95-95-95 targets, decreasing stigma, and improving access to care.

Comparison of oral iron chelators in the management of transfusion-dependent ß-thalassemia major based on serum ferritin and liver enzymes.

Background: Excess iron deriving from a chronic transfusion and dietary intake increases the risk for cardiac complications in ß-thalassemia major patients. Deferiprone and deferasirox are commonly prescribed to thalassemic patients who are at risk of iron overload. This study aimed to compare the performance and toxicity of deferiprone and deferasirox in ß-thalassemia major patients. Methods: A cross-sectional observation was performed on 102 patients with ß-thalassemia major. Serum ferritin along with total, indirect, and direct bilirubin levels were measured. Levels of liver enzymes, transaminase (ALT), and aspartate transaminase (AST), were also determined. Ferritin correlations with serum ALT, AST, and total bilirubin were constructed based on Spearman's rank correlation. Statistical differences based on the serum parameters were analyzed between deferiprone and deferasirox groups. The differences of iron chelators' effects between those receiving short-term (≤7 years) and long-term (>7 years) blood transfusion were also analyzed. Results: The averaged levels of bilirubin, ALT, AST, and ferritin were found to be high. Ferritin was positively correlated with ALT (r=0.508 and p<0.001) and AST ((r=0.569; p<0.001). There was no statistical difference in ferritin levels between the deferiprone and deferasirox groups ( p=0.776). However, higher total bilirubin and ALT were observed in the deferasirox group than in the deferiprone group ( p=0.001 and 0.022, respectively). Total ( p<0.001), indirect ( p<0.001), and direct bilirubin levels ( p=0.015) were significantly higher in patients with long-term transfusions than those receiving short-term transfusions. Higher ferritin was found with a statistical significance of p=0.008 in the long-term transfusions group. Conclusions: Ferritin is high in people with transfusion-dependent ß-thalassemia major and positively correlated with ALT and AST. Deferasirox might pose a higher risk of developing hepatic injury as compared with deferiprone. Yet, no significant change of deferasirox efficacy (based on ferritin level) was found between those receiving short-term and long-term transfusions.

Development and Validation of the Knowledge, Attitude, and Practice Questionnaire for Community Pharmacy Personnel in Tuberculosis Case Detection, Drug Monitoring, and Education: A Study from Indonesia.

Background: Validated and standardized structured questionnaires based on psychometric analysis are extremely limited, particularly for assessing community pharmacy personnel's knowledge, attitude, and practice (KAP) in tuberculosis (TB) case detection, drug monitoring, and education. We, therefore, developed and validated a questionnaire to assess the KAP of community pharmacy personnel in TB case detection, drug monitoring, and community education. Methods: This study was conducted in two phases. First, we developed the questionnaire, which included framework development, item generation, individual item content validity index (I-CVI), item screening, and pre-testing. Second, we validated the questionnaire with 400 participants using various analyses, including participant analysis, confirmatory factor analysis (CFA), adjusted goodness-of-fit index (AGFI), comparative fit index (CFI), non-normed fit index (NNFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR). We determined the reliability test using Cronbach's alpha and test-retest reliability using Pearson's correlation. Results: In the development phase, we defined 63 items that comprised 18 sociodemographic, 18 knowledge, 18 attitude, and 9 practice items. Across the 63 items, the I-CVI scores of sociodemographic and KAP items were one each. The CFA model parameter values were X2/df= 2.28; AGFI = 0.95; CFI = 0.99; NNFI = 0.98; RMSEA = 0.06; and SRMR = 0.03 (p < 0.05 for all). Cronbach's alpha coefficients of KAP items were 0.75, 0.91, and 0.95, respectively. The test-retest reliability coefficients of KAP were 0.84, 0.55, and 0.91, respectively (p < 0.01). Conclusion: This study indicates that the developed questionnaire is a valid and reliable instrument for assessing the KAP of community pharmacy personnel for TB case detection, drug monitoring, and community education in Indonesia. Community pharmacy personnel can support TB notification and treatment by assessing their prospective roles in surveys using this questionnaire, enabling TB eradication in 2030.

Knowledge, attitude and practice of community pharmacy personnel in tuberculosis patient detection: a multicentre cross-sectional study in a high-burden tuberculosis setting.

INTRODUCTION: Control of tuberculosis (TB) is hampered by suboptimal case detection and subsequent delays in treatment, which is worsened by the COVID-19 pandemic. The community pharmacy is reported as the place for first aid medication among patients with TB. We, therefore, analysed knowledge, attitude and practice (KAP) on TB patient detection (TBPD) of community pharmacy personnel, aiming to find innovative strategies to engage community pharmacies in TBPD. METHODS: A multicentre cross-sectional study was performed in four areas of Indonesia's eastern, central and western parts. Pharmacists and pharmacy technicians who worked in community pharmacies were assessed for their characteristics and KAP related to TBPD. Descriptive analysis was used to assess participant characteristics and their KAP, while multivariable regression analyses were used to analyse factors associated with the KAP on TBPD. RESULTS: A total of 1129 participants from 979 pharmacies, comprising pharmacists (56.6%) and pharmacy technicians (43.4%), were included. Most participants knew about TB. However, knowledge related to TB symptoms, populations at risk and medication for TB were still suboptimal. Most participants showed a positive attitude towards TBPD. They believed in their professional role (75.1%), capacity in TB screening (65.4%) and responsibility for TBPD (67.4%). Nevertheless, a lack of TBPD practice was identified in most participants. Several factors significantly associated with performing the TBPD practice (p<0.05), such as TB training experience (p<0.001), provision of a drug consultation service (p<0.001), male gender (p<0.05), a positive attitude towards TBPD (p<0.001), short working hours (p<0.001) and central city location of the pharmacy (p<0.05). CONCLUSIONS: Most participants had good knowledge and attitude, which did not translate into actual TBPD practice. We identified that TB educational programmes are essential in improving the KAP. A comprehensive assessment is needed to develop effective strategies to engage the community pharmacy in TBPD activities.

Pharmacists Intervention Reduced Drug-Related Problems in the Treatment of Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) remains as a global public health problem, including Indonesia due to its continuous increasing prevalence. AIM: To analyze the impact of pharmacist intervention on drug-related problems (DRPs) occurred in the management of patients with T2DM admitted to Tebing Tinggi Hospital (TTH), Indonesia, period March through August 2018. METHODS: This six-month retrospective prospective cohort study evaluated the impact of pharmacist intervention on the occurrence of DRPs in the management of patients with T2DM (n = 45) insured by Social Security Organizing Body in TTH, North Sumatera, Indonesia. The inclusion criteria were T2DM patients with age ≥ 18 years and under treatment of antidiabetic drugs. A questionnaire was used to assess the characteristics of the patients and antidiabetic drugs provided. The incidence of DRPs in groups with usual care for the previous three-month and with pharmacist interventions for the next three-month admissions were analyzed using Pharmaceutical Care Network Europe (PCNE) DRP classification system version 8.01 that consists of 3 primary domains for problems, 8 primary domains for causes, and 5 primary domains (PCNE, 2017) and trustable literatures. The obtained data were analyzed using descriptive statistics and paired t test in the program of Statistical Package for the Social Sciences version 19 (p < 0.05 was considered significant). RESULTS: Most (66.7%) of the patients were female. Their mean age was 61.96 ± 6.45 (years). The three most widely provided drugs were metformin, glimepirid, and gliclazide. Total incidence of DRPs in groups with: usual care, 128; intervention, 39. There was a significant difference between the incidence of DRPs in groups with usual care and intervention, p ≤ 0.001. CONCLUSION: Pharmacist intervention reduced the incidence of DRPs in the management of T2DM patients.

Sociological and Psychological Factors on Prohibited Substances Abuse in Rehabilitation Centre of Medan City, Indonesia.

INTRODUCTION: Prohibited substances issue and their abuse have become a scourge for people in Indonesia. This situation creates concern for every level of society since this is very influential to damage and can even eliminate generations at a later time. AIM: This study aims to determine the characteristics of age, education, psychological and social problems related to substance dependence experienced by individuals with substance disorders who undergo rehabilitation in Medan, Indonesia. METHODS: This study is a cross-sectional analytic, in which the sample of this study was individuals who underwent rehabilitation in the Rehabilitation Center in Medan City who fulfilled the inclusion and exclusion criteria. A structured interview was carried out with the MINI ICD-10 on part M. disorders related to psychoactive substances. Furthermore, to see the level of dependence, WHO ASSIST questionnaire (The Alcohol, Smoking and Substance Involvement Screening Test) was used. RESULTS: This study discovered that subjects with age above 21 years were the most dominant of the prohibited substance users group as many as 87 people (69%), Batak tribe with 73 people (57.9%), residence originating from outside the city with 70 people (55.6%), Unmarried with 87 people (70.2%), education level is medium (junior high school) with 117 people (92.9%) and work as many as 77 people (61.1%). The study also found that the most dominant number of prohibited substances users were single users of methamphetamine and a combination of two substances, each of which was 49 people (38.9%). There is no relationship between social factors and patterns of prohibited substance use. Also, the most dominant users of prohibited substances who undergo rehabilitation are those based on family and police (involuntary admission). Finally, as many as 70 people used methamphetamine require intensive intervention. CONCLUSION: This study shows that social and demographic factors are not related to the pattern of prohibited substance use.