A Case-Based Monitoring Approach to Evaluate Safety of COVID-19 Vaccines in a Partially Integrated Health Information System: A Study Protocol.

In response to Coronavirus disease 2019 (COVID-19) global pandemic, various COVID-19 vaccines were rapidly administered under emergency use authorization. Rare outcomes associated with COVID-19 vaccines might be less likely to be captured in clinical trials, leading to a knowledge gap in real-world vaccine safety. In contrast with high-income countries, many low-to-middle income countries have limited capacity to conduct active surveillance, owing to the absence of large and fully-integrated health information databases. This paper describes the study protocol, which aims to investigate risk of prespecified adverse events of special interests following COVID-19 vaccination in a partially integrated health information system with non-shareable electronic health records. The SAFECOVAC study is a longitudinal, observational retrospective study of active safety surveillance using case-based monitoring approach. This involves linkage of several administrative databases and hospitalization data monitoring to identify adverse events of special interests following administration of COVID-19 vaccines in Malaysia. The source population comprises of all individuals who received at least one dose of COVID-19 vaccine. Self-controlled design and vaccinated case-coverage design will be employed to assess risk of adverse events of special interests and determine the association with vaccine exposure. Data on vaccination records will be obtained from the national COVID-19 vaccination register to identify the vaccination platforms, doses and the timing of vaccinations. The outcome of this study is hospitalization for the adverse events of special interests between March 2021 and June 2022. The outcomes will be obtained through linkage with hospital admission database and national pharmacovigilance database. Findings will provide analysis of real-world data which can inform deliberations by government and public health decision makers relative to the refinement of COVID-19 vaccination recommendations.

Effects of CYP3A5 Polymorphism on Rapid Progression of Chronic Kidney Disease: A Prospective, Multicentre Study.

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of >5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy-Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.

Factors associated with the frequency of antihypertensive drug adjustments in chronic kidney disease patients: a multicentre, 2-year retrospective study.

Background Optimum antihypertensive drug effect in chronic kidney disease is important to mitigate disease progression. As frequent adjustments to antihypertensive drugs might lead to problems that may affect their effectiveness, the modifiable factors leading to frequent adjustments of antihypertensive drugs should be identified and addressed. Objective This study aims to identify the factors associated with frequent adjustments to antihypertensive drugs among chronic kidney disease patients receiving routine nephrology care. Setting Nephrology clinics at two Malaysian tertiary hospitals. Method This multi-centre, retrospective cohort study included adult patients under chronic kidney disease clinic follow-up. Demographic data, clinical information, laboratory data and medication characteristics from 2018 to 2020 were collected. Multiple logistic regression was used to identify the factors associated with frequent adjustments to antihypertensive drugs (≥ 1 per year). Main outcome measure Frequent adjustments to antihypertensive drugs. Results From 671 patients included in the study, 219 (32.6%) had frequent adjustments to antihypertensive drugs. Frequent adjustment to antihypertensive drugs was more likely to occur with follow-ups in multiple institutions (adjusted Odds Ratio [aOR] 1.244, 95% confidence interval [CI] 1.012, 1.530), use of traditional/complementary medicine (aOR 2.058, 95% CI 1.058, 4.001), poor medication adherence (aOR 1.563, 95% CI 1.037, 2.357), change in estimated glomerular filtration rate (aOR 0.970, 95% CI 0.951, 0.990), and albuminuria categories A2 (aOR 2.173, 95% CI 1.311, 3.603) and A3 (aOR 2.117, 95% CI 1.349, 3.322), after controlling for confounding factors. Conclusion This work highlights the importance of close monitoring of patients requiring initial adjustments to antihypertensive drugs. Antihypertensive drug adjustments may indicate events that could contribute to poorer outcomes in the future.

Continuous medication monitoring: A clinical model to predict adherence to medications among chronic kidney disease patients.

BACKGROUND: An adherence model is required to optimise medication management among chronic kidney disease (CKD) patients, as current assessment methods overestimate the true adherence of CKD patients with complex regimens. An approach to assess adherence to individual medications is required to assist pharmacists in addressing non-adherence. OBJECTIVE: To develop an adherence prediction model for CKD patients. METHODS: This multi-centre, cross-sectional study was conducted in 10 tertiary hospitals in Malaysia using simple random sampling of CKD patients with ≥1 medication (sample size = 1012). A questionnaire-based collection of patient characteristics, adherence (defined as ≥80% consumption of each medication for the past one month), and knowledge of each medication (dose, frequency, indication, and administration) was performed. Continuous data were converted to categorical data, based on the median values, and then stratified and analysed. An adherence prediction model was developed through multiple logistic regression in the development group (n = 677) and validated on the remaining one-third of the sample (n = 335). Beta-coefficient values were then used to determine adherence scores (ranging from 0 to 7) based on the predictors identified, with lower scores indicating poorer medication adherence. RESULTS: Most of the 1012 patients had poor medication adherence (n = 715, 70.6%) and half had good medication knowledge (n = 506, 50%). Multiple logistic regression analysis determined 4 significant predictors of adherence: ≤7 medications (constructed score = 2, p < 0.001), ≤3 co-morbidities (constructed score = 1, p = 0.015), absence of complementary/alternative medicine use (constructed score = 1, p = 0.003), and knowledge score ≥80% (constructed score = 3, p < 0.001). A higher total constructed score from the prediction model indicated a higher likelihood of adherence (odds ratio [OR]: 2.41; 95% confidence interval [CI]: 2.112-2.744; p < 0.001). The area under the receiver operating characteristic (ROC) curve of the developed model (n = 677) had good accuracy (ROC: 0.867, 95% CI: 0.840-0.896; p < 0.001). The validated model (n = 335) also had good accuracy (ROC: 0.812, 95% CI: 0.765-0.859; p < 0.001). There was no significant difference between the development and validation groups (p = 0.11, Z-value:1.62, standard error: 0.034). CONCLUSION: The score constructed from the medication adherence prediction model for CKD patients had good accuracy and could be useful for identifying patients with a higher risk of non-adherence, to ensure optimised adherence management.

Hepatic adverse drug reactions in Malaysia: An 18-year review of the national centralized reporting system.

PURPOSE: To determine the incidence, demographic profile, background of reporters, causative agents, severity and clinical outcomes of hepatic adverse drug reaction (ADR) reports in Malaysia using the national ADR reporting database. METHODS: The ADR reports recorded between 2000 and 2017 were retrospectively analysed to identify hepatic ADR reports. The trend and characteristics of hepatic ADR cases were described. Multivariate disproportionality analysis of the causative agents was performed to generate signals of hepatic ADRs. RESULTS: A total of 2090 hepatic ADRs (1.77% of all ADRs) were reported with mortality rate of 12.7% among cases with known clinical outcomes. The incidence of hepatic ADR reporting in Malaysia increased significantly over 18 years from 0.26 to 9.45 per million population (P < .001). Antituberculosis drugs (n = 268, 12.82%) was the most common suspected class of causative agents with a reporting odds ratio (ROR) and 95% CI of 8.39 (7.26-9.70), followed by traditional/complementary medicines or herbal/dietary supplements (TCM/HDS) (n = 235, 11.24%, ROR 3.26 [2.84-3.75]), systemic antibacterials (n = 159, 7.61%, ROR 2.65 [2.25-3.13]), lipid modifying agents (n = 142, 6.79%, ROR 2.21 [1.86-2.63]) and amiodarone (n = 137, 6.56%, ROR 35.25 [28.40-43.75]). Most (72.9%) of the TCM/HDS were not registered with the authorities. CONCLUSIONS: Hepatic ADR cases have increased significantly in Malaysia, with antituberculosis drugs, systemic antibacterials, and TCM/HDS being the most common causative agents reported. Most TCM/HDS reported to be associated with hepatic ADR were not registered with the authorities.