Population Pharmacokinetic Model of Intravenous Immunoglobulin in Patients Treated for Various Immune System Disorders.

PURPOSE: Intravenous immunoglobulin (IVIG) is used to treat various immune system disorders, but the factors influencing its disposition are not well understood. This study aimed to estimate the population pharmacokinetic parameters of IVIG and to investigate the effect of genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor (FcRn) and clinical variability on the pharmacokinetic properties of IVIG in patients with immune system disorders. METHODS: Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis. FINDINGS: A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG. IMPLICATIONS: This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.

Effect of CYP3A5*3, ABCC2 C-24T, and ABCC2 C3972T Genetic Polymorphisms on Direct Cost of Kidney Transplant Recipients.

Introduction Genetic variations can influence how kidney transplant recipients (KTRs) respond to immunosuppressive drugs. However, limited resources necessitate a cost-benefit analysis of pharmacogenetic testing to determine its role in routine practice. This study investigated the cost-effectiveness of three genetic polymorphisms (CYP3A5*3, ABCC2 -24C>T, and ABCC2 3972C>T) in KTRs. Methods This was a multicenter, prospective observational cohort study that included patients on tacrolimus-mycophenolate-prednisolone treatment. Ethnically diverse adult KTRs who had undergone kidney transplantation between 2020 and 2021 and consented were enrolled in the study. Deoxyribonucleic acid (DNA) was extracted from the collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T, and ABCC2 3972C>T single nucleotide polymorphisms (SNPs) were determined by polymerase chain reaction (PCR). Results Data was analyzed from 39 KTRs with an average age of 32.2 ± 7.0 years. The median annual healthcare cost per patient was MYR 52,700 (laboratory tests and immunosuppressants being the highest expenses). Notably, the annual cost was significantly higher in patients with the CYP3A5*3 variant compared to the wildtype (p < 0.001). Furthermore, an incremental cost-effectiveness analysis revealed that carriers of the CYP3A5*1 wildtype allele, the ABCC2 -24C>T T variant allele, and the ABCC2 3972C>T T variant allele were associated with a more cost-effective approach to kidney transplantation management, potentially reducing the risk of graft rejection and acute tubular necrosis (ATN). Conclusion While these findings suggest potential cost benefits for specific genotypes, further research with larger and more diverse patient populations is necessary to definitively establish the role of pharmacogenetic testing in optimizing cost-effectiveness for KTRs.

Development and validation of a predictive scoring model for risk stratification of tuberculosis treatment interruption.

BACKGROUND: Tuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission. OBJECTIVES: This study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption. METHODS: A multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance. RESULTS: Of 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0-2), medium (3-5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001). CONCLUSION: The predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase.

Health-Related Quality of Life And Economic Analysis of Olanzapine Versus Aprepitant in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Malaysia.

OBJECTIVES: Olanzapine has been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) after highly emetogenic chemotherapy (HEC); however, there is limited work on the impact of CINV on health-related quality of life (HRQoL) and the comparative cost-effectiveness of CINV prophylaxis in the Malaysian context. Therefore, this study was conducted to determine the HRQoL using EQ-5D-5L and the cost-effectiveness of olanzapine compared with aprepitant for CINV prophylaxis in Malaysia using data from a local study. METHODS: Fifty-nine chemo-naive patients receiving either olanzapine or aprepitant were randomly recruited and completed the EQ-5D-5L before and day 5 after HEC. HRQoL utility scores were analyzed according to the Malaysian valuation set. The economic evaluation was conducted from a healthcare payer perspective with a 5-day time horizon. Quality-adjusted life days (QALD) and the rate of successfully treated patients were used to measure health effects. The incremental cost-effectiveness ratio is assessed as the mean difference between groups' costs per mean difference in health effects. A one-way sensitivity analysis was performed to assess variations that might affect outcomes. RESULTS: Aprepitant and olanzapine arms' patients had comparable baseline mean HRQoL utility scores of 0.920 (SD = 0.097) and 0.930 (SD = 0.117), respectively; however, on day 5, a significant difference (P value = .006) was observed with mean score of 0.778 (SD = 0.168) for aprepitant and 0.889 (SD = 0.133) for olanzapine. The cost per successfully treated patient in the aprepitant arm was 60 times greater than in the olanzapine arm (Malaysian Ringgit [MYR] 927 vs MYR 14.83). Likewise, the cost per QALD gain in the aprepitant arm was 36 times higher than in the olanzapine arm (MYR 57.05 vs MYR 1.57). Incremental cost-effectiveness ratio of MYR -937.00 (USD -200.98) per successfully treated patient and MYR -391.84 (USD -85.43) per QALD gained for olanzapine compared with the aprepitant-based regimen. CONCLUSIONS: An olanzapine-based regimen is a cost-effective therapeutic substitution in patients receiving HEC in Malaysia.

Safe use elements of finished herbal products: insights from consumers and practitioners in Malaysia.

BACKGROUND: The use of finished herbal products (FHPs) among Malaysians today is expanding rapidly leading to a huge market of FHPs in the country. However, the mass production of FHPs in today's market is alarming due to safety-use issues that could lead to serious adverse effects. Nevertheless, demands are still high for FHPs as most consumers perceived it as safe to consume as it is made from natural substances as the active ingredients. This study aims to explore the safe use elements of FHPs identified by two stakeholders: consumers and practitioners in Malaysia and further compare these elements with the current regulations. METHODS: As an exploratory study, its approach is to investigate at an in-depth level of understanding of safe use elements from the involved stakeholders: consumers and practitioners. We had a total of 4 focus group discussion sessions (1 FGD session with consumer and 3 FGD sessions with practitioners) as a method of collecting data from the participants. The FGDs were conducted in local native Malaysian and then being translated by researchers without changing their meanings. Thematic analysis was done which involves methodically reading through the verbatim transcripts and consequently segmenting and coding the text into categories that highlight what the participants have discussed. RESULTS: From the result, we found that both practitioners and consumers agreed a safe FHP must be in compliance with the guidelines from the Ministry of Health Malaysia (MOH). There are other safe use elements highlighted including halal certification, trusted over-the-counter outlets, and published reports on the safety, efficacy, and quality. CONCLUSIONS: In conclusion, both practitioners and consumers agreed that the most important safe-use element is compliance with MOH guidelines, but the depth of discussion regarding the safety elements among these stakeholders holds a very huge gap. Thus, initiatives must be planned to increase the knowledge and understanding about the MOH guidelines towards achieving a sustainable ecosystem in the safe use of FHPs.

The Impact of ABCC2 -24C>T Gene Polymorphism on Graft Survival in Kidney Transplant Recipients.

Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T and ABCC2 3972C>T SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype ABCC2 -24C>T C allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, p = 0.038). Recipients who had delayed graft function (aOR: 49.214, p = 0.012) and a history of CMV infection (aOR: 18.097, p = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the ABCC2 -24C>T genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on ABCC2 -24C>T effects in long-term KTR.

Methylprednisolone use in hospitalised COVID-19 patients: a retrospective study.

Introduction: Trials have demonstrated the benefits of methylprednisolone in the treatment of coronavirus disease 2019 (COVID-19). However, data on optimal dose, duration and timing of administration are limited. This study investigates the outcome of various methylprednisolone treatment regimens among hospitalised COVID-19 patients. Methods: A retrospective cohort study was conducted on hospitalised adult COVID-19 patients admitted between June and August 2021 in general COVID-19 wards, treated with methylprednisolone. Clinical outcomes evaluated include in-hospital mortality, thirty-day mortality, clinical efficacy (C-reactive protein (CRP), total white blood cells (TWBC) and oxygen requirement) as well as the safety of methylprednisolone. Results: Of 278 patients, 1(0.4%) received weight-based dosing of 1 mg/kg/day, 101(36.3%) received weight-based dosing of 2 mg/kg/day, 130(46.8%) received fixed dosing methylprednisolone 250 mg/day and 46(16.5%) received fixed dosing methylprednisolone 500 mg/day. There was a significant difference in in-hospital mortality rates following different methylprednisolone doses whereby in-hospital mortality occurred in 22.5% (n = 23) of patients with 1 or 2 mg/kg/day methylprednisolone, 32.3% (n = 42) with 250 mg/day and 39.1% (n = 18) with 500 mg/day (p = 0.023). On the other hand, no significant difference in thirty-day mortality, clinical efficacy and safety was observed between different dosing regimens (p > 0.05). Conclusion: The use of methylprednisolone weight-based dosing in hospitalised COVID-19 patients should be considered due to the positive outcome associated with lower in-hospital mortality.

Prevalence, Risk Factors, and Management of Metabolic Acidosis in Chronic Kidney Disease Patients: A Multicenter Retrospective Study in Malaysia.

Background Metabolic acidosis in chronic kidney disease (CKD) patients has lately gained attention due to the growing evidence of its treatment benefits. This study aims to provide baseline data on the prevalence, risk factors, and current management of metabolic acidosis among the pre-dialysis adult Malaysian CKD population. Methodology This multicenter cross-sectional retrospective study involved pre-dialysis CKD patients above 18 years old on regular nephrology clinic follow-up at three Malaysian government hospitals with nephrology subspecialty. Demographic data, clinical information, laboratory data, and a list of concomitant medications were collected. Factors associated with the occurrence of metabolic acidosis were identified via multiple logistic regression. Results Six hundred and fifty-seven CKD patients were screened for this study, in which only 39.4% (n=259) had available bicarbonate levels. From this, a total of 86.1% (n=223) had metabolic acidosis. Higher estimated glomerular filtration rate (odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-1.00, p=0.043) and those with cardiovascular disease (OR 0.33, 95% CI 0.15-0.73; p=0.007) were significantly associated with lower odds of metabolic acidosis. There were 43.0% (n=96) on alkali therapy with sodium bicarbonate solution being the most common (n=91, 94.8%). Among those receiving alkali therapy, only 19.8% (n=19) achieved bicarbonate levels of ≥ 22 mEq/L. Conclusion Our study showed that metabolic acidosis was highly prevalent, although few achieved target levels despite supplementation, supporting the need for focused management of metabolic acidosis in the CKD population.

Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

OBJECTIVES: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. METHODS: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. RESULTS: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). CONCLUSION: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Polypharmacy and medication regimen complexity in transfusion-dependent thalassaemia patients: a cross- sectional study.

BACKGROUND: Medication burden and complexity have been longstanding problems in chronically ill patients. However, more data are needed on the extent and impact of medication burden and complexity in the transfusion-dependent thalassaemia population. AIM: The aim of this study was to determine the characteristics of medication complexity and polypharmacy and determine their relationship with drug-related problems (DRP) and control of iron overload in transfusion-dependent thalassaemia patients. METHOD: Data were derived from a cross-sectional observational study on characteristics of DRPs conducted at a Malaysian tertiary hospital. The medication regimen complexity index (MRCI) was determined using a validated tool, and polypharmacy was defined as the chronic use of five or more medications. The receiver operating characteristic curve analysis was used to determine the optimal cut-off value for MRCI, and logistic regression analysis was conducted. RESULTS: The study enrolled 200 adult patients. The MRCI cut-off point was proposed to be 17.5 (Area Under Curve = 0.722; sensitivity of 73.3% and specificity of 62.0%). Approximately 73% and 64.5% of the patients had polypharmacy and high MRCI, respectively. Findings indicated that DRP was a full mediator in the association between MRCI and iron overload. CONCLUSION: Transfusion-dependent thalassaemia patients have high MRCI and suboptimal control of iron overload conditions in the presence of DRPs. Thus, future interventions should consider MRCI and DRP as factors in serum iron control.

Corrigendum: Drug-related problems among transfusion-dependent thalassemia patients: a real-world evidence study.

[This corrects the article DOI: 10.3389/fphar.2023.1128887.].

Digital Health in Enhancing Antiretroviral Therapy Adherence: A Systematic Review and Meta-Analysis.

Adherence to antiretroviral therapy (ART) is essential in determining successful treatment of human immunodeficiency virus (HIV). The adoption of digital health is suggested to improve ART adherence among people living with HIV (PLHIV). This study aimed to systematically determine the effect of digital health in enhancing ART adherence among PLHIV from published studies. The systematic search was conducted on Scopus, Web of Science (WoS), PubMed, Ovid, EBSCOHost, and Google Scholar databases up to June 2022. Studies utilized any digital health as an intervention for ART adherence enhancement and ART adherence status as study's outcome was included. Digital health refers to the use of information and communication technologies to improve health. Quality assessment and data analysis were carried out using Review Manager (RevMan) version 5.4. A random-effects model computed the pooled odds ratio between intervention and control groups. The search produced a total of 1864 articles. Eleven articles were eligible for analysis. Digital health was used as follows: six studies used short message service or text message alone, three studies used mobile applications, and two studies used combination method. Four studies showed statistically significant impacts of digital health on ART adherence, while seven studies reported insignificant results. Results showed studies conducted using combination approach of digital health produced more promising outcome in ART adherence compared to single approach. New innovative in combination ways is required to address potential benefits of digital health in promoting ART adherence among PLHIV.

Drug-related problems among transfusion-dependent thalassemia patients: A real-world evidence study.

Introduction: Thalassemia is among the most common genetic disorders globally and many patients suffer from iron overload (IOL) complications that mainly affect the heart, liver and endocrine system. These events may be further complicated by drug-related problems (DRP), an inherent issue among patients with chronic diseases. Objective: The study aimed to evaluate the burden, associated factors and impacts of DRP in transfusion-dependent thalassemia (TDT) patients. Method: Eligible TDT patients under follow-up in a tertiary hospital between 01 March 2020 to 30 April 2021 were interviewed and their medical records were reviewed retrospectively to identify any DRP. DRPs were classified using the Pharmaceutical Care Network Europe (PCNE) classification version 9.1. The incidence and preventability of DRP were assessed and the associated risk factors were estimated by univariate and multivariate logistic regression. Results: A total of 200 patients were enrolled with a median (interquartile range: IQR) age of 28 years at enrolment. Approximately 1 in 2 patients were observed to suffer from thalassemia-related complications. Throughout the study period, 308 DRPs were identified among 150 (75%) participants, with a median DRP per participant of 2.0 (IQR 1.0-3.0). Of the three DRP dimensions, treatment effectiveness was the most common DRP (55.8%) followed by treatment safety (39.6%) and other DRP (4.6%). The median serum ferritin level was statistically higher in patients with DRP compared with patients without DRP (3833.02 vs. 1104.98 µg/L, p < 0.001). Three risk factors were found to be significantly associated with the presence of DRP. Patients with frequent blood transfusion, moderate to high Medication Complexity Index (MRCI) and of Malay ethnicity were associated with higher odds of having a DRP (AOR 4.09, 95% CI: 1.83, 9.15; AOR 4.50, 95% CI: 1.89, 10.75; and AOR 3.26, 95% CI: 1.43, 7.43, respectively). Conclusion: The prevalence of DRP was relatively high amongst TDT patients. Increased medication complexity, more severe form of the disease and Malay patients were more likely to experience DRP. Hence, more viable interventions targeted to these groups of patients should be undertaken to mitigate the risk of DRP and achieve better treatment outcomes.

Psychometric evaluation of Oral Mucositis Daily Questionnaire: A cross-cultural adaptation of the Malay version in multiethnic adult autologous stem cell transplant.

Objective: Mucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. Methods: A total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann-Whitney U and CFA, respectively. Results: OMDQ-Mal demonstrated high internal consistency (α â€‹= â€‹0.874). Test-retest reliability between paired days were moderate to excellent (95% CI â€‹= â€‹0.676-0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ â€‹= â€‹0.503-0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708-0.952; composite reliability 0.879-0.974; average variant extracted 0.710-0.841; and heterotrait-monotrait ratio 0.528 established the convergent and divergent validity. Conclusions: In conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.

Prevalence and predictive factors of tuberculosis treatment interruption in the Asia region: a systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) treatment interruption remains a critical challenge leading to poor treatment outcomes. Two-thirds of global new TB cases are mostly contributed by Asian countries, prompting systematic analysis of predictors for treatment interruption due to the variable findings. METHODS: Articles published from 2012 to 2021 were searched through seven databases. Studies that established the relationship for risk factors of TB treatment interruption among adult Asian were included. Relevant articles were screened, extracted and appraised using Joanna Briggs Institute's checklists for cohort, case-control and cross-sectional study designs by three reviewers. Meta-analysis was performed using the random effect model in Review Manager software. The pooled prevalence and predictors of treatment interruption were expressed in ORs with 95% CIs; heterogeneity was assessed using the I2 statistic. The publication bias was visually inspected using the funnel plot. RESULTS: Fifty eligible studies (658 304 participants) from 17 Asian countries were included. The overall pooled prevalence of treatment interruption was 17% (95% CI 16% to 18%), the highest in Southern Asia (22% (95% CI 16% to 29%)), followed by Eastern Asia (18% (95% CI 16% to 20%)) and South East Asia (16% (95% CI 4% to 28%)). Seven predictors were identified to increase the risk of treatment interruption, namely, male gender (OR 1.38 (95% CI 1.26 to 1.51)), employment (OR 1.43 (95% CI 1.11 to 1.84)), alcohol intake (OR 2.24 (95% CI 1.58 to 3.18)), smoking (OR 2.74 (95% CI 1.98 to 3.78)), HIV-positive (OR 1.50 (95% CI 1.15 to 1.96)), adverse drug reactions (OR 2.01 (95% CI 1.20 to 3.34)) and previously treated cases (OR 1.77 (95% CI 1.39 to 2.26)). All predictors demonstrated substantial heterogeneity except employment and HIV status with no publication bias. CONCLUSION: The identification of predictors for TB treatment interruption enables strategised planning and collective intervention to be targeted at the high-risk groups to strengthen TB care and control in the Asia region.

Corticosteroid effectiveness among hospitalised COVID-19 patients in Malaysia.

INTRODUCTION: Using steroids to manage hospitalised coronavirus disease 2019 (COVID-19) patients caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been shown to reduce the need for mechanical ventilation and mortality. To date, low-dose dexamethasone and methylprednisolone corticosteroids have been effective in reducing the infection's progress in hospitalised patients. However, it is unknown if high dosages of corticosteroids can achieve a better clinical outcome. This study aims to compare the clinical outcomes of hospitalised COVID-19 patients who are given a 10-day low-dose corticosteroid treatment (IV 2 mg/kg/day methylprednisolone loading dose (LD) then 0.25 mg/kg four times a day (q.i.d.)) with patients given a 10-day high-dose corticosteroid treatment (IV 20 mg dexamethasone once daily (o.d.) or a 1.5 mg/kg prednisolone tablet o.d.). METHODOLOGY: Retrospective data on hospitalised COVID-19 patients were collected for this study, and the primary outcome measure was the patients' clinical status based on the World Health Organization's (WHO) Ordinal Scale for Clinical Improvement (OSCI) on Day-5 and Day-10 post-steroid. RESULTS: The results demonstrated that using steroids significantly improved patients' clinical outcomes from a WHO OSCI level of 4 (0.1) on Day-1 to 2.6 (2.5) on Day-5 (p < 0.001). There was no significant difference in clinical outcome between low-dose and high-dose corticosteroid treatment on Day-5 (H = 2.15; p = 0.34) and Day-10 (H = 1.12; p = 0.58). CONCLUSIONS: This study concludes that using low-dose corticosteroids is recommended for hospitalised COVID-19 patients to ensure clinical outcomes are optimised.

The survival impact of palliative chemotherapy dose modifications on metastatic colon cancer.

BACKGROUND: An uninterrupted dose of oxaliplatin-based cytotoxic therapy is an essential component in the standard treatment regimen of metastatic colon cancer (mCC). Data on the impacts of dose intensity reduction on the palliative treatment for patients with mCC remain scarce. Hence, this study aimed to investigate the impact of palliative chemotherapy dose modifications (DM) on the survival of patients with mCC. METHODS: Patients with stage IV colon cancer who received first-line palliative FOLFOX regimen chemotherapy between 2014 until 2018 in the Oncology Department of the National Cancer Institute were conveniently sampled retrospectively to analyse the treatment efficacy. The cumulative dose and duration of chemotherapy received by the patients were summarised as relative dose intensity (RDI) and stratified as High RDI (RDI ≥ 70%) or Low RDI (RDI < 70%). Progression-free survival (PFS) and 2-year overall survival (OS) between the two groups were analysed using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Out of the 414 patients identified, 95 patients with mCC were eligible and included in the final analysis. About half of the patients (n = 47) completed the 12-cycle chemotherapy regimen and one patient received the complete (100%) RDI. The overall median RDI was 68.7%. The Low RDI group (n = 49) had a 1.5 times higher mortality risk than the High RDI group [OS, Hazard Ratio (HR) = 1.5, 95% Cl: 1.19-1.82] with a significant median OS difference (9.1 vs. 16.0 months, p <  0.01). Furthermore, patients with lower dose intensity showed double the risk of disease progression (PFS, HR = 2.0, 95% CI: 1.23-3.13) with a significant difference of 4.5 months of median PFS (p <  0.01). Gender and RDI were the independent prognostic factors of both OS and PFS. CONCLUSION: Reduction in the dose intensity of palliative chemotherapy may adversely affect both disease progression and overall survival among mCC patients.

Prescribing Practices of Intravenous Immunoglobulin in Tertiary Care Hospitals in Malaysia: A Need for a National Guideline for Immunoglobulin Use.

Rational use of drug involves the use of medicine as per clinical guidelines. Given the steady increase in the clinical utility of intravenous immunoglobulin (IVIG) either as licensed or off-label use, concerns are being raised about the possibility of supply shortages that could significantly impact patient care. Therefore, there is a need to regulate and to promote the rational use of this valuable medication. This cross-sectional chart review study attempts to evaluate the prescribing patterns of IVIG at two tertiary hospitals in Malaysia. Patients' medical files and dispensing records were examined and compared with current guidelines. A total of 348 prescriptions for IVIG were written during the 1-year study period. The highest usage of IVIG was for neurological (47.9%), immunological (27.5%), and hematological conditions (20%). The number of prescriptions with the US Food and Drug Administration (FDA) licensed indications and off-label indications was 148 (42.5%) and 200 (57.5%), respectively. Age (OR: 1.02, 95% CI: 1.01-1.03, p = 0.003) and those admitted to the critical care units (OR: 11.11, 95% CI: 5.60-22.05, p < 0.001) were significant factors for receiving IVIG for an off-label indication. Most prescriptions (79%) had appropriate dosing. Significant factors associated with receiving inappropriate dose of IVIG include age (OR: 0.93, 95% CI: 0.89-0.97, p = 0.001) and those admitted to the critical care units (OR: 10.15, 95% CI: 3.81-27.06, p < 0.001). This study advocates the development and implementation of evidence-based clinical guidelines with prioritization protocol to ensure rational use of IVIG.

Adverse Drug Reactions of Antihypertensives and CYP3A5*3 Polymorphism Among Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.

A retrospective study on chemotherapy-induced nausea and vomiting in highly/moderately emetogenic chemotherapy: incidence and prescribing practice.

BACKGROUND: Chemotherapy-induced nausea vomiting (CINV) is a common and significant problem in oncology patients and rated as one of cancer chemotherapy's most distressing side effects. The objectives of this study are to describe the incidence of CINV in highly and moderately emetogenic chemotherapy-treated patients and the prescribing pattern of CINV prophylaxis. METHODS: This retrospective, cross-sectional single-center study randomly collected data on demographics, CINV episodes, and prescribing patterns for adult oncology patients receiving intravenous highly or moderately emetogenic chemotherapy (HEC/MEC) between January and December 2019. RESULTS: A total of 419 randomly selected records of HEC/MEC recipients with 2388 total chemotherapy cycles were included. The mean age was 53.6 ± 12.6 years old. The majority was female (66%), Malay (54.4%), diagnosed with cancer stage IV (47.7%), and with no comorbidities (47%). All patients were prescribed with IV granisetron and dexamethasone before chemotherapy for acute prevention, whereas dexamethasone and metoclopramide were prescribed for delayed prevention. Aprepitant was not routinely prescribed for the prevention of CINV. CINV incidence was 57% in the studied population and 20% in the total cycle. This study found a significant association between CINV incidence with performance status and cisplatin-based chemotherapy (OR = 3.071, CI = 1.515-6.223, p = 0.002; OR = 4.587, CI = 1.739-12.099, p = 0.02, respectively). CONCLUSION: CINV incidence was rather high per patient but relatively low per cycle. Most patients were prescribed with dual regimen antiemetic prophylaxis. IMPACT: This study provides evidence that there was suboptimal use of recommended agents for CINV, and there is a clear need for further improvements in CINV management.