Drug-Related Problems Among Peritoneal Dialysis Patients: A 12-Year Retrospective Cohort Study.

Introduction Studies regarding drug-related problems (DRPs) can be found in other diseases, but data are lacking among peritoneal dialysis (PD) populations. Despite advancements in PD care, there remains a significant gap in understanding and addressing DRPs in the PD population. DRPs can lead to serious consequences, including medication errors, adverse reactions, and nonadherence, affecting patient outcomes and healthcare costs. Aim The aim of this study was to identify the prevalence of DRPs, types, causes, interventions performed, acceptance of interventions, and outcomes of DRPs among patients undergoing PD. In addition to this, the study sought to identify factors associated with DRPs in the PD population. Methods This single-center retrospective study recruited adult PD patients with at least one medication from January 2009 until November 2021. Pharmacy medication therapy adherence clinic (MTAC) clinical activity sheets were reviewed, and DRPs were classified based on the Pharmaceutical Care Network Europe Classification (PCNE) v9.1. The PCNE system consists of five essential domains: Problems (P), Causes (C), Interventions (I), Acceptance of the Intervention (A), and Outcomes (O). As part of the pharmacists' MTAC activities, DRPs were meticulously documented. Three pharmacists initially gathered and examined these recorded DRPs. Each identified DRP was then classified according to the type of problem, the underlying cause, any intervention performed to address the DRP, the level of acceptance, and the resulting outcome. Subsequently, these classifications were reviewed by two independent pharmacists to ensure accuracy and consistency. Results Out of 562 patients, 70.6% (n = 397) were on more than 10 drugs. Most patients (n = 520, 92.5%) had at least one DRP. From the 3,333 DRPs identified, the most common were effects of drug treatment not optimal (n = 1,595, 47.8%), followed by untreated symptoms (n = 843, 25.3%) and adverse drug events (n = 730, 21.9%). The main cause of the suboptimal treatment effect was patients' noncompliance (n = 891, 55.9%). For untreated symptoms, the main cause was no drug prescribed despite existing indications (n = 789, 93.6%). Interventions for DRPs were at either prescriber level (n = 2,064, 61.9%), patient-level (n = 1,244, 37.3%), or at other levels, such as with nurses (n = 25, 0.8%). Prescribers accepted 83% (n = 1713) of interventions suggested by pharmacists. Overall, 73.2% (n = 2,439) of DRPs were resolved. Number of medications (b = 0.223, 0.102-0.345) and number of MTAC visits (b = 0.381, 0.344-0.419) were predictive factors of the number of DRPs (p < 0.001). Conclusion There is a high prevalence of DRPs in PD patients. Pharmacists play an important role in detecting, intervening, and resolving DRPs to improve patients' outcomes.

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.

Therapeutic drug monitoring-guided piperacillin dosing in critically ill patients undergoing continuous renal replacement therapy: a systematic review.

BACKGROUND: Continuous renal replacement therapy (CRRT) complicates antibiotic dosing in critically ill patients due to altered pharmacokinetics. The optimal dosing of piperacillin remains unclear. Therapeutic drug monitoring (TDM) can personalize piperacillin therapy and improve outcomes. OBJECTIVES: This review investigates the effects of TDM-guided piperacillin dosing on pharmacokinetic target attainment and clinical outcomes in CRRT patients, analyses correlations with clinical outcomes, provides optimal dosing strategies for piperacillin and identifies future research areas. METHODS: A systematic search of PubMed, Scopus and Web of Science was conducted until December 2023, identifying studies on piperacillin pharmacokinetics and clinical outcomes in adult CRRT patients. Data on study characteristics, piperacillin exposures, TDM use, target attainment rates, mortality and length of stay were extracted. The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Eleven observational studies were included. High pharmacokinetic variability was evident, with piperacillin target non-attainment in up to 74% of cases without TDM. Two studies with routine TDM showed increased target attainment rates of 80%-100%. Mortality ranged from 17% to 56%, with supratherapeutic concentrations (≥100 mg/L) associated with higher mortality. The impact of optimized piperacillin exposures on outcomes was inconclusive. Most studies demonstrated a low risk of bias. CONCLUSIONS: TDM-guided piperacillin dosing in CRRT patients improved target attainment rates (≥80%). Mortality rates ranged from 17% to 56%, with inconsistent correlations between drug exposures and survival. Supratherapeutic concentrations were linked to higher mortality. Standardized TDM protocols are needed. Future research should establish clear exposure-response relationships and the impact of TDM on clinical outcomes.

A systematic review of single nucleotide polymorphisms affecting allopurinol pharmacokinetics and serum uric acid level.

Aim: To summarize the effects of single nucleotide polymorphisms (SNPs) on the pharmacokinetics of allopurinol to control uric acid levels.Methods: A comprehensive search was conducted in PubMed, Web of Science and Scopus databases from inception to January 2024, includes 17 articles focusing on SNPs and pharmacokinetics of allopurinol and oxypurinol.Results: A total of 11 SNPs showed a significant association with pharmacokinetics of allopurinol and oxypurinol, as well as their potential clinical implications.Conclusion: SNPs in ATP-binding cassette super-family G member 2 (ABCG2), solute carrier family 2 member 9 (SLC2A9), solute carrier family 17 member 1 (SLC17A1), solute carrier family 22 member 12 (SLC22A12), solute carrier family 22 member 13 (SLC22A13) and PDZ domain containing 1 (PDZK1) genes were associated with allopurinol clearance, while SNPs in aldehyde oxidase 1 (AOX1) genes involved in metabolism of allopurinol. SNPs in gremlin 2, DAN family BMP antagonist (GREM2) gene impacted uric acid control, but the specific mechanism governing the expression of GREM2 remains unknown. Our study indicated that the identified SNPs show contradictory effects, reflecting inconsistencies and differences observed across various studies.

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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.

Challenges in Obtaining and Seeking Information Among Breast Cancer Survivors in an Asian Country: a Qualitative Study.

Breast cancer survivors on adjuvant endocrine therapy (AET) have distinct information-seeking experience compared to those in the diagnosis and intensive treatment phase. This study aimed to understand the challenges in obtaining and seeking information among Malaysian breast cancer survivors. We conducted semi-structured, one-to-one interviews among patients using AET from two hospitals and a local cancer organization. Interviews were conducted until theme saturation was achieved (N = 25). Interviews were de-identified, transcribed verbatim, and analysed using thematic analysis. To ensure rigor, coding was conducted through regular discussions between two researchers and the findings were shared with several participants after analysis was completed. Three main themes were identified: limitations in the healthcare system, pitfalls of seeking information online, and limited information from local sources. The participants perceived that their information needs were not met by their healthcare providers and sought information on the Internet to complement their information needs. However, they were faced with risks of misinformation, information overload, and unethical promotion of health products. Those with limited English proficiency had difficulties in accessing quality information, and suggested that there should be more content created by local health advocates in local languages, with information that is tailored for local cultures. As the Internet has become an important medium of health education, healthcare providers and patients should be equipped with the skills to share and search for information online. Digital health literacy needs to be incorporated in patient education modules to create a more informed and empowered patient community.

Breast cancer prevention and treatment misinformation on Twitter: An analysis of two languages.

Objective: To determine the prevalence and types of misinformation on Twitter related to breast cancer prevention and treatment; and compare the differences between the misinformation in English and Malay tweets. Methods: A total of 6221 tweets related to breast cancer posted between 2018 and 2022 were collected. An oncologist and two pharmacists coded the tweets to differentiate between true information and misinformation, and to analyse the misinformation content. Binary logistic regression was conducted to identify determinants of misinformation. Results: There were 780 tweets related to breast cancer prevention and treatment, and 456 (58.5%) contain misinformation, with significantly more misinformation in Malay compared to English tweets (OR = 6.18, 95% CI: 3.45-11.07, p < 0.001). Other determinants of misinformation were tweets posted by product sellers and posted before the COVID-19 pandemic. Less misinformation was associated with tweets utilising official/peer-reviewed sources of information compared to tweets without external sources and those that utilised less reliable information sources. The top three most common content of misinformation were food and lifestyle, alternative medicine and supplements, comprising exaggerated claims of anti-cancer properties of traditional and natural-based products. Conclusion: Misinformation on breast cancer prevention and treatment is prevalent on social media, with significantly more misinformation in Malay compared to English tweets. Our results highlighted that patients need to be educated on digital health literacy, with emphasis on utilising reliable sources of information and being cautious of any promotional materials that may contain misleading information. More studies need to be conducted in other languages to address the disparity in misinformation.

Effects of mobile apps intervention on medication adherence and type 2 diabetes mellitus control: A systematic review and meta-analysis.

INTRODUCTION: The prevalence of non-adherence to antidiabetic treatment remains high despite various efforts. Thus, the positive effects of the antidiabetic treatment cannot be optimised and the disease progresses to complications. This present systematic review and meta-analysis aimed to evaluate the effects of mobile applications (apps) intervention on medication adherence and type 2 diabetes mellitus (T2DM) control. METHODS: This research was conducted following the PRISMA guidelines. The databases that had been searched included Web of Science, PubMed, Scopus, Cochrane Library and Ovid from 2017 to 2022. Study characteristics were retrieved and study outcomes such as adherence status and diabetes control were extracted and quantitatively analysed through meta-analysis. RESULTS: Eight studies met the final inclusion criteria and were included in the analysis, contributing to a total of 884 subjects. The methodological quality of the included studies was variable. Three studies reported statistically significant improvement in medication adherence through mobile apps intervention. Additionally, the mobile apps intervention proved effective in reducing glycaemic outcomes. As compared to non-mobile apps users, glycated haemoglobin (HbA1c) significantly decreased by 0.36% (95% CI -0.47% to -0.25%), whereas fasting plasma glucose (FPG) significantly decreased by 16.75 mg/dL (95% CI -17.60 mg/dL to -15.80 mg/dL). CONCLUSION: Mobile apps intervention had beneficial impacts on medication adherence and glycaemic parameters. Future research should explore the best practical approach for real-world settings.

Vitamin D insufficiency is high in Malaysia: A systematic review and meta-analysis of studies on vitamin D status in Malaysia.

Purpose: To estimate the vitamin D status of participants residing in Malaysia. Methods: PubMed, Scopus, Web of Science, and MyJurnal were searched up to June 2022 without language restrictions. Studies that reported the 25-hydroxyvitamin D [25(OH)D] concentrations and defined their cut-off for deficiency or insufficiency from healthy participants residing in Malaysia were included. The random effects model was used to pool vitamin D status using established cut-offs of <30, <50, and <75 nmol/L according to age group. Results: From 299 studies screened, 32 studies were included in the meta-analysis. The pooled proportion for <30 nmol/L was 21% (95% CI 9-36, n = 2,438 from 10 studies), while the pooled proportion <50 nmol/L was 64% (95% CI 56-72, n = 13,977 from 30 studies), and <75 nmol/L was 85% (95% CI 61-100, n = 1,376 from five studies). Heterogeneity was high (I2 ranged from 98-99%). Higher proportions of vitamin D insufficiency (defined as <50 nmol/L) were found in participants living in the urban areas (compared to rural areas), in females (compared to males), and in Malays and Malaysian Indians (compared to Malaysian Chinese) ethnicities. Conclusion: More than half of Malaysians have insufficient vitamin D levels, despite being a country that is close to the equator. We strongly urge prompt public health measures to improve the vitamin D status in Malaysia. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021260259].

A systematic review and meta-analysis of dabigatran peak and trough concentration in adults.

Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real-world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random-effect meta-analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113-154, I2  = 86%, n = 655), while the pooled dabigatran trough concentration was 80 ng/mL (95% CI: 69-91, I2  = 93%, n = 1010). Metaregression analyses suggested that age is significantly correlated to trough concentration, while body weight and creatinine clearance significantly correlated to peak concentration. Subgroup results revealed that dabigatran concentration when measured with liquid chromatography-tandem mass spectrometry was higher than haemoclot thrombin inhibitor assay. Several guidelines have proposed dabigatran concentrations target range and the pooled dabigatran concentrations were in line with the suggested range. Further studies to correlate dabigatran concentrations and clinical outcomes is warranted to improve the safety and efficacy monitoring of dabigatran therapy.

Factors influencing five-year adherence to adjuvant endocrine therapy in breast cancer patients: A systematic review.

PURPOSE: This systematic review aimed to determine the rate and identify correlates of adherence and persistence over five years of treatment with adjuvant endocrine therapy in female breast cancer patients. METHODS: Relevant articles were identified from Medline, Embase, AMED, PsycINFO, International Pharmaceutical Abstracts, and APA PsycArticles. Studies that measured patient adherence in the implementation or persistence phase for a period of at least five years using objective or multiple measures of adherence and investigated correlates of adherence were included. The titles, abstracts and full articles were screened and reviewed by two authors and any discrepancies were discussed with a third author. RESULTS: Twenty-six studies were included. Mean rate of adherence at five-year for implementation phase was 66.2% (SD = 17.3%), and mean persistence was 66.8% (SD = 14.5%). On average, adherence decreased by 25.5% (SD = 9.3%) from the first to fifth year. Higher rate of adherence was observed through self-report in comparison to database or medical record. Older age, younger age, higher comorbidity index, depression and adverse effects were associated with lower adherence. Treatment with aromatase inhibitors, received chemotherapy, and prior medication use were associated with improved adherence. CONCLUSION: Adherence to adjuvant endocrine therapy decreased from the first to fifth year of treatment. On average, one-third of patients were not adherent to treatment by the fifth year. Nineteen recurring factors were found to be significantly associated with long-term adherence in multiple studies. Further research using objective or multiple measures of adherence are needed to improve validity of results.

A Meta-Analysis on the Performance of Cystatin C- versus Creatinine-based eGFR Equations in Predicting Vancomycin Clearance.

BACKGROUND: The objective of this study was to compare the performance of cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) equations in predicting the clearance of vancomycin. METHODS: MEDLINE and Embase databases were searched from inception up to September 2019 to identify all studies that compared the predictive performance of cystatin C- and/or creatinine-based eGFR in predicting the clearance of vancomycin. The prediction errors (PEs) (the value of eGFR equations minus vancomycin clearance) were quantified for each equation and were pooled using a random-effects model. The root mean squared errors were also quantified to provide a metric for imprecision. RESULTS: This meta-analysis included evaluations of seven different cystatin C- and creatinine-based eGFR equations in total from 26 studies and 1,234 patients. The mean PE (MPE) for cystatin C-based eGFR was 4.378 mL min-1 (95% confidence interval [CI], -29.425, 38.181), while the creatinine-based eGFR provided an MPE of 27.617 mL min-1 (95% CI, 8.675, 46.560) in predicting clearance of vancomycin. This indicates the presence of unbiased results in vancomycin clearance prediction by the cystatin C-based eGFR equations. Meanwhile, creatinine-based eGFR equations demonstrated a statistically significant positive bias in vancomycin clearance prediction. CONCLUSION: Cystatin C-based eGFR equations are better than creatinine-based eGFR equations in predicting the clearance of vancomycin. This suggests that utilising cystatin C-based eGFR equations could result in better accuracy and precision to predict vancomycin pharmacokinetic parameters.

Effects of CST3 Gene G73A Polymorphism on Cystatin C in a Prospective Multiethnic Cohort Study.

BACKGROUND/AIMS: G73A polymorphism in the CST3 gene of cystatin C has been associated with Alzheimer's disease, age-related macular degeneration, and cardiovascular disease. However, studies investigating the influence of this genetic variability on serum cystatin C and cystatin-based renal function estimate are limited. Therefore, the aim of this study is to investigate the possible association of single-nucleotide polymorphism (rs1064039) of the CST3 gene on the serum cystatin C level and cystatin C-based estimated glomerular filtration rate (eGFR). METHODS: Study subjects include patients with various levels of renal function recruited from the nephrology clinic and wards of a tertiary hospital. The blood samples collected were analyzed for serum cystatin C and creatinine levels by particle-enhanced turbidimetric immunoassay and kinetic alkaline picrate method, respectively. DNA was extracted using a commercially available kit. -Polymerase chain reaction results were confirmed by direct DNA Sanger sequencing. RESULTS: The genotype percentage (G/G = 73%, G/A = 24.1%, and A/A = 2.9%) adhere to the Hardy-Weinberg equilibrium. The dominant allele found in our population was CST3 73G allele (85%). The regression lines' slope of serum cystatin C against creatinine and cystatin C-based eGFR against creatinine-based eGFR, between G and A allele groups, showed a statistically significant difference (z-score = 3.457, p < 0.001 and z-score = 2.158, p = 0.015, respectively). Patients with A allele had a lower serum cystatin C level when the values were extrapolated at a fixed serum creatinine value, suggesting the influence of genetic factor. CONCLUSION: Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.