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.

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.

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.

Population pharmacokinetic modelling of intravenous immunoglobulin in patients with predominantly antibody deficiencies.

AIMS: There is considerable interpatient variability in the pharmacokinetics (PK) of intravenous immunoglobulin G (IVIG), causing difficulty in optimizing individual dosage regimen. This study aims to estimate the population PK parameters of IVIG and to investigate the impact of genetic polymorphism of the FcRn gene and clinical variability on the PK of IVIG in patients with predominantly antibody deficiencies. METHODS: Patients were recruited from four hospitals. Clinical data were recorded and blood samples were taken for PK and genetic studies. Population PK parameters were estimated by nonlinear mixed-effects modelling in Monolix®. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive check and bootstrap analysis. Monte Carlo simulation was conducted to evaluate different dosing regimens for IVIG. RESULTS: A total of 30 blood samples were analysed from 10 patients. The immunoglobulin G concentration data were best described by a one-compartment model with linear elimination. The final model included both volume of distribution (Vd) and clearance (CL) based on patient's individual weight. Goodness-of-fit plots indicated that the model fit the data adequately, with minor model mis-specification. Genetic polymorphism of the FcRn gene and the presence of bronchiectasis did not affect the PK of IVIG. Simulation showed that 3-4-weekly dosing intervals were sufficient to maintain IgG levels of 5 g L-1 , with more frequent intervals needed to achieve higher trough levels. CONCLUSIONS: Body weight significantly affects the PK parameters of IVIG. Genetic and other clinical factors investigated did not affect the disposition of IVIG.

A Systematic Review and Meta-regression Analysis on the Impact of Increasing IgG Trough Level on Infection Rates in Primary Immunodeficiency Patients on Intravenous IgG Therapy.

PURPOSE: We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment. METHODS: Systematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehensive Meta-analysis Software. Additional sensitivity analyses were undertaken to evaluate the robustness of the overall results. RESULTS: Twenty-eight clinical studies with 1218 patients reported from year 2001 to 2018 were included. The mean IVIG dose used ranges from 387 to 560 mg/kg every 3 to 4 weekly, and mean IgG trough obtained ranges from 660 to 1280 mg/dL. Random-effects meta-regression slope shows that IgG trough level increases significantly by 73 mg/dL with every increase of 100 mg/kg dose of IVIG (p < 0.05). Overall infection rates reduced significantly by 13% with every increment of 100 mg/dL of IgG trough up to 960 mg/dL (p < 0.05). CONCLUSION: This meta-analysis concludes that titrating the IgG trough levels up to 960 mg/dL progressively reduces the rate of infections, and there is less additional benefit beyond that. Further studies to validate this result are required before it can be used in clinical practice.

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 MAO-A and CYP450 on primaquine metabolism in healthy volunteers.

Eliminating the Plasmodium vivax malaria parasite infection remains challenging. One of the main problems is its capacity to form hypnozoites that potentially lead to recurrent infections. At present, primaquine is the only drug used for the management of hypnozoites. However, the effects of primaquine may differ from one individual to another. The aim of this work is to determine new measures to reduce P. vivax recurrence, through primaquine metabolism and host genetics. A genetic study of MAO-A, CYP2D6, CYP1A2 and CYP2C19 and their roles in primaquine metabolism was undertaken of healthy volunteers (n = 53). The elimination rate constant (Ke) and the metabolite-to-parent drug concentration ratio (Cm/Cp) were obtained to assess primaquine metabolism. Allelic and genotypic analysis showed that polymorphisms MAO-A (rs6323, 891G>T), CYP2D6 (rs1065852, 100C>T) and CYP2C19 (rs4244285, 19154G>A) significantly influenced primaquine metabolism. CYP1A2 (rs762551, -163C>A) did not influence primaquine metabolism. In haplotypic analysis, significant differences in Ke (p = 0.00) and Cm/Cp (p = 0.05) were observed between individuals with polymorphisms, GG-MAO-A (891G>T), CT-CYP2D6 (100C>T) and GG-CYP2C19 (19154G>A), and individuals with polymorphisms, TT-MAO-A (891G>T), TT-CYP2D6 (100C>T) and AA-CYP2C19 (19154G>A), as well as polymorphisms, GG-MAO-A (891G>T), TT-CYP2D6 (100C>T) and GA-CYP2C19 (19154G>A). Thus, individuals with CYP2D6 polymorphisms had slower primaquine metabolism activity. The potential significance of genetic roles in primaquine metabolism and exploration of these might help to further optimise the management of P. vivax infection.

Qualitative exploration of the modifiable factors for medication adherence among subsidised and self-paying patients in Malaysia.

BACKGROUND: Numerous studies have evaluated the related factors of medication adherence among patients with chronic disease. However, the factors influencing medication adherence and non-adherence among subsidised patients with chronic diseases-for whom medication costs may not be a constraint-remain unexplored. Thus, this study aims to identify and compare the potential factors that may influence subsidised and non-subsidised (i.e., self-paying) patients' adherence to medication. METHODS: Subsidised and self-paying patients were identified at public and private healthcare institutions in three states of Malaysia. Patients were then purposively selected for semi-structured, face-to-face interviews according to their medication adherence status (including adherent and non-adherent patients), which was measured using the Medication Event Monitoring System (MEMS). Adherence was defined as having 80% or more for the percentage of days in which the dose regimen was executed as prescribed. The interview was conducted from January to August 2016 and during the interviews, patients were asked to provide reasons for their medication adherence or non-adherence. The patient interviews were audio recorded and transcribed verbatim. Data were analysed using thematic analysis with NVivo 11 software. RESULTS: Thirteen subsidised and 12 self-paying patients were interviewed. The themes found among subsidised and self-paying patients were similar. The factors that influenced adherence to medication include the 'perceived importance of quality of life' and 'perceived benefit or value of the medications'. A unique factor reported by patients in this study included 'perceived value of the money spent on medications'; more specifically, patients adhered to their medications because they valued the money spent to buy/receive the medications. CONCLUSION: Medication adherence among subsidised and self-paying patients was influenced by many factors, including a unique factor relating to their perceptions of the value of money spent on medications.

Awareness of medication related falls and preferred interventions among the elderly.

Falls are a major problem among the elderly and can lead to serious injury. Adults older than 65 years suffer the greatest number of severe falls. This study aims to evaluate the knowledge and perception of medication related falls as well as preferred medication related fall prevention programs in the local population. A cross-sectional survey was conducted among the elderly patients in a tertiary hospital. A total of 86 patients (n=86) were interviewed. Approximately 23.3% (20 patients) of the elderly had a history of falls over the past 6 months. Majority of the elderly considered falls as a major concern (80 patients, 93%) and is preventable (55 patients, 64%). Patients with a medical condition reported a significantly greater number of falls within the past 6 months (p<0.001). Approximately 69% (59 patients) of the elderly were aware of their medication and associated risk of falls. In patients that were unaware of medication associated risk of falls, 81.5% (22 patients) had a potentially inappropriate medication preferred preventive interventions for medication related falls were related to strength and training programs (37 patients, 43%). The knowledge of falls, medication related falls and intervention strategies in the elderly were minimal.

A clinical tool to predict Plasmodium vivax recurrence in Malaysia.

BACKGROUND: Recurrence rates of Plasmodium vivax infections differ across various geographic regions. Interestingly, South-East Asia and the Asia-Pacific region are documented to exhibit the most frequent recurrence incidences. Identifying patients at a higher risk for recurrences gives valuable information in strengthening the efforts to control P. vivax infections. The aim of the study was to develop a tool to identify P. vivax- infected patients that are at a higher risk of recurrence in Malaysia. METHODS: Patient data was obtained retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016. Patients with incomplete data were excluded. A total of 2044 clinical P. vivax malaria cases treated with primaquine were included. Data collected were patient, disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were used to develop a clinical risk score, while the remaining third (n = 682) was used for validation. RESULTS: Using multivariate analysis, age (p = 0.03), gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found to be predictors of recurrence after controlling for other confounding factors; these predictors were then used in developing the final model. The beta-coefficient values were used to develop a clinical scoring tool to predict possible recurrence. The total scores ranged between 0 and 8. A higher score indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence interval [CI]: 1.562-2.487; p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve of the developed (n = 1362) and validated model (n = 682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value < 0.001, and ROC: 0.766, 95% CI: 0.700-0.833, p-value < 0.001, respectively). In both the developed and validated models, area under the ROC curves showed no significant difference in predicting recurrence based on the constructed scoring mechanism (p = 0.399; Z-value: -0.8441; standard error: 0.045). CONCLUSIONS: The developed model to predict recurrence was found to be of good accuracy and could be a useful tool in targeting patients at a higher risk for recurrence for closer monitoring during follow-up, after treatment with primaquine.

KNOWLEDGE, ATTITUDE AND PERCEPTION OF PARENTS ON THE USE OF COUGH AND COLD MEDICATIONS IN CHILDREN.

This study investigated the knowledge, attitude and perception of parents on the use of cough and cold medications in children. Questionnaires were distributed to parents of children aged < or =6 years in selected kindergartens. The overall knowledge of the parents (n=248) was satisfactory with a mean score of 5.87 +/- 1.70 (from a total of 10) and the overall attitude was positive with a mean score of 41.15 +/- 6.72 (from a total of 50). Ten percent of parents admitted administering cough and cold medications in children aged <2 years. Age of the parents, education level and monthly income were found to significantly influence knowledge level (p<0.05). Spearman's rank-order correlation between knowledge and attitude scores showed a statistically significant positive linear relationship (r(s), = 0.290, p<0.05). The study provides some insights into the use of cough and cold medications in children from the parents' perspectives.

Effectiveness and safety of a 10mg warfarin initiation nomogram in Asian population.

Anticoagulant responses to warfarin vary among patients, based on genetic factors, diet, concomitant medications, and disease state. We evaluated the effectiveness and safety of a 10mg warfarin initiation nomogram in an Asian population. Retrospective cross-sectional audit studies were conducted from March 2009 to March 2010. The use of a 10mg-loading dose to initiate warfarin treatment resulted in 33(84.6%) patients attaining a therapeutic INR within four days (mean time, 2.6 days). There was no significant correlation between age, gender, race, and serum albumin for the time to reach a therapeutic INR. A significant correlation was noted for patient's baseline INR and time to reach a therapeutic INR (P<0.05). No significant differences were observed in time to reach a therapeutic INR in patients treated with specific class of concomitant drugs or patients with specific disease states. The overall incidence of over-anticoagulation was 35.9%; however, no bleeding episodes were encountered. In conclusion, the use of a 10mg warfarin nomogram was effective in rapidly achieving a therapeutic INR. However, the nomogram's safety is debatable owing to the high over-anticoagulation rate warfarin-administered patients. Caution is recommended in the initiation of warfarin treatment using the 10mg nomogram.

KNOWLEDGE, ATTITUDES AND PRACTICES ABOUT ANTIBIOTIC USE AMONG THE GENERAL PUBLIC IN MALAYSIA.

Antibiotic resistance is a major problem globally. Awareness of the impact and significance of antibiotic resistance is a first step in hindering its progression. We conducted this survey to evaluate knowledge, attitudes and practices regarding antibiotic use in Malaysia. A total of 373 respondents were surveyed, 219 (58.1%) were female and 312 (83%) were Malay ethnicity. Eighty-four point two percent (314) had used antibiotics more than once (> 1) during the previous year. We found respondents who were less likely to take antibiotics (≤ 1) during the previous year were more likely to agree that antibiotic resistance was a serious public health issue compared to those that took antibiotic more than once during the previous year (p < 0.0001). A significantly greater number of patients (67.2%) who took antibiotics more than once during the previous year did not complete the full course than those who took antibiotics no more than once (55.9%) during the previous year (p < 0.01). We found the frequency of antibiotic use was related to knowledge about antibiotics among the study population. It is essential to develop educational interventions to correct the misuse and misunderstanding of antibiotics.

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.

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.

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.

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.

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.

Cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine.

Chloroquine (CQ) has been a mainstay of antimalarial drug treatment for several decades. Additional therapeutic actions of CQ have been described, including some reports of fungal inhibition. Here we investigated the action of CQ in fungi, including the yeast model Saccharomyces cerevisiae. A genomewide yeast deletion strain collection was screened against CQ, revealing that bck1Δ and slt2Δ mutants of the cell wall integrity pathway are CQ hypersensitive. This phenotype was rescued with sorbitol, consistent with cell wall involvement. The cell wall-targeting agent caffeine caused hypersensitivity to CQ, as did cell wall perturbation by sonication. The phenotypes were not caused by CQ-induced changes to cell wall components. Instead, CQ accumulated to higher levels in cells with perturbed cell walls: CQ uptake was 2- to 3-fold greater in bck1Δ and slt2Δ mutants than in wild-type yeast. CQ toxicity was synergistic with that of the major cell wall-targeting antifungal drug, caspofungin. The MIC of caspofungin against the yeast pathogen Candida albicans was decreased 2-fold by 250 µM CQ and up to 8-fold at higher CQ concentrations. Similar effects were seen in Candida glabrata and Aspergillus fumigatus. The results show that the cell wall is critical for CQ resistance in fungi and suggest that combination treatments with cell wall-targeting drugs could have potential for antifungal treatment.

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.