OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort.
METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA).
RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes.
CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.
MATERIALS AND METHODS: This was a retrospective cohort study undertaken at a public tertiary care centre in the state of Perak, Malaysia. Information of obese patients who underwent bariatric surgery was obtained from their medical records. The changes in the BMI, HbA1C, systolic and diastolic blood pressure (SBP and DBP), and lipid levels between three months before and after the surgery were assessed.
RESULTS: The patients (n=106) were mostly Malay (66.0%), had at least one comorbidity (61.3%), and had a mean age of 40.38±11.75 years. Following surgery, the BMI of the patients was found to reduce by 9.78±5.82kg/m2. For the patients who had diabetes (n=24) and hypertension (n=47), their mean HbA1C, SBP and DBP were also shown to reduce significantly by 2.02±2.13%, 17.19±16.97mmHg, and 11.45±12.63mmHg, respectively. Meanwhile, the mean total cholesterol, triglyceride and low-density lipoprotein levels of those who had dyslipidaemia (n=21) were, respectively, lowered by 0.91±1.18mmol/L, 0.69±1.11mmol/L and 0.47±0.52mmol/L.
CONCLUSION: The findings suggest that in addition to weight reduction, bariatric surgery is helpful in improving the diabetes, hypertension and dyslipidaemia control among obese patients. However, a large-scale trial with a control group is required to verify our findings.
MATERIALS AND METHODS: A literature search was performed across PubMed, EMBASE, Emerald Insight and grey literature sources. The key terms used in the search include 'distribution', 'method', and 'physician', focusing on research articles published in English from 2002 to 2022 that described methods or tools to measure hospital-based physicians' distribution. Relevant articles were selected through a two-level screening process and critically appraised. The primary outcome is the measurement tools used to assess the distribution of hospital-based physicians. Study characteristics, tool advantages and limitations were also extracted. The extracted data were synthesised narratively.
RESULTS: Out of 7,199 identified articles, 13 met the inclusion criteria. Among the selected articles, 12 were from Asia and one from Africa. The review identified eight measurement tools: Gini coefficients and Lorenz curve, Robin Hood index, Theil index, concentration index, Workload Indicator of Staffing Need method, spatial autocorrelation analysis, mixed integer linear programming model and cohortcomponent model. These tools rely on fundamental data concerning population and physician numbers to generate outputs. Additionally, five studies employed a combination of these tools to gain a comprehensive understanding of physician distribution dynamics.
CONCLUSION: Measurement tools can be used to assess physician distribution according to population needs. Nevertheless, each tool has its own merits and limitations, underscoring the importance of employing a combination of tools. The choice of measuring tool should be tailored to the specific context and research objectives.
CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy.
DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.
MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05.
RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs.
CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.
OBJECTIVE: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19.
DESIGN, SETTING, AND PARTICIPANTS: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease.
INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging.
MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events.
RESULTS: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04920942.
METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.
RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.
CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.
Objectives: To evaluate the effectiveness and tolerability of TNK in patients with ST-segment-elevation myocardial infarction in a secondary referral Malaysian hospital.
Methods: This was a single-center retrospective case series based on the medical records of patients with ST-segment-elevation myocardial infarction admitted to the cardiac care unit between January 2016 and May 2019. Data regarding the mortality status and date of death were collected from the database of the National Registration Department of Malaysia.
Results: Data for 30 patients with ST-segment-elevation myocardial infarction, who received weight-adjusted doses of TNK, were analyzed. The patients' mean (SD) age was 62 (14) years, and 77% were men. The median time to treatment was 265 minutes (interquartile range = 228-660 minutes), and the clinical success rate of thrombolysis was 79%. The overall all-cause in-hospital mortality rate was 33%. The 1-year survival rates were higher in patients achieving a time to treatment ≤360 minutes (P = 0.03), with a trend toward greater survival in this group at 30 days. Similarly, a trend toward lower in-hospital all-cause mortality was observed in this group (21% vs 50%; P = 0.12). Only 1 patient (3%), who had a HAS-BLED score based on hypertension, abnormal liver/renal function, stroke history, bleeding history or predisposition, labile international normalized ratio, old age, drug/alcohol use of 5, developed major bleeding that required blood transfusion. No cases of ischemic stroke, nonmajor bleeding, in-hospital reinfarction, or TNK-induced allergic reaction were identified.
Conclusions: We hypothesized that the mortality-related outcomes of TNK in patients with ST-segment-elevation myocardial infarction were influenced by TTT, with TTT ≤360 minutes indicating a better prognosis than TTT >360 minutes. TNK-induced bleeding-related complications were minimal in low-risk patients. Further local studies are needed to compare TNK's profile with that of streptokinase, which is a common agent currently used in clinical practice in Malaysian public hospitals. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).