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).
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.
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.
AIM: To develop a list of medications to facilitate appropriate prescribing among older adults.
METHODS: A preliminary list of PIM and potential prescribing omission (PPO) were generated from systematic review, supplemented with local pharmacovigilance data of adverse reaction incidents among older people. Twenty-one experts from nine specialties participated in two Delphi to determine the list of PIM and PPO in February and March 2023. Items that did not reach consensus after the second Delphi round were adjudicated by six geriatricians.
RESULTS: The preliminary list included 406 potential candidates, categorised into three sections: PIM independent of diseases, disease dependent PIM and omitted drugs that could be restarted. At the end of Delphi, 92 items were decided as PIM, including medication classes, such as antacids, laxatives, antithrombotics, antihypertensives, hormones, analgesics, antipsychotics, antidepressants, and antihistamines. Forty-two disease-specific PIM criteria were included, covering circulatory system, nervous system, gastrointestinal system, genitourinary system, and respiratory system. Consensus to start potentially omitted treatment was achieved in 35 statements across nine domains.
CONCLUSIONS: The newly developed PIM criteria can serve as a useful tool to guide clinicians and pharmacists in identifying PIMs and PPOs during medication review and facilitating informed decision-making for appropriate prescribing.
METHODS: This is an 18-month cluster-randomized, open-label, parallel-arm controlled trial conducted at 14 public hospitals in the Perak state of Malaysia. Patients aged 60 and above, who have at least one medication and one comorbidity are eligible. A stratified-cluster randomization design is employed, with 7 hospitals assigned to the control arm and 7 hospitals assigned to the intervention arm. The MALPIP screening tool will be used in the intervention group to review the medications. If PIM is detected, the pharmacists will discuss with doctors and decide whether to stop or reduce the dose. The primary outcomes of this trial are the total number of medications and number of PIM. The secondary outcomes include fall, emergency department visits, readmissions, quality of life and mortality. Outcomes will be measured during enrolment, discharge, 6, 12, and 18 months.
DISCUSSION: This REVMED trial aims to test the hypothesis that a pharmacist-led deprescribing intervention initiated in the hospital will reduce the total number of medications and PIM 18 months after hospital discharge, reducing fall, emergency department visits, readmissions, mortality and lead to improvement in quality of life. Trial findings will quantify the clinical outcomes associated with reducing medications and PIM for hospitalized older adults with polypharmacy.
TRIAL REGISTRATION NUMBER: This trial was prospectively registered at clinicaltrials.gov (NCT05875623) on the 25th of May 2023. NCT05875623 Clinicaltrials.gov URL: NCT05875623 registered on 25th July 2023.
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.