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The Vitamin E in Neuroprotection Study (VENUS) Investigators IMPORTANCE Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities.OBJECTIVE To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy. DESIGN, SETTING, AND PARTICIPANTSThe Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited.INTERVENTIONS Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level Ն2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups. MAIN OUTCOMES AND MEASURESThe primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result. RESULTSOf 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (−0.30; 95% CI, −1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, −1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A 1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses.CONCLUSIONS AND RELEVANCE Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration.

The rapid transmission of highly contagious infectious diseases within communities can yield potential hotspots or clusters across geographies. For COVID-19, the impact of population density on transmission models demonstrates mixed findings. This study aims to determine the correlations between population density, clusters, and COVID-19 incidence across districts and regions in Malaysia. This countrywide ecological study was conducted between 22 January 2021 and 4 February 2021 involving 51,476 active COVID-19 cases during Malaysia’s third wave of the pandemic, prior to the reimplementation of lockdowns. Population data from multiple sources was aggregated and spatial analytics were performed to visualize distributional choropleths of COVID-19 cases in relation to population density. Hierarchical cluster analysis was used to synthesize dendrograms to demarcate potential clusters against population density. Region-wise correlations and simple linear regression models were deduced to observe the strength of the correlations and the propagation effects of COVID-19 infections relative to population density. Distributional heats in choropleths and cluster analysis showed that districts with a high number of inhabitants and a high population density had a greater number of cases in proportion to the population in that area. The Central region had the strongest correlation between COVID-19 cases and population density (r = 0.912; 95% CI 0.911, 0.913; p < 0.001). The propagation effect and the spread of disease was greater in urbanized districts or cities. Population density is an important factor for the spread of COVID-19 in Malaysia.

Diabetes causes significant disabilities, reduced quality of life and mortality that imposes huge economic burden on societies and governments worldwide. Malaysia suffers a high diabetes burden in Asia, but the magnitude of healthcare expenditures documented to aid national health policy decision-making is limited. This systematic review aimed to document the economic burden of diabetes in Malaysia, and identify the factors associated with cost burden and the methods used to evaluate costs. Studies conducted between 2000 and 2019 were retrieved using three international databases (PubMed, Scopus, EMBASE) and one local database (MyCite), as well as manual searches. Peer reviewed research articles in English and Malay on economic evaluations of adult type 2 diabetes conducted in Malaysia were included. The review was registered with PROSPERO (CRD42020151857), reported according to PRISMA and used a quality checklist adapted for cost of illness studies. Data were extracted using a data extraction sheet that included study characteristics, total costs, different costing methods and a scoring system to assess the quality of studies reviewed. The review identified twelve eligible studies that conducted cost evaluations of type 2 diabetes in Malaysia. Variation exists in the costs and methods used in these studies. For direct costs, four studies evaluated costs related to complications and drugs, and two studies were related to outpatient and inpatient costs each. Indirect and intangible costs were estimated in one study. Four studies estimated capital and recurrent costs. The estimated total annual cost of diabetes in Malaysia was approximately USD 600 million. Age, type of hospitals or health provider, length of inpatient stay and frequency of outpatient visits were significantly associated with costs. The most frequent epidemiological approach employed was prevalence-based (n = 10), while cost analysis was the most common costing approach used. The current review offers the first documented evidence on cost estimates of diabetes in Malaysia.