Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy.

Design, Setting, and Participants: The 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 ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups.

Main Outcomes and Measures: The 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.

Results: Of 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 A1C 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.

Patients and methods: This cross-sectional study included 167 SLE patients (21 males, 146 females; mean age 38.2±9.8 years; range, 20 to 60 years) recruited from the outpatient Rheumatology and Nephrology clinics. Face-to-face interviews were conducted to record patients' socio- demographics (age, sex, ethnicity, marital status, and occupation) and SLE disease characteristics (system involvement, age onset, and presence of organ damage). Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K). Short form 36 (SF-36) was used to determine health-related quality of life (HRQoL) while Work Productivity and Activity Impairment (WPAI) questionnaire was used to assess the four domains of absenteeism, presenteeism, overall work productivity, and non-work related ADL impairment. Univariate analyses and multivariable regression analysis examined the association of demographic variables, SLE disease characteristics, and activity with reduced HRQoL and WPAI scores.

Results: The majority of the patients were Malays (59.3%), followed by Chinese (34.7%) and Indian (3.6%) patients. More than two-thirds of the patients reported some degree of impairment in their work productivity and ADL due to the disease. The absenteeism rate was 10.4% in the past one week and their indirect costs were 2,875.17 Malaysian ringgits (US $701.22) in the past seven days. Significant predictors of higher work productivity and ADL impairment scores were higher disease activity, more frequent SLE flares, lupus nephritis, and hematological involvement of SLE. Patients with higher work productivity and ADL impairment scores were also strongly associated with poor QoL. No ethnic disparities of work productivity and ADL impairment were found.

METHOD: This was a cross-sectional study involving SLE patients aged 18-56 years from Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Employment history was obtained from clinical interviews. WD was defined as unemployment, interruption of employment or premature cessation of employment due to SLE at any time after the diagnosis. SLE disease characteristics, presence of organ damage and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SLEDAI) flare index were determined from the medical records. Self-reported quality of life (QoL) was performed using the Medical Outcomes Study Short Form-36 (SF-36). Demographic factors, disease characteristics, and QoL were compared between patients with and without WD using statistical analyses.

RESULTS: A total of 215 patients were recruited and the majority were Malay (60.5%), followed by Chinese (33.5%), Indian (4.5%) and others (n = 4, 1.9%). The prevalence of WD was 43.2% (n = 93) with 22.3% (n = 48) patients were unemployed at the time of study. Over half the patients with WD (n = 51, 54.8%) had onset of disability at <5 years from diagnosis. Patients with WD had significantly lower health-related QoL. The independent factors associated with WD were SLEDAI score at diagnosis, frequency of flare, Systemic Lupus International Collaborating Clinics score, being married, had lower education and lupus nephritis.