Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial.

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 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. Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.

Risk of Peritoneal Dialysis-Related Peritonitis in a Multi-Racial Asian Population.

♦ BACKGROUND: Peritonitis is one of the most common complications of peritoneal dialysis (PD). Understanding the risk factors of peritonitis in a multi-racial Asian population may help to improve outcomes on PD. ♦ METHODS: We conducted a prospective observational study to identify risk factors for PD-related peritonitis over a 1-year period in 15 adult PD centers. All peritonitis episodes were independently adjudicated. ♦ RESULTS: A total of 1,603 participants with a mean age of 51.6 years comprising 52.7% females, 62.6% ethnic Malays, 27.0% Chinese, and 8.1% Indians were recruited. The overall peritonitis rate was 1 episode per 44.0 patient-months with 354 episodes recorded in 282 (17.6%) patients over 15,588 patient-months. Significant risk factors of peritonitis were severe obesity (incidence-rate ratio [IRR] 3.32, 95% confidence interval [CI]: 1.30, 8.45), hypoalbuminemia (IRR 1.61, 95% CI: 1.06, 2.46), Staphylococcus aureus nasal carriage (IRR 2.26, 95% CI: 1.46, 3.50), and use of Fresenius system (Fresenius Medical Care North America, Waltham, MA, USA) (IRR 2.49, 95% CI: 1.27, 4.89). The risk of peritonitis was lower in those on automated PD compared with standard PD (IRR 0.43, 95% CI: 0.25, 0.74), and in centers with a patient-staff ratio of 15 to 29.9 (IRR 0.67, 95% CI: 0.49, 0.90) and ≥ 30 (IRR 0.52, 95% CI: 0.34, 0.80). Prevalent patients and exit-site care with topical antibiotics were also protective against peritonitis. Peritonitis rates varied between racial groups. The IRRs of overall peritonitis and gram-positive peritonitis in Chinese versus other racial groups were 0.65 (95% CI: 0.46, 0.90) and 0.47 (95% CI: 0.24, 0.91), respectively. ♦ CONCLUSIONS: Multiple patient, center, and PD-system factors influence the risk of peritonitis. In the Asian population, there are racial differences in the risk of peritonitis.

Combining serum protein concentrations to diagnose schizophrenia: a preliminary exploration.

OBJECTIVE: It is difficult for clinicians to diagnose schizophrenia solely based on interviews. We explored the diagnostic efficiency and predictive capability of serum biomarkers for schizophrenia. METHOD: Levels of ß nerve growth factor (ß-NGF), brain-derived neurotrophic factor (BDNF), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), calcium binding protein S100ß, myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) were measured in the sera of 278 schizophrenia patients, 240 depression and bipolar disorder patients, and 260 healthy controls. DSM-IV-TR criteria were used as the diagnostic criteria for schizophrenia and depressive and bipolar disorders. The diagnostic efficiency was high in patients with schizophrenia compared with the healthy controls. Receiver operating characteristic (ROC) curve analysis was used to ascertain the diagnostic efficiency of the 8 proteins. Data were collected between July 2010 and December 2012. RESULTS: One-way analysis of variance significantly demonstrated lower serum BDNF, MBP, and GFAP levels (F = 16.504, P < .001; F = 207.209, P < .001; F = 33.668, P < .001, respectively) but higher serum IL-6 and S100ß concentrations (F = 15.250, P < .001; F = 12.751, P < .001, respectively) among patients with schizophrenia. ROC analysis of the discriminant scores of the serum ß-NGF, BDNF, IL-6, S100ß, MBP, and GFAP levels resulted in significant discrimination between the schizophrenia and control groups (AUC = 0.922) and the depressive/bipolar disorder and control groups (AUC = 0.762). CONCLUSIONS: Serum levels of 6 proteins (but not TNF-α and IFN-γ) contribute most to the diagnosis of schizophrenia. These proteins may prove to be useful adjuncts for the clinical assessment of this disease.

Prevalence and risk factors for proteinuria: the National Kidney Foundation of Malaysia Lifecheck Health Screening programme.

AIM: Treatment of chronic kidney disease (CKD) poses a huge burden to the healthcare system. To address the problem, the National Kidney Foundation of Malaysia embarked on a programme to screen for proteinuria and educate the public on CKD. METHODS: The public was invited for health screening and the data collected over a 21 month period was analyzed. RESULTS: In total, 40400 adults from all the states in Malaysia were screened. The screening population had a mean age of 41 years, 30.1% had hypertension and 10.6% had diabetes. Proteinuria was detected in 1.4% and haematuria in 8.9% of the participants. Factors associated with the highest risk for proteinuria were the presence of diabetes (adjusted odds ratio (OR) 2.63 (95% confidence interval (CI) 2.16-3.21)), hypertension (OR 2.49 (95% CI 2.03-3.07)) and cardiac disease (OR 2.05 (95% CI 1.50-2.81)). Other risk factors identified were lower educational level, family history of kidney disease, hypercholesterolaemia, obesity and lack of regular exercise. Chinese had the lowest risk for proteinuria among the races (OR 0.71 (95% CI 0.57-0.87) compared with Malays). The combination of high blood glucose and high blood pressure (BP) substantially increased the risk for proteinuria (OR 38.1 for glucose ≥ 10 mmol/L and systolic BP ≥ 180 mm Hg and OR 47.9 for glucose ≥ 10 mmol/L and diastolic BP ≥ 110 mm Hg). CONCLUSION: The prevalence of proteinuria in Malaysia is similar to other countries. The major risk factors for proteinuria were diabetes, hypertension and cardiac disease. The presence of both high blood pressure and high blood glucose exert a synergistic effect in substantially increasing the risk for proteinuria.