Multiple comorbidities increase the risk of death from invasive pneumococcal disease under the age of 65 years

IntroductionRisk factors for death from invasive pneumococcal disease (IPD) have not been clearly established in patients aged under 65 years. We aimed to evaluate contributions of host and bacterial factors to the risk of death from IPD in patients aged under 65 years in Japan.MethodsIn this prospective, observational, multicenter cohort study, patients with IPD (n = 581) aged 6–64 years were enrolled between 2010 and 2017. We investigated the role of host and bacterial factors in 28-day mortality.ResultsThe mortality rate increased from 3.4% to 6.2% in patients aged 6–44 years to 15.5%–19.5% in those aged 45–64 years. Multivariable analysis identified the following risk factors for mortality: age 45–64 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6–6.8, p = 0.001), bacteremia with unknown focus (HR, 2.0; 95% CI, 1.1–3.7, p = 0.024), meningitis (HR, 2.1; 95% CI, 1.1–4.0, p = 0.019), underlying multiple non-immunocompromising conditions (HR, 2.6; 95% CI, 1.1–7.4, p = 0.023), and immunocompromising conditions related to malignancy (HR, 2.4; 95% CI, 1.0–5.2, p = 0.039). Pneumococcal serotype was not associated with poor outcomes.ConclusionsHost factors, including age of 45–64 years and underlying multiple non-immunocompromising conditions, are important for the prognosis of IPD. Our results will contribute to the development of targeted pneumococcal vaccination strategies in Japan.     

维生素E抗肿瘤作用机制研究

本文就维生素E抗瘤的作用机制作一简述。     

多普勒超声评价维生素C和维生素E对高血压血管内皮舒张功能的影响

目的应用超声技术观察维生素C,维生素E对高血压患者肱动脉内皮依赖性舒张功能的影响。方法研究对象包括20例高血压患者和20例正常人分别服用维生素C、维生素E12个月前后,应用高分辩力超声测定静息状态下,反应性充血后,舌下含服硝酸甘油后的肱动脉内径,并计算反应性充血和硝酸甘油诱发的内径百分变化率。结果反应性充血前后肱动脉内径百分变化率,高血压组明显低于正常组(P<0.001),硝酸甘油诱发的肱动脉内径百分变化率高血压组和正常组无显著差异。服用维生素C、维生素E12个月后,高血压患者反应性充血前后肱动脉内径百分变化率明显高于治疗前(P<0.001)。但硝酸甘油诱发的肱动脉内径百分变化率无明显变化。结论服用维生素C、维生素E可改善高血压患者受损的内皮依赖性血管舒张功能。     

Vitamin E in human health and disease

Vitamin E in nature is comprised of a family of tocopherols and tocotrienols. The most studied of these is alpha-tocopherol (alpha-TOH), because this form is retained within the body, and vitamin E deficiency is corrected with this supplement. alpha-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes, and it potentially acts as a defense against oxidative stress. Many studies have investigated the metabolism, transport, and efficacy alpha-TOH in the prevention of sequelae associated with cardiovascular disease (CVD). Supplementation with vitamin E is considered to provide health benefits against CVD through its antioxidant activity, the prevention of lipoprotein oxidation, and the inhibition of platelet aggregation. However, the results from large prospective, randomized, placebo-controlled clinical trials with alpha-TOH have been largely negative. A recent meta-analysis suggests that alpha-TOH supplements may actually increase all-cause mortality; however, the mechanism for this increased risk is unknown. In vitro studies performed in human cell cultures and animal models suggest that vitamin E might increase the hepatic production of cytochrome P450s and MDR1. Induction of CYP3A4 or MDR1 by vitamin E could potentially lower the efficacy of any drug metabolized by CYP3A4 or MDR1. Other possibilities include an adverse effect of alpha-TOH on blood pressure in high-risk populations. Because of the wide popularity and use of vitamin E supplements, further research into potential adverse effects is clearly warranted.     

Vitamin E in the treatment of tardive dyskinesia

OBJECTIVE: To review the efficacy of vitamin E in the treatment of tardive dyskinesia (TD). DATA SOURCES: Published articles and abstracts in English were identified from January 1986 to March 1999 by MEDLINE and International Pharmaceutical Abstracts searches using the terms vitamin E, alpha-tocopherol, and tardive dyskinesia. Additional articles were identified from the references of the retrieved articles and cross- referencing selected articles. DATA EXTRACTION: All clinical trials evaluating the use of vitamin E in human subjects with TD were reviewed. Selected articles also included those considered to be helpful in providing a basic introduction to TD pathophysiology and management. DATA SYNTHESIS: TD occurs in approximately 20% of patients treated with neuroleptics. The resulting dyskinesias can be irreversible and are often psychologically and physically debilitating. Recent research suggests that TD may be a result of neuronal damage inflicted by free radicals generated from increased neurotransmitter turnover and metabolism. Vitamin E as a naturally occurring free radical scavenger has been evaluated in the treatment of TD. Eighteen completed trials are available either in completed or abstract form. Twelve of these trials have produced positive results with vitamin E in the treatment of TD. Patients who have had TD for less than five years appear to respond better than patients with long-standing TD. CONCLUSIONS: Research suggests that vitamin E offers benefit in the management of a subgroup of patients with TD. Further investigation is needed to ascertain continued efficacy with long-term use as well as the role of vitamin E in TD prophylaxis.     

Vitamin C and vitamin E for Alzheimer's disease

OBJECTIVE: To evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimer's disease (AD). DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimer's disease, and dementia. International Pharmaceutical Abstracts (1970-March 2005), Current Contents (1996-March 2005), Cochrane Database of Systematic Reviews (1994-March 2005), and Ebsco's Academic Search Elite (1975-March 2005) were searched with the same key words. STUDY SELECTION AND DATA EXTRACTION: Articles related to the objective that were identified through PubMed were included. DATA SYNTHESIS: Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E > or =400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses > or =400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted. CONCLUSIONS: In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.     

Vitamin E disturbances in chronic renal failure]

Plasma levels of alpha-tocopherol (vitamin E) in chronic renal insufficiency (CRI) patients may be decreased, normal or elevated. However, an abnormal distribution of vitamin E in each lipoprotein has been reported. In comparison to control subject low-density lipoprotein (LDL), patient LDL contained less vitamin E. On the contrary, malondialdehyde (MDA) in patient LDL was enhanced. According to the evaluation of the susceptibility of LDL to in vitro oxidation and the rate of lipid peroxidation by fluorescence development during copper exposure, the susceptibility of patient LDL was enhanced, suggesting a possible relationship between excessive LDL peroxidation and accelerated atherosclerosis. In a clinical small uncontrolled trial, the increments of an aortic calcification index estimated by CT scan in patients treated with vitamin E were suppressed compared to those treated without vitamin E, suggesting that vitamin E might prevent the progress of atherosclerosis in CRI patients.     

Vitamin E and coronary heart disease in Tunisians

BACKGROUND: Vitamin E (VE) is thought to be effective in preventing atherosclerosis. However, to date no consistent relationship has been identified between VE and coronary heart disease (CHD). This study was designed to assess the degree of association between VE and CHD in a sample of the Tunisian population. METHODS: Sixty-two angiographically confirmed coronary atherosclerotic patients and 65 age- and sex-matched controls were included. VE was measured in plasma and in the LDL fraction by HPLC. Cholesterol, triglycerides, and phospholipids were measured by enzymatic methods. RESULTS: A trend toward a meaningful decrease of plasma VE was observed in affected patients compared with controls (P: = 0.06). VE concentrations standardized for cholesterol and lipid concentrations were significantly lower (P: <0.02) in coronary patients than in controls (4.35 +/- 1.03 vs 4.82 +/- 1.23 mmol/mol for cholesterol-adjusted VE and 2.35 +/- 0.56 vs 2.66 +/- 0.65 mmol/mol for lipid-adjusted VE, respectively). In the LDL fraction, only cholesterol-standardized VE was significantly lower in cases than controls (3.84 +/- 1.13 vs 4.41 +/- 1.16 mmol/mol). This association between VE and CHD remained unchanged independent of age, sex, smoking habit, hypertension, and diabetes. In CHD patients, lower lipid-adjusted VE was associated with enhanced LDL susceptibility to oxidation but without alteration of the serum fatty acid profile. CONCLUSIONS: These results support the hypothesis that VE plays a role in preventing atherosclerosis.