Plasma cotinine is positively associated with homocysteine in smokers but not in users of smokeless tobacco

Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about the effect of snus on plasma homocysteine. Therefore, we studied, in a cross-section of subjects (n = 1375) from the Northern Sweden Health and Disease Study, with strictly defined current smokers (n = 194) and snus users (n = 47), the impact of tobacco exposure on tHcy, assessed by self-reported tobacco habits and plasma cotinine concentrations. The snus users had higher cotinine concentrations than the smokers. Cotinine, creatinine, methylmalonic acid, and the methylenetetrahydrofolate reductase genotype (MTHFR) T allele were positively associated with tHcy among the smokers, but not among the snus users. No association was observed between tHcy and the number of cigarettes/day. There was a positive association between cotinine and tHcy in the smokers, but not among the snus users. This indicates that substances other than nicotine in tobacco smoke could be responsible for the differential effects on homocysteine status. Self-reported smoking should be complemented by a cotinine assay whenever possible.publishedVersio

North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B₂ concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (P trend< 0·001). Vitamin B(6) concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (P trend< 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle

Effects of Pharmacists’ Interventions on Inappropriate Drug Use and Drug-Related Readmissions in People with Dementia—A Secondary Analysis of a Randomized Controlled Trial

Age-associated physiological changes and extensive drug treatment including use of potentially inappropriate medications (PIMs) pose a significant risk of drug–drug interactions and adverse drug events among elderly people with dementia. This study aimed at analysing the effects of clinical pharmacists’ interventions on use of PIMs, risk of emergency department visits, and time to institutionalization. Furthermore, a descriptive analysis was conducted of circumstances associated with drug-related readmissions. This is a secondary analysis of data from a randomized controlled intervention study conducted in two hospitals in Northern Sweden. The study included patients (n = 460) 65 years or older with dementia or cognitive impairment. The intervention consisted of comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team. There was a larger decrease in PIMs in the intervention group compared with the control group (p = 0.011). No significant difference was found in time to first all-cause emergency department visits (HR = 0.994, 95% CI = 0.755–1.307 p = 0.963, simple Cox regression) or time to institutionalization (HR = 0.761, 95% CI = 0.409–1.416 p = 0.389, simple Cox regression) within 180 days. Common reasons for drug-related readmissions were negative effects of sedatives, opioids, antidepressants, and anticholinergic agents, resulting in confusion, falling, and sedation. Drug-related readmissions were associated with living at home, heart failure, and diabetes. Pharmacist-provided interventions were able to reduce PIMs among elderly people with dementia and cognitive impairment

Blood Concentrations of Homocysteine and Methylmalonic Acid among Demented and Non-Demented Swedish Elderly with and without Home Care Services and Vitamin B(12) Prescriptions

BACKGROUND AND AIMS: Total plasma homocysteine (tHcy) has been suggested as a risk factor of dementia. Our aim was to investigate potential differences in tHcy status in relation to the prescription of vitamin B(12) and dementia diagnosis. We examined whether vitamin B(12) prescriptions, a family history of dementia, or the need for home care service might be associated with tHcy values. METHODS: A cross-sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit was conducted. RESULTS: Demented subjects being prescribed vitamin B(12) had higher serum vitamin B(12) (p = 0.025) but also higher tHcy (p &lt; 0.001) and serum methylmalonate (p = 0.032), and lower serum folate (p &lt; 0.001) than those who did not receive vitamin B(12) prescriptions. tHcy levels were significantly higher in non-demented subjects receiving home care service (p = 0.007). This group also had lower serum albumin (dementia: p &lt; 0.001; non-dementia: p = 0.004). There was no difference in renal function (estimated glomerular filtration rate) in demented or non-demented subjects with or without vitamin B(12) prescriptions (dementia with/without vitamin B(12) prescription: p = 0.561; non-dementia with/without vitamin B(12) prescription: p = 0.710). CONCLUSION: Despite vitamin B(12) prescriptions, demented subjects had higher tHcy and methylmalonate values. The elevated metabolite values could not be explained by differences in renal function. Thus, elderly subjects on vitamin B(12) prescription appear to have unmet nutritional needs

Pharmacist participation in hospital ward teams and hospital readmission rates among people with dementia : a randomized controlled trial

Purpose: To assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment. Methods: This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years with dementia or cognitive impairment admitted to three wards at two hospitals located in Northern Sweden were included. Results: Of the 473 deemed eligible for participation, 230 were randomized to intervention and 230 to control group by block randomization. The primary outcome, risk of drug-related hospital readmissions, was assessed at 180 days of follow-up by intention-to-treat analysis. During the 180 days of follow-up, 18.9% (40/212) of patients in the intervention group and 23.0% (50/217) of those in the control group were readmitted for drug-related reasons (HR = 0.80, 95% CI = 0.53–1.21, p = 0.28, univariable Cox regression). Heart failure was significantly more common in the intervention group. After adjustment for heart failure as a potential confounder and an interaction term, multiple Cox regression analysis indicated that pharmacist participation significantly reduced the risk of drug-related readmissions (HR = 0.49, 95% CI = 0.27–0.90, p = 0.02). A post-hoc analysis showed a significantly reduced risk of 30-day readmissions due to drug-related problems in the total sample (without adjustment for heart failure). Conclusion: Participation of clinical pharmacists in healthcare team conducting comprehensive medication reviews did not significantly reduce the risk of drug-related readmissions in patients with dementia or cognitive impairment; however, post-hoc and subgroup analyses indicated significant effects favoring the intervention. More research is needed. Trial registration: Clinical trials NCT01504672

Healthy Nordic diet and associations with plasma concentrations of metabolites in the choline oxidation pathway: a cross-sectional study from Northern Sweden

Abstract Background The choline oxidation pathway and metabolites involved have been linked to diseases including cardiovascular disease, type 2 diabetes and cancer. A healthy Nordic diet is a recently defined dietary pattern associated with decreased risk for these diseases. Our aim was to explore associations between adherence to a healthy Nordic diet and plasma concentrations of metabolites of the choline oxidation pathway. Methods The Healthy Nordic Food Index (HNFI) and Baltic Sea Diet Score (BSDS) were applied to cross-sectional data (n = 969) from the Västerbotten Intervention Programme in Northern Sweden to score adherence to a healthy Nordic diet. Data included responses to a dietary questionnaire and blood sample analyses (1991–2008). Associations of diet scores with plasma concentrations of metabolites of the choline oxidation pathway and total homocysteine (tHcy), seven metabolites in total, were evaluated with linear regression, adjusting for age, BMI, education and physical activity. Results HNFI scores showed linear relationships with plasma choline (β = 0.11), betaine (β = 0.46), serine (β = 0.98) and tHcy (β =  − 0.38), and BSDS scores with betaine (β = 0.13) and tHcy (β =  − 0.13); unstandardized beta coefficients, all significant at P < 0.05. The regression models predicted changes in plasma metabolite concentrations (± 1 SD changes in diet score) in the range of 1–5% for choline, betaine, serine and tHcy. No other statistically significant associations were observed. Conclusions A healthy Nordic diet was associated with plasma concentrations of several metabolites of the choline oxidation pathway. Although relationships were statistically significant, effect sizes were moderate. Further research is warranted to explore the underlying mechanisms and associations with health outcomes

Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p &lt; 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p &lt; 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r s = −0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD

Untangling the role of one-carbon metabolism in colorectal cancer risk : a comprehensive Bayesian network analysis

The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation to CRC risk in 613 cases and 1190 controls from the prospective Northern Sweden Health and Disease Study. The estimated networks corresponded largely to known biochemical relationships. Plasma concentrations of folate (direct), vitamin B6 (pyridoxal 5-phosphate) (inverse), and vitamin B2 (riboflavin) (inverse) had the strongest independent associations with CRC risk. Our study demonstrates the importance of incorporating B-vitamins in future studies of 1CM and CRC development, and the usefulness of Bayesian network learning for investigating complex biological systems in relation to disease

Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk

BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate. METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort. RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06). CONCLUSIONS: In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk. See Video Abstract at http://links.lww.com/EDE/B83