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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 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.

Objective: Smoking has previously been associated with inflammatory bowel disease (IBD), but no study has reported on cotinine, an objective, biochemical measure of tobacco use. We aimed at testing the hypothesis that cotinine levels among healthy subjects are associated with an increased risk of developing IBD in later life.

Design: We analysed plasma cotinine and evaluated corresponding lifestyle questionnaires that included tobacco habits in subjects (n = 96) who later developed late-onset IBD (70 ulcerative colitis (UC) and 26 Crohn’s disease (CD)) and in sex and age-matched controls (n = 191).

Results: Patients who later developed IBD had significantly higher plasma cotinine levels compared to controls. In multivariable analysis, higher log-cotinine was associated with a higher risk of developing IBD (OR 1.34 (95% CI 1.01–1.63)). After stratifying for time to diagnosis, the association was only significant in subjects with shorter time (< 5.1 years) to diagnosis (OR 1.45 (1.09–1.92)). The findings were similar for UC- and CD-cases, but did not reach statistical significance in CD-cases. Although plasma cotinine concentrations were higher in snuff users compared to combusted tobacco users, no increase in the risk of IBD and lower risk of developing IBD among subjects with shorter time (< 5.1 years) to diagnosis was seen among snuff users.

Conclusions: Cotinine, a biomarker of tobacco use, is associated with increased risk of developing late-onset IBD in general, and UC in particular. No increased risk among snuff users indicates that other components in combusted tobacco than nicotine may be involved in the pathogenesis of IBD among smokers.

Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis.

Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation.

Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22–2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring.

Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (>= 353 mu g/day) compared to the lowest (<241 mu g/day) was 0.81 (95% CI: 0.51, 1.31; p(trend) = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles [HR = 4.42 (95% CI: 1.05, 18.62) for >= 353 mu g/day vs. <241 mu g/day, p(trend) = 0.01]. Nonetheless, there was no significant interaction between smoking and dietary folate intake (p(interaction) = 0.99). We found no association between dietary folate intake and PC risk in this large European study.

BACKGROUND: Clinical pharmacists play an increasing role in the pharmacological treatment of hospital-admitted older patients with dementia or cognitive impairment. In an earlier randomised controlled trial, clinical pharmacist involvement in the ward team could significantly reduce drug-related readmissions in patient subgroups. However, the economic impact of the intervention has not been addressed so far.

OBJECTIVES: To evaluate the economic impact of clinical pharmacist engagement in hospital ward teams for medication therapy management in older patients with dementia or cognitive impairments.

METHODS: Economic evaluation of a randomised controlled trial conducted in two hospitals in Northern Sweden between January 2012 and December 2014. Participants included 460 hospital-admitted older patients with dementia or cognitive impairments. Patients were randomly assigned to usual care, or usual care with pharmacist intervention; the intervention consisted of medication reconciliation, medication review, and participation in ward rounds. The outcomes were measured as drug-related readmissions to hospital as assessed by a group of external experts, 180 and 30 days after discharge. Costs included pharmacists' direct labour costs for the interventions, average costs for drug-related readmissions, and from this the total cost per person was calculated.

RESULTS: The effect of the intervention on drug-related readmissions within 180 days was significant in patients without heart failure (subgroup analysis), and the intervention resulted in cost savings of €950 per person in this subgroup. Drug-related readmissions within 30 days were reduced in the total sample (post-hoc analysis), and the cost-savings in this intervention group were €460 per person.

CONCLUSIONS: Post-hoc and subgroup analyses indicate that engagement of pharmacists in hospital ward teams reduced the number of drug-related readmissions, and that the cost per person was lower in the intervention group compared to the control group. Including clinical pharmacists created savings in the subgroups of older patients with dementia or cognitive impairments.

Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

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.

Background: The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear.

Objective: To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men.

Design: Randomized controlled trial. (ClinicalTrials.gov: NCT00119912)

Setting: Oslo and Telemark County, Norway. Participants: Adults aged 50 to 64 years at baseline without prior CRC.

Intervention: Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy.

Measurements: Age-adjusted CRC incidence and mortality stratified by sex.

Results: Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, -0.19 percentage point [95% CI, -0.49 to 0.11 percentage point]; HR, 0.92 [CI, 0.79 to 1.07]). In men, the corresponding risks were 1.72% and 2.50%, respectively (risk difference, -0.78 percentage point [CI, -1.08 to -0.48 percentage points]; hazard ratio [HR], 0.66 [CI, 0.57 to 0.78]) (P for heterogeneity = 0.004). The absolute risks for death from CRC in women were 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, -0.16 to 0.18 percentage point]; HR, 1.01 [CI, 0.77 to 1.33]). The corresponding risks for death from CRC in men were 0.49% and 0.81%, respectively (risk difference, -0.33 percentage point [CI, -0.49 to -0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014).

Limitation: Follow-up through national registries.

Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women.