Anticholinergic drug use and its association with self-reported symptoms among older persons with and without diabetes

What is known and objective Anticholinergic drug use has been associated with a risk of central and peripheral adverse effects. There is a lack of information on anticholinergic drug use in persons with diabetes. The aim of this study is to investigate anticholinergic drug use and the association between anticholinergic drug use and self-reported symptoms in older community-dwelling persons with and without diabetes. Methods The basic population was comprised of Finnish community-dwelling primary care patients aged 65 and older. Persons with diabetes were identified according to the ICD-10 diagnostic codes from electronic patient records. Two controls adjusted by age and gender were selected for each person with diabetes. This cross-sectional study was based on electronic primary care patient records and a structured health questionnaire. The health questionnaire was returned by 430 (81.6%) persons with diabetes and 654 (73.5%) persons without diabetes. Data on prescribed drugs were obtained from the electronic patient records. Anticholinergic drug use was measured according to the Anticholinergic Risk Scale. The presence and strength of anticholinergic symptoms were asked in the health questionnaire. Results and discussion The prevalence of anticholinergic drug use was 8.9% in the total study cohort. There were no significant differences in anticholinergic drug use between persons with and without diabetes. There was no consistent association between anticholinergic drug use and self-reported symptoms. What is new and conclusion There is no difference in anticholinergic drug use in older community-dwelling persons with and without diabetes. Anticholinergic drug use should be considered individually and monitored carefully.Peer reviewe

Association between suicidal behaviour and impaired glucose metabolism in depressive disorders

Background: Disturbances in lipid metabolism have been linked to suicidal behaviour, but little is known about the association between suicide risk and abnormal glucose metabolism in depression. Hyperglycaemia and hyperinsulinaemia may increase the risk of depression and also the risk for suicide, we therefore studied associations between suicidal behaviour and disturbances in glucose metabolism in depressive patients who had been referred to depression nurse case managers. Methods: Patients aged 35 years and older (N = 448, mean age 51 years) who were experiencing a new depressive episode, who were referred to depression nurse case managers in 2008-2009 and who scored = 10 on the Beck Depression Inventory were enrolled in this study. The study was conducted in municipalities within the Central Finland Hospital District (catchment area of 274 000 inhabitants) as part of the Finnish Depression and Metabolic Syndrome in Adults study. The patients' psychiatric diagnoses and suicidal behaviour were confirmed by the Mini-International Neuropsychiatric Interview. Blood samples, for glucose and lipid determinations, were drawn from participants after 12 h of fasting, which was followed by a 2-hour oral glucose tolerance test (OGTT) when blood was drawn at 0 and 2 h. Insulin resistance was measured by the Quantitative Insulin Sensitivity Check Index (QUICKI) method.' Results: Suicidal ideation (49 %) and previous suicide attempts (16 %) were common in patients with major depressive disorder or dysthymia. Patients with depression and suicidal behaviour had higher blood glucose concentrations at baseline and at 2 hours in the OGTT. Glucose levels associated positively with the prevalence of suicidal behaviour, and the linearity was significant at baseline (p for linearity: 0.012, adjusted for age and sex) and for 2-hour OGTT glucose (p for linearity: 0.004, adjusted for age and sex). QUICKI levels associated with suicidal behavior (p for linearity across tertiles of QUICKI: 0.026). Total and LDL cholesterol and triglyceride levels were also higher in those patients with suicidal behaviour. Multivariate analysis revealed that blood glucose levels, BDI scores and antidepressive medications associated with suicidal behaviour. Conclusion: Insulin resistance and disturbances in glucose and lipid metabolism may be more common in middle-aged depressive patients with suicidal behaviour.Peer reviewe

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms

Purine metabolism is dysregulated in patients with major depressive disorder

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Pain interference type and level guide the assessment process in chronic pain : Categorizing pain patients entering tertiary pain treatment with the Brief Pain Inventory

Chronic pain patients enter treatment with different problem profiles making careful assessment a necessity for more individualized treatment plans. In this cross-sectional study we assigned 320 patients entering tertiary multidisciplinary pain treatment into four categories based on whether they scored low or high on the activity and the affective pain interference dimensions of the Brief Pain Inventory (BPI). To determine whether this categorization system delineates issues that should be assessed further, the categories were compared with ANOVA and MANOVA analyses on three domains: variables affecting physical well-being (body mass index, exercise, substance use), psychological resources (mood), and painspecific psychological factors (pain anxiety, pain acceptance). The results indicated that subjects who scored low on both interference dimensions compared similarly in weight: mean Body Mass Index (BMI) 27.0 (SD 6.0) kg/m(2), and exercise: mean of 2.4 (SD 1.7) exercising sessions over 20 minutes per week, to the general population, had no depressive symptoms on average: mean Beck Depression Index II (BDI-II) score 11.7 (SD 7.5), and had the most favorable psychological reactions to pain relative to the other categories: mean total Pain Anxiety Symptoms Scale-20 (PASS-20) score 36.4 (SD 17.9). In contrast, when interference was high on activity, more physical well-being problems were evident e.g. weight: mean BMI 31.0 (SD 7.3) kg/m(2), diminished exercise: mean of 1.5 (SD 1.6) exercising sessions per week, and avoidance behavior: mean PASS-20 Escape/Avoidance subscale 3.7 (95% CI: 1.7 to 5.8) scores higher in comparison to activity interference remaining low. With high affective interference, more depressive symptoms: mean BDI-II score 17.7 (SD 7.3), and more cognitive pain anxiety: mean PASS-20 Cognitive Anxiety subscale 2.8 (95% CI 0.7 to 4.8) scores higher in comparison to affective interference remaining low, emerged. Having high interference on both dimensions indicated accumulated risks for reduced physical well-being: mean BMI 29.9 (SD 6.1) kg/m(2), mean of 1.2 (SD 1.7) exercising sessions per week, mood problems: mean BDI-II 20.3 (SD 10.6), and negative psychological reactions to pain: mean total PASS-20 score 53.2 (18.4). The results suggest that low interference on both dimensions may allow assessment with only physician consultations, while high interference on either dimension may call attention to distinct issues to be addressed with the help of a physiotherapist or a psychologist, whereas high interference on both dimensions highlights the need for a full multidisciplinary assessment.Peer reviewe

Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial : a randomized controlled trial

Background Vitamin D insufficiency is associated with risks of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited. Objectives To investigate the effects of vitamin D-3 supplementation on CVD and cancer incidences. Methods The study was a 5-year, randomized, placebo-controlled trial among 2495 male participants >= 60 years and post-menopausal female participants >= 65 years from a general Finnish population who were free of prior CVD or cancer. The study had 3 arms: placebo, 1600 IU/day, or 3200 IU/day vitamin D-3. Follow-up was by annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers, and cancer death. Results During the follow-up, there were 41 (4.9%), 42 (5.0%), and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (compared with placebo: HR: 0.97; 95% CI: 0.63-1.49; P = 0.89), and 3200 IU/d (HR: 0.84; 95% CI: 0.54-1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%), and 40 (4.8%) participants in the placebo, 1600 IU/d (HR: 1.14; 95% CI: 0.75-1.72; P = 0.55), and 3200 IU/d (HR: 0.95; 95% CI: 0.61-1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the subcohort, the mean baseline serum 25-hydroxyvitamin D concentration was 75 nmol/L (SD, 18 nmol/L). After 12 months, the concentrations were 73 nmol/L (SD, 18 nmol/L), 100 nmol/L (SD, 21 nmol/L), and 120 nmol/L (SD, 22 nmol/L) in the placebo, 1600 IU/d, and 3200 IU/d arms, respectively. Conclusions Vitamin D-3 supplementation did not lower the incidences of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline.Peer reviewe

Cross-sectional and longitudinal associations of circulating omega-3 and omega-6 fatty acids with lipoprotein particle concentrations and sizes: population-based cohort study with 6-year follow-up

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Pain, agitation, and behavioural problems in people with dementia admitted to general hospital wards

Pain is underdetected and undertreated in people with dementia. We aimed to investigate the prevalence of pain in people with dementia admitted to general hospitals and explore the association between pain and behavioural and psychiatric symptoms of dementia (BPSD). We conducted a longitudinal cohort study of 230 people, aged above 70, with dementia and unplanned medical admissions to 2 UK hospitals. Participants were assessed at baseline and every 4 days for self-reported pain (yes/no question and FACES scale) and observed pain (Pain Assessment in Advanced Dementia scale [PAINAD]) at movement and at rest, for agitation (Cohen–Mansfield Agitating Inventory [CMAI]) and BPSD (Behavioural Pathology in Alzheimer Disease Scale [BEHAVE-AD]). On admission, 27% of participants self-reported pain rising to 39% on at least 1 occasion during admission. Half of them were able to complete the FACES scale, this proportion decreasing with more severe dementia. Using the PAINAD, 19% had pain at rest and 57% had pain on movement on at least 1 occasion (in 16%, this was persistent throughout the admission). In controlled analyses, pain was not associated with CMAI scores but was strongly associated with total BEHAVE-AD scores, both when pain was assessed on movement (b 5 0.20, 95% confidence interval [CI] 5 0.07- 0.32, P 5 0.002) and at rest (b 5 0.41, 95% CI 5 0.14-0.69, P 5 0.003). The association was the strongest for aggression and anxiety. Pain was common in people with dementia admitted to the acute hospital and associated with BPSD. Improved pain management may reduce distressing behaviours and improve the quality of hospital care for people with dementia