The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.
Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5.2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.
Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22.5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1.41, 95% CI 1.09-1.82), and the lowest risk for clozapine (0.74, 0.60-0.91; p=0.0045 for the difference between clozapine vs perphenazine, and p
Comment In: Lancet. 2009 Nov 7;374(9701):1591; author reply 1592-319897117
Comment In: Lancet. 2009 Nov 7;374(9701):1591; author reply 1592-319897118
Comment In: Lancet. 2009 Aug 22;374(9690):590-219595448
Comment In: Lancet. 2009 Nov 7;374(9701):1592; author reply 1592-319897121
Comment In: Lancet. 2009 Nov 7;374(9701):1592; author reply 1592-319897120
Altered immune responses are seen in depression, and recent data suggest that similar changes could also be observable in alexithymia. We examined whether the inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 are independently related to alexithymia or its factors in a population-based sample.
This study formed a clinical part of the Kuopio Depression (KUDEP) general population study focusing on the mental health of a general population of adults aged 25-64 years (n = 308). Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20), and depressive symptoms were assessed using the Beck Depression Inventory (BDI-21).
The levels of IL-6 (in picograms per milliliter) and hs-CRP (in milligrams per liter) were significantly higher in alexithymic than in nonalexithymic subjects (IL-6 effect size, ES: 0.50; hs-CRP ES: 0.27). The BDI scores, hs-CRP and IL-6 explained 33.5% of the variation in TAS scores in the whole study population. According to logistic regression analysis, hs-CRP but not IL-6 increased the likelihood of belonging to the alexithymic group. This observation remained unaltered after additional adjustments for chronic inflammation-related disorders, the use of inflammation-modulating medications and depressive symptoms.
Our findings suggest that the association between hs-CRP and alexithymia resembles that observed in depressed patients. It is, however, independent of depressive symptoms. These findings widen our view on the stress-alexithymia concept.
In this study, the bioelectrical impedance analysis (BIA), skinfold thickness measurement (STM) and dual-energy X-ray absorptiometry (DXA), as a reference method, were compared with each other in the assessment of body composition in elderly (62-72-year-old) Finnish women (n=93). BIA had better agreement with DXA in the assessment of fat free mass (FFM, R2=0.70, Sres=2.1) and fat mass (FM, R2=0.93, Sres=2.3) than the STM (FFM, R2=0.62, Sres=2.4; FM, R2=0.89,Sres=2.8). There was quite a large variation in the estimates when different BIA prediction equations were used. The equation developed in this study, FFM (kg)=-128.06 + 1.85 x BMI-0.63 x weight + 1.07 x height - 0.03 x resistance +10.0 x waist-hip ratio, yielded a small and unbiased error (0.5 +/- 1.6 kg), with a small residual standard deviation (R2=0.83, Sres=1.6). However, error associated with the estimate of FM was positively related to the degree of FM. BIA(Heitmann) equation yielded unbiased estimates of both FFM and FM (FFM, R2=0.77, Sres=1.8; FM, R2=0.95, Sres=1.9). Both the STM and BIA (manufacturer's equation) resulted in error which was statistically significant and positively correlated with FFM and FM. These results indicate that BIA prediction equations, chosen with care, can improve the performance of equations based upon anthropometric measurements alone in the assessment of body composition in elderly women.
1Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 2Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland 3Department of Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland 4Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Recent studies of perimenopausal women have observed associations of follicle-stimulating hormone (FSH) levels with markers of insulin resistance, independent of estradiol. Whether FSH is related to type 2 diabetes (T2D) in older women who have completed the menopause transition remains unknown. We assessed the association of FSH levels with diabetes and measures of insulin resistance among 588 postmenopausal Finnish women.
Study participants were aged 53 to 73 years and not using hormone therapy at baseline (1998-2001) when FSH was measured. Prevalence of T2D was assessed at baseline, along with fasting insulin and glucose levels. Incident T2D, and insulin and glucose levels were assessed 7 to 9 years later at follow-up examination.
After adjustment for age, estradiol, body mass index, smoking, lipids levels, and other factors, women with higher FSH (>50?IU/L) had a lower prevalence of T2D (odds ratio 0.49, 95% confidence interval [CI] 0.28-0.86) than women with lower FSH. Each 1 unit increase in FSH level was associated with a significant 1.9% lower risk of T2D (95% CI 0.966-0.997, P?=?0.02). Higher FSH was associated with marginally significant lower incidence of T2D at follow-up (hazard ratio 0.53, 95% CI 0.27-1.02). Baseline FSH levels were inversely correlated with fasting insulin and glucose levels at both baseline and follow-up visits (all P?
Low serum 25-hydroxyvitamin D (25OHD) level has been associated with an increased risk of several chronic diseases. Our aim was to determine lifestyle and clinical factors that are associated with 25OHD level and to investigate connection of 25OHD level with metabolic and cardiovascular disease markers.
In total, 2868 Finnish men and women aged 45-74 years participated in FIN-D2D population-based health survey in 2007. Participants that had a serum sample available (98.4%; n?=?2822) were included in this study. 25OHD was measured with chemiluminescent microparticle immunoassay method.
The mean 25OHD level was 58.2 nmol/l in men (n?=?1348) and 57.1 nmol/l in women (n?=?1474). Mean 25OHD level was lower in the younger age groups than in the older ones (p
Starch in white wheat bread (WB) induces high postprandial glucose and insulin responses. For rye bread (RB), the glucose response is similar, whereas the insulin response is lower. In vitro studies suggest that polyphenol-rich berries may reduce digestion and absorption of starch and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of berries consumed with WB or RB on postprandial glucose and insulin responses. Healthy females (n = 13-20) participated in 3 randomized, controlled, crossover, 2-h meal studies. They consumed WB or RB, both equal to 50 g available starch, with 150 g whole-berry purée or the same amount of bread without berries as reference. In study 1, WB was served with strawberries, bilberries, or lingonberries and in study 2 with raspberries, cloudberries, or chokeberries. In study 3, WB or RB was served with a mixture of berries consisting of equal amounts of strawberries, bilberries, cranberries, and blackcurrants. Strawberries, bilberries, lingonberries, and chokeberries consumed with WB and the berry mixture consumed with WB or RB significantly reduced the postprandial insulin response. Only strawberries (36%) and the berry mixture (with WB, 38%; with RB, 19%) significantly improved the glycemic profile of the breads. These results suggest than when WB is consumed with berries, less insulin is needed for maintenance of normal or slightly improved postprandial glucose metabolism. The lower insulin response to RB compared with WB can also be further reduced by berries.
Obesity protects against osteoporosis, but the magnitude of this association has been difficult to assess from cross-sectional or short term studies. We examined the time course of bone loss as a function of body mass index (BMI) in early and late postmenopausal women. Our study population (n = 300) was a random sample of the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. We excluded women without complete BMD results, premenopausal women during the second bone densitometry and women who had used hormone replacement therapy, bisphosphonates or calcitonin. BMI along with femoral neck and spinal bone mineral density (BMD) were assessed three times by dual-energy X-ray absorptiometry during a mean follow-up of 10.5 years (SD 0.5). The mean baseline age was 53.6 years (SD 2.8), time since menopause 2.9 years (SD 4.3) and BMI 27.3 kg/m(2) (SD 4.4). The data was analyzed by linear mixed models. Thus, we were able to approximate the bone loss up to 20 postmenopausal years. To illustrate, a woman with a baseline BMI of 20 kg/m(2) became osteopenic 2 (spine) and 4 (femoral neck) years after menopause, while obesity (BMI of 30 kg/m(2)) delayed the incidence of osteopenia by 5 (spine) and 9 (femoral neck) years, respectively. The delay was due to high baseline BMD of the obese, while bone loss rate was similar for both lean and obese subjects. This lean versus obese difference may also be partly due to altered X-ray attenuation due to fat mass.
To study screening of high-risk individuals as part of a national diabetes prevention programme in primary health care settings in Finland between 2003 and 2007, and evaluate the cardiometabolic risk profile of persons identified for intervention.
High-risk individuals were identified by the Finnish Diabetes Risk Score (FINDRISC), history of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), cardiovascular disease (CVD), or gestational diabetes. Participants subsequently underwent an oral glucose tolerance test. CVD morbidity risk was estimated by the Framingham Study Risk Equation and CVD mortality risk by the Systematic Coronary Risk Evaluation Formula (SCORE).
A high-risk cohort of 10,149 (of whom 30.3% men) was identified (mean age 54.7 for men, 53.0 for women). Altogether 18.8% of men and 11.5% of women had screen-detected diabetes. In total 68.1% of men and 49.4% of women had abnormal glucose tolerance (IFG, IGT or screen-detected diabetes). Furthermore, 43.2% and 41.5% of men, and 13.3% and 11.3% of women, respectively, had a high predicted risk of CVD morbidity or mortality.
Prevalence of dysglycemia including undiagnosed diabetes and the predicted risk for CVD was alarmly high in the identified high-risk cohort, particularly in men.
To assess the cost-effectiveness of insulin detemir compared with Neutral Protamine Hagedorn (NPH) insulin when initiating insulin treatment in people with type 2 diabetes mellitus (T2DM) in Denmark, Finland, Norway, and Sweden.
Efficacy and safety data were derived from a 20-week multi-centre randomized controlled head-to-head clinical trial comparing insulin detemir and NPH insulin in insulin naïve people with T2DM, and short-term (1-year) cost effectiveness analyses were performed. As no significant differences in HbA1c were observed between the two treatment arms, the model was based on significant differences in favour of insulin detemir in frequency of hypoglycaemia (Rate-Ratio?=?0.52; CI?=?0.44-0.61) and weight gain (??=?0.9?kg). Model outcomes were measured in Quality Adjusted Life Years (QALYs) using published utility estimates. Acquisition costs for insulin and direct healthcare costs associated with non-severe hypoglycaemic events were obtained from National Health Service public sources. One-way and probabilistic sensitivity analyses were performed.
Based on lower incidence of non-severe hypoglycaemic events and less weight gain, the QALY gain from initiating treatment with insulin detemir compared with NPH insulin was 0.01 per patient per year. Incremental cost-effectiveness ratios for the individual countries were: Denmark, Danish Kroner 170,852 (€22,933); Finland, €28,349; Norway, Norwegian Kroner 169,789 (€21,768); and Sweden, Swedish Krona 226,622 (€25,097) per QALY gained. Possible limitations of the study are that data on hypoglycaemia and relative weight benefits from a clinical trial were combined with hypoglycaemia incidence data from observational studies. These populations may have slightly different patient characteristics.
The lower risk of non-severe hypoglycaemia and less weight gain associated with using insulin detemir compared with NPH insulin when initiating insulin treatment in insulin naïve patients with type 2 diabetes provide economic benefits in the short-term. Based on cost/QALY threshold values, this represents good value for money in the Nordic countries. Using a short-term modelling approach may be conservative, as reduced frequency of hypoglycaemia and less weight gain may also have positive long-term health-related implications.
This study evaluated the long-term cost-effectiveness of atorvastatin 20 mg, rosuvastatin 10 mg and simvastatin 40 mg in primary and secondary prevention of CHD in Finland.
The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3-6.6% baseline risk of dying from cardiovascular disease within a 10-year period.
Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (euro/LYG) and cost of quality adjusted life years gained (euro/QALY).
The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was euro10 834 and the cost of one QALY gained was euro36 548 (discount rate 5% per annum). Corresponding figures for atorvastatin were euro31 286/LYG and euro105 599/QALY.
If the decision makers' willingness to pay for a QALY gained is around euro40 000 there is a high probability (>50%) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3-6.6% risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.