ABSTRACT: Background Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample. Methods The present analysis was based on the DIAB-Core project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described. Results The pooled data set comprised individual data of 15,071 participants aged 45-74 years, including 1287 (8.5%) participants with T2D. Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of >= 140/90 mmHg (OR = 1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio >= 5 (OR = 1.80, 95% CI 1.59-2.04) than participants without T2D. Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated. In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated. Conclusions Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death.

Brain inflammation plays a central role in multiple sclerosis (MS). Besides lymphocytes, the astroglia and microglia mainly contribute to the cellular composition of the inflammatory infiltrate in MS lesions. Several studies were able to demonstrate that cortical lesions are characterized by lower levels of inflammatory cells among activated microglia/macrophages. The underlying mechanisms for this difference, however, remain to be clarified. In the current study, we compared the kinetics and extent of microglia and astrocyte activation during early and late cuprizone-induced demyelination in the white matter tract corpus callosum and the telencephalic gray matter. Cellular parameters were related to the expression profiles of the chemokines Ccl2 and Ccl3. We are clearly able to demonstrate that both regions are characterized by early oligodendrocyte stress/apoptosis with concomitant microglia activation and delayed astrocytosis. The extent of microgliosis/astrocytosis appeared to be greater in the subcortical white matter tract corpus callosum compared to the gray matter cortex region. The same holds true for the expression of the key chemokines Ccl2 and Ccl3. The current study defines a model to study early microglia activation and to investigate differences in the neuroinflammatory response of white vs. gray matter.

Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activator. A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to enhance the plasma levels of PAI-1. In particular, the 4G allele (guanosine deletion) has been linked with increased plasma PAI-1 levels, which may lead to impaired activity of the fibrinolytic system, thus increasing the incidence of thrombotic events. The aim of this case-control study was to analyze whether variants of the PAI-1 promotor genotype 4G/4G, 4G/5G and 5G/5G, in particular the 4G/5G-variant, constitute an independent risk factor of cerebral venous thrombosis (CVT). A total of 136 consecutive patients with proven CVT were compared to 1,054 DNA specimens of healthy controls from a population-based cohort. PAI-1 promotor polymorphisms were evaluated using polymerase chain reaction. No significant association of CVT with PAI-1 4G/5G was found in either the additive (OR 1.04; 95 % CI 0.78-1.38) or in the dominant model (OR 1.24; 95 % CI 0.72-2.13). Also, the prevalence of the other genotypes (4G/4G and 5G/5G) in patients was not significantly different from controls. When considering the variants of the PAI-1 promoter genotype in combination with known genetical thrombophilias, no differences were found either. As was expected, the prothrombin (G20210A) genotype was confirmed as an independent risk factor for CVT. We conclude that the 4G allele of the PAI-1 polymorphism does not increase the risk of CVT in adults.

Summary.  Severe haemophilia results in increased mortality and poorer quality of life. Factor prophylaxis leads to a more normal life, but is very costly; most of the cost is due to the high cost of replacement factor. Despite its high cost, factor prophylaxis has been adopted throughout the developed world - even in different health care systems. We argue that there are at least five possible reasons why societies may value factor prophylaxis despite its cost:(i) it is directed towards an inherited disease,(ii) the treatment is largely directed towards children,(iii) the disease is rare and the overall cost to society is small,(iv) the treatment is preventative, and v) the high cost is largely the result of providing safe products. In an era of rising health care costs, there is a strong research agenda to establish the factors that determine the value of expensive therapies for rare diseases like haemophilia.

OBJECTIVES To evaluate the association between restless legs syndrome (RLS) and incident cardiovascular disease (CVD). DESIGN Prospective cohort study. SETTING Women's Health Study (WHS) and Physicians' Health Study (PHS), USA. PARTICIPANTS 29 756 female health professionals aged ≥45 years and 19 182 male physicians aged ≥40 years at baseline. MAIN OUTCOME MEASURES Main outcome was incidence of major CVD; secondary outcomes were first incidence of myocardial infarction, stroke, death due to CVD or coronary revascularisation. RESULTS 3487 (11.7%) women and 1373 (7.2%) men met International Restless Legs Study Group criteria for RLS. In the WHS 450 major CVD events occurred and 1064 major CVD events were confirmed in the PHS. In both cohorts, RLS was not associated with increased risk of major CVD, stroke, myocardial infarction, CVD death or coronary revascularisation. After adjustment for major vascular risk factors, the HRs (95% CI) for major CVD were 1.15 (0.88 to 1.50) in women and 1.01 (0.81 to 1.25) in men. Highest multivariable-adjusted HRs were 1.29 (0.91 to 1.82) for total stroke in women and 1.22 (0.87 to 1.70) for CVD death in men. Excluding participants with comorbidities potentially leading to RLS did not substantially change the effect estimates. CONCLUSIONS In these large prospective studies of female and male health professionals, RLS was not associated with an increased risk of any incident CVD event. The data do not support the hypothesis that RLS is a marker of increased risk of vascular disease.

Scientific research about patients with substance use disorders (SUD) treated within the context of forensic compulsory addiction treatment is seldom available. Scientifically supported surveys regarding the treatability of SUD patients are rare. Some authors claim that the Psychopathy-Checklist-Revised (PCL-R) has value for predicting therapeutic success. PCL-R scores rely on extensive interview data and a detailed review of criminal records and social history. The scores reflect 1) the affective and interpersonal psychological traits; and 2) socially deviant conduct. This study was conducted by the forensic professional clinic at the hospital for Psychiatry and Neurology Hildburghausen. We assessed 102 male patients using the PCL-R. This investigation evaluated the Total score of the PCL-R and the score of Factor 1 and Factor 2 in relation to the end of treatment by court order. The results showed significant differences between patients who completed treatment and those who did not. Patients that dropped out of treatment had a higher score in PCL-R. With the use of the PCL-R it is possible to make a quantitative statement about which patients will complete treatment.

OBJECTIVE: In multimorbidity indices, chronic conditions are often weighted according to their severity or their impact on different outcomes. These weights are mostly developed on the basis of only one study population by using very specific study participants, such as hospital patients. To overcome the limited validity of the indices, mean weights across five population-based studies were calculated according to the impact of diseases on self-reported health status. STUDY DESIGN AND SETTING: Individual data was provided from the National Health Interview and Examination Survey (n=1,010), Dortmund Health Study (n=281), Memory and Morbidity in Augsburg Elderly Study (n=385), Survey of Health, Aging and Retirement in Europe Study (n=1,278), and Study of Health in Pomerania Study (n=962). By using logistic regression analysis, odds ratios (ORs) were calculated for reporting a fair or poor health status resulting from one of 10 different chronic conditions compared with a reference group without the specific disease, controlling for age and sex. If the results were homogenous across studies (I(2)<40%), significant pooled ORs were considered valid weights for a multimorbidity index. RESULTS: Myocardial infarction has the highest impact on self-reported health status across studies with a pooled OR of 3.9, followed by chronic obstructive pulmonary disease (pooled OR: 3.1). A medium impact was observed for arthrosis, asthma, diabetes mellitus, and osteoporosis. CONCLUSION: This method provided valid weights for seven chronic conditions.

BACKGROUND AND AIMS Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles in liver cirrhosis were identified in screening approaches on liver parenchyma, mostly in rodent models. Therefore, in the present study we performed a systematic screening approach in order to identify miRNAs with altered levels in the serum of patients with chronic liver disease and liver cirrhosis. METHODS We performed a systematic, array-based miRNA expression analysis on serum samples from patients with liver cirrhosis. In functional experiments we evaluated the relationship between alterations of miRNA serum levels and their role in distinct cellular compartments involved in hepatic cirrhosis. RESULTS The array analysis and the subsequent confirmation by qPCR in a larger patient cohort identified significant alterations in serum levels of miR-513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum levels closely correlated with disease stages, thus revealing potential as a novel biomarker for hepatic cirrhosis. Further analysis revealed that up-regulation of miR-571 in serum reflected a concordant regulation in cirrhotic liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic cytokine TGF-β. In contrast, alterations in serum levels of miR-652 were stage-independent, reflecting a concordant down-regulation of this miRNA in circulating monocytes of patients with liver cirrhosis, which was inducible by proinflammatory stimuli like bacterial lipopolysaccharide. CONCLUSION Alterations of miR571 and miR-652 serum levels in patients with chronic liver disease reflect their putative roles in the mediation of fibrogenic and inflammatory processes in distinct cellular compartments involved in the pathogenesis of liver cirrhosis.

Background: Few clinic-based studies report an association between migraine and restless legs syndrome (RLS); however, population-based data are unavailable.Methods: Cohort study among 31,370 women participating in the Women's Health Study. We had detailed self-reported information on migraine, including aura status, and RLS. RLS was ascertained at the 9-year follow-up. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between migraine and RLS. We investigated any indication of migraine until RLS ascertainment as well as migraine with and without aura at baseline, prior migraine before baseline, and new reports of migraine during follow-up.Results: At baseline or during follow-up 6857 (21.9%) women reported any migraine. These women had an increased risk for RLS (multivariable-adjusted OR = 1.22; 95%CI 1.13-1.32). Further analyses indicated a similar association for migraine with aura (multivariable-adjusted OR = 1.27; 95%CI 1.10-1.48) and migraine without aura (multivariable-adjusted OR = 1.24; 95%CI 1.09-1.40) as well as for new reports of migraine during follow-up (multivariable-adjusted OR = 1.30; 95%CI 1.10-1.54). Prior migraine did not appear to be associated with RLS.Conclusions: Our data suggest an association between migraine and RLS at the population level. The association is similar for migraine with and without aura and for new reports of migraine during follow-up.

Few and controversial data exist about the relationship between socio-economic status and restless legs syndrome, and prospective analyses are lacking. We aimed to explore the associations between socio-economic factors and incident restless legs syndrome in the general population. Two prospective population-based cohort studies were conducted: the Dortmund Health Study with a mean follow-up of 2.2 years; and the Study of Health in Pomerania with a mean follow-up of 5.2 years. The studies included 1312 subjects and 4308 subjects, respectively. Restless legs syndrome was assessed twice according to the standard minimal criteria. The modified Winkler Index of social class, education, job status, partnership and income were assessed by interviews at baseline. The risk of restless legs syndrome associated with each socio-economic factor was estimated by multivariable logistic regression adjusted for behavioural factors and co-morbidities. Female gender, being retired and unemployment were independent risk factors of incident restless legs syndrome in both studies. Low level of education and income were independently associated with incident restless legs syndrome only in the Dortmund Health Study, but not in the other study. Migrational background and shiftwork were further independent risk factors of restless legs syndrome that were only assessed in the Dortmund Health Study. People with less favourable socio-economic situation are at an increased risk of developing restless legs syndrome. Behavioural variables and co-morbidities did not explain this association, thus further studies are required to reveal the mechanism behind the proposed relationship.