Differences in risk profile associated with varicose veins and chronic venous insufficiency - results from the Bonn Vein Study 1.

Background: The aim of this publication is to demonstrate similarities and differences in the association of risk factors with the prevalence of different manifestations of chronic venous disease (CVD), like varicose veins (VV), venous oedema (C3) and severe chronic venous insufficiency (CVI) in the population-based cross-sectional Bonn Vein Study 1 (BVS). Patients and methods: In the BVS 1 between 13.11.2000 and 15.3.2002, 3.072 participants, 1350 men and 1722 women, from a simple random sample of the general population of the city of Bonn and two rural townships aged 18-79 years were included. The overall response proportion was 59%. All participants answered a standardized questionnaire including information about socio-economic data, lifestyle, physical activity, medical history, and quality of life. Venous investigations were performed clinically and by a standardized duplex examination by trained investigators. The CEAP classification in the version of 1996 was used to classify the findings. Logistic regression models were performed for the association of possible risk factors with VV, venous edema (C3) and severe CVI (C4-C6). The predictive risk (PR) describes the association of the diseases and the possible influencing factors. Results: VV, venous oedema (C3) and severe CVI (C4-C6) have common risk factors like higher age, number of pregnancies, family history of VV and overweight or obesity. Female gender is significantly associated with VV and C3 but not with severe CVI (C4-C6). High blood pressure and urban living are only associated with C3 and C4-C6 disease whereas prolonged sitting is associated with C3 and lower social class with C4-C6 exclusively. Discussion: In many epidemiological studies risk factors were associated with chronic venous disorders in general. Our data show that VV, venous edema and severe CVI may have different risk profiles. Venous edema is more often associated with arterial hypertension and sedentary lifestyle whereas lower social class seems to be a risk factor for severe CVI including venous ulcers. Conclusions: The differences in the association of risk factors to VV, venous edema and severe CVI should be considered if prevention and treatment of chronic venous diseases are planned. As examples, compression stockings could be proposed in sitting profession to prevent oedema, VV patients with risk factors like obesity might benefit from early treatment for VV and obesity. More longitudinal evaluation of risk factors is necessary to evaluate the true risk profile of CVD.

The association between stress and headache: A longitudinal population-based study.

INTRODUCTION: We studied the association between stress intensity and headache frequency for tension-type headache (TTH), migraine and migraine with coexisting TTH (MigTTH). METHOD: We studied a population-based sample of 5159 participants (21-71 years) who were asked quarterly between March 2010 and April 2012 about headache and stress. Log-linear regression in the framework of generalized estimating equations was used to estimate regression coefficients presented as percent changes to describe the association between stress intensity (modified visual analog scale (VAS) from 0 to 100) and headache frequency (days/month) stratified by headache subtypes and age groups and adjusted for sex, age, frequent intake of acute pain drugs, drinking, smoking, BMI and education. RESULTS: TTH was reported in 31% participants (48.1 ± 12.5years, 51.5% women, 2.2 ± 3.9 mean headache days/month, 52.3 ± 26.7 mean stress), migraine in 14% (44.8 ± 11.3years, 73.3%, 4.5 ± 5.2 days/month, 62.4 ± 23.3), MigTTH in 10.6% (43.5 ± 11.5 years, 61.0%, 3.6 ± 4.8 days/month, 58.6 ± 24.1), 23.6% were unclassifiable, and 20.8% had no headache. In participants with TTH an increase of 10 points on VAS was associated with an increase of headaches days/month of 6.0% (adjusted). Higher effects were observed in younger age groups (21-30/31-40/41-50/51-60/61-71 years: 9.8/10.2/7.0/6.5/3.5%). Slightly lower effects were observed for migraine (4.3%, 8.1/5.1/3.4/6.3/0.3%) and MigTTH (4.2%, 5.5/6.8/6.9/5.8/-0.7%). CONCLUSION: Our study provides evidence for an association between stress intensity and headache frequency.

Therapy with compression stockings in Germany - results from the Bonn Vein Studies.

BACKGROUND: Despite the frequent use of medical compression stockings (MCS), reliable data are lacking on the frequency of MCS use and experience of patients with the treatment. PATIENTS AND METHODS: The Bonn Vein Study included 3,072 participants from the general population aged 18 to 79 years (1,350 men/1,722 women). Between 2007 and 2008 (Bonn Vein Study 2) 1,978 participants from the Bonn Vein Study 1 were reinvestigated. This paper combines the results of both investigations. RESULTS: 14.6% (7.5% men, 20.3% women) reported having previously undergone treatment with compression stockings. A mean of 71.3% reported an improvement in their venous disease as a result of MCS treatment. During the 6.6 years of follow-up (Bonn Vein Study 2), significantly more prescriptions of MCS were given to patients in higher CEAP clinical stages. 12.2% of the population in C2 was treated with MCS as were 19.1% in C3 and 27.0% in C4-C6. Among participants with chronic venous insufficiency (CVI) (skin changes up to venous ulcers), about 60% were not treated by MCS or bandages in the past years. CONCLUSIONS: These results show that MCS is the most common treatment of venous disorders in the German population. At the same time, these figures also demonstrate severely lacking treatment with MCS in CVI.

Ultrasound versus Computed Tomography Assessment of Focal Lung Aeration in Invasively Ventilated ICU Patients.

It is unknown whether and to what extent the penetration depth of lung ultrasound (LUS) influences the accuracy of LUS findings. The current study evaluated and compared the LUS aeration score and two frequently used B-line scores with focal lung aeration assessed by chest computed tomography (CT) at different levels of depth in invasively ventilated intensive care unit (ICU) patients. In this prospective observational study, patients with a clinical indication for chest CT underwent a 12-region LUS examination shortly before CT scanning. LUS images were compared with corresponding regions on the chest CT scan at different subpleural depths. For each LUS image, the LUS aeration score was calculated. LUS images with B-lines were scored as the number of separately spaced B-lines (B-line count score) and the percentage of the screen covered by B-lines divided by 10 (B-line percentage score). The fixed-effect correlation coefficient (ß) was presented per 100 Hounsfield units. A total of 40 patients were included, and 372 regions were analyzed. The best association between the LUS aeration score and CT was found at a subpleural depth of 5 cm for all LUS patterns (ß = 0.30, p < 0.001), 1 cm for A- and B1-patterns (ß = 0.10, p < 0.001), 6 cm for B1- and B2-patterns (ß = 0.11, p < 0.001) and 4 cm for B2- and C-patterns (ß = 0.07, p = 0.001). The B-line percentage score was associated with CT (ß = 0.46, p = 0.001), while the B-line count score was not (ß = 0.07, p = 0.305). In conclusion, the subpleural penetration depth of ultrasound increased with decreased aeration reflected by the LUS pattern. The LUS aeration score and the B-line percentage score accurately reflect lung aeration in ICU patients, but should be interpreted while accounting for the subpleural penetration depth of ultrasound.

Nanoscale arrangement of apoptotic ligands reveals a demand for a minimal lateral distance for efficient death receptor activation.

Cellular apoptosis, the prototype of programmed cell death, can be induced by activation of so-called death receptors. Interestingly, soluble and membrane-bound members of death receptor ligands can differentially activate their receptors. Using the death receptor ligand tumor necrosis factor (TNF) presented on a surface in a nanoscaled pattern with spacings between 58 and 290 nm, we investigated its requirements for spatial arrangement and motility to efficiently activate TNF receptor (TNFR)1 and TNFR2 as well as its chimeras TNFR1-Fas and TNFR2-Fas. We show that the mere mechanical fixation of TNF is insufficient to efficiently activate TNFR2 that is responsive to only the membrane bound form of TNF but not its soluble form. Rather, an additional stabilization of TNFR2(-Fas) by cluster formation seems to be mandatory for efficient activation. In contrast, TNFR1(-Fas) is strongly activated by TNF spaced within up to 200 nm distances, whereas larger spacings of 290 nm fails completely. Furthermore, unlike for TNFR2(-Fas) no dose-response relationship to increasing distances of nanostructured ligands could be observed for TNFR1-(Fas), suggesting that compartmentalization of the cell membrane in confinement zones of approximately 200 nm regulates TNFR1 activation.

Assembly of multilayer arrays of viral nanoparticles via biospecific recognition: a quartz crystal microbalance with dissipation monitoring study.

The development of multilayered thin film assemblies containing (bio)molecules is driven by the need to miniaturize sensors, reactors, and biochips. Viral nanoparticles (VNPs) have become popular nanobuilding blocks for material fabrication, and our research has focused on the well-characterized plant virus Cowpea mosaic virus (CPMV). In a previous study, we have reported the construction of multilayer VNP assemblies. Here we extend these studies by providing further details on the formation and properties of arrays that are made by the alternating deposition of biotinylated CPMV particles and streptavidin molecules. Array formation was followed in real time by a quartz crystal microbalance with dissipation monitoring. Our data provide indications that multiple interactions between biotin and streptavidin not only promote the assembly of a multilayered structure but also generate cross-links within each layer of CPMV particles. The degree of intralayer and interlayer cross-linking and hence the mechanical properties and order of the array can be modulated by the grafting density and spacer length of the biotin moieties on the CPMV particles.

The impact of self-stigmatization on medication attitude in schizophrenia patients.

Negative attitudes towards medication in schizophrenia patients are one major factor contributing to non-adherence behavior. Besides, self-stigmatization represents another frequent and important obstacle in patients suffering from psychotic disorders. Here, we investigated possible associations between medication adherence attitude and the extent of self-stigmatization, while also exploring factors related to self-stigmatization. Sociodemographic characteristics, clinical variables, medication attitude and self-stigmatization were assessed among 81 subjects with schizophrenia or schizoaffective disorder. The cross-sectional data was then analyzed by multivariate analyses. A more positive attitude towards medication was predicted by better insight into illness, lower degree of self-stigmatization and good subjective knowledge about medication (adjusted R2 = 0.23). Furthermore, a higher level of self-stigmatization was associated with lower subjective wellbeing, more severe depressive symptoms and male gender (adjusted R2 = 0.58). Other clinical variables had no additional predictive value for medication adherence attitude or the extent of self-stigmatization. Our findings support the notion that self-stigmatization is an influential factor on medication attitude that should therefore be appreciated in clinical practice. Besides this, special emphasis should be taken on depressive symptoms and reduced wellbeing, especially in male patients, to lower the extent of self-stigmatization.

The importance of strengthening competence and control beliefs in patients with psychosis to reduce treatment hindering self-stigmatization.

Different aspects of self-stigmatization represent barriers for recovery in patients with psychosis disorders. It is unclear whether addressing patient's competence and control beliefs could attenuate the extent of self-stigmatization. The major aim of this study was to identify predictors of self-stigmatization derived from competence and control beliefs in patients (N = 80). Sociodemographic characteristics, clinical variables, competence and control beliefs and self-stigmatization were assessed among 80 patients with psychosis disorders. The cross-sectional data was analyzed by correlation and regression analyses. Results indicate deficits in self-concept of own competences, i.e. the capability of acting in new, difficult or ambiguous situations, resulting in also impaired self-efficacy and relatively increased externality in patients compared to a general population sample. Subjective well-being under neuroleptics, trait-anxiety and defining oneself as religious were the most influential predictors of competence and control beliefs. A weaker self-concept of own competences was also revealed as the strongest predictor of overall high self-stigmatization. Our results stress the importance of orienting treatment strategies towards strengthening the self-concept of own competences in patients in order to reduce self-stigmatization and enhance resilience.

Botulinum neurotoxin type A in the treatment of classical Trigeminal Neuralgia (BoTN): study protocol for a randomized controlled trial.

BACKGROUND: Trigeminal neuralgia is characterized by paroxysmal facial pain attacks. Adequate prophylactic drug therapy is often limited by the lack of efficacy and intolerance due to central nervous system side effects. Subcutaneous injections of botulinum toxin type A are a promising treatment option for patients with unsatisfactory response to drug therapy or neurosurgical intervention. Its effects are expected to last for at least 3 months, so it could be a potential long-term treatment. This is the study protocol of a prospective, placebo-controlled, double blind clinical trial investigating the add-on therapy of subcutaneous administration of botulinum toxin type A injections to standard treatment in therapy-refractory classical trigeminal neuralgia. METHODS AND DESIGN: BoTN is a prospective, double blind, placebo-controlled trial with a randomized withdrawal design in which a single blind phase is followed by a double blind phase (see also Methods and design). Eligible patients with classical trigeminal neuralgia who are otherwise refractory to medical and neurosurgical treatment will receive subcutaneous injections of botulinum toxin type A into injection sites of the affected trigeminal branch. In the first phase all patients will receive botulinum toxin type A in a single blinded intervention. Twelve weeks later therapy responders will be allocated to the verum or placebo (saline) arm in a double blind, randomized manner. These injections will be performed at the same sites as the first injections. This trial will be conducted in a tertiary outpatient clinic specialized in the treatment of headache and facial pain. There will be three investigators performing the injections who are experienced in the treatment of headache and facial pain and trained in botulinum toxin type A injections. DISCUSSION: BoTN is designed to assess the efficacy and safety of subcutaneous botulinum toxin type A injections in addition to standard prophylactic treatment in therapy-refractory trigeminal neuralgia. TRIAL REGISTRATION NUMBER: EU Clinical Trials Register: EudraCT-No: 2014-001959-24 https://www.clinicaltrialsregister.eu/ctr-search/rest/download/trial/2014-001959-24/DE Date of trial registration 26 August 2014.

Long-term outcome of vertigo and dizziness associated disorders following treatment in specialized tertiary care: the Dizziness and Vertigo Registry (DiVeR) Study.

To investigate the long-term outcome of interdisciplinary treatment in a tertiary care neuro-otology institution after 2 years as part of the Dizziness and Vertigo Registry study. Risk factors associated with unfavourable outcome were assessed. 3113 consecutive patients with disorders of vertigo and dizziness were recruited prospectively between March 2010 and February 2012. Patients were clinically assessed and treated according to their diagnosis. Standardized instruments were used at baseline and at 2-year follow-up [Dizziness Handicap Inventory (DHI), Quality of Life Questionnaire, General Depression Scale, Stait-Trait Anxiety Index], as well as a custom health-related questionnaire. The primary outcome variable of this observational study was the change in DHI after 2 years. Patients suffered from phobic postural vertigo (23%), benign peripheral paroxysmal vertigo (14.4%), unilateral vestibulopathy (10.5%), central vestibular disorders (8%), Menière's disease (9.8%), vestibular migraine (6.9%), bilateral vestibulopathy (5.5%), and vestibular paroxysmia (3.1%). Mean disease duration was 4.6 ± 6.3 years. 1272 patients were available for follow-up, 1159 completed the DHI score. 72.1% of patients improved in DHI score from baseline to 2 years follow-up. Mean reduction in DHI score was 14 points (p = 0.02). Long-term outcome following diagnosis and treatment in a specialized tertiary care centre is good and persistent after 2 years. Risk factors for an unfavourable outcome were advanced age, severe disability, constant vertigo or dizziness, and concomitant back pain, while depression and anxiety did not contribute to this risk considerably.

Impact of order and disorder in RGD nanopatterns on cell adhesion.

We herein present a novel platform of well-controlled ordered and disordered nanopatterns positioned with a cyclic peptide of arginine-glycine-aspartic acid (RGD) on a bioinert poly(ethylene glycol) background, to study whether the nanoscopic order of spatial patterning of the integrin-specific ligands influences osteoblast adhesion. This is the first time that the nanoscale order of RGD ligand patterns was varied quantitatively, and tested for its impact on the adhesion of tissue cells. Our findings reveal that integrin clustering and such adhesion induced by RGD ligands is dependent on the local order of ligand arrangement on a substrate when the global average ligand spacing is larger than 70 nm; i.e., cell adhesion is "turned off" by RGD nanopattern order and "turned on" by the RGD nanopattern disorder if operating at this range of interligand spacing.

Prone positioning improves oxygenation in post-traumatic lung injury--a prospective randomized trial.

BACKGROUND: In a prospective randomized trial the effect of prone positioning on the duration of mechanical ventilation was evaluated in multiple trauma patients and was compared with patients ventilated in supine position. METHOD: Multiple trauma patients of the intensive care units of two university hospitals were considered eligible if they met the criteria for acute lung injury or the acute respiratory distress syndrome. Patients in the prone group (N = 21) were kept prone for at least eight hours and a maximum of 23 hours per day. Prone positioning was continued until a PaO2:FiO2 ratio of more than 300 was present in prone as well as supine position over a period of 48 hours. Patients in the supine group (N = 19) were positioned according to standard care guidelines. RESULTS: The duration of ventilatory support did not differ significantly (30 +/- 17 days in the prone group and 33 +/- 23 days in the supine group). Worst case analysis (death and deterioration of gas exchange) displayed ventilatory support for 41 +/- 29 days in the prone group and 61 +/- 35 days in the supine group (p = 0.06). The PaO2:FiO2 ratio increased significantly more in the prone group in the first four days (p = 0.03). The prevalence of Acute Respiratory Distress Syndrome (ARDS) following acute lung injury (p = 0.03) and the prevalence of pneumonia (p = 0.048) were reduced also. One patient in the prone and three patients in the supine group died due to multi organ failure (p = 0.27). CONCLUSIONS: Intermittent prone positioning was not able to reduce the duration of mechanical ventilation in this limited number of patients. However the oxygenation improved significantly over the first four days of treatment, and the prevalence of ARDS and pneumonia were reduced.