Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study.

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

4G versus 3G-enabled telemedicine in prehospital acute stroke care.

BACKGROUND: Time to reperfusion treatment is closely related to outcome in ischemic stroke. Prehospital stroke work-up in CT-equipped mobile stroke units is effective in reducing time to thrombolytic treatment. Current evidence predominantly comes from mobile stroke units staffed with neurologists but telemedicine-guided management may be acceptable for providing neurological expertise in ambulances. With unsatisfactory experiences in third-generation (3G)-based approaches, fourth-generation (4G) networks may provide adequate audio-visual quality but systematic comparisons of technological parameters and decision-making are lacking. METHODS: Trained actors presented stroke symptoms and paramedics assisted the remotely guided extended National Institutes of Health Stroke Scale (eNIHSS) assessment on the mobile stroke unit in Berlin, Germany. We compared technical parameters of 4G and 3G connections, assessed audio-visual quality of examination, and analyzed reliability of neurological assessment and treatment decisions made by the remote neurologist versus the mobile stroke unit neurologist. RESULTS: 4G and 3G connections were evaluated in 40 scenarios each. Connectivity was not available in 17% of 4G- and 15% of 3G-attempts with 6% simultaneous unavailability of both networks. The remote examiners graded audio and video quality in 4G better than in 3G with slightly shorter assessment duration in 4G (mean: 9 (SD:5) vs. mean 11 (SD:3) min, p = 0.10). Reliability of the eNIHSS sum scores was high with intraclass correlation coefficients of 0.99 (95% CI: 0.987-1.00) for 4G and 0.98 (95% CI: 0.96-0.99) for 3G. None of the remote treatment decisions differed from onsite decisions. CONCLUSIONS: 4G mobile communications provided higher quality of video-examination and allowed reliable remote assessment of stroke symptoms but coverage was still incomplete in both networks.

Characteristics associated with outcome in patients with first-ever posterior fossa stroke.

BACKGROUND AND PURPOSE: Factors such as infarct volume, infarct location and symptom severity can considerably influence long-term outcome in posterior fossa strokes. The decision about therapy can sometimes be complicated by discrepancies between infarct volume and clinical severity. We aimed to evaluate imaging and clinical parameters possibly influencing long-term outcome in patients with first-ever posterior fossa stroke. METHODS: Imaging was performed on a 3-T magnetic resonance imaging scanner. Sixty-one of 1795 patients from the observational 1000Plus and LOBI studies (NCT00715533 and NCT02077582, clinicaltrials.org) were enrolled, meeting the inclusion criteria of first-ever posterior fossa stroke and magnetic resonance imaging examination within 24 h after symptom onset. Infarcts were classified as belonging to a proximal, middle or distal territory location in the posterior fossa. Good outcome was defined as a modified Rankin scale score of ≤1 at 3 months. RESULTS: The largest lesion volumes on diffusion-weighted imaging on day 0 and fluid attenuation inversion recovery (FLAIR) on day 6 were found in the middle territory location with a median volume of 0.4 mL on diffusion-weighted imaging and 1.0 mL on FLAIR on day 6 versus 0.1/0.3 mL in the proximal and 0.1/0.1 mL in the distal territory location of the posterior fossa, respectively. Parameters associated with poor outcome were older age (P = 0.005), higher National Institutes of Health Stroke Scale score on admission/discharge (P = 0.016; P = 0.001), larger lesion volumes on FLAIR on day 6 (P = 0.013) and dysphagia (P = 0.02). There was no significant association between infarct location and modified Rankin scale score on day 90. CONCLUSION: Infarct volume and clinical severity, but not infarct location, were the main contributors to poor long-term outcome in first-ever posterior fossa strokes.

Effects of Omega-3 Fatty Acids on Resting Cerebral Perfusion in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

Alteration of cerebral perfusion can be considered as a possible therapeutic target in mild cognitive impairment. This randomized, placebo-controlled, double-blind proof-of-concept study assessed effects of omega-3 fatty acids on cerebral perfusion in patients with mild cognitive impairment. In thirteen patients (omega:n=5; placebo:n=8) cerebral perfusion was measured before and after 26-weeks intervention within posterior cortical regions using magnetic resonance imaging. There was a medium effect of intervention on cerebral blood flow (η2=0.122) and blood volume (η2=0.098). The omega group showed an increase in blood flow (mean difference: 0.02 [corresponds to 26.1%], 95% confidence interval:0.00-0.05) and blood volume (mean difference: 0.08 [corresponds to 18.5%], 95% confidence interval:0.01-0.15), which was not observed in the placebo group. These preliminary findings suggest that omega-3 fatty acids supplementation may improve perfusion in cerebral regions typically affected in mild cognitive impairment.Regulation of perfusion may help to maintain brain structure and function and potentially delay conversion to dementia.

Biomechanical strength and failure mechanism of different tubercula refixation methods within the framework of an arthroplasty for shoulder fracture.

BACKGROUND: Tuberosity repair in shoulder fracture prosthesis implantation still remains a challenge often leading to poor functional outcomes, despite a variety of materials and suggested suture patterns. We aimed to evaluate, which forces currently used suture and cerclage materials withstand and to assess whether they are useful with regard to stability of reconstruction of tuberosities and which failure modes they display. MATERIAL AND METHODS: Using sheep infraspinatus tendons with attached tuberosities three different suture materials (suture 1: Ethibond size 2; suture 2: Orthocord size 2; suture 3: Fiberwire size 5) and a 0.8mm titanium cerclage wire were investigated. For each suture material as well as the cerclage wire 6 tests were carried out. A material testing machine was used to perform cyclic loading tests (20mm/min, Fmin=50N, Fmax=100N, respectively after 50 cycles: Fmax+50N until failure). Outcome measures and thus comparison criteria were the maximum holding force, number of cycles reached, total elongation of the system (tendon and suture) and qualitative appraisal and documentation of the mechanism of failure. RESULTS: Overall average maximum forces between the fixation materials differed significantly (P=0.003), especially suture 3 (braided polyethylene coating, non-resorbable polyfile UHMW core) displayed superior results in comparison to the cerclage wire (P=0.016). Although, primary elongation of the cerclage technique was significantly lower compared to the suture materials (P=0.002). All tests showed a high initial lengthening and caused incision-like defects in the bone or tendon and led to failure and huge displacement of the tuberosities. DISCUSSION: Currently used suture and cerclage materials have a limited usefulness for refixation of tuberosities due to an increased risk of obstruction for bony consolidation. LEVEL OF EVIDENCE: Basic science, Biomechanics.

Right insular infarction and mortality after ischaemic stroke.

BACKGROUND AND PURPOSE: Several studies have described an association between insular infarction and mortality. Large infarcts often include the insula and lesion size is associated with mortality. We hypothesized that there is an association between insular infarction and mortality independent of lesion volume. METHODS: We included consecutive stroke patients between 1 September 2008 and 11 November 2012 from the 1000Plus database with an acute ischaemic lesion on diffusion-weighted imaging on day 1 and a completed 90-day follow-up. Insular infarct location was determined using the in-house software Stroke Lesion Atlas. In multiple Cox regression analysis (dependent variable: mortality), we adjusted for insular infarcts, age, lesion volume, history of atrial fibrillation, National Institutes of Health Stroke Scale and previous stroke. RESULTS: We included 736 patients, of whom 168 had an insular infarction. Within a medium follow-up time of 107 days, cumulative survival was 90% in patients with insular infarction and 99% in patients without insular infarction (P < 0.001). Right insular infarction was independently associated with mortality (hazard ratio, 2.60; confidence interval, 1.3-5.4; P = 0.010). CONCLUSIONS: In our study, right insular involvement was a prognostic marker for mortality after ischaemic stroke. A selection bias towards patients able to give informed consent warrants further studies.

Impact of heart rate on admission on mortality and morbidity in acute ischaemic stroke patients - results from VISTA.

BACKGROUND AND PURPOSE: Elevated heart rate (HR) is associated with worse outcomes in patients with cardiovascular disease. Its predictive value in acute stroke patients is less well established. We investigated the effects of HR on admission in acute ischaemic stroke patients. METHODS: Using the Virtual International Stroke Trials Archive (VISTA) database, the association between HR in acute stroke patients without atrial fibrillation and the pre-defined composite end-point of (recurrent) ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) and vascular death within 90 days was analysed. Pre-defined secondary outcomes were the composite end-point components and any death, decompensated heart failure and degree of functional dependence according to the modified Rankin Scale after 90 days. HR was analysed as a categorical variable (quartiles). RESULTS: In all, 5606 patients were available for analysis (mean National Institutes of Health Stroke Scale 13; mean age 67 years; mean HR 77 bpm; 44% female) amongst whom the composite end-point occurred in 620 patients (11.1%). Higher HR was not associated with the composite end-point. The frequencies of secondary outcomes were 3.2% recurrent stroke (n = 179), 0.6% TIA (n = 35), 1.8% MI (n = 100), 6.8% vascular death (n = 384), 15.0% any death (n = 841) and 2.2% decompensated heart failure (n = 124). Patients in the highest quartile (HR> 86 bpm) were at increased risk for any death [adjusted hazard ratio (95% confidence interval) 1.40 (1.11-1.75)], decompensated heart failure [adjusted hazard ratio 2.20 (1.11-4.37)] and worse modified Rankin Scale [adjusted odds ratio 1.29 (1.14-1.52)]. CONCLUSIONS: In acute stroke patients, higher HR (>86 bpm) is linked to mortality, heart failure and higher degree of dependence after 90 days but not to recurrent stroke, TIA or MI.

Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack.

BACKGROUND AND PURPOSE: Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. METHODS: The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. RESULTS: The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). CONCLUSIONS: In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.

[The Rostock Headache Questionnaire ("Rokoko")--validation of a tool to screen and to qualify primary headaches]. / Der Rostocker Kopfschmerzfragen-Komplex ("Rokoko")--Validierung einer schnellen diagnostischen Hilfe bei der Einordnung primärer Kopfschmerzen.

Primary headache disorders should be diagnosed based on the detailed history of the patient. However, only few questions are necessary to allocate the symptoms to migraine, tension-type headache or other primary headaches in most cases. The "Rostock Headache Questionnaire" (Rokoko) is suitable for being completed by the investigator or the patient him/herself within a few minutes. Validation parameters of a sample of n = 87 patients (median: 44 years), diagnosed by headache experts in a personal interview ("gold standard"), are presented. Sensitivity and specificity for migraine without aura (0.87/0.51), migraine with aura (0.71/0.95), tension-type headache (0.57/0.93), or a combination of both (0.22/0.93) are based on the parameters pain frequency (recurrent vs. permanent), and the presence or absence of aura symptoms. To differentiate tension-type headache into episodic or chronic forms, the questionnaire can be analysed individually based on the frequency of headache days. The questionnaire enables the fast acquisition of relevant data in headache diagnosis and headache research with sufficient sensitivity and specificity. In addition, further information about triggering and symptoms of headaches can be assessed. The questionnaire can be used both by neurologists or psychiatrists and by general practitioners. The questionnaire does not replace the physical examination.

[Residential mobility in old age. Age-appropriate housing as a primary preventive strategy]. / Wohnmobilität im Alter. Altersgerechtes Wohnen als primärpräventive Strategie.

BACKGROUND: Unfavorable living conditions in old age have negative physical, psychological and social implications and increase the risk of institutionalization. The aim of this study is to examine older adults' readiness to relocate to age-appropriate housing versus the wish to stay where they are. METHODS: A total of 103 older men and women were questioned prospectively, face-to-face, regarding their readiness to relocate. In addition to assessing several established predictors of residential mobility, data on objective living situations were collected. The data were subjected to bi- and multivariate analysis. RESULTS: At 70.9%, the proportion of respondents who are not willing to move (stayers) far exceeds the proportion of those who are (movers, 29.1%). Older respondents are more satisfied with their living situation and less likely to move. This study provides empirical evidence for the "satisfaction paradox" with respect to living conditions and for the importance of the subjective standard of living for quality of life in old age. CONCLUSION: Modern housing counseling should more strongly reflect the variety of needs, requirements and living situations of older people today than it has done in the past. It is therefore recommended that the currently dominating paradigm of "aging in place" be critically re-evaluated.

Predicting post-stroke pneumonia: the PANTHERIS score.

OBJECTIVES: Stroke-associated pneumonia (SAP) is a common complication with a known negative impact on neurological outcome. We developed a score to identify patients at highest risk of SAP in order to promote prophylactic measures. MATERIALS AND METHODS: We conducted a cohort study on a neurological intensive care unit in patients suffering from acute ischemic MCA infarction. Association of predefined demographics, comorbidities, and clinical characteristics with SAP was investigated using logistic regression analysis. RESULTS: Between 2003 and 2010, a total of 335 patients were included in this analysis. Frequency of SAP was 31.3%. A 12-point scoring system was developed based on the following factors: Glasgow Coma Scale (GCS) [GCS < 9 = 5, GCS 9-12 = 2, GCS > 12 = 0], age [<60 = 0, 60-80 = 1, >80 = 2], increase in systolic arterial blood pressure >200 mmHg within the first 24 h after admission [no = 0, yes = 2], and white blood cell count >11.000/µl [no = 0, yes = 3]. The score revealed excellent discrimination (AUC = 0.85) and calibration (Nagelkerke's R² = 0.46) properties. Predictive properties were reproduced in an internal validation group. CONCLUSIONS: The PANTHERIS score is a simple scoring system for the prediction of SAP based on easy-to-assess parameters. By identifying patients at high risk, it may guide intense monitoring or prophylactic measures. This score needs to be validated within external datasets.

[Health-care reforms and insurees' preferences: a cluster analysis with data from the representative KBV survey 2010]. / Gesundheitsreformen und Versichertenpräferenzen. Eine Clusteranalyse mit Daten der bevölkerungsrepräsentativen KBV-Befragung 2010.

This study examines insurees' knowledge of and attitudes towards a number of recent reforms of the German healthcare system (electronic health insurance card, reimbursement tariff, etc.). It further examines whether it is possible to identify groups of respondents with similar patterns of preferences and knowledge. The analysis draws on a representative survey conducted by the German National Association of Statutory Health Insurance Physicians (Kassenärztliche Bundesvereinigung, KBV, 2010), in which 6 065 respondents aged between 18 and 79 years were interviewed. 4 groups of respondents can be distinguished: the "quality oriented," the "uninformed," the "internet savvy," and the "informed." The most striking finding is that members of the "uninformed" group, who knew the least about recent reforms, tended to be employed middle-aged men with a high level of formal education. To foster the successful implementation of reforms in the health-care system and their communication to specific target groups, it is recommended to take into account not only specific social determinants, but the full personal circumstances and situation of insurees.

[Patients with minor injuries in a Berlin inner-city emergency room : substance misuse, residential area, and sociodemographics]. / Leichtverletzte Patienten einer innerstädtischen Rettungsstelle in Berlin : Substanzmissbrauch, Wohnbereich und Sozialstruktur.

BACKGROUND: The aim of this post hoc study was to evaluate the association of substance use disorders (SUD) and residential neighborhood affiliation in a group of patients with minor injuries presenting to an inner-city emergency room (ER) in Berlin. METHODS: A total of 2,716 patients with minor injuries presenting to the ER were evaluated concerning alcohol use disorders (AUDIT, cut-off: males 8 points, females 5 points), smoking status, and illicit drug use in the past year. Information about residential area (zip code) and sociodemographics (paper-pencil questionnaire) were also obtained. RESULTS: With respect to residential area, significant differences concerning SUD were identified: from the perspective of the inner-city ER, living close to the ER was associated with substance misuse. Here, alcohol use disorders (AUD), smokers, and illicit drug use were found more frequently compared to patients living in the periphery of the city. In addition, patients living close to the ER were more often unemployed, had a lower income, or were students. CONCLUSION: There are differences in SUD with respect to residential area. However, in order to be able to draw reliable conclusions, an approach collecting representative data at the city district level as well as using a multicenter approach at the city ER level is necessary.

[Biomechanical investigation on refixation of tuberosities on shoulder prostheses. Does refixation with different suture materials offer enough stability?]. / Biomechanische Untersuchung zur Refixation der Tuberkula an Frakturschulterendoprothesen. Bietet die Rekonstruktion der Tuberkula mittels unterschiedlicher Nahtmaterialien eine ausreichende Stabilität?

BACKGROUND: Elderly patients suffering from complex, non-reconstructable fractures of the proximal humerus are commonly treated by primary implantation of a shoulder endoprosthesis. One of the most critical factors for success or failure of treatment is still the refixation of the tuberosities. METHOD: Using sheep infraspinatus tendons with attached tuberosities three different suture materials were investigated. For 2 of the suture materials 4 tests were accomplished and 5 tests were carried out for the third suture material. A material testing machine was used to perform cyclic loading tests (20 mm/min, Fmin=50 N, Fmax=100 N, respectively after 50 cycles: Fmax+50 N until failure). RESULTS: The results showed large variations in the average maximum forces (152.4 N for suture 1, 219.9 N for suture 2 and 452.3 N for suture 3). All tests showed a high initial lengthening and caused incision-like defects in the bone or tendon and led to failure and high displacement of the tuberosities. CONCLUSION: Due to these results suture materials have a limited usefulness for refixation of tuberosities as an increased risk of obstruction for bony consolidation can result.

[The construction of an empirically based social status index through optimal scaling as illustrated by Germany]. / Die Konstruktion eines empirisch bestimmten Sozialschichtindexes mittels optimaler Skalierung am Beispiel von Deutschland.

Numerous epidemiological studies have shown an association between social status and disease. In alcohol research, socio-economic status (SES) has been associated with drinking patterns, misuse and alcohol problems. SES is a construct which is usually built by using the indicators education, occupation or income separately or combined as a summary score. However, either approach involves theoretical assumptions about the explanatory value of a chosen indicator before the data have been analysed. In this study we have created a gender-specific metric social status indicator for Germany by using all three single SES-indicators (education, occupation, income). We used national representative data from a postal survey from 2000. The age range was restricted to 25 - 59 years. To construct the indicator we used optimal scaling (categorical principal components analysis). Therefore no theoretical assumptions were necessary about the hierarchical order of educational or occupational categories. The optimal-scaling approach allows variables to be scaled on different levels. We used education and occupation as the original categorical data and income (equivalent income) as continuous data. The result of the scaling is a two-dimensional solution. The first dimension explains that variance which could be described by status consistencies (corresponding levels for education, occupation and income). The second dimension of the indicator results from the low correlation between education and income for some individuals (status inconsistencies). The two-dimensional indicator yields differentiated results which would not be visible using a one-dimensional SES-indicator such as education or a summary score. With regard to drinking patterns there are clear differences between middle or low-educated women or men with higher incomes and other social groups. Middle or low-educated men or women with a high income are more likely to be heavy episodic drinkers than people in other social status groups.