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Objectives Affective disorders are among the most prevalent disorders in the elderly. The present study aims to examine the sociodemographic and clinical correlates of major depressive disorder (MDD) and dysthymia in different European and Associated countries using standardized interview techniques. Furthermore, service utilization for the elderly with depression is assessed. Methods The MentDis_ICF65+ study is a cross-sectional survey (N = 3,142) that was conducted in six different European and Associated countries (Germany, Italy, Spain, Switzerland, England and Israel) with a subsample of n = 463 elderly with any depressive disorder. Results Sociodemographic and clinical correlates, such as gender, age and symptom severity, were significantly associated with MDD and dysthymia in the elderly. Only 50% of elderly with any depressive disorder were treated with psycho- or pharmacotherapy. Conclusion Our findings identified sociodemographic and clinical characteristics for depression risk in the elderly and highlight the need to improve service delivery to older adults who suffer from depression.

IntroductionMental healthcare is one of the biggest challenges for healthcare systems. Comorbidities between different mental disorders are common, and patients suffer from a high burden of disease. While the effectiveness of collaborative and stepped care models has been shown for single disorders, comorbid mental disorders have rarely been addressed in such care models. The aim of the present study is to evaluate the effectiveness of a collaborative and stepped care model for depressive, anxiety, somatoform and alcohol use disorders within a multiprofessional network compared with treatment as usual.Methods and analysisIn a cluster-randomised, prospective, parallel-group superiority trial, n=570 patients will be recruited from primary care practices (n=19 practices per group). The intervention is a newly developed collaborative and stepped care model in which patients will be treated using treatment options of various intensities within an integrated network of outpatient general practitioners, psychiatrists, psychotherapists and inpatient institutions. It will be compared with treatment as usual with regard to effectiveness, cost-effectiveness and feasibility, with the primary outcome being a change in mental health-related quality of life from baseline to 6 months. Patients in both groups will undergo an assessment at baseline, 3, 6 and 12 months after study inclusion.Ethics and disseminationThe study has been approved by the ethics committee of the Hamburg Medical Association (No. PV5595) and will be carried out in accordance with the principles of the Declaration of Helsinki. For dissemination, the results will be published in peer-reviewed journals and presented at conferences. Within the superordinate research project Hamburg Network for Health Services Research, the results will be communicated to relevant stakeholders in mental healthcare.Trial registration numberNCT03226743.

IntroductionCatheter ablation (CA) has shown to effectively reduce the burden of ventricular tachycardia in patients with implanted cardioverter-defibrillator (ICD). However, in patients with ICD implantation for secondary prevention of ventricular tachycardia (VT), the appropriate time point of CA and its effect on mortality and heart failure progression remains a matter of debate.Methods and analysisWe present the design of the ongoing preventiveaBlation ofvEntriculartachycaRdia in patients with myocardiaLINfarction (BERLIN VT) study that aims to prospectively enrol 208 patients with a stable ischaemic cardiomyopathy, a left ventricular ejection fraction of 30% to 50% and documented ventricular tachycardia. Patients will be 1:1 randomised to undergo CA at the time of ICD implantation or CA after the third appropriate ICD shock for ventricular tachycardia. ICD implantation will be performed in all patients. The primary endpoint is defined as the time to first event comprising all-cause mortality and unplanned hospital admission for congestive heart failure or for symptomatic VT/ventricular fibrillation. The patients will be followed until study termination according to the event driven design. Completion of enrolment is expected for mid of 2019.Ethics and disseminationThe study had been approved by the “Ethik-kommission der Landesärztekammer Hamburg” as well as the local institutional review boards for each of the participation sites. The results of the trial will be published in peer-reviewed journalsTrial registration numberNCT02501005.

OBJECTIVE Since the beginning of the integrated care model for severely ill patients with psychotic disorders ("Hamburg model") in 2007 different clinical parameters have been consecutively assessed within a naturalistic, observational, prospective study. METHODS Clinical outcome of the 2-year and 4-year follow-ups of n = 158 patients. RESULTS A significant and ongoing improvement of psychopathology, severity of illness, functional outcome, quality of life and satisfaction with care in this sample of severely ill and merely chronic patients with psychosis was shown. Moreover, medication adherence improved and quality and quantity of outpatient treatment increased. CONCLUSION The ongoing psychosocial stabilisation of the patients most likely result from a combination of various factors: continuity of care, multimodal and individualized care, therapeutic specialisation and the multidisciplinary ACT team. RESULTS provide clinical and scientific evidence for future implementations of the integrated care model "Hamburg Model" for the treatment of psychosis.

Objective The "Hamburg model" designates an integrated care model for severely ill patients with psychotic disorders financed by the health insurance system in accordance with § 140 SGB V. Methods It comprises comprehensive and long-term treatment within a regional network of the psychosis center of the University Medical Center Hamburg-Eppendorf (UKE) and private psychiatrists. The treatment model consists of therapeutic assertive community treatment (ACT) provided by a highly specialized treatment team and need-adapted in- and outpatient care. Results and conclusions The present article summarizes the disease- and treatment-specific rationales for the model development as well as the model structure and treatment contents. The article further summarizes the effectiveness and efficiency results of a study comparing the Hamburg model and treatment as usual (without ACT) within a 12-month follow-up study (ACCESS trial).

Zielsetzung ist die systematische Zusammenfassung der empirischen Evidenz der 4-Wochen-, 12-Monats- und Lebenszeitpravalenz der Anpassungsstorung, Akuter (ABS) und Posttraumatischer Belastungsstorung (PTBS) sowie somatoformen Storungen bei Krebspatienten. Es wurden 64 englisch- und deutschsprachige Original- sowie systematische Ubersichtsarbeiten des Veroffentlichungszeitraums 1995–2010, die die Haufigkeiten psychischer Storungen anhand strukturierter klinischer Interviews erfassten, ausgewertet. Die adjustierten Pravalenzen wurden anhand eines Random-Intercept-Modells berechnet. Die adjustierten Punktpravalenzen liegen fur die Anpassungsstorung bei 12,5% (95% CI 9,9–15,7), fur die PTBS bei 2,6% (95% CI 1,7–4,0), fur die ABS bei 4,8% (95% CI 2,2–10,0) und fur somatoforme Storungen bei 3,1% (95% CI 1,6–5,8). Der Forschungsbedarf an reprasentativen Studien, die die Bandbreite psychosozialer Belastungen und supportive Unterstutzungsbedurfnisse berucksichtigen, wird aufgezeigt.

Objective In Spring 2011, an unprecedented outbreak of Shiga toxin-producing Escherichia coli serotype O104:H4-associated hemolytic uremic syndrome occurred in Northern Germany. The aim of this study was to describe the clinical characteristics, treatments, and outcomes of critically ill patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome during this outbreak. Design, setting, and patients Multicenter, retrospective, observational study of critically ill adult patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome in six hospitals in Hamburg, Germany, between May 2011 and August 2011. Measurements and main results During the study period, 106 patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome were admitted to eight ICUs. The median age was 40 years (range, 18-83) with a female:male ratio of 3:1. The median time from onset of clinical symptoms to hospital admission was 3 days and from hospital to ICU admission an additional 3 days. A total of 101 patients (95.3%) had acute renal failure and 78 (73.6%) required renal replacement therapy. Intubation and mechanical ventilation were required in 38 patients (35.8%) and noninvasive ventilation was required in 17 patients (16.0%). The median duration of invasive ventilation was 7 days (range, 1-32 days) and the median ICU stay was 10 days (range, 1-45 days). Fifty-one patients (48.1%) developed sepsis; of these 51 patients, 27 (25.4%) developed septic shock. Seventy patients (66.0%) developed severe neurological symptoms. Ninety-seven patients (91.5%) were treated with plasma exchange and 50 patients (47.2%) received eculizumab (monoclonal anti-C5 antibody). The mortality rate was 4.7%. Mild residual neurological symptoms were present in 21.7% of patients at ICU discharge, and no patient required renal replacement therapy 6 months after ICU admission. Conclusions During the 2011 Shiga toxin-producing E. coli-associated hemolytic uremic syndrome outbreak in Germany, critical illness developed rapidly after hospital admission, often in young women. The infection was associated with severe neurological and renal symptoms, requiring mechanical ventilation and renal replacement therapy in a substantial proportion of patients. Overall, recovery was much better than expected.

Aims To assess, and identify predictors of, 2-year adverse outcomes of surgical high-risk patients after successful MitraClip therapy (MC), differentiated by the aetiology of mitral regurgitation (MR). Methods and results Kaplan–Meier analysis was used to assess survival free from death, heart failure rehospitalization, and reintervention up to 2 years in 202 successfully treated patients [74 ± 9 years, 132 men (65%); secondary MR aetiology in 140 patients, primary MR in 62]. Predictors for study endpoints were determined using Cox regression analyses. Mortality was 20% at 1 year and 33% at 2 years in both primary and secondary MR patients; independent predictors of death were reduced forward stroke volume, impaired LV function, and renal failure in primary MR, yet only an increased logistic EuroSCORE in functional MR patients. The rate of rehospitalizations was not different between the patient subgroups for 6 months, but then diverged significantly in favour of primary MR patients (estimated 2-year incidence, primary MR 40% vs. secondary MR 66%). No predictor was found for primary MR patients, but increased LV end-diastolic volume significantly increased the risk of rehospitalization in functional MR patients. Reinterventions were overall rare (7.4% at 1 year, 9.7% at 2 years); primary MR patients required all except one reintervention within 2 months of MC, with again no predictors found, whereas secondary MR patients (all except one with discharge MR of 2+) exhibited a steadily declining freedom from reintervention curve throughout follow-up. Conclusion MR aetiology affects rehospitalization and reintervention, but not mortality, differently after successful MC.

Background As screening colonoscopy becomes more widespread, the costs for histopathological assessment of resected polyps are rising correspondingly. Reference centres have published highly accurate results for endoscopic polyp classification. Therefore, it has been proposed that, for smaller polyps, the differential diagnosis that guides follow-up recommendations could be based on endoscopy alone. Objective The aim was to prospectively assess whether the high accuracy for endoscopic polyp diagnosis as reported by reference centres can be reproduced in routine screening colonoscopy. Design Ten experienced private practice endoscopists had initial training in pit patterns. Then they assessed all polyps detected during 1069 screening colonoscopies. Patients (46% men; mean age 63 years) were randomly assigned to colonoscopy with conventional or latest generation HDTV instruments. The main outcome measure was diagnostic accuracy of in vivo polyp assessment (adenomatous vs hyperplastic). Secondary outcome measures were differences between endoscopes and reliability of image-based follow-up recommendations; a blinded post hoc analysis of polyp photographs was also performed. Results 675 polyps were assessed (461 adenomatous, 214 hyperplastic). Accuracy, sensitivity and specificity of in vivo diagnoses were 76.6%, 78.1% and 73.4%; size of adenomas and endoscope withdrawal time significantly influenced accuracy. Image-based recommendations for post-polypectomy surveillance were correct in only 69.5% of cases. Post hoc analysis of polyp photographs did not improve accuracy. Conclusions In everyday practice, endoscopic classification of polyp type is not accurate enough to abandon histopathological assessment and use of latest generation colonoscopes does not improve this. Image-based surveillance recommendations after polypectomy would consequently not meet guideline requirements. TrialRegNo NCT01297712.

Nach dem Zweiten Weltkrieg war die so genannte Neopsychoanalyse von Harald Schultz-Hencke bis in die 80er Jahre des letzten Jahrhunderts eine wichtige Theorie fur Psychoanalytiker der Deutschen Psychoanalytischen Gesellschaft (DPG). Aber gleichzeitig bezogen sie sich wieder zunehmend auf klassische psychoanalytische Quellen, was sich auch in der psychoanalytischen Ausbildung zeigte. Es wurde die Literaturverwendung der Examensarbeiten eines psychoanalytischen DPG-Instituts von 1971–2008 mit der Literaturverwendung klinischer Publikationen im International Journal of Psychoanalysis verglichen. Dabei zeigt sich, dass der Einfluss der Neopsychoanalyse in den Examensarbeiten des psychoanalytischen Instituts seit den 90er Jahren des letzten Jahrhunderts stark abnahm und im 21. Jahrhundert bedeutungslos wurde.

Aims Central sleep apnoea/Cheyne–Stokes respiration (CSA/CSR) is a risk factor for increased mortality and morbidity in heart failure (HF). Adaptive servo-ventilation (ASV) is a non-invasive ventilation modality for the treatment of CSA/CSR in patients with HF. Methods SERVE-HF is a multinational, multicentre, randomized, parallel trial designed to assess the effects of addition of ASV (PaceWave™, AutoSet CS™; ResMed) to optimal medical management compared with medical management alone (control group) in patients with symptomatic chronic HF, LVEF ≤45%, and predominant CSA. The trial is based on an event-driven group sequential design, and the final analysis will be performed when 651 events have been observed or the study is terminated at one of the two interim analyses. The aim is to randomize ∼1200 patients to be followed for a minimum of 2 years. Patients are to stay in the trial up to study termination. The first patient was randomized in February 2008 and the study is expected to end mid 2015. The primary combined endpoint is the time to first event of all-cause death, unplanned hospitalization (or unplanned prolongation of a planned hospitalization) for worsening (chronic) HF, cardiac transplantation, resuscitation of sudden cardiac arrest, or appropriate life-saving shock for ventricular fibrillation or fast ventricular tachycardia in implantable cardioverter defibrillator patients. Perspectives The SERVE-HF study is a randomized study that will provide important data on the effect of treatment with ASV on morbidity and mortality, as well as the cost-effectiveness of this therapy, in patients with chronic HF and predominantly CSA/CSR. Trial registration ISRCTN19572887

Surgery followed by platinum-taxane chemotherapy is the current standard approach to treat advanced ovarian cancer. The impact of the time interval between surgery and initiation of chemotherapy for clinical outcome has not been clarified yet.Individual patient data analysis of 3326 patients from three prospective randomised phase III trials conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Time to chemotherapy (TTC) was analysed and correlated with outcome.Median TTC was 19 days (range 1-56). The effect of TTC differed significantly for patients with or without residual disease for progression-free (PFS; interaction p=0.004) and for overall survival (OS; interaction p=0.028). A delayed start of chemotherapy was associated with earlier disease recurrence (HR 1.038, 95% CI 0.973; 1.106, p=0.257 per week delay) and a significantly decreased OS (HR 1.087, 95% CI 1.005; 1.176 p=0.038) in patients with no residual tumour after surgery. In contrast, in patients with residual disease, a longer TTC was significantly associated with later progression (HR 0.931, 95% CI 0.895; 0.969, p0.001) and no effect towards OS (HR 0.983, 95% CI 0.940; 1.028, p=0.452).Our results provide evidence that early initiation of chemotherapy might result in slightly improved survival in patients with complete cytoreduction while patients with residual disease after surgery did not benefit from earlier chemotherapy. A prospective study randomising patients to different time intervals could clarify the definitive relevance of the time between surgery and chemotherapy.

BACKGROUND The authors report the results of a study on frequent attenders in ambulatory medical care among elderly people in Germany and on the factors related to frequent attendance such as age, sex, multi-morbidity and long-term care dependency. METHODS The study was based on claims data of all policy holders aged 65 and over of a statutory health insurance company operating nationwide in Germany in 2004 (n=123,224). Utilisation was analysed by the number of contacts with practices of physicians working in the ambulatory medical care sector and by the number of different practices contacted. The criteria for frequent attendance included greater than or equal to 50 contacts and/or greater than or equal to 10 different practices contacted and/or greater than or equal to 3 practices of the same discipline contacted within one year. Descriptive statistical analysis and logistic regression were used. RESULTS 19% of the elderly were identified as frequent attenders, which corresponds to some 3.5 million people in Germany. Two main types of frequent attendance were identified: one is characterised by very many contacts, old age, frequent presence of multi-morbidity, and/or long-term care dependency. The other type is the younger, less frequently multi-morbid attender who is considerably less often dependent on long-term care, and characterised by large numbers of contacted practices and/or practices of the same discipline. CONCLUSION Frequent attendance is due to several factors. The problem of frequent attendance needs further research that is not exclusively based on claims data. We found a high rate of frequent attendance. Further research should clarify if this is to the benefit of elderly people.

To compare a cardiovascular risk (CVR)-adjusted with the traditional blood pressure (BP) control rate for assessing BP control and consequent target populations for intensified treatment.Model calculation using cross-sectional data retrieved from 89 German general practices; a random sample of 3355 patients with known hypertension was consecutively enrolled by their general practitioners. Cardiovascular history and risk factors were documented. In addition to the traditional control rate (fixed BP target140/90), we calculated CVR-adjusted control rates, stratifying analyses according to three CVR categories and their corresponding BP targets on the basis of the European Cardiovascular Society's SCORE tables: (1) very high CVR, owing to manifest cardiovascular disease (CVD), BP target130/80; (2) high CVR, BP target140/90; and (3) low CVR, BP target160/100 mmHg.Traditional vs. CVR-adjusted BP control rates were 55.1 vs. 14.9% (manifest CVD, kappa 0.27), 36.7 vs. 35.8% (high CVR, kappa 0.98), 52.6 vs. 88.5% (low CVR, kappa 0.25), and 45.8 vs. 46.5% (overall, kappa 0.61). Among the study patients, 19.2% switched from 'controlled' to 'uncontrolled' or vice versa depending on the criterion applied.Compared with the traditional BP control rate, the CVR-adjusted approach identifies a substantially different - although overall similarly large - target group for intensified cardiovascular risk reduction. Using CVR-adjusted BP control rates in surveys describing hypertension management could help to focus attention and resources on reducing CVR in patients who are likely to benefit from additional treatment efforts.

Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD.This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541.Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported.The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia.German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.

Introduction: The SERVE-HF study (Cowie et al., NEJM 2015) showed that treatment of predominant central sleep apnoea with ASV has detrimental effects on mortality in systolic heart failure patients. Aim: To investigate associations between ASV and individual SERVE-HF primary endpoint components, and interactions with predefined phenotypes; to better understand mechanisms underlying the observed effects of allocation to ASV. Methods: A post-hoc multistate model based on SERVE-HF data (n=1325) was developed separating the primary endpoint components; the effect of randomisation to ASV on each component was tested; interactions between ASV and implanted cardioverter defibrillator (ICD) presence, left ventricular ejection fraction (LVEF) and Cheyne-Stokes respiration (CSR) were tested. Results: The increased mortality in the ASV group was due to an increase in cardiac death without prior hospitalisation or life-saving cardiovascular intervention; risk was modified by the degree of left ventricular impairment (worse impairment = higher risk; hazard ratio (HR) for ASV with LVEF ≤30%: 5.21, 95% CI 2.11-12.89). Hospitalisation risk was significantly modified by both LVEF (lower LVEF = higher HR) and CSR (higher CSR = higher HR), and risk of noncardiac death after hospitalisation by the presence of an ICD. Conclusion: The increased mortality risk in patients randomised to ASV is attributable to cardiac death without prior hospitalisation. This risk is highest in patients with the lowest LVEF.

Introduction: The SERVE-HF study showed that treatment of predominant central sleep apnoea (CSA) with ASV increased the risk of all-cause and CV death in systolic heart failure patients. It has been suggested that higher ASV pressures might be a contributor to worse outcomes. Aim: To investigate whether CV mortality risk was modified by different ASV pressure levels in SERVE-HF. Methods: CV mortality rates were determined in patient subgroups based on delivered end-expiratory positive airway pressure (EPAP), pressure, peak inspiratory pressure (PIP) and leak (median, maximum, 95 th percentile values). Results: There were no significant differences in the risk of CV death, CV death without prior hospitalisation or all-cause mortality between any patient subgroups based on ASV pressures (median, maximum, 95 th percentile values for EPAP, pressure and PIP) or leak. Partial pressures of oxygen and carbon dioxide, base excess and pH remained stable throughout the study. Conclusion: This analysis did not show any relationship between ASV pressures and risk of CV death in SERVE-HF. In addition, blood gases were similar throughout the treatment period. This suggests that the increased risk of CV death associated with randomization to ASV in patients with chronic heart failure with left ventricular ejection fraction ≤45% and predominant CSA is independent of pressure settings.

BackgroundOne-to-one peer support is a resource-oriented approach for patients with severe mental illness. Existing trials provided inconsistent results and commonly have methodological shortcomings, such as poor training and role definition of peer supporters, small sample sizes, and lack of blinded outcome assessments.MethodsThis is a randomised controlled trial comparing one-to-one peer support with treatment as usual. Eligible were patients with severe mental illnesses: psychosis, major depression, bipolar disorder or borderline personality disorder of more than two years’ duration. A total of 216 patients were recruited through in- and out-patient services from four hospitals in Hamburg, Germany, with 114 allocated to the intervention group and 102 to the control group. The intervention was one-to-one peer support, delivered by trained peers and according to a defined role specification, in addition to treatment as usual over the course of six months, as compared to treatment as usual alone. Primary outcome was self-efficacy measured on the General Self-Efficacy Scale at six-month follow-up. Secondary outcomes included quality of life, social functioning, and hospitalisations.ResultsPatients in the intervention group had significantly higher scores of self-efficacy at the six-month follow-up. There were no statistically significant differences on secondary outcomes in the intention to treat analyses.ConclusionsThe findings suggest that one-to-one peer support delivered by trained peer supporters can improve self-efficacy of patients with severe mental disorders over a one-year period. One-to-one peer support may be regarded as an effective intervention. Future research should explore the impact of improved self-efficacy on clinical and social outcomes.

Shaping one's own life and feeling equal in society is an essential aspect of participation. Based on the UN Convention on the Rights of Persons with Disabilities, the Social Security Code IX and the International Classification of Functioning, Disability and Health (ICF), participation is relevant for the German health system. The cross-sectional discipline of participation research investigates conditions for self-determined and equal participation in society. Research results can reinforce and promote the participation of humans with disabilities. Participation research uses established quantitative and qualitative approaches. Moreover, participatory research is a relevant approach that demands involving persons with disabilities in decisions in the research process. In the future, it will be important to concentrate findings and to connect researchers. The participation research action alliance (Aktionsbündnis Teilhabeforschung), which was established in 2015, aims to make funding accessible as well as strengthen and profile participation research.

BACKGROUND: A large randomised treatment trial (SERVE-HF) showed that treatment of central sleep apnoea with adaptive servoventilation in patients with heart failure and reduced ejection fraction (HFREF) increased mortality, although the analysis of the composite primary endpoint (time to first event of death from any cause, life-saving cardiovascular intervention, or unplanned hospital admission for worsening heart failure) was neutral. This secondary multistate modelling analysis of SERVE-HF data investigated associations between adaptive servoventilation and individual components of the primary endpoint to try to better understand the mechanisms underlying the observed increased mortality. METHODS: In SERVE-HF, participants were randomly assigned to receive either optimum medical treatment for heart failure alone (control group), or in combination with adaptive servoventilation. We analysed individual components of the primary SERVE-HF endpoint separately in a multistate model, with and without three covariates suggested for effect modification (implantable cardioverter defibrillator at baseline, left ventricular ejection fraction [LVEF], and proportion of Cheyne-Stokes Respiration [CSR]). The SERVE-HF study is registered with ClinicalTrials.gov, number NCT00733343. FINDINGS: Univariate analysis showed an increased risk of both cardiovascular death without previous hospital admission (hazard ratio [HR] 2·59, 95% CI 1·54-4·37, p

Confidentiality and informed consent are important concepts enabling the sharing of sensitive data. In a paper on this topic of this issue, Williams and Pigeot () discuss that these have to be balanced with openness to ensure research standards. In this opinion paper, we give some background on how the paper by Williams and Pigeot evolved, reflect on their concepts, and provide some examples of the application of these concepts in various settings relevant to biostatisticians working in health research.

Recommended follow-up intervals after endoscopic removal of hyperplastic polyps (HP) and sessile serrated adenomas (SSA) differ because of assumed differences in biological behaviour. However, histopathologic differentiation is difficult, with higher SSA rates reported from specialist GI histopathologists.The objective of this study was to clarify the relevance of histologic reassessment of HP.From a prospective screening colonoscopy study relevant serrated lesions (excluding distal small HP ≤5 mm) diagnosed by private practice pathologists were reassessed by four specialized GI pathologistsOne thousand sixty-nine screening colonoscopies were performed in patients.In terms of main outcome measurements, there is a likelihood of changes of the HP diagnosis on reassessment, as well as interrater variability.SSA were initially diagnosed in 7 cases (0.7%) and relevant HP in 83 (7.8%; 101 lesions). Of the latter, the chance of a change in diagnosis from HP to SSA by any of the four specialist histopathologists was higher for larger (5 mm) and right-sided lesions (19.1 vs 1.3%, OR 18.4, p = 0.04) including a higher likelihood to change recommended follow-up intervals (32.1 vs 3.3%, p 0.01). However, follow-up intervals were determined by concomitant adenomas in 41%. Interrater variability was also higher for these lesions (p = 0.04), with an overall kappa value of 0.48. However, this issue related to only 1.2% of the 1069 study cases.The limitations this study are the limited case number as well as limited retrospective assessment.Right-sided HP5 mm had a higher chance of change in diagnosis to SSA; therefore, they should probably be treated like adenomas and be removed. However, reliable data for recommendations on follow-up intervals of HP or SSA will require follow-up studies.

Background— Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients’ clinical outcome. Methods and Results— Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients ( P Conclusions— This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs. Clinical Trial Registration— URL: http://clinicaltrials.gov ; Unique identifier: NCT00293943.

Aim: We aimed to identify patient characteristics and comorbidities that correlate with the initial exercise capacity of cardiac rehabilitation (CR) patients and to study the significance of patient characteristics, comorbidities and training methods for training achievements and final fitness of CR patients. Methods: We studied 557 consecutive patients (51.7 Æ 6.9 years; 87.9% men) admitted to a three-week in-patient CR. Cardiopulmonary exercise testing (CPX) was performed at discharge. Exercise capacity (watts) at entry, gain in training volume and final physical fitness (assessed by peak O 2 utilization (VO 2peak ) were analysed using analysis of covariance (ANCOVA) models. Results: Mean training intensity was 90.7 Æ 9.7% of maximum heart rate (81% continuous/19% interval training, 64% additional strength training). A total of 12.2 Æ 2.6 bicycle exercise training sessions were performed. Increase of training volume by an average of more than 100% was achieved (difference end/beginning of CR: 784 Æ 623 watts  min). In the multivariate model the gain in training volume was significantly associated with smoking, age and exercise capacity at entry of CR. The physical fitness level achieved at discharge from CR as assessed by VO 2peak was mainly dependent on age, but also on various factors related to training, namely exercise capacity at entry, increase of training volume and training method. Conclusion: CR patients were trained in line with current guidelines with moderate-to-high intensity and reached a considerable increase of their training volume. The physical fitness level achieved at discharge from CR depended on various factors associated with training, which supports the recommendation that CR should be offered to all cardiac patients.

Objective: To explore the possibility of using interleukin-17 (IL-17) production by CD4+ T cells in the CSF as a potential biomarker for cerebral vasculitis in stroke patients. Methods: In this consecutive case study, we performed prospective analysis of CSF and blood in patients admitted to a university medical center with symptoms of stroke and suspected cerebral vasculitis. Flow cytometry was performed for intracellular detection of inflammatory cytokines in peripheral blood lymphocytes and expanded T cells from CSF. Results: CSF CD4+ lymphocytes from patients with cerebral vasculitis showed significantly higher levels of the proinflammatory cytokine IL-17 compared to patients with stroke not due to vasculitis or with other, noninflammatory neurologic diseases. There was no difference in the production of interferon-γ in the CSF and no overall differences in the relative frequencies of peripheral immune cells. Conclusions: Intracellular IL-17 in CSF cells is potentially useful in discriminating cerebral vasculitis as a rare cause in patients presenting with ischemic stroke. Classification of evidence: This study provides Class II evidence that an increased proportion of IL-17-producing CD4+ cells in CSF of patients presenting with stroke symptoms is indicative of cerebral vasculitis (sensitivity 73%, 95% confidence interval [CI] 39–94%; specificity 100%, 95% CI 74%–100%).

The association between socioeconomic status (SES) and knowledge/belief about depression, schizophrenia and eating disorders will be analysed. Data stem from a telephone survey in two large German cities (Hamburg and Munich, n = 2,014, response rate 51 %). Written vignettes with typical signs and symptoms suggestive of a depression, schizophrenia and eating disorders were presented to the respondents. Respondents were then asked about knowledge/belief about causes, symptoms, prevalence and treatment using a standardised questionnaire. Education, occupational position and income were used as SES indicators. Results of mixed hierarchal logistic regression analyses show that individuals with a low SES know less about symptoms and prevalences of depression, schizophrenia and eating disorders. Moreover, people with a high SES are more likely to consider medication as effective in case of depression and schizophrenia, but are less likely to believe that activities such as sports or relaxation are an effective measure to treat the three mental disorders under study. Respondents with a high SES are less likely to believe that a weak will is a possible cause of depression, schizophrenia and eating disorders. We found large similarities in the associations between SES and beliefs across the three mental disorders. Finally, associations of beliefs about mental disorders with education are stronger and more consistent than with income and occupational position. Results indicate an inequality in mental health literacy and underline that information campaigns on causes, symptoms, prevalence and treatment of mental disorders should consider information needs of people with a low SES.

Rona Reibis,1,2 Andras Treszl,3 Karl Wegscheider,3 Kurt Bestehorn,4 Barbara Karmann,4 Heinz Völler1,51Department of Cardiology, Klinik am See, Rehabilitation Center of Cardiovascular Diseases, Rüdersdorf, 2Kardiologische Gemeinschaftspraxis am Park Sanssouci Potsdam, Potsdam, 3Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, 4Medical Department, MSD Sharp and Dohme GmbH, Haar, 5Center of Rehabilitation Research, University of Potsdam, Potsdam, GermanyBackground: There are few data available regarding the specificity and modifiability of major cardiovascular (CV) risk factors in patients with premature versus (vs) late-onset coronary artery disease (CAD). This study was designed to analyze and compare these risk factors.Patients and methods: Data from 15,381 consecutive patients (mean age, 62.3 ± 11.7 years; female, 33.8%) hospitalized with CAD were collected from a large-scale registry (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management) and analyzed. The patients were divided into two groups, depending on age at inclusion: group 1 patients (n = 5725; mean age, 50.5 ± 7.2 years) were males aged < 55 years and females aged < 65 years; group 2 patients (n = 9656; mean age, 69.4 ± 7.4 years) were males aged > 55 years and females aged > 65 years and had a low-density lipoprotein cholesterol level of >100 mg/dL on admission to cardiac rehabilitation. Besides the conventional risk factors, lipoprotein(a) concentrations and glucose tolerance were measured facultatively. Univariate (chi-square test) and multivariate logistic regression models were used.Results: Cigarette smoking (group 1 at 31.5% vs group 2 at 9.4%; P < 0.001), family history of CAD (group 1 at 43.6% vs group 2 at 26.5%; P < 0.001), and dyslipidemia (group 1 at 92.7% vs group 2 at 91.8%; P < 0.001) were dominant risk factors in the younger group. Arterial hypertension (group 1 at 71.4% vs group 2 at 87.0%; P < 0.001) and diabetes (group 1 at 23.5% vs group 2 at 30.1%; P < 0.001) were dominant risk factors in the older group. Impaired glucose tolerance and diabetes were less frequent in the younger group (Ptrend = 0.038), and identical lipoprotein(a) concentration levels of >30 mg/dL were found in both groups (8.0%; P = 0.810). Modification of lipid profile and blood pressure was more effective in the younger group (low-density lipoprotein cholesterol < 100 mg/dL: group 1 at 66.3% vs group 2 at 61.1%; systolic blood pressure < 140 mmHg: group 1 at 91.7% vs group 2 at 83.0%; P < 0.001).Conclusion: CV risk factors differ markedly between premature and non-premature CAD. Cardiac rehabilitation provides an opportunity to reinforce secondary prevention after acute coronary syndrome.Keywords: acute coronary syndrome, premature manifestation, cardiovascular risk factors, diabetes, cholesterol

To evaluate whether extracorporeal carbon dioxide removal by means of a pumpless extracorporeal lung-assist (PECLA) device could be an effective and safe alternative to invasive mechanical ventilation in patients with chronic pulmonary disease and acute hypercapnic ventilatory failure not responding to noninvasive ventilation (NIV).In this multicentre, retrospective study, 21 PECLA patients were compared with respect to survival and procedural outcomes to 21 matched controls with conventional invasive mechanical ventilation. Matching criteria were underlying diagnosis, age, Simplified Acute Physiology Score II and pH at ICU admission.Of the 21 patients treated with PECLA, 19 (90 %) did not require intubation. Median PaCO(2) levels and pH in arterial blood prior to PECLA were 84.0 mmHg (54.2-131.0) and 7.28 (7.10-7.41), respectively. Within 24 h, median PaCO(2) levels and pH had significantly improved to 52.1 (33.0-70.1; p0.001) and 7.44 (7.27-7.56; p0.001), respectively. Two major and seven minor bleeding complications related to the device occurred. Further complications were one pseudoaneurysm and one heparin-induced thrombocytopenia type 2. Compared to the matched control group, there was a trend toward a shorter hospital length of stay in the PECLA group (adjusted p = 0.056). There was no group difference in the 28-day (24 % vs. 19 %, adjusted p = 0.845) or 6-month mortality (33 % vs. 33 %).In this study the use of extracorporeal carbon dioxide removal allowed avoiding intubation and invasive mechanical ventilation in the majority of patients with acute on chronic respiratory failure not responding to NIV. Compared to conventional invasive ventilation, short- and long-term survivals were similar.

Information about prognostic utility is limited for numerous electrocardiogram (ECG) abnormalities and is particularly scarce in women with coronary heart disease (CHD) or at increased risk of CHD occurrence.This study used a prospectively planned observational post-hoc analysis of a negative randomised trial designed for other purposes.ECGs of 9789 postmenopausal women were analysed at a core laboratory. ECG abnormalities were determined and evaluated for mortality risk on top of established clinical risk factors and simultaneously with all other ECG abnormalities.During a median follow-up of 5.6 years, 500 women sustained coronary death. Normal versus abnormal baseline ECGs were associated with an annual rate of 0.53% versus 1.28% coronary deaths. Ten clinically common ECG abnormalities, including left atrial abnormality, fragmented QRS, and Cornell voltage-only left ventricular hypertrophy, emerged as independent significant predictors of coronary death, eight of them also predicted all-cause mortality. Each ECG abnormality acted as a risk multiplier for a coexisting ECG abnormality. Two or three of any of the ECG abnormalities simultaneously present on the baseline ECG identified subsets with hazard ratios for coronary death of 3.3 or 5.5 respectively. Consideration of ECG abnormalities significantly improved risk stratification by common clinical parameters.The presence of ECG abnormalities provides independent risk information over and above that of established risk factors, both for women with CHD or at increased risk of occurrence of CHD. Normal ECG assures a low mortality risk regardless of whether CHD exists or not. The data derived could be applied to corresponding postmenopausal women in daily clinical practice.

Zielsetzung ist die systematische Zusammenfassung der empirischen Evidenz der 4-Wochen-, 12-Monats- und Lebenszeitpravalenz affektiver und Angststorungen bei Krebspatienten. Ausgewertet wurden 89 englisch- und deutschsprachige Original- sowie systematische Ubersichtsarbeiten des Veroffentlichungszeitraums 1995–2010, die die Haufigkeiten affektiver und Angststorungen anhand strukturierter klinischer Interviews erfassten. Die adjustierten Pravalenzen wurden anhand eines Random-Intercept-Modells berechnet. Die adjustierte Punktpravalenz fur affektive Storungen liegt bei 11,1% (95% CI 8,1–15,1), bezogen auf deutsche Studien bei 10,8% (95% CI 6,8–16,7). Die adjustierte Punktpravalenz fur Angststorungen liegt bei 10,2% (95% CI 6,9–14,8), bezogen auf deutsche Studien bei 13,5% (95% CI 7,1–24,3). Die Ergebnisse zeigen den Forschungsbedarf an reprasentativen Studien, die neben der Pravalenz psychischer Storungen die Bandbreite psychosozialer Belastungen und supportive Unterstutzungsbedurfnisse berucksichtigen.

The aim of this study was to describe the neurological syndrome in the largest cohort of adult patients with a complicated Shiga toxin-producing Escherichia coli infection. The recent outbreak of Shiga toxin-producing E. coli serotype O104:H4 in northern Germany affected more than 3842 patients, 22% of whom developed haemolytic uraemic syndrome. The proportion of adult patients was unusually high, and neurological complications were frequent and severe. In three hospitals, population-based evaluation of 217 patients with complicated Shiga toxin-producing E. coli infection was carried out, including neurological, neuroradiological, neurophysiological, cerebrospinal fluid and neuropathological analyses. Of the 217 patients with complicated Shiga toxin-producing E. coli infection, 104 (48%) developed neurological symptoms. Neurological symptoms occurred 5.3 days (mean) after first diarrhoea and 4 days after onset of haemolytic uraemic syndrome. Of the infected patients with neurological symptoms, 67.3% presented with cognitive impairment or aphasia. During the course of the disease, 20% of the patients developed epileptic seizures. The onset of neurological symptoms was paralleled by increases in blood urea nitrogen and serum creatinine. In 70 patients with cerebral magnetic resonance imaging, the most common findings were symmetrical hyperintensities in the region of abducens nucleus and lateral thalamus. On follow-up scans, these abnormalities were resolved. Neuropathological analysis revealed regionally accentuated astrogliosis and microgliosis, more predominant in the thalamus and brainstem than in the cortex, and neuronal expression of globotriaosylceramide. There were no signs of microbleeds, thrombotic vessel occlusion or ischaemic infarction. The neurological syndrome in adult patients with complicated Shiga toxin-producing E. coli infection is a rapidly progressive and potentially life-threatening disease necessitating intensive care unit treatment and intubation in >30% of cases. The outcome of neurological patients in the 2011 northern German Shiga toxin-producing E. coli O104:H4 outbreak was surprisingly good. Magnetic resonance imaging and neuropathological findings point to a mixed toxic and inflammatory pathomechanism leading to largely reversible damage of neuronal function.

Telomere length has emerged as a biological correlate for ageing, which in turn is a risk factor for the manifestation of cardiovascular diseases. This study investigated the relation between leucocyte telomere length (LTL) and its genetic background to cardiac structure and function in patients with arterial hypertension. We analysed a cohort of 1,106 treated hypertensive patients (83.3% males; mean age, 57.9 ± 9.8 years) with an ejection fraction (EF) over 40% and documented cardiovascular disease or target organ damage. LTL and genotypes of single nucleotide polymorphisms (SNPs), previously implicated in LTL, were determined by real-time PCR. The mean left ventricular mass index (LVMI) and EF were 51.8 ± 21.0 g/H2.7 and 61.1 ± 9.6%, respectively. In multivariate adjusted analysis, a 1.5-fold LTL was positively related with a 2.2% increase of LVMI (CI = 0.1% to 4.2%, p = 0.044) and an absolute increase in EF of 0.6% (CI = 0.1% to 1.1%, p = 0.028). One SNP near TERC (rs16847897) showed a significant absolute difference in EF dependent on allele status (rs16847897, G allele 2.7%; CI = 0.7% to 4.6%; p raw = 0.008, p mt = 0.048, after adjustment for multiple testing). This applied also for two SNPs in BICD1 (rs2630578, C allele −1.8%; CI = −2.8% to −0.7%; p raw = 0.002, p mt = 0.018; rs1151026, G allele −1.9%, CI = −3.0% to −0.8%; p raw

Background Data on prevalence of chronic diseases are important for planning health care services. Such prevalence data are mostly based on patient self-reports, claims data, or other research data-with limited validity and reliability partially due to their cross-sectional character. Currently, only claims data of statutory health insurance offer longitudinal information. In Germany, these data show a loss of diagnoses of chronic health conditions over time. This study investigated whether there is a similar tendency of loss in the documentation of chronic diseases in data specifically collected for a longitudinal cohort study by general practitioners. In addition, the explanatory power of patient or GP characteristics regarding these losses is investigated. Patients and methods A total of 3,327 patients aged 75 years and older were recruited for the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). For 1,765 patients, GP diagnoses of four chronic conditions at three time points were available for a total period of 4.5 years. In order to explain the loss of chronic diagnoses, a multilevel mixed-effects logistic regression was performed. Results Over the course of 4.5 years, 18.6% of the diagnoses of diabetes mellitus, 34.5% of the diagnoses of coronary heart disease, and 44.9% of the diagnoses of stroke disappeared in the GP documentation for the longitudinal study. The diagnosis of coronary heart disease was less often lost in men than in women. The risk of losing the diagnosis of diabetes was higher in patients who were well known by the GP for a long time. An essential part of the variance of the losses can be explained by practice (owner) effects. Conclusion Data on morbidity collected in epidemiological studies and reported by physicians should always be checked for validity and reliability. Appropriate options (e.g., an investigator collecting the data directly in the field or the comparison of the data with health insurance companies' claims data) are presented and discussed.

The aim of the study was to evaluate the feasibility and safety of avoiding invasive mechanical ventilation (IMV) by using extracorporeal CO2 removal (ECCO2R) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure refractory to noninvasive ventilation (NIV). Case–control study. Patients with acute hypercapnic respiratory failure refractory to NIV being treated with a pump-driven veno-venous ECCO2R system (iLA-Activve®; Novalung, Heilbronn, Germany) were prospectively observed in five European intensive care units (ICU). Inclusion criteria were respiratory acidosis (pH ≤ 7.35, PaCO2 > 45 mmHg) with predefined criteria for endotracheal intubation (ClinicalTrials.gov NCT01784367). The historical controls were patients with acute hypercapnic respiratory failure refractory to NIV who were treated with IMV. The matching criteria were main diagnosis, age, SAPS-II score and pH. Twenty-five cases (48.0 % male, mean age 67.3 years) were matched with 25 controls. Intubation was avoided in 14 patients (56.0 %) in the ECCO2R group with a mean extracorporeal blood flow of 1.3 L/min. Seven patients were intubated because of progressive hypoxaemia and four owing to ventilatory failure despite ECCO2R and NIV. Relevant ECCO2R-associated adverse events were observed in 11 patients (44.0 %), of whom 9 (36.0 %) suffered major bleeding complications. The mean time on IMV, ICU stay and hospital stay in the case and control groups were 8.3 vs. 13.7, 28.9 vs. 24.0 and 36.9 vs. 37.0 days, respectively, and the 90-day mortality rates were 28.0 vs. 28.0 %. The use of veno-venous ECCO2R to avoid invasive mechanical ventilation was successful in just over half of the cases. However, relevant ECCO2R-associated complications occurred in over one-third of cases. Despite the shorter period of IMV in the ECCO2R group there were no significant differences in length of stay or in 28- and 90-day mortality rates between the two groups. Larger, randomised studies are warranted for further assessment of the effectiveness of ECCO2R.

Objective: Although chronic pain in elderly patients with osteoporosis is extremely common it has rarely been addressed in pharmacotherapy studies. The efficacy and tolerability of flupirtine (CAS 56995-20-1, Trancopal Dolo®) up to 600 mg/day was investigated under daily practice conditions. Design: This was an open-label, multicentre, prospective, observational phase IV study on 869 patients performed in 290 practices (mainly orthopedists) throughout Germany. Main outcome measure: Decrease in pain scores on a visual analogue scale (VAS, from 0 = none to 10 = maximum) after an average 3-week therapy, and evaluation of adverse events. Multivariate analyses were performed to identify factors associated with the efficacy of pain reduction. Results: 81 % of patients were female; the mean age of all patients was 67 years, and the mean body mass index was 25.7 kg/m 2 . 81 % of patients had reduced bone density, 30 % had a family history of osteoporosis, and 32 % had previous bone fractures. The mean daily flupirtine dose was 270 ±12 mg. The mean baseline pain VAS scores were 7.1 (low back pain), 5.8 (neck pain), 5.6 (shoulder-arm pain), and 6.6 (other pain). Mean pain reduction at the end of flupirtine treatment was 43 % for low back pain, 44 % for neck pain, 40 % for shoulder-arm pain, and 40 % for other pain (all reductions p Conclusion: This trial performed under daily practice conditions in a large unselected sample of patients confirms the efficacy and safety of flupirtine in the treatment of chronic pain in patients with osteoporosis, independent of the age of the patient.

Background Besides its well-established role in atherosclerosis, myeloperoxidase (MPO) has gained attention as a prognostic indicator in cardiovascular disease. Previous studies assessed MPO retrospectively and at a single time point. The current study aimed to evaluate the prognostic information of MPO prospectively and in consecutive measurements in patients presenting with chest pain. Methods MPO plasma levels were determined in 274 consecutive chest pain patients admitted to the emergency room. Results A total of 100 patients (36.5%) were finally diagnosed for acute myocardial infarction (AMI). Patients with AMI had significantly higher MPO levels than patients without AMI. Importantly, MPO levels were elevated in patients finally diagnosed for AMI even when troponin I (TNI) was negative (cutoff: 0.032ng/ml). Overall, MPO yielded a negative predictive value (NPV) of 85.5% (95% confidence interval (CI): 82.6–88.4) and a sensitivity for diagnosing AMI of 80.0% (95% CI: 75.8–84.2) compared to a NPV of 91.7% (95% CI: 89.5–94.0) and a sensitivity of 85.9% (95% CI: 82.3–89.5) for TNI. For patients with a symptom onset of ≤2h the sensitivity of MPO increased to 95.8% (95% CI: 93.7–97.9) whereas the sensitivity of TNI dropped to 50.0% (95% CI: 44.8–55.2). The negative predictive value of MPO for this group of patients was 95.6% (95% CI: 94.0–97.3) compared to 73.3% (95% CI: 69.8–76.9) for TNI. Discussion The current data underscore the role of MPO as diagnostic marker in acute coronary disease; however the additive information derived from MPO is restricted to patients presenting in the early phase of symptom onset.

SummaryThere are exciting new developments in several areas of atrial fibrillation (AF) management that carry the hope of improving outcomes in AF patients. This paper is an executive summary that summarises the proceedings from the 3rd AFNET/EHRA consensus conference on atrial fibrillation, held in Sophia Antipolis from November 7th to 9th 2010, shortly after the release of the new ESC guidelines on AF. The conference was jointly organised by the German Atrial Fibrillation competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). This executive summary report covers four sections: 1. Risk factors and risk markers for AF, 2. Pathophysiological classification of AF, 3. Relevance of monitored AF duration for AF-related outcomes, and 4. Perspectives and needs for implementing better antithrombotic therapy.

Objectives The aim of this study was to assess the outcomes of patients at prohibitive surgical risk undergoing MitraClip therapy (Abbott Vascular, Redwood City, California) for severe mitral regurgitation (MR). Background The safety of percutaneous mitral valve repair has been documented. However, midterm development of mitral valve function, ventricular remodeling, and clinical outcomes in patients not amenable to surgery are unknown. Methods A total of 104 consecutive patients (mean age 74 ± 9 years; 64 men; 49 and 54 with MR 3+ and 4+, respectively; 69 with functional MR; 59 and 45 in New York Heart Association classes III and IV, respectively) were followed for a median of 359 days. Results Device success was achieved in 96 patients (92%). In patients with successful index procedures, MR grade ≤2+ was present at follow-up in 82.5%, left ventricular end-diastolic and -systolic volumes were reduced, and forward stroke volumes were significantly increased. Improvements in New York Heart Association functional class were observed in 80% of patients, with 69% in class I or II; 75% improved in the 6-min walk test; and 74% reported improvements in quality of life. One-year estimates of mortality and rehospitalization were 22% and 31%, respectively. Forward stroke volume at discharge emerged as a predictor of event-free survival. Conclusions MitraClip therapy improves clinical and echocardiographic outcomes at 1 year in about three-quarters of critically ill, elderly patients with moderate to severe MR not amenable to surgery.

Background Stepwise ablation is an effective treatment for persistent atrial fibrillation (AF), although it often requires multiple procedures to eliminate recurrent arrhythmias. Objective This study evaluated single- and multiple-procedure long-term success rates and potential predictors of a favorable single-procedure outcome of stepwise ablation for persistent AF. Methods This study comprised 395 patients with persistent AF (duration 16 months) undergoing de novo catheter ablation using the stepwise approach. Procedural success was defined as the absence of any arrhythmia recurrence. Patient characteristics and electrophysiological parameters were analyzed with respect to single- and multiple-procedure outcomes. Results After a follow-up of 27 ± 7 months, 108 (27%) patients were free of arrhythmia recurrences with a single procedure. After 2.3 ± 0.6 procedures, 312 (79%) patients were free of arrhythmia with concomitant antiarrhythmic treatment in 38% (23% on β-blocker). Female gender, duration of persistent AF, and congestive heart failure were predictive for the outcome after first ablation. However, the strongest predictors for single-procedure success were longer baseline AF cycle length (CL) and procedural AF termination. Moreover, procedural AF termination during the index procedure also predicted a favorable outcome after the last procedure, while the existence of congestive heart failure was associated with an increased risk for eventual arrhythmia recurrences. Conclusions Single-procedure long-term success is anticipated in approximately a quarter of patients undergoing de novo ablation of persistent AF. Baseline AFCL emerged as the strongest predictor of single-procedure success, while AF termination during index ablation predicts the overall outcome. However, an overall success rate of 79% is achievable with multiple procedures.

Aims Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans. Methods and results A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPOlow), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group ( P < 0.01), but not in MPOlow individuals ( P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction ( P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals ( P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine ( P < 0.01) and nitroglycerine as opposed to controls ( P < 0.001). Conclusion Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo . These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.

Context: Nodular goiter is common worldwide, but there is still debate over the medical treatment. Objective: The objective of the study was the measurement of the effect of a treatment with (nonsuppressive) T4, iodine, or a combination of both compared with placebo on volume of thyroid nodules and thyroid. Design: This was a multicenter, randomized, double-blind trial in patients with nodular goiter in Germany [LISA (Levothyroxin und Iodid in der Strumatherapie Als Mono-oder Kombinationstherapie) trial]. Setting: The study was conducted in outpatient clinics in university hospitals and regional hospitals and private practices. Participants: One thousand twenty-four consecutively screened and centrally randomized euthyroid patients aged 18–65 yr with one or more thyroid nodules (minimal diameter 10 mm) participated in the study. Intervention: Intervention included placebo, iodine (I), T4, or T4+I for 1 yr. T4 doses were adapted for a TSH target range of 0.2–0.8 mU/liter. Outcome Measures: The primary end point was percent volume reduction of all nodules measured by ultrasound, and the main secondary end point was a change in goiter volume. Results: Nodule volume reductions were −17.3% [95% confidence interval (CI) −24.8/−9.0%, P < 0.001] in the T4+I group, −7.3% (95% CI −15.0/+1.2%, P = 0.201) in the T4 group, and −4.0% (95% CI −11.4/+4.2%, P = 0.328) in the I group as compared with placebo. In direct comparison, the T4+I therapy was significantly superior to T4 (P = 0.018) or I (P = 0.003). Thyroid volume reductions were −7.9% (95% CI −11.8/−3.9%, P < 0.001), −5.2% (95% CI −8.7/−1.6%, P = 0.024) and −2.5% (95% CI −6.2/+1.4%, P = 0.207), respectively. The T4+I therapy was significantly superior to I (P = 0.034) but not to T4 (P = 0.190). Conclusion: In a region with a sufficient iodine supply, a 1-yr therapy with a combination of I and T4 with incomplete suppression of thyrotropin reduced thyroid nodule volume further than either component alone or placebo.

Moxifloxacin penetrates well into oromaxillary tissue and covers the causative pathogens that show an increasing resistance to standard antibiotics. Clinical reports suggest that moxifloxacin may be effective for the treatment of odontogenic infections that can lead to serious complications. The objective of this prospective, randomized, double-blind, multicenter study was to compare the efficacies and safeties of moxifloxacin and clindamycin for the medical treatment of patients with gingival inflammatory infiltrates and as an adjuvant therapy for patients with odontogenic abscesses requiring surgical treatment. Patients received either 400 mg moxifloxacin per os once daily or 300 mg clindamycin per os four times daily for 5 days consecutively. The primary efficacy endpoint was the percent reduction in patients' perceived pain on a visual analogue scale at days 2 to 3 from baseline. Primary analysis included 21 moxifloxacin- and 19 clindamycin-treated patients with infiltrates and 15 moxifloxacin- and 16 clindamycin-treated patients with abscesses. The mean pain reductions were 61.0% (standard deviation [SD], 46.9%) with moxifloxacin versus 23.4% (SD, 32.1%) with clindamycin ( P = 0.006) for patients with infiltrates and 55.8% (SD, 24.8%) with moxifloxacin versus 42.7% (SD, 48.5%) with clindamycin ( P = 0.358) for patients with abscesses. A global efficacy assessment at days 2 to 3 and 5 to 7 showed faster clinical responses with moxifloxacin in both abscess and infiltrate patients. Rates of adverse events were lower in moxifloxacin- than in clindamycin-treated patients. In patients with inflammatory infiltrates, moxifloxacin was significantly more effective in reducing pain at days 2 to 3 of therapy than clindamycin. No significant differences between groups were found for patients with odontogenic abscesses.

Aims Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy for primary prevention of sudden cardiac death in patients with the reduced left ventricular function (LVEF ≤30%) not earlier than 40 days after myocardial infarction (MI). The aim of the prospective Prevention of Sudden Cardiac Death II (PreSCD II) registry was to investigate the clinical practice of ICD therapy in post-MI patients and to assess the impact on survival. Methods and results 10 612 consecutive patients (61 ± 12 years, 76% male) were enrolled 4 weeks or later after MI in 19 cardiac rehabilitation centres in Germany from December 2002 to May 2005. All patients with left ventricular ejection fraction (LVEF) ≤40% ( n = 952) together with a randomly selected group of patients with preserved left ventricular function ( n = 1106) were followed for 36 months. Cox proportional hazard models were used to correlate ICD implantation and survival with baseline characteristics. Of all patients studied, 75.9% were enrolled within 4–8 weeks, 10.7% more than 1 year after MI. Pre-specified Group 1 with an LVEF ≤30% consisted of 269 patients (2.5%), Group 2 with LVEF 31–40% of 727 patients (6.9%), and Group 3 with LVEF >40% of 1148 randomly selected patients from the cohort of 9616 patients with preserved LV function. After 36 months, only 142 patients (6.9%) had received an ICD; 82 (31.7%) of Group 1, 49 (7%) of Group 2, and 11 (1%) in Group 3. The ICD was implanted in 47% of all patients within 1 year after their index MI. Implantable cardioverter-defibrillator patients were predominantly characterized by low ejection fraction, but also by several other independent risk factors. Patients who received an ICD had an adjusted 44% lower mortality (hazard ratio 0.56, 95% confidence intervals 0.32–1.01; P = 0.053) than comparable patients without ICD therapy. All cause mortality of ICD recipients was significantly lower if the ICD was implanted later than 11 months after acute MI ( P < 0.001). Conclusions The PreSCD II registry demonstrated that the number of patients who develop a low LVEF (≤30%) after acute MI is small. However, only few patients with guideline-based ICD indication received ICD therapy. All cause mortality was significantly reduced only if the ICD was implanted late (>11 months) after MI.

Background— Termination of persistent atrial fibrillation (AF) can be achieved through ablation, with the majority of patients terminating to an atrial tachycardia (AT) and fewer directly to sinus rhythm (SR). We aimed to identify potential predictors for the existence of a substrate for AT on termination to SR. Methods and Results— We assessed 95 persistent AF patients (age, 60±10 years) who underwent catheter ablation to the end point of AF termination. Forty patients terminated directly to SR (SRterm) and 55 to ATs (ATterm). Compared with the ATterm group, the SRterm group were younger (56±10 versus 63±9 years, P =0.001), had shorter durations of AF before ablation (9±26 versus 14±20 months, P P =0.015), and longer baseline AF cycle lengths (178±23 versus 159±31 ms, P =0.005). However, AF cycle length was the sole independent predictor of direct termination to SR. The most frequent AF termination site in SRterm patients was the pulmonary veins (53%), whereas in ATterm patients this was within the left atrium (58%). After follow-up of 12±6 months, there was a trend toward a greater proportion of patients in SR among those who terminated directly to SR after a single procedure. The most frequent type of recurrence was paroxysmal AF in SRterm patients and AT in ATterm patients. Conclusions— Patients who terminate to SR through ablation without an intermediate AT are characterized by a less altered arrhythmogenic substrate. Baseline AF cycle lengths emerged as a sole independent predictor of a substrate for consecutive arrhythmias.

Despite efforts to ensure more accurate prescribing of antibiotics for respiratory tract infections, inappropriate selection of antibiotic treatment remains a big issue. We tried to ascertain which factors best predict the nature of fluoroquinolone prescribing for acute cough in primary care.Random effects logistic regression models were applied to the baseline prescription data taken from a cluster-randomized controlled trial based on 104 general practitioners (GPs) and 2745 patients.Significant predictors for the prescription of fluoroquinolones from both patient and GP data were identified. Predictors from a patient's perspective were the severity of illness {odds ratio (OR) 3.56 [95% confidence interval (CI) 2.45-5.19] P0.001}, the duration of illness before seeing the GP [OR 1.09 (95% CI 1.04-1.14) P0.020] and the individual patient's age [OR 1.01 (95% CI 1.00-1.01) P0.015]. Predictors from the GP's perspective were extent/lack of specific vocational training [OR 3.10 (95% CI 1.54-6.22) P0.001], status as a general internist [OR 2.00 (95% CI 1.10-3.70) P0.002], the physician's overall antibiotic prescription rate for acute cough [OR 1.02 (95% CI 1.01-1.04) P0.001], the duration of illness before contact with patient [OR 0.81 (95% CI 0.69-0.95) P0.010] and the severity of illness [OR 0.27 (95% CI 0.12-0.63) P0.002].Whether a fluoroquinolone is prescribed by a GP seems to be determined not only by the patient's characteristics but also by the GP's vocational training and overall antibiotic prescribing rate. As the prescription of fluoroquinolones for the treatment of acute coughing can rarely be justified, such prescriptions may serve as a quality indicator for antibiotic prescribing in primary care.

Robotic Remote Ablation for AF. Aims: A robotic navigation system (RNS, Hansen™) has been developed as an alternative method of performing ablation for atrial fibrillation (AF). Despite the growing application of RNS-guided pulmonary vein isolation (PVI), its consequences and mechanisms of subsequent AF recurrences are unknown. We investigated the acute procedural success and persistence of PVI over time after robotic PVI and its relation to clinical outcome. Methods and Results: Sixty-four patients (60.7 ± 9.8 years, 53 male) with paroxysmal AF underwent robotic circumferential PVI with 3-dimensional left atrial reconstruction (NavX™). A voluntary repeat invasive electrophysiological study was performed 3 months after ablation irrespective of clinical course. Robotic PVI was successful in all patients without complication (fluoroscopy time: 23.5 [12–34], procedure time: 180 [150–225] minutes). Fluoroscopy time demonstrated a gradual decline but was significantly reduced after the 30th patient following the introduction of additional navigation software (34 [29–45] vs 12 [9–17] minutes; P < 0.001). A repeat study at 3 months was performed in 63% of patients and revealed electrical conduction recovery in 43% of all PVs. Restudied patients without AF recurrence (n = 28) showed a significantly lower number of recovered PVs (1 (0–2) vs 2 (2–3); P = 0.006) and a longer LA-PV conduction delay than patients with AF recurrences (n = 12). Persistent block of all PVs was associated with freedom from AF in all patients. At 3 months, 67% of patients were free of AF, while reablation of recovered PVs led to an overall freedom from AF in 81% of patients after 1 year. Conclusion: Robotic PVI for PAF is safe, effective, and requires limited fluoroscopy while yielding comparable success rates to conventional ablation approaches with PV reconduction as a common phenomenon associated with AF recurrences. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1079-1084)

Background: Health care professionals worldwide attend courses and workshops to learn evidence-based medicine (EBM), but evidence regarding the impact of these educational interventions is conflicting and of low methodologic quality and lacks generalizability. Furthermore, little is known about determinants of success. We sought to measure the effect of EBM short courses and workshops on knowledge and to identify course and learner characteristics associated with knowledge acquisition. Methods: Health care professionals with varying expertise in EBM participated in an international, multicentre before– after study. The intervention consisted of short courses and workshops on EBM offered in diverse settings, formats and intensities. The primary outcome measure was the score on the Berlin Questionnaire, a validated instrument measuring EBM knowledge that the participants completed before and after the course. Results: A total of 15 centres participated in the study and 420 learners from North America and Europe completed the study. The baseline score across courses was 7.49 points (range 3.97–10.42 points) out of a possible 15 points. The average increase in score was 1.40 points (95% confidence interval 0.48–2.31 points), which corresponded with an effect size of 0.44 standard deviation units. Greater improvement in scores was associated (in order of greatest to least magnitude) with active participation required of the learners, a separate statistics session, fewer topics, less teaching time, fewer learners per tutor, larger overall course size and smaller group size. Clinicians and learners involved in medical publishing improved their score more than other types of learners; administrators and public health professionals improved their score less. Learners who perceived themselves to have an advanced knowledge of EBM and had prior experience as an EBM tutor also showed greater improvement than those who did not. Interpretation: EBM course organizers who wish to optimize knowledge gain should require learners to actively participate in the course and should consider focusing on a small number of topics, giving particular attention to statistical concepts.

Background: There are few data about predictors of cardiovascular mortality and rehospitalization rate in patients with left ventricular systolic dysfunction (LVSD) after myocardial revascularization and optimization of pharmacological treatment. Patients and Methods: 1,346 consecutive patients with left ventricular ejection fraction (LVEF) < 45% (64 ± 10 years, 73% male, LVEF 36.3% ± 8%), who were referred for inpatient cardiac rehabilitation, were followed prospectively for 731 ± 215 days in a unicentric prospective longitudinal registry. Multivariate logistic regression Cox models were used to analyze demographic, echocardiographic and exercise variables in order to determine independent predictors of cardiovascular mortality and rehospitalization. Results: LVEF failed to show prognostic power (hazard ratio [HR] 0.99 [95% confidence interval, CI, 0.94–1.03]; p = not significant), whereas moderate to severe mitral regurgitation (HR, 5.71 [95% CI 1.75–18.6]; p = 0.004) and atrial fibrillation (HR 1.67 [95% CI 1.15–2.44]; p = 0.008) were associated with a poorer prognosis. In an optimized multivariate model, 6-min walk test (HR 0.93 [95% CI 0.86–1.00] per 50 m; p = 0.049) and symptom-limited maximum exercise capacity test (HR 0.83 [95% CI 0.76–0.91] per 10 W; p < 0.001) as well as female gender (HR 0.58 [95% CI 0.39–0.84]; p = 0.005) were strong predictors for reduced overall mortality. Conclusion: In patients with LVSD, independently of LVEF, traditional prognostic factors including atrial fibrillation or mitral regurgitation predict poorer survival, whereas symptom-limited exercise capacity and walking distance performed in 6-min walk test were highly predictive for a good prognosis.