Quality of Life and Work Ability among Healthcare Personnel with Chronic Viral Hepatitis. Evaluation of the Inpatient Rehabilitation Program of the Wartenberg Clinic.

The aim of this study was to research the impact of inpatient rehabilitation on work ability and health-related quality of life factors for healthcare personnel (HP) with chronic hepatitis B and C virus (HBV and HCV) infection. A prospective evaluation study with three data collection times without an external control group was conducted. HP (n = 163) with an occupational acquired chronic hepatitis B/C infection who participated in an inpatient rehabilitation program were surveyed. Information was collected on work ability (WAI-Work Ability Index), quality of life (SF-36-Short Form-36 Health Survey), and anxiety and depression-related symptoms (HADS-D-Hospital Anxiety and Depression Scale). The majority of participants had HCV infection. Work ability was poor, improved significantly until the end of treatment, and remained at a moderate level six months later. The SF-36 showed no change in physical health over the study period, the results regarding mental health were in the average range with a significant improvement directly after intervention. The HADS-D results indicate noteworthy anxiety and depression symptoms during the study period. The inpatient rehabilitation program proved to be effective in the short term regarding mental health (SF-36) and WAI. To ensure long lasting positive results, services aimed at enhancing physical and mental health should be provided as early as possible and on a recurring basis.

Real-world outcomes of endovascular treatment in a non-selected population with peripheral artery disease - prospective study with 2-year follow-up.

Background: The study aimed to evaluate the outcomes of percutaneous transluminal angioplasty (PTA) in lower-extremity peripheral artery disease (PAD) patients. Patients and methods: A multi-centre, observational study was performed with 32 German and Austrian centres contributing data to the PTA registry. Data of 1,781 patients with lower-leg and pelvic PAD who were suitable for endovascular PTA treatment were contributed from participating centres. Data from 1,533 patients are reported here (1,055 male and 478 female). This study did not have exclusion criteria. Quality of life (QOL) questionnaire (EQ-5D) scores, Rutherford classification, mortality, patency rate and details of major adverse cardiovascular events were collected at 6-, 12-, 18-, and 24-month follow ups. Results: PTA with/without stenting achieved 90.3 %, 86.5 %, 82.7 %, and 71.9 % technical success (recanalisation achieving ≥ 70 % patency, no evidence of embolisation, recoiling or dissection) in iliac, femoral, popliteal, and below-the-knee arteries, respectively. Procedural/postprocedural complications occurred in 142 (9.3 %, 1 death) and 74 (4.8 %) patients. QOL, mobility, self-care, activity, and pain/discomfort scores improved (p < 0.01), anxiety/depression was insignificantly improved. During follow-up, 409 (26.7 %) patients were hospitalised for PAD, 281 (18.3 %) required reintervention, and 145 (9.5 %) died or needed amputation (n = 49; 3.2 %). Multivariate analysis demonstrated poorer outcomes in patients with comorbidities. Conclusions: PTA with/without stenting is effective, safe, and widely applicable, with few complications. It improves QOL, but not anxiety/depression.

Immune cell subsets, cytokine and cortisol levels during the first week of life in neonates born to pre-eclamptic mothers.

PROBLEM: To address the hypothesis that pre-eclampsia (PE) impacts the fetal immune system, we investigated the prevalence of distinct immune cell subsets along with plasma cortisol and cytokine levels in pre-term newborns of PE mothers. METHOD OF STUDY: Cord blood and peripheral blood samples on the 1st, 3rd and 7th postnatal days of life were collected from 14 pre-term infants affected by PE and 14 non-PE pregnancies. We measured plasma cortisol and cytokine levels with immunoassays and assessed the prevalence of T, NK and DC subsets using flow cytometry. RESULTS: The prevalence of CD4+ cells was lower in PE infants, while that of memory T cells was higher. Myeloid DCs had a lower prevalence in PE neonates. Cytokine and cortisol levels were lower in PE neonates. CONCLUSION: Our observations show that PE pregnancies are associated with altered newborn immune status during the first week of life.

Predictive values derived from lower wisdom teeth developmental stages on orthopantomograms to calculate the chronological age in adolescence and young adults as a prerequisite to obtain age-adjusted informed patient consent prior to elective surgical procedures in young patients with incomplete or mismatched personal data.

Introduction: Surgical procedures require informed patient consent, which is mandatory prior to any procedure. These requirements apply in particular to elective surgical procedures. The communication with the patient about the procedure has to be comprehensive and based on mutual understanding. Furthermore, the informed consent has to take into account whether a patient is of legal age. As a result of large-scale migration, there are eventually patients planned for medical procedures, whose chronological age can't be assessed reliably by physical inspection alone. Age determination based on assessing wisdom tooth development stages can be used to help determining whether individuals involved in medical procedures are of legal age, i.e., responsible and accountable. At present, the assessment of wisdom tooth developmental stages barely allows a crude estimate of an individual's age. This study explores possibilities for more precise predictions of the age of individuals with emphasis on the legal age threshold of 18 years. Material and Methods: 1,900 dental orthopantomograms (female 938, male 962, age: 15-24 years), taken between the years 2000 and 2013 for diagnosis and treatment of diseases of the jaws, were evaluated. 1,895 orthopantomograms (female 935, male 960) of 1,804 patients (female 872, male 932) met the inclusion criteria. The archives of the Department of Diagnostic Radiology in Dentistry, University Medical Center Hamburg-Eppendorf, and of an oral and maxillofacial office in Rostock, Germany, were used to collect a sufficient number of radiographs. An effort was made to achieve almost equal distribution of age categories in this study group; 'age' was given on a particular day. The radiological criteria of lower third molar investigation were: presence and extension of periodontal space, alveolar bone loss, emergence of tooth, and stage of tooth mineralization (according to Demirjian). Univariate and multivariate general linear models were calculated. Using hierarchical multivariate analyses a formula was derived quantifying the development of the four parameters of wisdom tooth over time. This model took repeated measurements of the same persons into account and is only applicable when a person is assessed a second time. The second approach investigates a linear regression model in order to predict the age. In a third approach, a classification and regression tree (CART) was developed to derive cut-off values for the four parameters, resulting in a classification with estimates for sensitivity and specificity. Results: No statistically significant differences were found between parameters related to wisdom tooth localization (right or left side). In univariate analyses being of legal age was associated with consecutive stages of wisdom tooth development, the obliteration of the periodontal space, and tooth emergence, as well with alveolar bone loss; no association was found with tooth mineralization. Multivariate models without repeated measurements revealed imprecise estimates because of the unknown individual-related variability. The precision of these models is thus not very good, although it improves with advancing age. When calculating a CART-analysis and a receiver operating characteristics - area under the curve of 78% was achieved; when maximizing both specificity and sensitivity, a Youden's index of 47% was achieved (with 73% specificity and 74% sensitivity). Discussion: This study provides a basis to help determine whether a person is 18 years or older in individuals who are assumed to be between 15 and 24 years old. From repeated measurements, we found a linear effect of age on the four parameters in the individuals. However, this information can't be used for prognosis, because of the large intra-individual variability. Thus, although the development of the four parameters can be estimated over time, a direct conclusion with regard to age can't be drawn from the parameters without previous biographic information about a person. While a single parameter is of limited value for calculating the target age of 18 years, combining several findings, that can be determined on a standard radiography, may potentially be a more reliable diagnostic tool for estimating the target age in both sexes. However, a high degree of precision can't be achieved. The reason for persistent uncertainty lies in the wide chronological range of wisdom tooth development, which stretches from well below to above the 18th life year. The regression approach thus seems not optimal. Although sensitivity and specificity of the CART-model are moderately high, this model is still not reliable as a diagnostic tool. Our findings could have impact, e.g. on elective surgeries for young individuals with unknown biography. However, these results cannot replace social engagement, in particular thorough physical examination of patients and careful registration of their histories. Further studies on the use of this calculation method in different ethnic groups would be desirable.

Plasma vitamin D levels at birth and immune status of preterm infants.

BACKGROUND: Vitamin D has an important immunomodulatory role. We investigated whether vitamin D levels at birth may associate with immune status in preterm infants. METHODS: Cord blood samples were collected from 28 preterm infants born ≤30 weeks of gestation. Infants were divided into groups below and above median vitamin D level. We measured plasma cortisol and cytokine levels and also assessed the peripheral prevalence of distinct immune cell subsets using flow cytometry. The mixed effect model was used to analyse the effects of vitamin D, plasma cortisol levels and gestational age on cytokine levels and immune phenotype. RESULTS: Vitamin D level in our cohort was 23.3 [9.9-45.4]ng/ml (median [range]). In infants with vitamin D level below the median the prevalence of CD4+ CXCR3+ (Th1) and CD8+ CXCR3+ cell subsets was higher, while the prevalence of CD4+ CCR4+ (Th2), CD8+ CCR4+ and plasmacytoid dendritic cell (pDC) subsets was lower than in those with vitamin D level above median. pDCs and Th2 lymphocytes were the only cell subsets which were only influenced by vitamin D levels, but not by plasma cortisol and gestational age. No association between vitamin D level and any of the tested plasma cytokine levels was detected. CONCLUSIONS: Vitamin D levels may together with cortisol levels and gestational age have an effect on Th1/Th2 balance and the prevalence of plasmocytoid dendritic cells in the preterm newborn.

Expression of lymphocyte activation markers of preterm neonates is associated with perinatal complications.

BACKGROUND: Inappropriate activation of T lymphocytes plays an important role in perinatal complications. However, data on T lymphocyte activation markers of preterm infants is scarce. We investigated the association between gender, gestational and postnatal age, preeclampsia (PE), premature rupture of membranes (PROM) as well as prenatal steroid treatment (PS) and the frequency of activated T lymphocyte subsets (HLA-DR+, CD69+, CD25+, CD62L+) and major T lymphocyte subpopulations (CD4, CD8, Th1, Th2, naïve, memory) in peripheral blood during the first postnatal week in preterm infants. RESULTS: Cord blood and peripheral blood samples were collected from 43 preterm infants on the 1st, 3rd, and 7th days of life. We assessed the frequency of the above T lymphocyte subsets using flow cytometry. The 'mixed effect model' was used to analyze the effects of clinical parameters on T lymphocyte markers. The frequency of CD25+ T lymphocytes was higher in PROM. The frequency of CD4+ and CD8+ cells and the CD4+/CD8+ cell ratio was decreased in PE. The frequency of CD62L+ T lymphocytes was higher in male compared with female infants. PS did not affect the frequency of the investigated markers. CD4+ CD25+ cells had a lower frequency at birth than on day 7. Th2 lymphocytes had a lower frequency on postnatal days 1 and 3 when compared to day 7. CONCLUSIONS: Our observations indicate that alterations affecting the expression of T lymphocyte activation markers are associated with the above factors and may play a role in the development of perinatal complications.

Skin conductance in neonates suffering from abstinence syndrome and unexposed newborns.

UNLABELLED: The aims of this study were to compare the skin conductance (SC) of newborns with opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns and to evaluate the potential of SC readings to detect distress in the context of NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was measured at nine specific times during their first 6 weeks of life. The number of SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the mean level of SC were recorded and analyzed. The SC of newborns treated for symptoms of NAS differed significantly from the SC of unexposed newborns with regard to the NSCF/s (p = 0.04). With the mean level of SC, we observed an interaction between groups over time (p value for interaction = 0.02). With increasing postnatal age, we observed higher values in all three SC parameters. CONCLUSION: The NSCF/s and the mean level of SC appear to be suitable to reflect the distress of newborns suffering from NAS. As it is known that the sensitivity of SC increases with the level of stress experienced, its potential to indicate elevated stress levels in infants with NAS should be investigated in future studies evaluating different therapy regimens. WHAT IS KNOWN: • Skin conductance is a result of the filling of palmar and plantar sweat glands innervated by the sympathetic nervous system • Skin conductance can be used as a measure of stress and pain in newborns What is New: • Skin conductance of newborns with neonatal abstinence syndrome (NAS) differs significantly from the SC of non-substance-exposed newborns during the first 6 weeks of life • Skin conductance appears to reflect the increased distress of infants with NAS.

Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up.

BACKGROUND: In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany. OBJECTIVES: As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors. METHODS: A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables. RESULTS: Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association. CONCLUSIONS: PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation.

Impact of Complete Versus Incomplete Circumferential Lines Around the Pulmonary Veins During Catheter Ablation of Paroxysmal Atrial Fibrillation: Results From the Gap-Atrial Fibrillation-German Atrial Fibrillation Competence Network 1 Trial.

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<0.001), for a difference in favor of complete PVI of 17.1% (95% confidence interval, 5.3%-28.9%). Invasive restudy in 103 group A patients and 93 group B patients revealed conduction gaps in 92 (89.3%) and 65 (69.9%) patients, respectively. 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.

Use of vitamin K antagonists for secondary stroke prevention depends on the treating healthcare provider in Germany - results from the German AFNET registry.

BACKGROUND: Anticoagulation using vitamin K antagonists (VKAs) significantly reduces the risk of recurrent stroke in stroke patients with atrial fibrillation (AF) and is recommended by guidelines. METHODS: The German Competence NETwork on Atrial Fibrillation established a nationwide prospective registry including 9,574 AF patients, providing the opportunity to analyse AF management according to German healthcare providers. RESULTS: On enrolment, 896 (9.4 %) patients reported a prior ischaemic stroke or transient ischaemic attack. Stroke patients were significantly older, more likely to be female, had a higher rate of cardiovascular risk factors, and more frequently received anticoagulation (almost exclusively VKA) than patients without prior stroke history. Following enrolment, 76.4 % of all stroke patients without VKA contraindications received anticoagulation, which inversely associated with age (OR 0.95 per year; 95 % CI 0.92-0.97). General practitioners/internists (OR 0.40; 95 % CI 0.21-0.77) and physicians working in regional hospitals (OR 0.47; 95 % CI 0.29-0.77) prescribed anticoagulation for secondary stroke prevention less frequently than physicians working at university hospitals (reference) and office-based cardiologists (OR 1.40; 95 % CI 0.76-2.60). The impact of the treating healthcare provider was less evident in registry patients without prior stroke. CONCLUSIONS: In the AFNET registry, anticoagulation for secondary stroke prevention was prescribed in roughly three-quarters of AF patients, a significantly higher rate than in primary prevention. We identified two factors associated with withholding oral anticoagulation in stroke survivors, namely higher age and-most prominently-treatment by a general practitioner/internist or physicians working at regional hospitals.

A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy.

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥ 40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.

Effect of cardiac rehabilitation on functional and emotional status in patients after transcatheter aortic-valve implantation.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) is an established alternative therapy in patients with severe aortic stenosis and a high surgical risk. Despite a rapid growth in its use, very few data exist about the efficacy of cardiac rehabilitation (CR) in these patients. We assessed the hypothesis that patients after TAVI benefit from CR, compared to patients after surgical aortic-valve replacement (sAVR). METHODS: From September 2009 to August 2011, 442 consecutive patients after TAVI (n = 76) or sAVR (n = 366) were referred to a 3-week CR. Data regarding patient characteristics as well as changes of functional (6-min walk test. 6-MWT), bicycle exercise test), and emotional status (Hospital Anxiety and Depression Scale) were retrospectively evaluated and compared between groups after propensity score adjustment. RESULTS: Patients after TAVI were significantly older (p < 0.001), more female (p < 0.001), and had more often coronary artery disease (p = 0.027), renal failure (p = 0.012) and a pacemaker (p = 0.032). During CR, distance in 6-MWT (both groups p ≤ 0.001) and exercise capacity (sAVR p ≤ 0.001, TAVI p ≤ 0.05) significantly increased in both groups. Only patients after sAVR demonstrated a significant reduction in anxiety and depression (p ≤ 0.001). After propensity scores adjustment, changes were not significantly different between sAVR and TAVI, with the exception of 6-MWT (p = 0.004). CONCLUSIONS: Patients after TAVI benefit from cardiac rehabilitation despite their older age and comorbidities. CR is a helpful tool to maintain independency for daily life activities and participation in socio-cultural life.

Magnetically guided capsule versus conventional gastroscopy for upper abdominal complaints: a prospective blinded study.

OBJECTIVES: Upper gastrointestinal endoscopy is mostly performed under sedation and has a low yield of relevant gastric lesions in patients without alarm symptoms. Simpler screening tests such as capsule endoscopy could be helpful, but gastric visualization is insufficient with the current passive capsules. A magnetically guided gastric capsule was prospectively evaluated in patients with routine indications for gastroscopy. METHODS: A total of 189 symptomatic patients (105 male; mean age 53 y) from 2 French centers subsequently and blindly underwent capsule and conventional gastroscopy by 9 and 6 examiners, respectively. The final gold standard was unblinded conventional gastroscopy with biopsy under propofol sedation. Main outcome was accuracy (sensitivity/specificity) of capsule gastroscopy for diagnosis of major gastric lesions, defined as those lesions requiring conventional gastroscopy for biopsy or removal. RESULTS: Twenty-three major lesions were found in 21 patients. Capsule accuracy was 90.5% [95% confidence interval (CI), 85.4%-94.3%] with a specificity of 94.1% (95% CI, 89.3%-97.1%) and a sensitivity of 61.9% (95% CI, 38%-82%). Accuracy did not correlate with lesion location, gastric luminal visibility, examiner case volume, or examination time. Of the remaining 168 patients, 94% had minor and mostly multiple lesions; the capsule made a correct diagnosis in 88.1% (95% CI, 82.2%-92.6%), with gastric visibility and lesion location in the proximal stomach having significant influence. All patients preferred capsule gastroscopy. CONCLUSIONS: In a prospective and strictly blinded study, magnetically guided capsule gastroscopy was shown to be feasible in clinical practice and was clearly preferred by patients. Improvements in capsule technology may render this technique a future alternative to gastroscopy.

Morbidity and treatment in patients with atrial fibrillation and chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality but there are few studies available about atrial fibrillation, the most frequent arrhythmia in CKD, and the applied treatment. Based on the prospective German Competence NETwork on Atrial Fibrillation, data of 3138 patients with atrial fibrillation were analyzed and categorized by their estimated glomerular filtration rate (stages 1-3 and 4 plus 5). With advanced CKD, significantly more patients suffered from a more severe form of atrial fibrillation. Despite significantly higher CHADS2 scores in advanced CKD, oral anticoagulation was not prescribed more frequently while antiarrhythmic drugs and catheter ablations were used significantly less often, in contrast to more pacemaker implantations. However, in multivariate hierarchical logistic regression analyses of in-hospital treatments and complications, only hemorrhages and pacemaker implantations turned out to be independently and significantly associated with higher CKD stages. This nationwide study shows that patients with CKD and atrial fibrillation suffer from a markedly higher comorbidity. Thus, while CKD patients have received cardioversions, ablations, antiarrhythmic, or anticoagulation drugs significantly less often in their history, current treatments were not different if adjusted for multiple comorbidities. This might indicate an improvement in the often reported therapeutic nihilism in CKD.

Impact of Severe Extracranial ICA Stenosis on MRI Perfusion and Diffusion Parameters in Acute Ischemic Stroke.

PURPOSE: The aim of this study was to investigate the impact of a coexisting internal carotid artery (ICA) stenosis on lesion volumes as well as diffusion and perfusion parameters in acute ischemic stroke resulting from middle cerebral artery (MCA) occlusion. MATERIAL AND METHODS: Magnetic resonance imaging data of 32 patients with MCA occlusion with or without additional ICA stenosis imaged within 4.5 h of symptom onset were analyzed. Both groups consisted of 16 patients. Acute diffusion lesions were semi-automatically segmented in apparent diffusion coefficient (ADC) MRI datasets. Perfusion maps of cerebral blood volume (CBV), cerebral blood flow, mean transit time and T max were calculated using perfusion-weighted MRI datasets. Tissue-at-risk (TAR) volumes were generated by subtracting the ADC lesion from the hypoperfusion lesion defined by T max >6 s. Median ADC and perfusion parameter values were extracted separately for the diffusion lesion and TAR and used for statistical analysis. RESULTS: No significant differences were found between the groups regarding the diffusion lesion and TAR volumes. Statistical analysis of diffusion and perfusion parameters revealed CBV as the only parameter with a significant difference (p = 0.009) contributing a small effect (η(2) = 0.11) to the group comparison with higher CBV values for the patient group with a coexisting ICA stenosis, while no significant effects were found for the other diffusion and perfusion parameters analyzed. CONCLUSION: The results of this study suggest that a coexisting ICA stenosis does not have a strong effect on tissue status or perfusion parameters in acute stroke patients except for a moderate elevation of CBV. This may reflect improved collateral circulation or ischemic preconditioning in patients with a pre-existing proximal stenosis balancing impaired perfusion from the stenosis.

Sustained and "sleeper" effects of group metacognitive training for schizophrenia: a randomized clinical trial.

IMPORTANCE: Cognitive interventions increasingly complement psychopharmacological treatment to enhance symptomatic and functional outcome in schizophrenia. Metacognitive training (MCT) is targeted at cognitive biases involved in the pathogenesis of delusions. OBJECTIVE: To examine the long-term efficacy of group MCT for schizophrenia in order to explore whether previously established effects were sustained. DESIGN, SETTING, AND PARTICIPANTS: A 2-center, randomized, controlled, assessor-blind, parallel group trial was conducted. A total of 150 inpatients or outpatients with DSM-IV diagnoses of schizophrenia spectrum disorders were enrolled. All patients were prescribed antipsychotic medication. The second follow-up assessment took place 3 years later after the intervention phase was terminated. INTERVENTIONS: Group MCT targeting cognitive biases vs neuropsychological training (COGPACK). Patients received a maximum of 16 sessions. MAIN OUTCOMES AND MEASURES: The primary outcome measure was a delusion score derived from the Positive and Negative Syndrome Scale (PANSS). The PANSS positive syndrome and total scores, the Psychotic Symptom Rating Scales, the jumping to conclusions bias, self-esteem, and quality of life served as secondary outcome measures. RESULTS: The intention-to-treat analyses demonstrated that patients in the MCT group had significantly greater reductions in the core PANSS delusion score, after 3 years compared with the control group (η2partial = .037; P = .05). Among the secondary outcomes, the intention-to-treat analyses also demonstrated that patients in the MCT group had significantly greater reductions in the PANSS positive syndrome score (η2partial = .055; P = .02) and the Psychotic Symptom Rating Scales delusion score (η2partial = .109; P = .001). Significant group differences at the 3-year follow-up were also found on measures of self-esteem and quality of life, which did not distinguish groups at earlier assessment points. Attention was improved in the neuropsychological training group relative to the MCT group. The completion rate was 61.3% after 3 years. CONCLUSIONS AND RELEVANCE: Metacognitive training demonstrated sustained effects in the reduction of delusions, which were over and above the effects of antipsychotic medication. Moreover, there were some unanticipated ("sleeper") effects as both self-esteem and quality of life were improved after 3 years. Effects on self-esteem and well-being were found even in the absence of an improvement on the jumping to conclusions bias. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN95205723.

German multicenter real-world registry of stenting for superficial femoral artery disease: clinical results and predictive factors for revascularization.

PURPOSE: To investigate nitinol stent treatment of superficial femoral artery (SFA) lesions and the impact of different risk factors on the need for clinically driven target lesion revascularization (TLR) in a large, real-world population of claudicants. METHODS: Patients presenting with symptomatic SFA stenosis >70% were consecutively enrolled in the 13-center MARIS prospective registry (ClinicalTrials.gov identifier NCT01067885). There was no restriction on lesion length, thus leading to the inclusion of a real-world as well as high-risk patient cohort. The 998 participating patients (657 men; mean age 67.4±9.2 years) had 1050 lesions treated with the same nitinol stent type. The mean lesion length was 9.5±9.6 cm (range 0.5-44; median 8.0); more than a third of the lesions (450, 42.9%) were total occlusions. The primary endpoint was the need for clinically driven target lesion revascularization (TLR) at 12 months. RESULTS: Acute technical success was achieved in 1042 (99.2%) lesions. Restenosis occurred in 187 (23.7%) and reocclusion in 79 (10.0%) lesions at 12 months. The primary endpoint of TLR at 12 months was reached by 136 (17.2%) patients. The periprocedural complication rate was 5.4%. Independent predictors of TLR were female gender [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.3 to 0.7, p<0.001] and lesion length >20 cm vs. 10 cm (OR 2.7, 95% CI 1.1 to 6.6, p=0.029) and 10-20 cm vs. 10 cm (OR 1.9, 95% CI 1.0 to 4.1, p=0.047). CONCLUSION: Stent implantation in the SFA is safe and associated with favorable acute and midterm results in a real-world setting. Lesion length and female gender were identified as independent risk factors for TLR.

Impact of biatrial defragmentation in patients with paroxysmal atrial fibrillation: results from a randomized prospective study.

BACKGROUND: Single procedure success rates of pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (PAF) are still unsatisfactory. In patients with persistent atrial fibrillation (AF), ablation of complex fractionated atrial electrograms (CFAEs) after PVI results in improved outcomes. OBJECTIVE: We aimed to investigate if PAF-patients with intraprocedurally sustained AF after PVI might benefit from additional CFAE ablation. METHODS: A total of 1134 consecutive patients underwent a first catheter ablation procedure of PAF between June 2008 and December 2012. In most patients, AF was either not inducible or terminated during PVI. In 68 patients (6%), AF sustained after successful PVI. These patients were randomized to either cardioversion (PVI-alone group; n = 33) or additional CFAE ablation (PVI+CFAE group; n = 35) and followed up every 1-3 months and serial Holter recordings were also obtained. The primary end point was the recurrence of AF/atrial tachycardia (AT) after a blanking period of 3 months. RESULTS: Procedure duration (127 ± 6 minutes vs 174 ± 10 minutes), radiofrequency application time (44 ± 3 minutes vs 74 ± 5 minutes), and fluoroscopy time (26 ± 2 minutes vs 41 ± 3 minutes) were longer in the PVI+CFAE group (all P < .001). In 30 of 35 patients (86%) in the PVI+CFAE group, ablation terminated AF. There was no significant group difference with respect to freedom from AF/AT (22 of 33 [67%] vs 22 of 35 [63%]; P = .66). Subsequently, 10 of 11 patients in the PVI-alone group (91%) and 11 of 13 patients in PVI+CFAE group (85%) underwent repeat ablation (P = 1.00). Overall, 29 of 33 [88%] vs 30 of 35 [86%] patients (P = 1.00) were free from AF/AT after 1.4 ± 0.1 vs 1.4 ± 0.2 (P = .87) procedures. CONCLUSION: Patients with sustained AF after PVI in a PAF cohort are rare. Regarding AF/AT recurrence, these patients did not benefit from further CFAE ablation compared to PVI alone, but are exposed to longer procedure duration, fluoroscopy time, and radiofrequency application time.

Investigation of the role of the jumping-to-conclusions bias for short-term functional outcome in schizophrenia.

Symptom severity and neuropsychological deficits negatively influence functional outcomes in patients with schizophrenia. Recent research implicates specific types of biased thinking styles (e.g. jumping-to-conclusions) in the pathogenesis of schizophrenia. This is the first study to test the impact of jumping-to-conclusions on functional outcome in schizophrenia. The aim of the study was to investigate the association of psychopathology, neuropsychology and JTC with subjective quality of life, vocational outcome and housing status in schizophrenia. Analyses were carried out both cross-sectionally at baseline, and longitudinally over the course of symptomatic improvement in the immediate aftermath of a psychotic exacerbation. Seventy-nine patients with schizophrenia were included in the study. Data concerning the variables of interest were collected at baseline, after one month, and after six months. Positive symptomatology was the most significant predictor of subjective and vocational outcome and changes across time. Verbal memory deficits were associated with functional status cross-sectionally, whereas general cognitive capacity significantly predicted functional changes over time. Improvement of the jumping-to-conclusions bias positively affected vocational outcome. Though limited, the observed effect of this bias on real-world functioning highlights the possible usefulness of interventions aimed at improving (meta)cognitive deficits in schizophrenia.

Targeting class IA PI3K isoforms selectively impairs cell growth, survival, and migration in glioblastoma.

The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancer and plays a crucial role in glioblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K isoforms as a novel anti-tumor approach in glioblastoma. Consistent expression of the PI3K catalytic isoform PI3K p110α was detected in a panel of glioblastoma patient samples. In contrast, PI3K p110ß expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110α/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p110α activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p110α or PI3K p110ß also led to impaired anchorage-independent growth, a decreased migratory capacity of glioblastoma cells, and reduced the activation of the Akt/mTOR pathway. These effects were selective, because targeting of PI3K p110δ did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110α can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110α/p-S6.