Image-guided transcranial Doppler sonography for monitoring of vasospasm after subarachnoid hemorrhage.

Transcranial Doppler ultrasound (TCD) is a standard method for bedside vasospasm monitoring after subarachnoid hemorrhage (SAH). Image guidance has previously been shown to reduce intra- and interobserver variability of this method. The aim of the present study was to compare image-guided and conventional TCD in vasospasm monitoring after SAH.418 TCD exams of 24 consecutive SAH patients registered in a database were evaluated. Of these, 130 image-guided exams were identified which had been performed on the same day as conventional Doppler exams. These matched pairs were taken for statistical analysis. Data were tested statistically using the sign test applied at patient level to aggregated …

Health‐Related Quality of Life in Hereditary Hemorrhagic Telangiectasia

Objective To assess and differentiate the health-related quality of life (HR-QoL) in patients with hereditary hemorrhagic telangiectasia (HHT). Study Design and Setting A prospective, open, cross-sectional questionnaire-based study (including the Short Form-36 Health Survey [SF-36]) performed by a tertiary care center. Results A total of 77 patients (36 females) were included. Except for one domain (bodily pain), the scores for all scales of the SF-36 were significantly reduced in comparison with normative data. The duration of epistaxis, the presence of hepatic involvement and gastrointestinal bleeding, and the number of visible telangiectases correlated with lower scores on several scales…

Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

Abstract Introduction Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. Materials and Methods In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. Results 22 patients were included in the int…

Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial.

BACKGROUND: European guidelines recommend intravenous methylprednisolone as first-line treatment for active and severe Graves' orbitopathy; however, it is common for patients to have no response or have relapse after discontinuation of treatment. We aimed to compare the efficacy and safety of add-on mycophenolate to methylprednisolone in comparison with methylprednisolone alone in patients with moderate-to-severe Graves' orbitopathy.METHODS: MINGO was an observer-masked, multicentre, block-randomised, centre-stratified trial done in two centres in Germany and two in Italy. Patients with active moderate-to-severe Graves' orbitopathy were randomly assigned to receive intravenous methylprednis…

Amino Acid Polymorphisms in Hla Class II Differentiate Between Thyroid and Polyglandular Autoimmunity.

Abstract Context The structure of the human leucocyte antigen (HLA) peptide-binding clefts strongly contributes to monoglandular and polyglandular autoimmunity (AP). Objective To investigate the impact of amino acid polymorphisms on the peptide-binding interactions within HLA class II and its association with AP. Design Immunogenetic study. Setting Tertiary referral center for autoimmune endocrine diseases. Subjects 587 subjects with AP, autoimmune thyroid disease (AITD), type 1 diabetes (T1D), and healthy unrelated controls were typed for HLA class II. Methods Amino acids within the peptide binding cleft that are encoded by HLA class II exon 2 were listed for all codon positions in all sub…

Case Management for Depression by Health Care Assistants in Small Primary Care Practices

BACKGROUND: Case management by health care assistants in small primary care practices provides unclear benefit for improving depression symptoms. OBJECTIVE: To determine whether case management provided by health care assistants in small primary care practices is more effective than usual care in improving depression symptoms and process of care for patients with major depression. DESIGN: Cluster randomized, controlled trial. A central automated system generated the randomization scheme, which was stratified by urban and rural practices; allocation sequence was concealed until groups were assigned. SETTING: 74 small primary care practices in Germany from April 2005 to September 2007. PATIEN…

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood.

The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations.Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and lab…

Declaration and Handling of Conflicts of Interest in Guidelines

Clinical guidelines are developed in order to support physicians and patients in specific clinical situations when decisions concerning diagnosis and treatment are made. Recommendations provided in guidelines are based on the findings of clinical studies and on expert opinion. Identical study findings may be evaluated differently depending on whether or not guideline authors have conflicts of interest (1). A conflict of interest is defined as a circumstance that gives rise to a risk that professional judgement or actions concerning a primary interest may be inappropriately influenced by a secondary interest (2, 3). A conflict of interest is therefore a state of affairs, not a biased evaluat…

Evaluation einer ICF-CY-basierten komplexen Versorgungsmaßnahme zur Verbesserung der partizipativen Entscheidungsfindung an Sozialpädiatrischen Zentren (SPZ) und der sozialen Teilhabe von Kindern mit chronischen Erkrankungen: Design der Studie PART-CHILD

Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.

Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells af…

Depression in the nursing home: a cluster-randomized study to probe the effectiveness of a novel case management approach to improve treatment (the DAVOS project)

Abstract Background Depression is the second most common psychiatric illness in old people. Up to 30% of nursing home residents suffer from minor or major depression. Although depressive disorders in old age can be improved and even cured with adequate therapy, they often go unnoticed in nursing home residents and remain untreated. This highlights a striking deficit in health care and might results not only in lower quality of life among those concerned but also in poor physical functioning, premature mortality and increased hospitalization rates. Methods The aim of the interdisciplinary research project DAVOS is to implement an innovative and stepped structural case management program to i…

Evaluation der Sprachaufgaben des sozialpädiatrischen Entwicklungsscreenings für Schuleingangsuntersuchungen (SOPESS): Ergebnisse der prospektiven Kindergesundheitsstudie ikidS

Zusammenfassung Hintergrund Eine frühe Diagnostik und Behandlung von Entwicklungsstörungen vor der Einschulung ist für den weiteren Bildungserfolg maßgeblich. Deshalb wurde das Sozialpädiatrische Entwicklungsscreening für Schuleingangsuntersuchungen (SOPESS) konzipiert und in mehreren Bundesländern flächendeckend eingeführt. Fragestellung Wir untersuchten die Zusammenhänge zwischen den Screening-Ergebnissen der SOPESS-Sprachaufgaben vor der Einschulung und den schulischen Sprachkompetenzen am Ende der ersten Klasse als Teil einer umfassenden Evaluation des SOPESS. Methoden Daten der rheinland-pfälzischen Schuleingangsuntersuchung und der prospektiven Kindergesundheitsstudie ikidS wurden zus…

Einstellungen und Erwartungen von Patienten in Bezug auf Interessenkonflikte ihrer behandelnden Ärzte

Zusammenfassung Hintergrund Patienten durfen zu Recht erwarten, dass im Vertrauensverhaltnis zu ihrem Arzt sekundare Interessen keine unangemessene Rolle spielen. Was Patienten uber Interessenkonflikte ihrer Arzte durch die Zusammenarbeit mit pharmazeutischen Unternehmern wissen und ob und wie sie daruber informiert werden wollen, ist in Deutschland wenig bekannt. Methode 765 Patienten in verschiedenen Arztpraxen und Kliniken (Ambulanzen und Stationen) zweier deutscher Stadte erhielten ein Informationsblatt zu Interessenkonflikten und einen Fragebogen mit 19 Fragen. 80% (n = 612) der Fragebogen wurden anonym ausgefullt abgegeben. Ergebnisse 65% der Patienten waren keine moglichen Interessen…

Peripapillary Choroidal Thickness and Choroidal Area in Glaucoma, Ocular Hypertension and Healthy Subjects by SD-OCT.

Background: The exact pathogenesis of open angle glaucoma and ocular hypertension remains unclear. Hemodynamic influences are discussed as potential risk factors and the choroid may play an important role in the pathogenesis of open angle glaucoma or ocular hypertension. The current study investigates peripapillary choroidal thickness and choroidal area in patients with open angle glaucoma, subjects with ocular hypertension and healthy subjects using spectral-domain OCT. It furthermore assesses the association between peripapillary choroidal thickness and age, central corneal thickness, refractive error and intraocular pressure. Patients and Methods: Prospectively recorded data of 213 eyes …

United States and European Multicenter Prospective Study for the Analytical Performance and Clinical Validation of a Novel Sensitive Fully Automated Immunoassay for Calcitonin.

Abstract BACKGROUND The objective of this study is the validation and proof of clinical relevance of a novel electrochemiluminescence immunoassay (ECLIA) for the determination of serum calcitonin (CT) in patients with medullary thyroid carcinoma (MTC) and in different diseases of the thyroid and of calcium homeostasis. METHODS This was a multicenter prospective study on basal serum CT concentrations performed in 9 US and European referral institutions. In addition, stimulated CT concentrations were measured in 50 healthy volunteers after intravenous calcium administration (2.5 mg/kg bodyweight). RESULTS In total, 1929 patients and healthy controls were included. Limits of blank, detection, …

Outcomes of pneumatic dilation in achalasia: Extended follow-up of more than 25 years with a focus on manometric subtypes

Background and aim Pneumatic dilation (PD) is the most popular nonsurgical treatment for achalasia. This study investigated predicting factors, including manometric subtypes for symptom recurrence in the long term, in patients with achalasia treated with a single PD. Methods Between 1983 and 2013, a total of 107 patients were treated initially with a single PD and included in this longitudinal cohort study. Outcomes were correlated with demographics, symptoms (Eckardt score), and esophagographic and manometric features. Manometric tracings were retrospectively classified according to the three subtypes of the Chicago classification. Results Ninety-one (85%) patients were successfully treate…

EPA-0703 – Performance of the hamilton depression rating subscales to predict antidepressant treatment response in the early course of treatment

Early improvement ( EI ), i.e. a symptom reduction from baseline of at least 20% after 2 weeks, has been proven to be a clinically useful predictor for later treatment outcome. In most studies EI is identified by using the sum score of the Hamilton Depression Rating Scale (HAMD). Several unidimensional subscales of the HAMD exist, which have proven to be an economic measure of treatment change. Their ability to detect onset of improvement in comparison to the full HAMD has not been researched yet. The present study investigated in patients with major depression (MD) (1) whether the HAMD subscales are a valid and economic option to predict antidepressant treatment response in the early cours…

A randomized trial comparing conventional cytology to liquid-based cytology and computer assistance.

Liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical cancer screening in some countries. However, it remains unclear whether LBC is superior to CC. A randomized controlled trial was conducted between August 2007 and March 2009 in Germany to compare LBC, alone and in combination with computer-assisted imaging technology (CAS), to CC in the detection of histologically confirmed cervical intraepithelial neoplasia (CIN). The main outcome measures were detection rates, relative sensitivities, positive predictive values (PPVs) and relative PPVs comparing LBC without and with CAS to CC. Primary histological outcome was CIN2 or higher. Included were 20,627 women particip…

Pressure pain thresholds: Subject factors and the meaning of peak pressures.

Background The assessment of pressure pain has become an integral part in pain research. The distribution of pressure under a plunger can be uneven. However, measurements based on conventional devices show the applied force or mean pressure, failing to take local pressure peaks into account. Our main question was whether peak pressures under the probe are responsible for pain onset. Methods A force-controlled algometer was fitted with a newly developed pressure-indicating film. Pressure pain thresholds (PPTs) of 100 healthy subjects (57 men, age 18-66 years) were assessed at 29 sites across the body. Each site was measured three times, nonconsecutively and presented in randomized order. For…

Planning and Analysis of Trials Using a Stepped Wedge Design: Part 26 of a Series on Evaluation of Scientific Publications

Background The stepped-wedge design (SWD) of clinical trials has become very popular in recent years, particularly in health services research. Typically, study participants are randomly allotted in clusters to the different treatment options. Methods The basic principles of the stepped wedge design and related statistical techniques are described here on the basis of pertinent publications retrieved by a selective search in PubMed and in the CIS statistical literature database. Results In a typical SWD trial, the intervention is begun at a time point that varies from cluster to cluster. Until this time point is reached, all participants in the cluster belong to the control arm of the trial…

Standard treatment of female patients with breast cancer decreases substantially for women aged 70 years and older: a German clinical cohort study

Standard treatment of patients with breast cancer decreases with age and older persons are mostly excluded from clinical trials. We hypothesized that non-adherence to treatment guidelines occurs for women agedor =70 years and changes overall survival (OAS) and disease-free survival (DFS).We enrolled 1922 women agedor =50 years with histologically confirmed invasive breast cancer treated at the University of Ulm from 1992 to 2005. Adherence to guidelines and effects on OAS and DFS for women agedor =70 years was compared with that for younger women (50-69 years).Women70 years less often received recommended breast-conserving therapy (70-79 years: 74%-83%;79 years: 54%) than women agedor =69 y…

Depression in the nursing home: a cluster-randomized stepped-wedge study to probe the effectiveness of a novel case management approach to improve treatment (the DAVOS project)

Abstract Background Depression is the second most common psychiatric illness in old people. Up to 30% of nursing home residents suffer from minor or major depression. Although depressive disorders in old age can be improved and even cured with adequate therapy, they often go unnoticed in nursing home residents and remain untreated. This highlights a striking deficit in health care and might results not only in lower quality of life among those concerned but also in poor physical functioning, premature mortality and increased hospitalization rates. Methods The aim of the interdisciplinary research project DAVOS is to implement an innovative and stepped structural case management program to i…

Positive impact of a family practice-based depression case management on patient's self-management.

Abstract Objective Family practice-based depression case management improves depression symptoms and adherence to medication. The aim of this study was to explore the long-term effects of practice-based depression case management on patient depression-related self-management knowledge and activities. Methods This long-term follow-up of a randomized controlled trial study took place 12 months after the end of the 1-year case management intervention. We used a modified version of the depression-specific self-management questionnaire described in Ludman et al. [ Psychol Med , 33 (2003) 1061–1070]. Analyses of self-management knowledge and activities used a linear mixed model accounting for pra…

The Influence of Oxidative Stress on Neurological Outcomes in Spontaneous Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient’s outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume &gt

A weighted combined effect measure for the analysis of a composite time-to-first-event endpoint with components of different clinical relevance

Composite endpoints combine several events within a single variable, which increases the number of expected events and is thereby meant to increase the power. However, the interpretation of results can be difficult as the observed effect for the composite does not necessarily reflect the effects for the components, which may be of different magnitude or even point in adverse directions. Moreover, in clinical applications, the event types are often of different clinical relevance, which also complicates the interpretation of the composite effect. The common effect measure for composite endpoints is the all-cause hazard ratio, which gives equal weight to all events irrespective of their type …

Participation in adjuvant clinical breast cancer trials: Is there a difference in survival compared to guideline adherent adjuvant treatment? A retrospective multicenter cohort study of 5,326 patients.

1082 Background: Clinical trials (CT) usually compare a standard treatment regime versus innovative new substances or regimens. However participation in CT is available for only few patients and exclusion criteria is usually very strict. Therefore this study tries to answer the following questions: (1) Does participation in adjuvant CT improve survival in breast cancer (BC)? (2) Is there a difference in survival compared to guideline adherence and what is the role of the other treatments surrounding adjuvant breast cancer treatment? Methods: This German multi-center [17 participating hospitals all are certified as breast cancer centers] retrospective cohort study called BRENDA (BRENDA = qu…

Psychological interventions for resilience enhancement in adults

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of resilience‐enhancing interventions in clinical and non‐clinical populations.

Participation in adjuvant clinical breast cancer trials: does study participation improve survival compared to guideline adherent adjuvant treatment? A retrospective multi-centre cohort study of 9,433 patients.

Abstract Adjuvant clinical trials (CTs) usually compare a standard treatment regime versus an innovative new substance or regimen. Participation in CT however, is available for only few patients and exclusion criteria are usually very strict. Therefore we used an unselected patient cohort to investigate the following questions: (1) Is participation in adjuvant CT associated with improved survival in breast cancer (BC)? (2) What is the impact of guideline conform therapy on survival in BC compared to that of participants in CT? Does guideline-conform adjuvant treatment provide an equal impact? Material and methods This German retrospective multi-centre cohort study included 9433 patients wit…

Assessing the extent of shared decision making in Pediatrics: Preliminary psychometric evaluation of the German CollaboRATEpediatric scales for patients aged 7–18 years, parents and parent-proxy reports

Abstract Objective To conduct a preliminary evaluation of psychometric properties of CollaboRATEpediatric, a set of three scales to assess shared decision making (SDM) with pediatric patients, parents and parents on behalf of their children (parent-proxy reports). As secondary objectives we examined the scales’ distributional characteristics, acceptability, and agreement between scales. Methods Patients aged ≥ 7 years and parents were recruited in two outpatient facilities providing healthcare services for children with neurological and behavioral health conditions. We collected 46, 169 and 227 pediatric patient, parent-proxy and parent reports, respectively. Convergent, divergent and discr…

Clinical relevance of thyroid-stimulating autoantibodies in pediatric graves' disease-a multicenter study.

Context and Objective: The incidence of TSH receptor (TSHR) stimulating autoantibodies (TSAbs) in pediatric Graves' disease (GD) is controversial. This large, multicenter study evaluated the clinical relevance of TSAbs in children with GD both with Graves' orbitopathy (GO) and without orbital disease. Design: We conducted a cross-sectional retrospective study. Setting: Sera were collected in seven American and European academic referral centers and evaluated in a central laboratory. Patients and Samples: A total of 422 serum samples from 157 children with GD, 101 control individuals with other thyroid and nonthyroid autoimmune diseases, and 50 healthy children were studied. Main Outcome Me…

Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease

Summary The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and…

Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism.

Abstract Context Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Objective Evaluate efficacy of add-on Se on medical treatment in GD. Design Double-blind, placebo-controlled, randomized supplementation trial. Setting Academic endocrine outpatient clinic. Patients Seventy untreated hyperthyroid patients with GD. Intervention Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Main Outcome Measures Response rate (week 24), recurrence rate (week 36), and safety. Results A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) a…

Noise annoyance predicts symptoms of depression, anxiety and sleep disturbance 5 years later. Findings from the Gutenberg Health Study

Abstract Background Cross-sectional studies have shown that noise annoyance is strongly associated with mental distress, however, its long-term effects on mental health is unknown. We therefore investigated whether noise annoyance predicts depression, anxiety and sleep disturbance in a large, representative sample 5 years later. Methods We investigated longitudinal data of N = 11 905 participants of the Gutenberg Health Study, a population-based, prospective, single-centre cohort study in mid-Germany (age at baseline 35–74 years). Noise annoyance was assessed at baseline and 5-year follow-up (sources: road traffic, aircraft, railways, industrial, neighbourhood indoor and outdoor noise; and …

Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome : a randomised, prospective, controlled study

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to r…

PTPN22 and CTLA-4 Polymorphisms Are Associated With Polyglandular Autoimmunity

Context Single nucleotide polymorphisms (SNPs) of various genes increase susceptibility to monoglandular autoimmunity. Data on autoimmune polyglandular syndromes (APSs) are scarce. Objective Evaluate potential associations of eight SNPs with APSs. Setting Academic referral endocrine clinic. Patients A total of 543 patients with APS and monoglandular autoimmunity and controls. Intervention The SNP protein tyrosine phosphatase nonreceptor type 22 (PTPN22) rs2476601 (+1858); cytotoxic T-lymphocyte‒associated antigen 4 (CTLA-4) rs3087243 (CT60) and rs231775 (AG49); vitamin D receptor (VDR) rs1544410 (Bsm I), rs7975232 (Apa I), rs731236 (Taq I); tumor necrosis factor α rs1800630 (-863); and inte…

Psychosomatische Medizin in der Gutenberg- Gesundheitsstudie (GHS) – Fragestellungen, Messverfahren, ausgewählte Ergebnisse

Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results Goal: Main questions from the Gutenberg Health Study (GHS) related to psychosomatic medicine are presented: (1) Prevalence and incidence of mental illnesses, (2) Sex-specific risk- and protective factors for mental health, (3) Interplay between psychological and somatic diseases and (4) methodical-psychometric developments. Methods: The GHS is an ongoing, prospective and interdisciplinary cohort study in Mainz. The comprehensive examinations include psychological characteristics and clinical and laboratory tests. 15010 respondents were selected in the baseline study fro…

Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage.

Abstract Objective Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. Methods In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48…

Predictors of suicidal ideation in depressive primary care patients.

Suicidal ideation is common in patients suffering from depression, but it often remains undetected. General practitioners play an important role in the management of depression and suicidality. The aim of this study was to identify predictors for suicidal ideation in patients with major depression in primary health care.We conducted a cross-sectional study. Patients were recruited from 74 primary care practices in Germany. Data was collected between April 2005 and July 2006. We calculated a binary logistic regression model to evaluate whether depression severity (Patient Health Questionnaire, PHQ-9), physical pain (SF-36 Physical Pain Scale), physical comorbidity, intake of antidepressant m…

Psychological interventions to foster resilience in healthcare professionals.

Background Resilience can be defined as the maintenance or quick recovery of mental health during or after periods of stressor exposure, which may result from a potentially traumatising event, challenging life circumstances, a critical life transition phase, or physical illness. Healthcare professionals, such as nurses, physicians, psychologists and social workers, are exposed to various work-related stressors (e.g. patient care, time pressure, administration) and are at increased risk of developing mental disorders. This population may benefit from resilience-promoting training programmes. Objectives To assess the effects of interventions to foster resilience in healthcare professionals, t…

Acoustic radiation force impulse point shear wave elastography of the liver and spleen in patients with Gaucher disease type 1: Correlations with clinical data and markers of disease severity.

To evaluate the feasibility of acoustic radiation force impulse point shear wave elastography (ARFI-pSWE) of the liver and spleen in patients with Gaucher disease type 1 (GD1), and to assess correlations between organ stiffness and clinico-radiologic data, particularly the GD1 Severity Scoring System (GD-DS3).We retrospectively evaluated the results of ARFI-pSWE as measures of liver and spleen stiffness in 57 patients with GD1. The feasibility of the method was assessed. Correlations between elastography data and clinical data related to the metabolic syndrome, laboratory tests, and GD1-related clinico-radiologic data (bone marrow burden score, GD-DS3) were assessed.ARFI-pSWE provided relia…

Quantification of intramuscular fat in patients with late-onset Pompe disease by conventional magnetic resonance imaging for the long-term follow-up of enzyme replacement therapy

Objective The objective of this study was to evaluate a quantitative method based on conventional T1-weighted magnetic resonance (MR) imaging to assess fatty muscular degeneration in patients with late-onset Pompe disease and to compare it with semi-quantitative visual evaluation (the Mercuri score). In addition, a long-term retrospective data analysis was performed to evaluate treatment response to enzyme replacement therapy with alglucosidase alfa. Methods MR images of the lumbar spine were acquired in 41 patients diagnosed with late-onset Pompe disease from 2006 through 2015. Two independent readers retrospectively evaluated fatty degeneration of the psoas and paraspinal muscles by apply…

Vascular effects of diet supplementation with plant sterols.

Objectives The purpose of this study was to evaluate vascular effects of diet supplementation with plant sterol esters (PSE). Background Plant sterol esters are used as food supplements to reduce cholesterol levels. Their effects on endothelial function, stroke, or atherogenesis are not known. Methods In mice, plasma sterol concentrations were correlated with endothelial function, cerebral lesion size, and atherosclerosis. Plasma and tissue sterol concentrations were measured by gas-liquid chromatography-mass spectrometry in 82 consecutive patients with aortic stenosis. Results Compared with those fed with normal chow (NC), wild-type mice fed with NC supplemented with 2% PSE showed increase…

Is guideline-adherent adjuvant treatment an equivalent option for elderly patients who cannot participate in adjuvant clinical breast cancer trials? A retrospective multicenter cohort study of 4,142 patients.

1063 Background: It is well accepted that innovation in oncology is transported through randomized clinical trials (CT). However, elderly patients (>65) are usually excluded from CT. Therefore this...

Linking cancer and mental health in men and women in a representative community sample

Abstract Objective In aging populations, a growing number of individuals are affected by cancer. However, the relevance of the disease for mental health is still controversial, especially after treatment. We drew from a representative community sample to explore the link of cancer with mental health assessing different dimensions and different periods of time. Methods A cohort of 14,375 men and women (35–74 years) underwent medical assessments and was queried about cancer history, previous diagnoses of mental disorders, current mental distress symptoms, and current subjective health appraisal. Results 1066 participants (7.4%) reported a diagnosis of cancer (survival time M = 9.79 (SD = 9.07…

Image guidance to improve reliability and data integrity of transcranial Doppler sonography.

Abstract Background Principles and accuracy of image-guided transcranial Doppler (IG TCD) sonography have been published recently. However, it remains open whether combination of image guidance and TCD offers an additional clinical advantage. This study scores the accuracy of conventional TCD examinations and investigates the potential improvement of TCD data integrity and reliability regarding the additional use of IG. Methods Conventional TCD was performed by a group of experienced investigators, who were blinded to images of a navigation system tracking the Doppler probe, whereas an independent observer documented the TCD findings, acquired by the investigators, due to saving spatial dat…

Cytokine Plasma Levels: Reliable Predictors for Radiation Pneumonitis?

BackgroundRadiotherapy (RT) is the primary treatment modality for inoperable, locally advanced non-small-cell lung cancer (NSCLC), but even with highly conformal treatment planning, radiation pneumonitis (RP) remains the most serious, dose-limiting complication. Previous clinical reports proposed that cytokine plasma levels measured during RT allow to estimate the individual risk of patients to develop RP. The identification of such cytokine risk profiles would facilitate tailoring radiotherapy to maximize treatment efficacy and to minimize radiation toxicity. However, cytokines are produced not only in normal lung tissue after irradiation, but are also over-expressed in tumour cells of NSC…

Airway management techniques in a restricted-access situation: a manikin study

Background Access to patients can be restricted in emergency situations. A variety of techniques and devices are available for use in patients who require oxygenation in a restricted-access situation. Objectives The aim of this study was to investigate whether there is one ventilation technique that is superior to others. Materials and methods Fifty-four emergency medical services providers including emergency medical technicians, paramedics and physicians were asked to use a bag-valve mask (BVM), a laryngeal mask airway (LMA), and a laryngeal tube (LT) to ventilate a full-scale manikin sitting upright in the driver's seat of a motor vehicle. Access to the manikin was gained through the sid…

Therapy for Recurrent High-Grade Gliomas: Results of a Prospective Multicenter Study on Health-Related Quality of Life

Objective To assess the impact of therapy on patients' health-related quality of life (HRQoL) in recurrent high-grade glioma (HGG) in an unselected cohort. Methods In this prospective multicenter study, we analyzed European Organization for Research and Treatment of Cancer Quality of Life core questionnaire and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm module questionnaires of 92 patients within 1 year after diagnosis of tumor recurrence of a HGG and respective treatment. We evaluated the influence of re-radiation, second- and third-line chemotherapies, and number of recurrent surgeries on summary scores for functioning, symptoms…

Visualizing the flow of evidence in network meta-analysis and characterizing mixed treatment comparisons

Network meta-analysis techniques allow for pooling evidence from different studies with only partially overlapping designs for getting a broader basis for decision support. The results are network-based effect estimates that take indirect evidence into account for all pairs of treatments. The results critically depend on homogeneity and consistency assumptions, which are sometimes difficult to investigate. To support such evaluation, we propose a display of the flow of evidence and introduce new measures that characterize the structure of a mixed treatment comparison. Specifically, a linear fixed effects model for network meta-analysis is considered, where the network estimates for two trea…

Einfluss der Kenntnisse über Bestrahlungsplanung und Primärdiagnostik auf die Beurteilungssicherheit in der Rezidivdiagnostik des NSCLC mittels PET/CT

Chromogranin Serves as Novel Biomarker of Endocrine and Gastric Autoimmunity

Abstract Context The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. Objective To investigate CgA utility as a marker of endocrine autoimmunity. Methods CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology. Results Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy…

Analytical performance and clinical utility of a bioassay for thyroid-stimulating immunoglobulins.

Abstract The analytical performance and the clinical utility of a thyrotropin receptor (TSHR)–stimulating immunoglobulin (TSI) bioassay were compared with those of a TSHR-binding inhibitory immunoglobulin (TBII) assay. Limits of detection (LoD) and quantitation (LoQ), assay cutoff, and the half-maximal effective concentration (EC50) were measured. Dilution analysis was performed in sera of hyperthyroid patients with Graves disease (GD) during antithyroid treatment (ATD). Titer was defined as the first dilution step at which measurement of TSI or TBII fell below the assay cutoff. The LoD, LoQ, cutoff, and EC50 of the bioassay were 251-, 298-, 814-, and 827-fold lower than for the TBII assay.…

Psychodynamic motivation and training program (PMT) for the secondary prevention in patients with stable coronary heart disease : study protocol for a randomized controlled trial of feasibility and effects

Recommendation for ophthalmic care in German preschool health examination and its adherence: Results of the prospective cohort study ikidS.

BackgroundEach child in Germany undergoes a preschool health examination including vision screening and recommendations for further ophthalmic care. This study investigated the frequency of and adherence to these recommendations.MethodsA population-based prospective cohort study was performed in the area of Mainz-Bingen (Rhineland-Palatinate, Germany). All preschoolers were examined at the statutory preschool health examination, which includes vision testing (Rodenstock vision screener) with available correction in the last preschool year. Based on the results, recommendations for further ophthalmic care were given to the parents. Six weeks prior to school entry, parents were surveyed conce…

Is assessment of depression equivalent for migrants of different cultural backgrounds? Results from the German population-based Gutenberg Health Study (GHS)

BACKGROUND Bearing in mind the multicultural background of a national population, little is known about the measurement invariance across different cultures or ethnicities of frequently used screeners for depression. For this reason, the main objective of the current study is to assess the measurement invariance of the Patient Health Questionnaire (PHQ-9) across groups with different migration backgrounds. METHODS We provided psychometric analyses (descriptive statistics at item and scale level, reliability analysis, exploratory [EFA] and confirmatory factor analyses [CFA]) comparing a native population with first- and second-generation migrants of the German population-based Gutenberg Heal…

Short telomeres in aggressive non-Hodgkin's lymphoma as a risk factor in lymphomagenesis

Objective Telomeres cap chromosomal ends and help to maintain chromosomal integrity. Telomere shortening may result in chromosomal instability and, ultimately, malignant transformation of cells. It has not been systematically studied whether patients with malignancy have shortened telomeres in their normal, nontransformed cells, which might point to a preexisting disposition for chromosomal instability. Methods We designed an (age-) matched pair analysis that compared telomere length in nonmalignant peripheral leukocytes from previously untreated patients who recently developed an aggressive non-Hodgkin's lymphoma, with leukocytes from healthy individuals. Results Telomere lengths in B and …

Systematic Analysis of Combined Thrombolysis Using Ultrasound and Different Fibrinolytic Drugs in an in Vitro Clot Model of Intracerebral Hemorrhage.

Adequate removal of blood clots by minimally invasive surgery seems to correlate with a better clinical outcome in patients with intracerebral hemorrhages (ICHs). Moreover, neurotoxic effects of recombinant tissue plasminogen activator have been reported. The aim of this study was to improve fibrinolysis using an intra-clot ultrasound application with tenecteplase and urokinase in our established ICH clot model. One hundred thirty clots were produced from 25 or 50 mL of human blood, incubated for different periods and equipped with drainage, through which an ultrasound catheter was placed in 65 treatment clots for 1 h, randomly allocated into three groups: administration of ultrasound, admi…

Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery.

Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery.Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment.According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially …

Treatment concepts of horizontally deficient ridges-A retrospective study comparing narrow-diameter implants in pristine bone with standard-diameter implants in augmented bone.

OBJECTIVES To compare clinical and radiological outcomes of narrow-diameter implants (NDI) placed in pristine bone to standard-diameter implants placed in combination with horizontal bone augmentation procedures (SDI+A) for horizontally deficient alveolar ridges. MATERIAL AND METHODS For this retrospective study, the outcome of 597 NDI (∅ 3.3 mm, 272 patients), inserted in pristine bone, were compared with 180 SDI (∅ 4.1 mm, 83 patients), inserted in combination with horizontal augmentation procedures. Oral health-related quality of life was assessed in patients available for recall. RESULTS After a mean follow-up of 37.6 ± 40 months for the NDI and of 42.4 ± 49 months for the SDI+A, surviv…

Type I Diabetes is the Main Cost Driver in Autoimmune Polyendocrinopathy

Abstract Context Autoimmune polyendocrinopathy (AP), a chronic complex orphan disease, encompasses at least two autoimmune-induced endocrine diseases. Objective To estimate for the first time total, indirect and direct costs for patients with AP, as well as cost drivers. Design Cross-sectional cost of illness study. Setting Academic tertiary referral center for AP. Patients 146 consecutive, unselected AP patients. Intervention Interviews pertaining to patients’ socioeconomic situation covered a recall period of 12 months. Both the human capital (HCA) and the friction cost approaches (FCAs) were applied as estimation methods. Main outcome measures Direct and indirect annual costs, and sick l…

Performance and Specificity of 6 Immunoassays for TSH Receptor Antibodies: A Multicenter Study

Background: The measurement of TSH receptor (TSHR) antibodies is warranted for diagnosis of Graves’ disease (GD). Objective: The performance, detection sensitivity, and specificity of 6 TSHR immunoassays were compared. Methods: Two bioassays and 4 binding assays (Kronus, Immulite, Kryptor, Dynex) were compared in a dilution study performed in patients with autoimmune thyroid disease. Both bioassays were compared to 2 binding assays using stimulatory (M22) and blocking (K1–70) monoclonal antibody (MAb) mixtures. Results: Thirty samples from stimulatory (TSAb)-positive/blocking (TBAb)-negative patients with GD were diluted serially and measured in all assays. Samples were positive until dilut…

Comments on "Identifying inconsistency in network meta-analysis: Is the net heat plot a reliable method?"

One of the biggest challenges for network meta‐analysis is inconsistency, which occurs when the direct and indirect evidence conflict. Inconsistency causes problems for the estimation and interpretation of treatment effects and treatment contrasts. Krahn and colleagues proposed the net heat approach as a graphical tool for identifying and locating inconsistency within a network of randomized controlled trials. For networks with a treatment loop, the net heat plot displays statistics calculated by temporarily removing each design one at a time, in turn, and assessing the contribution of each remaining design to the inconsistency. The net heat plot takes the form of a matrix which is displaye…

Thyroid Stimulating Antibodies Are Highly Prevalent in Hashimoto's Thyroiditis and Associated Orbitopathy

Thyroid-associated orbitopathy (TAO) rarely occurs in patients with Hashimoto's thyroiditis (HT).There is evidence that TSH receptor stimulating antibodies (TSAb) play a role in the pathogenesis of TAO. In this report, the prevalence of TSAb in HT patients with and without TAO was studied.This is a longitudinal observational study.The study took place in an academic joint thyroid-eye clinic.A total of 1055 subjects were included.TSAb was measured with a Food and Drug Administration-cleared bioassay that uses Chinese hamster ovary cells expressing a chimeric TSH receptor and a cAMP response element-dependent luciferase. Results of TSAb activity were reported as percentage of specimen-to-refe…

Indikatoren schulischen Wohlbefindens bei gesunden und chronisch kranken Kindern: Psychometrische Prüfung und Validierung adaptierter FEESS-Skalen

Zusammenfassung. Das schulbezogene Wohlbefinden (SBWB) ist eine wichtige Voraussetzung für schulischen Erfolg. Trotzdem existieren – insbesondere mit Blick auf die Erfassung des SBWB von Erstklässlern – im deutschsprachigen Raum nur vereinzelt Studien. Dies lässt sich möglicherweise durch das Fehlen geeigneter Instrumente begründen. Dies gilt auch und insbesondere dann, wenn der Gesundheitszustand der Kinder berücksichtigt werden soll. Das Ziel der vorliegenden Arbeit besteht in der Validierung des adaptierten Fragebogens zur Erfassung von emotionalen und sozialen Schulerfahrungen (FEESS 1 – 2; Rauer & Schuck, 2004 ) mit Fokus auf die Eignung des Instruments für chronisch kranke und ge…

Long-term quality of life in inoperable non-small cell lung cancer patients treated with conventionally fractionated compared to hyperfractionated accelerated radiotherapy – Results of the randomized CHARTWEL trial

Abstract Background and purpose To evaluate the quality of life (QoL) of patients with inoperable non-small cell lung cancer treated with conventionally fractionated radiotherapy (CF) vs. continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL). Material and methods The largest monocentric subgroup of the phase III CHARTWEL trial was analyzed up to three years after randomization. QoL was assessed with the European Organization for Research and Treatment of Cancer QoL Core Questionnaire (QLQ-C30) and lung cancer module (QLQ-LC13) and compared using linear mixed models. QoL interrelations with recurrence, metastasis, and death were explored by multi-state modeling. Resul…

Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study

Abstract Aim To investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities in an ecological study. Methods On the basis of the Rhineland-Palatinate cancer-registry, we calculated age-adjusted incidence rate ratios for communities with a medium area under wine cultivation (>5 to 20 percent) and a large area under wine cultivation (>20 percent) in comparison with communities with a small area under wine cultivation (>0 to 5 percent). In a side analysis, standardized cancer incidence ratios (SIR) were computed separately for winegrowing communities with small, medium and large area under wine cultivation using estimated German incidence rates as refere…

Improved inter-observer agreement of an expert review panel in an oncology treatment trial--Insights from a structured interventional process.

Abstract Purpose Oncologic imaging is a key for successful cancer treatment. While the quality assurance (QA) of image acquisition protocols has already been focussed, QA of reading and reporting offers still room for improvement. The latter was addressed in the context of a prospective multicentre trial on fluoro-deoxyglucose (FDG)–positron-emission tomography (PET)/CT-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Material and methods An expert panel was prospectively installed performing blinded reviews of mediastinal NSCLC involvement in FDG–PET/CT. Due to a high initial reporting inter-observer disagreement, the independent data monitoring committee (I…

Assessing psychological and supportive care needs in glioma patients - feasibility study on the use of the Supportive Care Needs Survey Short Form (SCNS-SF34-G) and the Supportive Care Needs Survey Screening Tool (SCNS-ST9) in clinical practice

Neuro-oncological patients experience high symptom and psychosocial burden. The aim was to test feasibility and practicability of the Supportive Care Needs Survey Short Form (SCNS-SF34-G) and the SCNS-Screening Tool (SCNS-ST9) to assess supportive care needs of neuro-oncological patients in clinical routine. A total of 173 patients, most with a primary diagnosis of high-grade glioma (81%), were assessed first using SCNS-SF34-G in comparison to two well-established patient-reported outcome measures, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30 + QLQ-BN20) and Distress Thermometer (DT). In a follow-up assessment, SCNS-ST9 was used …

Probability of hysterectomy in Germany

Introduction Hysterectomy is the most common gynecological surgery in many industrialized countries. In Germany, the hysterectomy rate is high in comparison to other European countries. The aim of this analysis was to determine the distribution of age at hysterectomy as well as the age-specific probability of undergoing a hysterectomy between the ages of 0–64 in the German female population. Methods Analyses were based on data from the MARZY study, a prospective, randomized, population-based cohort study investigating early detection of cervical cancer in western Germany. At baseline, 6429 women were invited to attend cervical cancer screening. The distribution of age at hysterectomy as wel…

Sex Alters the MHC Class I HLA-A Association With Polyglandular Autoimmunity.

Abstract Context The major histocompatibility complex (MHC) strongly contributes to the development of polyglandular autoimmunity (PGA). Objective To evaluate the impact of sex on human leukocyte antigen (HLA) association with PGA for the first time. Design Cross-sectional immunogenetic study. Setting Academic tertiary referral Orphan Disease Center for PGA (ORPHA 282196) and immunogenetics laboratory. Subjects Patients (158) with coexistent type 1 diabetes and autoimmune thyroid disease (adult type 3 PGA, ORPHA 227982) and 479 unrelated healthy controls. Interventions All 637 white subjects were typed for HLA-A, -B, -DRB1, -DQA1, and -DQB1 alleles at a two-field level. Main Outcome Measure…

Recalled parental rearing behavior in adult women and men with depressive and anxiety symptoms: Findings from a community study.

Objectives: Addressing the lack of population-based data, the purpose of this representative study was to assess sex- and age-specific associations of maternal and paternal rearing behavior with depressiveness and anxiety controlling for sociodemographic and somatic variables. Methods: 8,175 subjects participating in a population-based study completed standardized questionnaires measuring Recalled Parental Rearing Behavior and distress. Results: Women recalled their fathers as more controlling and warmer, and their mothers as more rejecting than men. Comparisons between age groups (≤ 60 vs. > 60 years) revealed that younger participants recalled more parental control and emotional warmth. I…

Psychological interventions to foster resilience in healthcare students

Background Resilience can be defined as maintaining or regaining mental health during or after significant adversities such as a potentially traumatising event, challenging life circumstances, a critical life transition or physical illness. Healthcare students, such as medical, nursing, psychology and social work students, are exposed to various study- and work-related stressors, the latter particularly during later phases of health professional education. They are at increased risk of developing symptoms of burnout or mental disorders. This population may benefit from resilience-promoting training programmes. Objectives To assess the effects of interventions to foster resilience in healthc…

Is faster better? A randomised crossover study comparing algorithms for closed-loop automatic oxygen control

ObjectiveClosed-loop automatic control (CLAC) of the fractional inspired oxygen (FiO2) improved oxygen administration to preterm infants on respiratory support. We investigated whether a revised CLAC algorithm (CLACfast, ≤2 FiO2 adjustments/min), compared with routine manual control (RMConly), increased the proportion of time with arterial haemoglobin oxygen saturation measured by pulse oximetry within prespecified target ranges (Target%) while not being inferior to the original algorithm (CLACslow: ≤0.3 FiO2 adjustments/min).DesignUnblinded randomised controlled crossover study comparing three modes of FiO2 control in random order for 8 hours each: RMC supported by CLACfast was compared wi…

Trends in Epidemiology, Treatment, and Survival of Hepatocellular Carcinoma Patients Between 1998 and 2009

The aim of this study was to analyze clinical presentation, course of disease, and management of patients with hepatocellular carcinoma (HCC) in a German referral center between 1998 and 2009.HCC is a rare tumor in Germany, but its incidence has increased over the last 30 years. New therapies such as chemoembolization with drug-eluting beads, selective internal radiotherapy, and sorafenib were introduced recently; however, the impact on clinical management and overall survival (OS) is unclear.In this retrospective analysis, 1066 patients with HCC, separated into two 6-year periods (n=385; 1998 to 2003 and n=681; 2004 to 2009) were evaluated.The number of patients presenting each year (64 vs…