@article{StoerkBernhardtBoehmetal.2022, author = {St{\"o}rk, Stefan and Bernhardt, Alexandra and B{\"o}hm, Michael and Brachmann, Johannes and Dagres, Nikolaos and Frantz, Stefan and Hindricks, Gerd and K{\"o}hler, Friedrich and Zeymer, Uwe and Rosenkranz, Stephan and Angermann, Christiane and Aßmus, Birgit}, title = {Pulmonary artery sensor system pressure monitoring to improve heart failure outcomes (PASSPORT-HF): rationale and design of the PASSPORT-HF multicenter randomized clinical trial}, series = {Clinical Research in Cardiology}, volume = {111}, journal = {Clinical Research in Cardiology}, number = {11}, doi = {10.1007/s00392-022-01987-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324026}, pages = {1245-1255}, year = {2022}, abstract = {Background Remote monitoring of patients with New York Heart Association (NYHA) functional class III heart failure (HF) using daily transmission of pulmonary artery (PA) pressure values has shown a reduction in HF-related hospitalizations and improved quality of life in patients. Objectives PASSPORT-HF is a prospective, randomized, open, multicenter trial evaluating the effects of a hemodynamic-guided, HF nurse-led care approach using the CardioMEMS™ HF-System on clinical end points. Methods and results The PASSPORT-HF trial has been commissioned by the German Federal Joint Committee (G-BA) to ascertain the efficacy of PA pressure-guided remote care in the German health-care system. PASSPORT-HF includes adult HF patients in NYHA functional class III, who experienced an HF-related hospitalization within the last 12 months. Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy. Patients will be randomized centrally 1:1 to implantation of a CardioMEMS™ sensor or control. All patients will receive post-discharge support facilitated by trained HF nurses providing structured telephone-based care. The trial will enroll 554 patients at about 50 study sites. The primary end point is a composite of the number of unplanned HF-related rehospitalizations or all-cause death after 12 months of follow-up, and all events will be adjudicated centrally. Secondary end points include device/system-related complications, components of the primary end point, days alive and out of hospital, disease-specific and generic health-related quality of life including their sub-scales, and laboratory parameters of organ damage and disease progression. Conclusions PASSPORT-HF will define the efficacy of implementing hemodynamic monitoring as a novel disease management tool in routine outpatient care. Trial registration ClinicalTrials.gov; NCT04398654, 13-MAY-2020.}, language = {en} } @article{WeibelPoppReisetal.2023, author = {Weibel, Stephanie and Popp, Maria and Reis, Stefanie and Skoetz, Nicole and Garner, Paul and Sydenham, Emma}, title = {Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis}, series = {Research Synthesis Methods}, volume = {14}, journal = {Research Synthesis Methods}, number = {3}, doi = {10.1002/jrsm.1599}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318236}, pages = {357 -- 369}, year = {2023}, abstract = {Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40\% of studies in the first update of the review. RIA is a complementary tool prior to assessing "Risk of Bias" aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.}, language = {en} } @article{PittigHeinigGoerigketal.2021, author = {Pittig, Andre and Heinig, Ingmar and Goerigk, Stephan and Thiel, Freya and Hummel, Katrin and Scholl, Lucie and Deckert, J{\"u}rgen and Pauli, Paul and Domschke, Katharina and Lueken, Ulrike and Fydrich, Thomas and Fehm, Lydia and Plag, Jens and Str{\"o}hle, Andreas and Kircher, Tilo and Straube, Benjamin and Rief, Winfried and Koelkebeck, Katja and Arolt, Volker and Dannlowski, Udo and Margraf, J{\"u}rgen and Totzeck, Christina and Schneider, Silvia and Neudeck, Peter and Craske, Michelle G. and Hollandt, Maike and Richter, Jan and Hamm, Alfons and Wittchen, Hans-Ulrich}, title = {Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial}, series = {Depression and Anxiety}, volume = {38}, journal = {Depression and Anxiety}, number = {11}, doi = {10.1002/da.23204}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257331}, pages = {1169-1181}, year = {2021}, abstract = {Background The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32\% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. Conclusions Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.}, language = {en} } @article{SchuhmannBittnerMeuthetal.2015, author = {Schuhmann, Michael K. and Bittner, Stefan and Meuth, Sven G. and Kleinschnitz, Christoph and Fluri, Felix}, title = {Fingolimod (FTY720-P) does not stabilize the blood-brain barrier under inflammatory conditions in an in vitro model}, series = {International Journal of Molecular Sciences}, volume = {16}, journal = {International Journal of Molecular Sciences}, doi = {10.3390/ijms161226177}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145047}, pages = {29454-29466}, year = {2015}, abstract = {Breakdown of the blood-brain barrier (BBB) is an early hallmark of multiple sclerosis (MS), a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P), a signaling protein, via S1P receptors (S1P\(_1\)). Fingolimod phosphate (FTY720-P) a functional S1P\(_1\) antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeabilityin particular, on the tight junction proteins occludin, claudin 5 and ZO-1has not been well elucidated to date. In the present study, FTY720-P did not change the transendothelial electrical resistance in a rat brain microvascular endothelial cell (RBMEC) culture exposed to inflammatory conditions and thus did not decrease endothelial barrier permeability. In contrast, occludin was reduced in RBMEC culture after adding FTY720-P. Additionally, FTY720-P did not alter the amount of endothelial matrix metalloproteinase (MMP)-9 and MMP-2 in RBMEC cultures. Taken together, our observations support the assumption that S1P\(_1\) plays a dual role in vascular permeability, depending on its ligand. Thus, S1P\(_1\) provides a mechanistic basis for FTY720-P-associated disruption of endothelial barrierssuch as the blood-retinal barrierwhich might result in macular edema.}, language = {en} } @article{SemrauHentschkeBuchmannetal.2015, author = {Semrau, Jana and Hentschke, Christian and Buchmann, Jana and Meng, Karin and Vogel, Heiner and Faller, Hermann and Bork, Hartmut and Pfeifer, Klaus}, title = {Long-term effects of interprofessional biopsychosocial rehabilitation for adults with chronic non-specific low back pain: a multicentre, quasi-experimental study}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/ journal.pone.0118609}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143594}, pages = {e0118609}, year = {2015}, abstract = {Background Improvement of the long-term effectiveness of multidisciplinary ortho-paedic rehabilitation (MOR) in the management of chronic non-specific low back pain (CLBP) remains a central issue for health care in Germany. We developed an interprofessional and interdisciplinary, biopsychosocial rehabilitation concept named "PASTOR" to promote self-management in adults with CLBP and compared its effectiveness with the current model of MOR. Methods A multicentre quasi-experimental study with three measurement time points was implemented. 680 adults aged 18 to 65 with CLBP were assed for eligibil-ity in three inpatient rehabilitation centres in Germany. At first the effects of the MOR, with a total extent of 48 hours (control group), were assessed. Thereafter, PASTOR was implemented and evaluated in the same centres (intervention group). It consisted of six interprofessional modules, which were provided on 12 days in fixed groups, with a total extent of 48 hours. Participants were assessed with self-report measures at baseline, discharge, and 12 months for functional ability (primary outcome) using the Hannover Functional Ability Questionnaire (FFbH-R) and vari-ous secondary outcomes (e.g. pain, health status, physical activity, pain coping, pain-related cognitions). Results In total 536 participants were consecutively assigned to PASTOR (n=266) or MOR (n=270). At 12 months, complete data of 368 participants was available. The adjusted between-roup difference in the FFbH-R at 12 months was 6.58 (95\% CI 3.38 to 9.78) using complete data and 3.56 (95\% CI 0.45 to 6.67) using available da-ta, corresponding to significant small-to-medium effect sizes of d=0.42 (p<0.001) and d=0.10 (p=0.025) in favour of PASTOR. Further improvements in secondary out-comes were also observed in favour of PASTOR. Conclusion The interprofessional and interdisciplinary, biopsychosocial rehabilita-tion program PASTOR shows some improvements of the long-term effectiveness of inpatient rehabilitation in the management of adults with CLBP. Further insights into mechanisms of action of complex intervention programs are required.}, language = {en} } @article{LeistnerBenikLaumeieretal.2012, author = {Leistner, Stefanie and Benik, Steffen and Laumeier, Inga and Ziegler, Annerose and Nieweler, Gabriele and Nolte, Christian H. and Heuschmann, Peter U. and Audebert, Heinrich J.}, title = {Secondary Prevention after Minor Stroke and TIA - Usual Care and Development of a Support Program}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {12}, doi = {10.1371/journal.pone.0049985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135247}, pages = {e49985}, year = {2012}, abstract = {Background: Effective methods of secondary prevention after stroke or TIA are available but adherence to recommended evidence-based treatments is often poor. The study aimed to determine the quality of secondary prevention in usual care and to develop a stepwise modeled support program. Methods: Two consecutive cohorts of patients with acute minor stroke or TIA undergoing usual outpatient care versus a secondary prevention program were compared. Risk factor control and medication adherence were assessed in 6-month follow-ups (6M-FU). Usual care consisted of detailed information concerning vascular risk factor targets given at discharge and regular outpatient care by primary care physicians. The stepwise modeled support program additionally employed up to four outpatient appointments. A combination of educational and behavioral strategies was employed. Results: 168 patients in the observational cohort who stated their openness to participate in a prevention program (mean age 64.7 y, admission blood pressure (BP): 155/84 mmHg) and 173 patients participating in the support program (mean age 67.6 y, BP: 161/84 mmHg) were assessed at 6 months. Proportions of patients with BP according to guidelines were 50\% in usual-care and 77\% in the support program (p<0.01). LDL<100 mg/dl was measured in 62 versus 71\% (p = 0.12). Proportions of patients who stopped smoking were 50 versus 79\% (p<0.01). 72 versus 89\% of patients with atrial fibrillation were on oral anticoagulation (p = 0.09). Conclusions: Risk factor control remains unsatisfactory in usual care. Targets of secondary prevention were met more often within the supported cohort. Effects on (cerebro-)vascular recurrence rates are going to be assessed in a multicenter randomized trial.}, language = {en} } @article{CoenenAmtageVolkmannetal.2015, author = {Coenen, Volker A. and Amtage, Florian and Volkmann, Jens and Schl{\"a}pfer, Thomas E.}, title = {Deep Brain Stimulation in Neurological and Psychiatric Disorders}, series = {Deutsches {\"A}rzteblatt International}, volume = {112}, journal = {Deutsches {\"A}rzteblatt International}, doi = {10.3238/arztebl.2015.0519}, pages = {519 -- 526}, year = {2015}, abstract = {Background: Deep brain stimulation (DBS) is the chronic electrical stimulation of selected target sites in the brain through stereotactically implanted electrodes. More than 150 000 patients around the world have been treated to date with DBS for medically intractable conditions. The indications for DBS include movement disorders, epilepsy, and some types of mental illness. Methods: This review is based on relevant publications retrieved by a selective search in PubMed and the Cochrane Library, and on the current guidelines of the German Neurological Society (Deutsche Gesellschaft fur Neurologie, DGN). Results: DBS is usually performed to treat neurological diseases, most often movement disorders and, in particular, Parkinson's disease. Multiple randomized controlled trials (RCTs) have shown that DBS improves tremor, dyskinesia, and quality of life in patients with Parkinson's disease by 25\% to 50\%, depending on the rating scales used. DBS for tremor usually involves stimulation in the cerebello-thalamo-cortical regulatory loop. In an RCT of DBS for the treatment of primary generalized dystonia, the patients who underwent DBS experienced a 39.3\% improvement of dystonia, compared to only 4.9\% in the control group. Two multicenter trials of DBS for depression were terminated early because of a lack of efficacy. Conclusion: DBS is an established treatment for various neurological and psychiatric diseases. It has been incorporated in the DGN guidelines and is now considered a standard treatment for advanced Parkinson's disease. The safety and efficacy of DBS can be expected to improve with the application of new technical developments in electrode geometry and new imaging techniques. Controlled trials would be helpful so that DBS could be extended to further indications, particularly psychiatric ones.}, language = {en} } @article{BrevoordKrankeKuijpersetal.2012, author = {Brevoord, Daniel and Kranke, Peter and Kuijpers, Marijn and Weber, Nina and Hollmann, Markus and Preckel, Benedikt}, title = {Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0042179}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134471}, pages = {e42179}, year = {2012}, abstract = {Background: Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. Methods and Results: Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95\% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference -0.28 [-0.47, -0.09]). Conclusion: There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.}, language = {en} } @article{TerposKleberEngelhardtetal.2015, author = {Terpos, Evangelos and Kleber, Martina and Engelhardt, Monika and Zweegman, Sonja and Gay, Francesca and Kastritis, Efstathios and van de Donk, Niels W. C. J. and Bruno, Benedetto and Sezer, Orhan and Broijl, Annemiek and Bringhen, Sara and Beksac, Meral and Larocca, Alessandra and Hajek, Roman and Musto, Pellegrino and Johnsen, Hans Erik and Morabito, Fortunato and Ludwig, Heinz and Cavo, Michele and Einsele, Hermann and Sonneveld, Pieter and Dimopoulos, Meletios A. and Palumbo, Antonio}, title = {European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications}, series = {Haematologica}, volume = {100}, journal = {Haematologica}, number = {10}, doi = {10.3324/haematol.2014.117176}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141913}, pages = {1254 -- 1266}, year = {2015}, abstract = {The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging. In asymptomatic myeloma, bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given continuously, but it is not clear if patients who achieve at least a very good partial response benefit from its continuous use (grade 1B). Treatment with erythropoietic-stimulating agents may be initiated in patients with persistent symptomatic anemia (hemoglobin < 10g/dL) in whom other causes of anemia have been excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if no adequate hemoglobin response is achieved. For renal impairment, bortezomib-based regimens are the current standard of care (grade 1A). For the management of treatment-induced peripheral neuropathy, drug modification is needed (grade 1C). Vaccination against influenza is recommended; vaccination against streptococcus pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or valacyclovir) is recommended for patients receiving proteasome inhibitors, autologous or allogeneic transplantation (grade 1A).}, language = {en} } @article{WeidemannSanchezNinoPoliteietal.2013, author = {Weidemann, Frank and Sanchez-Nino, Maria D. and Politei, Juan and Oliveira, Jo{\~a}o-Paulo and Wanner, Christoph and Warnock, David G. and Oritz, Alberto}, title = {Fibrosis: a key feature of Fabry disease with potential therapeutic implications}, series = {Orphanet Journal of Rare Diseases}, volume = {8}, journal = {Orphanet Journal of Rare Diseases}, number = {116}, issn = {1750-1172}, doi = {10.1186/1750-1172-8-116}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124773}, year = {2013}, abstract = {Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease.}, language = {en} }