Journal of the American College of Cardiology, Apr 1, 2019
Up to one-third of patients undergoing transcatheter aortic valve replacement (TAVR) for the trea... more Up to one-third of patients undergoing transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis have an indication for long-term oral anticoagulation. In such patients, physicians have to balance periprocedural thromboembolic and bleeding risk. So far, data for
OBJECTIVES The authors investigated whether transcatheter aortic valve replacement (TAVR) with pe... more OBJECTIVES The authors investigated whether transcatheter aortic valve replacement (TAVR) with periprocedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with periprocedural interruption of anticoagulation. BACKGROUND A significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal periprocedural management of such patients is unknown. METHODS Consecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality. RESULTS Of 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89, CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59, 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90, 95% CI: 0.73 to 1.12; p = 0.36). CONCLUSIONS Continuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation.
Journal of the American College of Cardiology, Apr 1, 2019
Up to one-third of patients undergoing transcatheter aortic valve replacement (TAVR) for the trea... more Up to one-third of patients undergoing transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis have an indication for long-term oral anticoagulation. In such patients, physicians have to balance periprocedural thromboembolic and bleeding risk. So far, data for
OBJECTIVES The authors investigated whether transcatheter aortic valve replacement (TAVR) with pe... more OBJECTIVES The authors investigated whether transcatheter aortic valve replacement (TAVR) with periprocedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with periprocedural interruption of anticoagulation. BACKGROUND A significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal periprocedural management of such patients is unknown. METHODS Consecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality. RESULTS Of 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89, CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59, 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90, 95% CI: 0.73 to 1.12; p = 0.36). CONCLUSIONS Continuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation.
B12019 is being developed as a biosimilar to Neulasta{\textless}sup{\textgreater}{\circledR}{\tex... more B12019 is being developed as a biosimilar to Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater} (INN pegfilgrastim), a long-acting, pegylated form of recombinant human granulocyte-colony stimulating factor (r-metHuG-CSF, INN filgrastim) for the prevention of chemotherapy-induced neutropenia. A comprehensive analytical, functional and preclinical comparability program has already demonstrated a high degree of similarity of B12019 as compared to Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}. In order to confirm the similarity on the clinical level, a pharmacokinetics/pharmacodynamics (PK/PD) study was conducted with B12019 in comparison to EU-authorised Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}.{\textless}/p{\textgreater}
The study was designed as a single-dose, randomized, double-blind, two-way crossover study. The study statistics were based on a two-stage design derived from to {\textless}i{\textgreater}Potvin et al, 2007{\textless}/i{\textgreater} to address potential high variability for the PK endpoints. 172 healthy male volunteers were enrolled in stage 1 of the study, whereas stage 2 would allow the recruitment of additional 102 subjects. The subjects received B12019 as well as Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}. The primary PK endpoints were the Area Under the Curve for concentration (AUC{\textless}sub{\textgreater}0-last{\textless}/sub{\textgreater}) and maximum concentration (C{\textless}sub{\textgreater}max{\textless}/sub{\textgreater}). The primary PD endpoint was the Area Under the Effect Curve (AUEC) for Absolute Neutrophil Count (ANC). PK endpoints were assessed with a 94.32{\%} confidence interval (CI) accounting for the two-stage study design, whereas the PD endpoint was assessed with a 95{\%} CI. Furthermore, safety and immunogenicity were investigated.{\textless}/p{\textgreater}
161 subjects were eligible to contribute to the model-based PK and PD comparison based upon the first stage of the study. For the PK endpoints, the 94.32{\%} CIs for the geometric mean ratios were 86.60-104.73{\%} for AUC{\textless}sub{\textgreater}0-last{\textless}/sub{\textgreater} and 84.36-102.18{\%} for C{\textless}sub{\textgreater}max{\textless}/sub{\textgreater}. Both PK endpoints fulfilled the predefined acceptance criteria of being within the range of 80-125{\%}. For the PD endpoint, the 95{\%} CI for the geometric mean ratio of the ANC AUEC was 98.67-101.75{\%}, also falling within the predefined acceptance criteria of 80-125{\%}. Since the primary PK endpoints were met in stage 1 of the study, stage 2 was not required. The safety profile of B12019 did not show any clinically meaningful difference as compared to Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}. Neither anti-G-CSF nor neutralising antibodies were detected for both, B12019 and Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}.{\textless}/p{\textgreater}
The study demonstrated PK and PD comparability as well as comparable safety and immunogenicity profiles of B12019 as compared to EU-authorised Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}. No clinically meaningful differences were detected between B12019 and Neulasta{\textless}sup{\textgreater}{\circledR}{\textless}/sup{\textgreater}. The high analytical and functional similarity of B12019 was confirmed on clinical level.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Disclosures{\textless}/h3{\textgreater}
{\textless}b{\textgreater}Roth:{\textless}/b{\textgreater}{\textless}i{\textgreater}Cinfa Biotech:{\textless}/i{\textgreater} Employment. {\textless}b{\textgreater}Gastl:{\textless}/b{\textgreater}{\textless}i{\textgreater}Cinfa Biotech:{\textless}/i{\textgreater} Consultancy. {\textless}b{\textgreater}Lehnick:{\textless}/b{\textgreater}{\textless}i{\textgreater}Nuvisan GmbH:{\textless}/i{\textgreater} Employment. {\textless}b{\textgreater}Jacob:{\textless}/b{\textgreater}{\textless}i{\textgreater}Cinfa Biotech:{\textless}/i{\textgreater} Employment. {\textless}b{\textgreater}Jankowsky:{\textless}/b{\textgreater}{\textless}i{\textgreater}Cinfa Biotech:{\textless}/i{\textgreater} Employment.{\textless}/p{\textgreater
Objectives: This Multi Centre study is performed in order to evaluate foreign language acquisitio... more Objectives: This Multi Centre study is performed in order to evaluate foreign language acquisition at school in cochlear implant patients in the German speaking part of Switzerland. Material and Methods: In October 2016, 125 CI patients (10-18 years) were registered in the na-tional CI Database. CI non-users and mentally retarded patients were excluded. Additional data (type of schooling, foreign language learning and bilingualism) were obtained with questionnaires. German-speaking children with foreign language tuition (English and/or French) in mainstream were enrolled for further testing (n=31). The normal-hearing control group consisted of matched-pairs. Results: Hundred returned questionnaires were available for analysis. Forty-eight were in main-stream and 52{\%} attained special schools. 88{\%} of CI users attended foreign language tuition. The 12 CI users without foreign language learning were all enrolled in special schools. CI users with foreign language education had better German speech comprehension (89{\%} vs. 51{\%}; p {\textless} 0.05). Thirtyone patients were further tested. The 10 students in 6th grade had all reached the school norms in English reading and listening. For French, 3 out of 7 CI students (44{\%}) reached the school norm for French reading and one (14{\%}) in French listening. The normal hearing group had higher scores (83.6 vs. 76.4{\%}) which was statistical significant for English reading. Those with bi-modal fitting also had higher test-scores (on average 84{\%} vs. 71{\%}; p{\textless}0.05). Conclusion: Almost 90{\%} of our CI children attain foreign language tuition. Those without foreign language learning were all in special schools. Overall, most of the tested patients reached the cur-rent school norm for English reading and listening, whereas the French school norms appeared to be more difficult to reach. A trend for better test scores was found in the normal hearing group. Also CI users with bimodal fitting seem to perform better than bilateral implantation. [ABSTRACT FROM AUTHOR]
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BACKGROUND AND AIMS
The results of studies comparing two-dimensional (2D) and three-dimensional ... more BACKGROUND AND AIMS
The results of studies comparing two-dimensional (2D) and three-dimensional (3D) laparoscopy have shown variable results. We aimed to review the literature and develop an appropriate instrument to compare 2D and 3D laparoscopy. We further aimed to use the data extracted to perform a pilot study.
METHODS
Sixty-seven recent articles on 3D laparoscopy were reviewed and data extracted on factors influencing outcome variables. These variables were used to design a pilot study of 28 novices using a randomized crossover design. The results were analyzed using descriptive statistics and the Wilcoxon signed-rank tests.
RESULTS
Seven themes were identified to influence the outcome of 3D studies: applied technique (1), experience of subjects (2), study design (3), learning curve (4), subjective qualitative reports (5), laparoscopic tasks (6), and chosen outcome variables (7). The consecutively developed five laparoscopic simulation tasks contained placing a rubber band over hooks, ring and pearl transfer, threading a pipe cleaner through loops, and placing a suturise. The pilot study showed a primary benefit of 3D laparoscopy that was unrelated to repetition. Two tasks served well to assess first-time performance, and two tasks promise to serve well to assess a learning curve if performed repeatedly.
CONCLUSION
We were able to identify important issues influencing the outcome of studies analyzing 3D laparoscopy. These may help evaluate future studies. The developed tasks resulted in meaningful data in favor of 3D visualization, but further studies are necessary to confirm the pilot test results.
Temporary fixation with an external fixator is used for numerous indications in orthopedic trauma... more Temporary fixation with an external fixator is used for numerous indications in orthopedic trauma surgery. It is unclear whether primary wound healing or secondary open-wound healing after removal of the external fixator should be advocated for the pin site. This study compares primary wound closure with secondary wound healing for the pin site. The primary aim is to compare pin-site infection rates. The secondary aim is to compare time to wound healing and esthetic outcome. The hypothesis was that primary wound closure does not lead to more infections than secondary wound healing. This is a prospective, randomized controlled, blinded, monocenter study based on a non-inferiority design. To obtain an equal patient population and groups, all pin-entry sites of the patients are treated alternately at the time of removal of the external fixator with primary wound closure and secondary wound healing. Patients are randomized according to whether the proximal pin-entry site is treated with wound closure or by secondary open-wound healing, from which the further sequence develops. The pre- and postoperative protocol is standardized for all pin-entry sites. A photo documentation of the pin-entry sites takes place 2 and 52 weeks postoperatively during the routine clinical follow-up visits. Further controls take place at 6, 12 and 26 weeks after pin removal. The primary outcome was to demonstrate the non-inferiority of primary wound closure compared to secondary wound healing in terms of postoperative wound infections according to the Center of Disease Control and Prevention (CDC) definitions. The secondary outcomes are time to complete wound healing (days) and esthetical outcome (subjective preference of patients and Vancouver Scar Scale score). This study aims to answer how to deal with the pin site after removal of the external fixator. To date, no routine and generally accepted protocol exists for the management of pin sites after removal of the external fixator. This prospective, randomized controlled, blinded monocenter trial should determine whether primary wound closure or secondary wound healing should be advocated after removal of the external fixator. ClinicalTrials.gov, ID: NCT03842956. Registered retrospectively on 13 February 2019.
\textless}h2{\textgreater}Abstract{\textless}/h2{\textgreater}{\textless}h3{\textgreater}Backgrou... more \textless}h2{\textgreater}Abstract{\textless}/h2{\textgreater}{\textless}h3{\textgreater}Background{\textless}/h3{\textgreater}
: To date, limited evidence exists regarding follow-up imaging during the non-operative management (NOM) of blunt splenic injury (BSI), especially concerning ultrasound as first-line imaging modality. The aim of this study was to investigate the incidence and time to failure of NOM as well as to evaluate the relevance of follow-up imaging.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Methods{\textless}/h3{\textgreater}
: All adult patients with BSI admitted to our level I trauma center, including two associated hospitals, between 01/01/2010 and 31/12/2017 were retrospectively analyzed. Demographic data, comorbidities, injury pattern, trauma mechanism, Injury Severity Score, splenic injury grade and free intra-abdominal fluid were reviewed. Additional analysis of indication, frequency, modality, results and consequences of follow-up imaging was performed. Risk factors for failure of NOM were evaluated using fisher's exact test.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Results{\textless}/h3{\textgreater}
: A total of 122 patients with a mean age of 43.8 $\pm$ 20.7 years (16-84 years) met inclusion criteria. Twenty patients (16.4{\%}) underwent immediate intervention. One-hundred-and-two patients (83.6{\%}) were treated by NOM. Failure of NOM occurred in 4 patients (3.9{\%}). Failure was significantly associated with active bleeding (3 of 4 [75{\%}] failures vs. 8 of 98 [8.2{\%}] non-failures, OR 33.75, 95{\%} CI 3.1, 363.2, p = 0.004), and liver cirrhosis (2 of 4 [50{\%}] failures vs. 0 of 98 [0{\%}] non-failures, OR 197, 95{\%} CI 7.4, 5265.1, p = 0.001). Eighty patients (78.4{\%}) in the NOM-Group received follow-up imaging by ultrasound (US, n = 51) or computed tomography (CT, n = 29). In 57 cases, routine imaging examinations were conducted (43 US and 14 CT scans) without prior clinical deterioration. Fifty-fife (96.4{\%}) of these imaging results revealed no new significant findings. Every failure of NOM was detected following clinical deterioration in the first 48 hours.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Conclusion{\textless}/h3{\textgreater}
: To our knowledge this study includes the largest single centric patient cohort undergoing ultrasound as first-line follow-up imaging modality in the NOM setting of BSI in adult patients. The results indicate that a routine follow-up imaging, regardless of the modality, has limited therapeutic advantage. Indication for radiological follow-up should be based on clinical findings. If indicated, a CT scan should be used as preferred imaging modality.{\textless}/p{\textgreater
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