Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry

Aims

We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke.

Methods

The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke.

Results

At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA₂DS₂-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05–7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04–10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24–9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01–0.47, P < 0.01; n = 56], CHA₂DS₂-VASc score [OR per point 1.47, 95% CI 1.08–2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28–2.84, P < 0.01].

Conclusion

At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.

Clinical trial registration

NCT02306824.

     

Sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy

Background: It is difficult to quantify the impact of surgical trauma on patients with conventional measurement techniques. We report our preliminary experience with the determination of sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy. Methods: The electroconductivity of representative dermatomes (24 measuring points) was recorded prior, during, and after performing laparoscopic and needlescopic cholecystectomy on 40 consecutive patients according to the method of Nakatani (Ryodoraku). Fifty-five healthy adults served as a control group. Results: Median age in the two groups was 52.4 and 54.1 years, respectively. Prior to the operation and on the 1st postoperative day, sympathetic nervous activity was equal in both groups. In the needlescopic patients, sympathetic activity was lesser at 30 min after the start of the laparoscopic procedure (p <0.05). Conclusions: The measurement of electroconductivity is a useful noninvasive technique for the evaluation of sympathetic nervous activity. As far as activation of sympathetic nervous system is concerned, the needlescopic technique was found to be superior.     

Ergebnisse der sonographisch-gesteuerten percutanen Drainage intraabdomineller Abscesse im chirurgischen Alltag

Zusammenfassung. Im Rahmen einer retrospektiven Studie wurden die Indikationen, Ergebnisse und Komplikationen von 62 sonographisch-gesteuerten, percutanen Absce?drainagen bei 60 Patienten untersucht. Zun?chst wurde unter sonographischer Kontrolle eine Probepunktion durchgeführt. Anschlie?end konnte in gleicher Technik ein Pigtail- oder van Sonnenberg-Katheter in Seldinger- oder Trokartechnik mit Hilfe eines Punktionsschallkopfes in den Verhalt eingebracht werden. Die percutane Drainage hatte eine prim?re Erfolgsrate von 85 %, bei einer Komplikationsrate von 6,4 %. Die methodenspezifische Letalit?t lag bei 0 %. Die vorgestellte Methode stellt bei strenger Indikationsstellung eine sinnvolle Alternative zur chirurgischen Therapie dar. Die sonographisch-gesteuerte, percutane Absce?drainage ist insbesondere bei kritisch kranken Patienten die Methode der ersten Wahl.      

Target volume coverage and dose to organs at risk in prostate cancer patients

Purpose

On the basis of correct Hounsfield unit to electron density calibration, cone-beam computed tomography (CBCT) data provide the opportunity for retrospective dose recalculation in the patient. Therefore, the consequences of translational positioning corrections and of morphological changes in the patient anatomy can be quantified for prostate cancer patients.

Materials and methods

The organs at risk were newly contoured on the CBCT data sets of 7 patients so as to evaluate the actual applied dose. The daily dose to the planning target volume (PTV) was recalculated with and without the translation data, which result from the real patient repositioning.

Results

A CBCT-based dose recalculation with uncertainties less than 3?% is possible. The deviations between the planning CT and the CBCT without the translational positioning correction vector show an average dose difference of ??8?% inside the PTV. An inverse proportional relation between the mean bladder dose and the actual volume of the bladder could be established. The daily applied dose to the rectum is about 1–54?% higher than predicted by the planning CT.

Conclusion

A dose calculation based on CBCT data is possible. The daily positioning correction of the patient is necessary to avoid an underdosage in the PTV. The new contouring of the organs at risk— the bladder and rectum—allows a better appraisal to be made of the total applied dose to these organs.     

Morphological changes in cultures of hippocampus following prenatal irradiation in the rat

The effect of prenatal irradiation was studied in organotypic cultures of hippocampus, prepared from newborn rats that had been exposed to whole-body irradiation of 1 Gy from a 60Co-source at day 13 of pregnancy. Light and electron microscopic observations showed remarkable damage to neuronal mitochondria accompanied by extensive swelling, vacuolation of the Golgi complex, and formation of multilamellar bodies and vesicles of the lysosomal type. In contrast to neuronal alterations, no delay in synaptogenesis or onset of myelination was observed based upon the absence of significant morphological changes in synapses and myelin sheaths. Using this tissue culture model it could be confirmed that prenatal exposure to irradiation, even at low doses, induces specific morphological changes in the brain.     

The value of fractionated afterloading therapy in the treatment of inoperable malignant brain tumor

Since 1985, inoperable brain tumors, astrocytoma III or glioblastoma multiforme, have been treated by means of fractionated afterloading therapy combines with subsequent percutaneous irradiation. A screw that was specifically designed, allowed us to fix a precious metal tube to the skull cap for about eight days making possible the application of a marginal tumor dose of 30 Gy at a daily fractionation of 2 X 2 Gy using the iridium-afterloading-technique. Percutaneous saturation with another 30-40 Gy followed. Supported by radiobiological considerations, fractionation also appears to have a favorable influence on the perifocal edema formation in the brachytherapy of malignant brain tumors. After an observation period of four years probabilities of survival amounting to six months and twelve months can be calculated (according to Kaplan-Meier) for 68% and 27% of the total collective, respectively (n = 38). The survival rate for patients without pretreatment (n = 16) was 81% and 41% after six and twelve months respectively.     

Digital rectal examination, imaging, and systematic-sextant biopsy in identifying operable lymph node-negative prostatic carcinoma.

The value of digital rectal examination, computerized tomography, magnetic resonance imaging, prostate-specific antigen, transrectal ultrasonography, and systematic-sextant biopsy in the identification of lymph node-positive patients before radical prostatectomy was analyzed in 103 men who had pelvic lymph node dissection, CT had a sensitivity of only 7% and a specificity of 96% in detecting lymph nodes, whereas magnetic resonance imaging had a sensitivity of 50% and a specificity of 100%. To evaluate the use of tumor volume in predicting lymph node metastasis, we counted the number of positive core biopsies and compared the results with the incidence of positive lymph nodes. If fewer than 5 positive core biopsies were considered negative for predicting lymph node metastasis, the sensitivity would be 67% (12 of 18), and the specificity 94% (50 of 53). To investigate tumor volume more precisely, we measured the extent of tumor volume in every biopsy as a percentage of the total biopsy core and added the percentage for the 6 biopsies. The lowest score was 10% (10% prostatic cancer in 1 of 6 cores), the highest score 580% (4 cores with 100% each and 2 with 90% each). The score was analyzed for sensitivity and specificity in predicting lymph node metastasis. If a score of 280% was used as a cutoff point, the sensitivity was 71% (10 of 14) and the specificity 91% (52 of 57). When we include the grading system by multiplying the percentage of tumor volume with tumor grade, the difference between the lymph node-positive state and lymph node-negative state becomes even more readily apparent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ergebnisse der sonographisch-gesteuerten percutanen Drainage intraabdomineller Abscesse im chirurgischen Alltag

Im Rahmen einer retrospektiven Studie wurden die Indikationen, Ergebnisse und Komplikationen von 62 sonographisch-gesteuerten, percutanen Absce?drainagen bei 60 Patienten untersucht. Zun?chst wurde unter sonographischer Kontrolle eine Probepunktion durchgeführt. Anschlie?end konnte in gleicher Technik ein Pigtail- oder van Sonnenberg-Katheter in Seldinger- oder Trokartechnik mit Hilfe eines Punktionsschallkopfes in den Verhalt eingebracht werden. Die percutane Drainage hatte eine prim?re Erfolgsrate von 85 %, bei einer Komplikationsrate von 6,4 %. Die methodenspezifische Letalit?t lag bei 0 %. Die vorgestellte Methode stellt bei strenger Indikationsstellung eine sinnvolle Alternative zur chirurgischen Therapie dar. Die sonographisch-gesteuerte, percutane Absce?drainage ist insbesondere bei kritisch kranken Patienten die Methode der ersten Wahl.