Kevin Kunzmann

Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation: The Prospective, Randomized, Controlled, Noninferiority FreezeAF Study

Background— There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Methods and Results— In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, −0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, −0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002). Conclusion— This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774566.

Ketamine modulation of the haemodynamic response to spreading depolarization in the gyrencephalic swine brain.

Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit.

One-stage tooth-borne distraction versus two stage bone-borne distraction in surgically assisted maxillary expansion (SARME)

OBJECTIVE To evaluate and compare the effects of tooth-borne and bone-borne distraction devices in surgically assisted maxillary expansion (SARME) on dental and skeletal structures. STUDY DESIGN A sample of 33 skeletally mature patients with transverse maxillary deficiencies was examined with cone beam computed tomography (CBCT) before and 3 months after surgery. Fourteen patients were treated with tooth-borne devices and 19 patients with bone-borne devices. RESULTS Dental crown expansion in the first premolars did not differ significantly between the two groups, and median expansion was 5.55 mm (interquartile range [IQR] 5.23) in the tooth-borne device group and 4.6 mm (IQR 3.4) in the bone-borne device group. In the first molars, crown expansion and lateral tipping were significantly greater in the tooth-borne device group (P ≤ .02). The median skeletal nasal isthmus increase was significantly more in the bone-borne device group at 3.0 mm than in the tooth-borne device group at 0.98 mm (P ≤ .02). CONCLUSIONS Both tooth-borne and bone-borne devices are effective treatment modalities to correct maxillary transverse deficiencies. Bone-borne devices produced greater widening of the skeletal nasal floor and fewer dental side effects in the first molars.

Lower prevalence of chronic itch in haemodialysis patients on loop diuretics: results from GEHIS (German Epidemiological Hemodialysis Itch Study)

Chronic itch (CI) is a very tormenting symptom in haemodialysis (HD) patients. GEHIS (German Epidemiological Hemodialysis Itch Study) is a representative cross‐sectional study showing that current chronic itch (CI) affects 25.2% of haemodialysis (HD) patients.

Point estimation in adaptive enrichment designs

Adaptive enrichment designs are an attractive option for clinical trials that aim at demonstrating efficacy of therapies, which may show different benefit for the full patient population and a prespecified subgroup. In these designs, based on interim data, either the subgroup or the full population is selected for further exploration. When selection is based on efficacy data, this introduces bias to the commonly used maximum likelihood estimator. For the situation of two-stage designs with a single prespecified subgroup, we present six alternative estimators and investigate their performance in a simulation study. The most consistent reduction of bias over the range of scenarios considered was achieved by a method combining the uniformly minimum variance conditionally unbiased estimator with a conditional moment estimator. Application of the methods is illustrated by a clinical trial example.

Grundlagen für den Umgang mit Daten

In diesem Kapitel soll anhand der Daten, die fur die nachfolgenden Auswertungen herangezogen werden, das Vorgehen beim Importieren von Exceldaten in SPSS erlautert und auf die Bearbeitung bzw. Berechnung neuer Variablen eingegangen werden.

Statistische Tests und Grafiken

Der primare Endpunkt in einer klinischen Studie ist jenes Zielkriterium bzw. Outcome, anhand dessen der Erfolg der Studie (z.B. Nachweis der Wirksamkeit einer neuen Therapie) beurteilt wird. Zur Analyse des primaren Endpunkts stehen zum einen deskriptive, zum anderen konfirmatorische Methoden zur Verfugung. Mittels konfirmatorischer Methoden sollen Ruckschlusse auf die interessierende Grundgesamtheit gezogen und die Studienergebnisse somit verallgemeinert werden.

Assessing abrasion of orthodontic surface sealants using a modified ophthalmic optical coherence tomography device

ObjectiveOptical coherence tomography (OCT) is a clinical standard in ophthalmology. Currently, its application in dentistry is gaining increasing interest. In this study, we tested the possibility to use a modified commercially available spectral domain OCT (SD-OCT) to assess the layer thickness of orthodontic surface sealants.Materials and methodsReference samples of surface sealants for calibration and repeatability testing were measured using a micrometer screw. SD-OCT measurements were compared with micro-CT and light microscopic analyses. After validating the calibration of the SD-OCT, surface sealant layer thickness after aging (thermo cycling) and simulation of professional tooth cleaning (PTC) was assessed using the SD-OCT on 45 extracted teeth assigned to three test groups (n = 15 each): Light Bond™ Sealant, Pro Seal®, and Opal® Seal.ResultsSD-OCT showed excellent repeatability and accuracy for measurements of surface sealant layer thickness. Compared with micro-CT, SD-OCT showed better accordance with the reference measurements. The analysis of surface sealants after thermo cycling and PTC revealed poor resistance of Light Bond after only aging and demonstrated substantial wear of all sealants after aging and PTC.ConclusionImaging using commercially available ophthalmic SD-OCT might represent a suitable non-invasive methodology for longitudinal assessments of surface sealant layer thickness in vitro and in vivo.Clinical relevanceSD-OCT might be a suitable non-invasive method for longitudinal assessments of surface sealant durability in clinical trials.

Test-compatible confidence intervals for adaptive two-stage single-arm designs with binary endpoint

Inference after two-stage single-arm designs with binary endpoint is challenging due to the nonunique ordering of the sampling space in multistage designs. We illustrate the problem of specifying test-compatible confidence intervals for designs with nonconstant second-stage sample size and present two approaches that guarantee confidence intervals consistent with the test decision. Firstly, we extend the well-known Clopper-Pearson approach of inverting a family of two-sided hypothesis tests from the group-sequential case to designs with fully adaptive sample size. Test compatibility is achieved by using a sample space ordering that is derived from a test-compatible estimator. The resulting confidence intervals tend to be conservative but assure the nominal coverage probability. In order to assess the possibility of further improving these confidence intervals, we pursue a direct optimization approach minimizing the mean width of the confidence intervals. While the latter approach produces more stable coverage probabilities, it is also slightly anti-conservative and yields only negligible improvements in mean width. We conclude that the Clopper-Pearson-type confidence intervals based on a test-compatible estimator are the best choice if the nominal coverage probability is not to be undershot and compatibility of test decision and confidence interval is to be preserved.

Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial FibrillationCLINICAL PERSPECTIVE

Background— There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Methods and Results— In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, −0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, −0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002). Conclusion— This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774566.