Meinhard Kieser

Bio: Meinhard Kieser is an academic researcher from Heidelberg University. The author has contributed to research in topics: Sample size determination & Randomized controlled trial. The author has an hindex of 43, co-authored 267 publications receiving 6615 citations.

Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial

Abstract: Importance Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials Objective To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy Design, Setting, and Participants SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery Intervention Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy Main Outcomes and Measures Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]) Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety Results Among 150 patients (60 women [40%]; mean age, 715 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 168 at admission vs 136 after 24 hours; difference, −32 points [95% CI, −56 to −08]) vs the conscious sedation group (mean NIHSS score, 172 at admission vs 136 after 24 hour; difference, −36 points [95% CI, −55 to −17]); mean difference between groups, −04 (95% CI, −34 to 27; P = 82) Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 91%; difference, 91%; P = 008), but postinterventional complications were more frequent for hypothermia (329% vs 91%; P P P = 03) More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [370% in the general anesthesia group vs 182% in the conscious sedation group P = 01]) There were no differences in mortality at 3 months (247% in both groups) Conclusions and Relevance Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours The study findings do not support an advantage for the use of conscious sedation Trial Registration clinicaltrialsgov Identifier:NCT02126085

Combining different phases in the development of medical treatments within a single trial

Abstract: In the development of medical treatments, identification of promising therapies and inference on selected treatments are usually performed in subsequent separate trials. An adaptive two-stage design is proposed for the situation of multiple treatments to be compared with a control, allowing integration of both steps within a single confirmatory trial controlling the multiple level alpha. After the interim analysis, the trial may be terminated early or is continued with a second stage, where the set of treatments may be reduced due to lack of efficacy or to safety problems. The procedure is highly flexible with respect to the distributional assumptions, stopping rules and selection criteria and allows a completely free recalculation of the sample size for the second stage. Simulations show that the method may be substantially more powerful than classical one-stage multiple treatment designs with the same total sample size. As in conventional strategies with a series of separate experiments, a reasonable selection strategy has to be applied in order to prevent proceeding with non-optimal treatments.

Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.

Abstract: Objective To investigate the efficacy of hypericum extract WS 5570 (St John9s wort) compared with paroxetine in patients with moderate to severe major depression. Design Randomised double blind, double dummy, reference controlled, multicentre non-inferiority trial. Setting 21 psychiatric primary care practices in Germany. Participants 251 adult outpatients with acute major depression with total score ≥ 22 on the 17 item Hamilton depression scale. Interventions 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks. In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks. Main outcome measures Change in score on Hamilton depression scale from baseline to day 42 (primary outcome). Secondary measures were change in scores on Montgomery-Asberg depression rating scale, clinical global impressions, and Beck depression inventory. Results The Hamilton depression total score decreased by mean 14.4 (SD 8.8) points, corresponding to 56.6% (SD 34.3%) of the baseline value, in the hypericum group and by 11.4 (SD 8.6) points (44.8% (SD 33.5%) of baseline value) in the paroxetine group (intention to treat analysis; similar results were observed in the per protocol analysis). The intention to treat analysis (lower one sided 97.5% confidence limit 1.5 points for the difference hypericum minus paroxetine) and the per protocol analysis (lower confidence limit 0.7 points) showed non-inferiority of hypericum and statistical superiority over paroxetine. The lower limits in both cases exceeded the pre-specified non-inferiority margin of −2.5 points and the superiority margin of 0. The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine, respectively. Conclusions In the treatment of moderate to severe major depression, hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated.

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

Abstract: 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: . Unique identifier: [NCT00774566][1]. # CLINICAL PERSPECTIVE {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00774566&atom=%2Fcirculationaha%2F132%2F14%2F1311.atom

Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541).

Abstract: Objective: In patients undergoing midline incisions, the abdominal fascia can be closed with a continuous or interrupted suture using various materials. The aim of this study is to compare: (1) interrupted technique with rapidly absorbable sutures and (2) continuous techniques with different slowly absorbable sutures, focusing on the incidence of incisional hernias within 1 year. of Background Data: A meta-analysis suggested that the incidence of incisional hernias can be more effectively reduced with slowly absorbable continuous sutures. Methods: Multicenter randomized surgical trial with 3 parallel groups. Patients were scheduled for primary elective midline incisions. All surgeons were trained (4:1 suture wound length in continuous groups) and monitored. Primary end point, measured within 1 year after surgery, was the frequency of incisional hernias diagnosed by clinical examination and confirmed by ultrasound. Complications and safety were used as secondary end points. This study has been registered with the ISRCTN Register (INSECT: ISRCTN24023541). Results: Conducted on 625 randomized patients (210 interrupted Vicryl, 205 continuous polydioxanone suture (PDS), 210 continuous Monoplus), the primary analysis showed an incidence of 28 incisional hernias (15.9%) versus 15 (8.4%) versus 22 (12.5%) for the 3 closure techniques, respectively (P = 0.09). No significant difference was observed between the 3 groups with regard to burst abdomen (4 [2.0%] vs. 6 [3.0%] vs. 8 [4.0%], P = 0.46), wound infection (26 [12.7%] vs. 39 [19.4%] vs. 33 [16.3%], P = 0.19), pulmonary infections (9 [4.4%] vs. 5 [2.5%] vs. 5 [2.5%], P = 0.46), serious adverse events (63 [30.0%] vs. 57 [27.8%] vs. 61 [29.1%], P = 0.89), and 1-year mortality (16 [7.9%] vs. 11 [5.5%] vs. 16 [7.9%], P = 0.54). Conclusions: The incidence of incisional hernias and the frequency of wound infection was higher than expected in all groups. New concepts need to be developed and studied to substantially reduce the frequency of incisional hernias.

The control of the false discovery rate in multiple testing under dependency

Abstract: Benjamini and Hochberg suggest that the false discovery rate may be the appropriate error rate to control in many applied multiple testing problems. A simple procedure was given there as an FDR controlling procedure for independent test statistics and was shown to be much more powerful than comparable procedures which control the traditional familywise error rate. We prove that this same procedure also controls the false discovery rate when the test statistics have positive regression dependency on each of the test statistics corresponding to the true null hypotheses. This condition for positive dependency is general enough to cover many problems of practical interest, including the comparisons of many treatments with a single control, multivariate normal test statistics with positive correlation matrix and multivariate $t$. Furthermore, the test statistics may be discrete, and the tested hypotheses composite without posing special difficulties. For all other forms of dependency, a simple conservative modification of the procedure controls the false discovery rate. Thus the range of problems for which a procedure with proven FDR control can be offered is greatly increased.

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

Abstract: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO)

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2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Abstract: Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."