Development of a Chronic Canine Ovariohysterectomy Model to Evaluate Vaginal Cuff Healing Using Two Closure Systems

2021 ◽  
pp. 155335062110393
Author(s):  
David Wiseman ◽  
Josa A. Hanzlik ◽  
James A. Richardson ◽  
John M. Shelton ◽  
Bret M. Evers ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Significance ◽  
Test Group ◽  
Analysis Data ◽  
Closure Device ◽  
Vaginal Cuff ◽  
Suitable Animal Model ◽  
Secondary Endpoints ◽  
The Difference ◽  
Muscle Changes

Background and Purpose. This study established a suitable animal model of ovariohysterectomy; characterized the course and pattern of vaginal healing after ovariohysterectomy; and compared healing obtained after closure of the vaginal cuff with a novel cuff-closure device (Zip-stitch® clips) and VICRYL® sutures. Research Design and Study Sample. This prospective, randomized, controlled, blinded animal study was conducted in 27 mongrel hounds according to an IACUC-approved protocol. Each animal underwent ovariohysterectomy followed by vaginal cuff closure with Zip-stitch or VICRYL. At two or six weeks, animals were sacrificed for gross and histological analysis. Data Collection. The primary endpoint was the difference in the fraction of vaginal cuff healed six weeks after application of the closure device. Secondary endpoints included histopathologic cellular and tissue responses, including inflammation, necrosis, infection, and vascular and muscle changes. Results. In the test group, there were two distinct locations where fibrotic or granular tissue fusion between the anterior and posterior vaginal walls was observed: in tissue “captured” by a clip or in tissue around the clip. The fraction of the vaginal cuff healed was similar in animals treated with Zip-stitch clips and those treated with sutures at six weeks (68±10% vs 67±18%; P=.148, test for non-inferiority) after surgery. The test article performed similarly or better than the control article in terms of the intensity or extent of the secondary endpoints. Conclusions. Subject to further confirmation, this study supports Zip-stitch clips as a method to maintain immediate post-operative approximation of the vaginal cuff leading to healing but did not achieve statistical significance in its primary endpoint.

Vascular closure devices in TAVI: MANTA versus ProGlide in a propensity-matched population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Sa Mendes ◽  
A Oliveira ◽  
R Campante Teles ◽  
P Araujo Goncalves ◽  
J Brito ◽  
...  
Keyword(s):  
Propensity Score ◽  
Learning Curve ◽  
Primary Endpoint ◽  
Femoral Artery ◽  
Statistical Significance ◽  
Vascular Complications ◽  
Artery Stenosis ◽  
Closure Device ◽  
Efficacy And Safety ◽  
Life Threatening

Abstract Background Vascular complications increase morbidity and mortality in transcatheter aortic valve implantation (TAVI). A collagen plug-based closure device - MANTA® was recently introduced as an alternative to the suture-mediated ProGlide® vascular closure device (VCD). Data regarding the efficacy and safety comparing both VCD is scarce. The present study sought to compare the effectiveness of both devices. Methods Single center retrospective analysis on prospectively collected data of 300 consecutive patients who underwent TAVI using MANTA® or ProGlide® since 2018. A 1:1 propensity-score matched population derived by a multivariate logistic regression model based on age, sex, body mass index, pre-procedural haemoglobin, EuroSCORE II, main access calcification and the sheath-to-artery ratio. The primary endpoint was the composite of major or life-threatening bleeding (VARC-2 definition), femoral artery stenosis/dissection, pseudoaneurysm and need for endovascular/surgical bailout intervention. Results The propensity score matching resulted in 129 matched pairs. The median age was 84 years old [IQR 80–87], 42% males with a median EuroSCOREII of 4.29% [IQR 3.05–6.24]. There were no differences in the primary endpoint between MANTA ® and ProGlide® cohorts (3.9% vs 7.8%, p=0.287, respectively). The rates of the primary endpoint with the MANTA® device decreased with center experience, with relatively steep learning curve effect concerning device success. Major or life-threatening bleeding (3.1% vs 5.4%, p=0.540) and pseudoaneurysm (0.8% vs 2.3%, p=0.622) occurred less frequently in MANTA® cohort, but the differences did not reach statistical significance. Endovascular (stent or balloon) or surgical rescue intervention (9.3% vs 5.4%, p=0.341) and femoral artery stenosis/dissection (6.2% vs 3.1%, p=0.376), were also similar rates. In ProGlide® cohort, to achieve VCD success (without primary endpoint events), 15.5% needed more than 2 devices, significantly different from MANTA ® (p<0,001). Conclusions In patients undergoing transfemoral TAVI, the MANTA® VCD showed a similar efficacy and safety compared to the ProGlide® device and it reduced significantly the need of additional VCDs for completion of hemostasis. These results were obtained despite a clear learning curve associated with MANTA. Funding Acknowledgement Type of funding source: None

scholarly journals Efficacy and Safety of Different Doses of Bevacizumab Combined With Pemetrexed and Platinum in First-Line Treatment of Advanced NSCLC: A Retrospective-Real World Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun-Hua Zhou ◽  
Feng Yang ◽  
Wen-Juan Jiang ◽  
Yong-Chang Zhang ◽  
Hai-Yan Yang ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
First Line ◽  
Free Survival ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
The Cost ◽  
Different Doses

Background: Bevacizumab was demonstrated to have efficacy in patients with NSCLC. However, application of different doses of bevacizumab in different clinical trials was overlooked. This study aims to investigate the effects and safety of different doses of bevacizumab in the treatment.Methods: From January 2016 to March 2020, 79 patients with NSCLC received first-line combination treatment with chemotherapy (pemetrexed + platinum) and bevacizumab for four cycles; patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab combined with pemetrexed, of which 57 patients received bevacizumab at a dose of 7.5 mg/kg and 22 patients at a dose of 15 mg/kg. The primary endpoint was progression-free survival, and secondary endpoints were overall response rate, disease control rate, and adverse events.Results: There was no significant difference between two groups in effectiveness; Median PFS in 7.5 mg/kg group and in 15 mg/kg group were 8.0 and 8.7 months, respectively (p = 0.663), reaching the primary endpoint. The ORR and DCR in the bevacizumab 7.5 and 15 mg/kg group were 45.46 and 86.0% vs. 50 and 90.9% showing no statistical significance (p = 0.804 and 0.717). Most of side effects were tolerable. The incidences of overall toxicities were higher in 15 mg/kg group (p = 0.001). No new safety signals were observed.Conclusion: We did not detect significant difference of efficacy and safety between 7.5 mg/kg group and 15 mg/kg group for bevacizumab administration, the cost-effectiveness of the 7.5 mg/kg group was significantly better than that of the 15 mg/kg group.

Possible mechanisms of serotonin and aprepitant actions in chemotherapy induced nausea and vomiting (CINV): Insights into the mechanisms of serotonin and aprepitant actions in CINV—According to recent multi-institutional double-blind randomized clinical research on the AC regimen.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6587-6587
Author(s):  
Michiko Tsuneizumi ◽  
Mitsue Saito ◽  
Hideaki Ogata ◽  
Goro Kutomi ◽  
Keiko Hosoya ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Significance ◽  
Complete Response ◽  
Antiemetic Therapy ◽  
Double Blind ◽  
Nk1 Receptor Antagonist ◽  
The Difference ◽  
Two Peaks ◽  
Delayed Phase ◽  
Clinical Trial Information

6587 Background: One of our interests has been whether palonosetron(P) would be superior to granisetron(G) when administering triplet antiemetic therapy for the prevention of CINV, since a prior trial demonstrated P to be superior to G for controlling CINV induced by highly emetogenic chemotherapy (HEC) in doublet therapy. In this study(TTT; trial for antiemetic therapy), we assessed the efficacies of P and G for use as triplet antiemetic therapy for AC, by monitoring CINV, focusing complete response (CR; no vomiting and no rescue medicine) in the delayed phase. The primary endpoint of TTT was a CR during the delayed phase with 5-HT3ra plus dexamethasone and aprepitant administration for AC.　The purpose of gaining insights into the possible mechanism of action of aprepitant and P was to obtain ideas for the next strategy against CINV. Methods: Between 2012 and 2015, 491 breast cancer receiving AC were recruited from 11 institutions, and randomly assigned to either single-dose P(0.75mg) or G(40μg/kg) prior to AC on day 1, both with dexamethasone (9.9 mg) and aprepitant (125mg) on day 1 followed by additional doses (80mg) on days 2 and 3. Age, institution and habitual alcohol intake were used as stratification factors. The primary endpoint was a CR. Results: All 491 patients were included in efficacy analyses: 246 patients in the group P and 245 in the group G. The difference in CR during the delayed phase, i.e. 24 hrs after the administration of AC, did not reach statistical significance, however, there was a remarkable difference between 48 and 72 hrs in the day-to-day analysis(p < 0.02). Conclusions: P showed better efficacy in controlling CINV between 48 to 72 hours after AC, than G as triplet antiemetic therapy for AC. We can reasonably speculate that the influence of serotonin has two peaks (0-24 hrs and 48-72 hrs). For controlling CINV in the delayed phase, not only an NK1 receptor antagonist but also administering a 5-HT3ra with long life should be considered until 72 hrs after HEC. Clinical trial information: UMIN 000007882.

Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis

2010 ◽  
Vol 16 (11) ◽  
pp. 1349-1359 ◽  
Author(s):  
RBC Kavia ◽  
D De Ridder ◽  
CS Constantinescu ◽  
CG Stott ◽  
CJ Fowler
Keyword(s):  
Multiple Sclerosis ◽  
Overactive Bladder ◽  
Primary Endpoint ◽  
Bladder Dysfunction ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Double Blind ◽  
Parallel Group ◽  
Secondary Endpoints ◽  
Global Impression Of Change

Background: Bladder dysfunction is a common feature of multiple sclerosis (MS). Objective: In this study we aimed to assess the efficacy, tolerability and safety of Sativex® (nabiximols) as an add-on therapy in alleviating bladder symptoms in patients with MS. Methods: We undertook a 10-week, double-blind, randomized, placebo-controlled, parallel-group trial in 135 randomized subjects with MS and overactive bladder (OAB). Results: The primary endpoint was the reduction in daily number of urinary incontinence episodes from baseline to end of treatment (8 weeks). Other endpoints included incidence of nocturia and urgency, overall bladder condition (OBC), daytime frequency, Incontinence Quality of Life (I-QOL), Patient’s Global Impression of Change (PGIC) and volume voided. The primary endpoint showed little difference between Sativex and placebo. Four out of seven secondary endpoints were significantly in favour of Sativex: number of episodes of nocturia (adjusted mean difference -0.28, p = 0.010), OBC (-1.16, p = 0.001), number of voids/day (-0.85, p = 0.001) and PGIC ( p = 0.005). Of the other endpoints, number of daytime voids was statistically significantly in favour of Sativex (-0.57, p = 0.044). The improvement in I-QOL was in favour of Sativex but did not reach statistical significance. Conclusions: Although the primary endpoint did not reach statistical significance, we conclude that Sativex did have some impact on the symptoms of overactive bladder in patients with MS, providing evidence of some improvement in symptoms associated with bladder dysfunction in these subjects.

Use of nalbuphine as a substitute for butorphanol in combination with dexmedetomidine and tiletamine/zolazepam: a randomized non-inferiority trial

2019 ◽  
Vol 22 (2) ◽  
pp. 100-107 ◽  
Author(s):  
Rachael E Kreisler ◽  
Heather N Cornell ◽  
Veronica A Smith ◽  
Samantha E Kelsey ◽  
Erik H Hofmeister
Keyword(s):  
Primary Endpoint ◽  
Clinical Score ◽  
Mobile Clinic ◽  
Reversal Agent ◽  
Clinician Satisfaction ◽  
Secondary Endpoints ◽  
The Mean ◽  
The Difference ◽  
Individual Scores ◽  
Number Of Injections

Objectives The goal of this study was to determine whether a drug combination using nalbuphine with dexmedetomidine and tiletamine/zolazepam is non-inferior to one that uses butorphanol. Methods All healthy cats presenting solely for gonadectomy to two trap–neuter–return mobile clinic days were randomly assigned to induction with a combination of tiletamine/zolazepam 3 mg/kg, dexmedetomidine 7.5 µg/kg and either butorphanol or nalbuphine at 0.15 mg/kg. All participants were blinded to the identity of the combinations. The primary endpoint was clinician satisfaction, comprised of the mean of four satisfaction ratings on a 7-point Likert scale (highly dissatisfied through to highly satisfied) recorded for induction, maintenance of anesthesia, surgery and recovery. Exploratory endpoints included each individual score, number of injections, duration of induction, duration of recovery and need for reversal agent. To assess non-inferiority for the primary endpoint and individual scores, the difference and 95% confidence intervals (CIs) of the difference between the mean clinical scores for the nalbuphine and butorphanol-based combinations were calculated and compared with a prespecified non-inferiority margin of 20% (1.4 points). Results Seventy-two cats were enrolled, 36 in each group. The mean ± SD composite score for the combination with nalbuphine was 6.06 ± 0.59 (95% CI 5.86–6.25) points, while the combination with butorphanol was 6.22 ± 0.62 (95% CI 6.01–6.43). The difference between mean scores was 0.17 (–0.12 to 0.45), which did not exceed the prespecified boundary of 1.4, establishing the non-inferiority of nalbuphine. No individual clinical score for nalbuphine was inferior to butorphanol, and there were no significant differences for any secondary endpoints. Conclusions and relevance The clinical experience of the nalbuphine-based combination was non-inferior to the butorphanol-based combination. Nalbuphine is an effective substitute for butorphanol, providing another option if butorphanol is unavailable due to shortage, controlled status or cost, without requiring a change in anesthetic workflow.

Influence of prior intravenous thrombolysis on outcome after failed mechanical thrombectomy: ETIS registry analysis

2021 ◽  
pp. neurintsurg-2021-017867
Author(s):  
Claire Rozes ◽  
Benjamin Maier ◽  
Benjamin Gory ◽  
Romain Bourcier ◽  
Maeva Kyheng ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Intracranial Hemorrhage ◽  
Mechanical Thrombectomy ◽  
Statistical Significance ◽  
Intravenous Thrombolysis ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Shift Analysis ◽  
Secondary Endpoints ◽  
The Difference

BackgroundDespite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization.MethodsWe conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0–2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates.ResultsAmong 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54).ConclusionsAmong patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.

scholarly journals Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study)

Rheumatology ◽  
2021 ◽  
Author(s):  
Frank Behrens ◽  
Michaela Koehm ◽  
Tanja Rossmanith ◽  
Rieke Alten ◽  
Martin Aringer ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Response Rate ◽  
Inadequate Response ◽  
Phase 3 ◽  
Double Blind ◽  
Efficacy Outcome ◽  
Clinical Benefits ◽  
Secondary Endpoints ◽  
The Difference ◽  
N 93

Abstract Objective To investigate the efficacy and safety of rituximab + LEF in patients with RA. Methods In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators’ control. Results Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders. Conclusion The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring. Trial registration EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958.

Use of vascular closure devices for endovascular interventions requiring a direct puncture of PETE grafts

VASA ◽  
2018 ◽  
Vol 47 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Artur I. Milnerowicz ◽  
Aleksandra A. Milnerowicz ◽  
Marcin Protasiewicz ◽  
Wiktor Kuliczkowski
Keyword(s):  
Statistical Significance ◽  
Vascular Complications ◽  
Vascular Complication ◽  
Inguinal Region ◽  
Closure Device ◽  
Manual Compression ◽  
Direct Puncture ◽  
Endovascular Interventions ◽  
Vascular Closure Devices ◽  
Closure Group

Abstract. Background: Effectiveness of vascular closure devices during endovascular procedures requiring a direct puncture of a vascular prosthesis placed in the inguinal region is unknown. Patients and methods: The retrospective analysis included 134 patients with a history of polyethylene terephthalate (PETE) graft implantation in the inguinal region. In 20 (15 %) patients, haemostasis was achieved with manual compression, in 21 (16 %) with the StarClose™, and in 93 (69 %) with the AngioSeal™ device. Results: The incidence of vascular complications in the manual compression group was higher (at a threshold of statistical significance) than in the device closure group (45.0 vs. 24.5 %, p = 0.059). The difference was considered statistically significant when manual compression was compared with the AngioSeal™ closure group (45.0 vs. 13.9 %, p < 0.01). The vascular complication rate in the StarClose™ group was significantly higher than in the AngioSeal™ group (71.4 vs. 13.9 %, p < 0.000001). While haematomas were the only vascular complications observed after application of AngioSeal™, both haematomas and pseudoaneurysms were found in the StarClose™ group. Conclusions: The AngioSeal™ vascular closure device provides better local haemostasis than the StarClose™ device or manual compression during endovascular interventions requiring a direct puncture of PETE grafts

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