scholarly journals Effect of Low-dose ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart Surgery Patients: END-AF Low Dose Trial

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093983
Author(s):  
Ramzi A. Tabbalat ◽  
Imad Alhaddad ◽  
Ayman Hammoudeh ◽  
Yousef S. Khader ◽  
Hassan Abu Khalaf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Side Effects ◽  
Low Dose ◽  
Heart Surgery ◽  
Small Sample Size ◽  
Open Heart Surgery ◽  
Small Sample ◽  
Controlled Study ◽  
Unique Identifier ◽  
Double Blind

Background Studies using 1 mg of colchicine to prevent postoperative atrial fibrillation (POAF) reported conflicting results. Moreover, colchicine was associated with significant gastrointestinal (GI) side effects. This study examined whether low-dose colchicine effectively prevents POAF and whether low-dose therapy is associated with lower rates of colchicine-induced GI side effects. Methods In this prospective, randomized, double-blind, placebo-controlled study, consecutive adult patients admitted for elective cardiac surgeries randomly received a 1-mg dose of colchicine (n = 81) or placebo (n = 71) orally 12 to 24 hours before surgery followed by a daily dose of 0.5 mg until hospital discharge. The primary efficacy endpoint was the development of at least one episode of POAF of ≥5 minutes. The primary safety endpoint was the development of adverse events, especially diarrhea. Results The in-hospital mortality rate was 3.9%. POAF occurred in 13 patients (16.1%) in the colchicine group and 13 patients (18.3%) in the placebo group (odds ratio 0.85 [95% Confidence Interval = 0.37−1.99]). Diarrhea occurred in two patients in each group and necessitated treatment discontinuation in one patient in each group. Conclusion Low-dose colchicine did not prevent POAF in patients undergoing cardiac surgery. These results should be interpreted cautiously because of the small sample size and early study termination. ClinicalTrials.gov Unique Identifier number: NCT03015831

Effect of coadministration of propranolol and etodolac (VT-122) plus sorafenib for patients with advanced hepatocellular carcinoma (HCC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 390-390 ◽  
Author(s):  
Andrew N de la Torre ◽  
Ismael Castaneda ◽  
Aram F. Hezel ◽  
Newell F. Bascomb ◽  
Gouri Shankar Bhattacharyya ◽  
...  
Keyword(s):  
Hepatitis Virus ◽  
Small Sample Size ◽  
Small Sample ◽  
Controlled Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Separate Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Duration Of Therapy ◽  
Significant Efficacy

390 Background: Propranolol and etodolac (designated VT-122) target the adrenergic and prostaglandin stress systems activated in HCC. These stress-induced systems are proposed to induce changes in the tumor microenvironment and immune system leading to tumor promotion and immune tolerance. In a separate study, administration of VT-122 prior to sorafenib showed an increase in median overall survival (OS) of 21 months when VT-122 is administered before sorafenib compared to 10 months OS for sorafenib alone. The aim of the current study was to evaluate the effect of administering VT-122 at least 30 days after starting sorafenib. Methods: Patients with HCC receiving sorafenib for at least 30 days were eligible for this double-blind, placebo-controlled study. Patients were randomized to receive sorafenib with either VT-122 or placebo. Patients received therapy for up to 12 months or until treatment failure. VT-122 was administered twice daily. The primary endpoint was duration of therapy (DoT) and the secondary endpoint was OS. Results: Twenty patients were randomized, 11 and 9 patients to the VT122 and placebo arm, respectively. Each arm was balanced with regards to age (mean of 60.4 years), Child Pugh status (9 Child Pugh A, 11 Child Pugh B7), hepatitis virus status (6 HBV and 1 HCV positive) and C-reactive protein (CRP) (20.4 mg/L). VT122 with sorafenib was well tolerated with no unexpected serious adverse events reported. Mean OS was 13.9 months and 9.6 months in the VT-122 and placebo arms, respectively. Mean DoT (unvalidated) was 10.1 months and 7.5 months in the VT-122 and placebo arms, respectively. Conclusions: Co-administration of VT-122 with sorafenib was well tolerated and showed an increase in duration of therapy and OS versus sorafenib alone. The small sample size and number of events precludes the ability to make any significant efficacy conclusions. The increase in survival was not as great as that seen in a separate study in which VT122 was started prior to sorafenib. A further Phase 3 study of VT122 administered prior to sorafenib in patients with HCC is warranted. Clinical trial information: NCT01265576.

Intranasal Scopolamine for Motion Sickness

2019 ◽  
Vol 90 (11) ◽  
pp. 917-924
Author(s):  
Aleksandra S. Stankovic ◽  
Donna L. Alvarenga ◽  
Vernie R. Coleman Daniels ◽  
Rita G. Simmons ◽  
Jay C. Buckey ◽  
...  
Keyword(s):  
Motion Sickness ◽  
Intranasal Administration ◽  
Low Dose ◽  
Small Sample Size ◽  
Vertical Axis ◽  
Rapid Onset ◽  
Small Sample ◽  
High Dose ◽  
Double Blind ◽  
Axis Rotation

INTRODUCTION: Rapid onset, noninjection methods are required to provide “as needed” therapy for motion sickness. Intranasal scopolamine (IN SCOP) is attractive because it can be fast acting and work when gastric motility is slowed. Intranasal administration can provide a time to maximal concentration (Tmax) of drugs (e.g., naloxone and midazolam) of 30 min or less. We evaluated the efficacy, pharmacodynamics, and pharmacokinetics of IN SCOP in a placebo-controlled, randomized, double-blind, dose-ranging study, and compared pharmacokinetic outcomes against other published results.METHODS: There were 18 healthy adult volunteers (10 M, 8F) who received placebo, low dose (0.2 mg), and high dose (0.4 mg) IN SCOP intranasally using a pump device and a gel formulation. Participants rode in an off-vertical axis rotation (OVAR) chair 1.25 h after dose administration and completed neurocognitive tests to evaluate secondary drug impacts. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in eight subjects. PK data were compared to results from previously published studies.RESULTS: Low and high dose IN SCOP increased chair time significantly compared to placebo. No significant sleepiness or cognitive impairment was seen, likely due to the small sample size. Tmax was long for both dosages (High dose 75.0 ± 49.4 min, Low dose 61.9 ± 37.1 min), compared to other intranasally administered drugs and some previous studies with IN SCOP. Average Tmax was not superior to previously published values for dose-matched (0.4–0.5 mg), orally-delivered SCOP.DISCUSSION: IN SCOP has potential as a rapid administration route for relieving MS symptoms, but more work is needed to identify optimal intranasal formulation and dispensing methods.KEYWORDS: Motion sickness, pharmacokinetics, scopolamine, intranasal administration.Stankovic AS, Alvarenga DL, Daniels VRC, Simmons RG, Buckey JC, Putcha L. Intranasal scopolamine for motion sickness. Aerosp Med Hum Perform. 2019; 90(11):917–924.

Effects of perioperative S (+) ketamine infusion added to multimodal analgesia in patients undergoing ambulatory haemorrhoidectomy

2010 ◽  
Vol 1 (2) ◽  
pp. 100-105 ◽  
Author(s):  
Ulrich J. Spreng ◽  
Vegard Dahl ◽  
Johan Ræder
Keyword(s):  
Side Effects ◽  
Postoperative Analgesia ◽  
Analgesic Effect ◽  
Low Dose ◽  
Isotonic Saline ◽  
Multimodal Analgesia ◽  
Controlled Study ◽  
Double Blind ◽  
Pain Scores ◽  
Pacu Stay

AbstractBackground and objectivePerioperative low-dose ketamine has been useful for postoperative analgesia. In this study we wanted to assess the analgesic effect and possible side-effects of perioperative low-dose S (+) ketamine when added to a regime of non-opioid multimodal pain prophylaxis.MethodsSeventy-seven patients scheduled for haemorrhoidectomy were enrolled in this randomized, double-blind, controlled study. They received oral paracetamol 1–2 g, total intravenous anaesthesia, intravenous 8 mg dexamethasone, 30 mg ketorolac and local infiltration with bupivacaine/epinephrine. Patients randomized to S (+) ketamine received an intravenous bolus dose of 0.35 mg kg−1 S (+) ketamine before start of surgery followed by continuous infusion of 5 μg kg−1 min−1 until 2 min after end of surgery. Patients in the placebo group got isotonic saline (bolus and infusion). BISTM monitoring was used. Pain intensity and side-effects were assessed by blinded nursing staff during PACU stay and by phone 1, 7 and 90 days after surgery.ResultsIn patients randomized to S (+) ketamine emergence from anaesthesia was significantly longer (13.1 min vs. 9.3 min; p < 0.001). BIS values were significantly higher during anaesthesia (maximal value during surgery: 62 vs. 57; p = 0.01) and when opening eyes (81 vs. 70, p < 0.001). Pain scores (NRS and VAS) did not differ significantly between groups.ConclusionsThe addition of perioperative S (+) ketamine for postoperative analgesia after haemorrhoidectomy on top of multimodal non-opioid pain prophylaxis does not seem to be warranted, due to delayed emergence and recovery, more side-effects, altered BIS readings and absence of additive analgesic effect.

scholarly journals EFFECT OF LOW DOSE COLCHICINE ON THE INCIDENCE OF ATRIAL FIBRILLATION IN OPEN HEART SURGERY PATIENTS: END-AF LOW DOSE TRIAL

2020 ◽  
Vol 75 (11) ◽  
pp. 464
Author(s):  
Ramzi A. Tabbalat ◽  
Jude Barakat ◽  
Yousef Khader ◽  
Ayman Hammoudeh ◽  
Imad Alhaddad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Low Dose ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Open Heart ◽  
Dose Trial

scholarly journals Safety and Efficacy of Dexmedetomidine in Treating Post Spinal Anesthesia Shivering: A Randomized Clinically Controlled Dose-Finding Trial

2016 ◽  
Vol 4;19 (4;5) ◽  
pp. 243-253
Author(s):  
Hala S. Abdel-Ghaffar
Keyword(s):  
Side Effects ◽  
Spinal Anesthesia ◽  
Response Rate ◽  
Small Sample Size ◽  
Onset Time ◽  
Small Sample ◽  
University Hospital ◽  
Tympanic Temperature ◽  
Controlled Study ◽  
Optimum Dose

Background: The optimum dose of dexmedetomidine for shivering control with the least hemodynamic derangements is still under research. Objective: To compare the efficacy, hemodynamic and side effects of dexmedetomidine in 3 different doses with those of meperidine for the treatment of shivering in patients undergoing spinal anesthesia for minor elective lower abdominal surgery. Study Design: Prospective double-blind randomized clinically controlled study. Setting: University hospital. Methods: One hundred twenty patients who developed shivering under spinal anesthesia. On shivering, patients were randomly allocated to receive an intravenous 2 mL bolus dose of meperidine 0.4 mg/kg (meperidine group, n = 30), dexmedetomidine 0.5 µg/kg (DEX I group, n = 30), 0.3 µg/kg (DEX II group, n = 30), or 0.2µg/kg (DEX III group, n = 30). Control of shivering, time taken for cessation of shivering, response rate, recurrence, hemodynamic changes, sedation score, tympanic temperature, and side effects were noted and compared between groups. Results: The groups were comparable regarding demographic profile, tympanic temperature decline, and shivering onset time (P > 0.05). Lower shivering cessation time (P < 0.001) and higher response rate (P < 0.01) were observed in DEX I and II groups compared with DEX III and meperidine groups, with a nonsignificant difference between DEX I and II groups. Recurrence of shivering activity was higher in DEX III group (36.7%, P < 0.01) compared with DEX I (10%), DEX II (6.7%) and meperidine (16.7%) groups. Lower heart rates, systolic and diastolic blood pressure mean values were recorded in DEX I group (P < 0.05). Nine patients (30%) in DEX I group were in levels 3 – 5 of sedation (P < 0.02) compared with 5 (16.66%), 2 (6.66%), and 4 (13.3) patients in DEX II, DEX III, and meperidine groups, respectively. Limitations: This study is limited by its small sample size. Conclusions: Among the 3 doses investigated, dexmedetomidine 0.3µg/kg effectively treated shivering associated with spinal anesthesia with modest hemodynamic and sedation effects. Trial Registration: ClinicalTrials.gov Identifier: NCT02382432. Key words: Dexmedetomidine, hypothermia, shivering, spinal anesthesia

Valpromide increases amplitude of heart rate circadian rhythm in remitted bipolar and unipolar disorders.A placebo-controlled study

2000 ◽  
Vol 15 (7) ◽  
pp. 424-432 ◽  
Author(s):  
P Lemoine ◽  
J Fondarai ◽  
T Faivre
Keyword(s):  
Heart Rate ◽  
Circadian Rhythm ◽  
Rating Scale ◽  
Small Sample Size ◽  
Bipolar Disorders ◽  
Small Sample ◽  
Sleep Diary ◽  
Controlled Study ◽  
Double Blind ◽  
Sleep Study

The aim of this study was to investigate for the effects of valpromide on heart rate circadian rhythm in remitted recurrent unipolar and bipolar disorders (DSM-III-R). It consisted of a comparative, randomized, double-blind, repeated cross-over study of valpromide versus placebo over four four-week periods. The primary evaluation criteria was heart rate (HR). Secondary criteria comprised motor activity (MA) and the Bech and Rafaelsen mania assessment scale, Horne and Ostberg questionnaire, Montgomery and Asberg depression rating scale, Spiegel questionnaire, a sleep diary, and Clinical Global Impression. Fifteen patients were included, giving 60 one-month periods (30 valpromide periods and 30 placebo periods).Cosinor analysis of HR and MA data revealed a difference in amplitude (P = 0.037, analysis of variance, one-tailed test).The clinical sleep study shows that the duration of sleep was greater with valpromide than with placebo (P = 0.007, one-tailed test). Similarly, evaluation of the quality of sleep by patients themselves showed valpromide to be superior to placebo (P = 0.045, one-tailed test). The results of analysis of the Spiegel questionnaire also confirm the superiority of valpromide over placebo. Safety and compliance were comparable for the active drug and the placebo.In conclusion, the relatively small sample size requires cautious interpretation of this study. Nevertheless, these initial results show a definite effect of valpromide on a biological rhythm that leads one to suppose that it may be effective through a ‘synchronizing’ effect.

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