Pharmacokinetics and Safety Assessment of Anti-HIV Dapivirine Vaginal Microbicide Rings with Multiple Dosing

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Ex Vivo ◽  
Oral Treatment ◽  
Plasma Concentrations ◽  
Vaginal Ring ◽  
Vaginal Fluid ◽  
Cervical Tissue ◽  
Double Blind ◽  
Group A ◽  
Group B ◽  
Anti Hiv

Objectives: Self-administered vaginal rings are a promising method for delivery of topical anti-HIV microbicidesand might offer an adherence advantage over daily or coitally-dependent dosage forms such as gels. This trialassessed the safety and pharmacokinetic aspects of the Dapivirine Vaginal Ring-004 when worn as multiple rings oversequential periods of ring use by healthy, sexually-active, HIV-negative women.Methods: This double-blind trial was conducted among 48 women (18-40 years). Participants were randomlyassigned to two groups (A or B) and received (3:1) either the dapivirine or a placebo vaginal ring. Group A used tworings over a 56-day period and Group B used three rings over a 57-day period. Safety evaluations were conductedthroughout the trial. Dapivirine concentrations were measured in plasma, vaginal fluid and cervical tissue samplescollected during and after the 56 days (Group A) or 57 days (Group B) of vaginal ring use.Results: Ring-004 was safe and well tolerated in all participants. The pharmacokinetic profile demonstrated arapid increase in plasma and vaginal fluid concentrations and achieved concentrations in vaginal fluids and cervicaltissue well above the in vitro IC99 in cervical tissue (3.3 ng/mL) that were sustained for a 28 to 35-day ring use period(approximately 3000 times higher in vaginal fluids and 14 -1000 times higher in cervical tissue). Drug levels wereassociated with significant inhibitory activity of genital secretions against HIV ex vivo, a biomarker of pharmacodynamics.Individual plasma dapivirine concentrations did not exceed 553 pg/mL and were well below plasma concentrations atthe maximum tolerated dose for oral treatment (mean Cmax 2286 ng/mL).Conclusions: The consecutive use of several rings over a period of up to 57 days was safe and well tolerated, andPK data indicate that a single Ring-004 is likely to be protective for at least 35 days.

Pregabalin As A Premedicant To Attenuate Pressor Response In Patients Undergoing Laparoscopic Cholecystectomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

2020 ◽  
Vol 11 (3) ◽  
pp. 3418-3423
Author(s):  
Sweety Agrawal ◽  
Shubdha Bhagat ◽  
Pratibha Deshmukh ◽  
Amol Singham
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Pressor Response ◽  
Controlled Study ◽  
Double Blind ◽  
Co2 Insufflation ◽  
Ramsay Sedation Scale ◽  
Minute Interval ◽  
Group A ◽  
Group B ◽  
Induction Of Anaesthesia

The present study was done to evaluate the ability of oral pregabalin to attenuate the pressor response to airway instrumentation in patients undergoing laparoscopic cholecystectomy under general anesthesia. Sixty-four adult patients aged between 25-55 year of either gender belonging to ASA-1 or ASA2 physical status weighing 50-70 kg were enrolled in this study. Thirty-two patients each were randomized to group A, or group B. Patients in group A received tablet Pregabalin (150mg) and those in group B received placebo orally one hour before induction of anaesthesia. Heart rate, blood pressure, and sedation were assessed preoperatively before giving the tablets and after 30 minutes, and just before induction of anaesthesia. Intraoperative, pulse rate, mean arterial pressure, ECG in the lead II, SPO2 and ETCO2 were monitored. All the above parameters were noted during laryngoscopy and intubation, 3 minutes after CO2 insufflation, and then at every 10-minute interval till the end of surgery. These parameters were also recorded after extubating the patient. The Ramsay sedation scale was used to assess the sedation at the baseline, one hour after drug intake , one hour after extubation and 4 hour after surgery. Any adverse effects in the postoperative period were recorded. The result of our study shows that pre-emptive administration of oral pregabalin 150 mg significantly reduced the pressor response at the time of laryngoscopy and intubation, after CO2 insufflation and just after extubation. We conclude that oral pregabalin premedication is effective in successful attenuation of hemodynamic pressor response to laryngoscopy, intubation and pneumoperitoneum in patients undergoing laparoscopic cholecystectomy

Comparison of the effects of Dexamethasone and Ondansetron on the Reduction of Postoperative Nausea and Vomiting following Cesarean Section under Spinal Anesthesia

2020 ◽  
Vol 15 ◽  
Author(s):  
Arash karimi ◽  
Jahanbakhsh Nejadi ◽  
Mahnaz Shamseh ◽  
Nooshin Ronasi ◽  
Mehdi Birjandi
Keyword(s):  
Cesarean Section ◽  
Spinal Anesthesia ◽  
Postoperative Nausea ◽  
Demographic Data ◽  
Postoperative Nausea And Vomiting ◽  
Nausea And Vomiting ◽  
Elective Cesarean Section ◽  
Double Blind ◽  
Group A ◽  
Group B

Background: Postoperative nausea and vomiting (PONV) is a common complication associated with the use of anesthesia. Several antiemetics are used to reduce the incidence and severity of PONV. The aim of this study is to investigate the role of dexamethasone and ondansetron to treat PONV in patients undergoing cesarean section (c-section) under spinal anesthesia. Methods: This double-blind clinical trial study was performed on patients who were referred to the operating room of Haji Karim Asali Hospital of Khorramabad for elective cesarean section in 2016-17. Upon meeting the inclusion criteria, patients were allotted into two groups (n=60). Group A received 8mg of dexamethasone and group B received 4mg of ondansetron after spinal anesthesia. The Visual Analog Scale (VAS) questionnaire and Depression-Anxiety-Stress Scale (DASS) questionnaire was used for the analysis. Patients with mild to moderate stress, anxiety, and depression were included in the study. Data were analyzed using SPSS 16 software. Results: There was no difference in the demographic data of the two groups. The mean severity of nausea in group A was significantly higher than in group B. The frequency of vomiting in group A was 20 times higher than group B, which was found to be statistically significant, p = 0.018. Concerning the type of delivery with the frequency of nausea, the results showed that the frequency of nausea in group A was 3.24 times higher than group B, however, this difference was not statistically significant, p = 0.106. Conclusion: Based on the results of this study, ondansetron had a significant effect on the alleviation of postoperative nausea and vomiting, as compared to dexamethasone in c-section surgical candidates.

Histopathological analysis of incompetent great saphenous veins after mechanochemical ablation treatment – An ex-vivo experiment

Vascular ◽  
2021 ◽  
pp. 170853812110076
Author(s):  
Bo Yang ◽  
Qiang-Qiang Nie ◽  
Xue-Qiang Fan ◽  
Jian-Bin Zhang ◽  
Peng Liu
Keyword(s):  
Ex Vivo ◽  
Endothelial Damage ◽  
Statistical Result ◽  
Histopathological Analysis ◽  
Saphenous Veins ◽  
Mechanochemical Ablation ◽  
Group A ◽  
Endothelium Damage ◽  
Group B ◽  
Group D

Background The endovascular technique of mechanochemical ablation (MOCA) has become popular in treating patients with saphenous reflux. We reported the histopathological findings in human ex-vivo incompetent great saphenous veins following treatment with saline, polidocanol, mechanical ablation and MOCA using ClariVein device. Methods Twenty-four vein GSV specimens were obtained via traditional surgery and treated with four methods: Group A: 0.9% normal saline (NS); Group B: 3% polidocanol; Group C: mechanical ablation + 0.9% NS; Group D: mechanical ablation + 3% polidocanol (MOCA). Hematoxylin and eosin (HE), Masson’s trichrome and immunohistochemical staining were performed on each specimen and integrated optical densities were measured with vWF and a-SMA stains and statistically evaluated. vWF staining was used to assess endothelial damage and a a-SMA staining was used to assess media injury. Results HE and Masson’s trichrome staining of Groups C and D revealed severe damage to the endothelium and media compared to Groups A and B. The statistical result of vWF staining showed the damage of endothelium was significantly increased by Group D compared to Groups A, B and C. The statistical result of a-SMA staining showed the damage of media was significantly increased by Groups C and D compared to Groups A and B. Conclusions The mechanism of MOCA was caused by both endothelium damage and media tearing. The damage of endothelium was significantly increased by MOCA when compared with mechanical ablation alone.

The effect of external ventricular drain tunneling length on CSF infection rate in pediatric patients: a randomized, double-blind, 3-arm controlled trial

2021 ◽  
pp. 1-8
Author(s):  
Esmaeil Mohammadi ◽  
Sara Hanaei ◽  
Sina Azadnajafabad ◽  
Keyvan Tayebi Meybodi ◽  
Zohreh Habibi ◽  
...  
Keyword(s):  
Infection Rate ◽  
Pediatric Patients ◽  
Controlled Trial ◽  
External Ventricular Drain ◽  
Hazard Ratio ◽  
Spontaneous Discharge ◽  
Standard Group ◽  
Double Blind ◽  
Group A ◽  
Group B

OBJECTIVE The role of tunneling an external ventricular drain (EVD) more than the standard 5 cm for controlling device-related infections remains controversial. METHODS This is a randomized, double-blind, 3-arm controlled trial done in the Children’s Medical Center in Tehran, Iran. Pediatric patients (< 18 years old) with temporary hydrocephalus requiring an EVD and no evidence of CSF infection or prior EVD insertion were enrolled. Patients were randomly assigned (1:1:1) into the following arms: 5-cm (standard; group A); 10-cm (group B); or 15-cm (group C) EVD tunnel lengths. The investigators, parents, and person performing the analysis were masked. The surgeon was informed of the length of the EVD by the monitoring board just before operation. Patients were followed until the EVD’s fate was established. Infection rate and other complications related to EVDs were assessed. RESULTS A total of 105 patients were enrolled in three random groups (group A = 36, group B = 35, and group C = 34). The EVD was removed because there was no further need in most cases (67.6%), followed by conversion to a new EVD or ventriculoperitoneal shunt (15.2%), infection (11.4%), and spontaneous discharge without further CSF diversion requirement (5.7%). No statistical difference was found in infection rate (p = 0.47) or EVD duration (p = 0.81) between the three groups. No group reached the efficacy point sooner than the standard group (group B: hazard ratio 1.21, 95% CI 0.75–1.94, p = 0.429; group C: hazard ratio 1.03, 95% CI 0.64–1.65, p = 0.91). CONCLUSIONS EVD tunnel lengths of 5 cm and longer did not show a difference in the infection rate in pediatric patients. Indeed, tunneling lengths of 5 cm and greater seem to be equally effective in preventing EVD infection. Clinical trial registration no.: IRCT20160430027680N2 (IRCT.ir)

scholarly journals Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (7) ◽  
pp. 4068-4074 ◽  
Author(s):  
Stefano Palomba ◽  
Francesco Orio ◽  
Angela Falbo ◽  
Francesco Manguso ◽  
Tiziana Russo ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Controlled Clinical Trial ◽  
Line Treatment ◽  
First Line ◽  
Ovary Syndrome ◽  
Double Blind ◽  
Group A ◽  
Group B ◽  
First Line Treatment

Abstract Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P &lt; 0.001). Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

scholarly journals Effects of Dexmedetomidine on Intraoperative Hemodynamic Responses in Patients Undergoing Laparoscopic Cholecystectomy: A Randomised Double Blind Trial

2021 ◽  
Author(s):  
Dhanashree Dongare ◽  
Smita Gharde
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Base Line ◽  
Loading Dose ◽  
Double Blind Trial ◽  
Hemodynamic Responses ◽  
Double Blind ◽  
Significant Difference ◽  
Group A ◽  
American Society ◽  
Group B

Background: Dexmedetomidine is selective alpha 2 agonist with sedative sympatholytic, analgesic properties and is used as an anaesthetic adjuvant. We have evaluated the effect of dexmedetomidine on various hemodynamic responses to incidences such as laryngoscopy, endotracheal intubation, exubation and pneumoperitoneum in patients who were undergoing surgeries like laparoscopic cholecystectomy. We have used loading dose of 0.5mcg/kg of inj. Dexmedetomidine given over 10 minutes followed by infusion of a dose of 0.3mcg/kg/hour for the control of hemodynamic response to laparoscopy. Methods: Patient of either sex aged between 18-50 yrs, belongs to ASA I and II (AMERICAN SOCIETY OF ANAESTHESIOLOGY) posted for laparoscopic cholecystectomy were included. Institutional ethical committee clearance was obtained prior to study. After enrolment and valid written consent was taken. 60 patients were enrolled written valid informed consent was taken. Patients were divided into two groups 30 each with computerized randomization. Base line parameters were noted. Observer and patient was blinded for the content of syringe. Group A received injection dexmedetomidine and group B received bolus and infusion of normal saline at same rate. Routine general anaesthesia was instituted. Parameters were noted after induction, after intubation, after co2 insufflation, after 20 min, after 40 min, after co2 deflation, after extubation, after 1 and 2 hrs post-extubation. Results: Group A showed significantly less rise in HR and MAP than Group B. Requirement of intraoperative propofol was more in Group B. There was no significant difference for time taken to awakening in both groups. Conclusion: We found Injection Dexmedetomidine in given doses gave good hemodynamic control with minimal undesired effects during laparoscopy.

Comparative Study Between Dexmedetomidine and Fentanyl as Sedatives in Awake Fiberoptic Intubation in Cervical Spine Surgeries

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Waleed Mohamed Abd El Mageed ◽  
Ahmad Kamal Mohamed Ali ◽  
Eeman Aboubakr ElSiddik Ahmed Bayoumi ◽  
Haitham Sabry Mahmoud Omar
Keyword(s):  
Cervical Spine ◽  
Sedation Score ◽  
Fiberoptic Intubation ◽  
Intubation Time ◽  
Hemodynamic Stability ◽  
Double Blind ◽  
Hemodynamic Variables ◽  
Group A ◽  
Group B ◽  
Awake Fiberoptic Intubation

Abstract Background Various drugs are used for providing favorable intubation conditions during awake fiberoptic intubation (AFOI). However, most of them have various side effects. Aim The aim of this study was to compare the effects of dexmedetomedine and fentanyl as regards sedative effects, hemodynamic stability, intubation time and intubation attempts success during awake fiberoptic intubation. Material and Methods A randomized double-blind prospective study was conducted on a total of 40 patients scheduled for elective cervical spine surgeries who were randomly allocated into two equal groups (n 20): (group A) patients received a bolus dose of dexmedetomidine of 1 mcg/kg over 10 min followed by a continuous infusion of dexmedetomidine at 0.5 mcg/kg/h. and fentanyl group (group B) received dose of 1 μg/kg over 10 min followed by 0.5 μg/kg/hr. Sedation score (Ramsy sedation score), hemodynamic variables, oxygen saturation, intubation time and intubation attempts were noted and compared between the two groups. Results Ramsy Sedation Score was significantly favorable (P &lt; 0.001) in group A in comparison to group B, moreover better hemodynamic stability during intubation (P &lt; 0.05) and less intubation attempts were observed in group A in comparison to group B. Conclusion The results of our study showed that dexmedetomidine provides optimum sedation without compromising airway or hemodynamic stability and with favorable intubation time and less intubation attempts during AFOI in comparison to fentanyl.

The role of tolvaptan in prevention of hyponatremia in patients undergoing transurethral resection of prostate surgery- A randomized double blind study

2021 ◽  
Vol 8 (2) ◽  
pp. 321-325
Author(s):  
Dinesh Kumar Singh ◽  
B B Baj ◽  
Vipin Goyal
Keyword(s):  
Transurethral Resection ◽  
Blind Study ◽  
Transurethral Resection Of Prostate ◽  
Double Blind Study ◽  
Double Blind ◽  
Significant Difference ◽  
Group A ◽  
The Mean ◽  
Group B

The aim of our study to determine the role of tolvaptan in prevention of hyponatremia in transurethral resection of prostate surgery. This is randomized double-blind study conducted in 60 ASA grade status 1 and 2 patients age group between 45-80 yrs undergoing TURP under spinal anaesthesia in urology operation theatre in Mahatma Gandhi hospital Jaipur after receiving permission from hospital ethical committee. A detailed history, complete physical examination and routine investigation were done for all patients followed by informed written consent was obtained. Patients are randomly divided into 2 groups. In group A -30 patients who received orally tab tolvaptan 15 mg and group B-30 patients who received orally tab multivitamin 2 hrs before surgery after doing electrolytes of the patients in the morning. In both groups age (in yrs), wt (in kg), ASA grade, volume of irrigating fluid (in litres), volume of prostate resected (in gm) and duration of surgery (in minutes) all demographic and surgical details data were compared. Electrolytes were compared in both groups pre and post-operatively and statistical analysis was done.There was significant difference in post-operative sodium level between the two groups (A and B). The mean level of sodium significantly reduced post-operatively in group –B (control grp). The mean level of sodium significantly increased post-operatively in group –A (tolvaptan grp). We conclude single dose of tolvaptan -15 mg found to effective in prevention of hyponatremia in patients undergoing TURP.

scholarly journals Use of Warm Local Anaesthetic Solution for Caudal Blocks

1992 ◽  
Vol 20 (4) ◽  
pp. 453-455 ◽  
Author(s):  
E. T. M. Lim ◽  
K. Y. Chong ◽  
B. Singh ◽  
W. Jong
Keyword(s):  
Adverse Effects ◽  
Local Anaesthetic ◽  
Room Temperature ◽  
Double Blind Study ◽  
Double Blind ◽  
Anaesthetic Solution ◽  
Group A ◽  
Group B ◽  
Local Anaesthetic Solution ◽  
Speed Of Onset

A double-blind study was undertaken to investigate the effect of prewarmed local anaesthetic solution on the latency of onset of caudal blocks. Forty-four (ASA I-II) patients were allocated into two equal groups. In Group A, the local anaesthetic solutions were injected at room temperature (25°C), while in Group B, they were injected at 37°C. All the caudal blocks were performed using 20 ml of lignocaine 1.5% with adrenaline 1:200,000. The speed of onset of perianal analgesia was found to be significantly faster (39%) with the prewarmed local anaesthetic solution (P < 0.05). No adverse effects were observed.

scholarly journals EMLA Cream Prior to Insertion of Elective Epidurals

1995 ◽  
Vol 23 (3) ◽  
pp. 339-341 ◽  
Author(s):  
J. A. Elson ◽  
M. J. Paech
Keyword(s):  
Elective Caesarean Section ◽  
Needle Insertion ◽  
Patient Comfort ◽  
Epidural Needle ◽  
Double Blind Study ◽  
Double Blind ◽  
Emla Cream ◽  
Skin Infiltration ◽  
Group A ◽  
Group B

A randomized double-blind study was conducted in 83 women scheduled for elective caesarean section to determine the efficacy of EMLA and lignocaine infiltration for epidural insertion. The patients were randomly allocated to one of three groups: Group A (EM/LIG) received EMLA and intradermal and subdermal 1% lignocaine infiltration, Group B (EM/SAL) EMLA and saline while Group C (PL/LIG) received placebo cream and 1% lignocaine. Assessments using a 100 mm pain score were performed on skin infiltration and after subsequent insertion of a 16 gauge Tuohy needle into the supraspinous ligament. Skin changes under the applied cream and nursing rating of patients’ response were also noted. Statistical analyses were performed using Kruskal-Wallis and Fisher's Exact Tests. Groups were comparable for age, weight, parity and EMLA application time (interquartile range 105-150 minutes) There were significantly higher pain scores for skin infiltration in Group C (PL/LIG) (P<0.01) and for epidural needle insertion in Group B (EM/SAL) (P<0.05). We concluded that in this patient population, the application of EMLA cream for at least 90 minutes plus 1% lignocaine infiltration optimized patient comfort for epidural insertion.

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