scholarly journals The effectiveness of combined topical product with fluocortolone pivalate and lidocaine for hemorrhoids: results of a multicenter observational study

2021 ◽  
Vol 20 (4) ◽  
pp. 70-86
Author(s):  
I. V. Kostarev ◽  
M. A. Agapov ◽  
V. S. Groshilin ◽  
L. G. Dvaladze ◽  
D. A. Tvorogov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Initial Data ◽  
Lifestyle Changes ◽  
Good Tolerability ◽  
Multicenter Observational Study ◽  
Topical Product ◽  
Days Of Therapy ◽  
Patient Questionnaires ◽  
Almost All

AIM: to assess the changes in hemorrhoids symptoms and satisfaction with treatment against the background of treatment with a combined topical product Relief® Pro.PATIENTS AND METHODS: multicenter prospective non-interventional cohort study was done in 13 clinical centers in Russia. The study included patients aged 18 to 65 years with acute hemorrhoids of stages 1–2 treated with the combined product Relief® Pro (rectal suppositories, cream or a combination thereof). The follow-up period was up to 14 days (in the case of 2 visits to the clinical center after receiving the initial data). The analysis was performed on the basis of data obtained at Visit 2 (5–7 days of therapy) and Visit 3 (10–14 days of therapy) vs the initial data (Visit 1). Following criteria were used: the severity of hemorrhoid symptoms on the Sodergren scale, the severity of hemorrhoid symptoms (pain, bleeding, itching, edema, the presence of discharge, a feeling of discomfort), the size of the largest hemorrhoid node, the satisfaction of the doctor and the patient with treatment, assessment of the patient’s adherence to recommendations for lifestyle changes and treatment, evaluation of the use of the drug Relief® were evaluated as endpoints About the treatment process and patient preferences regarding the dosage form of the prescribed drug. In addition, adverse events were evaluated.RESULTS: the study included 1000 patients aged 18 to 65 years (men — 54.5%, women — 45.5%) Patients had grade 1 acute hemorrhoids (330 patients), grade 2 acute hemorrhoids (345 patients) and exacerbation of chronic hemorrhoids (325 patients). The drug Relief® Pro rectal cream was used by 333 patients; suppositories — 383 patients; joint therapy with both dosage forms — 284 patients. During follow-up (visits 2 and 3), positive dynamics was observed in patients — a decrease in the severity of hemorrhoid symptoms both during objective examination and according to patient questionnaires. So, according to the patients’ estimates, the use of Relief® Pro, regardless of the form, led to a decrease in the severity or disappearance of the main symptoms of hemorrhoids — bleeding, itching, edema, the presence of discharge, discomfort already by Visit 2 and in almost all patients by the end of observation. A similar change of the symptoms due the digital examination: by day 5–7, the severity of edema and bleeding in the perianal region, bleeding decreased. About 96% of patients and about 97% of doctors were satisfied with the treatment. Application of both forms of Relief® The ABM was characterized by good tolerability: there were no adverse events associated, according to the researcher, with the studied drug.CONCLUSIONS: combined topical product Relief® Pro is effective for hemorrhoids.

scholarly journals RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G.F Watts ◽  
C Schwabe ◽  
R Scott ◽  
P Gladding ◽  
D Sullivan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Response ◽  
Minimal Change ◽  
Funding Source ◽  
Private Company ◽  
Good Tolerability ◽  
Duration Of Action ◽  
Mixed Dyslipidemia ◽  
Genetic Deficiency

Abstract Background Elevated LDL-C and triglyceride rich lipoproteins (TRLs) are independent risk factors for cardiovascular disease (CVD). Genetic deficiency of angiopoietin-like protein 3 (ANGPTL3) is associated with reduced circulating levels of LDL-C, triglycerides (TGs), VLDL-C, HDL-C and reduced CVD risk, with no described adverse phenotype. ARO-ANG3 is a RNA interference drug designed to silence expression of ANGPTL3. Single doses of ARO-ANG3 have been shown to reduce ANGPTL3, TGs, VLDL-C and LDL-C in healthy volunteers (HVs, AHA 2019). We report the effects of multiple doses of ARO-ANG3 in HVs with a focus on the duration of action. Methods ARO-ANG3 was administered subcutaneously to HVs on days 1 and 29 at doses of 100, 200 or 300 mg (n=4 per group). Measured parameters included ANGPTL3, LDL-C, TGs, VLDL-C and HDL-C. Follow up is ongoing. Results All HVs have received both doses and follow-up is currently through week 16 (12 weeks after second dose). Mean nadir for ANGPTL3 levels occurred 2 weeks after the second dose (−83–93%) with minimal change for 200 and 300 mg but 16% recovery for 100 mg at week 16. Mean TGs and VLDL-C reached nadir earlier (3 wks, −61–65%) without apparent dose response and minimal change for any dose at wk 16. LDL-C nadir occurred 4–6 wks after the second dose (−45–54%), again with minimal evidence for dose response or change through wk 16. HDL-C was reduced 14–37% at wk 16. ARO-ANG3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events have been headache and upper respiratory infections. Conclusions Genetic deficiency of ANGPTL3 is a cause of familial combined hypolipemia and is associated with a decreased risk of CVD. Using RNAi to selectively suppress ANGPTL3 production reproduces these genetic effects with a duration of at least 12 weeks following a second dose and with good tolerability over 16 wks. ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals

FP1-2 Implementation of duty of candor regulation within neurosurgery: a national cross-sectional survey

2019 ◽  
Vol 90 (3) ◽  
pp. e22.3-e22
Author(s):  
HJ Marcus ◽  
P Sayal ◽  
N Kitchen ◽  
B Surajit ◽  
L Thorne
Keyword(s):  
Adverse Events ◽  
Online Survey ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Statutory Duty ◽  
Safety Incident ◽  
Patient Safety Incident ◽  
Survey Responses ◽  
Almost All

ObjectivesStatutory Duty of Candor was introduced in 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons.MethodsFull members of the SBNS were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in each one whether they would trigger the process of Duty of Candor. Cases were stratified according to their likelihood and severity.ResultsIn all, 106/357 (29.7%) members participated in the survey. Responses varied widely with almost no members triggering the process of Duty of Candor in cases where adverse events were likely (>10% likelihood) and required only outpatient follow up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (<0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of Duty of Candor in cases where adverse events were unlikely (0.1%–10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%), or death (49/106; 46.2%).ConclusionsThere is considerable nationwide variation in the interpretation of definitions regarding the threshold for Duty of Candor; this has important implications with some providers at risk of penalties, and others unduly burdened by the associated administrative processes.

scholarly journals Efficacy of Transdermal Oxybutynin in the Treatment of Overactive Bladder Syndrome: Does It Make Sense Using It in 2017?

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Raúl Vozmediano-Chicharro ◽  
Blanca Madurga ◽  
Pedro Blasco
Keyword(s):  
Overactive Bladder ◽  
Adverse Events ◽  
Application Site ◽  
Overactive Bladder Syndrome ◽  
Good Tolerability ◽  
Subgroup Analyses ◽  
Voiding Diary ◽  
Previously Treated ◽  
Clinical Records

Objectives. Evaluation of changes in symptoms among patients with overactive bladder syndrome treated with transdermal oxybutynin and tolerability after 12 months of follow-up. Methods. This was a multicenter, retrospective, single-cohort, observational study. Changes in symptoms were evaluated primarily with a 3-day voiding diary. Results were compared to baseline. Subgroup analyses were performed in patients previously treated for OAB or not and aged < 65 years versus ≥65 years. Results. Clinical records of 105 patients were examined; 92.4% were women. At 12 months, 58 patients continued to receive transdermal oxybutynin. Changes in symptoms according to the voiding diary were evaluated in 47 patients. Significant improvements from baseline were observed in urinary frequency (−2.6 voids/24 hours (95% CI: −3.5; −1.8), p<0.001); daily number of urgent episodes (−4.7 episodes/day (95% CI: −6.1; −3.6), p<0.001); and urge incontinence (−1.9 episodes/day (95% CI: −2.9; −1.3), p<0.001). No statistically significant differences were found in subgroup analyses. In total, 38.1% of patients had adverse events, primarily in the application site (27.6%). No severe systemic adverse events occurred. Only 6 patients (5.7%) reported dry mouth. Conclusions. Improved symptoms and good tolerability observed after 1 year of treatment with transdermal oxybutynin shows that it currently has a place in the treatment of OAB patients.

scholarly journals The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study

2021 ◽  
Author(s):  
Kanefumi Yamashita ◽  
Yukinori Yube ◽  
Yukinao Yamazaki ◽  
Takehide Fukuchi ◽  
Masaki Kato ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Adverse Events ◽  
Advanced Parkinson’S Disease ◽  
Multicenter Observational Study ◽  
Exchange Time ◽  
Tube Exchange ◽  
The Mean ◽  
One Year ◽  
The Impact

Abstract Background Levodopa–carbidopa intestinal gel (LCIG) treatment, a new drug delivery system for patients with advanced Parkinson’s disease (PD), is covered by the health insurance in Japan since September 2016. Various LCIG procedure/device-associated adverse events (AEs) have been reported; however, reports on their treatment have been limited. This is the first multicenter study to clarify the frequency and timing of device-related AEs. Methods Between September 2016 and December 2018, 104 patients introduced to the LCIG treatment for advanced PD in 11 hospitals were included. The patients’ characteristics, AEs incidence, AEs time, and tube exchange time were investigated. Results The median follow-up period was 21.5 months. Minor AE cases were 29.4%, whereas major AE cases were 43.1%. Majority of major AEs (n = 55, 96.5%) were managed with endoscopic treatment, such as tube exchange. Few severe AEs required surgical treatment (n = 2, 3.5%). The mean (range) exposure to percutaneous endoscopic gastrojejunostomy (PEG-J) was 14.7 (0–33) months. One year after the LCIG treatment introduction, 55 patients (54.0%) retained the original PEG-J tube. The mean PEG-J tube exchange time was 10.8 ± 7.0 months in all patients, 11.6 ± 4.7 and 10.5 ± 7.7 months in patients with scheduled exchange and who underwent exchange due to AEs, respectively. Conclusions Some device-related AEs occurred during the LCIG treatment; however, only few were serious, most of which could be treated with simple procedures or tube replacement with endoscopy. Therefore, the LCIG treatment is feasible and safe and is a unique treatment option for PD, requiring endoscopists’ understanding and cooperation.

Effectiveness and Safety of Intrathecal Ziconotide: Final Results of the Patient Registry of Intrathecal Ziconotide Management (PRIZM)

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 2925-2938 ◽  
Author(s):  
Gladstone C McDowell ◽  
Michael F Saulino ◽  
Mark Wallace ◽  
Eric J Grigsby ◽  
Richard L Rauck ◽  
...  
Keyword(s):  
Adverse Events ◽  
Rating Scale ◽  
Single Agent ◽  
Pain Reduction ◽  
Patient Registry ◽  
Secondary Outcome ◽  
Intrathecal Therapy ◽  
Multicenter Observational Study ◽  
Almost All ◽  
Global Impression Of Change

Abstract Background and Objectives The Patient Registry of Intrathecal Ziconotide Management evaluated the long-term effectiveness and safety of intrathecal ziconotide. Methods The study was a prospective, multicenter observational study of intrathecal ziconotide in US clinical practice. Patients were adults with severe chronic pain that warranted intrathecal therapy. Ziconotide was initiated as the single agent in the pump; however, other intrathecal medications were permitted. The primary efficacy outcome was ≥30% reduction in numeric pain rating scale score from baseline at week 12. A secondary outcome was patient global impression of change. Adverse events were solicited at each visit. Results The registry enrolled 93 patients. Seventy-four and 28 patients completed 12 weeks and 18 months of treatment, respectively. In the overall patient population, 17.4% had ≥30% pain reduction from baseline at week 12, with a mean reduction in pain of 10.9%. At month 18, 38.5% of patients had ≥30% pain reduction from baseline, with a mean pain reduction of 24.7%. Patient-rated improvement was reported in 67% of patients at week 12 and 71% at month 18. Almost all patients experienced adverse events, the most common of which were nausea (25.8%), confusional state (22.6%), and dizziness (20.4%). Conclusions Final study analyses showed that intrathecal ziconotide provided clinically meaningful pain relief in 17.4% and 38.5% of patients at week 12 and month 18, respectively. At these same time points, patient-rated improvement was reported in at least two-thirds of patients. The safety profile was consistent with that listed in the ziconotide prescribing information.

scholarly journals RNA interference targeting apolipoprotein C-III with ARO-APOC3 in healthy volunteers mimics lipid and lipoprotein findings seen in subjects with inherited apolipoprotein C-III deficiency

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Schwabe ◽  
R Scott ◽  
D Sullivan ◽  
J Baker ◽  
P Clifton ◽  
...  
Keyword(s):  
Rna Interference ◽  
Adverse Events ◽  
Healthy Volunteers ◽  
Funding Source ◽  
Private Company ◽  
Good Tolerability ◽  
Genetic Studies ◽  
Apolipoprotein C ◽  
Increased Risk

Abstract Background Individuals with triglycerides (TGs) ≥1,000 mg/dL (11.1 mmol/L) are at increased risk of acute pancreatitis. Genetic studies indicate that individuals with apolipoprotein C-3 (APOC3) loss-of-function mutations have low TGs, reduced cardiovascular risk and no observed adverse phenotype. RNA interference (RNAi) with ARO-APOC3 has shown deep and durable knockdown (KD) of APOC3 after single doses in healthy volunteers (HVs, presented at AHA 2019) with good tolerability. We report here initial results using multiple doses of ARO-APOC3 to silence APOC3 expression in HVs. Methods ARO-APOC3 was administered subcutaneously to HVs on days 1 and 29 at doses of 10, 25 or 50 mg (n=4 per group). Measured parameters included plasma concentrations of APOC3, LDL-C, TGs, VLDL-C and HDL-C. Results All HVs have received both doses and follow-up for most parameters is available through week (wk) 14 (10 wks after second dose) for the 10 and 25 mg doses and through wk 10 for 50 mg. Mean nadir for APOC3 levels occurred at wk 3 for 10 mg (−73%) and remained similar at wk 10 (−66%), at wk 6 for 25 mg (−90%) with no change at wk 10 and at wk 2 for 50 mg (−94%) unchanged at wk 8. TGs fell faster in the 50 mg group (wk 1: 10 mg −41%; 25 mg −47%; 50 mg −72%). By wk 6 the 25 and 50 mg results were similar (−68% and −74%, respectively) and remained similar through wk 14. 10 mg was less active with a nadir of −56% and mean reductions between 42% and 56% post-nadir. VLDL-C values mirrored TGs. LDL-C reductions were more modest and did not manifest a dose response. Mean nadirs (−23–26%) occurred 4–6 wks after the first dose, again with minimal change through 10–14 wks of follow-up. Consistent with genetic studies, HDL-C increased to a maximum at approximately wk 8 (10 mg +42%, 25 mg +48%, 50 mg +84%). ARO-APOC3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events were mild injection site AEs and headache. Conclusions Genetic deficiency of APOC3 is associated with substantial reductions in TGs, VLDL-C and increases in HDL-C without an adverse phenotype. Using RNAi to selectively suppress APOC3 production mimics these lipid and lipoprotein effects, with a duration of at least 10 weeks following a second dose and with good tolerability over 16 wks using doses ranging from 10 to 50 mg. Investigation of optimal dosing regimen is ongoing, especially with respect to dosing interval. This therapeutic approach has potential for treating patients with chylomicronemia at risk of pancreatitis. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals

scholarly journals The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kanefumi Yamashita ◽  
Yukinori Yube ◽  
Yukinao Yamazaki ◽  
Takehide Fukuchi ◽  
Masaki Kato ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Adverse Events ◽  
Advanced Parkinson’S Disease ◽  
Multicenter Observational Study ◽  
Exchange Time ◽  
Tube Exchange ◽  
The Mean ◽  
One Year ◽  
The Impact

Abstract Background Levodopa–carbidopa intestinal gel (LCIG) treatment, a unique drug delivery system for patients with advanced Parkinson’s disease (PD), is covered by health insurance in Japan since September 2016. Various LCIG procedure/device-associated adverse events (AEs) have been reported; however, reports on their treatment have been limited. This is the first multicenter study to clarify the frequency and timing of device-related AEs. Methods Between September 2016 and December 2018, 104 patients introduced to the LCIG treatment for advanced PD in 11 hospitals were included. The patients’ characteristics, AEs incidence, AEs time, and tube exchange time were investigated. Results The median follow-up period was 21.5 months. Minor AE cases were 29.4%, whereas major AE cases were 43.1%. Majority of major AEs (n = 55, 94.8%) were managed with endoscopic treatment, such as tube exchange. Few severe AEs required surgical treatment (n =3, 5.2%). The mean (range) exposure to percutaneous endoscopic gastrojejunostomy (PEG-J) was 14.7 (0–33) months. One year after the LCIG treatment introduction, 55 patients (54.0%) retained the original PEG-J tube. The mean PEG-J tube exchange time was 10.8 ± 7.0 months in all patients, 11.6 ± 4.7 and 10.5 ± 7.7 months in patients with scheduled exchange and who underwent exchange due to AEs, respectively. Conclusions Some device-related AEs occurred during the LCIG treatment; however, only few were serious, most of which could be treated with simple procedures or tube replacement with endoscopy. Therefore, the LCIG treatment is feasible and safe and is a unique treatment option for PD, requiring endoscopists’ understanding and cooperation.

scholarly journals Implementation of duty of candour within neurosurgery: a national survey and framework for improved application in clinical practice

2020 ◽  
Vol 102 (2) ◽  
pp. 144-148
Author(s):  
S Basu ◽  
HJ Marcus ◽  
P Sayal ◽  
N Kitchen ◽  
R Ley ◽  
...  
Keyword(s):  
Patient Safety ◽  
Clinical Practice ◽  
Adverse Events ◽  
Online Survey ◽  
Statutory Duty ◽  
Safety Incident ◽  
Patient Safety Incident ◽  
Survey Responses ◽  
Almost All

Introduction Statutory duty of candour was introduced in November 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. However, it can be difficult to determine when the process should be implemented. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons. Materials and methods All full (consultant) members of the Society of British Neurological Surgeons were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in the case of each one whether they would trigger the process of duty of candour. Cases were stratified according to their likelihood and severity. Results In all, 106/357 (29.7%) members participated in the survey. Responses varied widely, with almost no members triggering the process of duty of candour in cases where adverse events were common (greater than 10% likelihood) and required only outpatient follow-up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (less than 0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of duty of candour in cases where adverse events were uncommon (0.1–10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%) or death (49/106; 46.2%). Conclusion There is considerable nationwide variation in the interpretation of definitions regarding the threshold for duty of candour. To this end, we propose a framework for the improved application of duty of candour in clinical practice.

scholarly journals Single-dose rufloxacin versus 3-day norfloxacin treatment of uncomplicated cystitis: clinical evaluation and pharmacodynamic considerations.

1996 ◽  
Vol 40 (2) ◽  
pp. 408-412 ◽  
Author(s):  
G Del Río ◽  
F Dalet ◽  
L Aguilar ◽  
J Caffaratti ◽  
R Dal-Ré
Keyword(s):  
Antibacterial Activity ◽  
Single Dose ◽  
Adverse Events ◽  
Drug Level ◽  
Long Term Follow Up ◽  
Almost All ◽  
Uncomplicated Cystitis ◽  
Cure Rates ◽  
Urine Levels

The efficacy and safety of rufloxacin (400 mg, single dose) were compared to those of norfloxacin (400 mg twice a day for 3 days) for the treatment of women with uncomplicated cystitis. In addition, urine levels, drug level/MIC ratio, and urine antibacterial activity 72 to 84 h after treatment initiation were determined in a subgroup of patients for pharmacodynamic assessment. A total of 203 women were included and treated in this open, randomized clinical trial; 100 patients received norfloxacin, whereas 103 received rufloxacin. Of these, 156 (74 and 82 patients in the norfloxacin and rufloxacin groups, respectively) were considered bacteriologically evaluable. At the first follow-up visits (3 to 12 days after starting the treatment), bacteriological cure rates were 99 and 94% for norfloxacin and rufloxacin, respectively. Seventy-nine percent (119 of 150) of bacteriologically cured patients attended a long-term follow-up visit (4 to 6 weeks after starting the treatment), where a relapse rate of 4% (2 of 54) and 5% (3 of 64) were found in the norfloxacin and rufloxacin groups, respectively. The pharmacodynamic evaluation performed in 35 patients showed similar median urine levels (approximately equal to 25 micrograms/ml) and urine antibacterial activity for both treatment groups against initial isolates, despite a higher norfloxacin level/MIC ratio due to the lower MIC of norfloxacin. Twenty-one patients (20%) in the rufloxacin group and 12 patients (12%) in the norfloxacin group reported 39 and 16 adverse events, respectively, almost all of them being mild and lasting < 24 h. Overall, gastrointestinal reactions were the most frequent adverse events reported. However, 12 patients treated with rufloxacin reported 15 central nervous system adverse events. This study shows that single doses of rufloxacin are as effective as a norfloxacin 3-day standard treatment in uncomplicated cystitis. The results obtained with rufloxacin are consistent with its pharmacodynamic properties.

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