scholarly journals Retrospective analysis of adverse effects associated with pyrethrins-containing products

2022 ◽  
Vol 6 ◽  
pp. 239784732110527
Author(s):  
Thomas G Osimitz ◽  
Kelly Sioris ◽  
John Gualtieri ◽  
Dean Filandrinos ◽  
Ryan Seaverson ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Telephone Interview ◽  
Significant Risk ◽  
Absolute Number ◽  
Wide Distribution ◽  
Phase Iii ◽  
Synthetic Pyrethroids ◽  
Stewardship Program ◽  
Exposed Individual ◽  
Additional Exposure

The Pyrethrins Stewardship Program (PSP) was established to better understand adverse effects following exposure to pyrethrins-containing insecticide products. Running from April 2010 through December 2016, symptomatic dermal and inhalation exposures were entered into Phase I of the PSP and analyzed for exposure details and nature of the effects reported. Phase II consisted of an in-depth telephone interview using an enhanced questionnaire to investigate additional exposure details. Phase III scored the association between exposure and reported effects. Based on the data collected and analyzed, we conclude that: (1) Both in absolute number and relative to the wide distribution and use by consumers, adverse respiratory or dermal events after product exposure were rare; (2) Most outcomes for the reported events involving either dermal or respiratory effects were of minor severity and self-limiting; (3) None of the data collected and analyzed indicate that pyrethrins-containing products, including those formulated with synthetic pyrethroids and/or synergists, pose a significant risk of serious dermal or respiratory reactions even in cases where the exposed individual reported having allergies or asthma; (4) No additional label warnings or other mitigation techniques are warranted with pyrethrins-containing products formulated with or without synthetic pyrethroids and/or synergists.

Potential of Mirabegron and its Extended-release Formulations for the Treatment of Overactive Bladder Syndrome

2020 ◽  
Vol 21 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Pankaj Mandpe ◽  
Bala Prabhakar ◽  
Pravin Shende
Keyword(s):  
Clinical Trials ◽  
Overactive Bladder ◽  
Adverse Effects ◽  
Symptomatic Relief ◽  
Phase Iii ◽  
Overactive Bladder Syndrome ◽  
Modified Release ◽  
Blurred Vision ◽  
Antimuscarinic Drugs ◽  
Tablet Dosage

Background: Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved β3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome. Objective: The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome. Results: The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting β3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.

Towards Breast Cancer Vaccines, Progress and Challenges

2019 ◽  
Vol 16 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Javad Behravan ◽  
Atefeh Razazan ◽  
Ghazal Behravan
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Cancer Vaccine ◽  
Cancer Vaccines ◽  
Weight Control ◽  
The Body ◽  
Phase Iii ◽  
Current Therapy ◽  
Surgical Ablation ◽  
Breast Cancer Vaccine

Breast cancer is the second leading cause of cancer death among women. National cancer institute of the US estimates that one in eight women will be diagnosed with breast cancer during their lifetime. Considering the devastating effects of the disease and the alarming numbers many scientists and research groups have devoted their research to fight breast cancer. Several recommendations are to be considered as preventing measures which include living a healthy lifestyle, regular physical activity, weight control and smoking cessation. Early detection of the disease by annual and regular mammography after the age of 40 is recommended by many healthcare institutions. This would help the diagnosis of the disease at an earlier stage and the start of the treatment before it is spread to other parts of the body. Current therapy for breast cancer includes surgical ablation, radiotherapy and chemotherapy which is often associated with adverse effects and even may lead to a relapse of the disease at a later stage. In order to achieve a long-lasting anticancer response with minimal adverse effects, development of breast cancer vaccines is under investigation by many laboratories. The immune system can be stimulated by a vaccine against breast cancer. This approach has attracted a great enthusiasm in recent years. No breast cancer vaccines have been approved for clinical use today. One breast cancer vaccine (NeuVax) has now completed clinical trial phase III and a few preventive and therapeutic breast cancer vaccines are at different steps of development. We think that with the recent advancements in immunotherapy, a breast cancer vaccine is not far from reach.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

Solithromycin as A Potential Novel Antibiotic Against Neisseria Gonorrhoeae Resistance

2020 ◽  
Author(s):  
Muhammad Habiburrahman ◽  
Vivian  Soetikno ◽  
Wani Riselia Sirait ◽  
Missy Savira
Keyword(s):  
Clinical Trial ◽  
Neisseria Gonorrhoeae ◽  
Wide Distribution ◽  
Phase Iii ◽  
Financial Loss ◽  
Anatomic Site ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Phase Iii Clinical Trials ◽  
New Treatment

Gonorrhea is one of the most often sexually transmitted infection in the world. In 2016, WHO stated the Southeast Asia region as the fourth-highest incidence rate and prevalence of gonorrhea. One of the current problems with gonorrhea is related to its emerging resistance to first-line drugs such as cephalosporins, macrolides, and fluoroquinolones. This resistance has an impact on the difficulty of finding effective antibiotics to eradicate the infection, thus risking financial loss and infertility in sexually active age patients. This literature review will discuss solithromycin, the first fluoroketolide in phase III clinical trial, and show its potential as a new antibiotic against infection with resistant Neisseria gonorrhoeae. Literatures are searched using Pubmed and Google Scholar search engines with keywords: antibiotics, CEM-101, clinical trial, Neisseria gonorrhoeae, new treatment, pharmacology, pharmacokinetics, resistance, safety, and solithromycin. This semisynthetic antibiotic is supported by a different chemical structure from previous macrolides; improving solithromycin becomes more stable and able to bind easier with bacterial ribosomes. Pharmacologically, solithromycin provides an advantage in its high bioavailability, easy oral administration route, wide distribution, metabolism mainly in the liver, but not required dosage adjustments due to hepatic impairment, and a single dosage preparation that can increase patient compliance in healing gonorrhea infections. Also, its lower MIC50 than previous antibiotics makes it well-tolerated, therefore making this antibiotic as a potential recommendation for the management of multi-drug resistant gonorrhea in the future. Solithromycin is not inferior to the standard therapy (ceftriaxone and azithromycin), with 80% vs. 84% gonorrhea eradication rates. Per the anatomic site, the eradication rate is 92% in genital, 94% in the pharynx, and 83% in the rectum. However, special attention needs to be paid to the side effects of the gastrointestinal tract of solithromycin, as observed in phase III clinical trials at a dose of 1000 mg in the form of diarrhea (24%) and nausea (21%).

Randomized double blind (DB) placebo (Plcb) controlled phase III study assessing the efficacy of xaliproden (X) in reducing the cumulative peripheral sensory neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in first-line treatment of patients (pts) with metastatic colorectal cancer (MCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
J. Cassidy ◽  
G. A. Bjarnason ◽  
T. Hickish ◽  
C. Topham ◽  
M. Provencio ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Significant Risk ◽  
Dose Intensity ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Grade 3

3507 Background: X, an orally administered non-peptide neurotrophic agent developed by sanofi-aventis, was shown in vitro to minimize neuritic damage induced by Ox (co-culture of Schwann cells and dorsal roots ganglia explant). The probability of occurrence of Grade (Gr) 3–4 PSN at a cumulative dose of Ox of 1000 mg/m2, was consistently reported to be of 18–20%. Methods: First line MCRC pts were randomized to receive, in a DB fashion, FOLFOX4 and either Plcb or X 1mg daily. X was administered from the 1st day of chemotherapy till 15 days post last Ox cycle. Co-primary objectives were reduction in the risk of occurrence of Gr 3–4 PSN relative to cumulative dose of Ox (Kaplan-Meier method) and non-inferiority in response rate (RR). Secondary endpoints included evaluation of sensory action potential (SAP) and safety. Results: From July 2002 to May 2004, 649 pts were randomized (324 Plcb, 325 X). Pts characteristics were well balanced across arms, median number of Ox cycles was 12 in both arms, median relative dose intensity (%) was 83.8 (Plcb) and 85.2 (X). A significant risk reduction of 39% in the probability of Grade 3–4 PSN in favor of X was reported (hazard ratio [95% CI] = 0.61 [0.40; 0.93], p= 0.0203). Overall RR [95 % CI] was: Plcb 42.6% [37.1; 48.2] and X 44.9% [39.4; 50.6]. As prospectively defined in the protocol, the lower bound of the CI of the RR ratio above 0.8 confirms noninferiority in RR (1.055 [0.88; 1.26]). In both arms the mean % of change in SAP worsens as a function of PSN severity. 17.3 (Plcb) and 13.5% (X) of the pts discontinued Ox because of PSN. Severe toxicities (% Gr 3–4), reported with a ≥2% difference between arms, were (plcb vs X): diarrhea 10.9 vs 13.0, pulmonary embolism 0.9 vs 3.1, fatigue 3.7 vs 1.5, neutropenia 43.0 vs 37.8. Conclusion: X was shown to be efficient in reducing the risk of Grade 3–4 oxaliplatin-induced PSN without impacting FOLFOX4 antitumor activity. No significant financial relationships to disclose.

Regional hyperthermia (RHT) improves response and survival when combined with systemic chemotherapy in the management of locally advanced, high grade soft tissue sarcomas (STS) of the extremities, the body wall and the abdomen: A phase III randomised pros

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10009-10009 ◽  
Author(s):  
R. D. Issels ◽  
L. H. Lindner ◽  
P. Wust ◽  
P. Hohenberger ◽  
K. Jauch ◽  
...  
Keyword(s):  
Systemic Chemotherapy ◽  
Body Wall ◽  
Locally Advanced ◽  
Significant Risk ◽  
Hazard Ratio ◽  
The Body ◽  
Phase Iii ◽  
Type I ◽  
High Grade ◽  
Free Survival

10009 Background: Patients (Pts) with locally advanced, high-grade STS are at significant risk for local failure and for metastasis. We evaluated the ability of RHT to improve the outcome in pts who are treated with neoadjuvant chemotherapy. Methods: Eligibility included pts with STS = 5 cm, grade II/III, deep and extracompartmental, stratified according to site (E = extremity vs. Non-E = body wall and abdomen). Pts were randomly assigned to systemic chemotherapy (etoposide 250 mg/m2; ifosfamide 6 g/m2; adriamycin 50 mg/m2) alone (EIA) or to systemic chemotherapy combined with RHT (EIA + RHT) administered for 4 cycles every 3 weeks both prior and after local aggressive therapy (surgery + radiotherapy), respectively. Primary endpoints were local progression free survival (LPFS) and disease free survival (DFS). Objective (CR + PR) response rate (ORR) evaluated after 4 cycles (EIA vs EIA + RHT) was a secondary endpoint. A total of 340 pts was required to show an improvement in median LPFS of 19.2 mos for EIA + RHT (a=5% type I, 20% type II error). Results: Pts characteristics were well balanced between treatment arms. After median follow-up of 24.9 months (mos) an intention-to-treat analysis showed a significantly superior DFS for pts who received EIA + RHT (n=169) compared to those treated with EIA alone (n=172) (median DFS: 31,7 mos and 16,2 mos; log-rank p=0.003; Hazard ratio=0.65; CI95=0.48- 0.87, p=0.004). The median LPFS was estimated 45,3 mos for EIA + RHT and 23,7 mos for EIA (log-rank p=0.015; Hazard ratio=0.66; CI95=0.48 - 0.90, p=0.01). At 2 years, LPFS rates for E (149 pts) and for Non-E (192 pts) were significantly better for EIA + RHT vs EIA alone (E: 84% vs 64%; Non-E: 57% vs 39%) (p<0.02). The ORR was significantly better for EIA + RHT (28,7%) vs EIA alone (12,6%) (p=0.002). Conclusions: Compared to chemotherapy alone, RHT combined with chemotherapy yields a statistically significant improvement in tumor response , DFS and LPS, in patients with locally advanced, high-grade STS. (Supported by Deutsche Krebshilfe and HGF VH-VI- 140) [Table: see text]

Retrospective analysis of risk factors for fatigue in clinical trial patients (pts) with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15624-e15624
Author(s):  
Martin Eric Gore ◽  
Viktor Gruenwald ◽  
Robert John Motzer ◽  
David I. Quinn ◽  
Brian I. Rini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Retrospective Analysis ◽  
Kinase Inhibitors ◽  
Significant Risk ◽  
Multivariate Logistic Regression Analysis ◽  
Female Gender ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Increased Risk ◽  
Ecog Ps

e15624 Background: Fatigue is a common toxicity in pts with mRCC, often associated with therapy, particularly with tyrosine kinase inhibitors (TKI). We performed a pooled retrospective analysis of pts with mRCC treated in clinical studies in order to explore predictors for fatigue. Methods: Data from pts treated in Pfizer mRCC trials (2003-2011) from phase III (NCT00083899, NCT00065468, NCT00678392) and phase II trials (NCT00054886, NCT00077974, NCT00083889, NCT00338884, NCT00137423) were included. Adverse event (CTCAE v3.0) terms of “fatigue” and “asthenia” were used. Hypothyroidism was defined as TSH>ULN or T4<LLN. A multivariate logistic regression analysis was performed to identify significant risk factors for grade (G) 2 (moderate or causing difficulty performing some ADL) or higher fatigue. Results: 2749 pts (71% male) with a median age 60 (33% ≥65) were treated (median 162 days) with axitinib (n=359), sunitinib (n=1059), temsirolimus (TEM) (n=208), interferon-alfa (IFN) (n=560), sorafenib (n=335), or TEM + IFN (n=208). Most pts had baseline ECOG PS of 0 (47%) or 1 (51%), clear cell histology (91%), and nephrectomy (84%). 553 (20%) pts reported fatigue prior to starting study therapy. During study, fatigue was reported in 1794 (65%) pts (21% G1, 26% G2, 17% G3, 1% G4); in 61% pts worst grade was reported within the first 2 months of therapy. Fatigue led to discontinuation in 2%, and dose interruption or adjustment in 8%. Of 1773 pts treated with TKIs, 42% had ≥G2 fatigue. Of pts treated with TEM, IFN or both, 39%, 50% and 50%, respectively, had ≥G2 fatigue. Baseline factors [Odds Ratio] associated (p < 0.05) with ≥G2 fatigue were pretreatment fatigue [1.7] or hypothyroidism [1.6], age ≥65 [1.6], time from diagnosis ≥1 yr [1.4], female gender [1.3], ECOG PS 0 [0.7], and Asian vs Caucasian race [0.5]. Baseline LDH, calcium, and anemia were not significant. Conclusions: Pt attributes and comorbidities at baseline, independent of therapy, are associated with increased risk of clinically significant fatigue in pts treated for mRCC, and can be used to generate a predictive model. Appropriate counseling and control of co-morbid conditions may be important in managing fatigue in pts on TKI therapy.

Focused Ultrasound Thalamotomy Sensory Side Effects Follow the Thalamic Structural Homonculus

2020 ◽  
pp. 10.1212/CPJ.0000000000001013
Author(s):  
Michelle Paff ◽  
Alexandre Boutet ◽  
Jürgen Germann ◽  
Gavin J. B. Elias ◽  
Clement T. Chow ◽  
...  
Keyword(s):  
Side Effects ◽  
Functional Connectivity ◽  
Adverse Effects ◽  
Focused Ultrasound ◽  
Univariate Analysis ◽  
Spatial Relationship ◽  
Significant Risk ◽  
Region Of Interest ◽  
Medial Lemniscus ◽  
Sensory Nucleus

AbstractIntroduction:Focused ultrasound thalamotomy is an effective treatment for tremor, however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects as well as their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML).Methods:Sensory adverse effects were categorized into four groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemi-body/limb paresthesia, and dysgeusia. Then, areas of significant risk (ASR) for each category were defined using voxel-wise mass univariate analysis and overlaid on corresponding odds ratio maps. The ASR area associated with the maximum risk was used as a region-of-interest in a normative functional connectome to determine side-effect specific functional connectivity. Finally, each ASR was overlaid on the medial lemniscus derived from normative template.Results:Of 103 patients, 17 developed sensory side effects after thalamotomy persisting 3 months after the procedures. Lesions producing sensory side effects extended posteriorly into the principle sensory nucleus of the thalamus or below the thalamus in the ML. The topography of sensory adverse effects followed the know somatotopy of the ML and the sensory nucleus. Functional connectivity patterns between each sensory-specific thalamic seed and the primary somatosensory areas supported the role of the middle insula in processing of gustatory information and in multisensory integration.Discussion:Distinct regions in the sensory thalamus and its afferent connections rise to specific sensory disturbances. These findings demonstrate the relationship between the sensory thalamus, ML, and bilateral sensory cortical areas.

scholarly journals Ocular Risk Factors for Exudative AMD: A Novel Semiautomated Grading System

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
João Pedro Marques ◽  
Miguel Costa ◽  
Pedro Melo ◽  
Carlos Manta Oliveira ◽  
Isabel Pires ◽  
...  
Keyword(s):  
Risk Factors ◽  
Significant Risk ◽  
Absolute Number ◽  
Grading System ◽  
Exudative Amd ◽  
Innovative Methodology ◽  
The Absolute ◽  
Fundus Photographs

Purpose. To evaluate the contribution of the ocular risk factors in the conversion of the fellow eye of patients with unilateral exudative AMD, using a novel semiautomated grading system. Materials and Methods. Single-center, retrospective study including 89 consecutive patients with unilateral exudative AMD and ≥3 years of followup. Baseline color fundus photographs were graded using an innovative grading software, RetmarkerAMD (Critical Health SA). Results. The follow-up period was 60.9±31.3 months. The occurrence of CNV was confirmed in 42 eyes (47.2%). The cumulative incidence of CNV was 23.6% at 2 years, 33.7% at 3 years, 39.3% at 5 years, and 47.2% at 10 years, with a mean annual incidence of 12.0% (95% CI= 0.088–0.162). The absolute number of drusen in the central 1000 and 3000 μm (P<0.05) and the absolute number of drusen ≥125 µm in the central 3000 and 6000 µm (P<0.05) proved to be significant risk factors for CNV. Conclusion. The use of quantitative variables in the determination of the OR of developing CNV allowed the establishment of significant risk factors for neovascularization. The long follow-up period and the innovative methodology reinforce the value of our results. This trial is registered with ClinicalTrials.gov NCT00801541.

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