North American Efficacy and Safety of a Novel Pediculicide Rinse, Isopropyl Myristate 50% (Resultz)

2007 ◽  
Vol 11 (5) ◽  
pp. 161-167 ◽  
Author(s):  
Nalini Kaul ◽  
Kathleen G. Palma ◽  
Stewart S. Silagy ◽  
J. John Goodman ◽  
Jack Toole
Keyword(s):  
Adverse Events ◽  
Safety Evaluation ◽  
Public Health Problem ◽  
The United States ◽  
Positive Control ◽  
Isopropyl Myristate ◽  
Head Lice ◽  
Proof Of Concept ◽  
Two Phase ◽  
End Points

Background: Head lice infestations are a major nuisance in school-aged children and are a worldwide public health problem. There are growing concerns about the effectiveness of current treatments owing to increasing resistance, safety, and patient noncompliance. A safe, easy to use, effective alternative is needed. Objective: A pediculicide rinse, 50% isopropyl myristate (IPM), was assessed in two phase 2 trials conducted in North America. The first trial was a nonrandomized (proof of concept) trial without a comparator conducted in Winnipeg, Canada. The second trial, conducted in the United States, was an evaluator-blinded, randomized superiority trial comparing 50% IPM rinse with a positive control (RID; pyrethrin 0.33%, piperonyl butoxide 4%). The primary end points were to determine the safety and efficacy of 50% IPM as a pediculicide rinse. Methods: Subjects meeting inclusion criteria were enrolled in the above-mentioned trials with efficacy end points 7 and 14 days post-treatment. Subjects were also evaluated on days 0, 7, 14, and 21 for the presence of erythema and edema using the Modified Draize Scale. Other comments associated with the safety evaluation (ie, pruritus) were collected. Results: IPM was found to be effective in the proof of concept study and comparator trial using a positive control. IPM was also well tolerated, with minimal adverse events. All adverse events were mild, resolving by completion of the study. Conclusion: Data suggest that IPM is a safe and effective therapy for the treatment of head lice in children and adults. IPM's mechanical mechanism of action makes development of lice resistance unlikely.

OBSERVE-5: Comparison of Etanercept-Treated Psoriasis Patients From Canada and the United States

2018 ◽  
Vol 22 (3) ◽  
pp. 297-303
Author(s):  
Kim A. Papp ◽  
Marc Bourcier ◽  
Yves Poulin ◽  
Charles W. Lynde ◽  
Martin Gilbert ◽  
...  
Keyword(s):  
United States ◽  
Adverse Events ◽  
Maintenance Dose ◽  
Management Strategies ◽  
The United States ◽  
Incidence Rates ◽  
Serious Adverse Events ◽  
End Points ◽  
Safety Outcome ◽  
Medical Interest

Background: OBSERVE-5 surveillance registry results evaluating etanercept safety and effectiveness in patients with moderate to severe psoriasis from Canada and the United States have been reported from data collected between May 2006 and December 2012. Although both countries have an identical indicated starting dose, the maintenance dose can differ and thus affect management strategies and outcomes. Objective: To compare the long-term safety and effectiveness outcomes of etanercept in the Canadian and US cohorts. Methods: Primary end points included exposure-adjusted event incidence rates of serious adverse events and serious infectious events. Secondary end points included exposure-adjusted event incidence rates of events of medical interest and efficacy outcomes. Results: Over 5 years, Canadian patients received a higher maintenance dose of etanercept (50 mg twice/week) more frequently than those from the United States. Safety outcome comparisons revealed that Canadian patients had a significantly lower occurrence of serious adverse events than patients from the United States, with an overall exposure-adjusted event incidence rate per 100 patient-years of 4.46 (95% confidence interval [CI], 3.05-6.29) vs 7.76 (95% CI 7.04-8.54), respectively. Serious infectious event rates were not significantly different between the 2 countries. Secondary outcomes of events of medical interest and effectiveness also did not reveal significant differences between the 2 cohorts. Conclusion: After 5 years of etanercept use, safety and effectiveness outcomes were similar between patients from Canada and the United States, with the exception of a significantly lower rate of serious adverse events in the Canadian population.

Do We have a Satisfactory Cell Viability Assay? Review of the Currently Commercially-Available Assays

2020 ◽  
Vol 17 (1) ◽  
pp. 2-22 ◽  
Author(s):  
Abdel-Baset Halim
Keyword(s):  
Cell Viability ◽  
Data Interpretation ◽  
Positive Control ◽  
Live Cells ◽  
Proof Of Concept ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Current Cell ◽  
Dying Cells ◽  
Differential Permeability

:Cell-based assays are an important part of the drug discovery process and clinical research. One of the main hurdles is to design sufficiently robust assays with adequate signal to noise parameters while maintaining the inherent physiology of the cells and not interfering with the pharmacology of target being investigated.:A plethora of assays that assess cell viability (or cell heath in general) are commercially available and can be classified under different categories according to their concepts and principle of reactions. The assays are valuable tools, however, suffer from a large number of limitations. Some of these limitations can be procedural or operational, but others can be critical as those related to a poor concept or the lack of proof of concept of an assay, e.g. those relying on differential permeability of dyes in-and-out of viable versus compromised cell membranes. While the assays can differentiate between dead and live cells, most, if not all, of them can just assess the relative performance of cells rather than providing a clear distinction between healthy and dying cells. The possible impact of relatively high molecular weight dyes, used in most of the assay, on cell viability has not been addressed. More innovative assays are needed, and until better alternatives are developed, setup of current cell-based studies and data interpretation should be made with the limitations in mind. Negative and positive control should be considered whenever feasible. Also, researchers should use more than one orthogonal method for better assessment of cell health.

An Insight Into Unani Hypoglycemic Drugs And Their Mechanism of Action

2019 ◽  
Vol 05 ◽  
Author(s):  
Sadia Nikhat ◽  
Mohd. Fazil
Keyword(s):  
Adverse Events ◽  
Scientific Evidence ◽  
Public Health Problem ◽  
Convincing Evidence ◽  
Major Public Health Problem ◽  
Significant Activity ◽  
Preparation Methods ◽  
Diabetes Mellitus Type Ii ◽  
Unani Medicine ◽  
Action Mechanisms

Background: Diabetes mellitus type-II is a major public health problem characterized by hypo-insulinemia and insulin resistance leading to hyperglycemia and its complications. In Unani medicine, it is known as ziyābetus. Several drugs are prescribed in Unani medicine as single and compound formulations for various abnormalities caused by the disease. Most of these drugs have been studied on scientific parameters and have shown significant activity in reducing the symptoms and complications of diabetes. Objectives: The literature research was planned with the objective to find out the action mechanisms of certain selected herbal drugs of Unani medicine, with evidence of their efficacy. Methods: Unani literature was first reviewed extensively and the most frequently-prescribed and easily available drugs for diabetes were selected, followed by a search on major internet search engines for scientific evidence of their efficacy alongwith information of their active ingredient and dosage. Ten drugs were selected for the present review. Results and Conclusion: There is convincing evidence to suggest that the selected drugs have a promising action against diabetes and its complications. Also, there are largely no adverse events reported and some of the preparation methods described in Unani medicine have been proven to reduce or eliminate the adverse events, if any.

scholarly journals Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review

2021 ◽  
Vol 12 ◽  
pp. 204209862095927
Author(s):  
Wei C. Yuet ◽  
Didi Ebert ◽  
Michael Jann
Keyword(s):  
Cognitive Impairment ◽  
Adverse Events ◽  
The United States ◽  
Narrative Review ◽  
Lipid Lowering ◽  
Patient Specific ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Receptor Modulation

Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed manufacturers of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors to monitor for neurocognitive adverse events due to their potent effects on LDL-C reduction, which is a proposed mechanism for neuronal cell dysfunction. Other proposed mechanisms for PCSK9 inhibitor-associated neurocognitive adverse events include N-methyl-d-aspartate receptor modulation, dysregulation of lipid and glucose metabolism, and patient-specific risk factors for cognitive impairment. The purpose of this narrative review article is to describe the proposed mechanisms, incidence of neurocognitive adverse events from phase II and III trials for PCSK9 inhibitors, neurocognitive assessments utilized in clinical trials, and clinical implications. Given the increasing prevalence of PCSK9 inhibitor use and the neurocognitive adverse events observed with prior lipid-lowering therapies, clinicians should be aware of the risks associated with PCSK9 inhibitors, especially when therapy is indicated for patients at high risk for cardiovascular events. Overall, the incidence of PCSK9 inhibitor-associated neurocognitive appears to be uncommon. However, additional prospective studies evaluating cognitive impairment may be beneficial to determine the long-term safety of these agents.

scholarly journals Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Egilius L. H. Spierings ◽  
Mikko Kärppä ◽  
Xiaoping Ning ◽  
Joshua M. Cohen ◽  
Verena Ramirez Campos ◽  
...  
Keyword(s):  
United States ◽  
Czech Republic ◽  
Adverse Events ◽  
Least Squares ◽  
The United States ◽  
Inadequate Response ◽  
Double Blind ◽  
Monthly Average ◽  
Preventive Medication ◽  
Subgroup Analyses

Abstract Background The FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes. Methods Overall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12 weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12 weeks of double-blind treatment, evaluated by country in these subgroup analyses. Results Of 14 countries contributing data, the Czech Republic (n = 188/838; 22%), the United States (n = 120/838; 14%), and Finland (n = 85/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12 weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, − 1.9 [− 3.25, − 0.47]; P = 0.009; monthly fremanezumab, − 3.0 [− 4.39, − 1.59]; P < 0.001), the United States (quarterly fremanezumab, − 3.7 [− 5.77, − 1.58]; P < 0.001; monthly fremanezumab, − 4.2 [− 6.23, − 2.13]; P < 0.001), and Finland (quarterly fremanezumab, − 3.0 [− 5.32, − 0.63]; P = 0.014; monthly fremanezumab, − 3.9 [− 6.27, − 1.44]; P = 0.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from – 5.6 to – 2.4 with quarterly fremanezumab and from − 5.3 to − 1.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups. Conclusions Monthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes. Trial registration ClinicalTrials.gov Identifier: NCT03308968.

scholarly journals The Use of the Oxygenated AirdriveTM Machine Perfusion System in Kidney Graft Preservation: A Clinical Pilot Study

2020 ◽  
Vol 61 (6) ◽  
pp. 153-162
Author(s):  
Julia H.E. Houtzager ◽  
Sebastiaan David Hemelrijk ◽  
Ivo C.J.H. Post ◽  
Mirza M Idu ◽  
Frederike J. Bemelman ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Pilot Study ◽  
Adverse Events ◽  
Deceased Donor ◽  
Kidney Graft ◽  
Machine Perfusion ◽  
End Points ◽  
Viable Solution ◽  
Technical Failures

Background: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the AirdriveTM HMP system in clinical kidney transplantation. Methods: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored. Results: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3–15 h), pressure 25 mm Hg (18–25 mm Hg), flow 49.77 mL/min (19–58 mL/min), resistance 0.57 mm Hg/min/mL (0.34–1.3 mm Hg/min/mL), and temperature 8.2 °C (2–13°C). Mean cold ischemia time (CIT) was 20.2 h (11–29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up. Conclusions: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.

scholarly journals Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score–Matched, Retrospective Cohort Analysis

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Niyati H Shah ◽  
Kathleen A Shutt ◽  
Yohei Doi
Keyword(s):  
Infective Endocarditis ◽  
Propensity Score ◽  
Adverse Events ◽  
Cohort Analysis ◽  
Hospital Readmissions ◽  
Length Of Hospital Stay ◽  
The United States ◽  
Aminoglycoside Resistance ◽  
Definitive Therapy ◽  
Significant Difference

Abstract Background Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited. Methods We conducted a retrospective, propensity score–matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes. Results A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score–matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P &lt; .0001). Conclusions Patients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score–matched EIE cohort.

scholarly journals In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine

2021 ◽  
Author(s):  
Antonio Munafò ◽  
Stefano Frara ◽  
Norberto Perico ◽  
Rosaria Di Mauro ◽  
Monica Cortinovis ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Public Health Problem ◽  
Cardiovascular Death ◽  
Regulation Of Transcription ◽  
Major Public Health Problem ◽  
Obese Patients ◽  
Ephedra Sinica ◽  
The Central Nervous System ◽  
Treatment Of Obesity

AbstractObesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

scholarly journals The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

2011 ◽  
Vol 301 (3) ◽  
pp. G401-G424 ◽  
Author(s):  
M. Andrea Azcárate-Peril ◽  
Michael Sikes ◽  
José M. Bruno-Bárcena
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Microbiota ◽  
Defense Mechanisms ◽  
High Throughput Sequencing ◽  
Safety Evaluation ◽  
Health Benefit ◽  
The United States ◽  
Dietary Factors ◽  
Colorectal Adenomas ◽  
Food Allergies

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” ( 219 ), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.

scholarly journals Validation of Sexological Worldview

SAGE Open ◽  
2012 ◽  
Vol 2 (1) ◽  
pp. 215824401243907 ◽  
Author(s):  
Justin A. Sitron ◽  
Donald A. Dyson
Keyword(s):  
Attitude Change ◽  
Service Provision ◽  
Perspective Transformation ◽  
The United States ◽  
Qualitative Approach ◽  
Second Phase ◽  
Two Phase ◽  
Convenience Sample ◽  
Developmental Characteristics ◽  
Definition Of

The authors originally posited that a new construct must be developed to measure the success of affective training for sexologists, particularly the Sexuality Attitudes Reassessment (SAR) modality. Couching their critique in studies that have been conducted to measure the SAR’s effectiveness as a method used to evoke perspective transformation and more sensitive and humanistic service provision, the authors argued that the development of a professional’s sexological worldview would be a more accurate construct than attitude change to measure when considering the outcomes of SAR training. This study in the United States used a two-phase qualitative approach to validate the proposed sexological worldview construct. In the first phase, they surveyed a panel of 16 sexologists regarding their original proposed definition of sexological worldview and refined it. In the second phase, they completed 30 one-on-one interviews with a convenience sample of sexologists and sexology students. Using an inductive content analysis of the interview transcripts, seven themes emerged in support of the proposed definition of sexological worldview, including its components and its developmental characteristics. The article concludes with a discussion of the implications for the use of the construct for the training of sexologists.

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