scholarly journals 0743 The Pharmacokinetic Adverse Event Relationship for FT218, a Once-Nightly Sodium Oxybate Formulation

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A282-A283
Author(s):  
D Seiden ◽  
J Grassot ◽  
D Monteith ◽  
J Dubow
Keyword(s):  
Adverse Event ◽  
Sodium Oxybate ◽  
Clear Correlation ◽  
Release Formulation ◽  
Crossover Studies ◽  
Gamma Hydroxybutyrate ◽  
Scatter Plots ◽  
The Mean ◽  
Favorable Safety ◽  
System Organ

Abstract Introduction Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The approved formulation requires twice-nightly dosing: at bedtime and 2.5 - 4 hours later, which results in two distinct Cmax’s. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology. The objective of this study was to evaluate the pharmacokinetic-adverse event (AE) relationship for FT218, an investigational once-nightly sodium oxybate formulation. Methods Six single-dose, randomized, crossover studies that assessed the pharmacokinetics of FT218 at 4.5, 6, 7.5 and 9 g in healthy voluntters were used in this analysis. Lattice plots, “spaghetti” plots, and scatter plots of individual gamma hydroxybutyrate concentrations and indicators when AEs by system, organ, or class (SOC) were created to determine any PK-AE relationship. Results A total of 129 healthy volunteers received single doses of FT218 between 4.5 - 9 g. Most AEs, specifically for the neurological and gastrointestinal SOC, occurred close to Tmax, during the Cmax period, which for FT218 was around 1.5-2 hours after dosing. These AEs were known AEs associated with sodium oxbyate. There appeared to be no clear correlation between individual plasma GHB concentrations levels and AEs between subjects. Individual AEs were equally distributed above and below the mean population Cmax and AUCinf for the dataset. Conclusion In general, adverse events for FT218 occurred around Tmax. There was no clear population toxicokinetic range for when AEs occur with FT218, but mostly individual thresholds. Since it appears AEs are related to Cmax, and FT218 only has one Cmax compared to two with the currently available product, it is hypothesized that FT218 will have a favorable safety profile compared to twice-nightly dosing. Support This work was supported by Avadel Pharmaceuticals

Descriptive statistics

2017 ◽  
Author(s):  
Andrew Gelman ◽  
Deborah Nolan
Keyword(s):  
Descriptive Statistics ◽  
Metabolic Rates ◽  
World Record ◽  
Linear Combinations ◽  
Record Times ◽  
Starting Point ◽  
Statistics Course ◽  
Scatter Plots ◽  
Economic Indexes ◽  
The Mean

Descriptive statistics is the typical starting point for a statistics course, and it can be tricky to teach because the material is more difficult than it first appears. The activities in this chapter focus more on the topics of data displays and transformations, rather than the mean, median, and standard deviation, which are covered easily in a textbook and on homework assignments. Specific topics include: distributions and handedness scores; extrapolation of time series and world record times for the mile run; linear combinations and economic indexes; scatter plots and exam scores; and logarithmic transformations and metabolic rates.

scholarly journals Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis

2015 ◽  
Vol 35 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Raja Zabaneh ◽  
Simon D. Roger ◽  
Mohamed El-Shahawy ◽  
Michael Roppolo ◽  
Grant Runyan ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Adverse Event ◽  
Peritoneal Dialysis ◽  
Kidney Disease ◽  
Common Adverse Event ◽  
Erythropoietin Receptor ◽  
Open Label ◽  
Evaluation Period ◽  
Red Blood Cell Transfusions ◽  
The Mean

♦BackgroundPeginesatide is a novel, synthetic, peptide-based pegylated erythropoiesis-stimulating agent that is designed specifically to stimulate the erythropoietin receptor. The purpose of the present study was to assess, for the first time, the efficacy and safety of peginesatide in chronic kidney disease (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin treatment.♦MethodsIn this open-label multicenter study, 59 PD patients with CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide. Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL during the 25 weeks of the study. The primary endpoint was change from baseline in mean hemoglobin values during the evaluation period (weeks 20 – 25).♦ResultsThe mean hemoglobin value during the evaluation period was 11.3 ± 1.07 g/dL, and the mean change from baseline was 0.10 ± 1.15 g/dL (95% confidence limits: –0.24, 0.44 g/dL). During the evaluation period, most patients maintained hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within ±1.0 g/dL of baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients (72.9%) completed the study. Six patients (10.2%) received red blood cell transfusions. The observed adverse event profile was consistent with underlying conditions in the PD patient population. The most common adverse event was peritonitis (20.3%), a complication commonly associated with PD. Four deaths occurred during the study (2 related to septic shock, and 1 each to myocardial ischemia and myasthenia gravis).♦ConclusionsIn this study, once-monthly peginesatide maintained hemoglobin levels in PD patients after conversion from epoetin.

The Race for Online Reputation: Implications for Platforms, Firms, and Consumers

2021 ◽  
Author(s):  
Mingwen Yang ◽  
Zhiqiang (Eric) Zheng ◽  
Vijay Mookerjee
Keyword(s):  
Adverse Event ◽  
Marketing Mix ◽  
Digital Economy ◽  
The Other ◽  
The Mean ◽  
The Absolute ◽  
The Cost ◽  
Online Reputation ◽  
Better Than

Online reputation has become a key marketing-mix variable in the digital economy. Our study helps managers decide on the effort they should use to manage online reputation. We consider an online reputation race in which it is important not just to manage the absolute reputation, but also the relative rating. That is, to stay ahead, a firm should try to have ratings that are better than those of its competitors. Our findings are particularly significant for platform owners (such as Expedia or Yelp) to strategically grow their base of participating firms: growing the middle of the market (firms with average ratings) is the best option considering the goals of the platform and the other stakeholders, namely incumbents and consumers. For firms, we find that they should increase their effort when the mean market rating increases. Another key insight for firms is that, sometimes, adversity can come disguised as an opportunity. When an adverse event strikes the industry (such as a reduction in sales margin or an increase in the cost of effort), a firm’s profit can increase if it can manage this event better than its competitors.

Mechanism of action of narcolepsy medications

CNS Spectrums ◽  
2014 ◽  
Vol 19 (S1) ◽  
pp. 25-34 ◽  
Author(s):  
Chandan R. Gowda ◽  
Leslie P. Lundt
Keyword(s):  
Neuronal Activity ◽  
Mechanism Of Action ◽  
Tricyclic Antidepressants ◽  
Sodium Oxybate ◽  
Side Effect Profile ◽  
First Line ◽  
Excessive Sleepiness ◽  
Gamma Hydroxybutyrate ◽  
Clinical Strategies ◽  
Tuberomamillary Nucleus

The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.

Crisis in Admission Beds

1995 ◽  
Vol 167 (6) ◽  
pp. 765-769 ◽  
Author(s):  
Robin B. Powell ◽  
Doris Hollander ◽  
Robert I. Tobiansky
Keyword(s):  
National Health Service ◽  
Health Service ◽  
National Health ◽  
Corrective Action ◽  
Clear Correlation ◽  
Bed Occupancy ◽  
Careful Monitoring ◽  
Psychiatric Units ◽  
The Mean ◽  
Occupancy Rates

BackgroundThis study was carried out to measure bed occupancy in Greater London's psychiatric units, in response to the apparent shortage of admission beds.MethodThe bed occupancy of London's 54 National Health Service (NHS) acute psychiatric units within 29 districts was ascertained by telephone on 16 bank holidays covering the period 1990–93.ResultsThe mean occupancy level for all London over the 4 years was 97.54% (95% CI = ±0.94%). The number of beds occupied in inner London was significantly greater (99.79 ± 1.11%) than in outer London (95.1 ± 1.49%) (t = 3.85, d.f. = 462, P < 0.001). Bed occupancy for inner London units was ≥ 100% on over 49% of occasions. There has been a steady decline in the number of beds over the four-year period. There was a clear correlation between occupancy levels and the Jarman UPA8 Underprivilege Score (r = 0.504) and between bed provision and the UPA8 (r = 0.67).ConclusionOccupancy rates have become unacceptably high and require careful monitoring. Corrective action may be required in order to prevent a breakdown in services.

Myeloperoxidase deficiency in dogs observed with the ADVIA®120

2010 ◽  
Vol 38 (03) ◽  
pp. 139-146 ◽  
Author(s):  
J. Richartz ◽  
N. Bauer ◽  
A. Moritz ◽  
S. Klenner
Keyword(s):  
Screening Tool ◽  
High Standard ◽  
Pancreatic Abscess ◽  
High Standard Deviation ◽  
Diagnostic Use ◽  
Cellular Volume ◽  
Myeloperoxidase Deficiency ◽  
Scatter Plots ◽  
The Mean

Summary Objective: In contrast to humans, neutrophil myeloperoxidase deficiency (MPOD) has been rarely investigated in dogs. The hematology analyzer ADVIA®120 differentiates leukocytes based on the cellular volume and their myeloperoxidase concentration. The aim of this study was the characterization of myeloperoxidase deficiency in dogs and the evaluation of the diagnostic use of the ADVIA®120 Myeloperoxidase Index (MPXI). Material and methods: ADVIA® peroxidase scatter plots indicative of MPOD were reviewed. Severity of MPOD was classified semiquantitatively in three groups (MPOD grade 1–3): MPOD grade 1 (MPOD-1): neutrophils showing an abnormal shift of the population, < 25% extending in the monocyte cluster and therefore misclassified, MPOD-2: ~25–50% of neutrophils misclassified, MPOD-3: 50–100% of the neutrophils misclassified due to their location in the monocyte cluster. Sex, age, and breed of the dogs as well as diagnosis, and MPXI were recorded. Results: 29 dogs (nine females and 20 males belonging to 23 breeds) with 38 analyses consistent with MPOD were found. Diseases were characterized by severe leukocyte consumption and included mainly parvovirosis (8/29), DIC/sepsis (3/29), pyometra, pyothorax, pneumonia, pancreatic abscess, and cystitis. A significantly lower mean MPXI in MPOD-3 was present in comparison to the mean MPXI of MPOD-1 (p < 0.05), however, there was a great overlap between the groups. Conclusion: Diseases associated with neutrophil consumption may show an acquired MPOD in dogs. High standard deviation limits the diagnostic use of the MPXI for detection of MPOD. Clinical relevance: The ADVIA®120 cytograms are a good screening tool for detection of MPOD in dogs, but the use of the MPXI is impaired in this species.

scholarly journals Infrared Thermography Follow-Up After Lower Limb Revascularization

2020 ◽  
pp. 193229682091231
Author(s):  
Arjaleena Ilo ◽  
Pekka Romsi ◽  
Matti Pokela ◽  
Jussi Mäkelä
Keyword(s):  
Skin Temperature ◽  
Infrared Thermography ◽  
Lower Limb ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Clear Correlation ◽  
Before And After ◽  
Patients With Diabetes ◽  
The Mean

Background: The purpose of this study was with a simple clinical setting to compare skin temperature changes in the feet before and after revascularization and to identify possible correlation between ankle brachial index (ABI) and toe pressure (TP) values and foot skin temperature patient with and without diabetes. Methods: Forty outpatient clinic patients were measured ABI, TP, and the skin temperature using infrared thermography (IRT) at the foot before and after revascularization. Patients in the revascularization group were divided into subgroups depending on whether they had diabetes or not and a wound or not. Results: There were clear correlation between increase of ABI and TP and increase of the mean skin temperature on the feet after revascularization. The temperature was higher and the temperature change was greater among patients with diabetes. Side-to-side temperature difference between the revascularized feet and contralateral feet decreased after treatment. The mean temperature was higher in the feet with wound whether patient had diabetes mellitus or not. Conclusion: The simple, prompt, and noninvasive IRT procedure showed its potential as a follow-up tool among patients with diabetes or peripheral arterial disease and previous lower limb revascularization.

Phase I/II Study of Galiximab, an Anti-CD80 Antibody, for Relapsed or Refractory Follicular Lymphoma

2005 ◽  
Vol 23 (19) ◽  
pp. 4390-4398 ◽  
Author(s):  
Myron S. Czuczman ◽  
Aron Thall ◽  
Thomas E. Witzig ◽  
Julie M. Vose ◽  
Anas Younes ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Primary Therapy ◽  
Dose Escalation Study ◽  
Best Response ◽  
The Mean ◽  
Favorable Safety ◽  
Dose Dependent

Purpose This multicenter, dose-escalation study evaluates the safety, pharmacokinetics, and efficacy of galiximab (anti-CD80 monoclonal antibody) in patients with relapsed or refractory follicular lymphoma. Patients and Methods Patients had follicular lymphoma that had relapsed or failed to respond to primary therapy; the majority (90%) presented with stage III or IV disease. Four weekly intravenous infusions of galiximab were administered at doses of 125, 250, 375, or 500 mg/m2. Results Thirty-seven patients received galiximab treatment and were evaluated for safety; 35 were assessable for response. Antibody infusions were safe and well tolerated with no dose-limiting toxicities. A total of 22 (60%) of 37 patients experienced adverse events related to galiximab. All but one of the events were grade 1 or 2; the most common were fatigue, nausea, and headache. Cytopenias were rare; only one patient experienced anemia and febrile neutropenia, which were unrelated to galiximab and resolved after treatment. No patient developed antigaliximab antibody formation. The mean serum half-life ranged from 13 to 24 days. The overall response rate was 11% (two complete responses and two partial responses). Time to best response was delayed (months 3, 6, 9, and 12). Twelve patients (34%) maintained stable disease. Nearly half of all patients (49%) had a decrease in indicator lesions. Two responders remain on study without progression (22 and 24.4 months). Conclusion The favorable safety profile of galiximab and evidence of single-agent biologic activity and dose-dependent pharmacokinetics support further evaluation of galiximab as a treatment for follicular lymphoma, possibly in combination with other lymphoma therapies.

Evaluation of reported bone pain in patients (pts) receiving chemotherapy in pegfilgrastim clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9621-9621 ◽  
Author(s):  
J. Sierra ◽  
R. Harms ◽  
M. Mo ◽  
C. L. Vogel
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Adverse Event ◽  
Growth Factors ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Bone Pain ◽  
The Mean ◽  
Grade 3

9621 Background: Bone pain is the most commonly reported treatment-related adverse event (AE) associated with colony-stimulating growth factors. Some authors have suggested that pegfilgrastim-induced bone pain is unpredictable and refractory to analgesics (Kirshner 2007), though that impression may not be uniformly accepted. To better characterize this adverse event we evaluated bone pain across pegfilgrastim clinical trials. Methods: Completed Amgen-sponsored trials that both incorporated pegfilgrastim 6mg administered 24 hours after chemotherapy and utilized MedDRA library coding of AEs were examined. Included were 2 studies comparing pegfilgrastim with placebo (Vogel 2005, Hecht 2007) and 2 studies comparing pegfilgrastim with filgrastim (Sierra 2008, Lopez 2004). The incidence of bone pain was determined by treatment (pegfilgrastim, filgrastim, or placebo), chemotherapy (taxane-containing or not), cycle, severity, age, and body surface area (BSA). Analysis and recoding of studies with preferred AEs coded to nonMedDRA dictionaries is ongoing. Results: 1310 pts (filgrastim=67, pegfilgrastim=665, placebo=578) were analyzed. In studies comparing pegfilgrastim (n=74) and filgrastim (n==7) in pts with AML and NHL, 52% were female, and the mean (SD) age was 50 (15.1) years. Similar proportions (CI) of pts reported bone pain (24.3% [16.1, 35.7] vs 25.4% [15.5, 37.5], respectively), and grade 3/4 bone pain was reported in 3% [0.3, 9] versus 0% [-, -] of pts, respectively. Studies comparing pegfilgrastim (n=591) and placebo (n=578) pts in breast and colorectal cancer are below ( Table ). Conclusions: Bone pain of any grade was commonly reported in all 3 groups (pegfilgrastim, filgrastim, and placebo) and was marginally higher in pts receiving pegfilgrastim compared with placebo. Bone pain was most common in cycle 1. Severe bone pain was infrequently reported. Bone pain was similar in pts receiving pegfilgrastim and filgrastim. Chemotherapy (eg, taxanes) may also contribute to bone pain. [Table: see text] [Table: see text]

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