341 Acute effects of seltorexant, a selective orexin-2 antagonist (JNJ- 42847922), on driving after bedtime administration

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A136-A136
Author(s):  
S Brooks ◽  
R G J A Zuiker ◽  
G E Jacobs ◽  
I Kezic ◽  
A Savitz ◽  
...  
Keyword(s):  
Postural Stability ◽  
Driving Simulator ◽  
Motor Vehicle ◽  
Subjective Effects ◽  
Driving Ability ◽  
Post Dose ◽  
Double Blind ◽  
Increased Risk ◽  
Subjective Sleepiness ◽  
The Difference

Abstract Introduction Seltorexant (JNJ-42847922), a potent and selective antagonist of the human orexin-2 receptor, is being developed for the treatment of major depressive disorder. Seltorexant also has sleep-promoting properties. Investigating the effects of sleep-promoting medications on driving is important because some of these agents (e.g. GABAA receptor agonists) may be associated with increased risk of motor vehicle accidents. We evaluated the effect of seltorexant on driving after forced awakening at night, using a validated driving simulator. Methods This double-blind, placebo and active-controlled, randomized, 3-way cross-over study was conducted in 18 male and 18 female healthy subjects. All subjects received seltorexant 40 mg, zolpidem 10 mg, or placebo 15 minutes before bedtime. Eighteen subjects were awakened at 2- and 6-hours post-dose, and the other 18 at 4- and 8-hours post-dose. At those timepoints, pharmacokinetics, objective (standard deviation of the lateral position [SDLP]) and subjective effects (using Perceived Driving Quality and Effort Scales) on driving ability, postural stability and subjective sleepiness were assessed. Results For seltorexant, the SDLP difference from placebo (95% confidence interval) at 2-, 4-, 6- and 8-hours post-dose was 3.9 cm (1.26, 6.60), 0.9 cm (-1.08, 2.92), 1.1 cm (-0.42, 2.63), and 0.6 cm (-2.75, 1.55), respectively vs. 9.6 cm (6.97, 12.38), 6.6 cm (3.53, 9.60), 4.7 cm (1.46, 7.85), and 1.3cm (-1.16, 3.80), respectively for zolpidem. The difference from placebo was significant at 2-hours after taking seltorexant, while the difference from placebo was significant at 2, 4 and 6-hours after zolpidem. Subjective driving quality was decreased for both drugs at all time points and driving effort was increased up to 4-hours post-dose for both medications. Subjective sleepiness showed a significant increase compared to placebo 2- and 4-hours after administration of either drug. Postural stability was decreased up to 2-hours after administration of seltorexant, and up to 4-hours after administration of zolpidem. Conclusion Compared to zolpidem, objective effects on driving performance were more transient after seltorexant administration and largely normalized by 4–6 hours post-dose. Support (if any) This work was sponsored by Janssen R&D.

scholarly journals The Medical Referral Process and Motor-Vehicle Crash Risk for Drivers with Dementia

Geriatrics ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. 91
Author(s):  
Jonathan Davis ◽  
Cara Hamann ◽  
Brandon Butcher ◽  
Corinne Peek-Asa
Keyword(s):  
Review Process ◽  
Motor Vehicle ◽  
The United States ◽  
Motor Vehicle Crash ◽  
Driving Ability ◽  
Crash Risk ◽  
Referral Process ◽  
Vehicle Crash ◽  
Increased Risk ◽  
Medical Referral

Cognitive and physical impairment can occur with dementia and reduce driving ability. In the United States, individual states have procedures to refer and evaluate drivers who may no longer be fit to drive. The license review process is not well understood for drivers with dementia. This study uses comprehensive data from the Iowa Department of Transportation to compare the referral process for drivers with and without dementia from January 2014 through November 2019. The likelihood of failing an evaluation test was compared between drivers with and without dementia using logistic regression. The risk of motor-vehicle crash after referral for review of driving ability was compared using a Cox proportional hazard model. Analysis controlled for the age and sex of the referred driver. Drivers with dementia performed worse on all tests evaluated except the visual screening test. After the referral process, the risk of crash was similar between those with and without dementia. Drivers with dementia were denied their license more frequently than referred drivers without dementia. However, drivers with dementia who successfully kept their license as a result of the license review process were not at an increased risk of crash compared to other referred drivers.

Potential for limited reinforcing and abuse-related subjective effects of intranasal oxytocin

2019 ◽  
Vol 34 (3) ◽  
pp. 336-347
Author(s):  
Sean B Dolan ◽  
Meredith S Berry ◽  
Patrick S Johnson ◽  
Matthew W Johnson
Keyword(s):  
Repeated Measures ◽  
Demand Curve ◽  
Subjective Effects ◽  
Small Sample ◽  
Limited Data ◽  
Nonsignificant Trend ◽  
Double Blind ◽  
Reinforcing Effects ◽  
The Difference ◽  
Drug Liking

Background: There has been growing interest in using oxytocin as a pharmacotherapy for psychiatric disorders, including substance use disorder. Limited data exist regarding oxytocin’s reinforcing efficacy, which is a necessary consideration for novel pharmacotherapies, especially in substance-using populations. Aims: This study aimed to determine the potential reinforcing effects of intranasally administered oxytocin by assessing behavioral economic demand and subjective effects. Methods: Healthy adults ( n = 23) participated in a double-blind, repeated-measures, laboratory study wherein they received intranasal oxytocin (40 IU) or placebo in a randomized order across two sessions. Participants completed drug purchasing tasks at the conclusion of both sessions. Throughout both sessions, subjective and physiological effects were assessed. Results: Demand-curve analysis of purchasing tasks revealed greater median purchasing for oxytocin relative to placebo. Physiological and subjective effects did not significantly differ between oxytocin and placebo. However, a nonsignificant trend was observed for moderately greater drug liking for oxytocin relative to placebo. There was a significant, positive correlation between the difference in drug liking (between oxytocin and placebo) and the difference in lowest-price purchasing (between oxytocin and placebo). Conclusions: These data suggest the potential for limited reinforcing and abuse-related subjective effects of intranasal oxytocin. Given the small sample, the greater drug liking of oxytocin compared to placebo, and the positive relation between demand and drug liking, it is possible that oxytocin may produce reinforcing effects in some participants. Therefore, additional studies of oxytocin reinforcement are warranted.

Cognitive predictors of unsafe driving in older drivers: a meta-analysis

2009 ◽  
Vol 21 (4) ◽  
pp. 637-653 ◽  
Author(s):  
J. L. Mathias ◽  
L. K. Lucas
Keyword(s):  
Driving Simulator ◽  
Motor Vehicle ◽  
Motor Vehicle Accident ◽  
Meta Analysis ◽  
Block Design ◽  
Older Drivers ◽  
Driving Ability ◽  
Cognitive Differences ◽  
Attention Task ◽  
Cognitive Predictors

ABSTRACTBackground: Older drivers are at a higher risk of being involved in a motor vehicle accident. However, on-road assessments of all older drivers are impractical, highlighting the need to screen for potentially unsafe drivers. This study undertook a meta-analysis of research examining the cognitive predictors of driving ability in older drivers in order to provide an evidence-based method for screening drivers.Methods: Comprehensive searches were undertaken of the PubMed, PsycINFO, CINAHL, and Health-Source Nursing electronic databases between 1980 and 2007 in order to identify studies that examined cognitive differences between drivers aged over 55 years who either passed or failed a driving assessment. Twenty-one studies were eligible for inclusion. Weighted Cohen's d effect sizes, percentage overlap statistics, Fail-safe Ns and 95% CIs were calculated for all cognitive tests.Results: The best predictors of on-road driving were the Ergovision and Useful Field of View (UFOV) tests, a complex RT task, Paper Folding task, Dot Counting, WMS Visual Reproduction, and Computerized Visual Attention Task. Simulator driving performance was best predicted by the Benton Line Orientation Task, Clock Drawing, a Driver Scanning task, the UFOV, WAIS Picture Arrangement and MMSE. Finally, the Trail Making Test, Stroop, UFOV, WAIS Block Design, and Automated Psychophysical Test were good predictors of driving problems.Conclusions: There are a variety of tests that appear suitable for screening older drivers, the exact choice of which depends on the “gold standard” for determining driving ability (on-road driving, driving simulator, driving problems) and whether a computerized or paper-and-pencil task is required.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

Predictors of Success Using a mHealth Intervention in Adults with Prediabetes: Results of a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Nestoras Mathioudakis ◽  
Estelle Everett ◽  
Noora Al-Hajri ◽  
Mohammed Abusamaan ◽  
Clare Lee ◽  
...  
Keyword(s):  
Pilot Study ◽  
Intervention Program ◽  
Area Deprivation ◽  
Inverse Association ◽  
Small Pilot Study ◽  
Mhealth Intervention ◽  
Increased Risk ◽  
Metabolic Equivalent Of Task ◽  
Mobile Intervention ◽  
The Difference

BACKGROUND About one-third of American adults have prediabetes and are at increased risk of type 2 diabetes. Mobile health (mHealth) technologies provide a scalable approach to diabetes prevention by encouraging physical activity (PA), weight loss, and adherence to a healthy diet in large numbers of patients. OBJECTIVE To identify factors associated with improvements in PA and glycated hemoglobin (A1c) measures among prediabetic adults who received a mobile intervention program (smartphone app in combination with a digital body weight scale) in a previously completed pilot study. METHODS We conducted a post hoc analysis of a 3-month prospective, single-arm, observational study using the Sweetch™ mHealth intervention among adults with prediabetes. Change in A1C was calculated as the difference between the 3-month and baseline A1C measurements and was categorized as decrease vs. no decrease. PA was evaluated using the total minutes and metabolic equivalent of task (MET)-hours per week. Change in MET-hours/week was categorized as increase vs. no increase. Age, sex, race, education, employment status, area deprivation, smartphone usage attitudes, and PA stage of change were compared between groups by outcomes of change in A1C and change in MET-hour/week. RESULTS A total of 37 adults received the final Sweetch mobile intervention and were included in the analysis. 62% were female and 81% were white, with average age of 57 years. The median [IQR] baseline A1C was 6.0% [5.8, 6.2]. A1C measure at 3-month was decreased in 24 (65%) participants when compared to baseline A1C. There was an inverse association between average MET-hours per week and change in A1C. Among participants whose A1C decreased vs. did not decrease, the MET-hours per week in last 2 weeks of study was 18.7 (8.4) and 15.0 (7.1), respectively (P=0.19), and the change in MET-hours per week was 2.1 (7.1) and 4.1(6.1), respectively (P=0.41). There were otherwise no statistically significant differences in participant factors by A1C and PA outcomes. CONCLUSIONS In this small pilot study, Sweetch mHealth intervention achieved comparable A1C response prediabetic adults with different individual, sociodemographic and anthropometric characteristics. CLINICALTRIAL ClincialTrials.gov NCT02896010; https://clinicaltrials.gov/ct2/show/NCT02896010 (Archived by WebCite at http://www.webcitation.org/6xJYxrgse)

scholarly journals Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

2020 ◽  
Author(s):  
Elena V Esaulenko ◽  
Aleksey A Yakovlev ◽  
Genady A Volkov ◽  
Anastasia A Sukhoruk ◽  
Kirill G Surkov ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Geometric Mean ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Antigen Vaccine ◽  
Single Antigen ◽  
Antibody Titers ◽  
The Russian Federation ◽  
The Difference ◽  
Mean Concentration

Abstract Background This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. Methods We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: > − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). Results Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was >97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions 3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

scholarly journals Relative absorption of silicon from different formulations of dietary supplements: a pilot randomized, double-blind, crossover post-prandial study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Boqué ◽  
R. M. Valls ◽  
A. Pedret ◽  
F. Puiggrós ◽  
L. Arola ◽  
...  
Keyword(s):  
Dietary Supplements ◽  
Inductively Coupled Plasma ◽  
Aloe Vera ◽  
Emission Spectrometry ◽  
Orthosilicic Acid ◽  
Post Dose ◽  
Double Blind ◽  
Gold Standard Method ◽  
Healthy Humans ◽  
Relative Absorption

AbstractThe purpose of the present study was to compare the relative absorption of a new powder presentation of silicon (Si) as orthosilicic acid with maltodextrin (Orgono Powder) compared to usual Si liquid presentations as orthosilicic acid with Equisetum arvense and Rosmarinus officinalis (G5 Siliplant) and orthosilicic acid with aloe vera (G7 Aloe). All dietary supplements were administered at the same Si oral dose (21.6 mg) in a randomized, double-blind, crossover post-prandial study conducted in 5 healthy men. Urine was collected at baseline and over the 6-h post-dose period in 2 separate 3-h collections for the analysis of Si concentration, which was conducted by inductively coupled plasma optical emission spectrometry as the gold standard method. No significant differences in total urinary Si excretion were found after the intake of these 3 dietary supplements; 34.6%, 32.4% and 27.2% of the ingested Si from G7 Aloe, G5 Siliplant and Orgono Powder, respectively, was excreted in urine over the 6-h follow-up period. The 3 different oral Si formulations tested, in powder and liquid presentations, provide highly bioavailable Si and present an equivalent relative absorption in healthy humans.

scholarly journals Increased risk of preeclampsia after use of paracetamol during pregnancy – causal or coincidence?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hetti von Hellens ◽  
Leea Keski-Nisula ◽  
Heidi Sahlman
Keyword(s):  
Third Trimester ◽  
Retrospective Case ◽  
Reverse Causation ◽  
Gestational Period ◽  
The Third ◽  
Precise Data ◽  
Increased Risk ◽  
Study Population ◽  
The Difference ◽  
Risk Of Preeclampsia

Abstract Background The maternal use of paracetamol during pregnancy has been associated with the development of preeclampsia. This study aims to clarify whether the connection is causal or whether it is due to reverse causation. Methods This study is a continuation of the retrospective case cohort study examining 2,508 pregnant women using a variety of drugs and the development of preeclampsia (1,252 women with preeclampsia and 1,256 controls). For the purposes of this study, more precise data was collected from several hospital databases of the women among this cohort who had reported taking paracetamol during pregnancy (indications, gestational period etc.); this was evaluated in association with the development of preeclampsia. Results 5.5% (100 cases and 37 controls) of all the study population (2,508) had clearly reported paracetamol use. Women with preeclampsia had used significantly more often paracetamol during pregnancy compared to controls (cases 8.0%, controls 2.9%, p < 0.001). The difference was most evident in the third trimester (after the 29th GW) and the use of paracetamol was associated with both mild and severe preeclampsia. Headache and “general pain” were the most common indications for medication among all paracetamol users. Conclusions The use of paracetamol in the third trimester of pregnancy was associated with preeclampsia. This observation indicates that association between paracetamol use and preeclampsia is probably due to reverse causation, i.e. women with preeclampsia experience more headaches due to preeclampsia symptoms since this association was not detected with the use of paracetamol in earlier stages of pregnancy.

scholarly journals A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

2021 ◽  
Author(s):  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Martin Croce ◽  
Daniel Rodriguez Gonzalez ◽  
Satoshi Fujimi ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Double Blind Study ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Intention To Treat ◽  
The Difference ◽  
Hospital Acquired ◽  
Noninferiority Margin

Abstract Background Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. Methods In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. Results Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. Conclusions Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. Clinical Trials Registration NCT02019420.

The Role of Obesity in Motor Vehicle Injuries and Fatalities in the Pediatric Population: A Systematic Review

2021 ◽  
pp. 088506662199273
Author(s):  
Zana Alattar ◽  
Shelby Hoebee ◽  
Eyal Ron ◽  
Paul Kang ◽  
Eric vanSonnenberg
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Motor Vehicle ◽  
Pediatric Population ◽  
Extremity Injury ◽  
Obese Children ◽  
Patients Âgés ◽  
Vehicle Accidents ◽  
Increased Risk ◽  
Extremity Injuries

Purpose: A systematic review done to evaluate obesity as a risk factor for injuries and mortality in motor vehicle accidents (MVAs) in the pediatric population, as there has not been a systematic review done in over 10 years. This study aims to update the literature regarding obesity as a risk factor for injuries in MVAs in the pediatric population. Materials and Methods: A systematic review was conducted according to the PRISMA guidelines with strict inclusion and exclusion criteria, resulting in the use of 3 total articles to analyze obesity as a risk factor for overall injury and mortality in the pediatric population. Results: Zaveri et al demonstrated a statistically significant, but weak, decrease in the odds of extremity injury in overweight patients ages 2 to 17 years old (odds ratio [OR] = 0.6, 95% confidence interval [CI] = 0.4-1.0, P ≤ 0.05). On the other hand, Pollack et al and Haricharan et al found an increase in extremity injury in the obese population, in ages 9 to 15 years (OR = 2.54, 95% CI = 1.15-5.59, P ≤ 0.05), and 10 to 17 years (Age 10-13: OR = 6.06, 95% CI = 2.23-16.44, P ≤ 0.05, Age 14-17 OR = 1.44, 95% CI = 1.04-2.00, P ≤ 0.05), respectively. Haricharan et al also found an increase in thoracic injuries in obese children, ages 2 to 13 and increased risk of head/face/neck injury in obese children ages 2 to 5 (OR = 3.67, 95% CI = 1.03-13.08, P ≤ 0.05), but a decreased risk of head injury in obese children ages 14 to 17 (OR = 0.33, 95% CI = 0.18-0.60, P ≤ 0.05). Conclusions: There are sparse data that are conflicting, regarding the effect of obesity on extremity injuries in the pediatric population. Obesity is not protective against thoracic, head, or abdominal injuries. However, it was found to be a risk factor for trunk injuries in ages 2 to 13, as well as head/face/neck injuries for ages 2 to 5. Since the literature is so sparse, further research is warranted in these areas.

Sign in / Sign up

Export Citation Format

Share Document