The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform
Emily Clay - One of the best experts on this subject based on the ideXlab platform.
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evaluation and management of Orthostatic hypotension
American Family Physician, 2011Co-Authors: Jeffrey B Lanier, Matthew B Mote, Emily ClayAbstract:Orthostatic hypotension is defined as a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with blood pressure from the sitting or supine position. It results from an inadequate physiologic response to postural changes in blood pressure. Orthostatic hypotension may be acute or chronic, as well as symptomatic or asymptomatic. Common symptoms include dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache. Less common symptoms include syncope, dyspnea, chest pain, and neck and shoulder pain. Causes include dehydration or blood loss; disorders of the neurologic, cardiovascular, or endocrine systems; and several classes of medications. Evaluation of suspected Orthostatic hypotension begins by identifying reversible causes and underlying associated medical conditions. Head-up tilt-table testing can aid in confirming a diagnosis of suspected Orthostatic hypotension when standard Orthostatic Vital Signs are nondiagnostic; it also can aid in assessing treatment response in patients with an autonomic disorder. Goals of treatment involve improving hypotension without excessive supine hypertension, relieving Orthostatic symptoms, and improving standing time. Treatment includes correcting reversible causes and discontinuing responsible medications, when possible. Nonpharmacologic treatment should be offered to all patients. For patients who do not respond adequately to nonpharmacologic treatment, fludrocortisone, midodrine, and pyridostigmine are pharmacologic therapies proven to be beneficial.
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evaluation and management of Orthostatic hypotension
American Family Physician, 2011Co-Authors: Jeffrey B Lanier, Matthew B Mote, Emily ClayAbstract:Orthostatic hypotension is defined as a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with blood pressure from the sitting or supine position. It results from an inadequate physiologic response to postural changes in blood pressure. Orthostatic hypotension may be acute or chronic, as well as symptomatic or asymptomatic. Common symptoms include dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache. Less common symptoms include syncope, dyspnea, chest pain, and neck and shoulder pain. Causes include dehydration or blood loss; disorders of the neurologic, cardiovascular, or endocrine systems; and several classes of medications. Evaluation of suspected Orthostatic hypotension begins by identifying reversible causes and underlying associated medical conditions. Head-up tilt-table testing can aid in confirming a diagnosis of suspected Orthostatic hypotension when standard Orthostatic Vital Signs are nondiagnostic; it also can aid in assessing treatment response in patients with an autonomic disorder. Goals of treatment involve improving hypotension without excessive supine hypertension, relieving Orthostatic symptoms, and improving standing time. Treatment includes correcting reversible causes and discontinuing responsible medications, when possible. Nonpharmacologic treatment should be offered to all patients. For patients who do not respond adequately to nonpharmacologic treatment, fludrocortisone, midodrine, and pyridostigmine are pharmacologic therapies proven to be beneficial.
Leah Millheiser - One of the best experts on this subject based on the ideXlab platform.
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effects of alcohol administered with flibanserin in healthy premenopausal women a randomized double blind single dose crossover study
The Journal of Sexual Medicine, 2019Co-Authors: James A Simon, Anita H Clayton, Sharon J Parish, Stuart C Apfel, Leah MillheiserAbstract:Abstract Introduction Flibanserin is approved in the United States and Canada for the treatment of hypoactive sexual desire disorder in premenopausal women. Aim The purpose of this trial was to evaluate the safety of concomitant administration of flibanserin with alcohol. Methods In this single-center, randomized, double-blind, single-dose, crossover study, participants were randomly assigned to 1 of 12 sequences to receive each of 7 treatments: flibanserin 100 mg or placebo with ethanol 0.2 g/kg, 0.4 g/kg, or 0.6 g/kg, or flibanserin 100 mg only. Treatments were administered using a worst-case approach that included morning dosing and consumption of alcohol within 10 minutes. Main Outcome Measure The primary end point was the proportion of participants who experienced dizziness, syncope, or hypotension. Safety end points included Orthostatic Vital Signs. Results The study included 96 premenopausal women (mean age 31 ± 8 years). The incidence of dizziness for ethanol + flibanserin was 39.8% for ethanol 0.6 g/kg, 34.1% for 0.4 g/kg, and 27.4% for 0.2 g/kg compared with 31.1% for flibanserin without ethanol. Based on the available Vital Signs data, there was no effect of ethanol concentration on Orthostatic blood pressure, vertigo, or hypotension; no instances of syncope were observed. The overall incidence of adverse events (AEs) was similar when flibanserin was administered alone (96.7%) or with ethanol (90.5–97.6%). Clinical Implications Consumption of the tested amounts of alcohol (0.2–0.6 g/kg) does not have an additive effect on the AE profile of flibanserin 100 mg in healthy premenopausal women. Strengths & Limitations Strengths include the study population (premenopausal women, as indicated for flibanserin) and range of ethanol doses. Limitations include the morning dosing of study medication, which is inconsistent with the bedtime dosing recommended for flibanserin, and the method of handling missing Vital sign measurements. Conclusion Co-administration of flibanserin 100 mg with varying doses of ethanol resulted in few AEs of special interest, with no notable alcohol dose response. However, a significantly greater percentage of participants administered flibanserin with 0.6 g/kg and 0.4 g/kg of alcohol were characterized as “Participants in Whom Standing Blood Pressure Was Not Obtained” compared with participants administered flibanserin alone. Simon JA, Clayton AH, Parish SJ, et al. Effects of Alcohol Administered With Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study. J Sex Med 2020;17:83–93.
Bradford B Walters - One of the best experts on this subject based on the ideXlab platform.
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A Double-Blind, Placebo-Controlled Trial Demonstrating the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of RTI-336
Frontiers Media S.A., 2018Co-Authors: Ivy F. Carroll, Jeffrey J Buda, Thomas R Kosten, Laurene Wang, Bradford B WaltersAbstract:Background: Preclinical and clinical data suggest that a compound which binds potently to and inhibits the dopamine transporter, but with a slower onset and offset rate than cocaine and with less abuse potential and psychomotor stimulant activity, could be a useful adjunct in the treatment of cocaine dependence.Methods: We assessed the safety, tolerability, and pharmacokinetics (PK) of oral single doses (0.3, 1, 3, 6, 12, and 20 mg) of such an analog, RTI-336, in a randomized, double-blind, and placebo-controlled trial in healthy adult males. Pre-dose and post-dose safety assessments included physical examinations (including neurological examination); Orthostatic Vital Signs; 6-lead continuous electrocardiogram (ECG) telemetry monitoring pre-dose to 8 h post-dose; 12-lead ECGs; clinical chemistry, hematology, and urinalysis; mini mental status examinations; and adverse events. RTI-336 PK was assessed in plasma and urine.Results: 22 participants were enrolled. RTI-336 was well-tolerated up to the maximum evaluated dose of 20 mg. PK analyses demonstrated good absorption with peak plasma maximum concentrations (Cmax) occurring around 4 h post-dose and consistent half-lives of around 17 h for the 6, 12, and 20 mg doses. Plasma drug exposure and Cmax increased in proportion to dose. Only 0.02% of RTI-336 excreted was unchanged in urine. Active metabolites UC-M5, UC-M8, and UC-M2 were measurable in plasma and urine, with plasma Cmax of UC-M5 and UC-M8 exceeding that of RTI-336. Three AE possibly were related to RTI-336 and resolved with discontinuation; the one serious AE was unrelated to RTI-336. 2 participants had transient and mild serum total bilirubin elevations (<1.5× upper limit of normal) at day 3 post-dose which resolved by day 8 post-dose.Conclusion: All doses including the highest (20 mg) showed excellent safety and tolerability, and further studies in humans are warranted.Trial Registration:ClinicalTrials.gov Identifier: NCT00808119
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OPEN A Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of JDTic
2016Co-Authors: Jeffrey J Buda, Fi Carroll, Thomas R Kosten, Dennis Swearingen, Bradford B WaltersAbstract:Animal studies suggest that kappa opioid receptor antagonists (KORAn) potentially could treat a wide variety of addictive and depressive disorders. We assessed the KORAn JDTic for safety, tolerability, and pharmacokinetics in a double-blind, placebo-controlled, randomized trial evaluating single oral doses in healthy adult males. Predose and postdose safety assessments included Orthostatic Vital Signs; 6-lead continuous telemetry monitoring (approximately 16 h predose to 24 h postdose); 12-lead electrocardiograms (ECGs); clinical chemistry, hematology, coagulation, and urinalysis; psychomotor functioning (using the Wayne Saccadic Fixator (WSF)); and adverse events. As a potential indicator of JDTic effects on affect, the POMS Standard instrument was administered predose and daily postdose Days 1–6. At 1mg, 2 of the 6 JDTic (and 0/6 placebo) subjects experienced a single, asymptomatic event of multiple beats of nonsustained ventricular tachycardia (NSVT). Their events were temporally similar with respect to time postdose (and the postdose timing of an NSVT event in a monkey). These events triggered a study stopping rule. No differences were observed between the placebo and JDTic subjects with respect to clinical chemistry, hematology, coagulation, urinalysis, Orthostatic Vital Signs, WSF, or 12-lead ECG parameters. Plasma JDTic levels were below the lower limit of quantitation (0.1 nM) in all subjects. There were no significant differences in POMS scores between the placebo and JDTic groups. Although the evidence is circumstantial, it suggests that NSVT is a potential JDTic toxicity in humans. Given the therapeutic potential of KORAn, further investigation is needed to determine whether a significant JDTic human cardiac effect indee
Satish R Raj - One of the best experts on this subject based on the ideXlab platform.
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postural tachycardia syndrome pots
Circulation, 2013Co-Authors: Satish R RajAbstract:Patient O.T. is a 26-year-old white woman who works in the music industry. She was diagnosed with pneumonia and treated with inhalers. Shortly afterward, she developed spells of tachycardia. Her episodes of tachycardia were primarily associated with upright posture. In addition to rapid palpitations, she complained of lightheadedness and presyncope on standing, intermittent stabbing chest pains (typically on standing), mental clouding with an inability to concentrate, severe fatigue, and exercise intolerance. Orthostatic Vital Signs recorded a supine heart rate (HR) of 73 bpm with a blood pressure (BP) of 103/72 mm Hg. After standing for 1 minute, her HR increased to 106 bpm with a BP of 109/80 mm Hg, and after 5 minutes, her HR was 122 bpm with a BP of 118/75 mm Hg. She was diagnosed with postural tachycardia syndrome (POTS). Under normal conditions, the assumption of upright posture effects an instantaneous shift of ≈500 mL of blood from the thorax to the lower abdomen, buttocks, and legs. There is a secondary shift of plasma volume (10% to 25%) out of the vasculature and into the interstitial tissue, which decreases venous return to the heart (preload), resulting in a transient decline in cardiac filling and BP. This unloads the baroreceptors and triggers a compensatory decrease in parasympathetic tone and an increase in sympathetic activation, with a resultant increase in HR and systemic vasoconstriction (countering the initial decline in BP). The net hemodynamic effect of transition to upright posture is a 10- to 20-bpm increase in HR, a negligible change in systolic BP, and a ≈5-mm Hg increase in diastolic BP. Orthostatic dysregulation occurs when this gravitational regulatory mechanism does not respond properly. Patients can present with Orthostatic hypotension (seen in autonomic nervous system failure) or with Orthostatic tachycardia (seen in POTS). Patients with POTS typically maintain (or …
Robert S Sheldon - One of the best experts on this subject based on the ideXlab platform.
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canadian cardiovascular society position statement on postural Orthostatic tachycardia syndrome pots and related disorders of chronic Orthostatic intolerance
Canadian Journal of Cardiology, 2020Co-Authors: Juan C Guzman, Paula J Harvey, Lawrence Richer, Ronald Schondorf, Colette Seifer, Nicolas Thibodeaujarry, Robert S SheldonAbstract:Abstract The current definition of postural Orthostatic tachycardia syndrome (POTS) dates back to a small case series of patients with a subacute illness who presented with excessive Orthostatic tachycardia and Orthostatic intolerance, in the absence of another recognized disease. Conventional POTS criteria require an excessive Orthostatic tachycardia in the absence of substantial Orthostatic hypotension, and predominant symptoms of Orthostatic intolerance, worse with upright posture and better with recumbence. POTS is a heterogeneous syndrome with likely several underlying pathophysiological processes, and not a specific disease. The primary panel for this Canadian Cardiovascular Society position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, and developed recommendations on the basis of the Canadian Cardiovascular Society approach to position statements. One identified problem was that numerous patients who did not meet criteria for POTS would still be given that diagnoses by providers to validate the illness even though this diagnosis is incorrect. This includes patients with postural symptoms without tachycardia, Orthostatic tachycardia without symptoms, and those with Orthostatic tachycardia but another overt cause for excessive tachycardia. We developed a novel nomenclature ecosystem for Orthostatic intolerance syndromes to increase clarity. We also provide more clarity on how to interpret the Orthostatic Vital Signs. These concepts will need to be prospectively assessed.