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JAMA Nov 2019Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine.
OBJECTIVE
To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack.
DESIGN, SETTING, AND PARTICIPANTS
Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month.
INTERVENTIONS
Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity.
MAIN OUTCOMES AND MEASURES
Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication.
RESULTS
Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P = .01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P = .03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P = .01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P = .07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]).
CONCLUSIONS AND RELEVANCE
Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02867709.
Topics: Adult; Aged; Analgesics; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; Nausea; Pain; Pain Management; Pyridines; Pyrroles; Young Adult
PubMed: 31742631
DOI: 10.1001/jama.2019.16711 -
Audiology Research May 2022Translational research moves promising primary research results from the laboratory to practical application. The transition from basic science to clinical research and... (Review)
Review
Translational research moves promising primary research results from the laboratory to practical application. The transition from basic science to clinical research and from clinical research to routine healthcare applications presents many challenges, including ethical. This paper addresses issues in the ethics of translational audiology and discusses the ethical principles that should guide research involving people with hearing loss. Four major ethical principles are defined and explained, which are as follows: beneficence, nonmaleficence, autonomy, and justice. In addition, the authors discuss issues of discrimination and equal access to medical services among people with hearing loss. Despite audiology's broad field of interest, which includes evaluation and treatment of auditory disorders (e.g., deafness, tinnitus, misophonia, or hyperacusis) and balance disorders, this study focuses primarily on deafness and its therapies.
PubMed: 35645198
DOI: 10.3390/audiolres12030028 -
Frontiers in Neurology 2020Seemingly unrelated symptoms in the head and neck region are eliminated when a patch is applied on specific locations on the Tympanic Membrane. Clinically, two distinct...
Seemingly unrelated symptoms in the head and neck region are eliminated when a patch is applied on specific locations on the Tympanic Membrane. Clinically, two distinct patient populations can be distinguished; cervical and masticatory muscle tensions are involved, and mental moods of anxiety or need. Clinical observations lead to the hypothesis of a "Tympanic Resonance Regulating System." Its controller, the Trigeminocervical complex, integrates external auditory, somatosensory, and central impulses. It modulates auditory attention, and directs it toward unpredictable external or expected domestic and internal sounds: peripherally by shifting the resonance frequencies of the Tympanic Membrane; centrally by influencing the throughput of auditory information to the neural attention networks that toggle between scanning and focusing; and thus altering the perception of auditory information. The hypothesis leads to the assumption that the Trigeminocervical complex is composed of a dorsal component, and a ventral one which may overlap with the concept of "Trigeminovagal complex." "Tympanic Dissonance" results in a host of local and distant symptoms, most of which can be attributed to activation of the Trigeminocervical complex. Diagnostic and therapeutic measures for this "Tympanic Dissonance Syndrome" are suggested.
PubMed: 32117001
DOI: 10.3389/fneur.2020.00014 -
Frontiers in Neurology 2020Migraine is a common and disabling brain disorder with a broad and heterogeneous phenotype, involving both pain and painless symptoms. Over recent years, more clinical... (Review)
Review
Migraine is a common and disabling brain disorder with a broad and heterogeneous phenotype, involving both pain and painless symptoms. Over recent years, more clinical and research attention has been focused toward the premonitory phase of the migraine attack, which can start up to days before the onset of head pain. This early phase can involve symptomatology, such as cognitive and mood change, yawning, thirst and urinary frequency and sensory sensitivities, such as photophobia and phonophobia. In some patients, these symptoms can warn of an impending headache and therefore offer novel neurobiological insights and therapeutic potential. As well as characterization of the phenotype of this phase, recent studies have attempted to image this early phase using functional neuroimaging and tried to understand how the symptoms are mediated, how a migraine attack may be initiated, and how nociception may follow thereafter. This review will summarize the recent and evolving findings in this field and hypothesize a mechanism of subcortical and diencephalic brain activation during the start of the attack, including that of basal ganglia, hypothalamus, and thalamus prior to headache, which causes a top-down effect on brainstem structures involved in trigeminovascular nociception, leading ultimately to headache.
PubMed: 32269547
DOI: 10.3389/fneur.2020.00140 -
Journal of Vestibular Research :... 2021This paper describes the diagnostic criteria for superior semicircular canal dehiscence syndrome (SCDS) as put forth by the classification committee of the Bárány...
Superior semicircular canal dehiscence syndrome: Diagnostic criteria consensus document of the committee for the classification of vestibular disorders of the Bárány Society.
This paper describes the diagnostic criteria for superior semicircular canal dehiscence syndrome (SCDS) as put forth by the classification committee of the Bárány Society. In addition to the presence of a dehiscence of the superior semicircular canal on high resolution imaging, patients diagnosed with SCDS must also have symptoms and physiological tests that are both consistent with the pathophysiology of a 'third mobile window' syndrome and not better accounted for by another vestibular disease or disorder. The diagnosis of SCDS therefore requires a combination of A) at least one symptom consistent with SCDS and attributable to 'third mobile window' pathophysiology including 1) hyperacusis to bone conducted sound, 2) sound-induced vertigo and/or oscillopsia time-locked to the stimulus, 3) pressure-induced vertigo and/or oscillopsia time-locked to the stimulus, or 4) pulsatile tinnitus; B) at least 1 physiologic test or sign indicating that a 'third mobile window' is transmitting pressure including 1) eye movements in the plane of the affected superior semicircular canal when sound or pressure is applied to the affected ear, 2) low-frequency negative bone conduction thresholds on pure tone audiometry, or 3) enhanced vestibular-evoked myogenic potential (VEMP) responses (low cervical VEMP thresholds or elevated ocular VEMP amplitudes); and C) high resolution computed tomography (CT) scan with multiplanar reconstruction in the plane of the superior semicircular canal consistent with a dehiscence. Thus, patients who meet at least one criterion in each of the three major diagnostic categories (symptoms, physiologic tests, and imaging) are considered to have SCDS.
Topics: Consensus; Humans; Semicircular Canal Dehiscence; Semicircular Canals; Vestibular Diseases; Vestibular Evoked Myogenic Potentials
PubMed: 33522990
DOI: 10.3233/VES-200004 -
Age and Ageing Aug 2023Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life....
Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life. Hearing is affected by multiple factors, including heredity, noise exposure, age, sex, ear disorders and lifestyle factors. Globally, hearing loss affects over 80% of adults aged 80 years and older, is often experienced in combination with other long-term health conditions and is a mid-life risk factor for dementia. To form a themed collection, we searched Age and Ageing for articles on hearing conditions published from 2000 onwards. This resulted in 22 articles included within the collection. They examined a range of important topics related to hearing healthcare and research, including noise-induced hearing loss, health service quality and safety, psychological and psychosocial consequences of hearing loss and co-morbidities of hearing loss. All articles reported on hearing loss; there were no published articles with a primary focus on other hearing conditions such as tinnitus or hyperacusis, on the health of older people from the Deaf community or on users of Cochlear implants, suggesting key gaps in knowledge and targets for future research. This New Horizons article highlights novel directions in research and practice and takes a forward look at how research into hearing conditions may develop in years to come. It highlights opportunities for the growth of patient-centred research and hearing healthcare supported by the better integration of health and care services as well as cross-speciality working to include common co-morbid health conditions.
Topics: Humans; Aged; Tinnitus; Hyperacusis; Quality of Life; Hearing; Aging
PubMed: 37604677
DOI: 10.1093/ageing/afad150 -
Frontiers in Neurology 2022To investigate the auditory features of patients with vestibular migraine (VM) and to analyze the possible relevant factors of hearing loss.
OBJECTIVES
To investigate the auditory features of patients with vestibular migraine (VM) and to analyze the possible relevant factors of hearing loss.
METHODS
A total of 166 patients with VM were enrolled. Demographic variables, age of onset, disease course, distribution of vestibular attacks, characteristics of hearing loss, and the coexistence of related disorders, such as visual aura, familial history, motion sickness, nausea, headache, photophobia, otalgia, tinnitus, aural fullness, and phonophobia, were analyzed and compared.
RESULTS
Patients with VM can manifest otalgia (8.4%), tinnitus (51.8%), aural fullness (41%), and phonophobia (31.9%). Of 166 patients, the prevalence of VMw was 21.1% ( = 35). Patients with VMw mainly manifested mild and easily reversible low-frequency hearing loss. The proportions of tinnitus and aural fullness were significantly larger in patients with VMw than that in patients with VMo ( < 0.05). The duration of vestibular symptoms was significantly shorter in patients with VMw ( < 0.05). However, the age of onset, disease course, gender, frequency of vestibular attacks, the coexistence of visual aura, familial history, motion sickness, nausea, headache, photophobia, otalgia, and phonophobia had no significant difference between the two groups.
CONCLUSION
Auditory symptoms were common in patients with VM. The hearing loss of VM was characterized by a mild and easily reversible low-frequency hearing loss, accompanied by higher proportions of tinnitus and aural fullness, and a shorter duration of vestibular symptoms compared with patients with VMo.
PubMed: 35911900
DOI: 10.3389/fneur.2022.944001 -
International Journal of Environmental... Dec 2020Occupational noise exposure accounts for approximately 16% of all disabling hearing losses, but the true value and societal costs may be grossly underestimated because... (Review)
Review
Occupational noise exposure accounts for approximately 16% of all disabling hearing losses, but the true value and societal costs may be grossly underestimated because current regulations only identify hearing impairments in the workplace if exposures result in audiometric threshold shifts within a limited frequency region. Research over the past several decades indicates that occupational noise exposures can cause other serious auditory deficits such as tinnitus, hyperacusis, extended high-frequency hearing loss, and poor speech perception in noise. Beyond the audiogram, there is growing awareness that hearing loss is a significant risk factor for other debilitating and potentially life-threatening disorders such as cardiovascular disease and dementia. This review discusses some of the shortcomings and limitations of current noise regulations in the United States and Europe.
Topics: Auditory Threshold; Europe; Hearing; Hearing Loss, Noise-Induced; Humans; Noise, Occupational
PubMed: 33276507
DOI: 10.3390/ijerph17238963