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Journal of Medical Economics 2024Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and...
AIMS
Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75 mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated.
MATERIALS AND METHODS
A model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-h). Responders and non-responders followed different pain trajectories over 48-h cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon.
RESULTS
Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain.
CONCLUSION
This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans.
Topics: Humans; Migraine Disorders; Cost-Benefit Analysis; Quality-Adjusted Life Years; Piperidines; Pyridines; United Kingdom; Adult; Male; Female; Markov Chains; Administration, Oral; Middle Aged
PubMed: 38590236
DOI: 10.1080/13696998.2024.2340932 -
Frontiers in Cellular Neuroscience 2024Efferent feedback to the mammalian cochlea includes cholinergic medial olivocochlear neurons (MOCs) that release ACh to hyperpolarize and shunt the voltage change that... (Review)
Review
Efferent feedback to the mammalian cochlea includes cholinergic medial olivocochlear neurons (MOCs) that release ACh to hyperpolarize and shunt the voltage change that drives electromotility of outer hair cells (OHCs). Via brainstem connectivity, MOCs are activated by sound in a frequency- and intensity-dependent manner, thereby reducing the amplification of cochlear vibration provided by OHC electromotility. Among other roles, this efferent feedback protects the cochlea from acoustic trauma. Lesion studies, as well as a variety of genetic mouse models, support the hypothesis of efferent protection from acoustic trauma. Genetic knockout and gain-of-function knockin of the unique α9α10-containing nicotinic acetylcholine receptor (nAChR) in hair cells show that acoustic protection correlates with the efficacy of cholinergic inhibition of OHCs. This protective effect was replicated by viral transduction of the gain-of-function α9L9'T nAChR into α9-knockout mice. Continued progress with "efferent gene therapy" will require a reliable method for visualizing nAChR expression in cochlear hair cells. To that end, mice expressing HA-tagged α9 or α10 nAChRs were generated using CRISPR technology. This progress will facilitate continued study of the hair cell nAChR as a therapeutic target to prevent hearing loss and potentially to ameliorate associated pathologies such as hyperacusis.
PubMed: 38560293
DOI: 10.3389/fncel.2024.1372948 -
PloS One 2024Migraine is a common chronic brain disorder, characterized by recurring and often disabling attacks of severe headache, with additional symptoms such as photophobia,... (Observational Study)
Observational Study
Migraine is a common chronic brain disorder, characterized by recurring and often disabling attacks of severe headache, with additional symptoms such as photophobia, phonophobia and nausea. Migraine affects especially the working age population. The objective of this retrospective observational register-based study was to analyze the use of healthcare services and associated costs in Finnish migraine patients. Study was based on aggregate data from January 1st, 2020, to December 31st, 2021, from the Finnish Institute for Health and Welfare's national registries. Patients were grouped into nine patient groups according to medication prescriptions and diagnoses. Healthcare resource utilization in specialty, primary, and occupational healthcare was assessed and analyzed separately for all-cause and migraine related healthcare contacts from a one-year period. The total number of patients was 175 711, and most (45%) of the patients belonged to a group that had used only one triptan. Migraine related total healthcare resource utilization was greater for patients that had used two or more triptans compared to those that had used only one. The patients with three or more preventive medications had the highest total migraine related healthcare resource utilization of the studied patient cohorts. Of the total annual healthcare costs 11.5% (50.6 million €) was associated to be migraine related costs. Total per patient per year healthcare costs were highest with patients that had used three or more preventive medications (5 626 €) and lowest in those with only one triptan (2 257 €). Our findings are in line with the recent European Headache Federation consensus statement regarding the unmet need in patients who have had inadequate response to two or more triptans. When assessing the patient access and cost-effectiveness of novel treatments for the treatment of migraine within different healthcare systems, a holistic analysis of the current disease burden along with potential gains for patients and healthcare service providers are essential information in guiding decision-making.
Topics: Humans; Finland; Retrospective Studies; Migraine Disorders; Health Care Costs; Headache; Tryptamines; Serotonin 5-HT1 Receptor Agonists
PubMed: 38507402
DOI: 10.1371/journal.pone.0300816 -
Hearing Research Apr 2024Noise sensitivity and hyperacusis are decreased sound tolerance conditions that are not well delineated or defined. This paper presents the correlations and... (Review)
Review
Noise sensitivity and hyperacusis are decreased sound tolerance conditions that are not well delineated or defined. This paper presents the correlations and distributions of the Noise Sensitivity Scale (NSS) and the Hyperacusis Questionnaire (HQ) scores in two distinct large samples. In Study 1, a community-based sample of young healthy adults (n = 103) exhibited a strong correlation (r = 0.74) between the two questionnaires. The mean NSS and HQ scores were 54.4 ± 16.9 and 12.5 ± 7.5, respectively. NSS scores displayed a normal distribution, whereas HQ scores showed a slight positive skew. In Study 2, a clinical sample of Veterans with or without clinical comorbidities (n = 95) showed a moderate correlation (r = 0.58) between the two questionnaires. The mean scores were 66.6 ± 15.6 and 15.3 ± 7.3 on the NSS and HQ, respectively. Both questionnaires' scores followed a normal distribution. In both samples, participants who self-identified as having decreased sound tolerance scored higher on both questionnaires. These findings provide reference data from two diverse sample groups. The moderate to strong correlations observed in both studies suggest a significant overlap between noise sensitivity and hyperacusis. The results underscore that NSS and HQ should not be used interchangeably, as they aim to measure distinct constructs, however to what extent they actually do remains to be determined. Further investigation should distinguish between these conditions through a comprehensive psychometric analysis of the questionnaires and a thorough exploration of psychoacoustic, neurological, and physiological differences that set them apart.
Topics: Adult; Humans; Hyperacusis; Tinnitus; Surveys and Questionnaires; Sound; Psychoacoustics
PubMed: 38492447
DOI: 10.1016/j.heares.2024.108992 -
Taiwanese Journal of Obstetrics &... Mar 2024Recurrent disseminated coccidioidal meningitis in two subsequent pregnancies is rare and can pose a challenge in ensuring the health of both mother and baby. In this...
OBJECTIVE
Recurrent disseminated coccidioidal meningitis in two subsequent pregnancies is rare and can pose a challenge in ensuring the health of both mother and baby. In this unique case we highlight this rare occurrence and subsequent treatment.
CASE REPORT
A 29-year-old G4P1021 with a history of disseminated coccidioidomycosis in a previous pregnancy presented at 8 weeks gestation with nausea, headache, and neck pain. Cerebrospinal fluid analysis was positive for recurrent coccidioidal infection. She was started on Amphotericin and discharged. She re-presented at 30 week's gestation with phonophobia and photophobia, emesis, neck pain and swelling. MRI showed evidence of ventriculomegaly with communicating hydrocephalus. She was treated with therapeutic lumbar punctures throughout her pregnancy and a ventriculoperitoneal shunt following delivery. She had a spontaneous vaginal delivery at 38 weeks and 3 days with no complications.
CONCLUSION
This unique case highlights the susceptibility of recurrent disseminated coccidioidomycosis in subsequent pregnancies and treatment thereof.
Topics: Humans; Infant; Female; Pregnancy; Adult; Coccidioidomycosis; Neck Pain; Meningitis, Fungal; Amphotericin B; Hydrocephalus
PubMed: 38485323
DOI: 10.1016/j.tjog.2024.01.022 -
Surgical Neurology International 2024Adhesive arachnoiditis (AA) is a debilitating condition characterized by chronic inflammation of the arachnoid membrane, leading to the formation of intrathecal scars...
BACKGROUND
Adhesive arachnoiditis (AA) is a debilitating condition characterized by chronic inflammation of the arachnoid membrane, leading to the formation of intrathecal scars and dural adhesions. The etiology of AA is multifactorial, including factors such as infections, trauma, and iatrogenic damage. We present a case of a female patient who developed communicating hydrocephalus after spinal anesthesia complicated by severe AA.
CASE DESCRIPTION
A 33-year-old female underwent a cesarean section with epidural anesthesia. Five hours postoperatively, she experienced transient difficulty standing, which was resolved with assistance. Weeks later, she developed a severe holocephalic headache accompanied by nausea, vomiting, photophobia, and phonophobia. Imaging revealed hydrocephalus and pronounced AA. Lumbar puncture provided symptomatic improvement. The patient underwent ventriculoperitoneal shunt insertion, resulting in further symptom improvement and successful shunt function.
CONCLUSION
AA is a challenging condition associated with inflammation and scarring of the arachnoid membrane. The development of hydrocephalus following epidural anesthesia, in this case, highlights a rare manifestation of arachnoiditis. Further research and documentation are needed to understand better the underlying mechanisms and risk factors contributing to hydrocephalus in the context of AA following epidural anesthesia.
PubMed: 38468646
DOI: 10.25259/SNI_933_2023 -
Cureus Jan 2024Arteriovenous malformation is a developmental anomaly of the vascular system characterized by arteriovenous shunt through a collection of tortuous vessels without...
Arteriovenous malformation is a developmental anomaly of the vascular system characterized by arteriovenous shunt through a collection of tortuous vessels without intervening capillary bed. Brain arteriovenous malformations (AVMs) may cause hemorrhagic stroke, epilepsy, and chronic headache. Migraine with aura was reported in up to 58% of females with AVM. A 23-year-old female presented with episodes of severe left-side headache for five months, throbbing in character with photophobia, phonophobia, and nausea. Brain MRI showed a large AVM in the left cerebellar hemisphere. She was diagnosed with grade six AVM, which is inoperable, and secondary migraine. Her migraine symptoms didn't respond to oral medications. However, it responded dramatically to Botox injections. Seven days after Botox injection, her headache disappeared, and her well-being improved. Three years post-diagnosis and treatment, she got married, then three months later became pregnant. During pregnancy, she followed up with neurology, obstetrics, and gynecology. She was delivered by cesarean section to minimize the risk of intracranial hemorrhage and delivered without complications. The female patient in this case with migraine secondary to inoperable brain AVM treated with Botox; she got married and delivered by C-section without complications. This case raises the following important lessons: large AVMs can present with migraine only, and Botox has a dramatic effect on the treatment and the ability to have a safe pregnancy and delivery in large AVM cases.
PubMed: 38435940
DOI: 10.7759/cureus.53326 -
Frontiers in Neuroanatomy 2024Auditory information is relayed from the cochlea via the eighth cranial nerve to the dorsal and ventral cochlear nuclei (DCN, VCN). The organization, neurochemistry and...
INTRODUCTION
Auditory information is relayed from the cochlea via the eighth cranial nerve to the dorsal and ventral cochlear nuclei (DCN, VCN). The organization, neurochemistry and circuitry of the cochlear nuclei (CN) have been studied in many species. It is well-established that glycine is an inhibitory transmitter in the CN of rodents and cats, with glycinergic cells in the DCN and VCN. There are, however, major differences in the laminar and cellular organization of the DCN between humans (and other primates) and rodents and cats. We therefore asked whether there might also be differences in glycinergic neurotransmission in the CN.
METHODS
We studied brainstem sections from humans, chimpanzees, and cats. We used antibodies to glycine receptors (GLYR) to identify neurons receiving glycinergic input, and antibodies to the neuronal glycine transporter (GLYT2) to immunolabel glycinergic axons and terminals. We also examined archival sections immunostained for calretinin (CR) and nonphosphorylated neurofilament protein (NPNFP) to try to locate the octopus cell area (OCA), a region in the VCN that rodents has minimal glycinergic input.
RESULTS
In humans and chimpanzees we found widespread immunolabel for glycine receptors in DCN and in the posterior (PVCN) and anterior (AVCN) divisions of the VCN. We found a parallel distribution of GLYT2-immunolabeled fibers and puncta. The data also suggest that, as in rodents, a region containing octopus cells in cats, humans and chimpanzees has little glycinergic input.
DISCUSSION
Our results show that glycine is a major transmitter in the human and chimpanzee CN, despite the species differences in DCN organization. The sources of the glycinergic input to the CN in humans and chimpanzees are not known.
PubMed: 38425805
DOI: 10.3389/fnana.2024.1331230 -
Frontiers in Neurology 2024In addition to hearing loss, damage to the cochlea can lead to gain of function pathologies such as hyperacusis. It has been proposed that painful hyperacusis,... (Review)
Review
In addition to hearing loss, damage to the cochlea can lead to gain of function pathologies such as hyperacusis. It has been proposed that painful hyperacusis, noxacusis, may be carried to the central nervous system by type II cochlear afferents, sparse, unmyelinated neurons that share morphological and neurochemical traits with nociceptive C-fibers of the somatic nervous system. Also like in skin, damage elicits spreading calcium waves within cochlear epithelia. These are mediated by extracellular ATP combined with IP3-driven release from intracellular calcium stores. Type II afferents are excited by ATP released from damaged epithelia. Thus, the genesis and propagation of epithelial calcium waves is central to cochlear pathology, and presumably hyperacusis. Damage-evoked signals in type II afferents and epithelial cells have been recorded in cochlear explants or semi-intact otic capsules. These efforts have included intracellular electrical recording, use of fluorescent calcium indicators, and visualization of an activity-dependent, intrinsic fluorescent signal. Of relevance to hyperacusis, prior noise-induced hearing loss leads to the generation of prolonged and repetitive activity in type II neurons and surrounding epithelia.
PubMed: 38419694
DOI: 10.3389/fneur.2024.1361747 -
Cephalalgia : An International Journal... Feb 2024To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a...
BACKGROUND
To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity.
METHODS
This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month).
RESULTS
Patients reported an increased sensitivity to light ( = 0.0297), touch ( = 0.0077), and smell (p = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high ( = 1.4e-06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity ( = 1.4e-06).
CONCLUSIONS
Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.
Topics: Humans; Longitudinal Studies; Migraine Disorders; Headache; Touch Perception; Sensory Thresholds
PubMed: 38416486
DOI: 10.1177/03331024241230279