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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 -
Korean Journal of Ophthalmology : KJO Jun 2024To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population. (Observational Study)
Observational Study
PURPOSE
To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population.
METHODS
The Korean Intermittent Exotropia Multicenter Study (KIEMS) is a nationwide, observational, cross-sectional, multicenter study conducted by the Korean Association for Pediatric Ophthalmology and Strabismus including 5,385 patients with intermittent exotropia. Subjective symptoms and medical history of patients with intermittent exotropia were extracted by a comprehensive survey based on a self-administered questionnaire according to the study protocol of the KIEMS.
RESULTS
The mean age of symptom onset was 5.5 years. The most common symptom reported in patients with intermittent exotropia was photophobia (52.1%), followed by diplopia at near fixation (7.3%) and distance fixation (6.2%). Preterm birth was found in 8.8%, and 4.1% had perinatal complications. A family history of strabismus was present in 14.9%, and 5.5% of patients had a family member who underwent strabismus surgery.
CONCLUSIONS
The KIEMS is one of the largest clinical studies on intermittent exotropia. Intermittent exotropia frequently caused photophobia and diplopia, and patients with a family history was not uncommon.
Topics: Humans; Exotropia; Male; Female; Cross-Sectional Studies; Republic of Korea; Child; Child, Preschool; Surveys and Questionnaires; Self Report; Adolescent; Adult; Young Adult; Middle Aged; Infant
PubMed: 38584440
DOI: 10.3341/kjo.2023.0129 -
Journal of Clinical Neuroscience :... May 2024This study aimed to assess abnormalities in the insular cortex of individuals suffering from migraines and examine their associations with pain duration, medication...
BACKGROUND
This study aimed to assess abnormalities in the insular cortex of individuals suffering from migraines and examine their associations with pain duration, medication usage, and clinical symptoms.
METHODS
We analyzed radiological data from 38 migraine patients who had undergone 3D iso T1-weighted brain MRI at our university hospital between 2019 and 2023. Structured questionnaires were used to collect information on participants' age, migraine type, disease duration, clinical symptoms, and medication use. Volumetric analysis was performed on the insular regions using Volbrain and 3DSlicer. The results were statistically analyzed.
RESULTS
Comparing groups with chronic pain to normal groups revealed significant differences in several insular regions, including the posterior insula (p = 0.034), parietal operculum (p = 0.04), and the entire insular cortex (p = 0.023). Further group comparisons (Group 1, 2, and 3) showed significant differences in specific insular regions. For instance, the anterior insula (p = 0.032) was associated with taste changes, the posterior insula (p = 0.010) with smell-related changes, and the central operculum (p = 0.046) with sensations of nausea. Additionally, significant changes were observed in the parietal operculum concerning nausea, photophobia, phonophobia, and changes in smell.
CONCLUSION
To the best of our knowledge, there have been no studies investigating the relationship between clinical manifestations and volumetric correlation. This study provides insights into abnormalities in the insular cortex among migraine patients and their potential relevance to pain duration, severity, and migraine type. The results suggest that understanding alterations in insular regions possibly linked to pain could contribute to the development of innovative approaches to managing chronic pain.
Topics: Humans; Migraine Disorders; Female; Male; Adult; Middle Aged; Magnetic Resonance Imaging; Chronic Pain; Insular Cortex; Young Adult; Cerebral Cortex
PubMed: 38579522
DOI: 10.1016/j.jocn.2024.03.034 -
Retinal Cases & Brief Reports Apr 2024Alström Syndrome (AS) is a rare autosomal recessive monogenic ciliopathy which is caused by a mutation of the Alström syndrome 1 (ALMS1) gene. It is a multisystemic...
PURPOSE
Alström Syndrome (AS) is a rare autosomal recessive monogenic ciliopathy which is caused by a mutation of the Alström syndrome 1 (ALMS1) gene. It is a multisystemic disorder characterized by insulin resistance, childhood obesity, cardiomyopathy, progressive hepatic and renal failure, sensorineural hearing loss and retinal degeneration. Herein, we aimed to report a novel variant in ALMS1 gene causing AS in a patient presenting with visual impairment.
METHODS
Case report.
RESULTS
A 10-year-old male patient presented with photophobia and visual impairment in both eyes. Anterior and posterior segment examinations were unremarkable bilaterally. Optical coherence tomography (OCT) showed attenuated ellipsoid zone. Electroretinography revealed diminished cone and rod responses consistent with cone rod dystrophy (CRD). Genetic testing demonstrated a novel homozygous variant in ALMS1 (NM_015120.4) gene. The patient also was found to have early-stage dilated cardiomyopathy through systemic evaluation after the diagnosis of AS.
CONCLUSION
Cone-rod dystrophy in pediatric population is relatively rare condition that can be associated with syndromic ciliopathies. The authors presented a case of AS with a novel variant in ALMS1 gene based on ophthalmic findings. Ophthalmologists play an important role in the diagnosis of this syndrome and early detection of systemic manifestations.
PubMed: 38569205
DOI: 10.1097/ICB.0000000000001578 -
The Journal of Headache and Pain Apr 2024Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in...
Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse: activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation.
BACKGROUND
Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated.
METHODS
We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1β, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C.
RESULTS
At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2.
CONCLUSIONS
Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine.
Topics: Mice; Animals; Calcitonin Gene-Related Peptide; NF-E2-Related Factor 2; Neuroinflammatory Diseases; Reactive Oxygen Species; Photophobia; Mice, Inbred C57BL; Oxidative Stress; Nitroglycerin; Inflammation; Migraine Disorders; Benzofurans
PubMed: 38565987
DOI: 10.1186/s10194-024-01750-1 -
Clinical Neurology and Neurosurgery May 2024Pineal region lesions can result in tectal plate compression, hydrocephalus, and associated symptoms including headache, Parinaud's Syndrome, and epileptic phenomena. No... (Review)
Review
INTRODUCTION
Pineal region lesions can result in tectal plate compression, hydrocephalus, and associated symptoms including headache, Parinaud's Syndrome, and epileptic phenomena. No studies have looked at the relationship between these lesions and the autonomic nervous system.
METHODS
To evaluate the clinical presentation of pineal lesions secondary to tectal plate compression with a focus on autonomic dysfunction, a systematic review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Case reports and prospective and retrospective studies on patients with pineal or tectal region lesions were included.
RESULTS
Of 73 identified studies, 43 underwent full text screening. 26 studies (n=363 patients; age range 0-69 years) were included. 47.1% of patients were male (n=171). Obstructive hydrocephalus was identified in 119 patients (32.8%). The most common symptom was headache (n=228, 62.8%), followed by epileptic phenomena (n=76, 20.9%). Vision related symptoms were identified in 88 patients (24.2%). 251 patients (69.1%) had symptoms associated with autonomic dysfunction including dizziness, nausea, pupillary dysfunction, photophobia and fatigue. Of the 200 (55%) patients who underwent surgery, 135 patients (67.5%) had improved or resolved symptoms post-operatively, including 120 patients with improved autonomic dysfunction symptoms.
CONCLUSIONS
Though these lesions are most characterized by Parinaud's syndrome and hydrocephalus, this review suggests dysfunction of the autonomic nervous system may be at play and require consideration at initial presentation and treatment.
Topics: Humans; Autonomic Nervous System Diseases; Hydrocephalus; Pineal Gland; Male; Adult; Headache; Tectum Mesencephali; Adolescent; Child, Preschool; Aged; Child; Middle Aged; Young Adult; Female
PubMed: 38547628
DOI: 10.1016/j.clineuro.2024.108247 -
Journal of AAPOS : the Official... Jun 2024A 3-year-old boy presented with repeated episodes of corneal erosions and ulceration and absence of tear secretion since birth. Examination under anesthesia revealed a...
A 3-year-old boy presented with repeated episodes of corneal erosions and ulceration and absence of tear secretion since birth. Examination under anesthesia revealed a dry ocular surface, with corneal scarring and vascularization. Computed tomography of the orbit showed complete absence of lacrimal glands bilaterally. Minor salivary gland transplantation was performed in the right eye, which was more severely affected. This procedure has been used to manage severe dry eyes but not previously for congenital alacrimia. On long-term follow-up, 5 years after surgery, we observed considerable improvement in the photophobia, corneal transparency, and neovascularization.
Topics: Humans; Male; Child, Preschool; Salivary Glands, Minor; Tomography, X-Ray Computed; Follow-Up Studies; Lacrimal Apparatus
PubMed: 38537898
DOI: 10.1016/j.jaapos.2024.103903 -
Neurological Sciences : Official... Mar 2024Migraine is the comorbidity most frequently associated with visual snow syndrome (VSS), but the prevalence of VSS in patients with migraine (PWM) has not been studied....
PURPOSE
Migraine is the comorbidity most frequently associated with visual snow syndrome (VSS), but the prevalence of VSS in patients with migraine (PWM) has not been studied. Our objective was to evaluate the frequency of VSS in PWM and to analyze if symptoms of VSS happened in a permanent or episodic manner (eVSS) in this population.
METHODS
We conducted a multicenter observational cross-sectional study. PWM was recruited from headache units, and a survey about the presence of visual snow symptoms was administered. The frequency and characteristics of patients that met current VSS criteria were analyzed. Demographic and clinical features of patients with VSS, eVSS, and PWM with no visual snow were compared.
RESULTS
A total of 217 PWM were included. Seventeen patients (7.8%) met the VSS criteria. VSS patients had visual aura more frequently (58.8% vs. 31%; p = 0.019) and a higher MIDAS score (96.6 vs. 47.7; p = 0.014). Fifty-eight PWM (26.7%) showed visual snow and associated features in an episodic way and were classified as eVSS. Patients with VSS showed a tendency towards a higher frequency of visual symptoms than patients with eVSS (p > 0.05). No statistically significant differences in sociodemographic characteristics and comorbid conditions were found between VSS and eVSS.
CONCLUSION
The prevalence of VSS in PWM may be higher than that described for the general population. Some PWM may present similar visual symptoms to patients with VSS but in an episodic manner. Our study reinforces the observation that the clinical spectrum of visual snow is likely to be broader than previously described.
PubMed: 38536549
DOI: 10.1007/s10072-024-07483-y -
BMJ Case Reports Mar 2024Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever....
Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever. Clozapine-induced fever often occurs in the first 2 weeks of treatment and settle after a few days. We report a case of a woman in her mid-30s who developed fever and infective symptoms suggestive of an atypical pneumonia while on clozapine titration. She was on clozapine for 16 days before developing high-grade fever, dry cough, diarrhoea, headache and photophobia with a very high CRP. We performed an extensive infection workup that returned negative results except for bilateral upper lobe ground glass changes of the lungs on CT. Despite antibiotic therapy, which would cover an atypical pneumonia, her CRP remained elevated and her fever persisted. Focus was directed to clozapine-induced pneumonitis as the cause for her symptoms. Her antibiotics were ceased, and clozapine was downtitrated. With the adjustment of her clozapine dose, her fevers and associated symptoms resolved, and CRP downtrended. Her fevers did not return when clozapine was uptitrated in the community subsequently. Clozapine-induced fever or other immune-allergic reactions should be systematically considered when patients develop fever during the initiation phase of clozapine therapy. Ruling out infective causes is desirable prior to attributing fevers to clozapine especially when they are accompanied by infective symptoms and high inflammatory markers. Careful downtitration of clozapine should be considered rather than abrupt cessation in managing clozapine-induced fevers and subsequent slow uptitration could be considered.
Topics: Female; Humans; Clozapine; Antipsychotic Agents; Fever; Pneumonia, Mycoplasma
PubMed: 38531554
DOI: 10.1136/bcr-2023-259154 -
Cephalalgia : An International Journal... Mar 2024Visual snow syndrome comprises a whole-field static-like visual disturbance, with increased awareness of entopic phenomena, an inability to suppress the 'just seen' and...
PURPOSE
Visual snow syndrome comprises a whole-field static-like visual disturbance, with increased awareness of entopic phenomena, an inability to suppress the 'just seen' and photophobia. Visual snow syndrome is often associated with other problems such as headache, tinnitus, and anxiety. The earliest reported case of a patient experiencing symptoms consistent with visual snow syndrome dates only to 1995. This paper seeks to find patterns of experience in the medical literature of the past that are reminiscent of visual snow syndrome, to challenge the view that it is in any sense a novel disorder. Descriptions of subjective visual sensations such as experienced by patients suffering from visual snow syndrome were sought in treatises, textbooks and other literature generated by leading figures in 19th-century ophthalmology, physiology and physics.
CONCLUSION
While retrospective diagnosis of modern illness categories in historical medical literature is an enterprise fraught with pitfalls, it is nonetheless possible to see patterns of experience in the 19th-century medical literature that are strongly reminiscent of visual snow syndrome.
Topics: Humans; Retrospective Studies; Vision Disorders; Perceptual Disorders; Photophobia; Headache
PubMed: 38529897
DOI: 10.1177/03331024231209326