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Purpose To assess the performance of a local open-source large language model (LLM) in various information extraction tasks from real-life emergency brain MRI reports. Materials and Methods All consecutive emergency brain MRI reports written in 2022 from a French quaternary center were retrospectively reviewed. Two radiologists identified MRI scans that were performed in the emergency department for headaches. Four radiologists scored the reports conclusions as either normal or abnormal. Abnormalities were labeled as either headache-causing or incidental. Vicuna (LMSYS Org), an open-source LLM, performed the same tasks. Vicunas performance metrics were evaluated using the radiologists consensus as the reference standard. Results Among the 2398 reports during the study period, radiologists identified 595 that included headaches in the indication (median age of patients, 35 years [IQR, 26-51 years]; 68% [403 of 595] women). A positive finding was reported in 227 of 595 (38%) cases, 136 of which could explain the headache. The LLM had a sensitivity of 98.0% (95% CI: 96.5, 99.0) and specificity of 99.3% (95% CI: 98.8, 99.7) for detecting the presence of headache in the clinical context, a sensitivity of 99.4% (95% CI: 98.3, 99.9) and specificity of 98.6% (95% CI: 92.2, 100.0) for the use of contrast medium injection, a sensitivity of 96.0% (95% CI: 92.5, 98.2) and specificity of 98.9% (95% CI: 97.2, 99.7) for study categorization as either normal or abnormal, and a sensitivity of 88.2% (95% CI: 81.6, 93.1) and specificity of 73% (95% CI: 62, 81) for causal inference between MRI findings and headache. Conclusion An open-source LLM was able to extract information from free-text radiology reports with excellent accuracy without requiring further training. Keywords: Large Language Model (LLM), Generative Pretrained Transformers (GPT), Open Source, Information Extraction, Report, Brain, MRI Supplemental material is available for this article. Published under a CC BY 4.0 license. See also the commentary by Akinci DAntonoli and Bluethgen in this issue.

Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case-control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA in children with headaches based on clinically sensible and reliable variables. METHODS AND ANALYSIS: Prospective cohort study of 28 000 children with headaches presenting to any of 18 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). We include children aged 2-17 years with a chief complaint of headache. We exclude children with a clear non-intracranial alternative diagnosis, fever, neuroimaging within previous year, neurological or developmental condition such that patient history or physical examination may be unreliable, Glasgow Coma Scale score

The consumption of red wine induces headaches in some subjects who can drink other alcoholic beverages without suffering. The cause for this effect has been attributed to a number of components, often the high level of phenolics in red wine, but a mechanism has been elusive. Some alcohol consumers exhibit flushing and experience headaches, and this is attributed to a dysfunctional ALDH2 variant, the enzyme that metabolizes acetaldehyde, allowing it to accumulate. Red wine contains much higher levels of quercetin and its glycosides than white wine or other alcoholic beverages. We show that quercetin-3-glucuronide, a typical circulating quercetin metabolite, inhibits ALDH2 with an IC50 of 9.6 µM. Consumption of red wine has been reported to result in comparable levels in circulation. Thus, we propose that quercetin-3-glucoronide, derived from the various forms of quercetin in red wines inhibits ALDH2, resulting in elevated acetaldehyde levels, and the subsequent appearance of headaches in susceptible subjects. Human-subject testing is needed to test this hypothesis.

ObjectivesThe objective of this study is to understand whether the hearing loss laterality in Menière's disease (MD) correlates with migraine symptoms laterality such as headache, neck stiffness, and otalgia.MethodsWe performed a retrospective review of prospectively obtained data on patients presenting between September 2015 and October 2021 with definite or probable MD. A custom-designed, comprehensive questionnaire was used to identify patients' migraine-related symptoms. The clinical and audiometric data were used to diagnose patients with definite or probable MD using criteria set by the American Academy of Otolaryngology-Head and Neck Surgery.ResultsIn total, 113 patients with definite or probable MD were included in the study. The mean age of the patients was 60 ± 15 years with no gender predominance (49.6% male and 50.4% female). A total of 57 (50%) patients were presented with headaches. Among the migraine headache cohort, headache and otalgia were on the same side as the MD ear affected by hearing loss. In addition, in patients who present with otalgia as the primary feature of headache, otalgia was more likely to be on the same side as the ear affected by the hearing loss.ConclusionsThe high prevalence of migraine symptoms on the same side of the ear affected by MD among this cohort could suggest a shared pathophysiology in both MD and migraine, possibly involving migraine-related changes in both the cochlea and vestibule.

BackgroundMonoclonal antibody (mAb) treatment for COVID-19 is associated with improved clinical outcomes. However, there is limited information regarding the impact of treatment on symptoms and the prevalence of post-COVID Conditions (PCC). Understanding of the association between time to mAb infusion and the development of PCC is also limited.MethodsThis longitudinal study was conducted among patients with COVID-19 who received mAb infusions at a Federally Qualified Health Center in San Diego, CA. A series of telephone interviews were conducted at baseline and follow-up (14 days and 28+ days). A comprehensive symptom inventory was completed and physical and mental health status were measured using PROMIS-29 and PHQ-2. Pearson's Chi-squared tests and independent two-sample t-tests were performed to test for association between time to mAb infusion and outcomes at follow-up. A Poisson regression model was used to analyze whether time to mAb infusion predicts risk of developing PCC.ResultsParticipants (N = 411) were 53% female, ranged in age from 16 to 92 years (mean 50), and a majority (56%) were Latino/Hispanic. Cross-sectional findings revealed a high symptom burden at baseline (70% of patients had cough, 50% had fever, and 44% had headache). The prevalence of many symptoms decreased substantially by the final follow-up survey (29% of patients had cough, 3% had fever, and 28% had headache). Longitudinal findings indicated that 10 symptoms decreased in prevalence from baseline to final follow-up, 2 remained the same, and 14 increased. The severity of symptoms and most patient-reported physical and mental health measure scores decreased over time. The prevalence of PCC was 69% when PCC was defined as ≥ 1 symptom at final follow-up. Time to mAb infusion was not significantly associated with any outcome at follow-up. Time to infusion was not associated with PCC status at final follow-up in the crude or adjusted Poisson regression models.ConclusionsThe prevalence of PCC was high among this patient population following COVID-19 mAb treatment. Time to mAb infusion did not predict the development of PCC. Further research in these areas is essential to answer urgent clinical questions about effective treatments of COVID-19.

BackgroundPatient-reported outcome measures are needed to assess the impact of treatments for COVID-19 on symptoms. The ACTIV-2 COVID-19 Symptom Diary (ACSD) is being used in the ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines-2 (ACTIV-2) platform clinical trial. The purpose of the current study was to conduct qualitative interviews to assess content validity of the ACSD.MethodsInterviews were conducted with adults who had tested positive for SARS-CoV-2. The ACSD begins with global items, followed by a symptom checklist. Each interview began with concept elicitation focusing on participant experiences with COVID-19. Then, participants completed the ACSD, and cognitive interviews were conducted to evaluate the questionnaire. Interviews were recorded, transcribed, and coded following a qualitative content analysis. For the qualitative analysis, a coding dictionary was developed with a list of all potential codes and instructions for how the codes should be applied and combined.ResultsInterviews were conducted with 30 participants (mean age = 39 years; 57% female; 17% Latinx; 17% Black/African American; 40% meeting at least one criterion for classification as high risk of progression to severe COVID-19). Commonly reported symptoms included fatigue (reported by 100% of the sample), body pain/muscle pain/aches (87%), headaches (87%), cough (83%), loss of smell (73%), shortness of breath/difficulty breathing (70%), and chills (70%). The 13 symptoms most commonly reported in this study are included in the ACSD. After completing the ACSD, participants consistently reported that it was clear and easy to complete, and all items were generally interpreted as intended. Based on participants' input, the ACSD was edited slightly after the first 13 interviews, and the revised version was used for the final 17 interviews. Two additional items assessing "brain fog" and dizziness were recommended for addition to the ACSD in future research.ConclusionsThis qualitative study supports the content validity of the ACSD for assessment of COVID-19 symptoms. Quantitative research with larger samples will be needed to examine the questionnaire's measurement properties.

Purpose of reviewThis study explores legal aspects of migraine in the workplace. While the high prevalence of migraine is well-documented, its effects on the livelihoods of those living with the disease are less understood. Because migraine symptoms are often invisible, discussions concerning migraine in the workplace can be challenging. What are the rights of persons with migraine in the workplace? Time off may provide a brief respite, but it is not a long-term solution. Claiming disability for migraine has challenges, including barriers to doing so and required paperwork. How can persons with migraine remain employed and productive? How can persons with migraine receive accommodation from their employer or take time off to treat their condition?Recent findingsMany employers offer comprehensive benefit packages that allow for sick days, time off, mental health days, and accommodations that may give persons with migraine temporary reprieve. However, it may not be sufficient, particularly for those with chronic migraine. Further, not all employers offer comprehensive benefits. Employees with migraine may need to seek protection under the law. Our research closely examines the primary legal avenues that persons with migraine may pursue while living and working with migraine. In exploring the legal aspects of migraine, we couple our exploration with relevant case law. Through this lens, we conclude that migraine is becoming less stigmatized and more legitimized in the eyes of the court. It is the belief of the authors that at least some of the change in the attitude towards migraine is the result of strong patient advocacy and significant advances in research over the past several years.

ObjectiveThis study assesses the concordance in migraine diagnosis between an online, self-administered, Computer-based, Diagnostic Engine (CDE) and semi-structured interview (SSI) by a headache specialist, both using International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.BackgroundDelay in accurate diagnosis is a major barrier to headache care. Accurate computer-based algorithms may help reduce the need for SSI-based encounters to arrive at correct ICHD-3 diagnosis.MethodsBetween March 2018 and August 2019, adult participants were recruited from three academic headache centers and the community via advertising to our cross-sectional study. Participants completed two evaluations: phone interview conducted by headache specialists using the SSI and a web-based expert questionnaire and analytics, CDE. Participants were randomly assigned to either the SSI followed by the web-based questionnaire or the web-based questionnaire followed by the SSI. Participants completed protocols a few minutes apart. The concordance in migraine/probable migraine (M/PM) diagnosis between SSI and CDE was measured using Cohen's kappa statistics. The diagnostic accuracy of CDE was assessed using the SSI as reference standard.ResultsOf the 276 participants consented, 212 completed both SSI and CDE (study completion rate = 77%; median age = 32 years [interquartile range: 28-40], female:male ratio = 3:1). Concordance in M/PM diagnosis between SSI and CDE was: κ = 0.83 (95% confidence interval [CI]: 0.75-0.91). CDE diagnostic accuracy: sensitivity = 90.1% (118/131), 95% CI: 83.6%-94.6%; specificity = 95.8% (68/71), 95% CI: 88.1%-99.1%. Positive and negative predictive values = 97.0% (95% CI: 91.3%-99.0%) and 86.6% (95% CI: 79.3%-91.5%), respectively, using identified migraine prevalence of 60%. Assuming a general migraine population prevalence of 10%, positive and negative predictive values were 70.3% (95% CI: 43.9%-87.8%) and 98.9% (95% CI: 98.1%-99.3%), respectively.ConclusionThe SSI and CDE have excellent concordance in diagnosing M/PM. Positive CDE helps rule in M/PM, through high specificity and positive likelihood ratio. A negative CDE helps rule out M/PM through high sensitivity and low negative likelihood ratio. CDE that mimics SSI logic is a valid tool for migraine diagnosis.

ObjectiveTo assess the initial features and evolution of neurologic Postacute Sequelae of SARS-CoV-2 infection (neuro-PASC) in patients with and without prior neurologic disease.MethodsParticipants with neurologic symptoms following acute SARS-CoV-2 infection were recruited from October 9, 2020 to October 11, 2021. Clinical data included a SARS-CoV-2 infection history, neurologic review of systems, neurologic exam, Montreal cognitive assessment (MoCA), and symptom-based self-reported surveys at baseline (conducted after acute infection) and 6-month follow-up assessments.ResultsFifty-six participants (69% female, mean age 50 years, 29% with prior neurologic disease such as multiple sclerosis) were enrolled, of which 27 had completed the 6-month follow-up visit in this ongoing study. SARS-CoV-2 infection severity was largely described as mild (39.3%) or moderate (42.9%). At baseline, following acute infection, the most common neurologic symptoms were fatigue (89.3%) and headaches (80.4%). At the 6-month follow-up, memory impairment (68.8%) and decreased concentration (61.5%) were the most prevalent, though on average all symptoms showed a reduction in reported severity score at the follow-up. Complete symptom resolution was reported in 33.3% of participants by 6 months. From baseline to 6 months, average MoCA scores improved overall though 26.3% of participants' scores decreased. A syndrome consisting of tremor, ataxia, and cognitive dysfunction (PASC-TAC) was observed in 7.1% of patients.InterpretationEarly in the neuro-PASC syndrome, fatigue and headache are the most commonly reported symptoms. At 6 months, memory impairment and decreased concentration were most prominent. Only one-third of participants had completed resolution of neuro-PASC at 6 months, although persistent symptoms trended toward improvement at follow-up.

(1) Background: Chronic migraine is a debilitating neurological condition affecting millions worldwide. This study delves into the facial point-of-care (POC) thermographic patterns of women with chronic migraine, aiming to shed light on the condition's pathophysiology and diagnostic potential. (2) Methods: Using infrared POC thermography, the facial temperature distribution of 24 female participants with chronic migraine were analyzed. (3) Results: The findings revealed significant temperature asymmetry in women with right-sided unilateral headaches, particularly in the right frontal and temporal regions. Notably, individuals with bilateral pain did not exhibit thermal pattern differences, suggesting potential diagnostic complexities. While these results offer valuable insights, further research with larger samples is warranted (4) Conclusions: Facial thermography holds promise as an adjunctive tool for migraine diagnosis and understanding its neurophysiological basis; however, cautious interpretation is advised, given the need for validation and expanded investigations. Improved diagnostic criteria and treatment strategies may emerge from this ongoing exploration, ultimately enhancing the quality of life of chronic migraine sufferers. [ABSTRACT FROM AUTHOR]

Purpose of reviewThe purpose of this narrative review is to discuss current literature about vestibular migraine and other cochleovestibular symptoms related to migraine.Recent findingsVestibular migraine affects 2.7% of the US population. Misdiagnosis is common. The pathophysiology is currently unknown but new research shows that calcitonin gene-related peptide, which is implicated in migraine headaches, is expressed in the audiovestibular periphery. A recent large-scale placebo-controlled trial looking at metoprolol for vestibular migraine was terminated early due to poor recruitment; however, at study completion, no differences were seen between treatment arms. Many other audiovestibular symptoms have been shown to be associated with migraine, including tinnitus, hearing loss, aural fullness, otalgia, and sinus symptoms. Migraine is also associated with risk for developing numerous otologic conditions, including Meniere's disease, vestibular loss, Benign Paroxysmal Positional Vertigo, and sudden sensorineural hearing loss. There is now some evidence that patients may experience fluctuating hearing loss and aural fullness without vertigo in association with migraine, which is called cochlear migraine.SummaryMigraine can cause a variety of audiologic and vestibular symptoms, and further research is required to understand how migraine affects the inner ear.

ObjectiveTo determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).MethodsUpon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure.ResultsNP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001).ConclusionIn a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.

Purpose of reviewTo discuss the treatment of post-traumatic headache (PTH) and how to choose pharmacotherapy based upon known pathophysiology.Recent findingsPreclinical models of traumatic brain injury are finally revealing some of the mechanisms of PTH, including the significant role that inflammatory neuropeptides like calcitonin gene-related peptide (CGRP) play in the initiation and persistence of symptoms. To effectively treat post-traumatic headache (PTH), one needs to understand the pathophysiology behind the initiation and persistence of symptoms. Recent animal models are starting to elucidate these mechanisms, but effective treatment will also likely rely on the identification of patients who are most at risk for persistent PTH. Trials of early, targeted therapy for at-risk patients will be needed to validate these hypotheses. Additionally, high powered clinical trials are lacking in the field of persistent PTH for medications that are known to be effective in primary headache disorders. Effective treatment for persistent PTH also requires understanding how headache interacts with the complex nature of persistent post-concussion symptoms, as this disease often necessitates a multi-disciplinary approach. Regardless, with the knowledge gained by new PTH models cited in this paper, and an increasing availability of novel headache medications, more effective treatment models are on the horizon.

BackgroundHeterogenous central nervous system (CNS) neurologic manifestations of polyarteritis nodosa (PAN) are underrecognized. We review three cases of patients with PAN that illustrate a range of nervous system pathology, including the classical mononeuritis multiplex as well as uncommon brain and spinal cord vascular manifestations.Case presentationCase 1 presented with mononeuritis multiplex and characteristic skin findings. Case 2 presented with thunderclap headache and myelopathy due to spinal artery aneurysm rupture. Both patients experienced disease remission upon treatment. Case 3 presented with headache and bulbar symptoms due to partially thrombosed intracranial aneurysms, followed by systemic manifestations related to visceral aneurysms. She demonstrated clinical improvement with treatment, was lost to follow-up, then clinically deteriorated and entered hospice care.ConclusionsAlthough the peripheral manifestations of PAN are well-known, PAN association with CNS neurovascular disease is relatively underappreciated. Clinician awareness of the spectrum of neurologic disease is required to reduce diagnostic delay and promote prompt diagnosis and treatment with immunosuppressants.

ObjectivesTo identify migraine features present in a cohort of patients with recurrent benign paroxysmal positional vertigo (BPPV).MethodsPatients presenting with recurrent BPPV were surveyed. Recurrent BPPV was defined as three episodes or greater in 6 months before presentation, with resolution of symptoms after Epley maneuver. Current or past migraine headache (MH) diagnosis was made according to the International Headache Society guidelines.ResultsFifty-eight patients with recurrent BPPV with a mean age of 53.8 ± 17.4 years were included. Half (29 patients) fulfilled criteria for MH and half (29 patients) did not meet the criteria for MH (non-MH). No statistically significant difference was found in a majority of migraine-related symptoms between the MH and non-MH cohorts with recurrent BPPV. History of migraine medication usage (p = 0.008), presence of a weekly headache (p = 0.01), and duration of dizziness after positional vertigo (p = 0.01) were the only variables that were different on multivariate analysis between the MH and non-MH cohorts.ConclusionsHalf of recurrent BPPV patients suffer from migraine headaches. The other half presented with migraine-related symptoms, but do not meet criteria for MH. The high comorbidity of MH in our recurrent BPPV cohort as well as the absence of a statistically significant difference in a majority of migraine-related features among patients who did and did not fulfill criteria for MH may suggest that recurrent BPPV has a relationship with migraine. Recurrent BPPV may potentially be a manifestation of migraine in the inner ear, which we term otologic migraine including cochlear, vestibular, or cochleovestibular symptoms.

Mild Traumatic Brain Injury (MTBI) patients with persistent headaches are known to have diminished supraspinal modulatory connectivity from their prefrontal cortices. Repetitive transcranial magnetic stimulation (rTMS) is able to alleviate MTBI-related headache (MTBI-HA). This functional magnetic resonance imaging (fMRI) study assessed supraspinal correlates associated with the headache analgesic effect of rTMS at left prefrontal cortex (LPFC), hypothesizing real rTMS would significantly increase modulatory functions at LPFC in comparison to sham treatment. Subjects with MTBI-HA were randomized to receive either real or sham rTMS treatments and subjected to pre- and post-treatment resting state and evoked heat-pain fMRI as described in a prior study. Real rTMS consisted of 2000 pulses delivered at 10 Hz and 80% of the resting motor threshold at left dorsolateral prefrontal cortex, whereas sham treatment was delivered with same figure-of-eight coil turned 180 degrees. Follow-up fMRI was performed one-week post-treatment. All fMRI data was processed using BrainVoyager QX Software. 14 subjects receiving real and 12 subjects receiving sham treatments completed the study. The REAL group demonstrated significant (P

Emerging evidence suggests mild traumatic brain injury related headache (MTBI-HA) is a form of neuropathic pain state. Previous supraspinal mechanistic studies indicate patients with MTBI-HA demonstrate a dissociative state with diminished levels of supraspinal prefrontal pain modulatory functions and enhanced supraspinal sensory response to pain in comparison to healthy controls. However, the relationship between supraspinal pain modulatory functional deficit and severity of MTBI-HA is largely unknown. Understanding this relationship may provide enhanced levels of insight about MTBI-HA and facilitate the development of treatments. This study assessed pain related supraspinal resting states among MTBI-HA patients with various headache intensity phenotypes with comparisons to controls via functional magnetic resonance imaging (fMRI). Resting state fMRI data was analyzed with self-organizing-group-independent-component-analysis in three MTBI-HA intensity groups (mild, moderate, and severe) and one control group (n = 16 per group) within a pre-defined supraspinal pain network based on prior studies. In the mild-headache group, significant increases in supraspinal function were observed in the right premotor cortex (T = 3.53, p

BackgroundWe performed a post hoc, subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled study of erenumab for prevention of episodic migraine (STRIVE) to determine the efficacy and safety of erenumab in women with self-reported menstrual migraine.MethodsPatients received placebo, erenumab 70 mg, or erenumab 140 mg subcutaneously once monthly during the 6-month double-blind treatment phase of STRIVE. Women who reported history of menstrual migraine and who were ≤ 50 years old were included in the analysis. Endpoints were change from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD; among patients who took acute migraine-specific medications at baseline), proportion of patients achieving ≥ 50% reduction from baseline in MMD, and incidence of adverse events.ResultsAmong 814 women enrolled in STRIVE, 232 (28.5%) reported a history of menstrual migraine and were ≤ 50 years old. Of the 232 patients, 214 (92%) had a baseline MMD > 5, suggesting a high proportion of women with attacks outside of the 5-day perimenstrual window (2 days before and 3 days after the start of menstruation). Information on "migraine days" includes (and does not discriminate between) perimenstrual and intermenstrual migraine attacks. Between-group differences from placebo over months 4-6 for erenumab 70 mg and 140 mg were - 1.8 (P = 0.001) and - 2.1 (P

ObjectivesTo determine the relationship between vestibular migraine (VM) and motion sickness (MoS) susceptibility and their comorbidity in a large student population, and to assess whether experiencing MoS is associated with higher susceptibility for VM.MethodsSurveys including Motion Sickness Susceptibility Questionnaire (MSSQ) and questions assessing migraine-related symptoms as well as family history of motion sickness and migraine headache were distributed to the university undergraduate students through Facebook and email. Diagnosis of definite VM (dVM) was based on the criteria of the International Classification of Headache Disorders.ResultsOf 277 survey responders, 148 (53%) were found to be susceptible to MoS in which 74 (50%) met the criteria for dVM. Only childhood MSSQ score was significantly higher in participants with dVM compared with those without dVM (25.78 ± 15.89 versus 20.77 ± 14.28, p = 0.04); however, its significance faded out by regression analysis. Multivariate logistic regression showed having 1st degree relative with migraine headache (p = 0.02), neck stiffness (p = 0.001), and sinus pain, facial pressure, or headache with wind exposure (p = 0.02) to be independently associated with presence of dVM in MoS subjects.ConclusionsThough participants with MoS and dVM had significantly greater rates of migraine-related symptoms and family history of migraine headache compared with those with MoS only, childhood and adulthood MSSQ scores were similar. This and the high prevalence of dVM in our MoS cohort may suggest an existing association between MoS susceptibility and VM.

BackgroundTesting for SARS-CoV-2 is important for decision making prior to surgery in otolaryngology. An understanding of current and developing testing methods is important for interpreting test results.MethodsWe performed a literature review of current evidence surrounding SARS-CoV-2 diagnostic testing highlighting its utility, limitations, and implications for otolaryngologists.ResultsThe currently accepted RT-PCR test for SARS-CoV-2 has varying sensitivity according to which subsite of the aerodigestive tract is sampled. Nasal swab sensitivities appear to be about 70%. Chest CT imaging for screening purposes is not currently recommended.ConclusionDue to the current sensitivity of RT-PCR based testing for SARS-CoV-2, a negative test cannot rule out COVID-19. Full PPE should be worn during high-risk procedures such as aerosol generating procedures even if testing is negative. Patients who test positive during screening should have their surgeries postponed if possible until asymptomatic and have tested negative for SARS-CoV-2.

ObjectiveTo determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features.MethodsWe report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes.ResultsOf 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions.ConclusionSpecific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

ObjectiveTo determine the interobserver agreement of history and physical examination findings in children undergoing evaluation in the emergency department (ED) for headaches.Study designWe conducted a prospective, cross-sectional study of children aged 2-17 years evaluated at 3 tertiary-care pediatric EDs for non-traumatic headaches. Two clinicians independently completed a standardized assessment of each child and documented the presence or absence of history and physical examination variables. Unweighted κ statistics were determined for 68 history and 24 physical examination variables.ResultsWe analyzed 191 paired observations; median age was 12 years, with 19 (9.9%) children younger than 7 years. Interrater reliability was at least moderate (κ ≥ 0.41) for 41 (60.3%) patient history variables. Eleven (61.1%) of 18 physical examination variables for which κ statistics could be calculated had a κ that was at least moderate.ConclusionsA substantial number of history and physical examination findings demonstrated at least moderate κ statistic values when assessed in children with headaches in the ED. These variables may be generalizable across different types of clinicians for evaluation of children with headaches. If also found to predict the presence or absence of emergent intracranial abnormalities, the more reliable clinical findings may be helpful in the development of clinical prediction rules or risk stratification models that could be used across settings for children with headaches.

ObjectiveWe aimed to assess the association between migraine headache and incident dementia.BackgroundMigraine is a risk factor for white matter hyperintensities and ischemic stroke, which are both associated with increased risk of dementia. However, it is unknown whether migraine is independently associated with dementia.MethodsHistory of migraine was ascertained via questionnaire. Adjudicated cases of dementia were identified using cognitive tests, neuropsychological exams, and clinician review of suspected cases. Incident dementia was identified using adjudicated cases, follow-up calls, and surveillance of hospital and death codes. We assessed hazards of incident dementia by migraine status. Sex differences were also examined and stratified results were presented.ResultsAnalysis included 12,495 White and African American participants ages 51-70 with a median follow-up time of 21 years. Prevalence of dementia was 18.5% (1821/9955) among those with no migraine history, 15.8% (196/1243) among those with severe non-migraine heading, and 16.7% (233/1397) among migraineurs. There was no association between migraine and incident dementia [hazard ratio: 1.04 (0.91, 1.20)]. There was also no statistically significant interaction between sex and migraine status on risk of dementia.ConclusionDespite evidence of brain abnormalities in migraineurs, there was no association between migraine and incident dementia in this prospective cohort.

ObjectivesTo evaluate if patients with a diagnosis of vestibular migraine (VM) by the International Classification of Headache Disorders (ICHD) criteria have meaningful differences in symptomatology and disease characteristics when compared to patients with concurrent vestibular symptoms and migraine that do not meet ICHD criteria.MethodsPatients who presented for the evaluation of vertigo were provided a detailed questionnaire about dizziness and migraine symptoms. Patients were assigned to either VM cohort (met ICHD criteria for VM) or migraine headache (MH) cohort (met ICHD criteria for migraine with or without aura but not VM). Disease characteristics, symptomatology, quality of life, and perceived stress score were compared between the cohorts.ResultsThe VM cohort demonstrated a shorter duration of vertigo episodes, 11 ± 22 hours versus 84 ± 146 hours in the MH cohort. In the VM cohort, 81% reported experiencing migraine headaches during episodes of vertigo, versus 61% in the MH cohort. All patients in the VM cohort reported a previous diagnosis of migraine headache, whereas 9% of the MH cohort had not been previously diagnosed by another physician. There was no difference in quality of life or perceived stress scores between the cohorts.ConclusionsA large proportion of vertigo patients with migrainous features do not meet the ICHD criteria for VM. The differences between cohorts represent selection bias rather than meaningful features unique to the cohorts. As such, VM and MH with vestibular symptoms may exist on a spectrum of the same disease process and may warrant the same treatment protocols.

Between 2016 and 2017, several U.S. Diplomats in Havana, Cuba, experienced perplexing vestibular and neurological symptoms attributed to an unknown source. They presented with significant vestibular and headache symptoms similar to individuals who experience vestibular migraine (VM). As such, we hypothesize that VM may be a possible explanation for the Havana cohort's presenting symptoms. To evaluate this hypothesis, we compared symptoms reported by the affected individuals in Havana, Cuba, to symptoms reported by corresponding patients from a tertiary academic neurotology clinic with a chief complaint of vertigo or disequilibrium, who met the International Classification of Headache Disorders criteria for VM. The prevalence of the Havana subjects experiencing various symptomatic domains was compared with the VM cohort, leading to 26 unique domains and statistical comparisons between the cohorts. Of the 26 domains compared between the two cohorts, 18 were not significantly different. This included the two most important components of meeting criteria for VM, namely the co-existence of headache and vestibular symptoms. On regression analysis, the only feature which kept its significant difference between the two cohorts was acute intense head pressure (P = 0.007). The domains with similar occurrence ratios included dizziness, headache, light sensitivity, hearing reduction, and tinnitus. In other words, multiple headache and vestibular symptoms, consistent with VM criteria, were similar between the two cohorts. The considerable similarities across various domains between VM patients and Havana subjects could be due to migraine as a possible common etiology for both groups. We propose VM as a potential etiology for the symptomatology in the U.S. diplomats in Cuba.

BackgroundHeavy load carrying has been associated with musculoskeletal discomfort (MSD) and disability. However, there is a lack of research investigating this association in resource-constrained settings where heavy load carrying by women is common.ObjectivesWe assessed the impact of heavy load carrying on musculoskeletal pain and disability among women in Shinyanga Region, Tanzania, in an exploratory cross-sectional study.MethodsEligible participants were a convenience sample of women, at least 18 years of age, who passed a study recruitment site carrying a load. We collected information on load-carrying practices, including frequency and time spent carrying water, wood, agricultural products, coal, sand, or rocks, and measured the weight of the load carried at the time. Outcomes included self-reported MSDs, defined as experiencing pain lasting >3 days in the neck, head, back, knees, feet and/or ankles within the last 1 year, and related disability. Using multivariable logistic regression we assessed for associations between load carrying exposures and MSDs and disability.FindingsResults showed a high prevalence of MSDs across the body regions assessed and evidence to suggest a relationship of back pain and related disability with several measures of load-carrying, including duration, frequency, and weight. Multivariable analyses revealed associations of increased load carrying exposures with low back pain (LBP) and related disability, including statistically significant increases in odds of LBP with increasing weight, total duration of load carrying/week and cumulative loads/week.ConclusionsFindings indicate a substantial burden of MSDs and disability in this population of women who carry heavy loads daily. The extent of discomfort and disability increased with increasing exposure to various load-carrying measures, especially for LBP. Larger epidemiologic studies that definitively assess relationships of load carrying with MSDs and disability are warranted.

Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as ⩾10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori-defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.

(1) Background: Chronic migraine is a debilitating neurological condition affecting millions worldwide. This study delves into the facial point-of-care (POC) thermographic patterns of women with chronic migraine, aiming to shed light on the condition’s pathophysiology and diagnostic potential. (2) Methods: Using infrared POC thermography, the facial temperature distribution of 24 female participants with chronic migraine were analyzed. (3) Results: The findings revealed significant temperature asymmetry in women with right-sided unilateral headaches, particularly in the right frontal and temporal regions. Notably, individuals with bilateral pain did not exhibit thermal pattern differences, suggesting potential diagnostic complexities. While these results offer valuable insights, further research with larger samples is warranted (4) Conclusions: Facial thermography holds promise as an adjunctive tool for migraine diagnosis and understanding its neurophysiological basis; however, cautious interpretation is advised, given the need for validation and expanded investigations. Improved diagnostic criteria and treatment strategies may emerge from this ongoing exploration, ultimately enhancing the quality of life of chronic migraine sufferers.

Sugar-sweetened beverages (SSBs) increase risk of cardiometabolic disease. Young people consume the largest amounts of SSBs and have experienced the greatest relative gains in obesity in the past several decades. There is evidence of addictive properties of both caffeine and sugar, the primary ingredients in SSBs, but little research into such properties of SSBs in naturally occurring consumption patterns. Thus, in this exploratory study, we sought to examine potentially addictive properties of SSBs during a 3-day SSB cessation intervention in overweight and obese adolescents who typically consume ≥3 SSBs daily. Participants (n = 25) were aged 13-18 years, mostly female (72%), and African American (56%) or Hispanic (16%) with a BMI≥95th percenttile (76%). Withdrawal symptoms and SSB craving were assessed approximately 1-week apart, during both regular SSB consumption and a 3-day period of SSB cessation in which participants were instructed to drink only plain milk and water. During SSB cessation, adolescents reported increased SSB cravings and headache and decreased motivation, contentment, ability to concentrate, and overall well-being (uncorrected Ps

BACKGROUND:Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES:To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS:We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA:For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS:Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS:We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS:Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

OBJECTIVE:To describe visits and visit rates of adults presenting to emergency departments (EDs) with a diagnosis of traumatic brain injury (TBI). TBI is a major cause of death and disability in the USA; yet, current literature is limited because few studies examine longer-term ED revisits and hospital readmission patterns of TBI patients across a broad spectrum of injury severity, which can help inform potential unmet healthcare needs. DESIGN:We performed a retrospective cohort study. SETTING:We analysed non-public patient-level data from California's Office of Statewide Health Planning and Development for years 2005 to 2014. PARTICIPANTS:We identified 1.2 million adult patients aged ≥18 years presenting to California EDs and hospitals with an index diagnosis of TBI. PRIMARY AND SECONDARY OUTCOME MEASURES:Our main outcomes included revisits, readmissions and mortality over time. We also examined demographics, mechanism and severity of injury and disposition at discharge. RESULTS:We found a 57.7% increase in the number of TBI ED visits, representing a 40.5% increase in TBI visit rates over the 10-year period (346-487 per 100 000 residents). During this time, there was also a 33.8% decrease in the proportion of patients admitted to the hospital. Older, publicly insured and black populations had the highest visit rates, and falls were the most common mechanism of injury (45.5% of visits). Of all patients with an index TBI visit, 40.5% of them had a revisit during the first year, with 46.7% of them seeking care at a different hospital from their initial hospital or ED visit. Additionally, of revisits within the first year, 13.4% of them resulted in hospital readmission. CONCLUSIONS:The large proportion of patients with TBI who are discharged directly from the ED, along with the high rates of revisits and readmissions, suggest a role for an established system for follow-up, treatment and care of TBI.

The discovery that intravenous (IV) infusions of the neuropeptide PACAP-38 (pituitary adenylyl cyclase activating peptide-38) induced delayed migraine-like headaches in a large majority of migraine patients has resulted in considerable excitement in headache research. In addition to suggesting potential therapeutic targets for migraine, the finding provides an opportunity to better understand the pathological events from early events (aura) to the headache itself. Although PACAP-38 and the closely related peptide VIP (vasoactive intestinal peptide) are well-known as vasoactive molecules, the dilation of cranial blood vessels per se is no longer felt to underlie migraine headaches. Thus, more recent research has focused on other possible PACAP-mediated mechanisms, and has raised some important questions. For example, (1) are endogenous sources of PACAP (or VIP) involved in the triggering and/or propagation of migraine headaches?; (2) which receptor subtypes are involved in migraine pathophysiology?; (3) can we identify specific anatomical circuit(s) where PACAP signaling is involved in the features of migraine? The purpose of this review is to discuss the possibility, and supportive evidence, that PACAP acts to induce migraine-like symptoms not only by directly modulating nociceptive neural circuits, but also by indirectly regulating the production of inflammatory mediators. We focus here primarily on postulated extra-dural sites because potential mechanisms of PACAP action in the dura are discussed in detail elsewhere (see X, this edition).

BackgroundThere are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.MethodsWe enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis.ResultsOf 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.ConclusionsIn a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).

ObjectiveTo better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions.BackgroundAdhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo.MethodsWe undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia.ResultsOf the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n = 79), phonophobia (n = 43), and nausea (n = 37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P = .02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P = .05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P = .01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P

Background & aimsWe report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens.MethodsThe RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12 weeks of LDV/SOF or LDV/SOF + RBV. Compensated cirrhotic participants were randomized to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). Both studies used SVR at 12 weeks post-treatment (SVR12) as the primary endpoint.ResultsIn the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF + RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF + RBV for 12 weeks or LDV/SOF for 24 weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n = 1; GT1a n = 5) and all attained SVR12, with no serious AEs or premature discontinuations.ConclusionsIn this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved.

ObjectiveTo evaluate lumbar drain (LD) efficacy in transnasal resection of pituitary macroadenomas in preventing postoperative cerebrospinal fluid (CSF) leak, technique safety, and effect on length of hospital stay.MethodsWe conducted a retrospective data review of pituitary tumor patients in our institution who underwent surgery between December 2006 and January 2013. All patients were operated on for complete surgical resection of pituitary macroadenoma tumors. Patients were divided into 2 groups: group 1 received a preoperative drain, while LD was not preoperatively inserted in group 2. In cases of tumors with suprasellar extension with anticipation of high-flow leak, LD was inserted after the patient was intubated and in a lateral position. Lumbar drain was used for 48 hours, and the drain was removed if no leak was observed postoperatively. In documented postoperative CSF leak patients with no preoperative drain, the leak was treated by LD trial prior to surgical reconstruction. Cases in which leak occurred 6 months postoperatively were excluded.ResultsOur study population consisted of 186 patients, 99 women (53%) and 87 men (47%), with a mean age of 50.3+/-16.1 years. Complications occurred in 7 patients (13.7%) in group 1 versus 21 (15.5%) in group 2 (p=0.72). Postoperative CSF leak was observed in 1 patient (1.9%) in group 1 and 7 (5%) in group 2 (Fisher exact test=0.3). Length of hospital stay was a mean of 4.7+/-1.9 days in group 1 and a mean of 2.7+/-2.4 days in group 2 (p

Objective: To determine whether glibenclamide, a non-selective adenosine 5′-triphosphate-sensitive K+ (KATP) channel blocker, attenuates pituitary adenylate cyclase-activating polypeptide-38 (PACAP38)-induced headache and vascular changes in healthy volunteers. Methods: In a double-blind, randomized, placebo controlled and crossover design, 22 healthy volunteers were assigned to receive an intravenous infusion of 10 picomole/kg/min pituitary adenylate cyclase-activating polypeptide-38 over 20 minutes followed by oral administration of 10 mg glibenclamide or placebo. The primary endpoint was the difference in incidence of headache (0–12 hours) between glibenclamide and placebo. The secondary endpoints were a difference in area under the curve for headache intensity scores, middle cerebral artery velocity (VmeanMCA), superficial temporal artery diameter, radial artery diameter, heart rate, mean arterial blood pressure and facial skin blood flow between the two study days. Results: Twenty participants completed the study. We found no difference in the incidence of pituitary adenylate cyclase-activating polypeptide-38-induced headache after glibenclamide (19/20, 95%) compared to placebo (18/20, 90%) (P = 0.698). The area under the curve for headache intensity, middle cerebral artery velocity, superficial temporal artery diameter, radial artery diameter, facial skin blood flow, heart rate and mean arterial blood pressure did not differ between pituitary adenylate cyclase-activating polypeptide-38-glibenclamide day compared to pituitary adenylate cyclase-activating polypeptide-38-placebo day (P > 0.05). Conclusions: Posttreatment with 5′-triphosphate-sensitive K+ channel inhibitor glibenclamide did not attenuate pituitary adenylate cyclase-activating polypeptide-38-induced headache and hemodynamic changes in healthy volunteers. We suggest that pituitary adenylate cyclase-activating polypeptide-38-triggered signaling pathway could be mediated by specific isoforms of sulfonylurea receptor subunits of 5′-triphosphate-sensitive K+ channels and other types of potassium channels. [ABSTRACT FROM AUTHOR]

Objective: To systematically review clinical studies investigating the involvement of adenosine and its receptors in migraine pathophysiology. Background: Adenosine is a purinergic signaling molecule, clinically used in cardiac imaging during stress tests. Headache is a frequent adverse event after intravenous adenosine administration. Migraine headache relief is reported after intake of adenosine receptor antagonist, caffeine. These findings suggest a possible involvement of adenosine signaling in migraine pathophysiology and its potential as a drug target. Methods: A search through PubMed and EMBASE was undertaken for clinical studies investigating the role of adenosine and its receptors in migraine, published until September 2021. Results: A total of 2510 studies were screened by title and abstract. Of these, seven clinical studies were included. The main findings were that adenosine infusion induced headache, and plasma adenosine levels were elevated during ictal compared to interictal periods in migraine patients. Conclusion: The present systematic review emphasizes a potentially important role of adenosine signaling in migraine pathogenesis. Further randomized and placebo-controlled clinical investigations applying adenosine receptors modulators in migraine patients are needed to further understand the adenosine involvement in migraine. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has necessitated the use of personal protective equipment (PPE) among the frontline health care workers (HCWs). Even though PPE helps in preventing infection, it poses significant physical and psychological impacts at varying levels. Correspondingly, multiple independent studies have brought out the PPE-associated problems. However, there exists a lacuna on comprehensive information of global prevalence related to the same. Aim: To estimate the prevalence and risk factors of PPE among HCWs during COVID-19 across the globe. Design: Systematic review and meta-analysis. Method: The review was undertaken as per the protocol registered in PROSPERO CRD42021272216 following Preferred Reporting Items for Systematic Reviews and Meta-Analysis(PRISMA) guidelines. Two independent reviewers have undertaken the search strategy, study selection, and methodological quality assessment. Discrepancies were addressed by the third reviewer. Heterogeneity was addressed through I2 statistics and forest plots generated by open meta-software. Results: A total of 16 articles conducted across 6 different countries among 10,182 HCWs were included in the review. The pooled prevalence of skin lesions, headache, sweating, breathing difficulty, vision difficulty, thirst/dry mouth, fatigue, and communication difficulty, anxiety, fear were 57 (47-66%), 51 (37-64%), 75 (56-90%), 44 (23-68%), 61 (21-94%), 54 (30-77%), 67 (58-76%), 74 (47-94%), 28 (24-33%), 14 (10-17%), respectively. Moreover, the various risk factors included are the use of PPE for >6 h and young females. In addition, the medical management of new-onset problems created an additional burden on the frontline health care personnel (HCP). Conclusion: The frontline HCWs encountered physical and psychological problems at varying levels as a result of wearing PPE which needs to be addressed to prevent the inadequate use of PPE leading to infections. [ABSTRACT FROM AUTHOR]

Background: Mastoid Pressure Dressing (MPD) has been commonly used by otolaryngologists from 1960 as a post-operative care after mastoid or middle ear surgeries. MPD may be removed after the first day or 5 days after the surgery but it is not clear whether early or late removal is associated with less side effects. To clarify the optimal time of MPD removal, we conducted this prospective study. Methods: A total of 56 patients, including 19 males and 37 females with the mean age of 38.23±15.9 years, were included in this study. Among these, 31 patients underwent early MPD removal (after one day) and for the other 25 patients, MPD was removed five days following the surgery, Tympanoplasty or Tympanomastoidectomy. Results: There was no significant difference between the two groups in gender distribution or mean age. In addition, no significant betweengroup difference was detected in developing hematoma and sleep disturbance, but patients with late MPD removal showed higher rates of headache and erythema. Conclusion: Current study suggests that MPD may be removed as soon as possible after the surgery due to its side effects inducing headache and irritation. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the common thinking, as reinforced by the International Classification of Headache Disorders, 3rd edition (beta), that occipital headaches in children are rare and suggestive of serious intracranial pathology.MethodsWe performed a retrospective chart review cohort study of all patients ≤18 years of age referred to a university child neurology clinic for headache in 2009. Patients were stratified by headache location: solely occipital, occipital plus other area(s) of head pain, or no occipital involvement. Children with abnormal neurologic examinations were excluded. We assessed location as a predictor of whether neuroimaging was ordered and whether intracranial pathology was found. Analyses were performed with cohort study tools in Stata/SE 13.0 (StataCorp, College Station, TX).ResultsA total of 308 patients were included. Median age was 12 years (32 months-18 years), and 57% were female. Headaches were solely occipital in 7% and occipital-plus in 14%. Patients with occipital head pain were more likely to undergo neuroimaging than those without occipital involvement (solely occipital: 95%, relative risk [RR] 10.5, 95% confidence interval [CI] 1.4-77.3; occipital-plus: 88%, RR 3.7, 95% CI 1.5-9.2; no occipital pain: 63%, referent). Occipital pain alone or with other locations was not significantly associated with radiographic evidence of clinically significant intracranial pathology.ConclusionsChildren with occipital headache are more likely to undergo neuroimaging. In the absence of concerning features on the history and in the setting of a normal neurologic examination, neuroimaging can be deferred in most pediatric patients when occipital pain is present.

ImportanceHospital-employed physicians provide primary care within the hospital or within community-based office practices. Yet, little is understood regarding the influence of hospital location and ownership on the delivery of low-value care.ObjectiveTo assess the association of hospital location and hospital ownership with the provision of low-value health services.Design, setting, and participantsThis study compared low-value service use after primary care visits at hospital-based outpatient practices from January 1, 1997, to December 31, 2011, vs community-based office practices and at hospital-owned vs physician-owned community-based office practices from January 1, 1997, to December 31, 2013. Logistic regression models adjusted for patient and health care professional characteristics and year, and weighted results were used to reflect population estimates. Results were also stratified by symptom acuity and whether a generalist physician (eg, general internist or family practitioner) was the patient's primary care provider. This study used nationally representative data from the National Ambulatory Medical Care Survey (January 1, 1997, to December 31, 2013) and the National Hospital Ambulatory Medical Care Survey (January 1, 1997, to December 31, 2011) on outpatient visits to generalist physicians. Participants were patients seen with 3 common primary care conditions, namely, upper respiratory tract infection, back pain, and headache.Main outcomes and measuresThe use of antibiotics (for upper respiratory tract infection), computed tomography or magnetic resonance imaging (for back pain and headache), radiographs (for upper respiratory tract infection and back pain), and specialty referrals (for all 3 conditions).ResultsThis study identified 31 162 visits for upper respiratory tract infection, back pain, and headache, representing an estimated 739 million US primary care visits from 1997 to 2013. Compared with visits with community-based physicians, patients in visits to hospital-based physicians were younger (mean age, 44.5 vs 49.1 years; P

ImportanceChemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited.ObjectivesTo evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life.Design, setting, and participantsA prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). The study was conducted between August 2013 and October 2014 with ongoing annual follow-up for 5 years.ExposuresUse of a scalp cooling system. Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward.Main outcomes and measuresSelf-estimated hair loss using the Dean scale was assessed 4 weeks after the last dose of chemotherapy by unblinded patient review of 5 photographs. A Dean scale score of 0 to 2 (≤50% hair loss) was defined as treatment success. A positive association between scalp cooling and reduced risk of hair loss would be demonstrated if 50% or more of patients in the scalp cooling group achieved treatment success, with the lower bound of the 95% CI greater than 40% of the success proportion. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later. Median follow-up was 29.5 months.ResultsAmong the 122 patients in the study, the mean age was 53 years (range, 28-77 years); 77.0% were white, 9.0% were black, and 10.7% were Asian; and the mean duration of chemotherapy was 2.3 months (median, 2.1 months). No participants in the scalp cooling group received anthracyclines. Hair loss of 50% or less (Dean score of 0-2) was seen in 67 of 101 patients (66.3%; 95% CI, 56.2%-75.4%) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0%) in the control group (P

ObjectivesIn evaluating the historical context of the first description of Menière's disease, its association with migraine headaches is compelling. We have outlined the events and observations of Prosper Menière, which led him to establish a link between migraine headaches and his eponymous disease.Study designProsper Menière's original French writings were translated by our group and used to recount his observations and thoughts. Miles Atkinson's English translations were used as a reference. Additional otological texts of the era were also reviewed as it relates to Menière's disease.MethodsProsper Menière wrote a series of four articles 1 year before his death. In one of these articles, he makes references to migraine headaches on several occasions. These original writings were analyzed, and the physical findings he described were interpreted based on their relation to migraine headaches.ResultsThe passages in his published articles provide historical insight into Menière's observations. His writings describe in detail symptoms of migraine headaches uniquely evident in his patient population. Through his observations, he recognized that in addition to exhibiting symptoms of tinnitus, hearing loss and vertigo his patients also suffered from migraine headaches.ConclusionsAlthough his colleagues discounted Menière's theory concerning migraine headaches, he continued to make deductive inferences and publish his findings, leading to the association of migraine headaches and Menière's disease. Today, this association continues to be debated, adding to Prosper Menière's legacy.