We thank Drs. Nguyen and Hu for their comments on our paper, and for suggesting the fragility index as a method to assess claims about statistical significance. Its major virtue is to draw attention to the number of events that would have to change in the control group in order to shift the P value to above .05. In a large series of randomized, controlled trials (RCTs), the median fragility index was 8, and such low numbers may help to identify less robust results. The calculation of fragility indices can probably be useful in methodological evaluation of RCTs, but it is most likely not suitable for evaluation of the clinical relevance of the results in an RCT. For this purpose, the calculation of therapeutic gain with 95% CI conveys more clinically relevant information. To us and to over 800 signatories of a recent editorial in the journal Nature, however, the larger problem seems to be the “dichotomania” that prevails in interpreting P values. Any P value threshold is artificial. It is naive and simplistic to use P values to claim that effects are present or absent. Instead, P values should be interpreted as a continuous measure and study findings should be framed in terms of clinical benefit. Researchers and readers should be encouraged to consider whether, across all values within the 95% confidence interval, there is evidence of meaningful medical effects. It can be difficult to decide whether trial findings are clinically important, and such determinations are often context-specific. No metric solves all problems of interpretation or can substitute for common sense and clinical judgment. Everyone should beware of claims that study findings are “highly statistically significant.” The next time someone invites you to admire a very tiny P value, consider that they may be hoping you will “pay no attention to that [equally tiny effect size] behind the curtain.”
{"title":"Further Questioning of the Significance of the Gepants: A Response","authors":"E. Loder, P. Tfelt-Hansen","doi":"10.1111/head.13683","DOIUrl":"https://doi.org/10.1111/head.13683","url":null,"abstract":"We thank Drs. Nguyen and Hu for their comments on our paper, and for suggesting the fragility index as a method to assess claims about statistical significance. Its major virtue is to draw attention to the number of events that would have to change in the control group in order to shift the P value to above .05. In a large series of randomized, controlled trials (RCTs), the median fragility index was 8, and such low numbers may help to identify less robust results. The calculation of fragility indices can probably be useful in methodological evaluation of RCTs, but it is most likely not suitable for evaluation of the clinical relevance of the results in an RCT. For this purpose, the calculation of therapeutic gain with 95% CI conveys more clinically relevant information. To us and to over 800 signatories of a recent editorial in the journal Nature, however, the larger problem seems to be the “dichotomania” that prevails in interpreting P values. Any P value threshold is artificial. It is naive and simplistic to use P values to claim that effects are present or absent. Instead, P values should be interpreted as a continuous measure and study findings should be framed in terms of clinical benefit. Researchers and readers should be encouraged to consider whether, across all values within the 95% confidence interval, there is evidence of meaningful medical effects. It can be difficult to decide whether trial findings are clinically important, and such determinations are often context-specific. No metric solves all problems of interpretation or can substitute for common sense and clinical judgment. Everyone should beware of claims that study findings are “highly statistically significant.” The next time someone invites you to admire a very tiny P value, consider that they may be hoping you will “pay no attention to that [equally tiny effect size] behind the curtain.”","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73626721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. J. Mancini, R. D. Glassman, Yu-Ming Chang, R. Burstein, S. Ashina
To report a case of petrous apicitis that manifested as chronic migraine without aura and to discuss the pathophysiological mechanisms behind this presentation.
报告一例表现为无先兆的慢性偏头痛的岩性阑尾炎，并讨论其病理生理机制。
{"title":"Headache in Petrous Apicitis: A Case Report of Chronic Migraine‐like Headache Due to Peripheral Pathology","authors":"A. J. Mancini, R. D. Glassman, Yu-Ming Chang, R. Burstein, S. Ashina","doi":"10.1111/head.13643","DOIUrl":"https://doi.org/10.1111/head.13643","url":null,"abstract":"To report a case of petrous apicitis that manifested as chronic migraine without aura and to discuss the pathophysiological mechanisms behind this presentation.","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80829441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dr. Fanella et al published in Headache, a possible additional case of “Ictal Epileptic Headache” (IEH), that they classified as a “non convulsive status epilepticus.” They reported a woman experiencing migraine attacks-featuring prolonged, intense, throbbing, left temporal pain associated with ipsilateral visual symptoms (ie, non-colored flashes and photophobia) and nausea or vomiting, unresponsive to painkillers – associated with epileptic activity over the right posterior cerebral regions and responsive to intravenous lacosamide. The first description of a documented isolated headache as a sole ictal manifestation of an epileptic seizure (erroneously reported by Dr. Fanella et al, as first published in 2011) was described and published in Epilepsia in 2007 by Parisi et al. These authors coined and published the “original criteria” for IEH diagnosis in 2012, although they have not yet been recognized by the International League Against Epilepsy classification. Indeed, IEH criteria should be applied to all cases where headache is the sole, or is the earliest and most evident feature, of a seizure, regardless of other possible “subtle” associated manifestations; in fact, the same authors have suggested that, to enable a IEH diagnosis, a careful and detailed neurologic exam must be carried, to rule out other associated ictal signs and symptoms. In particular, the availability of an ictal video-EEG recording confirming the clinical suspect of a headache of epileptic origin as well as the prompt response to anti-seizure therapy is of paramount importance in such cases, which may be challenging even for the most expert of clinicians. Fanella and colleagues’ description confirms that (video)-EEG recording – not routinely recommended in patients with headache – should be considered promptly in individuals reporting prolonged migraine/headache not responsive to analgesics. Moreover, ictal EEG recording does also allow the clinician to differentiate IEH from the misleading “migralepsy” concept that probably does not exist at all (ie, “an isolated ictal headache, immediately followed by other epileptic manifestation”). The pathophysiology of IEH is still a matter of on-going research. Although there is not a specific cortical substrate, the most frequently reported origin of IEH is in the posterior cerebral areas, particularly the occipital lobe, as it is a vulnerable region for the onset of both seizures and headache. Notably, 10 years before the epilepsy onset, the patient reported by Dr. Fanella et al had been hospitalized for eclampsia, followed by focal seizures and prolonged coma. Her brain MRI revealed right parietal-occipital ischemic damage. This clinical and neuroimaging picture is strongly suggestive of posterior reversible encephalopathy syndrome, a usually reversible condition that can sometimes result in death or irreversible neurological deficit, including chronic epilepsy. Therefore, it is likely that the cortical projections of headache p
{"title":"The Confirming Evidence for Ictal Epileptic Headache","authors":"P. Parisi, V. Belcastro, P. Striano","doi":"10.1111/head.13678","DOIUrl":"https://doi.org/10.1111/head.13678","url":null,"abstract":"Dr. Fanella et al published in Headache, a possible additional case of “Ictal Epileptic Headache” (IEH), that they classified as a “non convulsive status epilepticus.” They reported a woman experiencing migraine attacks-featuring prolonged, intense, throbbing, left temporal pain associated with ipsilateral visual symptoms (ie, non-colored flashes and photophobia) and nausea or vomiting, unresponsive to painkillers – associated with epileptic activity over the right posterior cerebral regions and responsive to intravenous lacosamide. The first description of a documented isolated headache as a sole ictal manifestation of an epileptic seizure (erroneously reported by Dr. Fanella et al, as first published in 2011) was described and published in Epilepsia in 2007 by Parisi et al. These authors coined and published the “original criteria” for IEH diagnosis in 2012, although they have not yet been recognized by the International League Against Epilepsy classification. Indeed, IEH criteria should be applied to all cases where headache is the sole, or is the earliest and most evident feature, of a seizure, regardless of other possible “subtle” associated manifestations; in fact, the same authors have suggested that, to enable a IEH diagnosis, a careful and detailed neurologic exam must be carried, to rule out other associated ictal signs and symptoms. In particular, the availability of an ictal video-EEG recording confirming the clinical suspect of a headache of epileptic origin as well as the prompt response to anti-seizure therapy is of paramount importance in such cases, which may be challenging even for the most expert of clinicians. Fanella and colleagues’ description confirms that (video)-EEG recording – not routinely recommended in patients with headache – should be considered promptly in individuals reporting prolonged migraine/headache not responsive to analgesics. Moreover, ictal EEG recording does also allow the clinician to differentiate IEH from the misleading “migralepsy” concept that probably does not exist at all (ie, “an isolated ictal headache, immediately followed by other epileptic manifestation”). The pathophysiology of IEH is still a matter of on-going research. Although there is not a specific cortical substrate, the most frequently reported origin of IEH is in the posterior cerebral areas, particularly the occipital lobe, as it is a vulnerable region for the onset of both seizures and headache. Notably, 10 years before the epilepsy onset, the patient reported by Dr. Fanella et al had been hospitalized for eclampsia, followed by focal seizures and prolonged coma. Her brain MRI revealed right parietal-occipital ischemic damage. This clinical and neuroimaging picture is strongly suggestive of posterior reversible encephalopathy syndrome, a usually reversible condition that can sometimes result in death or irreversible neurological deficit, including chronic epilepsy. Therefore, it is likely that the cortical projections of headache p","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83943280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah M. Haigh, Alireza Chamanzar, P. Grover, M. Behrmann
Individuals with migraine exhibit heightened sensitivity to visual input that continues beyond their migraine episodes. However, the contribution of color to visual sensitivity, and how it relates to neural activity, has largely been unexplored in these individuals.
{"title":"Cortical Hyper‐Excitability in Migraine in Response to Chromatic Patterns","authors":"Sarah M. Haigh, Alireza Chamanzar, P. Grover, M. Behrmann","doi":"10.1111/head.13620","DOIUrl":"https://doi.org/10.1111/head.13620","url":null,"abstract":"Individuals with migraine exhibit heightened sensitivity to visual input that continues beyond their migraine episodes. However, the contribution of color to visual sensitivity, and how it relates to neural activity, has largely been unexplored in these individuals.","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78252047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In a recent paper in Headache, titled “The Emperor’s New Gepants: Are the Effects of the New Oral CGRP Antagonists Clinically Meaningful?” by Tfelt-Hansen and Loder, the statistical and clinical significances of the trials for rimegepant and ubrogepant were called into question – and rightfully so. In their letter, the authors remark that while the gepants have achieved statistical significance in trials, their clinical effect may be marginal. However, the statistical significance of these trials may be worth a second look: In addition to using therapeutic gain and number needed to treat, calculating a fragility index (FI) can further assist in assessing statistical significance by complementing the P value. While a P value of <.05 is the current standard for indicating statistical significance, it may be too simplistic and ignore other factors that can affect significance. A shift of only a few events in 1 group could shift the statistically significant results to nonsignificant – or vice versa. Consider 2 statistically significant trials in which the number of randomized patients differs significantly by a factor of 10. In the smaller trial, statistical significance may hinge on only a few events, without which the P value could be shifted to nonsignificance – the P value when taken at face value is unable to communicate that limitation. The utility of the FI therefore is to identify the number of events required to make that shift. It is also important to identify the number of patients lost to follow up and make a direct comparison to the FI; ie, if the number of patients lost to follow up exceeds the FI, the clinician may question if including a certain number of outcomes could have resulted in a shift in statistical significance. Results that are deemed statistically significant with FI less than the number of patients lost to follow up should be interpreted with caution. The FI’s for some of the rimegepant and ubrogepant trials in Table 1 can help when evaluating the statistical significance of these trials. Take for example the ACHIEVE I trial: when comparing the ubrogepant 50 mg group and placebo, the FI is 11 and the number of patients lost to follow up is 45. Had the data for the patients lost to follow up been included, the results of the trial could have shifted from statistically significant to non-significant. Another example is trial 301 which investigated rimegepant: its FI is 2 for its first primary endpoint, meaning that the statistical significance of this study hinged on just 2 participants in a study with N = 1084. Originally the investigators had randomized 1162 subjects, which may indicate that the number of patients lost to follow up may exceed the FI. Reporting the FI can assist clinicians in drawing the appropriate conclusions when considering statistical and clinical significance by complementing the P value.
{"title":"Further Questioning of the Significance of the Gepants","authors":"Jennifer Nguyen, Daniel Hu","doi":"10.1111/head.13672","DOIUrl":"https://doi.org/10.1111/head.13672","url":null,"abstract":"In a recent paper in Headache, titled “The Emperor’s New Gepants: Are the Effects of the New Oral CGRP Antagonists Clinically Meaningful?” by Tfelt-Hansen and Loder, the statistical and clinical significances of the trials for rimegepant and ubrogepant were called into question – and rightfully so. In their letter, the authors remark that while the gepants have achieved statistical significance in trials, their clinical effect may be marginal. However, the statistical significance of these trials may be worth a second look: In addition to using therapeutic gain and number needed to treat, calculating a fragility index (FI) can further assist in assessing statistical significance by complementing the P value. While a P value of <.05 is the current standard for indicating statistical significance, it may be too simplistic and ignore other factors that can affect significance. A shift of only a few events in 1 group could shift the statistically significant results to nonsignificant – or vice versa. Consider 2 statistically significant trials in which the number of randomized patients differs significantly by a factor of 10. In the smaller trial, statistical significance may hinge on only a few events, without which the P value could be shifted to nonsignificance – the P value when taken at face value is unable to communicate that limitation. The utility of the FI therefore is to identify the number of events required to make that shift. It is also important to identify the number of patients lost to follow up and make a direct comparison to the FI; ie, if the number of patients lost to follow up exceeds the FI, the clinician may question if including a certain number of outcomes could have resulted in a shift in statistical significance. Results that are deemed statistically significant with FI less than the number of patients lost to follow up should be interpreted with caution. The FI’s for some of the rimegepant and ubrogepant trials in Table 1 can help when evaluating the statistical significance of these trials. Take for example the ACHIEVE I trial: when comparing the ubrogepant 50 mg group and placebo, the FI is 11 and the number of patients lost to follow up is 45. Had the data for the patients lost to follow up been included, the results of the trial could have shifted from statistically significant to non-significant. Another example is trial 301 which investigated rimegepant: its FI is 2 for its first primary endpoint, meaning that the statistical significance of this study hinged on just 2 participants in a study with N = 1084. Originally the investigators had randomized 1162 subjects, which may indicate that the number of patients lost to follow up may exceed the FI. Reporting the FI can assist clinicians in drawing the appropriate conclusions when considering statistical and clinical significance by complementing the P value.","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85228125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study sought to examine the association between early life stressors and adolescent headache in the Canadian population, and the potential mediating influence of symptoms of depression and anxiety.
本研究旨在探讨加拿大人群中早期生活压力源与青少年头痛之间的关系，以及抑郁和焦虑症状的潜在中介影响。
{"title":"Early Life Stress in Adolescent Migraine and the Mediational Influence of Symptoms of Depression and Anxiety in a Canadian Cohort","authors":"N. Hammond, Serena L. Orr, I. Colman","doi":"10.1111/head.13644","DOIUrl":"https://doi.org/10.1111/head.13644","url":null,"abstract":"This study sought to examine the association between early life stressors and adolescent headache in the Canadian population, and the potential mediating influence of symptoms of depression and anxiety.","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76037847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To evaluate the frequency and features of onabotulinumtoxinA (onabotA) wear‐off in chronic migraine (CM).
评估慢性偏头痛(CM)患者onabotuinumtoxina (onabotA)磨损的频率和特征。
{"title":"OnabotulinumtoxinA Wear‐off Phenomenon in the Treatment of Chronic Migraine","authors":"A. Masters-Israilov, M. Robbins","doi":"10.1111/head.13638","DOIUrl":"https://doi.org/10.1111/head.13638","url":null,"abstract":"To evaluate the frequency and features of onabotulinumtoxinA (onabotA) wear‐off in chronic migraine (CM).","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75942288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seniha Ozudogru, Anastasia Neufeld, B. Katz, S. Baggaley, Karly A. Pippitt, Yue Zhang, K. Digre
Patients with migraine frequently report ocular or visual symptoms including aura, photophobia, and eye pain. Using validated instruments, our group previously reported that due to these symptoms, patients have marked reductions in visual quality of life. In chronic migraine, these reductions can be as substantial as those reported for other neuro‐ophthalmic diseases such as multiple sclerosis with optic neuritis and idiopathic intracranial hypertension. Because the instruments take several different dimensions into account, we were unable to determine which ocular symptom(s) contributed to reduced visual quality of life. The purpose of this investigation was to attempt to determine which ocular symptom(s) were driving the observed reduction in visual quality of life.
{"title":"Reduced Visual Quality of Life Associated with Migraine is Most Closely Correlated with Symptoms of Dry Eye","authors":"Seniha Ozudogru, Anastasia Neufeld, B. Katz, S. Baggaley, Karly A. Pippitt, Yue Zhang, K. Digre","doi":"10.1111/head.13662","DOIUrl":"https://doi.org/10.1111/head.13662","url":null,"abstract":"Patients with migraine frequently report ocular or visual symptoms including aura, photophobia, and eye pain. Using validated instruments, our group previously reported that due to these symptoms, patients have marked reductions in visual quality of life. In chronic migraine, these reductions can be as substantial as those reported for other neuro‐ophthalmic diseases such as multiple sclerosis with optic neuritis and idiopathic intracranial hypertension. Because the instruments take several different dimensions into account, we were unable to determine which ocular symptom(s) contributed to reduced visual quality of life. The purpose of this investigation was to attempt to determine which ocular symptom(s) were driving the observed reduction in visual quality of life.","PeriodicalId":12845,"journal":{"name":"Headache: The Journal of Head and Face Pain","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87054352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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