Cephalalgia最新文献

{"title":"Triptan non-response in a London tertiary headache centre: What can we learn? A retrospective study.","authors":"Robyn-Jenia Wilcha, Peter J Goadsby","doi":"10.1177/03331024241278911","DOIUrl":"https://doi.org/10.1177/03331024241278911","url":null,"abstract":"<p><strong>Background: </strong>Triptans revolutionized the acute treatment of migraine; however, varied responses to triptans, as a result of poor efficacy and tolerability, are reported. A standardized definition of triptan non-response was recently proposed by the European Headache Federation (EHF). There is currently limited data available on the prevalence of triptan non-response.</p><p><strong>Methods: </strong>We used clinic letters over a two-year duration to evaluate the triptan response and triptan efficacy or tolerability failure, or both, in a London-based tertiary headache service.</p><p><strong>Results: </strong>In total, 419 adult migraine patients (females: 83.8%, age: 46 ± 18 years, chronic migraine: 88.5%) were included in a service evaluation. In line with the EHF definitions, \"triptan non-response\" was seen in 63.8% of patients (264/414), whereas 37.7% of patients (156/414) had failed at least two triptans (EHF \"triptan resistant\") and 4.6% of patients (19/414) had failed at least three triptans, including a subcutaneous formulation (EHF \"triptan refractory\"). Notably, 21.3% of patients (88/414) had failed at least three triptans inclusive and exclusive of subcutaneous triptan use. Advancing age (<i>p </i>< 0.001) and the presence of medication overuse (<i>p </i>= 0.006) increased the probability of triptan response, whereas an increased number of failed preventives (<i>p </i>< 0.001) and the use of calcitonin gene-related peptide monoclonal antibodies (<i>p </i>= 0.022) increased the probability of triptan non-response. The largest proportion of patients responded to eletriptan (49.5%), followed by nasal zolmitriptan (44.4%) and rizatriptan (35.7%).</p><p><strong>Conclusions: </strong>Our findings highlight an alarming prevalence of triptan non-response among adult migraineurs receiving treatment in a London-based tertiary headache service. It is imperative for clinicians to explore methods to optimize acute medication efficacy, whether this comprises changing to a triptan with a superior response rate, advocating for early intervention or considering alternative acute medication classes, such as gepants or ditans.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of GTN-induced migraine: Role of NOS isoforms, sGC and peroxynitrite in a migraine relevant mouse model.","authors":"Charlotte Ernstsen, Karina Obelitz-Ryom, David Møbjerg B Kristensen, Jes Olesen, Sarah Louise Christensen, Song Guo","doi":"10.1177/03331024241277542","DOIUrl":"10.1177/03331024241277542","url":null,"abstract":"<p><strong>Background: </strong>Migraine research has highlighted the pivotal role of nitric oxide (NO) in migraine pathophysiology. Nitric oxide donors such as glyceryl trinitrate (GTN) induce migraine attacks in humans, whereas spontaneous migraine attacks can be aborted by inhibiting NO production. The present study aimed to investigate how GTN triggers migraine through its three nitric oxide synthase (NOS) isoforms (neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)) via a suspected feed-forward phenomenon.</p><p><strong>Methods: </strong>Migraine-relevant hypersensitivity was induced by repeated injection of GTN in an <i>in vivo</i> mouse model. Cutaneous tactile sensitivity was assessed using von Frey filaments. Signaling pathways involved in this model were dissected using non-selective and selective NOS inhibitors, knockout mice lacking eNOS or nNOS and their wild-type control mice. Also, we tested a soluble guanylate cyclase inhibitor and a peroxynitrite decomposition catalyst (N_total= 312).</p><p><strong>Results: </strong>Non-selective NOS inhibition blocked GTN-induced hypersensitivity. This response was partially associated with iNOS, and potentially nNOS and eNOS conjointly. Furthermore, we found that the GTN response was largely dependent on the generation of peroxynitrite and partly soluble guanylate cyclase.</p><p><strong>Conclusions: </strong>Migraine-relevant hypersensitivity induced by GTN is mediated by a possible feed-forward phenomenon of NO driven mainly by iNOS but with contributions from other isoforms. The involvement of peroxynitrite adds to the notion that oxidative stress reactions are also involved.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of a direct link between macular cones function and photophobia in interictal migraine.","authors":"Francesco Casillo, Antonio Di Renzo, Gabriele Sebastianelli, Chiara Abagnale, Francesco Martelli, Cherubino Di Lorenzo, Mariano Serrao, Benedetto Falsini, Vincenzo Parisi, Gianluca Coppola","doi":"10.1177/03331024241276501","DOIUrl":"https://doi.org/10.1177/03331024241276501","url":null,"abstract":"<p><strong>Background: </strong>It is still debatable whether the mechanisms underlying photophobia are related to altered visual cortex excitability or specific abnormalities of colour-related focal macular retino-thalamic information processing.</p><p><strong>Methods: </strong>This cross-sectional study examined Ganzfeld blue-red (B-R) and blue-yellow (B-Y) focal macular cone flash ERG (ffERG) and focal-flash visual evoked potentials (ffVEPs) simultaneously in a group of migraine patients with (n = 18) and without (n = 19) aura during the interictal phase, in comparison to a group of healthy volunteers (HVs) (n = 20). We correlate the resulting retinal and cortical electrophysiological responses with subjective discomfort from exposure to bright light verified on a numerical scale.</p><p><strong>Results: </strong>Compared to HVs, the amplitude and phase of the first and second harmonic of ffERG and ffVEPs were non-significantly different in migraine patients without aura and migraine patients with aura for both the B-R and the B-Y focal stimuli. Pearson's correlation test did not disclose correlations between clinical variables, including the photophobia scale and electrophysiological variables.</p><p><strong>Conclusions: </strong>These results do not favour interictal functional abnormalities in L-M- and S-cone opponent visual pathways in patients with migraine. They also suggest that the discomfort resulting from exposure to bright light is not related to focal macular retinal-to-visual cortex pathway.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost of illness and labour market disaffiliation among patients with migraine discontinuing triptan treatment: A Danish nationwide register study from 1995 to 2021.","authors":"Messoud Ashina, Timothy J Steiner, Jakob Møller Hansen, Daniel Sloth Hauberg, Ulla Sofie Lønberg, Maria Spanggaard, Jens Olsen, Sandra Elkjær Stallknecht, Thomas Folkmann Hansen","doi":"10.1177/03331024241269758","DOIUrl":"https://doi.org/10.1177/03331024241269758","url":null,"abstract":"<p><strong>Background: </strong>Migraine presents significant health and economic challenges. Despite the widespread use of triptans, some patients discontinue them because of insufficient relief or adverse effects. Using national registers, the present study investigates the excess costs and labour market disaffiliation of Danish patients discontinuing triptan treatment.</p><p><strong>Methods: </strong>The study included all individuals ≥18 years (\"patients\") who discontinued redemption of triptan prescriptions between 1998 and 2019. They were categorized by number of distinct triptans redeemed before discontinuation: one, two or three or more. A control group was established from the general population without triptan redemptions, three per patient, matched by year of birth, sex and region of residence. We estimated excess direct and indirect costs from 5 years prior (\"year -5\") to 10 years post (\"year 10\") the first triptan redemption.</p><p><strong>Results: </strong>We identified 211,026 patients who discontinued triptan redemption, 82% after one, 14% after two and 4% after three or more distinct triptans. Over the period from year -5 to year 10, average excess healthcare costs per patient in these cohorts were EUR 9,554, EUR 10,942 and EUR 12,812 respectively. Over the same period, these patients earned EUR 27,964, EUR 35,920 and EUR 50,076 less than their respective controls, and received higher public transfer payments of EUR 20,181, EUR 23,264 and EUR 26,459.</p><p><strong>Conclusions: </strong>Triptan discontinuers, who appear to have exhausted all current treatment avenues, face high direct and very high indirect excess costs attributable to migraine, and experience substantial increased labour market disaffiliation.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are we closer to achieving precision medicine for migraine treatment? A narrative review.","authors":"Keiko Ihara,Francesco Casillo,Ahmed Dahshan,Hamit Genç,Asel Jusupova,Kunduz Karbozova,Wonwoo Lee,Yi Chia Liaw,Theodoros Mavridis,Hong-Kyun Park,Burcu Polat,Triin Helin Unt,Nina Vashchenko,Aisha Zhantleuova,Patricia Pozo-Rosich,Todd J Schwedt","doi":"10.1177/03331024241281518","DOIUrl":"https://doi.org/10.1177/03331024241281518","url":null,"abstract":"BACKGROUNDThe term 'precision medicine' encompasses strategies to optimize diagnosis and outcome prediction and to tailor treatment for individual patients, in consideration of their unique characteristics. The greater availability of multifaceted datasets and strategies to model such data have made precision medicine increasingly possible in recent years. Precision medicine is especially needed in the migraine field since the response to migraine treatments is not universal amongst all individuals with migraine.OBJECTIVETo provide a narrative review describing contributions to achieving precision medicine for migraine treatment.METHODSA search of PubMed for English language articles of human participants published from 2005 to January 2024 was conducted to identify articles that reported research contributing to precision medicine for migraine treatment. The published literature was categorized and summarized according to the type of data that were included: clinical phenotypes, genomics, proteomics, physiologic measures, and brain imaging.RESULTSPublished studies have investigated characteristics associated with acute and preventive treatment responses, such as nonsteroidal anti-inflammatory drugs, triptans, onabotulinumtoxinA, and anti-calcitonin gene-related peptide monoclonal antibodies, in patients with episodic or chronic migraine. There is evidence that clinical, genetic, epigenetic, proteomic, physiologic, and brain imaging features might associate with migraine treatment outcomes, although inconsistencies for such findings clearly exist.CONCLUSIONSThe published literature suggests that there are clinical and biological features which associate with, and might be useful for predicting, migraine treatment responses. To achieve precision medicine for migraine treatment, further research is needed that validates and expands on existing findings and tests the accuracy and value of migraine treatment prediction models in clinical settings.","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter to the editor: \"What predicts citation counts and translational impact in headache research? A machine learning analysis\".","authors":"Antonios Danelakis, Anker Stubberud","doi":"10.1177/03331024241266979","DOIUrl":"https://doi.org/10.1177/03331024241266979","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disability in migraine: Multicountry results from the Chronic Migraine Epidemiology and Outcomes - International (CaMEO-I) Study.","authors":"Zaza Katsarava, Dawn C Buse, Elizabeth Leroux, Michel Lanteri-Minet, Fumihiko Sakai, Manjit S Matharu, Aubrey Manack Adams, Karen Carr, Kristina M Fanning, Richard B Lipton","doi":"10.1177/03331024241274343","DOIUrl":"10.1177/03331024241274343","url":null,"abstract":"<p><strong>Background: </strong>Few studies of migraine have evaluated migraine disability across multiple countries using the same methodology.</p><p><strong>Methods: </strong>This cross-sectional, web-based survey was conducted in 2021-2022 in Canada, France, Germany, Japan, UK and USA. Respondents with migraine were identified based on modified International Classification of Headache Disorders, 3rd edition, criteria. Headache features (Migraine Symptom Severity Score (MSSS, range: 0-21), presence of allodynia (Allodynia Symptom Checklist, ASC-12)) and migraine burden (Patient Health Questionnaire-4 (PHQ-4), Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1), Work Productivity and Activity Impairment (WPAI) questionnaire) were evaluated.</p><p><strong>Results: </strong>Among 14,492 respondents with migraine across countries, the mean ± SD MSSS was 15.4 ± 3.2 and 48.5% (7026/14,492) of respondents had allodynia based on ASC-12. Of all respondents living with migraine, 35.5% (5146/14,492) reported moderate to severe anxiety and/or depression symptoms. Mean ± SD MSQ v2.1 Role Function-Restrictive, Role Function-Preventive and Emotional Function domain scores were 60.7 ± 22.9, 71.5 ± 23.0 and 65.1 ± 27.2, respectively. The WPAI mean ± SD percentages of respondents who missed work or worked impaired as a result of migraine were 6.8 ± 18.1% and 41.0 ± 30.1%, respectively.</p><p><strong>Conclusions: </strong>For every country surveyed, migraine was associated with high levels of symptom severity, with allodynia and with substantial burden.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety of zavegepant nasal spray for the acute treatment of migraine: A phase 2/3 open-label study.","authors":"Kathleen Mullin, Robert Croop, Linda Mosher, Terence Fullerton, Jennifer Madonia, Richard B Lipton","doi":"10.1177/03331024241259456","DOIUrl":"10.1177/03331024241259456","url":null,"abstract":"<p><strong>Background: </strong>Zavegepant is the first small molecule calcitonin gene-related peptide receptor antagonist for intranasal administration for the acute treatment of migraine. The objective of this study was to evaluate the safety and tolerability of zavegepant in the acute treatment of migraine under repeated, as-needed dosing for up to one year.</p><p><strong>Methods: </strong>This phase 2/3, one-year open-label safety study of zavegepant 10 mg nasal spray for the acute treatment of migraine enrolled adults aged ≥18 years with a history of two to eight moderate to severe monthly migraine attacks. Participants used one dose of zavegepant as needed to self-treat migraine attacks of any severity, up to eight times per month, for 52 weeks.</p><p><strong>Results: </strong>Participants were enrolled between 29 June and 4 December 2020. Of the 608 participants entering long-term treatment, 603 were treated with study drug. Participants administered a mean (SD) of 3.1 (1.55) zavegepant doses per month. There were no deaths. Of the seven serious adverse events reported, none was considered related to treatment. Altogether, 6.8% (41/603) of treated participants had an adverse event leading to study drug discontinuation. The most frequent adverse event leading to discontinuation was dysgeusia (1.5% [9/603]). The most common treatment-emergent adverse events (≥5% of participants) were dysgeusia (39.1% [236/603]); nasal discomfort (10.3% [62/603]); COVID-19 (7.5% [45/603]); nausea (6.1% [37/603]); nasal congestion and throat irritation (5.5% [33/603] each); and back pain (5.3% [32/603]). Aminotransferases >3x the upper limit of normal occurred in 2.6% [16/603] of participants; none had concurrent elevations in bilirubin >2x upper limit of normal.</p><p><strong>Conclusions: </strong>One year of zavegepant 10 mg nasal spray up to eight times per month was safe and well tolerated.<b>Trial registration:</b> Clinicaltrials.gov: NCT04408794.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence and headache.","authors":"Anker Stubberud, Helge Langseth, Parashkev Nachev, Manjit S Matharu, Erling Tronvik","doi":"10.1177/03331024241268290","DOIUrl":"https://doi.org/10.1177/03331024241268290","url":null,"abstract":"<p><strong>Background and methods: </strong>In this narrative review, we introduce key artificial intelligence (AI) and machine learning (ML) concepts, aimed at headache clinicians and researchers. Thereafter, we thoroughly review the use of AI in headache, based on a comprehensive literature search across PubMed, Embase and IEEExplore. Finally, we discuss limitations, as well as ethical and political perspectives.</p><p><strong>Results: </strong>We identified six main research topics. First, natural language processing can be used to effectively extract and systematize unstructured headache research data, such as from electronic health records. Second, the most common application of ML is for classification of headache disorders, typically based on clinical record data, or neuroimaging data, with accuracies ranging from around 60% to well over 90%. Third, ML is used for prediction of headache disease trajectories. Fourth, ML shows promise in forecasting of headaches using self-reported data such as triggers and premonitory symptoms, data from wearable sensors and external data. Fifth and sixth, ML can be used for prediction of treatment responses and inference of treatment effects, respectively, aiming to optimize and individualize headache management.</p><p><strong>Conclusions: </strong>The potential uses of AI and ML in headache are broad, but, at present, many studies suffer from poor reporting and lack out-of-sample evaluation, and most models are not validated in a clinical setting.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of migraine medication use in Norway: A nationwide registry-based observational study.","authors":"Anker Stubberud, Solveig Borkenhagen, Francisco Oteiza, Aud Nome Dueland, Christoffer Bugge, Erik Magnus Sæther, Erling Tronvik, Lars Jacob Stovner, Marte-Helene Bjørk","doi":"10.1177/03331024241268212","DOIUrl":"https://doi.org/10.1177/03331024241268212","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to describe and discuss patterns of migraine medication use in the entire Norwegian population.</p><p><strong>Methods: </strong>In this nationwide, observational study, all individuals with a migraine-related prescription between 2010 and 2020 were identified using the Norwegian Prescription Database. The outcomes of interest were the incidence and 1-year prevalence of migraine medication users, as well as individuals with triptan overuse. Patterns of medication use were statistically compared between women and men adjusted for age, year of treatment start, comorbidities and county of residence calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>We identified 327,904 migraine medication users. The incidence ranged from 0.39% to 0.46%, and the 1-year prevalence increased from 1.99% to 2.99%. Preventive use increased >50% during the study period. Preventives were significantly more often prescribed to women than to men (39.72% vs. 33.75%; aOR 1.41, 95% CI 1.38 to 1.44). Triptan overuse was significantly more common among women, but women with overuse were more often using preventives, as compared to men (56.64% vs 52.69%; aOR = 1.43, 95% CI 1.37 to 1.49).</p><p><strong>Conclusion: </strong>The prevalence of medically treated migraine is low. Overuse of triptans is frequent, especially among women. Clinicians should be encouraged to try out different triptans, recognize triptan overuse, and prescribe preventives when indicated.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}