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BACKGROUND: Using the Clinical Audit Research and Evaluation of Motor Neuron Disease (CARE-MND) database and the Scottish Regenerative Neurology Tissue Bank, we aimed to outline the genetic epidemiology and phenotypes of an incident cohort of people with MND (pwMND) to gain a realistic impression of the genetic landscape and genotype-phenotype associations. METHODS: Phenotypic markers were identified from the CARE-MND platform. Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for C9orf72 hexanucleotide expansions using repeat-prime PCR methodology. RESULTS: 339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic C9orf72 repeat expansion, including two with intermediate expansions. Having a C9orf72 expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score (p = 0.0005). The known pathogenic SOD1 variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in FUS and NEK1. One individual carried both a C9orf72 expansion and SOD1 variant. CONCLUSIONS: Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that C9orf72 carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the SOD1 p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments.
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Proteína C9orf72 , Doença dos Neurônios Motores , Fenótipo , Humanos , Escócia/epidemiologia , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Proteína C9orf72/genética , Genótipo , Adulto , Expansão das Repetições de DNA/genética , Estudos de Coortes , Idoso de 80 Anos ou mais , Superóxido Dismutase-1/genéticaRESUMO
Background: Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs. Method: We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC). Results: Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs. Conclusion: Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations. PROSPERO registration number: CRD42021265993.
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The evidence base for migraine prevention in both episodic and chronic migraine is outlined. The older oral preventatives, including antidepressants, antihypertensives, serotonin antagonists, antiepileptics, and calcium channel antagonists, and newer options including onabotulinumtoxinA and the CGRP monoclonal antibodies are covered. Many of the older oral preventatives were trialed before chronic migraine was defined, and they are used in chronic migraine based on the assumption that episodic migraine and chronic migraine are on a spectrum of the same condition. First- and second-line options are given, and a multicountry perspective is considered.
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Anticorpos Monoclonais , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controleRESUMO
Single-atom imaging resolution of many-body quantum systems in optical lattices is routinely achieved with quantum-gas microscopes. Key to their great versatility as quantum simulators is the ability to use engineered light potentials at the microscopic level. Here, we employ dynamically varying microscopic light potentials in a quantum-gas microscope to study commensurate and incommensurate 1D systems of interacting bosonic Rb atoms. Such incommensurate systems are analogous to doped insulating states that exhibit atom transport and compressibility. Initially, a commensurate system with unit filling and fixed atom number is prepared between two potential barriers. We deterministically create an incommensurate system by dynamically changing the position of the barriers such that the number of available lattice sites is reduced while retaining the atom number. Our systems are characterised by measuring the distribution of particles and holes as a function of the lattice filling, and interaction strength, and we probe the particle mobility by applying a bias potential. Our work provides the foundation for preparation of low-entropy states with controlled filling in optical-lattice experiments.
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BACKGROUND: Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence. AIM: To assess the cost-effectiveness of drugs used to treat adults with chronic migraine. METHODS: We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes. RESULTS: Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY. CONCLUSIONS: Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.
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Transtornos de Enxaqueca , Adulto , Humanos , Topiramato , Transtornos de Enxaqueca/tratamento farmacológico , Cefaleia , Análise Custo-Benefício , Tomada de Decisões , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults. METHODS: We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis. FINDINGS: We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small. INTERPRETATION: All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications. REGISTRATION: PROSPERO (number CRD42021265990).
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Transtornos de Enxaqueca , Adulto , Humanos , Topiramato/uso terapêutico , Metanálise em Rede , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resultado do Tratamento , Cefaleia , Método Duplo-CegoRESUMO
BACKGROUND: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG). METHODS: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH. RESULTS: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided. CONCLUSIONS: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH.
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Hipotensão Intracraniana , Humanos , Hipotensão Intracraniana/diagnóstico , Hipotensão Intracraniana/terapia , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Vazamento de Líquido Cefalorraquidiano/terapia , Vazamento de Líquido Cefalorraquidiano/complicações , Imageamento por Ressonância Magnética/efeitos adversos , Cefaleia/diagnóstico , Cefaleia/etiologia , Cefaleia/terapia , Diagnóstico DiferencialRESUMO
BACKGROUND: We investigated the phenotypes and genotypes of a cohort of 'long-surviving' individuals with motor neuron disease (MND) to identify potential targets for prognostication. METHODS: Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as > 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls. RESULTS: 58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions. CONCLUSIONS: Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication.
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Esclerose Lateral Amiotrófica , Doença dos Neurônios Motores , Paraplegia Espástica Hereditária , Humanos , Proteína C9orf72/genética , Diagnóstico Tardio , Superóxido Dismutase-1/genética , Doença dos Neurônios Motores/epidemiologia , Doença dos Neurônios Motores/genética , Genótipo , Fenótipo , Paraplegia Espástica Hereditária/genética , Esclerose Lateral Amiotrófica/genética , Espastina/genética , DNA Helicases/genética , RNA Helicases/genética , Enzimas Multifuncionais/genéticaRESUMO
Objective: To assess the knowledge, attitudes and practices of healthcare professionals regarding the diagnosis and management of spontaneous intracranial hypotension (SIH). Methods: We performed a cross-sectional, web-based survey of multiple healthcare professional groups in the UK from June to August 2021. There were 227 respondents to the survey, including 62 general practitioners, 39 emergency medicine physicians, 38 neurologists, 35 radiologists, 20 neurosurgeons, 18 anaesthetists and 15 headache nurse specialists. The majority of the respondents were at the consultant level and all worked in the UK National Health Service. Results: Few general practitioners or emergency medicine physicians had ever been involved in the care of a patient with SIH or received teaching about SIH. Only 3 of 62 (4.8%) general practitioners and 1 of 39 (2.5%) emergency medicine physicians were confident in recognising the symptoms of SIH. Most neurologists were confident in recognising SIH and performed MRI of the brain as a first-line investigation, although there was variability in the urgency of the request, whether contrast was given or MRI of the spine organised at the same time. Most said they never or rarely performed lumbar puncture for diagnosis of SIH. Most neuroradiologists, but few general radiologists, were confident in interpreting imaging of patients with suspected SIH. Lack of access to epidural blood patching, personnel able to perform myelography, and established management pathways were identified by many respondents as barriers to the treatment of SIH. Conclusions: We have identified a lack of awareness of SIH among non-specialists, several barriers to optimal treatment of SIH and a variation in current management pathways. The results highlight the need for education of healthcare professionals about SIH and the development of clinical practice guidelines to enable delivery of optimal and equitable care for patients with SIH.
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BACKGROUND AND AIMS: Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine. METHODS: We undertook systematic literature searches using terms for migraine/headache and prophylactic drug interventions, combined with economic/cost terms where appropriate. Using inclusion and exclusion criteria, two reviewers independently assessed the citations and abstracts, and full-text articles were retrieved. A review of study characteristics and methodological quality was assessed. RESULTS: Sixteen citations met the inclusion criteria and were model-based cost-utility studies evaluating: Botox (n = 6); Erenumab (n = 8); Fremanezumab (n = 2); and Galcanezumab (n = 1) as the main treatment. They varied in their use of comparators, perspective, and model type. Botox was cost-effective compared to placebo with an incremental cost-effectiveness ratio (ICER) ranging between £15,028 (17,720) and £16,598 (19,572). Erenumab, Fremanezumab and Galcanezumab when compared to Botox, was associated with ICERs ranging between £59,712 ($81,080) and £182,128 (218,870), with the ICERs above the most common willingness-to-pay thresholds (WTPs). But they were cost-effective within the commonly used WTPs among the population for whom the previous treatments including Botox were failed. Three studies compared the cost-effectiveness of Erenumab against the placebo and found that Erenumab was dominant. All studies performed sensitivity analyses to check the robustness of their results. None of the findings from the included articles were generalisable and none of the included studies fulfilled all the criteria mentioned in the CHEERS 2022 reporting checklist and Phillips's checklist for economic models. CONCLUSIONS: Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies.
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Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Adulto , Análise Custo-Benefício , Humanos , Transtornos de Enxaqueca/prevenção & controleRESUMO
Objective: The COVID-19 pandemic has broadened the use of teleneurology, how this compares with face-to-face (F2F) clinics is unclear. This study compared virtual with F2F new neurological consultations. Methods: We retrospectively evaluated new outpatient consultations in neurology clinics in Aberdeen Royal Infirmary. We compared sociodemographic data, time to consultation, time to diagnosis, the need for reassessment and re-investigation between traditional F2F and virtual clinics using the web-based Attend Anywhere platform or telephone into patients' own homes (or chosen location) without a trained assistant. We calculated the relative risk (RR) of the need for reassessment and re-investigation over 6-month periods by the suspected neurological diagnosis. Results: 73% of consultations were virtual (Attend Anywhere or telephone) between June and October 2020, this was almost non-existent (<0.1%) in June-October 2019. We analysed 352 F2F (June-July 2019) and 225 virtual consultations (June-July 2020). Compared with F2F clinics, virtual clinics had a longer time to diagnosis (p=0.019), were more likely to be reassessed (RR: 2.2, 95% CI: 1.5 to 3.2; p<0.0001) and re-investigated (RR: 1.50, 95% CI: 0.88 to 2.54; p=0.133), this was likelier in those aged ≥60 years. Patients with headaches and suspected seizures were less likely to need reassessment or re-investigation following virtual clinics than multiple sclerosis and neuroinflammatory disorders, spinal cord disorders and functional neurological disorders. Conclusion: This study demonstrates that virtual clinics have higher rates of reassessment and re-investigation than F2F clinics. As virtual clinics become a potential consultation alternative, this study should instruct the selection of patients for either consultation type.
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In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. The primary outcome was to interrogate the clinico-radiopathological correlates and prognostic indicators of stroke-like episode in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS). The secondary objective was to develop a multivariable prediction model to forecast stroke-like episode risk. The most common genetic cause of stroke-like episodes was the m.3243A>G variant in MT-TL1 (n = 66), followed by recessive pathogenic POLG variants (n = 22), and 11 other rarer pathogenic mitochondrial DNA variants (n = 23). The age of first stroke-like episode was available for 105 patients [mean (SD) age: 31.8 (16.1)]; a total of 35 patients (32%) presented with their first stroke-like episode ≥40 years of age. The median interval (interquartile range) between first and second stroke-like episodes was 1.33 (2.86) years; 43% of patients developed recurrent stroke-like episodes within 12 months. Clinico-radiological, electrophysiological and neuropathological findings of stroke-like episodes were consistent with the hallmarks of medically refractory epilepsy. Patients with POLG-related stroke-like episodes demonstrated more fulminant disease trajectories than cases of m.3243A>G and other mitochondrial DNA pathogenic variants, in terms of the frequency of refractory status epilepticus, rapidity of progression and overall mortality. In multivariate analysis, baseline factors of body mass index, age-adjusted blood m.3243A>G heteroplasmy, sensorineural hearing loss and serum lactate were significantly associated with risk of stroke-like episodes in patients with the m.3243A>G variant. These factors informed the development of a prediction model to assess the risk of developing stroke-like episodes that demonstrated good overall discrimination (area under the curve = 0.87, 95% CI 0.82-0.93; c-statistic = 0.89). Significant radiological and pathological features of neurodegeneration were more evident in patients harbouring pathogenic mtDNA variants compared with POLG: brain atrophy on cranial MRI (90% versus 44%, P < 0.001) and reduced mean brain weight (SD) [1044 g (148) versus 1304 g (142), P = 0.005]. Our findings highlight the often idiosyncratic clinical, radiological and EEG characteristics of mitochondrial stroke-like episodes. Early recognition of seizures and aggressive instigation of treatment may help circumvent or slow neuronal loss and abate increasing disease burden. The risk-prediction model for the m.3243A>G variant can help inform more tailored genetic counselling and prognostication in routine clinical practice.
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Síndrome MELAS , Doenças Mitocondriais , Acidente Vascular Cerebral , Adulto , DNA Mitocondrial/genética , Humanos , Síndrome MELAS/genética , Doenças Mitocondriais/complicações , Doenças Mitocondriais/genética , Mutação , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/genéticaRESUMO
Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.
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Tele-neurology is a neurological consultation at a distance, or not in person, using various technologies to achieve connectivity, including the telephone and the internet. The telephone is ubiquitous and is a standard part of how we manage patients. Video consulting has been used for a long time in some centres, particularly in those where the geography means that patients have to travel long distances. Various technologies can be used, and with the development of various internet-based video-calling platforms, real-time video consulting has become much more accessible. We have provided a tele-neurology service in the North East of Scotland since 2006 using video conferencing with far-end camera control. More recently, we have complemented this using an internet-based platform (NHS Near Me). Here we outline the practicalities of video consulting in 'ordinary' times and comment on its use in the 'extraordinary' times of the coronavirus pandemic.
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Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Exame Neurológico/tendências , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Encaminhamento e Consulta/tendências , Telemedicina/tendências , Comunicação por Videoconferência/tendências , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Exame Neurológico/métodos , Exame Neurológico/normas , Neurologia/métodos , Neurologia/normas , Neurologia/tendências , Pneumonia Viral/epidemiologia , Encaminhamento e Consulta/normas , SARS-CoV-2 , Escócia/epidemiologia , Telemedicina/métodos , Telemedicina/normas , Comunicação por Videoconferência/normasRESUMO
Objectives: Launched in 1989, the Scottish Motor Neuron Disease Register (SMNDR) has provided a resource for prospective clinical data collection. However, in 2015 we aimed to evolve a system to allow: i) A patient-centered approach to care based on recognized standards, ii) Harmonized data sharing between Scottish health professionals in "real-time", iii) Regular audit of care to facilitate timely improvements in service delivery, and iv) Patient participation in a diverse range of observational and interventional research studies including clinical trials. Methods: We developed a standardized national electronic data platform-Clinical Audit Research and Evaluation of MND (CARE-MND) which integrates clinical audit and research data fields. Data completion pre- and post-CARE-MND were compared, guided by recently published National Institute for Clinical Excellence (NICE) recommendations. Statistical difference in data capture between time periods was assessed using Z-test of proportions. Results: Data field completion for the historical 2011-2014 period ranged from 4 to 95%; median 50%. CARE-MND capture ranged from 32 to 98%; median 87%. 15/17 fields were significantly more complete post-CARE-MND (p < 0.001). All MND nurse/allied health specialists in Scotland use the CARE-MND platform. Management of MND in Scotland is now coordinated through a standardized template. Conclusions: Through CARE-MND, national audits of MND care and interventions have been possible, leading to protocols for harmonized service provision. Stratification of the MND population is facilitating participation in observational and interventional studies. CARE-MND can act as a template for other neurological disorders.
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Monitoramento Epidemiológico , Auditoria Médica , Doença dos Neurônios Motores/diagnóstico , Acesso à Informação , Pessoal Técnico de Saúde , Coleta de Dados , Atenção à Saúde/normas , Registros Eletrônicos de Saúde , Humanos , Monitorização Fisiológica , Enfermeiras e Enfermeiros , Participação do Paciente , Assistência Centrada no Paciente , Pesquisa , EscóciaRESUMO
We present experimental evidence of photon droplets in an attractive (focusing) nonlocal nonlinear medium. Photon droplets are self-bound, finite-sized states of light that are robust to size and shape perturbations due to a balance of competing attractive and repulsive forces. It has recently been shown theoretically, via a multipole expansion of the nonlocal nonlinearity, that the self-bound state arises due to competition between the s-wave and d-wave nonlinear terms, together with diffraction. The theoretical photon droplet framework encompasses both a solitonlike stationary ground state and the nonsolitonlike dynamics that ensue when the system is displaced from equilibrium, i.e., driven into an excited state. We present numerics and experiments supporting the existence of these photon droplet states and measurements of the dynamical evolution of the photon droplet orbital angular momentum.
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Headache is very common. In the United Kingdom, it accounts for 4.4% of primary care consultations, 30% of referrals to neurology services and 0.5-0.8% of alert patients presenting to emergency departments. Primary headache disorders account for the majority of patients and most patients do not require investigation. Warning features (red flags) in the history and on examination help target those who need investigation and what investigations are required. This article summarizes the typical presentations of the common secondary headaches and what neuroimaging and other investigations are appropriate for each headache type.