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INTRODUCTION: Multiple sclerosis (MS) causes a broad range of symptoms, with physical function being one of the most disabling consequences according to patients themselves. Exercise effectively improves lower extremity physical function. Nonetheless, it is unknown which exercise modality is most effective and it remains challenging to keep persons with MS adhering to exercise over a longer period. Therefore, the present study aims to investigate how exercise booster sessions (EBS) influence the sustainability of exercise-induced effects on physical function, and furthermore, to investigate which exercise modality (aerobic training or resistance training) is most effective in terms of improving physical function. MATERIALS AND METHODS: This study is a multi-arm, parallel-group, open-label multicentre randomised controlled trial investigating the effects of EBS. Participants (n=150) are initially randomised to 12 weeks of either resistance training+usual care, aerobic training+usual care or usual care. After 12 weeks of intervention, participants in the exercise groups will again be randomised to either EBS+usual care or usual care during a 40-week follow-up period. The primary outcome is physical function (composite score based on 6-min walk test and five-time sit to stand), and the secondary outcomes are fatigue, cognition, physical activity, symptoms of depression and quality of life. ETHICS AND DISSEMINATION: The study is approved by the Central Denmark Region Committees on Health Research Ethics (1-10-72-237-21) and is registered at the Danish Data Protection Agency (2016-051-000001) and at Clinicaltrials.gov (NCT04913012). All study findings will be published in scientific peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04913012.
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Terapia por Exercício , Esclerose Múltipla , Qualidade de Vida , Treinamento Resistido , Humanos , Esclerose Múltipla/terapia , Treinamento Resistido/métodos , Terapia por Exercício/métodos , Adaptação Fisiológica , Ensaios Clínicos Controlados Aleatórios como Assunto , Exercício Físico/fisiologia , Masculino , Estudos Multicêntricos como Assunto , Adulto , Feminino , FadigaRESUMO
BACKGROUND: AQP4-antibody seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) may cause reduced work capability due to disability. Here, we evaluated the socioeconomic status of patients with AQP4-Ab+NMOSD in off-label therapy era compared with the general population. METHODS: A longitudinal nationwide population-based study including all Danish patients with AQP4-Ab+NMOSD and matched controls from the general population. The cohort was linked to other Danish nationwide population-based databases. The study period was from 1992 to 2021. The main outcomes were loss of income from salary, limited work capability, disability pension and civil status. The longitudinal risks of outcomes were presented in cumulative incidence curves. Fisher's exact test, χ2 test or Wilcoxon test were applied for comparison. RESULTS: We included 65 patients with a median follow-up of 8.6 years. Annual income declined significantly after disease onset (index year) compared with the general population. One year after the index year, the median annual income in 2015-indexed Euro for patients averaged 13 285 (IQR: 139 to 36 336) versus controls 33 035 (IQR: 6870 to 45 978); p=0.04. Five years postindex year, the average income for patients further dropped to 276 (IQR: 0 to 23 691) versus controls 22 141 (IQR: 0 to 42 986); p=0.03. At the end of follow-up, significantly higher proportion of patients were either in 'flexjob' (36.9% patients vs 14% controls, p<0.00) or receiving disability pension (16.9% patients vs 4.3% controls, p<0.00). CONCLUSIONS: The socioeconomic status of patients with AQP4-Ab+NMOSD deteriorates rapidly following disease onset. A substantial proportion of these patients lose their work capacity leading to increased financial burden on both their families and society.
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BACKGROUND: Childhood sexual abuse can increase both body weight and inflammation later in life. Higher weight or faster changes in weight, as measured by changes in body mass index (BMI), may mediate the relationship between childhood sexual abuse and inflammation, however, most studies to date have used a cross-sectional design limiting causal inferences. OBJECTIVE: The current study aimed to investigate the interrelationships between childhood sexual abuse, BMI, and C-reactive protein (CRP) and interleukin-6 (IL6). PARTICIPANTS AND SETTING: Data from 461 adults who participated in the Midlife in the United States (MIDUS) study were utilized. METHODS: Growth curve modeling was used to test initial levels of BMI and changes of BMI over an 18-year period as mediators linking childhood sexual abuse to CRP and IL6. RESULTS: Sexual abuse was not significantly associated with the initial level of BMI; however, sexual abuse was associated with the slope of BMI (b = 0.072, p = .006). BMI intercept (b = 0.080, p = .001) and slope (b = 0.240, p = .002) predicted IL6 values whereas the slope of BMI (b = 0.398, p = .033) but not intercept predicted CRP values. The indirect effect from sexual abuse to IL6 through BMI slope was significant (b = 0.017, 95 % [CI.001, 0.033]) while the indirect effect from sexual abuse to CRP through BMI slope was not significant (b = 0.028, 95 % [CI -0.004, 0.061]). CONCLUSION: Childhood sexual abuse was indirectly associated with IL6 through rates of change in BMI over time.
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Índice de Massa Corporal , Proteína C-Reativa , Abuso Sexual na Infância , Interleucina-6 , Humanos , Feminino , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Proteína C-Reativa/metabolismo , Adulto , Estados Unidos/epidemiologia , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Criança , Idoso , Estudos Longitudinais , Estudos TransversaisRESUMO
BACKGROUND AND OBJECTIVES: We aimed to evaluate the mortality of patients with AQP4 antibody-seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in Denmark compared with that in the general population. METHODS: We identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis (IPND) criteria from multiple sources (laboratories and the Danish Multiple Sclerosis Registry). We obtained detailed information about patients from hospital records and about the general population matched on age, sex, and calendar year from Statistics Denmark. We calculated standardized mortality ratio (SMR), excess number of deaths per 1,000 person-years (EDR), and life expectancies compared with those of the matched general population. We examined predictive factors of mortality and the cause of death. RESULTS: Of 66 patients with AQP4-Ab+ NMOSD between 2008 and 2020, 15 died. Overall, the SMR was 2.54 (95% CI 1.47-4.09), and the EDR was 16.8 (95% CI 4.6-34.3). The median life expectancy for patients with AQP4-Ab+ NMOSD was 64.08 years (95% CI 53.02-83.9), compared with 83.07 years for the general population. Risk of death over time was increased in the patient population with a hazard ratio (HR) of 2.22 (1.34-3.68; p = 0.002). The cause of death was directly related to NMOSD in 93% of the cases. The age at disease onset was an independent predictor of death (HR 1.042; 95% CI 1.006-1.079; p = 0.02). DISCUSSION: AQP4-Ab+ NMOSD is associated with increased mortality and shorter life expectancy compared with that in the general population, underlining the need for highly effective treatment approaches.
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Esclerose Múltipla , Neuromielite Óptica , Humanos , Neuromielite Óptica/diagnóstico , Aquaporina 4 , Anticorpos , Esclerose Múltipla/complicações , Dinamarca/epidemiologia , AutoanticorposRESUMO
Shiga-toxin-producing Escherichia coli (STEC) strains of the serogroup O157 are foodborne pathogens associated with severe clinical disease. As antibiotics are counter-indicated for treatment of these infections, they represent prime candidates for targeted application of bacteriophages to reduce infection burden. In this study, we characterised lytic bacteriophages representing three phage genera for activity against E. coli O157 strains. The phages vb_EcoM_bov9_1 (Tequatrovirus), vb_EcoM_bov11CS3 (Vequintavirus), and vb_EcoS_bov25_1D (Dhillonvirus) showed effective lysis of enterohaemorrhagic E. coli EHEC O157:H7 strains, while also exhibiting activity against other strains of the O157 serogroup, as well as of the 'big six' (STEC) serogroups, albeit with lower efficiency. They had a burst size of 293, 127 and 18 per cell and a latent period of 35, 5 and 30 min, respectively. In situ challenge experiments using the O157 Sakai strain on minced beef showed a reduction by 2-3-fold when treated with phages at a 0.1 MOI (multiplicity of infection), and approximately 1 log reduction when exposed to MOI values of 10 and 100. A cocktail of the phages, applied at 10 × and 100 × MOI showed 2 to 3 log reduction when samples were treated at room temperature, and all treatments at 37 °C with 100 × MOI resulted in a 5 to 6 log reduction in cell count. Our results indicate that the phages vb_EcoM_bov9_1 and vb_EcoM_bov11CS3, which have higher burst sizes, are promising candidates for biocontrol experiments aimed at the eradication of E. coli O157 strains in animals or foodstuff.
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Bacteriófagos , Escherichia coli O157 , Escherichia coli Shiga Toxigênica , Siphoviridae , Animais , Bovinos , MyoviridaeRESUMO
BACKGROUND AND PURPOSE: Real-world evidence regarding the effectiveness and safety of ocrelizumab for the treatment of multiple sclerosis (MS) is limited. The aim was to evaluate the effectiveness and safety of ocrelizumab treatment for MS in a real-world setting. METHODS: A nationwide population-based cohort study was conducted where clinical and magnetic resonance imaging data of MS patients enrolled prospectively in the Danish Multiple Sclerosis Registry who initiated ocrelizumab treatment between January 2018 and November 2020 were analyzed. RESULTS: A total of 1104 patients (85.7% relapsing-remitting MS [RRMS], 8.8% secondary progressive MS [SPMS], 5.5% primary progressive MS [PPMS]) were included, with a median follow-up period of 1.3 years. At baseline, the mean age was 41.4 years in the RRMS group, 44.5 years in the PPMS group and 50.3 years in the SPMS group. Median Expanded Disability Status Scale score was 2.5, 3.5 and 5.5, respectively. Most RRMS and SPMS patients had received previous disease-modifying therapies (87.5% and 91.8%, respectively), whereas PPMS patients were mostly treatment naïve (78.7%). After ocrelizumab initiation, 9.3% of the patients experienced a relapse and 8.7% a 24 weeks confirmed disability worsening. Conversely, 16.7% showed a 24 weeks confirmed disability improvement. After ~1 year of treatment, most patients (94.5%) were free of magnetic resonance imaging activity. Ocrelizumab was generally well tolerated, as side effects were only reported for 10% of patients, mostly consisting of infusion-related reactions and infections. CONCLUSIONS: It is shown that most MS patients treated with ocrelizumab are clinically stabilized and with an adverse event profile consistent with the experience from the pivotal clinical trials.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Dinamarca/epidemiologia , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
AIMS: The primary aim of this study was to provide normative formant frequency (F) values for male and female speakers of Australian English. The secondary aim was to examine the effects of speaker sex, age, vowel quality, and geographical location on F. METHOD: The first three monophthong formant frequencies (F1, F2, and F3) for 244 female and 135 male speakers aged 18-60 years from a recent large-scale corpus of Australian English were analysed on a passage reading task. RESULTS: Mixed effects linear regression models suggested that speaker sex, speaker age, and vowel quality significantly predicted F1, F2, and F3 (P = 0.000). Effect sizes suggested that speaker sex and vowel quality contributed most to the variations in F1, F2, and F3 whereas speaker age and geographical location contributed a smaller amount. CONCLUSION: Both clinicians and researchers are provided with normative F data for 18-60 year-old speakers of Australian English. Such data have increased internal and external validity relative to previous literature. F normative data for speakers of Australian English should be considered with reference to speaker sex and vowel but it may not be practically necessary to adjust for speaker age and geographical location.
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Fonética , Acústica da Fala , Humanos , Adulto , Masculino , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Austrália , Leitura , Modelos LinearesRESUMO
AIMS: The aim of this study was to provide a description of normative speaking fundamental frequency (fos) characteristics for adult speakers of Australian English. The effects of age, sex, and geographical location on fos were also examined to assess whether variations existed. METHODS: fos data for 244 female and 135 male speakers aged 18-60 years from a recent large-scale corpus of Australian English were analyzed on a passage reading task. Creak phonation frequencies were first separated from the modal phonation frequencies algorithmically. Descriptive statistics were then generated for modal voice. RESULTS: The mixed effects linear regression model suggested that geographical location had no effect on fos (P = 0.0677). The multiple linear regression model suggested that both sex (P = 0.000) and age (P = 0.000) significantly predicted fos. fos of the female speakers was greater than males by 76 Hz, when accounted for by age, and for every increase in age by one year, fos decreased by 0.37 Hz. Normative data on fos were therefore provided with reference to speaker sex and age only. CONCLUSION: Both clinicians and researchers are provided with normative fos data for 18-60 year-old speakers of Australian English. These updated data have increased internal and external validity relative to previous literature. These increases were achieved by having a larger sample size, systematically sampling speakers of different age groups and geographical locations, sampling contemporary speakers of Australian English and excluding speakers with known concomitant factors that affect fos.
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Fonação , Voz , Adolescente , Adulto , Austrália , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores Sexuais , Adulto JovemRESUMO
Purpose The aim of the study was to examine associations between speaking fundamental frequency (f os), vowel formant frequencies (F), listener perceptions of speaker gender, and vocal femininity-masculinity. Method An exploratory study was undertaken to examine associations between f os, F 1-F 3, listener perceptions of speaker gender (nominal scale), and vocal femininity-masculinity (visual analog scale). For 379 speakers of Australian English aged 18-60 years, f os mode and F 1-F 3 (12 monophthongs; total of 36 Fs) were analyzed on a standard reading passage. Seventeen listeners rated speaker gender and vocal femininity-masculinity on randomized audio recordings of these speakers. Results Model building using principal component analysis suggested the 36 Fs could be succinctly reduced to seven principal components (PCs). Generalized structural equation modeling (with the seven PCs of F and f os as predictors) suggested that only F 2 and f os predicted listener perceptions of speaker gender (male, female, unable to decide). However, listener perceptions of vocal femininity-masculinity behaved differently and were predicted by F 1, F 3, and the contrast between monophthongs at the extremities of the F 1 acoustic vowel space, in addition to F 2 and f os. Furthermore, listeners' perceptions of speaker gender also influenced ratings of vocal femininity-masculinity substantially. Conclusion Adjusted odds ratios highlighted the substantially larger contribution of F to listener perceptions of speaker gender and vocal femininity-masculinity relative to f os than has previously been reported.
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Feminilidade , Masculinidade , Austrália , Feminino , Humanos , Masculino , Percepção , Acústica da FalaRESUMO
OBJECTIVE: Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019. METHODS: This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits. RESULTS: A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up. CONCLUSIONS: Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.
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Crotonatos/uso terapêutico , Hidroxibutiratos/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Nitrilas/uso terapêutico , Toluidinas/uso terapêutico , Adulto , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Sistema de Registros , Resultado do TratamentoRESUMO
Parent report data on 82 preschool children with complex neurodevelopmental disabilities including Down syndrome, dyspraxia, autism, and global developmental delay suggests communicative language use must reach a threshold level before vocabulary size becomes the best predictor of word combining. Using the Language Use Inventory and the MacArthur-Bates CDI (with sign vocabulary option), statistical modelling using regression trees and random forests suggests that, despite high linear correlations between variables, (1) pragmatic ability, particularly children's emerging ability to talk about things, themselves and others is a significantly better predictor of the earliest word combining than vocabulary size; and (2) vocabulary size becomes a better predictor of later word combining, once this pragmatic base has been established.
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Linguagem Infantil , Comunicação , Crianças com Deficiência/estatística & dados numéricos , Deficiência Intelectual/fisiopatologia , Desenvolvimento da Linguagem , Vocabulário , Criança , Pré-Escolar , Feminino , Humanos , Testes de Linguagem , Masculino , Modelos EstatísticosRESUMO
OBJECTIVE: Since the last epidemiologic review of neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), 22 additional studies have been conducted. We systematically review the worldwide prevalence, incidence, and basic demographic characteristics of NMOSD and provide a critical overview of studies. METHODS: PubMed, Ovid MEDLINE, and Embase using Medical Subject Headings and keyword search terms and reference lists of retrieved articles were searched from 1999 until August 2019. We collected data on the country; region; methods of case assessment and aquaporin-4 antibody (AQP4-Ab) test; study period; limitations; incidence (per 100,000 person-years); prevalence (per 100,000 persons); and age-, sex-, and ethnic group-specific incidence or prevalence. RESULTS: We identified 33 relevant articles. The results indicated the highest estimates of incidence and prevalence of NMOSD in Afro-Caribbean region (0.73/100 000 person-years [95% CI: 0.45-1.01] and 10/100 000 persons [95% CI: 6.8-13.2]). The lowest incidence and prevalence of NMOSD were found in Australia and New Zealand (0.037/100 000 person-years [95% CI: 0.036-0.038] and 0.7/100,000 persons [95% CI: 0.66-0.74]). There was prominent female predominance in adults and the AQP4-Ab-seropositive subpopulation. The incidence and prevalence peaked in middle-aged adults. African ethnicity had the highest incidence and prevalence of NMOSD, whereas White ethnicity had the lowest. No remarkable trend of incidence was described over time. CONCLUSION: NMOSD is a rare disease worldwide. Variations in prevalence and incidence have been described among different geographic areas and ethnicities. These are only partially explained by different study methods and NMO/NMOSD definitions, highlighting the need for specifically designed epidemiologic studies to identify genetic effects and etiologic factors.
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Saúde Global , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/epidemiologia , Humanos , Incidência , Neuromielite Óptica/sangue , PrevalênciaRESUMO
OBJECTIVE: To determine the effectiveness of high-efficacy disease-modifying therapies (heDMTs) vs medium-efficacy disease-modifying therapies (meDMT) as the first treatment choice in treatment-naive patients with multiple sclerosis (MS) on disability worsening and relapses. We assessed this using a nationwide population-based MS registry. METHODS: We identified all patients starting a heDMT as first-time treatment from the Danish Multiple Sclerosis Registry and compared treatment outcomes with a propensity score matched sample of patients starting meDMT. RESULTS: We included 388 patients in the study: 194 starting initial therapy with heDMT matched to 194 patients starting meDMT. At 4 years of follow-up, the probabilities of a 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening were 16.7% (95% confidence interval [CI] 10.4%-23.0%) and 30.1% (95% CI 23.1%-37.1%) for heDMT and meDMT initiators, respectively (hazard ratio [HR] 0.53, 95% CI 0.33-0.83, p = 0.006). Patients initiating heDMT also had a lower probability of a first relapse (HR 0.50, 95% CI 0.37-0.67). Results were similar after pairwise censoring and in subgroups with high baseline activity, diagnosis after 2006, or information on baseline T2 lesion load. CONCLUSION: We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting meDMT.
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Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Estudos de Coortes , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the risk of losing income from salaries and risk disability pension for multiple sclerosis patients with a clinically stable disease course 3 years after the start of disease-modifying therapy (DMT). METHODS: Data from the Danish Multiple Sclerosis Registry were linked to other Danish nationwide population-based databases. We included patients who started treatment with a DMT between 2001 and 2014. Patients were categorised into a clinically stable group (No Evidence of Disease Activity (NEDA-2)) and a clinically active group (relapse activity or 6-month confirmed Expanded Disability Status Scale worsening). Outcomes were: (1) loss of regular income from salaries and (2) a transfer payment labelled as disability pension. We used a Cox proportional hazards model to estimate confounder-adjusted HRs, and absolute risks were plotted using cumulative incidence curves accounting for competing risks. RESULTS: We included 2406 patients for the income analyses and 3123 patients for the disability pension analysis. Median follow-up from index date was ~5 years in both analyses. The NEDA-2 group had a 26% reduced rate of losing income (HR 0.74; 95% CI 0.60 to 0.92). HRs were calculated for 5-year intervals in the disability pension analysis: year 0-5: a 57% reduced rate of disability pension for the NEDA-2 group (HR 0.43; 95% CI 0.33 to 0.55) and year 5-10: a 36% reduced rate (HR 0.64; 95% CI 0.40 to 1.01). CONCLUSION: Clinically stable disease course (NEDA-2) is associated with a reduced risk of losing income from salaries and a reduced risk of disability pension.
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Avaliação da Deficiência , Renda , Esclerose Múltipla/economia , Esclerose Múltipla/patologia , Pensões/estatística & dados numéricos , Adolescente , Adulto , Bases de Dados Factuais , Dinamarca/epidemiologia , Progressão da Doença , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Recidiva , Sistema de Registros , Medição de Risco , Salários e Benefícios , Adulto JovemAssuntos
Neuromielite Óptica , Aquaporina 4 , Estudos de Coortes , Dinamarca , Humanos , PrevalênciaRESUMO
OBJECTIVES: To estimate the nationwide population-based incidence, prevalence, and geographical distribution of neuromyelitis optica (NMO) spectrum disorder (NMOSD) in Denmark based on the 2015 International Panel for NMO Diagnosis (IPND) criteria. METHODS: We conducted a multicentre, historically prospective study. Data were sourced from the Danish National Patient Registry, the Danish Multiple Sclerosis Registry, departments of neurology, and laboratories providing aquaporin-4 antibody test. Cases were selected based on the 2006 Wingerchuk and the 2015 IPND criteria and were individually validated by an expert panel. RESULTS: We confirmed NMO in 30 cases (2006 criteria) and NMOSD in 56 cases (2015 IPND criteria) between 2007 and 2014. Defined by the 2006 criteria, the incidence of NMO was 0.029 per 100,000 person-years (95% confidence interval [CI] 0.014-0.051), and the prevalence (aged 16 years and older) was 0.566 per 100,000 (95% CI 0.370-0.830). Based on the 2015 IPND criteria, the incidence of NMOSD was 0.070 per 100,000 person-years (95% CI 0.046-0.102), and the prevalence (aged 16 years and older) was 1.09 per 100,000 (95% CI 0.808-1.440), without regional differences. CONCLUSIONS: Our estimates of incidence and prevalence are similar to other Caucasian population-based studies using the 2015 IPND criteria. We found no geographical clustering in Denmark.
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Neuromielite Óptica/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , População Branca , Adulto JovemRESUMO
BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) can be found in different immune-mediated inflammatory CNS disorders. The full range of clinical manifestations may not have been fully discovered yet. METHODS: In a cross-sectional study 184 adults (ageâ¯≥â¯16) were tested for anti-MOG antibody (Ab) with a cell-based assay. To define the relevant target population for anti-MOG antibody testing in a neurology clinic, we divided the entire study population based on the presenting symptoms and classified cases followed for multiple sclerosis (MS) according to the clinical features and response to disease-modifying therapy. RESULTS: We identified eight (4.4%) MOG-Ab positive cases in the whole cohort. All eight cases had first manifestations suggestive of neuromyelitis optica spectrum disorder (NMOSD), but had highly variable disease courses and responses to therapy. This included a patient with chronic relapsing inflammatory optic neuropathy (CRION) responding only to therapy with infliximab. Four (3%) out of 134 cases followed for MS who tested positive for anti-MOG Ab showed atypical features and had poor response to therapy. CONCLUSION: A broad range of clinical and radiological features of anti-MOG associated disorder was observed in a single centre. MOG-Ab testing should be considered in patients with an NMOSD phenotype and in MS patients presenting atypical features. The potential use of infliximab therapy for MOG-Ab disease should be further investigated.
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Anti-Inflamatórios/farmacologia , Autoanticorpos/sangue , Infliximab/farmacologia , Esclerose Múltipla/sangue , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/sangue , Neurite Óptica/sangue , Adolescente , Adulto , Estudos Transversais , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: Thromboinflammatory molecules connect the prothrombotic state, endothelial dysfunction, and systemic/local inflammation in the acute phase of ischemic stroke. METHODS: We prospectively investigated (1) serial changes in the levels of thromboinflammatory biomarkers in 76 patients with acute ischemic stroke (6, 24, and 72 hours after onset); (2) compared with 44 patients with asymptomatic severe (≥70%) carotid stenosis and 66 patients with Parkinson disease; and (3) we applied multiple regression methods, relating biological biomarkers combined with demographic data and comorbidities to poststroke infection, death, and functional outcome, and assessed the ability of the models to predict each outcome. RESULTS: Interleukin 6 (IL-6) levels and change of IL-6 concentrations by 72 hours correlated with the size of tissue damage indicated by S100B titers. Levels of IL-6 and P-selectin at 72 hours were higher in patients with large-artery versus lacunar stroke. High concentration of IL-6, monocyte chemotactic protein 1, and S100B at 6 hours were associated with poststroke infections; high concentration of IL-6, S100B, and high-sensitivity C-reactive protein (hsCRP) correlated with death. Change of P-selectin from 6 to 72 hours by 1 unit increased the incidence of poststroke infections with an odds ratio of 22.7; each 100 units of IL-6 at baseline increased the odds of death by 9, and at 72 hours, the odds of poststroke infections by 4. Each unit of baseline hsCRP elevated the odds of death by 7%. CONCLUSIONS: In regression models, in which biological, demographic, and comorbid factors were combined, those biological biomarkers predicted poor outcome with high accuracy, which were characterized by an increasing concentration by 72 hours. Two particular biomarkers emerged to predict outcomes besides hsCRP: early dynamic changes in the systemic levels of P-selectin and IL-6.
Assuntos
Isquemia Encefálica/complicações , Interleucina-6/sangue , Selectina-P/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Quimiocina CCL2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Estatística como Assunto , Estatísticas não Paramétricas , Acidente Vascular Cerebral/mortalidade , Fatores de TempoRESUMO
BACKGROUND: Endothelial dysfunction is associated with increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) resulting in a decreased production of nitric oxide, which regulates the vascular tone. METHODS: Patients with acute ischemic stroke (AIS, n = 55) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring. RESULTS: Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting infarct size, positively correlated with the level of SDMA at 72 poststroke hours; changes in concentration of S100 B positively correlated with changes in the concentration of ADMA by 72 hours. Change in concentration of both ADMA and SDMA correlated with the change in concentration of hsCRP. Concentrations of L-arginine and hsCRP at 72 poststroke hours, respectively, were independent predictors of poststroke infection. S100 B level measured within 6 hours after the onset of AIS and hsCRP at 72 poststroke hours were independent predictors of death. CONCLUSIONS: Metabolites of the L-arginine pathway were elevated in the very acute phase of ischemic stroke indicating a more pronounced endothelial dysfunction compared with AsCS. An increased basal L-arginine level in patients with AIS might be an adaptive mechanism; such transient elevation of the L-arginine/ADMA ratio at 24 poststroke hours may suggest that a temporary increase of L-arginine along with decrease of ADMA might be related to the protective role of L-arginine. Changes in the L-arginine pathway are predictive of poststroke infections.