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Mashup Score: 2
Background To mimic as closely as possible a randomised controlled trial (RCT) and calibrate the real-world evidence (RWE) studies against a known treatment effect would be helpful to understand if RWE can support causal conclusions in selected circumstances. The aim was to emulate the TRANSFORMS trial comparing Fingolimod (FTY) versus intramuscular interferon β-1a (IFN) using observational data. Methods We extracted from the MSBase registry all the patients with relapsing-remitting multiple sclerosis (RRMS) collected in the period 2011–2021 who received IFN or FTY (0.5 mg) and with the same inclusion and exclusion criteria of the TRANSFORMS RCT. The primary endpoint was the annualised relapse rate (ARR) over 12 months. Patients were 1:1 propensity-score (PS) matched. Relapse-rate ratio (RR) was calculated by mean of a negative binomial regression. Results A total of 4376 patients with RRMS (1140 in IFN and 3236 in FTY) were selected. After PS, 856 patients in each group were matched.
Source: jnnp.bmj.comCategories: General Medicine News, NeurologyTweet
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Mashup Score: 12Head trauma results in manyfold increased risk of multiple sclerosis in genetically susceptible individuals - 4 month(s) ago
Background Large register-based studies have reported an association between head trauma and increased risk of multiple sclerosis (MS). We aimed to investigate possible interactions between head trauma and MS-associated HLA genes in relation to MS risk. Methods We used a Swedish population-based case-control study (2807 incident cases, 5950 matched controls with HLA genotypes available for 2057 cases, 2887 controls). Subjects with and without a history of self-reported head trauma were compared regarding MS risk, by calculating ORs with 95% CIs using logistic regression models. Additive interaction between head trauma, HLA-DRB1*1501 and absence of HLA-A*0201 , was assessed by calculating the attributable proportion (AP) due to interaction. Results A history of head trauma was associated with a 30% increased risk of subsequently developing MS (OR 1.34, 95% CI 1.17 to 1.53), with a trend showing increased risk of MS with increasing number of head impacts (p=0.03). We observed synergistic
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Mashup Score: 121PSCK9 inhibitors reduced early recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis - 4 month(s) ago
Background Symptomatic intracranial atherosclerotic stenosis (ICAS) is prone to cause early recurrent stroke (ERS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels and prevent cardiovascular events. This multicentre, hospital-based prospective cohort study was designed to investigate whether PCSK9 inhibitors would prevent ERS in patients with symptomatic ICAS. Methods From 1 October 2020 to 30 September 2022, consecutive patients with acute ischaemic stroke attributed to ICAS admitted within 1 week after onset were enrolled and followed up for 1 month. Patients were divided into two groups, the PCSK9 inhibitors group receiving PCSK9 inhibitors add-on therapy, and the control group receiving statins and/or ezetimibe. The primary outcome was ERS. Cox proportional hazard models and Kaplan-Meier survival curve were used to estimate the association between PCSK9 inhibitors and ERS. Results At the end of follow-up, the
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Mashup Score: 9
Background Delirium is an important risk factor for subsequent dementia. However, the field lacks large studies with long-term follow-up of delirium in subjects initially free of dementia to clearly establish clinical trajectories. Methods We undertook a retrospective cohort study of all patients over the age of 65 diagnosed with an episode of delirium who were initially dementia free at onset of delirium within National Health Service Greater Glasgow & Clyde between 1996 and 2020 using the Safe Haven database. We estimated the cumulative incidence of dementia accounting for the competing risk of death without a dementia diagnosis. We modelled the effects of age at delirium diagnosis, sex and socioeconomic deprivation on the cause-specific hazard of dementia via cox regression. Results 12 949 patients with an incident episode of delirium were included and followed up for an average of 741 days. The estimated cumulative incidence of dementia was 31% by 5 years. The estimated cumulative
Source: jnnp.bmj.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 7
Background Although CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient selection for endovascular treatment (EVT) in patients presenting within 6 hours after symptom onset with a large vessel occlusion. Methods Patients with a large vessel occlusion were included from a Dutch nationwide cohort (n=703) if CTP imaging was performed before EVT within 6 hours after stroke onset. Simulated cost and health effects during 5 and 10 years follow-up were compared between CTP based patient selection for EVT and providing EVT to all patients. Outcome measures were the net monetary benefit at a willingness-to-pay of €80 000 per quality-adjusted life year, incremental cost-effectiveness ratio), difference in costs from a healthcare payer perspective (ΔCosts) and quality-adjusted life years (ΔQALY) per 1000 patients for 1000 model iterations as outcomes. Results Compa
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Mashup Score: 2Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis - 5 month(s) ago
Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. Methods Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients’ blood and fibroblasts, was performed. Results All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction st
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Mashup Score: 3Pragmatic computerised perfusion diagnostics for non-convulsive status epilepticus: a prospective observational study - 5 month(s) ago
Background Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow. Methods We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for
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Mashup Score: 11Clinical biomarker-based biological ageing and future risk of neurological disorders in the UK Biobank - 6 month(s) ago
Background Many common neurological disorders are associated with advancing chronological age, but their association with biological age (BA) remains poorly understood. Methods We studied 325 870 participants in the UK Biobank without a diagnosed neurological condition at baseline and generated three previously-described measures of BA based on 18 routinely measured clinical biomarkers (PhenoAge, Klemera-Doubal method age (KDMAge), homeostatic dysregulation age). Using survival models, we assessed the effect of advanced BA on incident neurological diagnoses, including all-cause and cause-specific dementia, ischaemic stroke, Parkinson’s disease and motor neuron disease. Results During a mean follow-up of 9.0 years, there were 1397 incident cases of dementia and 2515 of ischaemic stroke, with smaller case numbers of other diagnoses. The strongest associations with a 1 SD in BA residual were seen for all-cause dementia (KDMAge HR=1.19, 95% CI=1.11 to 1.26), vascular dementia (1.41, 1.25 t
Source: jnnp.bmj.comCategories: General Medicine News, CardiologistsTweet
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Mashup Score: 1COVID-19 has no impact on disease activity, progression and cognitive performance in people with multiple sclerosis: a 2-year study - 6 month(s) ago
Background Sequelae of COVID-19 in people with multiple sclerosis (PwMS) have not been characterised. We explored whether COVID-19 is associated with an increased risk of disease activity, disability worsening, neuropsychological distress and cognitive dysfunction during the 18–24 months following SARS-COV-2 infection. Methods We enrolled 174 PwMS with history of COVID-19 (MS-COVID) between March 2020 and March 2021 and compared them to an age, sex, disease duration, Expanded Disability Status Scale (EDSS), and a line of treatment-matched group of 348 PwMS with no history of COVID-19 in the same period (MS-NCOVID). We collected clinical, MRI data and SARS-CoV2 immune response in the 18–24 months following COVID-19 or baseline evaluation. At follow-up, PwMS also underwent a complete neuropsychological assessment with brief repeatable battery of neuropsychological tests and optimised scales for fatigue, anxiety, depression and post-traumatic stress symptoms. Results 136 MS-COVID and 186
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Mashup Score: 24Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis - 6 month(s) ago
Background We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). Methods A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman’s r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods. Results Median (IQR) age of patients was 52.9 (46.4–58.5) years, and 58 (41
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Emulating randomised clinical trials in relapsing-remitting multiple sclerosis with non-randomised real-world evidence: an application using data from the MSBase Registry https://t.co/4BA1UG3fi4