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ObjectiveTo evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF).MethodsWe undertook a population-based cohort study with nested case–control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016–2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression.ResultsWe identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued.ConclusionsOur results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.

Acquired hemolytic disorders-autoimmune hemolytic anemia (AIHA), cold agglutinin disease (CAD), paroxysmal nocturnal hemoglobinuria (PNH), drug-induced hemolysis (DIHA), and acquired hemolysis not otherwise specified (AHNOS)-are considered rare. Despite their potentially major health implications, data regarding their incidence and prevalence are scarce. To fill this gap we collected data regarding all patients with acquired hemolytic disorder diagnoses in 1977-2016 from the Danish National Patient Register. These data were linked with vital and migration status information from the Danish Civil Registration System. From these data combined with annual demographic data for the background population, we calculated age- and sex-specific incidence rates and prevalence proportions of acquired hemolytic disorders for specified time periods. Our analysis included 5868 patients with acquired hemolytic disorders (2715 with AIHA, 112 CAD, 397 DIHA, 116 PNH, and 2154 AHNOS). The incidence rates per 100 000 person-years in 1980-1993 and 2008-2016 were 0.81 and 1.77 for AIHA, 0.31 and 0.12 for DIHA, and 0.04 and 0.08 for PNH, respectively. The 2008-2016 CAD incidence rate was 0.18/100 000 person-years, CAD diagnosis code was not defined before 1994. All incidence rates increased with age. The prevalence proportion per 100 000 persons in 1980 and 2015 was 2.52 and 17.01 for AIHA, 0.80 and 1.50 for DIHA, and 0.18 and 1.04 for PNH. CAD prevalence in 2015 was 1.04/100 000 persons. Acquired hemolytic anemia incidence rates and prevalence proportions with the exception of DIHA are markedly increasing.

Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems.

Background and aims Polyneuropathy is a common neurological disorder with many potential causes. An essential part in screening, diagnosis, and follow‐up evaluation of polyneuropathy is testing of the sensory function including vibratory sensation. The graduated Rydel‐Seiffer tuning fork and the biothesiometer have been developed to quantify vibratory sensation through detection thresholds. The aim of this study is to compare the vibration detection thresholds determined by the two instruments regarding intraindividual temporal changes, interindividual variation in healthy subjects and comparison of the diagnostic value in patients with a clinical suspicion of polyneuropathy. Methods Ninety‐four healthy subjects, 98 patients with and 97 patients without a diagnosis of polyneuropathy were included. Quantitative sensory testing including biothesiometry, structured clinical examination, and nerve conduction studies were performed three times during 52 weeks in healthy subjects and once in patients. Results There were no significant changes over time for neither the Rydel‐Seiffer tuning fork nor the biothesiometer, and both had larger between‐subject variation than within‐subject variation. Relative intertrial variability was largest for the biothesiometer. Diagnostic value (sensitivity, specificity, positive predictive value, and negative predictive value) was moderate for both methods (Rydel‐Seiffer tuning fork: 58%, 74%, 70%, 64%; biothesiometer: 47%, 77%, 68%, 59%). Interpretation The Rydel‐Seiffer tuning fork and the biothesiometer have a low test‐retest and time dependent variation. They perform almost equally as diagnostic tools in patients with suspected polyneuropathy with a tendency toward better performance of the tuning fork. The graduated Rydel‐Seiffer tuning fork and the biothesiometer have been developed to quantify vibratory sensation through detection thresholds. We compared intra‐individual temporal changes, inter‐individual variation in healthy subjects and comparison of diagnostic value in patients with a clinical suspicion of polyneuropathy. They both have a low test‐retest and time dependent variation and perform almost equally as diagnostic tools in patients with suspected polyneuropathy with a tendency towards better performance of the tuning fork.

ObjectivesThis systematic review and meta-analysis aimed to assess the stroke detection performance of artificial intelligence (AI) in magnetic resonance imaging (MRI), and additionally to identify reporting insufficiencies.MethodsPRISMA guidelines were followed. MEDLINE, Embase, Cochrane Central, and IEEE Xplore were searched for studies utilising MRI and AI for stroke detection. The protocol was prospectively registered with PROSPERO (CRD42021289748). Sensitivity, specificity, accuracy, and area under the receiver operating characteristic (ROC) curve were the primary outcomes. Only studies using MRI in adults were included. The intervention was AI for stroke detection with ischaemic and haemorrhagic stroke in separate categories. Any manual labelling was used as a comparator. A modified QUADAS-2 tool was used for bias assessment. The minimum information about clinical artificial intelligence modelling (MI-CLAIM) checklist was used to assess reporting insufficiencies. Meta-analyses were performed for sensitivity, specificity, and hierarchical summary ROC (HSROC) on low risk of bias studies.ResultsThirty-three studies were eligible for inclusion. Fifteen studies had a low risk of bias. Low-risk studies were better for reporting MI-CLAIM items. Only one study examined a CE-approved AI algorithm. Forest plots revealed detection sensitivity and specificity of 93% and 93% with identical performance in the HSROC analysis and positive and negative likelihood ratios of 12.6 and 0.079.ConclusionCurrent AI technology can detect ischaemic stroke in MRI. There is a need for further validation of haemorrhagic detection. The clinical usability of AI stroke detection in MRI is yet to be investigated.Critical relevance statementThis first meta-analysis concludes that AI, utilising diffusion-weighted MRI sequences, can accurately aid the detection of ischaemic brain lesions and its clinical utility is ready to be uncovered in clinical trials.Key PointsThere is a growing interest in AI solutions for detection aid.The performance is unknown for MRI stroke assessment.AI detection sensitivity and specificity were 93% and 93% for ischaemic lesions.There is limited evidence for the detection of patients with haemorrhagic lesions.AI can accurately detect patients with ischaemic stroke in MRI.

Congenital red blood cell (RBC) disorders, such as hemoglobinopathies, are frequent worldwide but with large geographical variation. Growing migration has increased the number of patients with RBC disorders in formerly low prevalence countries, eg, Denmark. However, accurate prevalences are unknown. Patients with a registered diagnosis of congenital hemolysis in the Danish National Patient Register between 1977 and 2016 were linked to a national laboratory database of RBC disorders and the Danish civil registration system. We calculate annual age- and sex-specific prevalences of the congenital hemolytic disorders from 2000 to 2016. Prevalences of all subtypes of congenital hemolytic disorders increased during the study period. The prevalence of hereditary spherocytosis increased 1.73 times between 2000 and 2015, from 10.2/10 persons to 17.7/10 persons. Alpha thalassemia trait had a prevalence of 0.5/10 persons in 2000, but increased 41 times to 19.2/10 persons in 2015. Beta thalassemia minor increased eightfold from 4.5/10 persons in 2000 to 34.9/10 persons in 2015. Likewise, sickle cell trait increased 11 times from 0.7/10 persons in 2000 to 8.1/10 persons in 2015, whereas sickle cell disease increased from 0.5/10 persons to 2.7/10 persons in 2015, a fivefold increase. The prevalence of congenital RBC disorders in Denmark is increasing. The hemoglobinopathy traits now have prevalences as high as hereditary spherocytosis. These estimates of congenital hemolytic disorders in Denmark emphasize that inborn hemoglobin disorders are a public health concern, even in some formerly low prevalence countries.

To establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). Based on discharge summaries and brain imaging reports, we estimated the positive predictive value (PPV) of a first-ever diagnosis code for ICH (ICD-10, code I61) for all patients in the Region of Southern Denmark (1.2 million) during 2009-2017 according to either DNPR or DSR. We estimated PPVs for any non-traumatic ICH (a-ICH) and spontaneous ICH (s-ICH) alone (ie, without underlying structural cause). We also calculated the sensitivity of these diagnoses in each of the registers. Finally, we classified the location of verified s-ICH. A total of 3,956 patients with ICH diagnosis codes were studied (DSR only: 87; DNPR only: 1,513; both registries: 2,356). In the DSR, the PPVs were 86.5% (95% CI=85.1-87.8) for a-ICH and 81.8% (95% CI=80.2-83.3) for s-ICH. The PPVs in DNPR (discharge code, primary diagnostic position) were 76.2% (95% CI=74.7-77.6) for a-ICH and 70.2% (95% CI=68.6-71.8) for s-ICH. Sensitivity for a-ICH and s-ICH was 76.4% (95% CI=74.8-78.0) and 78.7% (95% CI=77.1-80.2) in DSR, and 87.3% (95% CI=86.0-88.5) and 87.7% (95% CI=86.3-88.9) in DNPR. The location of verified s-ICH was lobar (39%), deep (33.6%), infratentorial (13.2%), large unclassifiable (11%), isolated intraventricular (1.9%), or unclassifiable due to insufficient information (1.3%). The validity of a-ICH diagnoses is high in both registries. For s-ICH, PPV was higher in DSR, while sensitivity was higher in DNPR. The location of s-ICH was similar to distributions seen in other populations.

Danish registries could be an attractive resource for studies of recurrent intracerebral hemorrhage (re-ICH). We developed and validated algorithms to identify re-ICH in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). Using multiple sources, we followed-up an inception cohort with verified first-ever spontaneous ICH (n = 2528) for their first re-ICH in 2009-2018 (study period). We used verified cases of re-ICH (n = 124) as the gold standard to assess the performance of register-based algorithms for identifying re-ICH. For each cohort member, we traced events of re-ICH (ICD-10-code I61) in the study period according to DSR and DNPR, respectively. For each registry, we tested algorithms with a blanking period (BP) - ie, a period immediately following the index ICH during which outcome events were ignored - of varying length (7 days-360 days). The algorithm with the shortest BP that returned a positive predictive value (PPV) of ≥80% was considered optimal. We also calculated negative predictive value (NPV), sensitivity, and specificity of each algorithm and [95% confidence intervals] for all proportions. The optimal algorithm for DSR (BP 30 days) had a PPV of 89.5% [82.2-94.0], NPV 98.8% [98.2-99.1], sensitivity 75.8% [67.6-82.5], and specificity 99.5% [99.2-99.7]. The optimal algorithm for DNPR (BP 120 days) had a PPV of 80.6% [71.7-87.2], NPV 98.1% [97.5-98.6], sensitivity 63.7% [55.0-71.6], and specificity 99.2% [98.8-99.5]. Simple algorithms accurately identified re-ICH in DSR and DNPR. Compared with DNPR, DSR achieved higher PPV and sensitivity with a shorter BP. The proposed algorithms could facilitate valid use of DSR and DNPR for studies of re-ICH.

The purpose of this study is to establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). We estimated the positive predictive value (PPV) of ICH diagnoses for a sample of 500 patients from the DSR (patients recorded under ICH diagnosis) and DNPR (International Classification of Diseases, version 10, code I61) during 2010-2015, using discharge summaries and brain imaging reports (minimal data). We estimated PPVs for any ICH (a-ICH) and spontaneous ICH (s-ICH) alone. Furthermore, we assessed PPVs according to whether patients were recorded in both or only one of the registries. Finally, in a subsample with ICH diagnoses with access to full medical records and original imaging studies (extensive data, n=100), we compared s-ICH diagnosis and hemorrhage location after use of extensive vs minimal data. In the DSR, the PPVs were 94% (95% CI, 91%-96%) for a-ICH and 85% (95% CI, 81%-88%) for s-ICH. In the DNPR, the PPVs were 88% (95% CI, 84%-91%) for a-ICH and 75% (95% CI, 70%-79%) for s-ICH. PPVs for s-ICH for patients recorded in both registries, DSR only, and DNPR only were 86% (95% CI, 82-99), 80% (95%CI, 71-87), and 49% (95%CI, 39-59), respectively. Evaluation of extensive vs minimal data verified s-ICH diagnosis in 98% and hemorrhage location in 94%. The validity of a-ICH diagnoses in DSR and DNPR is sufficiently high to support their use in epidemiologic studies. For s-ICH, validity was high in DSR. In DNPR, s-ICH validity was lower, markedly so for the small subgroup of patients only recorded in this registry. Minimal data including discharge summaries and brain imaging reports were feasible and valid for identifying ICH location.

Background and purposeChronic distal sensory or sensorimotor polyneuropathy is the most common pattern of polyneuropathy. The cause of this pattern is most often diabetes or unknown. This cross-sectional study is one of the first studies to compare the demographics, cardiovascular risk factors and clinical characteristics of diabetic polyneuropathy (DPN) with idiopathic polyneuropathy (IPN).MethodsPatients with DPN were included from a sample of 389 patients with type 2 diabetes mellitus (T2DM) enrolled from a national cohort of patients with recently diagnosed T2DM (Danish Centre for Strategic Research in Type 2 Diabetes cohort). Patients with IPN were included from a regional cohort of patients with symptoms of polyneuropathy referred for workup at a combined secondary and tertiary neurological centre (database cohort).ResultsA total of 214 patients with DPN were compared with a total of 88 patients with IPN. Patients with DPN were older (67.4 vs 59 years) and had a longer duration of neuropathy symptoms. Patients with DPN had greater body mass index (32 vs 27.4 kg/m2) and waist circumference (110 cm vs 97 cm); higher frequency of hypertension diagnosis (72.9% vs 30.7%); lower total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels; and a higher prevalence of use of statins (81.8% vs 19.3%). DPN was associated with a slightly higher autonomic score and total score on the Neuropathy Symptom Score; lower frequency of hyperalgesia, allodynia and decreased vibration on quantitative sensory testing; lower intraepidermal nerve fibre density count and higher frequency of small-fibre neuropathy.ConclusionDPN and IPN showed clear differences in neuropathy characteristics, indicating that these two entities are to be regarded as aetiologically and pathogenetically distinct.