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Background Swift reversal of oral anticoagulation is deemed essential for the outcome of patients with anticoagulation-related critical bleeding. The aim of this systematic review was to evaluate the benefits and harms of prothrombin complex concentrate (PCC) in patients with oral anticoagulants-related critical bleeding. Methods For this systematic review CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Web of Science, and clinical trial registries were systematically searched. Clinical study reports were also requested from competent authorities. Eligible for inclusion were randomised clinical trials comparing PCC versus no intervention, placebo, or other reversal interventions in participants with critical bleeding related to ongoing treatment with vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC). Pre-specified primary outcomes were all-cause mortality, health-related quality of life, and serious adverse events for which meta-analyses, Trial Sequential Analysis, and GRADE assessments were conducted. Results Three trials, randomising a total of 291 participants, evaluated PCC against two different active comparators in participants with VKA-related critical bleeding, and two trials, randomising a total of 534 participants, evaluated PCC against two different active comparators in participants with factor Xa-related critical bleeding. Among participants with VKA-related critical bleeding, meta-analyses showed no evidence of a difference between PCC versus fresh frozen plasma (FFP) when assessing all-cause mortality (risk ratio [RR] 1.05; 95% confidence interval (CI) 0.27 to 4.05; low certainty), health-related quality of life (mean difference 1.04; 95% CI − 0.94 to 3.02; very low certainty), and serious adverse events (RR 1.33; 95% CI 0.94 to 1.88; very low certainty), but information is currently sparse. Among participants with factor Xa-related critical bleeding, PCC could not be shown superior or inferior to other reversal strategies (FFP or andexanet alfa) on any patient-relevant outcome, but information is currently sparse. Conclusion Among participants with VKA or DOAC-related critical bleeding, evidence from randomised clinical trials is currently insufficient to establish if PCC is superior or inferior versus other interventions in decreasing the risk of undesirable patient-relevant outcomes or improving health-related quality of life.

Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.

Introduction Non-vitamin K-antagonist oral anticoagulants (NOAC) have become first choice oral anticoagulant (OAC) with decreasing use of vitamin K antagonists (VKA), partly due to lower risk of intracerebral hemorrhage (ICH). Aim: to identify trends in sale of OACs and relate them to trends in OAC-related ICH (OAC-ICH). Patients and methods Study was based on the population in the Capital Region of Denmark (1.8 million inhabitants). We identified all patients admitted with a non-traumatic OAC-ICH in 2010–2017 and ascertained diagnosis and drug use through medical charts. We used information available in the public domain on sale of defined daily doses (DDD) of OAC in the Capital Region of Denmark. Results 453 patients with OAC-ICH out of a total of 2877 ICH-events were identified. From 2010 to 2017 sale of NOAC rose from 0.1 to 11.8 DDD/1000 inhabitants/day (p < 0.001); while VKA sale decreased from 7.6 to 5.2 DDD/1000 inhabitants/day (p < 0.001). The total number of ICH events was stable between 2010 and 2017, but the proportion of OAC-ICH events increased from 13% in 2010 to 22% in 2017 (p < 0.001). The proportion of ICH events related to NOAC had a significant increasing trend (p < 0.001), whereas a decreasing trend was observed for VKA (p = 0.04). Discussion In Denmark, the population on OACs has increased; resulting from increased use of NOACs. Parallel to this development, the proportion of OAC-ICH overall has increased based on an increasing trend in NOAC-related ICH. Conclusion Our findings document a need for further research on prevention and treatment of this complication.

Background: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin resistance and diabetes are few and contradictory. Methods: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory and diabetes-related markers were measured pre- and post-surgically. Results: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative changes in S100A8/A9 and IL-6 correlated significantly (r = 0.905, p = 0.005) only in the group with persistent diabetes. In contrast, leukocyte count and C-reactive protein correlated significantly to S100A8/A9 only in the control group. Conclusion: Our study is suggestive of S100A8/A9 and IL-6 being related to a persistent diabetes status post-surgically and of different pathophysiological mechanisms being involved in the post-surgical changes in the three groups, despite similar decreases in BMI.

The incidence of intracerebral hemorrhage (ICH) associated with oral anticoagulants (OAC) is about one in five cases of ICH and associated with severe clinical presentation, frequently rapid clinical deterioration, and 30-days mortality of app 50%. This narrative review gives an overview of presentation and acute treatment of OAC-ICH. Oral anticoagulants do not cause ICH but lead to prolongation of bleeding and higher risk of hematoma expansion (HE). Clinicoradiological characteristics of oral anticoagulant associated ICH are not different from ICH in general. The therapeutic principle of reversal is to prevent or limit HE. The mode of action of the reversal agents for vitamin K antagonists, direct oral thrombin inhibitor and direct oral factor Xa inhibitors are described in the main text. We also discuss the principles of blood pressure lowering in the setting of acute OAC-ICH as it may be the second driving force of HE. Stroke unit care is needed to prevent further complications. Data from randomized controlled trials and observational data from unselected patients are needed to make stronger and more precise recommendations on acute therapy.

Introduction Organised stroke care and reperfusion therapies are key components of modern stroke treatment. We assessed accessibility of organised stroke care and reperfusion therapies in Europe and explored its association with key organisational indicators. Patients and methods Stroke Action Plan for Europe (SAP-E) Stroke Service Tracker data from 2023 reported by 47 European countries was assessed. Accessibility indicators included stroke unit (SU) admission proportions, intravenous thrombolysis (IVT) and EVT treatment proportions. Organisational indicators included the facility density of SU, IVT-capable centres and EVT-capable centres per capita (number of centres per 100,000 population), presence of national stroke plans and quality programmes. Results Across Europe, marked variations were observed in facility density of SU (0.21–0.48), IVT-capable centres (0.19–0.45) and EVT-capable centres (0.06–0.15). SU admission proportions ranked from 0.8% to 96.7%, IVT treatment proportions from 1.3% to 34.7% and EVT treatment proportions from 0.2% to 14.3%. Stroke unit admission proportions were associated with SU density (r = 0.42, P = .03). Density of reperfusion-capable centres showed a possible trending association with IVT treatment proportions (r = 0.34, P = .08), but no association with EVT treatment proportions (r = 0.22, P = .23). Neither the presence of a national stroke plan nor a quality programme were associated with accessibility of SU care, IVT or EVT. Conclusion Large inequities in access to organised stroke care and reperfusion therapies persist across Europe. At the country level, national stroke plans and quality programmes have not yet translated into effect on accessibility indicators, suggesting that achieving effective implementation takes time or could primarily manifest as within-country improvements.

Abstract Introduction Inequity in stroke care in Europe has previously been reported despite the existence of evidence-based cost-effective interventions for both prevention and treatment. This report aims to provide comprehensive data on stroke care in Europe in 2023 and explore associations to European regions, organisational and economic factors. Patients and methods The Stroke Service Tracker, an annually collected survey-based dataset of aggregate summary data from participating European nations, was used with key performance indicators (KPIs) from the Stroke Action Plan for Europe (SAP-E). European regions were defined based on United Nations Geoscheme regions. Gross domestic product (GDP) per capita and healthcare spending per capita were collected based on World Bank data. Results A total of 1,460,630 stroke events were reported in 2023 from 52 nations. Significant inequity was present in all data points and data quality varied significantly. Twenty (43.5%) nations have a national stroke plan in place, and in 19 (41.3%) work is ongoing. Quality programmes have been implemented in 20 (43.5%) nations. Implementation of a national stroke plan or a quality programme was associated with achieving more SAP-E KPIs (P < .001). There were regional differences in the number of met KPIs (P < .001). Both GDP and healthcare spending per capita were strongly correlated to meeting KPIs. Conclusion The inequity in stroke care persists in Europe. Implementation of a national stroke plan and a quality programme is associated with meeting more KPIs; however, economic factors may pose limitations. Access to high-quality data will support decision-making towards evidence-based and cost-effective care. Graphical Abstract Graphical Abstract