Potential effects of a mobile stroke unit on time to treatment and outcome in patients treated with thrombectomy or thrombolysis: A Danish-German cross-border analysis.

BACKGROUND AND PURPOSE: A mobile stroke unit (MSU) reduces delays in stroke treatment by allowing thrombolysis on board and avoiding secondary transports. Due to the beneficial effect in comparison to conventional emergency medical services, current guidelines recommend regional evaluation of MSU implementation. METHODS: In a descriptive study, current pathways of patients requiring a secondary transport for mechanical thrombectomy were reconstructed from individual patient records within a Danish (n = 122) and an adjacent German region (n = 80). Relevant timestamps included arrival times (on site, primary hospital, thrombectomy centre) as well as the initiation of acute therapy. An optimal MSU location for each region was determined. The resulting time saving was translated into averted disability-adjusted life years (DALYs). RESULTS: For each region, the optimal MSU location required a median driving time of 35 min to a stroke patient. Time savings in the German region (median [Q1; Q3]) were 7 min (-15; 31) for thrombolysis and 35 min (15; 61) for thrombectomy. In the Danish region, the corresponding time savings were 20 min (8; 30) and 43 min (25; 66). Assuming 28 thrombectomy cases and 52 thrombolysis cases this would translate to 9.4 averted DALYs per year justifying an annual net MSU budget of $0.8M purchasing power parity dollars (PPP-$) in the German region. In the Danish region, the MSU would avert 17.7 DALYs, justifying an annual net budget of PPP-$1.7M. CONCLUSION: The effects of an MSU can be calculated from individual patient pathways and reflect differences in the hospital infrastructure between Denmark and Germany.

Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms-a Danish longitudinal study.

The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics. We investigated NLR on mortality stratified by prevalent and incident MPN, essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), comorbidity burden (CCI-score), and the Triple-A risk score using hazard ratio (HR) and 95% confidence interval (95%CI). NLR 1-1.9 was the reference level. During a median follow-up of 11.2 years, 197,802 deaths were recorded. All-cause mortality increased for a stepwise increasing NLR with a HR (95%CI) for NLR ≥ 6 of 2.06(2.03-2.09) for the whole population and 2.93(2.44-3.50) in prevalent MPN. ET, PV, and MF had a HR (95%CI) for NLR ≥ 2 of 2.14(1.71-2.69), 2.19(1.89-2.54), and 2.31(1.91-2.80). Results were similar for incident MPN. Mortality was higher for stepwise increasing NLR and CCI-score(pinteraction < 2×10-16), with a HR for NLR ≥ 6 of 2.23(2.17-2.29), 4.10(4.01-4.20), and 7.69(7.50-7.89), for CCI-score 0, 1-2, or ≥3. The Triple-A risk score demonstrated alignment with NLR. Increasing NLR and comorbidity burden were associated with lower survival in individuals without MPN but were even worse in prevalent and incident MPN, ET, PV, and MF.

Elevated white blood cell counts in ischemic stroke patients are associated with increased mortality and new vascular events.

Background and purpose: High levels of white blood cells (WBC) in ischemic stroke have been shown to increase the risk of new vascular events and mortality in short and intermediate follow-up studies, but long-term effects remain unknown. We studied whether elevated levels of WBC in ischemic stroke patients are associated with new vascular events and mortality in a 10-year follow-up period. Methods: We included ischemic stroke patients hospitalized between 2011 and 2012, categorizing their WBC counts within 48 h of stroke onset as high or normal (3.5-8.8 × 109 mmol/L; >8.8 × 109 mmol/L). Using Aahlen Johansen and Cox proportional hazard models with competing risk, we analyzed the association between WBC levels and new vascular events. Kaplan-Meier and standard Cox proportional hazard models were used to assess the risk of all-cause mortality. Results: Among 395 patients (median age 69, [IQR: 63, 78], female patients 38,0%), 38.5% had elevated WBC at admission. During the 10-year follow-up, 113 vascular events occurred, with 46% in patients with elevated WBC and 54% in patients with normal WBC. After adjusting for relevant factors, elevated WBC levels were independently associated with increased risk of new vascular events (HR: 1.61, CI: 1.09-2.39 p < 0.05) and death (HR: 1.55, CI: 1.15-2.09, p < 0.05). Conclusion: Elevated WBC levels in ischemic stroke patients are linked to a higher risk of new vascular events and mortality. Thus, ischemic stroke patients with elevated WBC without clinical infection need special attention to investigate possible underlying conditions to prevent future vascular events and reduce mortality. The interpretation of our results is limited by the absence of adjustment to premorbid functional status, stroke severity, and stroke treatment.

JAK2V617F mutation is highly prevalent in patients with ischemic stroke: a case-control study.

Ischemic stroke has a high recurrence rate despite treatment. This underlines the significance of investigating new possible cerebrovascular risk factors, such as the acquired gene mutation JAK2V617F found in 3.1% of the general population. We aimed to investigate the prevalence of the JAK2V617F mutation in a population with ischemic stroke compared with that in matched controls. We enrolled 538 consecutive Danish patients with ischemic stroke (mean age, 69.5 ± 10.9 years; 39.2% female) within 7 days of symptom onset. Using multiple-adjusted conditional logistic regression analysis, we compared the prevalence of JAK2V617F with that in age- and sex-matched controls free of ischemic cerebrovascular disease (ICVD) from the Danish General Suburban Population Study. DNA was analyzed for JAK2V617F mutation using sensitive droplet digital polymerase chain reaction in patients and controls. Of the 538 patients with ischemic stroke, 61 (11.3%) had JAK2V617F mutation. There were no differences in patient demographics or cerebrovascular comorbidities between the patients with and without mutations. Patients with ischemic stroke were more likely to have the JAK2V617F mutation than matched controls, in whom the JAK2V617F prevalence was 4.4% (odds ratio, 2.37; 95% confidence interval, 1.57-3.58; P < .001). A subanalysis stratified by smoking history revealed that the association was strongest in current smokers (odds ratio, 4.78; 95% confidence interval, 2.22-10.28; P < .001). Patients with ischemic stroke were 2.4 times more likely to have the JAK2V617F mutation than matched controls without ICVD when adjusting for other cerebrovascular risk factors. This finding supports JAK2V617F mutation as a novel cerebrovascular risk factor.

Quality in stroke care during the early phases of the COVID-19 pandemic: A nationwide study.

Introduction: Evidence-based early stroke care as reflected by fulfillment of process performance measures, is strongly related to better patient outcomes after stroke and transient ischemic attack (TIA). Detailed data on the resilience of stroke care services during the COVID-19 pandemic are limited. We aimed to examine the quality of early stroke care at Danish hospitals during the early phases of the COVID-19 pandemic. Materials and methods: We extracted data from Danish national health registries in five time periods (11 March, 2020-27 January, 2021) and compared these to a baseline pre-pandemic period (13 March, 2019-10 March, 2020). Quality of early stroke care was assessed as fulfilment of individual process performance measures and as a composite measure (opportunity-based score). Results: A total of 23,054 patients were admitted with stroke and 8153 with a TIA diagnosis in the entire period. On a national level, the opportunity-based score (95% confidence interval [CI]) at baseline for ischemic patients was 81.1% (80.8-81.4), for intracerebral hemorrhage (ICH) 85.5% (84.3-86.6), and for TIA 96.0% (95.3-96.1). An increase of 1.1% (0.1-2.2) and 1.5% (0.3-2.7) in the opportunity-based score was observed during the first national lockdown period for AIS and TIA followed by a decline of -1.3% (-2.2 to -0.4) in the gradual reopening phase for AIS indicators. We found a significant negative association between regional incidence rates and quality-of-care in ischemic stroke patients implying that quality decreases when admission rates increase. Conclusion: The quality of acute stroke/TIA care in Denmark remained high during the early phases of the pandemic and only minor fluctuations occurred.

Development of a tailored intervention targeting sedentary behavior and physical activity in people with stroke and diabetes: A qualitative study using a co-creation framework.

Purpose: Type 2 diabetes and sedentary behavior pose serious health risks in stroke survivors. Using a co-creation framework, this study aimed to develop an intervention in collaboration with stroke survivors with type 2 diabetes, relatives, and cross-sectoral health care professionals to reduce sedentary behavior and increase physical activity. Materials and methods: This qualitative explorative study used a co-creation framework consisting of a workshop and focus group interviews with stroke survivors with type 2 diabetes (n = 3), relative (n = 1), and health care professionals (n = 10) to develop the intervention. A content analysis was used to analyze data. Results: The developed "Everyday Life is Rehabilitation" (ELiR) intervention consisted of a tailored 12-week home-based behavior change intervention with two consultations of action planning, goal setting, motivational interviewing, and fatigue management including education on sedentary behavior, physical activity, and fatigue. The intervention has a minimalistic setup using a double-page paper "Everyday Life is Rehabilitation" (ELiR) instrument making it implementable and tangible. Conclusions: In this study, a theoretical framework was used to develop a tailored 12-week home-based behavior change intervention. Strategies to reduce sedentary behavior and increase physical activity through activities of daily living along with fatigue management in stroke survivors with type 2 diabetes were identified.

Inter-rater reliability and agreement of 6 Minute Walk Test and 10 Meter Walk Test at comfortable walk speed in patients with acute stroke.

PURPOSE: Remediation of gait problems is a key feature of neurological physiotherapy We aimed to investigate the inter-rater reliability and agreement of the Six Minute Walk Test (6MWT) and Ten Meter Walk Test (10MWT), at comfortable walking speed, in hospitalized acute ischemic stroke patients. METHOD: Forty acute first-time patients with brain stem or hemispheric ischemic stroke aged 67.4 ± 12.5 (SD), able to walk with or without an assistive device, were tested by one of three physiotherapists. Test-retest reliability was evaluated using a one-way random effects single measures model (1,1) absolute agreement-type Interclass Correlation Coefficient (ICC). Agreement was evaluated using the Standard Error of Measurement (SEM) and Smallest Detectable Change (SDC). RESULTS: Both tests demonstrated good reliability; ICC1,1 0.83 (CI 95% 0.70-0.90) (6MWT) and 0.76 (CI 95% 0.59-0.87) (10MWT). The 6MWT-SEM was 27.2 m (m) and the SDC was 75.4 m. The 10MWT-SEM was 0.36 meters per second (m/s) and the SDC was 1.0 m/s. CONCLUSION: Both tests demonstrated good inter-rater reliability, confirming their discriminative ability on a group of hospitalized first-time acute ischemic stroke patients. However, the measurement error was large for both tests, which is likely due to spontaneous neurological recovery and stress in the acute phase severely affecting the individual-level agreement estimate.

COVID-19 did not result in increased hospitalization for stroke and transient ischemic attack: A nationwide study.

BACKGROUND: The risk of thrombosis increases in infectious diseases, yet observational studies from single centers have shown a decrease in admission of acute ischemic stroke patients during the COVID-19 pandemic. To investigate unselected stroke admission rates we performed a nationwide study in Denmark. METHODS: We extracted information from Danish national health registries. The following mutually exclusive time periods were compared to the year before the lockdown: (1) first national lockdown, (2) gradual reopening, (3) few restrictions, (4) regional lockdown, and (5) second national lockdown. RESULTS: Generally, admission rates were unchanged during the pandemic. In the unadjusted data, we observed a small decrease in the admission rate for all strokes under the first lockdown (incidence rate ratio: 0.93, confidence interval [CI]: 0.87-0.99) and a slight increase during the periods with gradual reopening, few restrictions, and the regional lockdown driven by ischemic strokes. We found no change in the rate of severe strokes, mild strokes, or 30-day mortality. An exception was the higher mortality for all strokes during the first lockdown (risk ratio: crude 1.30 [CI: 1.03-1.59]; adjusted 1.17 [CI: 0.93-1.47]). The quality of care remained unchanged. CONCLUSION: Stroke admission rates remained largely unchanged during the pandemic, while an increased short-term mortality rate in patients admitted with stroke observed during the first lockdown was seen, probably reflecting that the more frail patients constituted a higher proportion of admitted patients at the beginning of the pandemic.

Neuromuscular Electrical Stimulation Improves Activities of Daily Living Post Stroke: A Systematic Review and Meta-analysis.

Objectives: (1) To elucidate the effectiveness of neuromuscular electrical stimulation (NMES) toward improving activities of daily living (ADL) and functional motor ability post stroke and (2) to investigate the influence of paresis severity and the timing of treatment initiation for the effectiveness of NMES. Data Sources: PubMed, MEDLINE, Embase, Physiotherapy Evidence Database (PEDro) and Cochrane Library searched for relevant articles from database inception to May 2020. Study Selection: The inclusion criteria were randomized controlled trials exploring the effect of NMES toward improving ADL or functional motor ability in survivors of stroke. The search identified 6064 potential articles with 20 being included. Data Extraction: Two independent reviewers conducted the data extraction. Methodological quality was assessed using the PEDro scale and the Cochrane Risk of Bias Tool. Data Synthesis: Data from 428 and 659 participants (mean age, 62.4 years; 54% male) for outcomes of ADL and functional motor ability, respectively, were pooled in a random-effect meta-analysis. The analysis revealed a significant positive effect of NMES toward ADL (standardized mean difference [SMD], 0.41; 95% CI, 0.14-0.67; P=.003), whereas no effect on functional motor ability was evident. Subgroup analyses showed that application of NMES in the subacute stage (SMD, 0.44; 95% CI, 0.09-0.78; P=.01) and in the upper extremity (SMD, 0.34; 95% CI, 0.04-0.64; P=.02) improved ADL, whereas a beneficial effect was observed for functional motor abilities in patients with severe paresis (SMD, 0.41; 95% CI, 0.12-0.70; P=.005). Conclusions: The results of the present meta-analysis are indicative of potential beneficial effects of NMES toward improving ADL post stroke, whereas the potential for improving functional motor ability appears less clear. Furthermore, subgroup analyses indicated that NMES application in the subacute stage and targeted at the upper extremity is efficacious for ADL rehabilitation and that functional motor abilities can be positively affected in patients with severe paresis.

Stroke admissions and revascularization treatments in Denmark during COVID-19.

OBJECTIVE: The aim of this study was to assess the number of stroke-related admissions and acute treatments during the first two waves of COVID-19 and lockdowns in the Capital Region of Denmark and the Region of Zealand. MATERIALS & METHODS: The weekly numbers of admitted patients with stroke were retrieved from electronic patient records from January 2019 to February 2021 and analysed to reveal potential fluctuations in patient volumes during the pandemic. RESULTS: A total of 23,688 patients were included, of whom 2049 patients were treated with tissue-type plasminogen activators (tPA) and 552 underwent endovascular thrombectomy (EVT). We found a transient decrease in the number of weekly admitted patients (pts/week) with all strokes (-9.8 pts/week, 95% CI: -19.4; -0.2, p = .046) and stroke mimics (-30.1 pts/week, 95% CI: -39.9; -20.3, p < .001) during the first lockdown compared to pre-COVID-19. The number of subarachnoid haemorrhage, intracerebral haemorrhage, and ischaemic stroke admissions showed insignificant declines. Analysing all COVID-19 periods collectively revealed increased volumes of ischaemic stroke (+6.2 pts/week, 95% CI: +1.6; +10.7, p = .009) compared to pre-COVID levels, while numbers of stroke mimics remained lower than pre-COVID. Weekly tPA and EVT treatments remained constant throughout the study period. CONCLUSIONS: Our results are comparable with other studies in finding reductions in stroke-related admissions early in the pandemic. This is the first study to report increased stroke volumes following the first wave of the pandemic. The mechanisms behind the observed drop and subsequent rise in strokes are unclear and warrant further investigation.

[Elevated blood cell counts and vascular disease with the myeloproliferative neoplasms as model diseases].

Recent studies have shown the Philadelphia-negative myeloproliferative neoplasms (MPN) to be massively underdiagnosed and often preceded by a long pre-diagnostic phase of several years, in which many patients suffer serious vascular events. In this review, we focus on the urgent need for earlier diagnosis and treatment of MPN. Such efforts are foreseen to decrease morbidity and mortality for the individual patients and potentially reduce costs for health and social care systems.

Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care.

BACKGROUND AND PURPOSE: The diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor. METHODS: Patients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline. RESULTS: 7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14-37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)). CONCLUSIONS: A relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care follow-up.

Clopidogrel responder status is uninfluenced by CYP2C19*2 in Danish patients with stroke.

BACKGROUND: Antiplatelet therapy is a cornerstone of secondary stroke prevention, but the responsiveness to antiplatelet medication varies among patients. Clopidogrel is a pro-drug that requires hepatic transformation to reach its active metabolite. Single nucleotide polymorphisms (SNPs) in key enzymes or the target adenosine diphosphate (ADP) receptor on the platelet surface are believed to be involved in clopidogrel-mediated platelet inhibition and decreased antiplatelet effect with high-on-treatment platelet reactivity (HTPR). OBJECTIVE: This study investigated whether specific SNPs in key hepatic enzymes (CYP2C19*2, *3, *17, CYP3A4*1G, and NR1I2) or the ADP receptor (PR2Y12) are associated with HTPR to clopidogrel. PATIENTS & METHODS: This observational study included patients with ischemic stroke (IS) and transient ischemic attacks (TIAs) receiving clopidogrel at a dose of 75 mg/day. Patients were genotyped for eight different SNPs in the genes encoding CYP2C19, CYP3A4, NR1I2, and the P2Y12 receptor. RESULTS: Of the 103 patients that were included, 30.7% carried the CYP2C19*2 allele and had higher platelet reaction unit (PRU) values than non-carriers, but no patients showed HTPR. Carriers of the *17 allele had higher platelet inhibition but showed no difference in PRU values compared with non-carriers. The remaining SNPs were neither associated with PRU nor with platelet inhibition. CONCLUSIONS: Patients with IS and TIAs treated with 75 mg clopidogrel/day do not have HTPR. A genetic analysis of CYP2C19*2, *3, *17, CYP3A4*1G, and NR1I2 revealed no associations with clopidogrel HTPR. CYP2C19*2 carriers and patients with HTPR in the acute phase after ischemic stroke or transient ischemic attacks exhibit higher PRU values, but not long-term treatment HTPR.

Myeloproliferative blood cancers as a human neuroinflammation model for development of Alzheimer's disease: evidences and perspectives.

Chronic inflammation and involvement of myeloid blood cells are associated with the development of Alzheimer's disease (AD). Chronic inflammation is a highly important driving force for the development and progression of the chronic myeloproliferative blood cancers (MPNs), which are characterized by repeated thrombotic episodes years before MPN-diagnosis, being elicited by elevated erythrocytes, leukocytes, and platelets. Mutations in blood cells, the JAK2V617F and TET2-mutations, contribute to the inflammatory and thrombogenic state. Herein, we discuss the MPNs as a human neuroinflammation model for AD development, taking into account the many shared cellular mechanisms for reduction in cerebral blood, including capillary stalling with plugging of blood cells in the cerebral microcirculation. The therapeutic consequences of an association between MPNs and AD are immense, including reduction in elevated cell counts by interferon-alpha2 or hydroxyurea and targeting the chronic inflammatory state by JAK1-2 inhibitors, e.g., ruxolitinib, in the future treatment of AD.

Prehospital continuous ECG is valuable for very early detection of atrial fibrillation in patients with acute stroke.

INTRODUCTION: Early detection of atrial fibrillation (AF) after stroke is essential to achieve timely initiation of appropriate prophylactic treatment. We aimed to assess the diagnostic value of using prehospital continuous ECG (cECG) for AF detection after acute stroke. PATIENTS AND METHODS: In this retrospective cohort study, we included AF naïve ischemic stroke patients of 50 years or older. Medical records and corresponding digital prehospital cECGs were systematically reviewed. The proportion of AF detectable by prehospital cECG, in-hospital 12-lead ECG, telemetry and outpatient cECG was determined. McNemar's chi-squared test was used to compare probability of AF on prehospital cECG vs. in-hospital 12-lead ECG. RESULTS: In 500 included patients, a new onset AF was detectable by prehospital cECG in 27 patients (5.4% [95% CI 3.6-7.8]). In-hospital 12-lead ECG detected AF in 28 of 458 patients (6.1% [95% CI 4.1-8.7). Sixty-two (12.4% [95% CI 9.6-15.6]) were diagnosed with new onset AF by either prehospital cECG, in-hospital 12-lead ECG, in-hospital telemetry or outpatient cECG. Thus, 43.5% of all AF cases were detectable during prehospital transport. The probability of AF did not differ between prehospital cECG and in-hospital 12-lead ECG. Nevertheless, a lack in overlapping diagnoses meant number needed to screening with prehospital cECG was 16 for diagnosing one AF case not detected by in-hospital 12-lead ECG. CONCLUSION: Using prehospital cECG as an addition to very early AF evaluation after acute stroke had diagnostic value and could represent a low cost and easily accessible opportunity for very early AF detection. This may improve post-stroke care and save resources for further unnecessary AF screening. Conducting routine prehospital cECG after acute stroke and ensuring this is available to clinicians is encouraged.

Computed Tomography Perfusion Showing Cerebral Hypoperfusion in a Patient with Acute Cerebral Venous Sinus Thrombosis-A Case Report.

Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke. We report the case of a patient with acute CVST, showing perfusion abnormalities on computed tomography perfusion with perfusion defect in the relevant hemisphere. The defect was found in a region adjacent to the occluded sinus and was not corresponding to an arterial territory. To the best of our knowledge this is the first ever report on CT perfusion abnormalities few hours after acute symptom onset in CVST.

Electrical Stimulation in Lower Limb During Exercise to Improve Gait Speed and Functional Motor Ability 6 Months Poststroke. A Review with Meta-Analysis.

INTRODUCTION: Stroke is the third most common cause of disability in adults over 65 years of age and there are 30.7 million survivors after stroke worldwide. Stroke survivors have the highest odds of reporting severe disability and the greatest variety of individual domains of disability compared to a range of other conditions. Electrical stimulation of peripheral sensory-motor systems increases voluntary movement and muscle strength and thereby raises the activities of daily living (ADL). Little is known about electrical stimulation during physical activity in rehabilitation; the objective of this review is therefore to investigate whether external electrical stimulation combined with activity improves functional motor ability and gait speed in patients who have experienced a stroke within the last 6 months. METHODS: A review and random effects meta-analysis of randomized controlled clinical trials on gait speed and functional motor ability measured with Barthel Index (BI) and Bergs Balance Scale (BBS). RESULTS: Eight trials were included (n = 191). Explorative meta-analysis was performed on gait speed (5 trials, n = 120), BI (3 trials, n = 74), and BBS (3 trial n = 79). A small, significant difference on gait speed 0.15 (95% confidence interval [CI]: 0.08-0.21) m/s, but no difference in BI 2.88 (95 % CI: -3.3 to 9.07) and BBS 1.73 (95% CI: -2.8 to 6.27). CONCLUSIONS: Sparse, low-quality evidence indicates that electrical stimulation combined with activity is a relevant intervention to improve ADL within 6 months poststroke.

Treatment of medication overuse headache-A review.

Medication overuse headache (MOH) is the most prevalent chronic headache disorder with a prevalence between 1% and 2% worldwide. The disease has been acknowledged for almost 30 years, yet experts still disagree on how best to treat MOH. By performing a search in PubMed on the terms "medication overuse headache," "analgesics abuse headache," "rebound headache," "drug induced headache," and "headache AND drug misuse" limited to human studies published in English between January 1, 2004, and November 1, 2017, we aimed to evaluate current literature concerning predictors of treatment outcome, inpatient and outpatient treatment programs, initial versus latent administration of prophylactic medications, and to review the effect of prophylactic medications. Selection criteria were prospective, comparative, or controlled trials on treatment of MOH in persons of at least 18 years of age. Several studies evaluated risk factors to predict the outcome of MOH treatment, but many studies were underpowered. Psychiatric comorbidity, high dependence score, and overuse of barbiturates, benzodiazepines, and opioids predicted a poorer outcome of withdrawal therapy. Patients with these risk factors benefit from inpatient treatment, whereas patients without risk factors benefit equally from inpatient and outpatient treatment. Some medications for migraine prophylactics have shown better effect on MOH compared with placebo, but not when combined with withdrawal. We conclude that detoxification programs are of great importance in MOH treatment. Latent administration of prophylactic medications reduces the number of patients needing prophylactic medication. Individualizing treatment according to the predictors of outcome may improve treatment outcome and thus reduce work-related and treatment-related costs.

High On-Treatment Platelet Reactivity in Danish Hyper-Acute Ischaemic Stroke Patients.

Objective: Early anti-platelet therapy is a cornerstone in the prevention of recurrent ischaemic stroke (IS) and transient ischaemic attacks (TIAs), although the responsiveness to anti-platelet medications varies among patients. Several studies have reported that patients with ischaemic stroke who exhibit high on-treatment platelet reactivity (HTPR) 5-10 days after antiplatelet medication onset, have an increased risk of vascular events. In this study we aim to determine the prevalence of HTPR in the hyper-acute stroke phase less than 48 h from symptom onset, after the administration of a 300 mg bolus of oral clopidogrel in a real-world setting in Danish IS and TIA patients. Material and Methods: In total, 219 Danish patients with acute IS or TIA received 300 mg of oral clopidogrel on admission. Blood samples from all patients were analyzed using the VerifyNow P2Y12 system at 8-24 h after clopidogrel intake. Concomitant therapy and the intervals between ictus and blood collection, clopidogrel intake and blood collection, and blood sampling and analysis were recorded for all patients. Results: HTPR in the hyper-acute stroke phase was observed in 28.8% (63/219) samples. After adjustment for age, sex, co-morbidities, and co-medications, none of the tested variables exhibited an association with HTPR or the platelet reaction unit value measured using the VerifyNow P2Y12 system. Conclusions: The recognition of HTPR to specific anti-platelet agents in the hyper-acute phase after stroke may be the first step toward interventions that may further minimize the early recurrent stroke risk. Further large randomized trials including clinical outcome assessments are necessary.