In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for ...thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke.
Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored.
In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% 95% confidence interval 1%-69%). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients.
NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.
Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive ...telemedical stroke network comprising all levels of stroke care in a defined region.
The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals.
Overall, 7881 patients were included (mean age 74.6 years ±12.8; 48.4% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31%), mainly in secondary stroke prevention; b) improvement over time (44%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period.
The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.
Long-term support of stroke patients living at home is often delivered by family caregivers (FC). We identified characteristics of stroke patients being associated with receiving care by a FC ...3-months (3 M) after stroke, assessed positive and negative experiences and individual burden of FC caring for stroke patients and determined factors associated with caregiving experiences and burden of FC 3 M after stroke.
Data were collected within TRANSIT-Stroke, a regional telemedical stroke-network comprising 12 hospitals in Germany. Patients with stroke/TIA providing informed consent were followed up 3 M after the index event. The postal patient-questionnaire was accompanied by an anonymous questionnaire for FC comprising information on positive and negative experiences of FC as well as on burden of caregiving operationalized by the Caregiver Reaction Assessment and a self-rated burden-scale, respectively. Multivariable logistic and linear regression analyses were performed.
Between 01/2016 and 06/2019, 3532 patients provided baseline and 3 M-follow-up- data and 1044 FC responded to questionnaires regarding positive and negative caregiving experiences and caregiving burden. 74.4% of FC were older than 55 years, 70.1% were women and 67.5% were spouses. Older age, diabetes and lower Barthel-Index in patients were significantly associated with a higher probability of receiving care by a FC at 3 M. Positive experiences of FC comprised the importance (81.5%) and the privilege (70.0%) of caring for their relative; negative experiences of FC included financial difficulties associated with caregiving (20.4%). Median overall self-rated burden was 30 (IQR: 0-50; range 0-100). Older age of stroke patients was associated with a lower caregiver burden, whereas younger age of FC led to higher burden. More than half of the stroke patients in whom a FC questionnaire was completed did self-report that they are not being cared by a FC. This stroke patient group tended to be younger, more often male with less severe stroke and less comorbidities who lived more often with a partner.
The majority of caregivers wanted to care for their relatives but experienced burden at the same time. Elderly patients, patients with a lower Barthel Index at discharge and diabetes are at higher risk of needing care by a family caregiver.
The study was registered at "German Clinical Trial Register": DRKS00011696. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011696.
Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke ...dysphagia that has shown promise in 3 pilot randomized controlled trials.
We randomly assigned 162 patients with a recent ischemic or hemorrhagic stroke and dysphagia, defined as a penetration aspiration score (PAS) of ≥3 on video fluoroscopy, to PES or sham treatment given on 3 consecutive days. The primary outcome was swallowing safety, assessed using the PAS, at 2 weeks. Secondary outcomes included dysphagia severity, function, quality of life, and serious adverse events at 6 and 12 weeks.
In randomized patients, the mean age was 74 years, male 58%, ischemic stroke 89%, and PAS 4.8. The mean treatment current was 14.8 (7.9) mA and duration 9.9 (1.2) minutes per session. On the basis of previous data, 45 patients (58.4%) randomized to PES seemed to receive suboptimal stimulation. The PAS at 2 weeks, adjusted for baseline, did not differ between the randomized groups: PES 3.7 (2.0) versus sham 3.6 (1.9), P=0.60. Similarly, the secondary outcomes did not differ, including clinical swallowing and functional outcome. No serious adverse device-related events occurred.
In patients with subacute stroke and dysphagia, PES was safe but did not improve dysphagia. Undertreatment of patients receiving PES may have contributed to the neutral result.
URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25681641.
S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in ...a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke.
RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale NIHSS score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615.
Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 95% CI 0·64–1·31; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 95% CI 0·81–1·67; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 IQR 2–8 in 150 mg S44819 group, 4 2–7 in 300 mg S44819 group, and 4 2–6 in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 61% of 156 in 150 mg S44819 group, 106 66% of 161 in 300 mg S44819 group, and 104 66% of 157 in placebo group) versus more than 5 (61 39% in 150 mg S44819 group, 55 34% in 300 mg S44819 group, and 53 34% in placebo group). Likewise, the median MoCA score (22·0 IQR 17·0–26·0 in 150 mg S44819 group, 23·0 19·0–26·5 in 300 mg S44819 group, and 22·0 17·0–26·0 in placebo group), time needed to complete parts A (50 s IQR 42–68 in 150 mg S44819 group, 49 s 36–63 in 300 mg S44819 group, and 50 s 38–68 in placebo group) and B (107 s 81–144 in 150 mg S44819 group, 121 s 76–159 in 300 mg S44819 group, and 130 s 86–175 in placebo group) of the Trail Making Test, and the Barthel index (90 IQR 60–100 in 150 mg S44819 group, 90 70–100 in 300 mg S44819 group, and 90 70–100 in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths.
There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans.
Servier.
Background and purpose
Improving understanding of study contents and procedures might enhance recruitment into studies and retention during follow‐up. However, data in stroke patients on ...understanding of the informed consent (IC) procedure are sparse.
Methods
We conducted a cross‐sectional study among ischemic stroke patients taking part in the IC procedure of an ongoing cluster‐randomized secondary prevention trial. All aspects of the IC procedure were assessed in an interview using a standardized 20‐item questionnaire. Responses were collected within 72 h after the IC procedure and analyzed quantitatively and qualitatively. Participants were also asked their main reasons for participation.
Results
A total of 146 stroke patients (65 ± 12 years old, 38% female) were enrolled. On average, patients recalled 66.4% (95% confidence interval = 65.2%–67.5%) of the content of the IC procedure. Most patients understood that participation was voluntary (99.3%) and that they had the right to withdraw consent (97.1%); 79.1% of the patients recalled the study duration and 56.1% the goal. Only 40.3% could clearly state a benefit of participation, and 28.8% knew their group allocation. Younger age, higher graduation, and allocation to the intervention group were associated with better understanding. Of all patients, 53% exclusively stated a personal and 22% an altruistic reason for participation.
Conclusions
Whereas understanding of patient rights was high, many patients were unable to recall other important aspects of study content and procedures. Increased attention to older and less educated patients may help to enhance understanding in this patient population. Actual recruitment and retention benefit of an improved IC procedure remains to be tested in a randomized trial.
We conducted a cross‐sectional study among ischemic stroke patients taking part in the inforrmed consent (IC) procedure of an ongoing cluster‐randomized secondary prevention trial. On average, patients recalled 66.4% (95% CI 65.2%‐67.5%) of the content of the IC procedure. Multivariable modelling showed a significant association of age, education, and group allocation with understanding.
S44819, a selective GABA
α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in ...a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABA
α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke.
RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18-85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale NIHSS score 7-20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0-1 versus 2-6 and 0-2 versus 3-6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615.
Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 95% CI 0·64-1·31; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 95% CI 0·81-1·67; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0-2 vs 3-6 or mRS 0-1 vs 2-6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 IQR 2-8 in 150 mg S44819 group, 4 2-7 in 300 mg S44819 group, and 4 2-6 in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 61% of 156 in 150 mg S44819 group, 106 66% of 161 in 300 mg S44819 group, and 104 66% of 157 in placebo group) versus more than 5 (61 39% in 150 mg S44819 group, 55 34% in 300 mg S44819 group, and 53 34% in placebo group). Likewise, the median MoCA score (22·0 IQR 17·0-26·0 in 150 mg S44819 group, 23·0 19·0-26·5 in 300 mg S44819 group, and 22·0 17·0-26·0 in placebo group), time needed to complete parts A (50 s IQR 42-68 in 150 mg S44819 group, 49 s 36-63 in 300 mg S44819 group, and 50 s 38-68 in placebo group) and B (107 s 81-144 in 150 mg S44819 group, 121 s 76-159 in 300 mg S44819 group, and 130 s 86-175 in placebo group) of the Trail Making Test, and the Barthel index (90 IQR 60-100 in 150 mg S44819 group, 90 70-100 in 300 mg S44819 group, and 90 70-100 in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths.
There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans.
Servier.
Zusammenfassung
Ziel des digitalen Notfallmanagements ist, dass alle Akteure der Rettungskette sich bei einem Notfalleinsatz elektronisch miteinander austauschen und auf alle Informationen, die für ...die optimale Versorgung der Patientin relevant sind, zugreifen und miteinander kommunizieren können. Für den Einsatz der Digitalisierung im Notfallmanagement existieren mittlerweile zahlreiche Konzepte mit vielversprechenden Studienergebnissen und Implementierungserfahrungen, die in einer (über)regionalen Behandlungsstrategie mit einem kontinuierlichen Verbesserungsprozess mit Nachdruck zu verstetigen sind. Unter Berücksichtigung aktueller Möglichkeiten der Digitalisierung der Rettungskette hat der Expertenrat des Zentrums für Telemedizin Bad Kissingen (ZTM) wesentliche Inhalte und Kernfunktionen des digitalen Notfallmanagements definiert.
Abstract
The objective of digital emergency management is to enable all involved parties to electronically share, access, and communicate pertinent information for optimal patient care during an emergency intervention. Considering the current digitalization potential in acute and emergency medicine, the expert council of the Zentrum für Telemedizin Bad Kissingen (ZTM) has delineated the core elements and functions of digital emergency management. Presently, numerous digitalization concepts in emergency management have shown promising study outcomes and insights regarding implementation. These should be robustly integrated into a (supra-)regional care strategy with a continuous improvement process.
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