Dynamics of Water Diffusion Changes in Different Tissue Compartments From Acute to Chronic Stroke—A Serial Diffusion Tensor Imaging Study

Background and Purpose: The immediate decrease of the apparent diffusion coefficient (ADC) is the main characteristic change of water diffusion in acute ischemic stroke. There is only limited information on the time course of diffusion parameters in different tissue compartments of cerebral ischemia.Materials and Methods: In a longitudinal study, we examined 21 patients with acute ischemic stroke by diffusion tensor imaging within 5 h after symptom onset, 3 h later, 2 days, and 1 month after symptom onset. Acute diffusion lesion and the fluid-attenuated inversion recovery (FLAIR) after 2 days were used as volumes of interest to define persistent core, lesion growth, and reversible acute diffusion lesion. For all diffusion parameters ratios between the stroke lesion VOIs and the mirror VOIs were calculated for each time point. ADC ratio, fractional anisotropy ratios, and eigenvalues ratios were measured in these volumes of interest and in contralateral mirror regions at each time points.Results: In the persistent core, ADC ratio (0.772) and all eigenvalues ratios were reduced on admission up to 1 day after stroke and increased after 1 month (ADC ratio 1.067). Within the region of infarct growth time course of diffusion parameter changes was similar, but delayed. In the brain area with reversible diffusion lesion, a partial normalization of diffusion parameters over the time was observed, while after 1 month diffusion parameters did not show the signature of healthy brain tissue. There were significantly different trends for all parameters over time between the three tissue compartments.Conclusion: Diffusion tensor imaging displays characteristic changes of water diffusion in different tissue compartments over time in acute ischemic stroke. Even regions with reversible diffusion lesion show diffusion signatures of persisting tissue alterations

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

Quality of Stroke Patient Information Applied in Randomized Controlled Trials-Literature Review

Background: Strokes have a huge impact on patients' quality of life. Although there are potentially effective secondary preventions and treatment options for stroke patients, adherence is mostly low. Low disease and treatment-related knowledge and, consequently, a lack of informed decision-making in stroke patients may contribute to this problem. However, stroke patient information did not seem to have relevant effects on patients' knowledge in randomized controlled trials. One contributing factor may be the lack of thoroughly developed patient information materials. Methods: We aimed to evaluate the quality of patient information materials for stroke patients by using randomized controlled trials, applying quality criteria for evidence-based patient information (EBPI). We conducted a literature search (MEDLINE, Embase, CINAHL, PsycINFO, and CENTRAL). To be included in the review, research had to be randomized controlled trials that provided stroke patient information, were published in English, and had knowledge assessed as the primary endpoint. Authors of primary studies were contacted and asked for information materials applied. Results: We screened 15,507 hits and identified 30 eligible studies. Information materials were available for only eight studies. Analyses revealed that all available materials had important shortcomings concerning EBPI quality criteria [concerning, for example, structural information (e.g., reporting conflicts of interest), content information (e.g., reporting sources of information), or comprehensive descriptions of treatment effects and side effects]. Frequently, treatment effects were reported only narratively without providing absolute numbers, values, or frequencies. Conclusion: Quality of materials differed, but none sufficiently fulfilled EBPI quality criteria. Unsatisfactory trial results concerning patient knowledge and patient involvement in decision-making may at least partially be explained by limitations of the provided materials. Future patient information should consider EBPI quality criteria

Subjective and objective knowledge and decisional role preferences in cerebrovascular patients compared to controls

Background: Risk knowledge and active role preferences are important for patient involvement in treatment decision-making and adherence. Although knowledge about stroke warning signs and risk factors has received considerable attention, objective knowledge on secondary prevention and further self-esteem subjective knowledge have rarely been studied. The aim of our study was to investigate knowledge and treatment decisional role preferences in cerebrovascular patients compared to controls. Methods: We performed a survey on subjective and objective stroke risk knowledge and autonomy preferences in cerebrovascular patients from our stroke outpatient clinic (n=262) and from pedestrians on the street taken as controls during a “World Stroke Day” (n=274). The questionnaire includes measures for knowledge and decisional role preferences from previously published questionnaires and newly developed measures, for example, subjective knowledge, revealed on a visual analog scale. Results: The overall stroke knowledge was low to moderate, with no differences between patients and controls. Knowledge about secondary prevention was particularly low. Only 10%–15% of participants correctly estimated the stroke absolute risk reduction potential of aspirin. The medical data interpretation competence was moderate in both groups. Age and basic mathematical and statistical understanding (numeracy) were the only independent predictors of objective stroke knowledge, whereas previous stroke had no impact on stroke knowledge. However, patients were thought to be better informed than controls. Approximately 60% of both patients and controls claimed to prefer a shared decision-making approach in treatment decisions. Conclusion: The level of stroke risk knowledge in patients with cerebrovascular diseases was as low as in randomly selected pedestrians, although patients felt better informed. Both groups preferred involvement in treatment decision-making. We conclude that educational concepts for increasing awareness of knowledge gaps as well as for stroke risk and for prevention strategies are needed

Postmarketing observational study on the safety of 2021/2022 and 2022/2023 influenza vaccination campaigns in Italy: TheShinISS-Vax|Flu study protocol

Introduction The purpose of TheShinISS-Vax|Flu study is to examine the association between influenza vaccines and adverse events requiring hospital admission or emergency care during the influenza vaccination campaigns 2021/2022 and 2022/2023 in Italy.Methods and analysis This is a Self-Controlled Case Series multiregional study using linked routinely collected data from regional healthcare databases of the participating regions. Study participants will be persons aged ≥6 months, unvaccinated or who have received influenza vaccine during the influenza vaccination campaigns in the seasons 2021/2022 and 2022/2023 in Italy and who have experienced the outcome of interest for the first time during the study period (1 September 2021–30 June 2022 and 1 September 2022–30 June 2023 for the first and second vaccination campaigns, respectively). Risk periods will be specifically defined for each outcome and further subdivided into periods of 7 days. The exposures will be the first or second dose of the influenza vaccines administered during the two vaccination campaigns. Statistical analysis will be conducted separately for the data of the two campaigns. Exposure risk period will be compared with baseline risk period defined as any time of observation out of the risk periods. The modified SCCS method will be applied to handle event-dependent exposure and mortality and fitted using unbiased estimating equations to estimate relative incidences and excess of cases per 100 000 vaccinated by dose, age, sex and type of vaccine. Calendar period will be included as time-varying confounder in the model, where appropriate.Ethics and dissemination The study received the approval from the National ethics committee for clinical trials of public research bodies and other national public institutions (PRE BIO CE n.0036723, 23/09/2022). Results will be published in peer-reviewed journals and reports in accordance with the publication policies of the Italian National Institute of Health and of the Italian Medicines Agency

Comprehension of confidence intervals in audio-visual patient information materials for people with multiple sclerosis (COCO-MS): A web-based randomised controlled, parallel group trial

Objectives: To evaluate patient information materials on confidence intervals (CIs) in multiple sclerosis to be used with patient decision aids. Methods: Web-based randomised controlled parallel group trial with four study arms. Participants were equally allocated to one of three versions of audio-visual patient information or to a standard written information (arm IV). In the short version (arm III), CIs were explained without using an example, in the other two versions examples were used (arm I and arm II). The examples are based on an apple farmer who wants to estimate the average weight of his apples (arm I) and to test a treatment against worms (arm II). Primary endpoint was comprehension of CIs, assessed with a six-item multiple-choice questionnaire. Results: 855 of 1068 (80 %) randomised participants completed the survey (71 % arm I, 73 % arm II, 87 % arm III, 90 % arm IV). The median of correctly answered questions on CIs was 4 out of 6 questions in arms I and II and 5 out of 6 questions in arm III. Compared to the standard information (arm IV), all the other arms scored better on the comprehension questionnaire (ANOVA, p <= 0.003). Conclusions: Information about CIs can be presented comprehensibly. High scores and a high rate of completers indicate that the short version is the favourable one. Practice implications: Information materials on CIs should be used alongside absolute risk reductions in patient decision aids to enhance the interpretation of study results. (C) 2020 Elsevier B.V. All rights reserved

Machine Learning-Based Identification of Target Groups for Thrombectomy in Acute Stroke

Whether endovascular thrombectomy (EVT) improves functional outcome in patients with large-vessel occlusion (LVO) stroke that do not comply with inclusion criteria of randomized controlled trials (RCTs) but that are considered for EVT in clinical practice is uncertain. We aimed to systematically identify patients with LVO stroke underrepresented in RCTs who might benefit from EVT. Following the premises that (i) patients without reperfusion after EVT represent a non-treated control group and (ii) the level of reperfusion affects outcome in patients with benefit from EVT but not in patients without treatment benefit, we systematically assessed the importance of reperfusion level on functional outcome prediction using machine learning in patients with LVO stroke treated with EVT in clinical practice (N=5235, German-Stroke-Registry) and in patients treated with EVT or best medical management from RCTs (N=1488, Virtual-International-Stroke-Trials-Archive). The importance of reperfusion level on outcome prediction in an RCT-like real-world cohort equaled the importance of EVT treatment allocation for outcome prediction in RCT data and was higher compared to an unselected real-world population. The importance of reperfusion level was magnified in patient groups underrepresented in RCTs, including patients with lower NIHSS scores (0-10), M2 occlusions, and lower ASPECTS (0-5 and 6-8). Reperfusion level was equally important in patients with vertebrobasilar as with anterior LVO stroke. The importance of reperfusion level for outcome prediction identifies patient target groups who likely benefit from EVT, including vertebrobasilar stroke patients and among patients underrepresented in RCT patients with low NIHSS scores, low ASPECTS, and M2 occlusions