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Contains fulltext : 287508.pdf (Publisher’s version ) (Closed access) BACKGROUND: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. METHODS: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. FINDINGS: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17]). INTERPRETATION: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

IntroductionDuring a standard 70-degree head-up tilt test, 90% of adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develop an abnormal reduction in cerebral blood flow (CBF). A 70-degree test might not be tolerated by young ME/CFS patients because of the high incidence of syncopal spells. This study examined whether a test at 20 degrees would be sufficient to provoke important reductions in CBF in young ME/CFS patients.MethodsWe analyzed 83 studies of adolescent ME/CFS patients. We assessed CBF using extracranial Doppler measurements of the internal carotid and vertebral arteries supine and during the tilt. We studied 42 adolescents during a 20 degree and 41 during a 70 degree test.ResultsAt 20 degrees, no patients developed postural orthostatic tachycardia (POTS), compared to 32% at 70 degrees (p = 0.0002). The CBF reduction during the 20 degree tilt of −27(6)% was slightly less than during the reduction during a 70 degree test [−31(7)%; p = 0.003]. Seventeen adolescents had CBF measurements at both 20 and 70 degrees. The CBF reduction in these patients with both a 20 and 70 degrees test was significantly larger at 70 degrees than at 20 degrees (p ConclusionsA 20 degree tilt in young ME/CFS patients resulted in a CBF reduction comparable to that in adult patients during a 70 degree test. The lower tilt angle provoked less POTS, emphasizing the importance of using the 70 degree angle for that diagnosis. Further study is needed to explore whether CBF measurements during tilt provide an improved standard for classifying orthostatic intolerance.

Background Although cutting-edge chemistry research can be an interesting and motivating context for students in pre-university education, few characteristics of supportive and effective learning materials based on such contexts are available. Purpose In this study we investigated the design, implementation, and evaluation of context-based learning materials for both teachers and students. Specifically, we studied the characteristics of learning materials situated in the context of cutting-edge chemistry research that are supportive (have educative and usable features) for teachers and effective (have features that foster understanding and motivation) for students. Sample The designed learning materials were piloted by three teachers in four tenth-grade pre-university chemistry classes at three schools in The Netherlands. Design and methods The learning materials are shaped by the 5E instructional model and are situated in the context of research on early cancer diagnosis. In this exploratory, small-scale, mixed-methods study, data on teacher and student use of these learning materials were collected through teacher and student group interviews, student pre- and post-tests, and learner self-reports. Results This study shows that the piloted learning materials have features that are simultaneously supportive for teachers and effective for students. We identified several features that made the materials educative and usable for teachers, and that fostered student understanding and motivation. Conclusion We conclude that the cutting-edge research context used to situate the learning materials was valuable, and that the teachers in the study were eager to implement these types of materials in their regular practice. In addition, the materials contributed to student motivation and student understanding, and supported teacher learning. This study also describes crucial features that teachers and students valued in the design of the learning materials, which can help in designing other learning materials based on cutting-edge research.

Dilated cardiomyopathy (DCM) is a frequent cause of cardiac disability, congestive heart failure (CHF), and arrhythmic death in dogs. The etiology of DCM is usually idiopathic/genetic, but some causes of a DCM phenotype are reversible. The disease is classified into preclinical (occult) and clinical (overt) stages; the latter stems from heart failure with reduced ejection fraction. DCM is further characterized by clinical, electrocardiographic, circulating biomarker, and imaging abnormalities. The diagnosis of clinical DCM with CHF is straightforward; however, identification of the preclinical stage can be challenging. Echocardiography is central to the diagnosis of both stages and characterized by left ventricular (LV) systolic dysfunction with progressive chamber dilation and variable enlargements of the left atrium and right-sided chambers. Left ventricular dilation is defined by increased LV end-diastolic volumes, areas, and internal dimensions normalized to body size or indexed to the aorta. Systolic dysfunction is characterized by decreased LV ejection fraction, increased end-systolic volume, and reduced shortening across minor and longitudinal LV axes. Dyssynchrony can confound the interpretation of linear indices of systolic function. A comprehensive echocardiogram in DCM includes two-dimensional and M-mode studies, spectral and tissue Doppler imaging, and potentially three-dimensional echocardiography and myocardial strain imaging. Echocardiographic findings should be interpreted within the context of identifiable risks and comorbidities, physical diagnosis, complementary diagnostic testing, and limitations of current reference intervals. Ambiguous examinations should be repeated. Specific echocardiographic criteria for the diagnosis of DCM are proposed to encourage discussion and additional outcome and breed-specific echocardiographic studies of canine DCM.

BackgroundFactors associated with outcome in dogs diagnosed with infective endocarditis (IE) are not well characterized.ObjectivesEvaluate outcome and prognostic factors in dogs with IE.AnimalsOne hundred and thirteen dogs with IE.MethodsMedical records for dogs that fulfilled the modified Duke criteria between 2005 and 2020 were retrospectively reviewed. Signalment, preexisting conditions, clinicopathologic findings, treatment regimen, and outcomes were recorded. Univariate logistic regression was performed to identify categorical factors associated with mortality, and then multivariate analysis was performed.ResultsDogs were categorized as survivors (n=47), non-survivors (n=57), or lost to follow-up (n=9). Survival to discharge and at 1month was documented in 79 (70%) of 113 and 56 (54%) of 104 dogs, respectively, with median survival time (MST) of 72 days. Risk factors associated with mortality included development of congestive heart failure (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.4-97.8), thromboembolic events (OR, 5.7; 95% CI, 2.3-14.4), and acute kidney injury (OR, 6.2; 95% CI, 2.0-18.8). Administration of antithrombotic medications was associated with survival (OR, 0.35; 95% CI, 0.13-0.97). Dogs that were not treated with antithrombotics had MST of 92 days, whereas dogs treated with antithrombotics did not reach MST during the study period. The heart valves involved and etiologic agent identified did not correlate with outcome.Conclusion and clinical importanceDogs with IE that had thromboembolic events, acute kidney injury, or congestive heart failure had higher risk of mortality. Administration of antithrombotics was associated with prolonged survival time.

Background Enhanced Recovery After Surgery (ERAS) protocols have been successfully instituted for pancreaticoduodenectomy (PD). This study evaluates reasons patients fail to meet length of stay (LOS) and areas for pathway improvement. Materials and Methods A multidisciplinary team developed and implemented an ERAS protocol for open PD in 2017. The study includes a medical record review of all patients who were perioperatively managed with the ERAS protocol and failed to meet LOS after PD procedures. Target LOS was defined as 7 d. Results From 2017 to 2020, 44% (93 of 213) of patients using ERAS protocol after PD procedures failed to meet target LOS. The most common reason to fail target LOS was ileus or delayed gastric emptying (47 of 93, LOS 11). Additional reasons included work-up of leukocytosis or pancreatic leak (17 of 93, LOS 14), additional “night” of observation (14 of 93, LOS 8), and orthostatic hypotension (3 of 93, LOS 10). Of these additional 46 patients, 19 patients underwent computed tomography (on or after POD 7) and only four patients received additional inpatient intervention. Conclusions The most common reason for PD pathway failure included slow return of gastrointestinal function, a known complication after PD. The remaining patients were often kept for observation without additional intervention. This group represents an actionable cohort to target for improving LOS through surgeon awareness rather than protocol modification.

Supplemental Digital Content is available in the text., Background and Purpose: Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack. Methods: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were (1) cohort, cross-sectional, case-control, or randomized controlled trial design; (2) admission for (suspicion of) ischemic or hemorrhagic stroke or transient ischemic attack; and (3) comparisons possible between sexes in ≥1 nonfocal or focal acute stroke symptom(s). A random-effects model was used for our analyses. We performed sensitivity and subanalyses to help explain heterogeneity and used the Newcastle-Ottawa Scale to assess bias. Results: We included 60 studies (n=582 844; 50% women). In women, headache (pooled odds ratio [OR], 1.24 [95% CI, 1.11–1.39]; I2=75.2%; 30 studies) occurred more frequently than in men with any type of stroke, as well as changes in consciousness/mental status (OR, 1.38 [95% CI, 1.19–1.61]; I2=95.0%; 17 studies) and coma/stupor (OR, 1.39 [95% CI, 1.25–1.55]; I2=27.0%; 13 studies). Aspecific or other neurological symptoms (nonrotatory dizziness and non-neurological symptoms) occurred less frequently in women (OR, 0.96 [95% CI, 0.94–0.97]; I2=0.1%; 5 studies). Overall, the presence of focal symptoms was not associated with sex (pooled OR, 1.03) although dysarthria (OR, 1.14 [95% CI, 1.04–1.24]; I2=48.6%; 11 studies) and vertigo (OR, 1.23 [95% CI, 1.13–1.34]; I2=44.0%; 8 studies) occurred more frequently, whereas symptoms of paresis/hemiparesis (OR, 0.73 [95% CI, 0.54–0.97]; I2=72.6%; 7 studies) and focal visual disturbances (OR, 0.83 [95% CI, 0.70–0.99]; I2=62.8%; 16 studies) occurred less frequently in women compared with men with any type of stroke. Most studies contained possible sources of bias. Conclusions: There may be substantive differences in nonfocal and focal stroke symptoms between men and women presenting with acute stroke or transient ischemic attack, but sufficiently high-quality studies are lacking. More studies are needed to address this because sex differences in presentation may lead to misdiagnosis and undertreatment.

Introduction In the context of the development of pharmaceutical interventions, expectations and experiences of participants are essential. Their insights may be particularly helpful to address the challenges of recruiting and retaining participants for Alzheimer’s disease (AD) clinical trials. We examined clinical trial participants’ experiences to optimize trial design in Alzheimer’s disease (AD). Method In this mixed-methods study, we included adults who participated in sponsor-initiated AD trials at Brain Research Center, a clinical trial organization in the Netherlands. Participants (N = 71, age 69 ± 6.5, 54%F, 19 cognitively normal (CN), 19 mild cognitive impairment (MCI), and 33 AD dementia) first completed an online survey. Diagnostic group differences were investigated using chi-square tests or one-way ANOVAs. Next, a subsample (N = 12; 8 = CN, 4 = MCI) participated in focus groups to gain in-depth insight into their opinions on optimizing trial design from a participants’ point of view. Audio recordings from focus group interviews were transcribed verbatim and analyzed by thematic content analysis by two independent researchers. Results Most reported motives for enrolment included “to benefit future generations” (89%), followed by “for science” (66%) and “better monitoring” (42%). Frequent suggestions for increasing willingness to participate included a smaller chance to receive placebo (n = 38, 54%), shorter travel times (n = 27, 38%), and sharing individual results of different assessments (n = 57, 80%), as well as receiving trial results (n = 52, 73). Highest visual analogue burden scores (0–100) were found for the lumbar puncture (M = 47.2, SD = 38.2) and cognitive assessments (M = 27.2, SD = 25.7). Results did not differ between diagnostic groups, nor between patient and caregiver participants (all p-values>.05). Two additional themes emerged from the focus groups: “trial design,” such as follow-up visit(s) after participating, and “trial center,” including the relevance of a professional and empathic staff. Conclusion Relevant factors include expectation management and careful planning of high-burden assessments, provision of individual feedback, and prioritizing professionalism and empathy throughout conduct of the trial. Our findings provide insight into participants’ priorities to increase willingness to participate and can be used to optimize trial success.

Objectives: Adult spleens show extensive morphological variation, with a reported prevalence of 40–98% clefts (also called notches or fissures) on the splenic surface and 10–30% accessory spleens at autopsy. It is hypothesised that both anatomical variants result from a complete or partial failure of multiple splenic primordia to fuse to the main body. According to this hypothesis, fusion of the spleen primordia is completed after birth and spleen morphological variations are often explained as stagnation of spleen development at the foetal stage. We tested this hypothesis by studying early spleen development in embryos, and compared foetal and adult spleen morphology. Methods and materials: We assessed 22 embryonic, 17 foetal and 90 adult spleens on the presence of clefts using histology, micro-CT and conventional post-mortem CT-scans, respectively. Results: The spleen primordium was observed as a single mesenchymal condensation in all embryonic specimens. The number of clefts varied from 0 to 6 in foetuses, compared to 0–5 in adults. We found no correlation between foetal age and number of clefts (R2 = 0.004). The independent samples Kolmogorov–Smirnov test showed no significant difference in the total number of clefts between adult and foetal spleens (p = 0.068). Conclusion: We found no morphological evidence for a multifocal origin or a lobulated developmental stage of the human spleen. Advances in knowledge: Our findings show that splenic morphology is highly variable, independent of developmental stage and age. We suggest to abandon the term “persistent foetal lobulation” and to regard splenic clefts, regardless of their number or location, as normal variants.

Supplemental Digital Content is available in the text., Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (P=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Importance Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. Objective To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. Design, Setting, and Participants This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. Exposures Disclosure of amyloid-PET result. Main Outcomes and Measures Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale–Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). Results After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30]) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2]; P P P P P = .06) and Depression (–1.0 [–2.0 to 0.0] vs –1.0 [–3.0 to 0.0]; P = .46) deltas (score after disclosure – scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = –0.43; P = .02) whereas the presence of study partner was associated with higher disclosure-related distress (W = 7.5; P = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up. Conclusions and Relevance The disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern.

Chemical bonding is an important topic which is difficult to teach well, especially for novices. This study set out to support preservice teacher educators by developing a framework for understanding and addressing the complexity of teaching chemical bonding. A model of pedagogical content knowledge (PCK) in science education that has been widely endorsed by experts in the field was adopted as the theoretical lens. First, a systematic literature review was performed to articulate what recent empirical studies can tell us about the knowledge teachers require to teach chemical bonding. The review corpus consisted of 59 articles published over the past 20 years relating to four components of PCK: knowledge of how chemical bonding is embedded in curricula, knowledge of student understanding related to this topic, knowledge of instructional strategies and representations for teaching chemical bonding, and knowledge related to the assessment of chemical bonding understanding. This yielded current collective PCK for teaching chemical bonding in chemistry teacher education. Next, nine chemistry teacher educators were asked to portray their own personal knowledge for teaching chemical bonding through content representations. Analysis of the content representations revealed differences between several aspects of the collective PCK derived from the literature and the personal PCK articulated by our sample of Dutch chemistry teacher educators. Finally, findings from the literature and the teacher educator content representations were synthesized into a framework for chemistry teacher educators. Uses of the framework are discussed, and sample applications to the design of classroom activities are offered. Finally, implications of the findings and suggestions for future research are addressed.

Background Communicating a diagnosis is highly important, yet complex, especially in the context of cancer and mental disorders. The aim was to explore the communication style of an oncologist vs. psychotherapist in an online study. Methods Patients (N = 136: 65 cancer, 71 depression) were randomly assigned to watch a standardized video vignette with one of two communication styles (empathic vs. unempathic). Outcome measures of affectivity, information recall, communication skills, empathy and trust were applied. Results Regardless of diagnosis, empathic communication was associated with the perception of a significantly more empathic (p < 0.001, η2partial = 0.08) and trustworthy practitioner (p = 0.014, η2partial = 0.04) with better communication skills (p = 0.013, η2partial = 0.05). Cancer patients reported a larger decrease in positive affect (p < 0.001, η2partial = 0.15) and a larger increase in negative affect (p < 0.001, η2partial = 0.14) from pre- to post-video than depressive patients. Highly relevant information was recalled better in both groups (p < 0.001, d = 0.61–1.06). Conclusions The results highlight the importance of empathy while communicating both a diagnosis of cancer and a mental disorder. Further research should focus on the communication of a mental disorder in association with cancer., Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe; 817

Background The NIA-AA research framework proposes a purely biological definition of Alzheimer’s disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia. Methods A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer’s disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis. Results We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects. Conclusions We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.

Background Everyday functioning is a clinically relevant concept in dementia, yet little is known about the clinical meaningfulness of scores on functional outcome measures. We aimed to establish clinically meaningful scoring categories for the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q), representing no, mild, moderate and severe problems in daily functioning. Methods Informal caregivers (n = 6) of memory-clinic patients and clinicians (n = 13), including neurologists and nurse specialists, working at various memory clinics in The Netherlands. In focus groups, participants individually ranked nine summaries of fictional patients from least to most impairment in daily functioning. Then, they placed bookmarks to demarcate the thresholds for mild, moderate and severe problems. Individual bookmark placements were then discussed to reach consensus. Clinicians completed a survey in which they placed bookmarks, individually. Results While individual categorizations varied somewhat, caregivers and clinicians generally agreed on the thresholds, particularly about the distinction between ‘no’ and ‘mild’ problems. Score categories were no problems (T-score ≥ 60), mild problems (T-score 50–59), moderate problems (T-score 40–49), and severe problems in daily functioning (T-score Conclusions Our findings provide categories for determining the level of functional impairment, which can facilitate interpretation of A-IADL-Q scores. These categories can subsequently be used by clinicians to improve communication with patients and caregivers.

BackgroundWomen have been reported to have worse outcomes after endovascular treatment (EVT), despite a similar treatment effect in non-clinical trial populations. We aimed to assess sex differences at hospital presentation with respect to workflow metrics, prestroke disability, and presenting clinical symptoms.MethodsWe included consecutive patients from the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in The Netherlands (MR CLEAN) Registry (2014–2018) who received EVT for anterior circulation large vessel occlusion (LVO). We assessed sex differences in workflow metrics, prestroke disability (modified Rankin Scale (mRS) score ≥1), and stroke severity and symptoms according to the National Institutes of Health Stroke Scale (NIHSS) score on hospital admission with logistic and linear regression analyses and calculated the adjusted OR (aOR).ResultsWe included 4872 patients (47.6% women). Compared with men, women were older (median age 76 vs 70 years) and less often achieved good functional outcome at 90 days (mRS ≤2: 35.2% vs 46.4%, aOR 0.70, 95% CI 0.60 to 0.82). Mean onset-to-door time was longer in women (2 hours 16 min vs 2 hours 7 min, adjusted delay 9 min, 95% CI 4 to 13). This delay contributed to longer onset-to-groin times (3 hours 26 min in women vs 3 hours 13 min in men, adjusted delay 13 min, 95% CI 9 to 17). Women more often had prestroke disability (mRS ≥1: 41.1% vs 29.1%, aOR 1.57, 95% CI 1.36 to 1.82). NIHSS on admission was essentially similar in men and women (mean 15±6 vs 15±6, NIHSS ConclusionWomen with LVO had longer onset-to-door times and more often prestroke disability than men. Raising awareness of these differences at hospital presentation and investigating underlying causes may help to improve outcome after EVT in women.

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease. Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients. Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test. Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.

Background: Postural orthostatic tachycardia syndrome (POTS) has been described early after the onset of the COVID-19 infection, but also orthostatic hypotension (OH). In the present study, we hypothesized that orthostatic intolerance decreases over time. Methods: In 29 long-haul COVID-19 (LHC) patients, a tilt test was performed, including measurements of cerebral blood flow (CBF) by extracranial Doppler. The time interval between the onset of infection and the tilt test varied between 3 and 28 months. Results: In the first 12 months after the infection, 71% of the LHC patients showed POTS and after 24 months none of them. In the first 12 months, 29% of patients had a normal heart rate and blood pressure response (normHRBP) and after 24 months 75% (distribution of POTS, OH, and a normHRBP over time: p < 0.0001). Linear regression showed that, over time, there was a decrease in the abnormal CBF during the tilt (p = 0.024) but remained abnormal. Conclusion: In LHC patients, hemodynamic abnormalities of a tilt test change over time. Patients studied early after the onset of the disease mainly exhibit POTS, but patients studied later in the time course mainly show a normHRBP or OH. In addition, the abnormal CBF reduction improves over time, but CBF remains abnormal.

Objectives Acoustic noise in magnetic resonance imaging (MRI) negatively impacts patients. We assessed a silent gradient coil switched at 20 kHz combined with a T1-weighted magnetisation prepared rapid gradient-echo (MPRAGE) sequence at 7 T. Methods Five healthy subjects (21–29 years; three females) without previous 7-T MRI experience underwent both a quiet MPRAGE (Q-MPRAGE) and conventional MPRAGE (C-MPRAGE) sequence twice. Image quality was assessed quantitatively, and qualitatively by two neuroradiologists. Sound level was measured objectively and rated subjectively on a 0 to 10 scale by all subjects immediately following each sequence and after the whole examination (delayed). All subjects also reported comfort level, overall experience and willingness to undergo the sequence again. Results Compared to C-MPRAGE, Q-MPRAGE showed higher signal-to-noise ratio (10%; p = 0.012) and lower contrast-to-noise ratio (20%; p < 0.001) as well as acceptable to good image quality. Q-MPRAGE produced 27 dB lower sound level (76 versus 103 dB). Subjects reported lower sound level for Q-MPRAGE both immediate (4.4 ± 1.4 versus 6.4 ± 1.3; p = 0.007) and delayed (4.6 ± 1.4 versus 6.3 ± 1.3; p = 0.005), while they rated comfort level (7.4 ± 1.0 versus 6.1 ± 1.7; p = 0.016) and overall experience (7.6 ± 1.0 versus 6.0 ± 0.9; p = 0.005) higher. Willingness to undergo the sequence again was also higher, however not significantly (8.1 ± 1.0 versus 7.2 ± 1.3; p = 0.066). Conclusion Q-MPRAGE using a silent gradient coil reduced sound level by 27 dB compared to C-MPRAGE at 7 T while featuring acceptable-to-good image quality and a quieter and more pleasant subject experience.

A cat previously diagnosed with valvular aortic stenosis developed acute respiratory distress. A new continuous heart murmur was noted on physical exam. Echocardiographic examination revealed vegetative lesions on the aortic valve and continuously shunting blood flow from the aorta into the left atrium. Despite initial treatment for left-sided congestive heart failure, the cat died suddenly. In addition to confirming aortic valve endocarditis and an acquired aorto-left atrial shunt, pathological examination identified vegetative lesions on the luminal surface of the ascending aorta. Although antemortem aerobic blood culture, 16s bacterial ribosomal DNA PCR, and Bartonella PCR failed to identify causative organisms, Escherichia coli was identified on postmortem tissue culture of the aortic lesion. This represented a unique case of primary valvular aortic stenosis with secondary infective aortic endocarditis, infective aortic endarteritis, and aorto-left atrial fistula in a cat. It highlighted potential adverse outcomes of aortic stenosis that are more commonly recognized in humans and dogs.

A 10‐year‐old female spayed mixed breed dog was evaluated for diarrhea and vomiting. Diagnostic imaging demonstrated the presence of an intracardiac mass. A modified Seldinger technique was used to access the right jugular vein, and an endomyocardial biopsy forceps was introduced through a sheath to obtain several biopsies. Histopathology and immunohistochemistry demonstrated a paraganglioma. The dog underwent 1 fraction of radiotherapy and l‐asparaginase chemotherapy and was discharged. The dog developed a pulmonary thromboembolism 2 days after radiotherapy and chemotherapy, and the owner elected humane euthanasia. Although long‐term assessment of treatment response was unable to be performed, this novel diagnostic option could be considered for similar cases due to success in obtaining a histopathologic diagnosis, which is essential in developing a disease‐specific treatment plan. This report also describes the use of radiotherapy for primary treatment of an intracardiac neoplasm, which can be a consideration in the future.

BACKGROUND: There is evidence of unmet psychiatric needs in children under 6. These young children are dependent on their parents to identify their mental health needs. This study tested child and parent factors associations with Parent perception of mental health need in their young child. METHOD: Parents of 917 children (ages 2–6 years) completed a structured diagnostic interview about their child assessing depression, anxiety, ODD/CD, ADHD and impairment. Parents were surveyed about their own depression, anxiety and asked about their psychiatric impairment. Parents were also asked whether they perceived their child as having a mental health need. RESULTS: Only 38.8% of children who met criteria for a diagnosis were perceived by their parent as having a need, similar to previously studied rates in school-aged children. Perception of need was associated with higher levels of symptoms and impairment. Thresholds for at least half of parents perceiving their child as having a need were relatively high: 19 or more symptoms, or 4 or more impairments. There was also evidence of specificity: children with depressive disorders were more likely to be perceived as in need (OR: 6.53) compared with children with no disorder. In terms of parent factors, moderate-high parental depressive symptoms was associated with higher perception of child need when the child had a diagnosis than parents with no or mild depressive symptoms. CONCLUSIONS: Most preschool children that meet criteria for a psychiatric disorder are not perceived as needing help by their parents. Parent perception of need is dependent on both child and parent factors.

Background and purpose There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands. Methods We used data from the three hospitals that provide acute stroke care for the Amsterdam region. We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th–May 3th 2020) and one prior to the outbreak (October 21st–December 8th 2019). We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis. Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications. Results During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65–0.88). The proportion of men was higher during the COVID-19 period (59% vs. 47%, p p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times. Seven patients (all ischemic strokes) were diagnosed with COVID-19. Conclusion We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.

Background Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. Results Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. Conclusions In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.

An 8-year-old 28-kg male castrated rough collie was evaluated for persistent chylothorax secondary to right atrial mass. Cardiac ultrasound and computed tomography revealed a right atrial intra- and extraluminal mass with partial obstruction of the cranial vena cava and secondary chylothorax. Vascular stent placement was elected to alleviate cranial vena cava obstruction and secondary chylothorax. An 18 mm × 180 mm self-expanding stent was deployed in the region of the stricture, spanning the cranial vena cava and right atrium. An intrathoracic drainage catheter and subcutaneous port were placed within the right hemithorax, and antiplatelet therapy was initiated. Four weeks later, the dog underwent stereotactic body radiation therapy. Three months following treatment, the dog was diagnosed with supraventricular tachycardia and received antiarrhythmic therapy and antiangiogenic/antiproliferative medication (Palladia™). Subsequent evaluations confirmed the resolution of arrhythmia and pleural effusion. Combined vascular stent placement and stereotactic body radiation therapy for the treatment of a right atrial intraluminal and extraluminal mass leading to cranial vena cava compression and subsequent chylothorax may lead to long-term survival. A good outcome was achieved in this patient due to resolution of pleural effusion, as well as cytoreduction and presumably delayed progression of tumor growth.

Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines. Objectives. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population.A total of 1 104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification biasadjusted histology values.Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population).The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.