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Background: Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies., Methods: Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated., Findings: Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62])., Interpretation: Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy., Funding: Fonds NutsOhra., Competing Interests: Declaration of interests DWJD reports unrestricted research grants from Stryker Medtronic, Cerenovus, Penumbra, and Thrombolytic Science, all paid to his institution; and is chair of the data safety monitoring boards of the Act Global and LATE MT trials and a work package of the CONTRAST consortium. HBvdW reports research grants from the Dutch Heart Foundation (via the CONTRAST consortium), the European Commission, Stryker (via the CONTRAST consortium), Bayer, and Boehringer Ingelheim; consulting fees from TargED Biopharmaceuticals, Bayer, and Boehringer Ingelheim; and honoraria for presentations from the Netherlands Vascular Forum, all paid to his institution; is chair of the data safety monitoring board of the Ghrelin in Coma (GRECO) trial and a member of the advisory board of the TENSION trial; and is on the executive committee of—and is a past president of—the European Stroke Organisation. MJHW reports participation on the data safety monitoring board of the TRIDENT trial. YBWEMR is a minor shareholder of Nicolab. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

This article describes the 1-year follow-up of a study into the effectiveness of Schema Therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol use disorder (AUD). In the original study, 20 of these patients participated in a multiple baseline case series design study. The results of the original study were promising (a significant decrease of BPD and AUD symptoms). The present study is aimed at examining the longer term benefits of ST for BPD and comorbid AUD. One year after the cessation of the investigational therapy, 17 of the original participants agreed to participate in this follow-up study. T- or Wilcoxon signed rank tests were performed to compare 1-year follow-up to start of therapy (baseline). The results suggest that the main therapeutic improvements were generally preserved at 1-year follow-up. These findings add to the idea that integrated ST for BPD and comorbid AUD might be effective, also in the long term. A randomized clinical trial is indicated to substantiate this idea., (© 2024 The Author(s). Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

Haemorrhagic stroke is a severe condition with poor prognosis. Biological sex influences the risk factors, presentations, treatment, and patient outcomes of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and vascular malformations. Women are usually older at onset of intracerebral haemorrhage compared with men but have an increased risk of aneurysmal subarachnoid haemorrhage as they age. Female-specific factors such as pregnancy, eclampsia or pre-eclampsia, postmenopausal status, and hormone therapy influence a woman's long-term risk of haemorrhagic stroke. The presence of intracranial aneurysms, arteriovenous malformations, or cavernous malformations poses unique clinical dilemmas during pregnancy and delivery. In the absence of evidence-based guidelines for managing the low yet uncertain risk of haemorrhagic stroke during pregnancy and delivery in women with vascular malformations, multidisciplinary teams should carefully assess the risks and benefits of delivery methods for these patients. Health-care providers should recognise and address the challenges that women might have to confront when recovering from haemorrhagic stroke., Competing Interests: Declaration of interests ECS is national coordinator of the ANNEXAi trial (honoraria paid to the institution), is a steering committee member for the AXIOMATIC trial (BristolMyersSquibb) and OCEANIC trial (Bayer; also honoraria paid to the institution), and is on the European Stroke Organisation intracerebral haemorrhage committee. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

European marbled newts come in two species that have abutting ranges. The northern species, Triturus marmoratus, is found in France and the northern part of the Iberian Peninsula, whereas the southern species, T. pygmaeus, is found in the southwestern corner of the Iberian Peninsula. We study the intraspecific genetic differentiation of the group because morphological data show geographical variation and because the Iberian Peninsula is a recognized center of speciation and intraspecific genetic diversity for all kinds of organisms, amphibians included. We use target enrichment by sequence capture to generate c. 7 k nuclear DNA markers. We observe limited genetic exchange between the species, which confirms their distinctiveness. Both species show substantial genetic structuring that is only in part mirrored by morphological variation. Genetically differentiated groups are found in the south (T. marmoratus) and west (T. pygmaeus) of the species ranges. Our observations highlight the position of the Iberian Peninsula as a hotspot for genetic differentiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Differences in clinical presentation of acute ischemic stroke between men and women may affect prehospital identification of anterior circulation large vessel occlusion (aLVO). We assessed sex differences in diagnostic performance of 8 prehospital scales to detect aLVO., Methods: We analyzed pooled individual patient data from 2 prospective cohort studies (LPSS [Leiden Prehospital Stroke Study] and PRESTO [Prehospital Triage of Patients With Suspected Stroke Study]) conducted in the Netherlands between 2018 and 2019, including consecutive patients ≥18 years suspected of acute stroke who presented within 6 hours after symptom onset. Ambulance paramedics assessed clinical items from 8 prehospital aLVO detection scales: Los Angeles Motor Scale, Rapid Arterial Occlusion Evaluation, Cincinnati Stroke Triage Assessment Tool, Cincinnati Prehospital Stroke Scale, Prehospital Acute Stroke Severity, gaze-face-arm-speech-time, Conveniently Grasped Field Assessment Stroke Triage, and Face-Arm-Speech-Time Plus Severe Arm or Leg Motor Deficit. We assessed the diagnostic performance of these scales for identifying aLVO at prespecified cut points for men and women., Results: Of 2358 patients with suspected stroke (median age, 73 years; 47% women), 231 (10%) had aLVO (100/1114 [9%] women and 131/1244 [11%] men). The area under the curve of the scales ranged from 0.70 (95% CI, 0.65-0.75) to 0.77 (95% CI, 0.73-0.82) in women versus 0.69 (95% CI, 0.64-0.73) to 0.75 (95% CI, 0.71-0.79) in men. Positive predictive values ranged from 0.23 (95% CI, 0.20-0.27) to 0.29 (95% CI, 0.26-0.31) in women versus 0.29 (95% CI, 0.24-0.33) to 0.37 (95% CI, 0.32-0.43) in men. Negative predictive values were similar (0.95 [95% CI, 0.94-0.96] to 0.98 [95% CI, 0.97-0.98] in women versus 0.94 [95% CI, 0.93-0.95] to 0.96 [95% CI, 0.94-0.97] in men). Sensitivity of the scales was slightly higher in women than in men (0.53 [95% CI, 0.43-0.63] to 0.76 [95% CI, 0.68-0.84] versus 0.49 [95% CI, 0.40-0.57] to 0.63 [95% CI, 0.55-0.73]), whereas specificity was lower (0.79 [95% CI, 0.76-0.81] to 0.87 [95% CI, 0.84-0.89] versus 0.82 [95% CI, 0.79-0.84] to 0.90 [95% CI, 0.88-0.91]). Rapid arterial occlusion evaluation showed the highest positive predictive values in both sexes (0.29 in women and 0.37 in men), reflecting the different event rates., Conclusions: aLVO scales show similar diagnostic performance in both sexes. The rapid arterial occlusion evaluation scale may help optimize prehospital transport decision-making in men as well as in women with suspected stroke., Competing Interests: Disclosures Dr Wermer reports receiving Clinical Established Investigator grant 2016T086 from the Dutch Heart Foundation and VIDI grant 9171337 from the Netherlands Organization for Health Research and Development (ZonMw) during the conduct of the original LPSS (Leiden Prehospital Stroke Study). Dr Kruyt reports receiving grant HA20 15.01.02 from the Dutch Brain Foundation, grant 3.240 from the Dutch Innovation Funds, and grant LSHM16041 from Health-Holland during the conduct of the study. Dr Roozenbeek reports funding from the Dutch Heart Foundation and the Netherlands Organization for Health Research and Development (ZonMw) during the conduct of this study, paid to the institution. Dr Dippel reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, the Netherlands Organisation for Health Research and Development, Health-Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc, Stryker, Medtronic, Thrombolytic Science, LLC, and Cerenovus for research, all paid to institution outside the submitted work. Dr van den Wijngaard reports compensation from Philips for consultant services, compensation from Medtronic for consultant services, and stock holdings in Neurophyxia BV. The other authors report no conflicts.

Background: Women with anterior circulation large vessel occlusion (LVO) have been reported to have worse outcomes after endovascular treatment (EVT) than men. Whether these disparities also exist in LVO of the posterior circulation is yet uncertain. We assessed sex differences in clinical, technical, and safety outcomes of EVT in posterior circulation LVO., Methods: We used data of patients with posterior circulation LVO included in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2018). Primary outcome was the modified Rankin Scale (mRS) score at 90 days assessed with multivariable ordinal regression analysis. Secondary outcomes included favorable functional outcome (mRS ≤3), functional independence (mRS ≤2), death within 90 days, National Institutes of Health Stroke Scale (NIHSS) score 24-48 hours postintervention, complications, successful reperfusion (extended Thrombolysis in Cerebral Ischemia 2B-3), and procedure duration analyzed with multivariable logistic and linear regression analyses., Results: We included 264 patients (42% women). Compared with men, women were older (median age 68 vs 63 years), more often had prestroke disability (mRS ≥1: 37% vs 30%), and received intravenous thrombolytics less often (45% vs 56%). Clinical outcomes were similar between sexes (adjusted (common) OR (aOR) 0.82, 95% CI 0.51 to 1.34; favorable functional outcome 50% vs 43%, aOR 1.31, 95% CI 0.77 to 2.25; death 32% vs 29%, aOR 0.98, 95% CI 0.52 to 1.84). In addition, NIHSS score after 24-48 hours (median 7 vs 9), successful reperfusion (77% vs 73%), and complications did not differ between men and women., Conclusions: Outcomes in women treated with EVT for posterior circulation LVO were similar compared with men despite less favorable baseline characteristics in women. Therefore men and women may benefit equally from EVT., Competing Interests: Competing interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MJHW reports funding from NWO/ZonMw (VIDI 91717337 and Aspasia). JH reports funding from the Dutch Heart Foundation (CEI 2018T070). CBLMM reports funding from the TWIN Foundation, CVON/Dutch Heart Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker, all outside the submitted work (paid to institution). In addition, he is shareholder of Nicolab. IRvdW reports consulting fees from Philips, Medtronic, and Neurophyxia. DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus, all paid to the institution. The other authors had no conflicting interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)