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Background: Lasmiditan, an oral 5-HT1F receptor agonist, has been recently approved for acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, scarce data is available regarding effectiveness and tolerability in the real-world setting. Objectives: To evaluate lasmiditan effectiveness and tolerability in the real-world setting in 16 Italian headache centers. Design: LasmiDitan as Acute migRaine Treatment (DART) study is a prospective, multicentric, observational study. Methods: We enrolled 58 participants with migraine (84.5% females, age 49.0 (45.2–52.9) years, 24.1% with chronic migraine) reporting 9.4 (7.4–11.3) monthly migraine days. Participants were instructed to treat their migraine attacks with oral lasmiditan 50 or 100 mg. Using an ad hoc electronic diary, participants prospectively collected migraine attack features at baseline and every 30 min after lasmiditan administration, up to 2 h post-dose. The primary outcome was 2-h pain freedom for the first-treated attack after lasmiditan intake. We also collected the occurrence of treatment-emergent adverse events (AE) after administration. Results: Overall, participants treated 100 attacks, of which 58 first-treated attacks. Regarding first-treated attacks, 44.8% of subjects rated migraine intensity as severe at lasmiditan intake. Pain freedom 2-h post-dosing was reported in 32.8% (19/58) of individuals and was associated with baseline pain intensity, being higher in subjects treating a mild/moderate attack (p = 0.044). Conversely, it was not influenced by timing of intake (p = 0.375), dosage (p = 0.727), or previous triptan failure (p = 0.351). Regarding all-treated attacks, pain freedom 2-h post-dosing was 37.0% (37/100). At least one AE was reported by 53.4% of participants (31/58), predominantly asthenia, dizziness, somnolence, anxiety or agitation, and paresthesia. Tolerability was rated as good-to-excellent by 51.8% of subjects. Conclusion: Our study supports clinical effectiveness of oral lasmiditan 50 and 100 mg for the treatment of acute migraine attacks. Lasmiditan effectiveness was not associated with the previous triptan failure and may therefore represent a valuable therapeutic option in subjects who did not benefit from, or have contraindications to, triptans. Trail registration: The study was preregistered on clinicaltrial.gov, NCT05903040 (https://clinicaltrials.gov/study/NCT05903040?cond=migraine&intr=lasmiditan&rank=5).

BackgroundLeisure-time physical activity (LTPA) protects against vascular diseases. Whether and to what extent different levels of LTPA, including lower ones, benefit stroke prevention is still unclear.MethodsWe searched prospective cohort studies, indexed on PubMed and Scopus, published in English up to 22 April 2023, that investigated, in a general healthy population, the relationship between different predefined LTPA levels, compared with inactivity, and the risk of any type of stroke. We applied random effect modelling for meta-analyses and meta-regression to control for the impact of age and sex.ResultsOut of 3064 screened articles, 15 articles on 16 cohorts of subjects were included in meta-analyses, with a total of 752 050 followed-up subjects. Mean follow-up was 125.7±77.5 months. Included studies identified three (none, below target and ideal) to five (none, insufficient, low, moderate and intense) levels of LTPA. In the five studies identifying three levels of LTPA, compared with no LTPA, below target (risk ratio (RR)=0.82, 95% CI=0.75 to 0.88) and ideal LTPA significantly reduced stroke risk (RR=0.71, 95% CI=0.58 to 0.86).Lower levels of LTPA also mitigated stroke risk in studies reporting on four (n=6; RR=0.73, 95% CI=0.62 to 0.87 favouring moderate LTPA over no LTPA) and five levels (n=2; RR=0.71, 95% CI=0.58 to 0.88 favouring moderate LTPA over no LTPA). The benefits of LTPA were independent of age and sex.ConclusionsAccording to our results, all levels of LTPA can be beneficial for stroke prevention, including levels currently regarded as low or insufficient. People should be encouraged to be physically active even at the lowest levels.PROSPERO registration numberCRD42023425302.

IntroductionHeadache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce.Material and methodsWe searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8–18 years old individuals. The risk of bias was examined with the Joanna Briggs Institute (JBI) scale. A random-effects model was used to estimate the pooled prevalence of pediatric headache. Subgroup analyses based on headache subtypes were also conducted.ResultsOut of 5,486 papers retrieved electronically, we identified 48 studies that fulfilled our inclusion criteria. The pooled prevalence of primary headaches was 11% for migraine overall [95%CI: 9–14%], 8% for migraine without aura (MwoA) [95%CI: 5–12%], 3% for migraine with aura (MwA) [95%CI:2–4%] and 17% for tension-type headache (TTH) [95% CI: 12–23%]. The pooled prevalence of overall primary headache in children and adolescents was 62% [95% CI: 53–70%], with prevalence in females and males of 38% [95% CI: 16–66%] and 27% [95% CI: 11–53%] respectively. After the removal of studies ranked as low-quality according to the JBI scale, prevalence rates were not substantially different. Epidemiological data on less common primary headaches, such as trigeminal autonomic cephalalgias, were lacking.ConclusionWe found an overall remarkably high prevalence of primary headaches in children and adolescents, even if flawed by a high degree of heterogeneity. Further up-to-date studies are warranted to complete the picture of pediatric headache-related burden to enhance specific public interventions.

The use of antiplatelet therapy (APT) is prevalent among the general population, sometimes without clear indications. We provided updated figures on the incidence and prognosis of first-ever intracerebral hemorrhage occurring on APT (APT-ICH) over 10 years in a population-based stroke registry and investigated the rates of inappropriate APT prescription. We included all cases of first-ever ICH not on anticoagulants from January 2011 to December 2020 in the district of L’Aquila (Southern Italy). Indication to APT was adjudicated according to 2021 European Society of Cardiology (ESC) guidelines for cardiovascular prevention. We included 606 first-ever ICHs, of whom 251 (41.4%) were APT-related. One-hundred-forty-two APT-ICHs (56.6%) occurred in patients without clear indications to APT. While the incidence of non-APT-ICH decreased over time, the incidence of APT-ICH was stable. APT-ICH showed higher 30-day and 1-year case-fatality rates versus non-APT-ICH (44.7% versus 25.6%, 50.6% versus 34.4%; p  < 0.001). APT intake was independently associated with higher 30-day case-fatality (HR 1.51, 95%CI 1.03–2.14; p  = 0.023). Our findings suggest that APT-ICH exhibits sustained incidence over time and elevated mortality. Urgent initiatives are needed to enhance adherence to established guidelines for APT use. This effort has the potential to mitigate the risk of ICH and to reduce the associated mortality.

Background and purpose Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6‐month effectiveness and tolerability of anti‐CGRP mAbs in combination with other mAbs for different diseases. Methods Patients included in the Italian Headache Registry and treated concomitantly with an anti‐CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test‐6 (HIT‐6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. Results Thirty‐eight patients were included. In 27 patients (71.1%), the anti‐CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti‐CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti‐CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow‐up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT‐6 scores at 3 and 6 months (p < 0.001). For anti‐CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). Conclusions In this real‐world study, anti‐CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.

Background: Elevated baseline systolic blood pressure (SBP) was associated with poor outcomes following dual antiplatelet therapy (DAPT) in patients with non-cardioembolic minor ischemic stroke (MIS) or high-risk transient ischemic attack (TIA) in clinical trials. Objectives: We aimed to assess the impact of admission SBP on the short-term outcomes after DAPT in patients with non-cardioembolic MIS or high-risk TIA. Methods: We performed an inverse probability weighted (IPW) analysis from a prospective multicentric real-world study (READAPT) including patients with non-cardioembolic MIS (National Institute of Health Stroke Scale of 0–5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, 24-h early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleedings, symptomatic intracranial hemorrhage, and 24-h hemorrhagic transformation. We used Cox proportional hazards regression with restricted cubic splines to model the continuous relationship between SBP and the hazard ratio (HR) of new vascular events. We selected SBP = 124 mm Hg as cut-off point for the IPW weighting. Outcomes were compared using Cox and generalized logistic regression analyses, adjusted for residual confounders. Results: From 2278 patients in the READAPT cohort, we included 1291 MIS or high-risk TIAs (mean age 70.6 ± 11.4 years; 65.8% males). After IPW, patients with admission SBP ⩾124 mm Hg versus <124 mm Hg had a significantly higher risk of 90-day ischemic stroke or other vascular events (adjusted HR: 2.14 (95% CI 1.07%–4.98%); p = 0.033) and of 24-h early neurological deterioration (adjusted risk difference: 1.91% (95% CI 0.60%–3.41%); p = 0.006). The overall risk of safety outcomes was low, although patients with SBP ⩾124 mm Hg on admission showed higher rates of 90-day moderate-to-severe and any bleeding events (adjusted risk difference: 1.24% (95% CI 0.38%–2.14%); p = 0.004 and 6.18% (95% CI 4.19%–8.16%); p < 0.001; respectively), as well as of 24-h hemorrhagic transformation (adjusted risk difference: 1.57% (95% CI 0.60%–2.55%); p = 0.001). Subgroup analysis showed a significant interaction between admission SBP, sex, and time to DAPT start in predicting 90-day new vascular events (p for interaction <0.001 and 0.007, respectively). Conclusion: In patients with non-cardioembolic MIS or high-risk TIA, higher levels of admission SBP may be associated with an increased risk of new vascular events, early neurological deterioration, and bleeding after DAPT use. Future studies should further investigate if optimizing blood pressure management may further improve prognosis.

Background: Dual antiplatelet therapy (DAPT) is a cornerstone of secondary prevention in patients with minor ischemic stroke or high-risk transient ischemic attack. The effectiveness and safety of DAPT may differ between patients with posterior (PCI) and anterior circulation infarct (ACI). Objectives: We aimed to compare short-term outcomes following DAPT between mild-to-moderate stroke patients with PCI versus ACI. Design: Propensity-matched analysis from a prospective real-world multicentric cohort study (READAPT). Methods: We included patients with noncardioembolic mild-to-moderate stroke (National Institute of Health Stroke Scale of 0–10) who initiated DAPT within 48 h of symptom onset. Patients were categorized into ACI or PCI based on the infarct(s) location on brain neuroimaging. The primary effectiveness outcome was the 90-day risk of ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale (mRS) score distribution, 24-h early neurological improvement or deterioration, and all-cause mortality. The safety outcomes included the 90-day risk of any bleedings and 24-h hemorrhagic transformation. Results: We matched 281 PCI patients with 651 ACI patients. The 90-day risk of ischemic stroke or other vascular events was low and similar between PCI and ACI groups (3.1% vs 2.9%, respectively; hazard ratio 0.98, (95% confidence interval (CI) 0.45–2.14); p = 0.845). Patients with PCI had worse 90-day mRS ordinal distribution compared to those with ACI (odds ratio 1.18 (95% CI 1.01–1.39); p = 0.046). There were no differences in other secondary outcomes. Safety outcomes had low incidence and did not differ between groups (any bleedings: 3.2% vs 2.6%; 24-h hemorrhagic transformation: 1.8% vs 1.2%). We found no differences in the risk of ischemic stroke or other vascular events between patients with PCI and ACI across subgroups defined by sex, age, presumed stroke etiology, stroke severity, prestroke mRS, hypertension, diabetes, acute reperfusion therapies, DAPT loading dose, or presence of symptomatic intracranial stenosis. Conclusion: Our findings suggest that effectiveness and safety outcomes after DAPT in patients with mild-to-moderate noncardioembolic ischemic stroke are consistent regardless of infarct location in the anterior or posterior circulation territory. However, patients with PCI may experience worse short-term functional outcome. Trial registration: URL: www.clinicaltrials.gov; Unique identifier: NCT05476081.

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments. Graphical Abstract

Aerospace manufacturing companies, such as Thales Alenia Space, design, develop, integrate, verify, and validate products characterized by high complexity and low volume. They carefully document all phases for each product but analyses across products are challenging due to the heterogeneity and unstructured nature of the data in documents. In this paper, we propose a hybrid methodology that leverages Knowledge Graphs (KGs) in conjunction with Large Language Models (LLMs) to extract and validate data contained in these documents. We consider a case study focused on test data related to electronic boards for satellites. To do so, we extend the Semantic Sensor Network ontology. We store the metadata of the reports in a KG, while the actual test results are stored in parquet accessible via a Virtual Knowledge Graph. The validation process is managed using an LLM-based approach. We also conduct a benchmarking study to evaluate the performance of state-of-the-art LLMs in executing this task. Finally, we analyze the costs and benefits of automating preexisting processes of manual data extraction and validation for subsequent cross-report analyses.

During seasons 2018 and 2019, an intense monitoring activity was carried out on ten fields of common hazel (Corylus avellana L.), for a total of approximately 25.000 plants, located in the growing areas of Tuscia, the northern territory of Lazio region (Italy). Genomic DNA from pure mycelium of a reference isolate of the pathogen was extracted by using a commercial kit and it was used as template to amplify and sequence the Internal Transcribed Spacer (ITS) region by ITS1 and ITS4 primers. Pathogenicity test was carried out depositing a PDA disk, obtained from a pure culture of mycelium of the reference isolate numbered 2.7 preserved in the laboratory collection, on scalpel-wounded young branches of 2-years-old hazelnut cv.