A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial.

BACKGROUND: Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. DESIGN: TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0-1, mRS 0-2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. CONCLUSION: Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion. DATA ACCESS STATEMENT: Data will be available upon reasonable request.

Randomised controlled trials of non-pharmacological interventions to improve patient-reported outcomes of colonoscopy: a scoping review.

BACKGROUND AND AIMS: Non-pharmacological interventions to improve patient-reported outcomes of colonoscopy may be effective at mitigating negative experiences and perceptions of the procedure, but research to characterise the extent and features of studies of these interventions is limited. METHODS: We conducted a scoping review searching multiple databases for peer-reviewed publications of randomised controlled trials conducted in adults investigating a non-pharmacological intervention to improve patient-reported outcomes of colonoscopy. Study characteristics were tabulated and summarised narratively and graphically. RESULTS: We screened 5939 citations and 962 full texts, and included 245 publications from 39 countries published between 1992 and 2022. Of these, 80.8% were full publications and 19.2% were abstracts. Of the 41.9% of studies reporting funding sources, 11.4% were unfunded. The most common interventions were carbon dioxide and/or water insufflation methods (33.9%), complementary and alternative medicines (eg, acupuncture) (20.0%), and colonoscope technology (eg, magnetic scope guide) (21.6%). Pain was as an outcome across 82.0% of studies. Studies most often used a patient-reported outcome examining patient experience during the procedure (60.0%), but 42.9% of studies included an outcome without specifying the time that the patient experienced the outcome. Most intraprocedural patient-reported outcomes were measured retrospectively rather than contemporaneously, although studies varied in terms of when outcomes were assessed. CONCLUSION: Research on non-pharmacological interventions to improve patient-reported outcomes of colonoscopy is unevenly distributed across types of intervention and features high variation in study design and reporting, in particular around outcomes. Future research efforts into non-pharmacological interventions to improve patient-reported outcomes of colonoscopy should be directed at underinvestigated interventions and developing consensus-based guidelines for study design, with particular attention to how and when outcomes are experienced and measured. PROSPERO REGISTRATION NUMBER: 42020173906.

Sex differences in the symptom presentation of stroke: A systematic review and meta-analysis.

BACKGROUND: Early diagnosis through symptom recognition is vital in the management of acute stroke. However, women who experience stroke are more likely than men to be initially given a nonstroke diagnosis and it is unclear if potential sex differences in presenting symptoms increase the risk of delayed or missed stroke diagnosis. AIMS: To quantify sex differences in the symptom presentation of stroke and assess whether these differences are associated with a delayed or missed diagnosis. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched up to January 2021. Studies were included if they reported presenting symptoms of adult women and men with diagnosed stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) and were published in English. Mean percentages with 95% confidence intervals (CIs) of each symptom were calculated for women and men. The crude relative risks (RRs) with 95% CI of symptoms being present in women, relative to men, were also calculated and pooled. Any data on the delayed or missed diagnosis of stroke for women compared to men based on symptom presentation were also extracted. RESULTS: Pooled results from 21 eligible articles showed that women and men presented with a similar mean percentage of motor deficit (56% in women vs 56% in men) and speech deficit (41% in women vs 40% in men). Despite this, women more commonly presented with nonfocal symptoms than men: generalized nonspecific weakness (49% vs 36%), mental status change (31% vs 21%), and confusion (37% vs 28%), whereas men more commonly presented with ataxia (44% vs 30%) and dysarthria (32% vs 27%). Women also had a higher risk of presenting with some nonfocal symptoms: generalized weakness (RR 1.49, 95% CI 1.09-2.03), mental status change (RR 1.44, 95% CI 1.22-1.71), fatigue (RR 1.42, 95% CI 1.05-1.92), and loss of consciousness (RR 1.30, 95% CI 1.12-1.51). In contrast, women had a lower risk of presenting with dysarthria (RR 0.89, 95% CI 0.82-0.95), dizziness (RR 0.87, 95% CI 0.80-0.95), gait disturbance (RR 0.79, 95% CI 0.65-0.97), and imbalance (RR 0.68, 95% CI 0.57-0.81). Only one study linking symptoms to definite stroke/TIA diagnosis found that pain and unilateral sensory loss are associated with lower odds of a definite diagnosis in women compared to men. CONCLUSION: Although women showed a higher prevalence of some nonfocal symptoms, the prevalence of focal neurological symptoms, such as motor weakness and speech deficit, was similar for both sexes. Awareness of sex differences in symptoms in acute stroke evaluation, careful consideration of the full constellation of presenting symptoms, and further studies linking symptoms to diagnostic outcomes can be helpful in improving early diagnosis and management in both sexes.

National trends in hospital admission, case fatality, and sex differences in atrial fibrillation-related strokes.

BACKGROUND AND AIM: Atrial fibrillation is associated with increased risk of ischemic stroke and its global prevalence is increasing. We aimed to describe the contemporary temporal trends in hospital admissions, case fatality rate, as well as sex differences in atrial fibrillation-related stroke in Canada. METHODS: We conducted a retrospective cohort study using Canadian national administrative data to identify admissions to hospital for stroke with comorbid atrial fibrillation between 1 April 2007 and 31 March 2016. We determined temporal trends in the crude and the age- and sex-standardized admission and case fatality rates. We also evaluated for any sex differences in these outcomes. RESULTS: There were 222,100 admissions to hospital for ischemic (n = 182,990) or hemorrhagic (n = 39,110) stroke. Comorbid atrial fibrillation was present in 20.2% of admissions for ischemic strokes and 10.1% for hemorrhagic strokes. Over the study period, the age-sex adjusted proportion of admissions with atrial fibrillation increased from 16.3% to 20.5% (p = 0.02) for ischemic stroke and was stable for hemorrhagic stroke. In-hospital case fatality rate decreased for ischemic stroke with and without comorbid atrial fibrillation. Women aged 65 years and older with ischemic stroke were more likely to have comorbid atrial fibrillation compared to men, while this association was reversed in younger women. There were no sex differences in the case fatality rate for people with atrial fibrillation-related ischemic stroke. CONCLUSION: Atrial fibrillation is present in an increasing proportion of people hospitalized in Canada with ischemic stroke and disproportionately affects older women. Renewed focus is needed on atrial fibrillation-related stroke prevention with particular attention to sex disparities.