Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbased ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.

Summary Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding British Heart Foundation.

Objective To increase participation in cervical cancer screening of under-served women living in the Mississippi Delta, a U.S. population at high risk for cervical cancer Methods We conducted a door-to-door feasibility study of women living in the Mississippi Delta to increase participation in cervical cancer screening in 2009-10. Women (n=119) aged 26-65 years who had not been screened in last 3 years or more, were not pregnant, and had a cervix were offered a choice: clinic-based Pap testing or home self-collection with HPV DNA testing. Results Seventy-seven women (64.7%) chose self-collection with HPV testing, of which 62 (80.5%) returned their self-collected specimen. By comparison, 42 women (35.3%) chose Pap testing, of which 17 (40.5%) attended their clinic appointment. Thus there was an almost 4-fold greater participation of under-screened women in self-collection with HPV testing than in free Pap testing (78.4% vs. 21.5%). Conclusions We found that offering self-collection will increase participation in cervical cancer screening among under-screened populations living in the Mississippi Delta. Based on these preliminary results, we suggest that self-collection with HPV DNA testing might complement current Pap testing programs to reach under-screened populations of women, such as those living in the Mississippi Delta.

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.

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Objectives The aim of the study was to determine if amantadine improves owner-identified mobility impairment and quality of life associated with osteoarthritis in cats. Methods Using a blinded, placebo-controlled, randomized, crossover design, 13 healthy client-owned cats with clinical and radiographic evidence of osteoarthritis and owner-identified mobility impairment were studied. Cats received 5 mg/kg amantadine or placebo q24h PO for 3 weeks each with no washout period between. Locomotor activity was continuously assessed with a collar-mounted activity monitor system, and owners chose and rated two mobility-impaired activities using a client-specific outcome measures (CSOM) questionnaire on a weekly basis. Locomotor activity on the third treatment week was analyzed with two-tailed paired t-tests. The CSOM scores were analyzed using a mixed-effect model and the Bonferroni post-hoc test. Owner-perceived changes in quality of life were compared between treatments using the χ2 test. Statistical significance was set at P <0.05. Results Mean ± SD activity counts during the third week of each treatment were significantly lower with amantadine (240,537 ± 53,880) compared with placebo (326,032 ± 91,759). CSOM scores assigned by the owners were significantly better with amantadine on the second (3 ± 1) and third (3 ± 1) weeks compared with placebo (5 ± 2 and 5 ± 1, respectively). A significantly greater proportion of owners reported improvement in quality of life with amantadine compared with placebo. Conclusions and relevance Amantadine significantly decreased activity, but improved owner-identified impaired mobility and owner-perceived quality of life in cats with osteoarthritis. Amantadine appears to be an option for the symptomatic treatment of osteoarthritis in cats.

This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one‐week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial venous blood samples were collected for quantification of xylazine and dexmedetomidine, and the pharmacokinetic parameters were calculated. Two individuals blinded to treatment identity evaluated recovery quality with a visual analog scale. Times to stand were recorded. Results (mean ± SD) were compared using paired t tests or Wilcoxon signed‐ranked test with p < .05 considered significant. Elimination half‐lives (62.7 ± 21.8 and 30.1 ± 8 min for xylazine and dexmedetomidine, respectively) and steady‐state volumes of distribution (215 ± 123 and 744 ± 403 ml/kg) were significantly different between xylazine and dexmedetomidine, whereas clearances (21.1 ± 17.3 and 48.6 ± 28.1 ml/minute/kg), times to stand (47 ± 24 and 53 ± 12 min) and recovery quality (51 ± 24 and 61 ± 22 mm VAS) were not significantly different. When used for postanesthetic sedation following isoflurane anesthesia in healthy horses, dexmedetomidine displays faster plasma kinetics but is not associated with faster recoveries compared to xylazine.

Background: African-American women in the United States have an elevated risk of cervical cancer incidence and mortality. In the Mississippi Delta, cervical cancer disparities are particularly stark. Methods: We conducted a micro-costing study alongside a group randomized trial that evaluated the efficacy of a patient-centered approach (“Choice” between self-collection at home for HPV testing or current standard of care within the public health system in Mississippi) versus the current standard of care [“Standard-of-care screening,” involving cytology (i.e., Pap) and HPV co-testing at the Health Department clinics]. The interventions in both study arms were delivered by community health workers (CHW). Using cost, screening uptake, and colposcopy adherence data from the trial, we informed a mathematical model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis comparing the “Choice” and “Standard-of-care screening” interventions among un/underscreened African-American women in the Mississippi Delta. Results: When each intervention was simulated every 5 years from ages 25 to 65 years, the “Standard-of-care screening” strategy reduced cancer risk by 6.4% and was not an efficient strategy; “Choice” was more effective and efficient, reducing lifetime risk of cervical cancer by 14.8% and costing $62,720 per year of life saved (YLS). Screening uptake and colposcopy adherence were key drivers of intervention cost-effectiveness. Conclusions: Offering “Choice” to un/underscreened African-American women in the Mississippi Delta led to greater uptake than CHW-facilitated screening at the Health Department, and may be cost-effective. Impact: We evaluated the cost-effectiveness of an HPV self-collection intervention to reduce disparities.