Summary Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47–72) of patients had primary patency, 73% (57–81) had primary assisted patency, and 97% (85–98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17–40) had primary patency, 38% (26–51) had primary assisted patency, and 89% (74–93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health.

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At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. Further studies to assess the optimal oral dose and full efficacy and tolerability profile are under way. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this study is NCT00384774.

This double-blind, placebo-controlled, multicenter, parallel-group study assessed whether subcutaneous sumatriptan administered during the migraine aura would prolong or modify the aura and prevent or delay development of the headache. One hundred seventy-one patients (88 receiving 6 mg sumatriptan, 83 receiving placebo) treated a single attack of migraine with typical aura at home, by self-injection. The median duration of aura following the first injection was 25 minutes for the sumatriptan group and 30 minutes for the placebo group (NS). The aura symptom profile was similar for the two treatment groups. The proportion of patients who developed a moderate or severe headache within 6 hours after dose administration was similar in the two groups--68% among those receiving sumatriptan and 75% among those receiving placebo (NS). Sumatriptan given during the aura did not prolong or alter the nature of the migraine aura and did not prevent or significantly delay headache development.

The clinical development of sumatriptan has involved large international multicentre trials. To allow comparison of results obtained in a variety of clinical settings, great emphasis was placed on the use of consistent methodology across the programme. This applied to selection of patients, trial design, symptom evaluation and statistical analysis. Patients were selected for the major trials if they fulfilled the International Headache Society’s diagnostic criteria for migraine or cluster headache. Relief of the headache was used as the main efficacy measure and this was assessed using standardized self-rating scales. All major controlled trials in migraine employed a parallel group design to avoid carryover effects and to ensure blinding was not compromised; however, because of the rarity of cluster headache, a crossover trial was performed in this indication. Appropriate statistical analyses were then performed on the data. The rationale for the methodology adopted is discussed. Strict adherence to these principles has allowed us to compare the results of sumatriptan treatment across a wide range of countries and treatment settings, and a selection of different administration routes.