title: Within-day and weekly variations of thrombolysis in acute ischemic stroke: results from safe implementation of treatments in stroke-international stroke thrombolysis register.
abstract: OBJECTIVE
  Temporal variations of thrombolysis delivery and their influence on outcome have been reported with controversial results. In this large cohort study, we evaluated whether thrombolytic treatment has a within-day and weekly variability corresponding to circadian and weekly patterns of ischemic stroke onset, and whether these have impact on clinical outcome.
  
  
  METHODS
  We retrospectively analyzed patients with acute ischemic stroke receiving intravenous alteplase, prospectively included in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients were grouped by treatment on day hours (08:00-19:59) or night hours (20:00-07:59) and treatment on weekdays and weekends. For each subgroup, we analyzed frequency of thrombolytic treatments, time intervals, and outcomes (3-month modified Rankin Scale score 0-2 as good functional outcome, mortality, symptomatic intracerebral hemorrhage).
  
  
  RESULTS
  We included 21 513 patients. Considering the mean expected number of patients treated per hour (0.4) and per day of the week (9.8), if no temporal variations were present, patients were significantly treated more during day hours and weekdays (P<0.0001). Median door-to-needle and onset-to-treatment times were longer for patients treated during night hours and on weekends (P<0.01). After adjustment for confounding variables, treatment during day hours was an independent predictor of good functional outcome (odds ratio, 1.12; 95% confidence interval, 1.04-1.21; P=0.004), and patients treated during weekdays were at risk of higher mortality (odds ratio, 1.15; 95% confidence interval, 1.04-1.28; P=0.008).
  
  
  CONCLUSIONS
  Frequency of thrombolytic treatment seems to follow the same circadian pattern of stroke incidence, whereas its correspondence to a weekly pattern is less clear. Time of treatment is an independent predictor of outcome.
authors.affiliation: From the Emergency Department Stroke Unit, Department of Neurology and Psychiatry, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy (S.L., D.T.); Karolinska Stroke Research Unit, Department of Neurology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (N.A., N.W.); Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland (T.T.); Acute Stroke Unit, Department of Neuroscience, Hospital Universitari Germas Trias i Pujol, Universidad Autònoma de Barcelona, Barcelona, Spain (M.G., A.D.); International Clinical Research Center, Neurology Department, St. Anne's Hospital, Brno, Czech Republic (R.M.); Department of Neurology, University Hospital, Plzen, Czech Republic (P.S.); and Department of Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland (J.O.).
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lorenzano
authors.forename: Niaz
authors.initials: N
authors.lastname: Ahmed
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gomis
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.forename: Robert
authors.initials: R
authors.lastname: Mikulik
authors.forename: Petr
authors.initials: P
authors.lastname: Sevcik
authors.forename: Jyrki
authors.initials: J
authors.lastname: Ollikainen
authors.forename: Nils
authors.initials: N
authors.lastname: Wahlgren
authors.forename: Danilo
authors.initials: D
authors.lastname: Toni
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D003627:Data Interpretation, Statistical; D061345:Early Medical Intervention / Q000706:statistics & numerical data*; D005060:Europe; D006801:Humans; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000706:statistics & numerical data*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator
keywords: circadian rhythm; outcome assessment; stroke; thrombolytic therapy; tissue-type plasminogen activator