Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial.

BACKGROUND In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial

Background: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. Methods: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0–2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay.ResultsWe included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65–81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13–20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. Conclusion: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER clinicaltrials.gov NCT03192332

DARWIN: towards the ultimate dark matter detector

DARk matter WImp search with liquid xenoN (DARWIN) will be an experiment forthe direct detection of dark matter using a multi-ton liquid xenon timeprojection chamber at its core. Its primary goal will be to explore theexperimentally accessible parameter space for Weakly Interacting MassiveParticles (WIMPs) in a wide mass-range, until neutrino interactions with thetarget become an irreducible background. The prompt scintillation light and thecharge signals induced by particle interactions in the xenon will be observedby VUV sensitive, ultra-low background photosensors. Besides its excellentsensitivity to WIMPs above a mass of 5 GeV/c2, such a detector with its largemass, low-energy threshold and ultra-low background level will also besensitive to other rare interactions. It will search for solar axions, galacticaxion-like particles and the neutrinoless double-beta decay of 136-Xe, as wellas measure the low-energy solar neutrino flux with <1% precision, observecoherent neutrino-nucleus interactions, and detect galactic supernovae. Wepresent the concept of the DARWIN detector and discuss its physics reach, themain sources of backgrounds and the ongoing detector design and R&D efforts

Four-Stage Audit Demonstrating Increased Uptake of HIV Testing in Acute Neurology Admissions Using Staged Practical Interventions.

BACKGROUND: UK National Guidelines (UKNG) advise HIV testing in clinically indicated neurological presentations. We audited the impact of our practical strategies to increase uptake of HIV testing at a regional acute neurology admissions unit. METHODS: We audited HIV testing in 4 periods over 2 years: before we designed a UKNG-based "HIV testing in Neurology" protocol ("pre-protocol"); after dissemination of the protocol alone ("post-protocol"); post-protocol dissemination combined with both a tailored departmental admissions clerking proforma to prompt for HIV testing & consenting, and regular focussed tutorials to doctors on HIV testing in neurological patients ("post-proforma"); and finally one year after the post-proforma period ("+1 year"). We also looked at the total number of HIV tests sent from the unit during the two-year period. We assessed significance using Fisher's exact test. RESULTS: 47.8% of all acute neurology non-stroke admissions were eligible for HIV testing during all the audit periods. Testing rates were as follows: pre-protocol 21.9%; post-protocol 36.6%; post-proforma 83.3%; and at +1 year 65.4% (p<0.05 for both post-protocol and +1 year when compared to pre-protocol). Documentation of consent for HIV testing improved from 25% to 67.6% with the HIV-tailored clerking proforma. The total number of HIV tests requested from the unit doubled in the post-proforma period compared to pre-protocol (p<0.05). CONCLUSION: In conclusion: the combination of an HIV testing protocol, a tailored departmental clerking proforma and regular focussed teaching to doctors on indications for HIV testing led to a sustained increase in HIV testing uptake in our regional acute neurology admissions unit

Prevalence and risk factors of late presentation for HIV diagnosis and care in a tertiary referral centre in Switzerland.

QUESTIONS UNDER STUDY We sought to identify reasons for late human immunodeficiency virus (HIV) testing or late presentation for care. METHODS A structured chart review was performed to obtain data on test- and health-seeking behaviour of patients presenting late with CD4 cell counts below 350 cells/µl or with acquired immunodeficiency syndrome (AIDS), at the Zurich centre of the Swiss HIV Cohort Study between January 2009 and December 2011. Logistic regression analyses were used to compare demographic characteristics of persons presenting late with not late presenters. RESULTS Of 281 patients, 45% presented late, 48% were chronically HIV-infected non-late presenters, and an additional 7% fulfilled the <350 CD4 cells/µl criterion for late presentation but a chart review revealed that lymphopenia was caused by acute HIV infection. Among the late presenters, 60% were first tested HIV positive in a private practice. More than half of the tests (60%) were suggested by a physician, only 7% following a specific risk situation. The majority (88%) of patients entered medical care within 1 month of testing HIV positive. Risk factors for late presentation were older age (odds ratio [OR] for ≥50 vs <30 years: 3.16, p = 0.017), Asian versus Caucasian ethnicity (OR 3.5, p = 0.021). Compared with men who have sex with men (MSM) without stable partnership, MSM in a stable partnership appeared less likely to present late (OR 0.50, p = 0.034), whereas heterosexual men in a stable partnership had a 2.72-fold increased odds to present late (p = 0.049). CONCLUSIONS The frequency of late testing could be reduced by promoting awareness, particularly among older individuals and heterosexual men in stable partnerships