Videomicroscopy as a tool for investigation of the microcirculation in the newborn

The perinatal period remains a time of significant risk of death or disability. Increasing evidence suggests that this depends on microcirculatory behavior. Sidestream dark-field orthogonal polarized light videomicroscopy (OPS) has emerged as a useful assessment of adult microcirculation but the values derived are not delineated for the newborn. We aimed to define these parameters in well term newborn infants. Demographic details were collected prospectively on 42 healthy term neonates (n = 20 females, n = 22 males). OPS videomicroscopy (Microscan) was used to view ear conch skin microcirculation at 6, 24, and 72 h of age. Stored video was analyzed by a masked observer using proprietary software. There were no significant differences between the sexes for any structural parameters at any time point. There was a significant increase over time in small vessel perfusion in female infants only (P = 0.009). A number of 6- and 72-h measurements were significantly correlated, but differed from the 24-h values. These observations confirm the utility of the ear conch for neonatal microvascular videomicroscopy. They provide a baseline for studies into the use of OPS videomicroscopy in infants. The changes observed are comparable with previous studies of term infants using these and other microvascular techniques. It is recommended that studies for examining the mature neonatal microvascular structure be delayed until 72 h of life, but studies of the physiology of cardiovascular transition should include the 24-h time point after delivery

How can we improve stroke thrombolysis rates? : a review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care

Background: Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke. Methods: Published original English-language research from four electronic databases spanning 1997-2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted. Results: Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio=2.1, p=0.05). Conclusions: In order to improve IV tPA rates in acute stroke care, specific health system factors need to be targeted. Multi-component quality improvement approaches can improve IV tPA rates for stroke, although more thoughtfully designed and well-reported trials are required to safely increase rates of IV tPA to eligible stroke patients

Can a multicomponent multidisciplinary implementation package change physicians' and nurses' perceptions and practices regarding thrombolysis for acute ischemic stroke? : an exploratory analysis of a cluster-randomized trial

Background: The Thrombolysis ImPlementation in Stroke (TIPS) trial tested the effect of a multicomponent, multidisciplinary, collaborative intervention designed to increase the rates of intravenous thrombolysis via a cluster randomized controlled trial at 20 Australian hospitals (ten intervention, ten control). This sub-study investigated changes in self-reported perceptions and practices of physicians and nurses working in acute stroke care at the participating hospitals. Methods: A survey with 74 statements was administered during the pre-and post-intervention periods to staff at 19 of the 20 hospitals. An exploratory factor analysis identified the structure of the survey items and linear mixed modeling was applied to the final survey domain scores to explore the differences between groups over time. Result: The response rate was 45% for both the pre-(503 out of 1127 eligible staff from 19 hospitals) and post-intervention (414 out of 919 eligible staff from 18 hospitals) period. Four survey domains were identified: (1) hospital performance indicators, feedback, and training; (2) personal perceptions about thrombolysis evidence and implementation; (3) personal stroke skills and hospital stroke care policies; and (4) emergency and ambulance procedures. There was a significant pre-to post-intervention mean increase (0.21 95% CI 0.09; 0.34; p < 0.01) in scores relating to hospital performance indicators, feedback, and training; for the intervention hospitals compared to control hospitals. There was a corresponding increase in mean scores regarding perceptions about the thrombolysis evidence and implementation (0.21, 95% CI 0.06; 0.36; p < 0.05). Sub-group analysis indicated that the improvements were restricted to nurses' responses. Conclusion: TIPS resulted in changes in some aspects of nurses' perceptions relating to the evidence for intravenous thrombolysis and its implementation and hospital performance indicators, feedback, and training. However, there is a need to explore further strategies for influencing the views of physicians given limited statistical power in the physician sample

Thrombolysis implementation intervention and clinical outcome : a secondary analysis of a cluster randomized trial

Background: Multiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the "Thrombolysis ImPlementation in Stroke (TIPS)"study, which aimed to improve rates of intravenous thrombolysis in Australia. Methods: A posthoc analysis was conducted using individual-level patient data. Excellent (Three-month post treatment modified Rankin Score 0-2) and poor clinical outcome (Three-month post treatment modified Rankin Score 5-6) and post treatment parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups. Results: There was a non-significant higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73-3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73-2.44) during the active-And post-intervention period respectively, for the intervention compared to the control group. A non-significant lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56-2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61-3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active-(odds ratio: 0.53; 95% CI: 0.21-1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36-2.52). Conclusion: The TIPS multi-component implementation approach was not effective in reducing the odds of post-Treatment severe disability at 90 days, or post-thrombolysis hemorrhage

Seasonal variation in cervical artery dissection in the Hunter New England region, New South Wales, Australia: a retrospective cohort study

Background: Cervical artery dissection (CAD) is a leading cause of ischemic stroke among middle aged adults, yet the aetiology remains poorly understood. There are reports from colder northern hemisphere sites of a seasonal pattern in the incidence of CAD. Seasonality may suggest some transient putative pro-inflammatory mechanism but it is unknown whether this also exists in temperate climates

Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care

BACKGROUND Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke. OBJECTIVES To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months. METHODS AND DESIGN A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mRS <2) and the proportion with intracranial haemorrhage (mRS ≥2), compared to international benchmarks. DISCUSSION TIPS will trial a comprehensive, multi-component and multidisciplinary collaborative approach to improving thrombolysis rates at multiple sites. The trial has the potential to identify methods for optimal care which can be implemented for stroke patients during the acute phase. Study findings will include barriers and solutions to effective thrombolysis implementation and trial outcomes will be published whether significant or not. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry: ACTRN12613000939796

Cocaine- and Amphetamine-Regulated Transcript (CART) Signaling within the Paraventricular Thalamus Modulates Cocaine-Seeking Behaviour

Background: Cocaine- and amphetamine-regulated transcript (CART) has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the site(s) of action remains unclear. We investigated the paraventricular thalamus (PVT) as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). Methodology/Principal Findings: Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin (TTX; 2.5 ng), CART (0.625 µg or 2.5 µg) or no injection, followed by a cocaine prime (10 mg/kg, i.p.). Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls. Conclusions/Significance: We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking

Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care

BACKGROUND: Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke. OBJECTIVES: To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months. METHODS AND DESIGN: A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mRS <2) and the proportion with intracranial haemorrhage (mRS ≥2), compared to international benchmarks. DISCUSSION: TIPS will trial a comprehensive, multi-component and multidisciplinary collaborative approach to improving thrombolysis rates at multiple sites. The trial has the potential to identify methods for optimal care which can be implemented for stroke patients during the acute phase. Study findings will include barriers and solutions to effective thrombolysis implementation and trial outcomes will be published whether significant or not. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN1261300093979

Contemporary prognosis of transient ischemic attack patients:a systematic review and meta-analysis

Background: Transient ischemic attacks are common and place patients at risk of subsequent stroke. The 2007 EXPRESS and SOS-TIA studies demonstrated the efficacy of rapid treatment initiation. We hypothesized that with these findings having informed subsequent transient ischemic attacks management protocols, transient ischemic attacks prognosis in contemporary (2008 and later) patient cohorts would be more favorable than in historical cohorts. Methods: A systematic review and meta-analysis of cohort studies and randomized control trial placebo-arms of transient ischemic attack (published 2008–2015). The primary outcome was stroke. Secondary outcomes were mortality, transient ischemic attack, and myocardial infarction. Studies were excluded if the outcome of transient ischemic attack patients was not reported separately. The systematic review included all studies of transient ischemic attack. The meta-analysis excluded studies of restricted transient ischemic attack patient types (e.g. only patients with atrial fibrillation). The pooled cumulative risks of stroke recurrence were estimated from study-specific estimates at 2, 7, 30, and 90 days post-transient ischemic attack, using a multivariate Bayesian model. Results: We included 47 studies in the systematic review and 40 studies in the meta-analysis. In the systematic review (191,202 patients), stroke at 2 days was reported in 13/47 (27.7%) of studies, at 7 days in 20/47 (42.6%), at 30 days in 12/47 (25.5%), and at 90 days in 33/47 (70.2%). Studies included in the meta-analysis recruited 68,563 patients. The cumulative risk of stroke was 1.2% (95% credible interval (CI) 0.6–2.2), 3.4% (95% CI 2.0–5.5), 5.0% (95% CI 2.9–8.9), and 7.4% (95% CI 4.3–12.4) at 2, 7, 30, and 90 days post-transient ischemic attack, respectively. Conclusion: In contemporary settings, transient ischemic attack prognosis is more favorable than reported in historical cohorts where a meta-analysis suggests stroke risk of 3.1% at two days

Door-to-needle time for thrombolysis : a secondary analysis of the TIPS cluster randomised controlled trial

Objective: The current study aimed to evaluate the effects of a multi-component in-hospital intervention on the door-to-needle time for intravenous thrombolysis in acute ischaemic stroke. Design: This study was a post hoc analysis of door-to-needle time data from a cluster-randomised controlled trial testing an intervention to boost intravenous thrombolysis implementation. Setting: The study was conducted among 20 hospitals from three Australian states. Participant: Eligible hospitals had a Stroke Care Unit or staffing equivalent to a stroke physician and a nurse, and were in the early stages of implementing thrombolysis. Intervention: The intervention was multifaceted and developed using the behaviour change wheel and informed by breakthrough collaborative methodology using components of the health behaviour change wheel. Primary and secondary outcome measures: The primary outcome for this analysis was door-to-needle time for thrombolysis and secondary outcome was the proportion of patients received thrombolysis within 60 min of hospital arrival. Results: The intervention versus control difference in the door-to-needle times was non-significant overall nor significant by hospital classification. To provide additional context for the findings, we also evaluated the results within intervention and control hospitals. During the active-intervention period, the intervention hospitals showed a significant decrease in the door-to-needle time of 9.25 min (95% CI: -16.93 to 1.57), but during the post-intervention period, the result was not significant. During the active intervention period, control hospitals also showed a significant decrease in the door-to-needle time of 5.26 min (95% CI: -8.37 to -2.14) and during the post-intervention period, this trend continued with a decrease of 12.13 min (95% CI: -17.44 to 6.81). Conclusion: Across these primary stroke care centres in Australia, a secular trend towards shorter door-to-needle times across both intervention and control hospitals was evident, however the TIPS (Thrombolysis ImPlementation in Stroke) intervention showed no overall effect on door-to-needle times in the randomised comparison