Factors associated with time delay to carotid stenting in patients with a symptomatic carotid artery stenosis

Treatment of a symptomatic stenosis is known to be most beneficial within 14 days after the presenting event but this can frequently not be achieved in daily practice. The aim of this study was the assessment of factors responsible for this time delay to treatment. A retrospective analysis of a prospective two-center CAS database was carried out to investigate the potential factors that influence a delayed CAS treatment. Of 374 patients with a symptomatic carotid stenosis, 59.1% were treated beyond ≥14 days. A retinal TIA event (OR = 3.59, 95% CI 1.47–8.74, p < 0.01) was found to be a predictor for a delayed treatment, whereas the year of the intervention (OR = 0.32, 95% CI 0.20–0.50, p < 0.01) and a contralateral carotid occlusion (OR = 0.42, 95% CI 0.21–0.86, p = 0.02) were predictive of an early treatment. Similarly, within the subgroup of patients with transient symptoms, the year of the intervention (OR = 0.28, 95% CI 0.14–0.59, p < 0.01) was associated with an early treatment, whereas a retinal TIA as the qualifying event (OR = 6.96, 95% CI 2.37–20.47, p < 0.01) was associated with a delayed treatment. Treatment delay was most pronounced in patients with an amaurosis fugax, whereas a contralateral carotid occlusion led to an early intervention. Although CAS is increasingly performed faster in the last years, there is still scope for an even more accelerated treatment strategy, which might prevent future recurrent strokes prior to treatment

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

An exploratory study to assess the activity of the acarine growth inhibitor, fluazuron, against Sarcoptes scabei infestation in pigs

Background: The most common treatments for scabies in human and veterinary settings are topical 5% permethrin or systemic treatment with ivermectin. However, these treatments have very little activity against arthropod eggs, and therefore repeated treatment is frequently required. In-vitro, biochemical and molecular studies have demonstrated that human mites are becoming increasingly resistant to both acaricides. To identify alternate acaricides, we undertook a pilot study of the in vivo activity of the benzoylphenyl urea inhibitor of chitin synthesis, fluazuron, in pigs with sarcoptic mange. Findings. Pigs (n = 5) were infested with S. scabei var suis, and randomised to treatment at the start of peak infestation with fluazuron at a dose of 10 mg/kg/day per os for 7 days (n = 3) or no treatment (n = 2). Clinical scores, skin scrapings for mite counts and blood sampling for pharmacokinetic analysis were undertaken. Fluazuron was well absorbed in treated pigs with measureable blood levels up to 4 weeks post treatment. No adverse effects were observed. Modest acaricidal activity of the compound was observed, with a reduction in severity of skin lesions in treated pigs, as well as a reduction in number of scabies mite's early life stages. Conclusions: The moderate efficacy of fluazuron against scabies mites indicates a lead to the development of alternate treatments for scabies, such as combination therapies that maybe applicable for human use in the future

Patients' age as a determinant of care received following acute stroke: A systematic review

<p>Abstract</p> <p>Background</p> <p>Evidence-based care should improve acute stroke outcomes with the same magnitude of effect for stroke patients of all ages. However, there is evidence to suggest that, in some instances, older stroke patients may receive poorer quality care than younger patients.</p> <p>Our aim was to systematically review evidence of the quality of care provided to patients with acute stroke related to their age. Quality of care was determined by compliance with recommended care processes.</p> <p>Methods</p> <p>We systematically searched MEDLINE, CINAHL, ISI Web of Knowledge, Ageline and the Cochrane Library databases to identify publications (1995-2009) that reported data on acute stroke care process indicators by patient age. Data extracted included patient demographics and process indicator compliance. Included publications were critically appraised by two independent reviewers using the Critical Appraisal Skills Programme tool, and a comparison was made of the risk of bias according to studies' findings. The evidence base for reported process indicators was determined, and meta-analysis was undertaken for studies with sufficient similarity.</p> <p>Results</p> <p>Nine from 163 potential studies met the inclusion criteria. Of the 56 process indicators reported, eleven indicators were evidence-based. Seven of these indicators (64%) showed significantly poorer care for older patients compared to younger ones, while younger patients received comparatively inferior care for only antihypertensive therapy at discharge. Our findings are limited by the variable methodological quality of included studies.</p> <p>Conclusion</p> <p>Patients' age may be a factor in the care they receive after an acute stroke. However, the possible influence of patients' age on clinicians' decision-making must be considered in terms of the many complex issues that surround the provision of optimal care for older patients with acute stroke.</p

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Cumulative subgroup analysis to reduce waste in clinical research for individualised medicine

Background: Although subgroup analyses in clinical trials may provide evidence for individualised medicine, their conduct and interpretation remain controversial. Methods: Subgroup effect can be defined as the difference in treatment effect across patient subgroups. Cumulative subgroup analysis refers to a series of repeated pooling of subgroup effects after adding data from each of related trials chronologically, to investigate the accumulating evidence for subgroup effects. We illustrated the clinical relevance of cumulative subgroup analysis in two case studies using data from published individual patient data (IPD) meta-analyses. Computer simulations were also conducted to examine the statistical properties of cumulative subgroup analysis. Results: In case study 1, an IPD meta-analysis of 10 randomised trials (RCTs) on beta blockers for heart failure reported significant interaction of treatment effects with baseline rhythm. Cumulative subgroup analysis could have detected the subgroup effect 15 years earlier, with five fewer trials and 71% less patients, than the IPD meta-analysis which first reported it. Case study 2 involved an IPD meta-analysis of 11 RCTs on treatments for pulmonary arterial hypertension that reported significant subgroup effect by aetiology. Cumulative subgroup analysis could have detected the subgroup effect 6 years earlier, with three fewer trials and 40% less patients than the IPD meta-analysis. Computer simulations have indicated that cumulative subgroup analysis increases the statistical power and is not associated with inflated false positives. Conclusions: To reduce waste of research data, subgroup analyses in clinical trials should be more widely conducted and adequately reported so that cumulative subgroup analyses could be timely performed to inform clinical practice and further research

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease

Long-term prognosis of symptomatic isolated middle cerebral artery disease in Korean stroke patients

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the long-term mortality and recurrence rate of stroke in first-time stroke patients with symptomatic isolated middle cerebral artery disease (MCAD) under medical management.</p> <p>Methods</p> <p>We identified 141 first ever stroke patients (mean age, 64.4 ± 12.5 years; 53% male) with symptomatic isolated MCAD. MCAD was defined as significant stenosis of more than 50% or occlusion of the MCA as revealed by MR angiography. The median follow-up was 27.7 months. We determined a cumulative rate of stroke recurrence and mortality by Kaplan-Meier survival analyses and sought predictors using the Cox proportional hazard model.</p> <p>Results</p> <p>The cumulative composite outcome rate (stroke recurrence or any-cause death) was 14%, 19%, 22%, and 28% at years 1, 2, 3, and 5, respectively. The annual recurrence rate of stroke was 4.1%. The presence of diabetes mellitus was the only significant independent predictor of stroke recurrence or any cause of death in multivariate analyses of Cox proportional hazard model adjusted for any plausible potential confounding factors.</p> <p>Conclusions</p> <p>We estimated the long-term prognosis of stroke patients with isolated symptomatic MCAD under current medical management in Korea. Diabetes mellitus was found to be a significant predictor for stroke recurrence and mortality.</p

Systematic review of factors influencing patient and practitioner delay in diagnosis of upper gastrointestinal cancer

As knowledge on the causation of cancers advances and new treatments are developed, early recognition and accurate diagnosis becomes increasingly important. This review focused on identifying factors influencing patient and primary care practitioner delay for upper gastrointestinal cancer. A systematic methodology was applied, including extensive searches of the literature published from 1970 to 2003, systematic data extraction, quality assessment and narrative data synthesis. Included studies were those evaluating factors associated with the time interval between a patient first noticing a cancer symptom and presenting to primary care, between a patient first presenting to primary care and being referred to secondary care, or describing an intervention designed to reduce those intervals. Twenty-five studies were included in the review. Studies reporting delay intervals demonstrated that the patient phase of delay was greater than the practitioner phase, whilst patient-related research suggests that recognition of symptom seriousness is more important than recognition of the presence of the symptom. The main factors related to practitioner delay were misdiagnosis, application and interpretation of tests, and the confounding effect of existing disease. Greater understanding of patient factors is required, along with evaluation of interventions to ensure appropriate diagnosis, examination and investigation