Effectiveness of a clinical pathway for acute stroke care in a district general hospital: an audit

BACKGROUND: Organised stroke care saves lives and reduces disability. A clinical pathway might be a form of organised stroke care, but the evidence for the effectiveness of this model of care is limited. METHODS: This study was a retrospective audit study of consecutive stroke admissions in the setting of an acute general medical unit in a district general hospital. The case-notes of patients admitted with stroke for a 6-month period before and after introduction of the pathway, were reviewed to determine data on length of stay, outcome, functional status, (Barthel Index, BI and Modified Rankin Scale, MRS), Oxfordshire Community Stroke Project (OCSP) sub-type, use of investigations, specific management issues and secondary prevention strategies. Logistic regression was used to adjust for differences in case-mix. RESULTS: N = 77 (prior to the pathway) and 76 (following the pathway). The median (interquartile range, IQR) age was 78 years (67.75–84.25), 88% were European NZ and 37% were male. The median (IQR) BI at admission for the pre-pathway group was less than the post-pathway group: 6 (0–13.5) vs. 10 (4–15.5), p = 0.018 but other baseline variables were statistically similar. There were no significant differences between any of the outcome or process of care variables, except that echocardiograms were done less frequently after the pathway was introduced. A good outcome (MRS<4) was obtained in 66.2% prior to the pathway and 67.1% after the pathway. In-hospital mortality was 20.8% and 23.1%. However, using logistic regression to adjust for the differences in admission BI, it appeared that admission after the pathway was introduced had a significant negative effect on the probability of good outcome (OR 0.29, 95%CI 0.09-0.99). CONCLUSION: A clinical pathway for acute stroke management appeared to have no benefit for the outcome or processes of care and may even have been associated with worse outcomes. These data support the conclusions of a recent Cochrane review

Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation

Background: Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. Methods: We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. Results: We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470. Conclusions: Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Critical appraisal of the design and reporting of studies of imaging and measurement of carotid stenosis.

BACKGROUND AND PURPOSE: Several hundred studies have been published over the last few years on imaging and measurement of carotid stenosis. Despite all this research, there is still no consensus about how best to image and measure stenosis. One possible explanation for this is that many of the studies have not been large enough or methodologically sound enough to allow useful conclusions to be drawn. We aimed to assess the design and methods of a random sample of published studies of imaging and measurement of carotid stenosis using 9 simple criteria. METHODS: A formal literature search was performed for studies of imaging and measurement of carotid stenosis. Two subsets were randomly selected for detailed assessment: 20 studies published before 1991 and 20 published between 1993 and 1997 (some years after the initial publication of the ECST and NASCET trials). The criteria used to assess the selected studies were as follows: prospective rather than retrospective study design; patient selection based on a consecutive series or a random sample; adequate detail of study population; adequate detail of imaging techniques; inclusion of all investigations, ie, patients with poor-quality imaging were not excluded; blinded assessment of images; adequate detail of derivation of measurement of stenosis from images or data; adequate data on the reproducibility of measurements of stenosis; and study powered according to a sample-size calculation. RESULTS: There were many basic methodological deficiencies in both subsets of studies, with relatively little evidence of improvement with time. For example, only 33% of studies were prospective, only 45% studied a consecutive or random selection of patients, and only 38% reported any data on the reproducibility of measurements. More than half of the studies satisfied &lt; or =4 of the 9 quality criteria. However, there was considerable variation between studies, with 7 studies satisfying &gt; or = 7 criteria and 10 studies satisfying &lt; or =2. No study was based on a sample-size calculation. The number of patients studied was often small, particularly in the more recent studies: median sample size was 100 in the 1970-1990 studies and 58 in the 1993-1997 studies (P&lt;0.0001). CONCLUSIONS: The design and reporting of published studies of imaging and measurement of carotid stenosis are poor and have not improved much in recent years. The majority of published studies are not of a sufficient standard to enable the results to be used to inform clinical practice. The utility of future studies could be improved considerably by better adherence to 9 simple methodological guidelines