539 research outputs found

    Identifying the barriers and enablers for a triage, treatment, and transfer clinical intervention to manage acute stroke patients in the emergency department : A systematic review using the theoretical domains framework (TDF)

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    Background Clinical guidelines recommend that assessment and management of patients with stroke commences early including in emergency departments (ED). To inform the development of an implementation intervention targeted in ED, we conducted a systematic review of qualitative and quantitative studies to identify relevant barriers and enablers to six key clinical behaviours in acute stroke care: appropriate triage, thrombolysis administration, monitoring and management of temperature, blood glucose levels, and of swallowing difficulties and transfer of stroke patients in ED. Methods Studies of any design, conducted in ED, where barriers or enablers based on primary data were identified for one or more of these six clinical behaviours. Major biomedical databases (CINAHL, OVID SP EMBASE, OVID SP MEDLINE) were searched using comprehensive search strategies. The barriers and enablers were categorised using the theoretical domains framework (TDF). The behaviour change technique (BCT) that best aligned to the strategy each enabler represented was selected for each of the reported enablers using a standard taxonomy. Results Five qualitative studies and four surveys out of the 44 studies identified met the selection criteria. The majority of barriers reported corresponded with the TDF domains of “environmental, context and resources” (such as stressful working conditions or lack of resources) and “knowledge” (such as lack of guideline awareness or familiarity). The majority of enablers corresponded with the domains of “knowledge” (such as education for physicians on the calculated risk of haemorrhage following intravenous thrombolysis [tPA]) and “skills” (such as providing opportunity to treat stroke cases of varying complexity). The total number of BCTs assigned was 18. The BCTs most frequently assigned to the reported enablers were “focus on past success” and “information about health consequences.” Conclusions Barriers and enablers for the delivery of key evidence-based protocols in an emergency setting have been identified and interpreted within a relevant theoretical framework. This new knowledge has since been used to select specific BCTs to implement evidence-based care in an ED setting. It is recommended that findings from similar future reviews adopt a similar theoretical approach. In particular, the use of existing matrices to assist the selection of relevant BCTs

    The interaction between policy and education using stroke as an example

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    This paper discusses the interaction between healthcare policy at the European, UK and Scottish levels and the funding of education that underpins specific health policy priorities. Stroke is used throughout to illustrate the relationship between a designated European and UK health priority and the translation of that priority into clinical delivery. The necessity to build a responsive and sustainable culture to address the healthcare education that underpins changing healthcare policies is emphasized

    The prevalence of premenstrual dysphoric disorder: systematic review and meta-analysis

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    Background: Premenstrual dysphoric disorder is characterised by symptoms confined to the premenstrual phase of the menstrual cycle. Confirmed diagnosis requires prospective monitoring of symptoms over two cycles, otherwise the diagnosis is provisional. We aimed to measure the point prevalence of premenstrual dysphoric disorder. Methods: We searched for studies of prevalence using MEDLINE, EMBASE, PsycINFO and PubMed. For each study, the total sample size and number of cases were extracted. The prevalence across studies was calculated using random effects meta-analysis with a generalised linear mixed model. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses. Pre-registration was with PROSPERO (CRD42021249249). Results: 44 studies with 48 independent samples met inclusion criteria, consisting of 50,659 participants. The pooled prevalence was 3.2 % (95 % confidence intervals: 1.7 %–5.9 %) for confirmed and 7.7 % (95 % confidence intervals: 5.3 %–11.0 %) for provisional diagnosis. There was high heterogeneity across all studies (I2 = 99 %). Sources of heterogeneity identified by meta-regression were continent of sample (p < 0.0001), type of sample (community-based, university, high school) (p = 0.007), risk of bias (p = 0.009), and method of diagnosis (p = 0.017). Restricting the analysis to community-based samples using confirmed diagnosis resulted in a prevalence of 1.6 % (95 % confidence intervals: 1.0 %–2.5 %), with low heterogeneity (I2 = 26 %). Limitations: A small number of included studies used full DSM criteria in community settings. Conclusions: The point prevalence of premenstrual dysphoric disorder using confirmed diagnosis is lower compared with provisional diagnosis. Studies relying on provisional diagnosis are likely to produce artificially high prevalence rates

    Age of red blood cells and mortality in the critically ill

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    INTRODUCTION: In critically ill patients, it is uncertain whether exposure to older red blood cells (RBCs) may contribute to mortality. We therefore aimed to evaluate the association between the age of RBCs and outcome in a large unselected cohort of critically ill patients in Australia and New Zealand. We hypothesized that exposure to even a single unit of older RBCs may be associated with an increased risk of death. METHODS: We conducted a prospective, multicenter observational study in 47 ICUs during a 5-week period between August 2008 and September 2008. We included 757 critically ill adult patients receiving at least one unit of RBCs. To test our hypothesis we compared hospital mortality according to quartiles of exposure to maximum age of RBCs without and with adjustment for possible confounding factors. RESULTS: Compared with other quartiles (mean maximum red cell age 22.7 days; mortality 121/568 (21.3%)), patients treated with exposure to the lowest quartile of oldest RBCs (mean maximum red cell age 7.7 days; hospital mortality 25/189 (13.2%)) had an unadjusted absolute risk reduction in hospital mortality of 8.1% (95% confidence interval = 2.2 to 14.0%). After adjustment for Acute Physiology and Chronic Health Evaluation III score, other blood component transfusions, number of RBC transfusions, pretransfusion hemoglobin concentration, and cardiac surgery, the odds ratio for hospital mortality for patients exposed to the older three quartiles compared with the lowest quartile was 2.01 (95% confidence interval = 1.07 to 3.77). CONCLUSIONS: In critically ill patients, in Australia and New Zealand, exposure to older RBCs is independently associated with an increased risk of death

    Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages

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    RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line, in which the CD68 promoter ensures macrophage specific expression of human Mcl-1 (CD68.hMcl-1), was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AM had elevated levels of Mcl-1, an anti-apoptotic Bcl-2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AM phenocopied the microbicidal defect since transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (MDM) generated mitochondrial reactive oxygen species (mROS) in response to pneumococci, which co-localized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected BMDM but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AM also increased basal mROS expression, but failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS /superoxide dismutase 2. CONCLUSIONS: Upregulation of Mcl-1 and chronic adaption to oxidative stress alters mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD

    Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease

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    BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune disease. However, nothing is currently known about the potential role of aberrant DNA methylation in JIA. As a first step to addressing this knowledge gap, we have profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls. Genomic DNA was isolated from peripheral blood CD4+ T cells from 14 oligoarticular and polyarticular JIA cases with active disease, and healthy age- and sex-matched controls. Genome-scale methylation analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at &gt;25,000 CpGs was compared in a case-control study design. RESULTS: Methylation levels were significantly different (FDR adjusted p&lt;0.1) at 145 loci. Removal of four samples exposed to methotrexate had a striking impact on the outcome of the analysis, reducing the number of differentially methylated loci to 11. The methotrexate-naive analysis identified reduced methylation at the gene encoding the pro-inflammatory cytokine IL32, which was subsequently replicated using a second analysis platform and a second set of case-control pairs. CONCLUSIONS: Our data suggests that differential T cell DNA methylation may be a feature of JIA, and that reduced methylation at IL32 is associated with this disease. Further work in larger prospective and longitudinal sample collections is required to confirm these findings, assess whether the identified differences are causal or consequential of disease, and further investigate the epigenetic modifying properties of therapeutic regimens
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