169 research outputs found

    Prehospital critical care for out-of-hospital cardiac arrest: An observational study examining survival and a stakeholder-focused cost analysis

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    © 2016 The Author(s). Background: Survival rates from out-of-hospital cardiac arrest (OHCA) remain low, despite remarkable efforts to improve care. A number of ambulance services in the United Kingdom (UK) have developed prehospital critical care teams (CCTs) which attend critically ill patients, including OHCA. However, current scientific evidence describing CCTs attending OHCA is sparse and research to date has not demonstrated clear benefits from this model of care. Methods: This prospective, observational study will describe the effect of CCTs on survival from OHCA, when compared to advanced-life-support (ALS), the current standard of prehospital care in the UK. In addition, we will describe the association between individual critical care interventions and survival, and also the costs of CCTs for OHCA. To examine the effect of CCTs on survival from OHCA, we will use routine Utstein variables data already collected in a number of UK ambulance trusts. We will use propensity score matching to adjust for imbalances between the CCT and ALS groups. The primary outcome will be survival to hospital discharge, with the secondary outcome of survival to hospital admission. We will record the critical care interventions delivered during CCT attendance at OHCA. We will describe frequencies and aim to use multiple logistic regression to examine possible associations with survival. Finally, we will undertake a stakeholder-focused cost analysis of CCTs for OHCA. This will utilise a previously published Emergency Medical Services (EMS) cost analysis toolkit and will take into account the costs incurred from use of a helicopter and the proportion of these costs currently covered by charities in the UK. Discussion: Prehospital critical care for OHCA is not universally available in many EMS. In the UK, it is variable and largely funded through public donations to charities. If this study demonstrates benefit from CCTs at an acceptable cost to the public or EMS commissioners, it will provide a rationale to increase funding and service provision. If no clinical benefit is found, the public and charities providing these services can consider concentrating their efforts on other areas of prehospital care. Trial registration: ISRCTN registry ID ISRCTN18375201

    Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

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    Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required

    How does study quality affect the results of a diagnostic meta-analysis?

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    Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

    Influence of social support on cognitive function in the elderly

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    BACKGROUND: Social support is important in daily activities of the elderly. This study tests the hypothesis that there is an association between social support and cognitive function among the elderly in a community setting. METHODS: Face-to-face interviews were conducted in a cross-sectional stratified random sample of 4,993 elderly (≥65 years) city residents. Using multiple regression analysis, we investigated the influence of social support on cognitive function. RESULTS: 12% were over 80 years old. 53.28% were men. 67.14% were married. Higher Short Portable Mental Status Questionnaire (SPMSQ) scores (higher score means better cognitive function) were associated with strong social support, as measured by marital status and perceived positive support from friends. Lower cognitive function was associated with older and with female respondents. Only instrumental activities of daily living (IADL) were statistically and negatively related to SPMSQ. Lower functional status was associated with lower cognitive function. Elders with grade school educations had lower SPMSQ scores than did elders with high school educations. CONCLUSIONS: In Taiwan, higher cognitive function in community-living elderly was associated with increased social support. Life-style management should provide social activities for the elderly to promote a better quality of life

    Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium

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    β-Amyloid (Aβ) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as ι and α synuclein related lesions, also Aβ related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of Aβ, i.e. phase 1 = deposition of Aβ exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of Aβ phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of Aβ-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer’s disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the Aβ phase in AD is feasible even in large scale retrospective studies

    Whole blood lead levels are associated with radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis in the Johnston County Osteoarthritis Project

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    Abstract Introduction Lead (Pb) is known to affect bone, and recent evidence suggests that it has effects on cartilage as well. As osteoarthritis (OA) is a highly prevalent disease affecting bone and cartilage, we undertook the present analysis to determine whether whole blood Pb levels are associated with radiographic and symptomatic OA (rOA and sxOA, respectively) of the knee. Methods The analysis was conducted using cross-sectional data from the Johnston County Osteoarthritis Project, a rural, population-based study, including whole blood Pb levels, bilateral posteroanterior weight-bearing knee radiography and knee symptom data. rOA assessment included joint-based presence (Kellgren-Lawrence (K-L) grade 2 or higher) and severity (none, K-L grade 0 or 1; mild, K-L grade 2; moderate or severe, K-L grade 3 or 4), as well as person-based laterality (unilateral or bilateral). SxOA was deemed present (joint-based) in a knee on the basis of K-L grade 2 or higher with symptoms, with symptoms rated based on severity (0, rOA without symptoms; 1, rOA with mild symptoms; 2, rOA with moderate or severe symptoms) and in person-based analyses was either unilateral or bilateral. Generalized logit or proportional odds regression models were used to examine associations between the knee OA status variables and natural log-transformed blood Pb (ln Pb), continuously and in quartiles, controlling for age, race, sex, body mass index (BMI), smoking and alcohol drinking. Results Those individuals with whole blood Pb data (N = 1,669) had a mean (±SD) age of 65.4 (±11.0) years and a mean BMI of 31.2 (±7.1) kg/m2, including 66.6% women and 35.4% African-Americans, with a median blood Pb level of 1.8 μg/dl (range, 0.3 to 42.0 μg/dl). In joint-based analyses, for every 1-U increase in ln Pb, the odds of prevalent knee rOA were 20% higher (aOR, 1.20; 95% CI, 1.01 to 1.44), while the odds of more severe rOA were 26% higher (aOR, 1.26; 95% CI, 1.05 to 1.50, under proportional odds). In person-based analyses, the odds of bilateral rOA were 32% higher for each 1-U increase in ln Pb (aOR, 1.32; 95% CI, 1.03 to 1.70). Similarly for knee sxOA, for each 1-U increase in ln Pb, the odds of having sxOA were 16% higher, the odds of having more severe symptoms were 17% higher and the odds of having bilateral knee symptoms were 25% higher. Similar findings were obtained with regard to ln Pb in quartiles. Conclusions Increases in the prevalence and severity measures for both radiographically and symptomatically confirmed knee OA (although statistically significant only for rOA) were observed with increasing levels of blood Pb, suggesting that Pb may be a potentially modifiable environmental risk factor for OA

    Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

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    Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2–5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis

    Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS

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    Protein network analysis reveals selectively vulnerable regions and biological processes in FTD

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    CXCR4 involvement in neurodegenerative diseases

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