Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review

Background: Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. Methods: We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. Results: The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Conclusion: Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation

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

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

The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The ApcMin/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the ApcMin/+ mouse is not known. Cachexia progression was studied in ApcMin/+ mice that were either weight stable (WS) or had initial (≤5%), intermediate (6–19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process

Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia can findings from animal models be translated to humans?

Background: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. Discussion: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. Summary: More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future

Geological observations in the southern West Greenland basement from Ameralik to Frederikshåb Isblink in 2008

In 2008, the Geological Survey of Denmark and Greenland began a project in collaboration with the Bureau of Minerals and Petroleum of Greenland with the aim to publish a web-based, seamless digital map of the Precambrian bedrock between 61°30´ and 64°N in southern West Greenland. Such a map will be helpful for the mineral exploration industry and for basic research. Producing an updated digital map requires additional field work revisiting key localities to collect samples for geochemistry, geochronology and metamorphic petrology. The new data will help us to test and refine existing models and improve general understanding of the geological evolution of the area. Here we summarise some results from the 2008 field activities between Ame - ralik in the north and Frederikshåb Isblink in the south (Fig. 1). The area was mapped in the 1960s and 1970s, and although the 1:100 000-scale maps are of excellent quality, they do not include more recent developments in geochronology, thermobarometry and geochemistry. A notable exception is the Fiskenæsset complex (Fig. 1), which has received considerable attention after it was first mapped (Ellitsgaard-Rasmussen & Mouritzen 1954; Windley et al. 1973; Windley & Smith, 1974; Myers 1985). New tectonic models have been developed since the original 1:100 000 maps were produced, and the tectonic evolution has been com - monly ex plained in terms of terrane accretion (Friend et al. 1996)

Effect of Ischaemia-Reperfusion on Rabbit Kidney and Human Brain

Free radicals are produced in various organs at ischaemia-reperfusion. The final stage in radical damage is lipid peroxidation. We have demonstrated previously that a lipid-soluble antioxidant improves restoration of bioenergetics in rabbit kidneys after ischaemia, as reflected in 31P spectrometry. Radical production in the brain during surgery for carotid artery stenosis can be measured using an ex vivo spin trap method. Aims of the present study: 1. To examine whether pretreatment with a combination of a lipidsoluble and a water-soluble antioxidant causes improved restoration of bioenergetics in rabbit kidneys after ischaemia compared to single treatment with a lipid soluble antioxidant. 2. To examine whether pretreatment with allopurinol or acetylcysteine influences radical production in conjunction with surgery for carotid artery stenosis. 3. To study the relationship between various markers for arteriosclerosis and the production of free radicals in conjunction with surgery for carotid artery stenosis. Methods: New Zealand white rabbits were used for the NMR experiments. Volume-selective 31P spectrometry was used to determine changes in bioenergetics during and after ischaemia following various pretreatments. An ex vivo spin trap method was used to measure radical production in the brain during carotid endarterectomy in control patients as well as patients pretreated with allopurinol or acetylcysteine. ICAM-1, MCP-9, MMP-1 and oxLDL serum levels were determined in the control patients. Results: Pretreatment with a combination of a lipid-soluble and a water-soluble antioxidant resulted in improved restoration in cell bioenergetics after ischaemia compared to single treatment with a lipid-soluble antioxidant. Production of radicals can be measured reproducibly using the ex vivo spin trap method. Pretreatment with allopurinol eliminated the strong correlation between e.g. degree of stenosis and leucocyte counts and radical production, which might indicate a beneficial effect of pretreatment with a xanthine oxidase inhibitor. Pretreatment with acetylcysteine on the other hand appeared to increase radical production. High levels of MMP-1 and low levels of ICAM-1 were associated with high radical production. Conclusion: A combination of a lipid-soluble and a water-soluble antioxidant is most effective in improving cell bioenergetics after ischaemia in rabbit kidneys. Allopurinol appears to have a beneficial effect in conjunction with carotid endarterectomy while acetylcysteine appears to increase radical production. MMP-1 is associated with increased radical production