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    ABSTRACT: Introduction: The two-week wait (2WW) referral guideline for suspected central nervous system (CNS) tumours was implemented more than a decade ago to facilitate early cancer diagnosis with the aim of improving tumour survival rates. Short-term studies have shown poor compliance and low detection rates of the guideline. This study aimed to provide a decade analysis of referral patterns, and compliance and detection rates of the guideline. Methods: All patients referred via the 2WW pathway for suspected CNS tumour to the Newcastle Department of Neurosurgery from 1st January 2002 to 31st December 2011 were retrospectively identified from the local cancer registry. Data from referral letters, case notes, radiographic images and final outcomes were recorded. Trends in waiting time, time to diagnosis, compliance and detection rate of the guideline in identifying CNS tumours were analysed. Results: Over the last decade, there were no significant changes in trends in waiting time, time to diagnosis and compliance and detection rates of the guideline. Of 85 2WW referrals, 41.2% were non-compliant and 21.2% identified CNS tumours. The detection rate was higher in referrals that complied with the guideline compared to those that did not (32.0% vs 5.2%, p < 0.05). The non-compliant referrals which identified CNS tumours consisted of patients with cognitive decline. The guideline sensitivity and specificity were 88.8% (63.9%-98.1%, 95% CI) and 49.3% (40.0%-61.6%), respectively. Most of CNS tumour diagnoses were made independent of the 2WW pathway (N = 1093, 98.4%). Conclusion: There have not been any major changes in terms of waiting time, time to diagnosis, compliance and detection rates of the 2WW guideline during the last decade. The 2WW pathway generated very few referrals but among these, the positive detection rate was high and the addition of time-based cognitive decline onto the current guideline may further improve the detection rate.
    Full-text · Article · Mar 2013 · British Journal of Neurosurgery
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    ABSTRACT: Aims Previous genome-wide linkage analysis has suggested that chromosomal region 17p13.3 may harbour genes influencing left ventricular mass (LVM) in man. To date, the genetic factors accounting for LVM variability remain largely unknown but a non-coding RNA gene within this region, micro-RNA 22 (miR-22), has been implicated in cardiac hypertrophy and heart failure in animal models. We thus investigated the relationship between common genetic polymorphisms surrounding miR-22 and left ventricular mass in a family-based association study. Methods and Results We studied a cohort of 255 families comprising 1,425 individuals ascertained via a hypertensive proband. Ten single nucleotide polymorphisms which together tagged common genetic variation surrounding the miR-22 gene were genotyped. There was evidence of association between the rs7223247 polymorphism, which lies within the 3′UTR of a gene of unknown function, TLCD2, immediately downstream from miR-22, and left ventricular mass determined by Sokolow-Lyon voltage (Bonferroni corrected p-value = 0.038). The T allele at rs7223247 was associated with an 0.272 standard deviation higher Sokolow-Lyon voltage. Genotype was responsible for ∼1% of the population variability in LVM. Conclusions Genotype at the rs7223247 polymorphism affects left ventricular mass determined by Sokolow-Lyon voltage. The neighbouring genes miR-22 and TLCD2 are strong candidates to account for this observation.
    Full-text · Article · Jan 2013 · PLoS ONE
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    ABSTRACT: BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common and many affected individuals have normal-range alanine aminotransferase (ALT) levels. There is a need for a robust screening tool to triage individuals with advanced fibrosis for specialist care. AIM: The aim of this study was to assess the performance of noninvasive fibrosis tests in patients with biopsy-proven NAFLD and normal levels of ALT. METHODS: Patients presenting at a fatty liver clinic between 1999 and 2009 were included in the study. Liver biopsies were assessed using the Kleiner score. The aspartate aminotransferase (AST)/ALT ratio, BARD, FIB-4 and NAFLD fibrosis scores were calculated. RESULTS: A total of 305 patients were included [70 with normal ALT levels (women: ALT≤30 IU/l, men: ALT≤45 IU/l) and 235 with elevated levels]. In total, 24% of patients with normal ALT levels and 17% of those with elevated ALT levels had advanced fibrosis (Kleiner stage 3-4). The FIB-4 performed best in identifying advanced fibrosis in patients with normal ALT (area under receiver operating characteristic curve=0.86, 82% sensitivity, 77% specificity and 92% negative predictive value). The sensitivity of the AST/ALT ratio and BARD and NAFLD fibrosis scores for advanced fibrosis was good in patients with normal ALT levels (94, 94 and 82%, respectively), but the specificity was low (44, 26 and 51%, respectively). The FIB-4 yielded best results in patients with elevated ALT levels. Using the FIB-4, 61% of patients with normal ALT levels and 63% of those with elevated ALT levels could avoid liver biopsy to exclude advanced fibrosis. In contrast, AST/ALT ratio and BARD and NAFLD scores would have led to a high proportion of patients with mild disease having to undergo a biopsy. CONCLUSION: The FIB-4 yielded good results in patients with normal or elevated ALT levels, reliably excluding advanced fibrosis and reducing the need for liver biopsy.
    No preview · Article · Jan 2013 · European journal of gastroenterology & hepatology
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