Is whole-colon investigation by colonoscopy, computerised tomography colonography or barium enema necessary for all patients with colorectal cancer symptoms, and for which patients would flexible sigmoidoscopy suffice? A retrospective cohort study.

BACKGROUND: For patients referred to hospital with suspected colorectal cancer (CRC), it is current standard clinical practice to conduct an examination of the whole colon and rectum. However, studies have shown that an examination of the distal colorectum using flexible sigmoidoscopy (FS) can be a safe and clinically effective investigation for some patients. These findings require validation in a multicentre study. OBJECTIVES: To investigate the links between patient symptoms at presentation and CRC risk by subsite, and to provide evidence of whether or not FS is an effective alternative to whole-colon investigation (WCI) in patients whose symptoms do not suggest proximal or obstructive disease. DESIGN: A multicentre retrospective study using data collected prospectively from two randomised controlled trials. Additional data were collected from trial diagnostic procedure reports and hospital records. CRC diagnoses within 3 years of referral were sourced from hospital records and national cancer registries via the Health and Social Care Information Centre. SETTING: Participants were recruited to the two randomised controlled trials from 21 NHS hospitals in England between 2004 and 2007. PARTICIPANTS: Men and women aged ≥ 55 years referred to secondary care for the investigation of symptoms suggestive of CRC. MAIN OUTCOME MEASURE: Diagnostic yield of CRC at distal (to the splenic flexure) and proximal subsites by symptoms/clinical signs at presentation. RESULTS: The data set for analysis comprised 7380 patients, of whom 59% were women (median age 69 years, interquartile range 62-76 years). Change in bowel habit (CIBH) was the most frequently presenting symptom (73%), followed by rectal bleeding (38%) and abdominal pain (29%); 26% of patients had anaemia. CRC was diagnosed in 551 patients (7.5%): 424 (77%) patients with distal CRC, 122 (22%) patients with cancer proximal to the descending colon and five patients with both proximal and distal CRC. Proximal cancer was diagnosed in 96 out of 2021 (4.8%) patients with anaemia and/or an abdominal mass. The yield of proximal cancer in patients without anaemia or an abdominal mass who presented with rectal bleeding with or without a CIBH or with a CIBH to looser and/or more frequent stools as a single symptom was low (0.5%). These low-risk groups for proximal cancer accounted for 41% (3032/7380) of the cohort; only three proximal cancers were diagnosed in 814 low-risk patients examined by FS (diagnostic yield 0.4%). LIMITATIONS: A limitation to this study is that changes to practice since the trial ended, such as new referral guidelines and improvements in endoscopy quality, potentially weaken the generalisability of our findings. CONCLUSIONS: Symptom profiles can be used to determine whether or not WCI is necessary. Most proximal cancers were diagnosed in patients who presented with anaemia and/or an abdominal mass. In patients without anaemia or an abdominal mass, proximal cancer diagnoses were rare in those with rectal bleeding with or without a CIBH or with a CIBH to looser and/or more frequent stools as a single symptom. FS alone should be a safe and clinically effective investigation in these patients. A cost-effectiveness analysis of symptom-based tailoring of diagnostic investigations for CRC is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95152621. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 66. See the NIHR Journals Library website for further project information

CT colonography with minimal bowel preparation: evaluation of tagging quality, patient acceptance and diagnostic accuracy in two iodine-based preparation schemes

PURPOSE: The aim of this study was to compare a 1-day with a 2-day iodine bowel preparation for CT colonography in a positive faecal occult blood test (FOBT) screening population. MATERIALS AND METHODS: One hundred consecutive patients underwent CT colonography and colonoscopy with segmental unblinding. The first 50 patients (group 1) ingested 7 50 ml iodinated contrast starting 2 days before CT colonography. The latter 50 patients (group 2) ingested 4 50 ml iodinated contrast starting 1 day before CT colonography. Per colonic segment measurements of residual stool attenuation and homogeneity were performed, and a subjective evaluation of tagging quality (grade 1-5) was done. Independently, two reviewers performed polyp and carcinoma detection. RESULTS: The tagging density was 638 and 618 HU (p = 0.458) and homogeneity 91 and 86 HU for groups 1 and 2, respectively (p = 0.145). The tagging quality was graded 5 (excellent) in 90% of all segments in group 1 and 91% in group 2 (p = 0.749). Mean per-polyp sensitivity for lesions >or=10 mm was 86% in group 1 and 97% in group 2 (p = 0.355). Patient burden from diarrhoea significantly decreased for patients in group 2. CONCLUSIONS: One-day preparation with meglumine ioxithalamate results in an improved patient acceptability compared with 2-day preparation and has a comparable, excellent image quality and good diagnostic performanc

Identifying Cis-Regulatory Sequences by Word Profile Similarity

Recognizing regulatory sequences in genomes is a continuing challenge, despite a wealth of available genomic data and a growing number of experimentally validated examples.We discuss here a simple approach to search for regulatory sequences based on the compositional similarity of genomic regions and known cis-regulatory sequences. This method, which is not limited to searching for predefined motifs, recovers sequences known to be under similar regulatory control. The words shared by the recovered sequences often correspond to known binding sites. Furthermore, we show that although local word profile clustering is predictive for the regulatory sequences involved in blastoderm segmentation, local dissimilarity is a more universal feature of known regulatory sequences in Drosophila.Our method leverages sequence motifs within a known regulatory sequence to identify co-regulated sequences without explicitly defining binding sites. We also show that regulatory sequences can be distinguished from surrounding sequences by local sequence dissimilarity, a novel feature in identifying regulatory sequences across a genome. Source code for WPH-finder is available for download at http://rana.lbl.gov/downloads/wph.tar.gz

CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging

To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography (CTC). Ninety-five subjects underwent reduced-laxative (13 g senna/18 g magnesium citrate) CTC prior to same-day colonoscopy and were randomised to one of four tagging regimens using 20 ml 40%w/v barium sulphate: regimen A: four doses, B: three doses, C: three doses plus 220 ml 2.1% barium sulphate, or D: three doses plus 15 ml diatriazoate megluamine. Patient experience was assessed immediately after CTC and 1 week later. Two radiologists graded residual stool (1: none/scattered to 4: >50% circumference) and tagging efficacy for stool (1: untagged to 5: 100% tagged) and fluid (1: untagged, 2: layered, 3: tagged), noting the HU of tagged fluid. Preparation was good (76–94% segments graded 1), although best for regimen D (P = 0.02). Across all regimens, stool tagging quality was high (mean 3.7–4.5) and not significantly different among regimens. The HU of layered tagged fluid was higher for regimens C/D than A/B (P = 0.002). Detection of cancer (n = 2), polyps ≥6 mm (n = 21), and ≤5 mm (n = 72) was 100, 81 and 32% respectively, with only four false positives ≥6 mm. Reduced preparation was tolerated better than full endoscopic preparation by 61%. Reduced-laxative CTC with three doses of 20 ml 40% barium sulphate is as effective as more complex regimens, retaining adequate diagnostic accuracy

Experimental mutation-accumulation on the X chromosome of Drosophila melanogaster reveals stronger selection on males than females

<p>Abstract</p> <p>Background</p> <p>Sex differences in the magnitude or direction of mutational effect may be important to a variety of population processes, shaping the mutation load and affecting the cost of sex itself. These differences are expected to be greatest after sexual maturity. Mutation-accumulation (MA) experiments provide the most direct way to examine the consequences of new mutations, but most studies have focused on juvenile viability without regard to sex, and on autosomes rather than sex chromosomes; both adult fitness and X-linkage have been little studied. We therefore investigated the effects of 50 generations of X-chromosome mutation accumulation on the fitness of males and females derived from an outbred population of <it>Drosophila melanogaster</it>.</p> <p>Results</p> <p>Fitness declined rapidly in both sexes as a result of MA, but adult males showed markedly greater fitness loss relative to their controls compared to females expressing identical genotypes, even when females were made homozygous for the X. We estimate that these mutations are partially additive (h ~ 0.3) in females. In addition, the majority of new mutations appear to harm both males and females.</p> <p>Conclusions</p> <p>Our data helps fill a gap in our understanding of the consequences of sexual selection for genetic load, and suggests that stronger selection on males may indeed purge deleterious mutations affecting female fitness.</p

Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting

OBJECTIVES: To update the 2012 ESGAR consensus guidelines on the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer. METHODS: Fourteen abdominal imaging experts from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) participated in a consensus meeting, organised according to an adaptation of the RAND-UCLA Appropriateness Method. Two independent (non-voting) Chairs facilitated the meeting. 246 items were scored (comprising 229 items from the previous 2012 consensus and 17 additional items) and classified as 'appropriate' or 'inappropriate' (defined by ≥ 80 % consensus) or uncertain (defined by < 80 % consensus). RESULTS: Consensus was reached for 226 (92 %) of items. From these recommendations regarding hardware, patient preparation, imaging sequences and acquisition, criteria for MR imaging evaluation and reporting structure were constructed. The main additions to the 2012 consensus include recommendations regarding use of diffusion-weighted imaging, criteria for nodal staging and a recommended structured report template. CONCLUSIONS: These updated expert consensus recommendations should be used as clinical guidelines for primary staging and restaging of rectal cancer using MRI. KEY POINTS: • These guidelines present recommendations for staging and reporting of rectal cancer. • The guidelines were constructed through consensus amongst 14 pelvic imaging experts. • Consensus was reached by the experts for 92 % of the 246 items discussed. • Practical guidelines for nodal staging are proposed. • A structured reporting template is presented

Patient safety culture measurement in general practice. Clinimetric properties of 'SCOPE'

<p>Abstract</p> <p>Background</p> <p>A supportive patient safety culture is considered to be an essential condition for improving patient safety. Assessing the current safety culture in general practice may be a first step to target improvements. To that end, we studied internal consistency and construct validity of a safety culture questionnaire for general practice (SCOPE) which was derived from a comparable questionnaire for hospitals (Dutch-HSOPS).</p> <p>Methods</p> <p>The survey was conducted among caregivers of Dutch general practice as part of an ongoing quality accreditation process using a 46 item questionnaire. We conducted factor analyses and studied validity by calculating correlations between the subscales and testing the hypothesis that respondents' <it>patient safety grade </it>of their practices correlated with their scores on the questionnaire.</p> <p>Results</p> <p>Of 72 practices 294 respondents completed the questionnaire. Eight factors were identified concerning <it>handover and teamwork, support and fellowship, communication openness, feedback and learning from error, intention to report events, adequate procedures and staffing, overall perceptions of patient safety </it>and <it>expectations and actions of managers</it>. Cronbach's alpha of the factors rated between 0.64 and 0.85. The subscales intercorrelated moderately, except for the factor about intention to report events. Respondents who graded patient safety highly scored significantly higher on the questionnaire than those who did not.</p> <p>Conclusions</p> <p>The SCOPE questionnaire seems an appropriate instrument to assess patient safety culture in general practice. The clinimetric properties of the SCOPE are promising, but future research should confirm the factor structure and construct of the SCOPE and delineate its responsiveness to changes in safety culture over time.</p

Ministries of Health and the Stewardship of Health Evidence

This chapter describes how Ministries of Health have been mandated to act as stewards of populations’ health according to the World Health Organization. We argue that this mandate extends to them having (at least partial) responsibility for ensuring relevant evidence informs policy decisions. Yet this requires consideration of the evidence advisory systems serving Ministry needs, particularly whether or how such systems work to provide relevant information in a timely manner to key decision points in the policy process. Insights from our six cases are presented to illustrate the structural and practical differences which exist between evidence advisory systems and how, at certain times, key health decisions may in fact lie outside ministerial authority. These divergent experiences highlight a range of analytical challenges when considering the provision of evidence to inform health decisions from an institutional perspective

Keeping in Touch with One's Self: Multisensory Mechanisms of Self-Consciousness

BACKGROUND: The spatial unity between self and body can be disrupted by employing conflicting visual-somatosensory bodily input, thereby bringing neurological observations on bodily self-consciousness under scientific scrutiny. Here we designed a novel paradigm linking the study of bodily self-consciousness to the spatial representation of visuo-tactile stimuli by measuring crossmodal congruency effects (CCEs) for the full body. METHODOLOGY/PRINCIPAL FINDINGS: We measured full body CCEs by attaching four vibrator-light pairs to the trunks (backs) of subjects who viewed their bodies from behind via a camera and a head mounted display (HMD). Subjects made speeded elevation (up/down) judgments of the tactile stimuli while ignoring light stimuli. To modulate self-identification for the seen body subjects were stroked on their backs with a stick and the felt stroking was either synchronous or asynchronous with the stroking that could be seen via the HMD. We found that (1) tactile stimuli were mislocalized towards the seen body (2) CCEs were modulated systematically during visual-somatosensory conflict when subjects viewed their body but not when they viewed a body-sized object, i.e. CCEs were larger during synchronous than during asynchronous stroking of the body and (3) these changes in the mapping of tactile stimuli were induced in the same experimental condition in which predictable changes in bodily self-consciousness occurred. CONCLUSIONS/SIGNIFICANCE: These data reveal that systematic alterations in the mapping of tactile stimuli occur in a full body illusion and thus establish CCE magnitude as an online performance proxy for subjective changes in global bodily self-consciousness