Cardiff and Vale University Health Board

BACKGROUND: The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. METHODS: We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS: There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS: At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

OBJECTIVE: The purpose of this study was to finalize the development of the International Trauma Questionnaire (ITQ), a self-report diagnostic measure of post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD), as defined in the 11th version of the International Classification of Diseases (ICD-11). METHOD: The optimal symptom indicators of PTSD and CPTSD were identified by applying item response theory (IRT) analysis to data from a trauma-exposed community sample (n = 1051) and a trauma-exposed clinical sample (n = 247) from the United Kingdom. The validity of the optimized 12-item ITQ was assessed with confirmatory factor analyses. Diagnostic rates were estimated and compared to previous validation studies. RESULTS: The latent structure of the 12-item, optimized ITQ was consistent with prior findings, and diagnostic rates of PTSD and CPTSD were in line with previous estimates. CONCLUSION: The ITQ is a brief, simply worded measure of the core features of PTSD and CPTSD. It is consistent with the organizing principles of the ICD-11 to maximize clinical utility and international applicability through a focus on a limited but central set of symptoms. The measure is freely available and can be found in the body of this paper.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Anatomy has historically been a cornerstone in medical education regardless of nation or specialty. Until recently, dissection and didactic lectures were its sole pedagogy. Teaching methodology has been revolutionized with more reliance on models, imaging, simulation, and the Internet to further consolidate and enhance the learning experience. Moreover, modern medical curricula are giving less importance to anatomy education and to the acknowledged value of dissection. Universities have even abandoned dissection completely in favor of user-friendly multimedia, alternative teaching approaches, and newly defined priorities in clinical practice. Anatomy curriculum is undergoing international reformation but the current framework lacks uniformity among institutions. Optimal learning content can be categorized into the following modalities: (1) dissection/prosection, (2) interactive multimedia, (3) procedural anatomy, (4) surface and clinical anatomy, and (5) imaging. The importance of multimodal teaching, with examples suggested in this article, has been widely recognized and assessed. Nevertheless, there are still ongoing limitations in anatomy teaching. Substantial problems consist of diminished allotted dissection time and the number of qualified anatomy instructors, which will eventually deteriorate the quality of education. Alternative resources and strategies are discussed in an attempt to tackle these genuine concerns. The challenges are to reinstate more effective teaching and learning tools while maintaining the beneficial values of orthodox dissection. The UK has a reputable medical education but its quality could be improved by observing international frameworks. The heavy penalty of not concentrating on sufficient anatomy education will inevitably lead to incompetent anatomists and healthcare professionals, leaving patients to face dire repercussions.

ABSTRACT Background Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. Methods The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality. Results 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P&lt;0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p&lt;0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p&lt;0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14). Conclusions In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support. Trial registrations The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ). Funding Medical Research Council and National Institute for Health Research (Grant ref: MC_PC_19056).

BACKGROUND: Post-traumatic stress disorder (PTSD) is a distressing condition, which is often treated with psychological therapies. Earlier versions of this review, and other meta-analyses, have found these to be effective, with trauma-focused treatments being more effective than non-trauma-focused treatments. This is an update of a Cochrane review first published in 2005 and updated in 2007. OBJECTIVES: To assess the effects of psychological therapies for the treatment of adults with chronic post-traumatic stress disorder (PTSD). SEARCH METHODS: For this update, we searched the Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) all years to 12th April 2013. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). In addition, we handsearched the Journal of Traumatic Stress, contacted experts in the field, searched bibliographies of included studies, and performed citation searches of identified articles. SELECTION CRITERIA: Randomised controlled trials of individual trauma-focused cognitive behavioural therapy (TFCBT), eye movement desensitisation and reprocessing (EMDR), non-trauma-focused CBT (non-TFCBT), other therapies (supportive therapy, non-directive counselling, psychodynamic therapy and present-centred therapy), group TFCBT, or group non-TFCBT, compared to one another or to a waitlist or usual care group for the treatment of chronic PTSD. The primary outcome measure was the severity of clinician-rated traumatic-stress symptoms. DATA COLLECTION AND ANALYSIS: We extracted data and entered them into Review Manager 5 software. We contacted authors to obtain missing data. Two review authors independently performed 'Risk of bias' assessments. We pooled the data where appropriate, and analysed for summary effects. MAIN RESULTS: We include 70 studies involving a total of 4761 participants in the review. The first primary outcome for this review was reduction in the severity of PTSD symptoms, using a standardised measure rated by a clinician. For this outcome, individual TFCBT and EMDR were more effective than waitlist/usual care (standardised mean difference (SMD) -1.62; 95% CI -2.03 to -1.21; 28 studies; n = 1256 and SMD -1.17; 95% CI -2.04 to -0.30; 6 studies; n = 183 respectively). There was no statistically significant difference between individual TFCBT, EMDR and Stress Management (SM) immediately post-treatment although there was some evidence that individual TFCBT and EMDR were superior to non-TFCBT at follow-up, and that individual TFCBT, EMDR and non-TFCBT were more effective than other therapies. Non-TFCBT was more effective than waitlist/usual care and other therapies. Other therapies were superior to waitlist/usual care control as was group TFCBT. There was some evidence of greater drop-out (the second primary outcome for this review) in active treatment groups. Many of the studies were rated as being at 'high' or 'unclear' risk of bias in multiple domains, and there was considerable unexplained heterogeneity; in addition, we assessed the quality of the evidence for each comparison as very low. As such, the findings of this review should be interpreted with caution. AUTHORS' CONCLUSIONS: The evidence for each of the comparisons made in this review was assessed as very low quality. This evidence showed that individual TFCBT and EMDR did better than waitlist/usual care in reducing clinician-assessed PTSD symptoms. There was evidence that individual TFCBT, EMDR and non-TFCBT are equally effective immediately post-treatment in the treatment of PTSD. There was some evidence that TFCBT and EMDR are superior to non-TFCBT between one to four months following treatment, and also that individual TFCBT, EMDR and non-TFCBT are more effective than other therapies. There was evidence of greater drop-out in active treatment groups. Although a substantial number of studies were included in the review, the conclusions are compromised by methodological issues evident in some. Sample sizes were small, and it is apparent that many of the studies were underpowered. There were limited follow-up data, which compromises conclusions regarding the long-term effects of psychological treatment.

BACKGROUND: The aim was to determine the accuracy of preoperative magnetic resonance imaging (MRI) in the evaluation of pathological prognostic factors that influence local recurrence and survival in rectal cancer. METHODS: Ninety-eight patients undergoing total mesorectal excision for biopsy-proven rectal cancer were assessed prospectively using high-resolution MRI for tumour (T) and nodal (N) staging using the tumour node metastasis classification, depth of extramural tumour spread, the presence or absence of extramural venous invasion, a threatened circumferential resection margin and serosal involvement at or above the peritoneal reflection. Preoperative magnetic resonance assessment of these prognostic factors was compared with histopathological findings in carefully matched whole-mount sections of the resection specimen. RESULTS: There was 94 per cent weighted agreement (weighted kappa = 0.67) between MRI and pathology assessment of T stage. Agreement between MRI and histological assessment of nodal status was 85 per cent (kappa = 0.68). Although involvement of small veins by tumour was not discernible using MRI, large (calibre greater than 3 mm) extramural venous invasion was identified correctly in 15 of 18 patients (kappa = 0.64). MRI predicted circumferential resection margin involvement with 92 per cent agreement (kappa = 0.81). Seven of nine patients with peritoneal perforation by tumour (stage T4) were identified correctly using MRI. CONCLUSION: High-resolution MRI of the rectum allows preoperative identification of important surgical and pathological prognostic risk factors. This may allow both better selection and assessment of patients undergoing preoperative therapy.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.

BACKGROUND: The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. METHODS: This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1-2=fit; 3-4=vulnerable, but not frail; 5-6=initial signs of frailty but with some degree of independence; and 7-9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). FINDINGS: Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61-83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5-8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1-2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00-2·41) for CFS 3-4, 1·83 (1·15-2·91) for CFS 5-6, and 2·39 (1·50-3·81) for CFS 7-9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63-2·38) for CFS 3-4, 1·62 (0·81-3·26) for CFS 5-6, and 3·12 (1·56-6·24) for CFS 7-9. INTERPRETATION: In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19. FUNDING: None.

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management. INTRODUCTION: The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. METHODS: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement. CONCLUSION: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.

NKG2D is an activating receptor for NK, NKT, CD8(+), and gammadelta(+) T cells, whose aberrant loss in cancer is a key mechanism of immune evasion. Soluble NKG2D ligands and growth factors, such as TGFbeta1 emanating from tumors, are mechanisms for down-regulating NKG2D expression. Cancers thereby impair the capacity of lymphocytes to recognize and destroy them. In this study, we show that exosomes derived from cancer cells express ligands for NKG2D and express TGFbeta1, and we investigate the impact of such exosomes on CD8(+) T and NK cell NKG2D expression and on NKG2D-dependent functions. Exosomes produced by various cancer cell lines in vitro, or isolated from pleural effusions of mesothelioma patients triggered down-regulation of surface NKG2D expression by NK cells and CD8(+) T cells. This decrease was rapid, sustained, and resulted from direct interactions between exosomes and NK cells or CD8(+) T cells. Other markers (CD4, CD8, CD56, CD16, CD94, or CD69) remained unchanged, indicating the selectivity and nonactivatory nature of the response. Exosomal NKG2D ligands were partially responsible for this effect, as down-modulation of NKG2D was slightly attenuated in the presence of MICA-specific Ab. In contrast, TGFbeta1-neutralizing Ab strongly abrogated NKG2D down-modulation, suggesting exosomally expressed TGFbeta as the principal mechanism. Lymphocyte effector function was impaired by pretreatment with tumor exosomes, as these cells exhibited poor NKG2D-dependent production of IFN-gamma and poor NKG2D-dependent killing function. This hyporesponsiveness was evident even in the presence of IL-15, a strong inducer of NKG2D. Our data show that NKG2D is a likely physiological target for exosome-mediated immune evasion in cancer.

Awake tracheal intubation has a high success rate and a favourable safety profile but is underused in cases of anticipated difficult airway management. These guidelines are a comprehensive document to support decision making, preparation and practical performance of awake tracheal intubation. We performed a systematic review of the literature seeking all of the available evidence for each element of awake tracheal intubation in order to make recommendations. In the absence of high-quality evidence, expert consensus and a Delphi study were used to formulate recommendations. We highlight key areas of awake tracheal intubation in which specific recommendations were made, which included: indications; procedural setup; checklists; oxygenation; airway topicalisation; sedation; verification of tracheal tube position; complications; management of unsuccessful awake tracheal intubation; post-tracheal intubation management; consent; and training. We recognise that there are a range of techniques and regimens that may be effective and one such example technique is included. Breaking down the key practical elements of awake tracheal intubation into sedation, topicalisation, oxygenation and performance might help practitioners to plan, perform and address complications. These guidelines aim to support clinical practice and help lower the threshold for performing awake tracheal intubation when indicated.

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

OBJECTIVES: To systematically review published studies to identify the characteristics that distinguish fractures in children resulting from abuse and those not resulting from abuse, and to calculate a probability of abuse for individual fracture types. DESIGN: Systematic review. DATA SOURCES: All language literature search of Medline, Medline in Process, Embase, Assia, Caredata, Child Data, CINAHL, ISI Proceedings, Sciences Citation, Social Science Citation Index, SIGLE, Scopus, TRIP, and Social Care Online for original study articles, references, textbooks, and conference abstracts until May 2007. STUDY SELECTION: Comparative studies of fracture at different bony sites, sustained in physical abuse and from other causes in children <18 years old were included. Review articles, expert opinion, postmortem studies, and studies in adults were excluded. Data extraction and synthesis Each study had two independent reviews (three if disputed) by specialist reviewers including paediatricians, paediatric radiologists, orthopaedic surgeons, and named nurses in child protection. Each study was critically appraised by using data extraction sheets, critical appraisal forms, and evidence sheets based on NHS Centre for Reviews and Dissemination guidance. Meta-analysis was done where possible. A random effects model was fitted to account for the heterogeneity between studies. RESULTS: In total, 32 studies were included. Fractures resulting from abuse were recorded throughout the skeletal system, most commonly in infants (<1 year) and toddlers (between 1 and 3 years old). Multiple fractures were more common in cases of abuse. Once major trauma was excluded, rib fractures had the highest probability for abuse (0.71, 95% confidence interval 0.42 to 0.91). The probability of abuse given a humeral fracture lay between 0.48 (0.06 to 0.94) and 0.54 (0.20 to 0.88), depending on the definition of abuse used. Analysis of fracture type showed that supracondylar humeral fractures were less likely to be inflicted. For femoral fractures, the probability was between 0.28 (0.15 to 0.44) and 0.43 (0.32 to 0.54), depending on the definition of abuse used, and the developmental stage of the child was an important discriminator. The probability for skull fractures was 0.30 (0.19 to 0.46); the most common fractures in abuse and non-abuse were linear fractures. Insufficient comparative studies were available to allow calculation of a probability of abuse for other fracture types. CONCLUSION: When infants and toddlers present with a fracture in the absence of a confirmed cause, physical abuse should be considered as a potential cause. No fracture, on its own, can distinguish an abusive from a non-abusive cause. During the assessment of individual fractures, the site, fracture type, and developmental stage of the child can help to determine the likelihood of abuse. The number of high quality comparative research studies in this field is limited, and further prospective epidemiology is indicated.

: A recent increase in RCTs of psychological therapies for PTSD, results in a more confident recommendation of CBT-T and EMDR as the first-line treatments. Among the CBT-Ts considered by the review CPT, CT and PE should be the treatments of choice. The findings should guide evidence informed shared decision-making between patient and clinician.

In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with the aim of developing clear evidence-based and practice-based statements to provide guidance on the management of these conditions. Using a Delphi process, this group prioritized a list of key management areas. These included: depression, anxiety, psychotic disorders, nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)-related neurobehavioral disorders, suicidality, disorders in children and adolescents, disorders in children with intellectual disability, and epilepsy surgery. Clinical practice statements were developed for each area and consensus reached among members of the group. The assessment and management of these conditions needs to combine knowledge of psychiatric disorders, knowledge of the impact of epilepsy and its treatment on psychopathology, and an ability to deliver care within epilepsy services. The aim of these statements is to provide guidance on quality care for people with epilepsy that have a range of neuropsychiatric disorders.

This paper is based on the winning submission for the 1998 Chapman prize awarded by the British Orthodontic Society for an essay on a subject promoting the interests of orthodontics. The aim of the investigation is to develop a single index for assessing treatment inputs and outcomes. An international panel of 97 orthodontists gave subjective judgements on the need for treatment, treatment complexity, treatment improvement, and acceptability on a diverse sample of 240 initial and 98 treated study models. The occlusal traits in the study models were scored according to a defined numerical protocol. Five highly predictive occlusal traits were identified (IOTN Aesthetic Component, crossbite, upper arch crowding/ spacing, buccal segment antero-posterior relationships, and anterior vertical relationship) and then used to 'predict' the panelist's decisions using regression analysis. Cut-off values were determined for the dichotomous judgements by plotting specificity sensitivity and overall accuracy. Twenty percentile ranges were used to determine 5 grades of complexity and improvement. The index prediction of decisions for treatment need, had specificity 84.4 per cent, sensitivity 85.2 per cent, and overall accuracy 85 per cent. When used to predict treatment outcomes, the new index had specificity 64.8 per cent, sensitivity 70.1 per cent, and overall accuracy 68.1 per cent. The index could explain 75.6 per cent of the variance in the mean casewise complexity score and 63.5 per cent of the mean casewise improvement score. A new orthodontic index is proposed to assess treatment need, complexity, and outcome. It is based on international orthodontic opinion.