Analysis of exhaled breath to identify critically ill patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia.

The impact of endoscopic ultrasound on the management and outcome of patients with oesophageal cancer: an update of a systematic review.

AIM: To provide an updated systematic review concerning the impact of endoscopic ultrasound (EUS) in the modern era of oesophageal cancer staging. MATERIALS AND METHODS: To update the previous systematic review, databases including MEDLINE and EMBASE were searched and studies published from 2005 onwards were selected. Studies reporting primary data in patients with oesophageal or gastro-oesophageal junction cancer who underwent radiological staging and treatment, regardless of intent, were included. The primary outcome was the reported change in management after EUS. Secondary outcomes were recurrence rate and overall survival. Two reviewers extracted data from included articles. This study was registered with PROSPERO (CRD42021231852). RESULTS: Eighteen studies with 11,836 patients were included comprising 2,805 patients (23.7%) who underwent EUS compared to 9,031 (76.3%) without EUS examination. Reported change of management varied widely from 0% to 56%. When used, EUS fine-needle aspiration precluded curative treatment in 37.5%-71.4%. Overall survival improvements ranged between 121 and 639 days following EUS intervention compared to patients without EUS. Smaller effect sizes were observed in a randomised controlled trial, compared to larger differences reported in observational studies. CONCLUSION: Current evidence for the effectiveness of EUS in oesophageal cancer pathways is conflicting and of limited quality. In particular, the extent to which EUS adds value to contemporary cross-sectional imaging techniques is unclear and requires formal re-evaluation.

Are interventions in reproductive medicine assessed for plausible and clinically relevant effects? A systematic review of power and precision in trials and meta-analyses.

STUDY QUESTION: How much statistical power do randomised controlled trials (RCTs) and meta-analyses have to investigate the effectiveness of interventions in reproductive medicine? SUMMARY ANSWER: The largest trials in reproductive medicine are unlikely to detect plausible improvements in live birth rate (LBR), and meta-analyses do not make up for this shortcoming. WHAT IS KNOWN ALREADY: Effectiveness of interventions is best evaluated using RCTs. In order to be informative, these trials should be designed to have sufficient power to detect the smallest clinically relevant effect. Similar trials can subsequently be pooled in meta-analyses to more precisely estimate treatment effects. STUDY DESIGN, SIZE, DURATION: A review of power and precision in 199 RCTs and meta-analyses from 107 Cochrane Reviews was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: Systematic reviews published by Cochrane Gynaecology and Fertility with the primary outcome live birth were identified. For each live birth (or ongoing pregnancy) meta-analysis and for the largest RCT in each, we calculated the power to detect absolute improvements in LBR of varying sizes. Additionally, the 95% CIs of estimated treatment effects from each meta-analysis and RCT were recorded, as these indicate the precision of the result. MAIN RESULTS AND THE ROLE OF CHANCE: Median (interquartile range) power to detect an improvement in LBR of 5 percentage points (pp) (e.g. 25-30%) was 13% (8-21%) for RCTs and 16% (9-33%) for meta-analyses. No RCTs and only 2% of meta-analyses achieved 80% power to detect an improvement of 5 pp. Median power was high (85% for trials and 93% for meta-analyses) only in relation to 20 pp absolute LBR improvement, although substantial numbers of trials and meta-analyses did not achieve 80% power even for this improbably large effect size. Median width of 95% CIs was 25 pp and 21 pp for RCTs and meta-analyses, respectively. We found that 28% of Cochrane Reviews with LBR as the primary outcome contain no live birth (or ongoing pregnancy) data. LARGE-SCALE DATA: The data used in this study may be accessed at https://osf.io/852tn/?view_only=90f1579ce72747ccbe572992573197bd. LIMITATIONS, REASONS FOR CAUTION: The design and analysis decisions used in this study are predicted to overestimate the power of trials and meta-analyses, and the size of the problem is therefore likely understated. For some interventions, it is possible that larger trials not reporting live birth or ongoing pregnancy have been conducted, which were not included in our sample. In relation to meta-analyses, we calculated power as though all participants were included in a single trial. This ignores heterogeneity between trials in a meta-analysis, and will cause us to overestimate power. WIDER IMPLICATIONS OF THE FINDINGS: Trials capable of detecting realistic improvements in LBR are lacking in reproductive medicine, and meta-analyses are not large enough to overcome this deficiency. This situation will lead to unwarranted pessimism as well as unjustified enthusiasm regarding reproductive interventions, neither of which are consistent with the practice of evidence-based medicine or the idea of informed patient choice. However, RCTs and meta-analyses remain vital to establish the effectiveness of fertility interventions. We discuss strategies to improve the evidence base and call for collaborative studies focusing on the most important research questions. STUDY FUNDING/COMPETING INTEREST(S): There was no specific funding for this study. KS and SL declare no conflict of interest. AV consults for the Human Fertilisation and Embryology Authority (HFEA): all fees are paid directly to AV's employer. JW declares that publishing research benefits his career. SR is a Statistical Editor for Human Reproduction. JW and AV are Statistical Editors for Cochrane Gynaecology and Fertility. DRB is funded by the NHS as Scientific Director of a clinical IVF service. PROSPERO REGISTRATION NUMBER: None.

Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients undergoing surgery for esophageal cancer.

PURPOSE: PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. RESULTS: Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28-1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer.

Additional value of EUS in oesophageal cancer patients staged N0 on PET/CT: validation of a prognostic model.

BACKGROUND: Lymph node metastases are a major prognostic indicator in oesophageal cancer. Radiological staging largely influences treatment decisions and is becoming more reliant on PET and CT. However, the sensitivity of these modalities is suboptimal and is known to under-stage disease. The primary aim of this study was to validate a published prognostic model in oesophageal cancer patients staged N0 with PET/CT, which showed that EUS nodal status was an independent predictor of survival. The secondary aim was to assess the prognostic significance of pathological lymph node metastases in this cohort. METHODS: An independent validation cohort included 139 consecutive patients from a regional upper gastrointestinal cancer network staged N0 with PET/CT between 1st January 2013 and 31st June 2015. Replicating the original study, two Cox regression models were produced: one included EUS T-stage and EUS N-stage, and one included EUS T-stage and EUS N0 versus N+. The primary outcome of the prognostic model was overall survival (OS). Kaplan-Meier analysis assessed differences in OS between pathological node-negative (pN0) and node-positive (pN+) groups. A p value of < 0.05 was considered statistically significant. RESULTS: The mean OS of the validation cohort was 29.8 months (95% CI 27.1-35.2). EUS T-stage was significantly and independently associated with OS in both models (p = 0.011 and p = 0.012, respectively). EUS N-stage and EUS N0 versus N+ were not significantly associated with OS (p = 0.553 and p = 0.359, respectively). There was a significant difference in OS between pN0 and pN+ groups (χ2 13.315, df 1, p < 0.001). CONCLUSION: Lymph node metastases have a significant detrimental effect on OS. This validation study did not replicate the results of the developed prognostic model but the continued benefit of EUS in patients staged N0 with PET/CT was demonstrated. EUS remains a valuable component of a multi-modality approach to oesophageal cancer staging.

Developments in IVF warrant the adoption of new performance indicators for ART clinics, but do not justify the abandonment of patient-centred measures.

Recent advances in embryo freezing technology together with growing concerns over multiple births have shifted the paradigm of appropriate IVF. This has led to the adoption of new performance indicators for ART clinics by national reporting schemes, such as those curated by the Society for Assisted Reproductive Technology (SART) and the Human Fertilization and Embryology Authority (HFEA). Using these organizations as case studies, we review several outcome measures from a statistical perspective. We describe several denominators that are used to calculate live birth rates. These include cumulative birth rates calculated from all fresh and frozen transfer procedures arising from a particular egg collection or cycle initiation, and live birth rates calculated per embryo transferred. Using data from both schemes, we argue that all cycles should be included in the denominator, regardless of whether or not egg collection and fertilization were successful. Excluding cancelled cycles reduces the impact of confounding due to patient characteristics but also removes policy and performance differences which we argue represent relevant sources of variation. It may be misleading to present prospective patients with essentially hypothetical measures of performance predicated on parity of ovarian stimulation and transfer policies. Although live birth per embryo has the advantage of encouraging single embryo transfer, we argue that it is prone to misinterpretation. This is because the likelihood of live birth is not proportional to the number of embryos transferred. We conclude that it is not possible to present a single measure that encompasses both effectiveness and safety. Instead, we propose that a set of clear, relevant outcome indicators is necessary to enable subfertile patients to make informed choices regarding whether and where to be treated.

Comparison of different insulin pump makes under routine care conditions in adults with Type 1 diabetes.

AIMS: To compare long-term HbA1c changes associated with different insulin pumps during routine care in a large cohort of adults with Type 1 diabetes representative of other clinic populations. METHODS: Observational, retrospective study of 508 individuals starting pump therapy between 1999 and 2014 (mean age, 40 years; 55% women; diabetes duration, 20 years; 94% Type 1 diabetes; median follow-up, 3.7 years). Mixed linear models compared covariate-adjusted HbA1c changes associated with different pump makes. RESULTS: The pumps compared were: 50% Medtronic, 24% Omnipod, 14% Roche and 12% Animas. Overall HbA1c levels improved and improvements were maintained during a follow-up extending to 10 years (HbA1c : pre-continuous subcutaneous insulin infusion (pre-CSII) vs. 12 months post CSII, 71 (61, 82) vs. 66 (56, 74) mmol/mol; 8.7 (7.7, 9.6) vs. 8.2 (7.3, 8.9)%; P < 0.0001). The percentage of individuals with HbA1c ≥ 64 mmol/mol (8.0%) reduced from a pre-CSII level of 68% to 55%. After adjusting for baseline confounders, there were no between-pump differences in HbA1c lowering (P = 0.44), including a comparison of patch pumps with traditional catheter pumps (P = 0.63). There were no significant (P < 0.05) between-pump differences in HbA1c lowering in pre-specified subgroups stratified by pre-pump HbA1c , age or diabetes duration. HbA1c lowering was positively related to baseline HbA1c (P < 0.001) and diabetes duration (P = 0.017), and negatively related to the number of years of CSII use (P = 0.024). CONCLUSIONS: Under routine care conditions, there were no covariate-adjusted differences in HbA1c lowering when comparing different pump makes, including a comparison of patch pumps vs. traditional catheter pumps. Therefore, the choice of CSII make should not be influenced by the desired degree of HbA1c lowering.

Accuracy of contemporary oesophageal cancer lymph node staging with radiological-pathological correlation.

AIM: To evaluate the accuracy of contemporary N-staging and provide radiological-pathological correlation in patients with lymph node metastases (LNMs) that were radiologically staged N0. MATERIALS AND METHODS: One hundred and twelve patients were included who underwent surgery alone (n=41) or neoadjuvant therapy (n=71) between October 2010 and December 2015. Contrast-enhanced computed tomography (CECT), endoscopic ultrasound (EUS), and combined positron-emission tomography (PET) and CT N-stage were compared to pathological N-stage [node-negative (N0) versus node-positive (N+) groups]. Fifty LNMs from 15 patients preoperatively staged as N0 were measured and the maximum size recorded. RESULTS: Accuracy, sensitivity, and specificity of N0 versus N+ disease with CECT, EUS, and PET/CT was 54.5%, 39.7% and 77.3%, 55.4%, 42.6% and 75%, and 57.1% 35.3%, and 90.9%, respectively. All techniques were more likely to under-stage nodal disease; CECT (X2 32.890, df=1, p<0.001), EUS (X2 28.471, df=1, p<0.001), and PET/CT (X2 50.790, df=1, p<0.001). PET/CT was more likely to under-stage nodal disease than EUS (p=0.031). Median LNM size was 3 mm, with 41 (82%) of LNMs measuring <6 mm and 22 (44%) classified as micro-metastases (≤2 mm). CONCLUSION: This study has demonstrated poor N-staging accuracy in the modern era of radiological staging. Eighty-two percent of LNMs measured <6 mm, making direct identification extremely challenging on medical imaging. Future research should focus on investigating and developing alternative surrogate markers to predict the likelihood of LNMs.

Replacing sedentary time with sleep, light, or moderate-to-vigorous physical activity: effects on self-regulation and executive functioning.

Recent attention has highlighted the importance of reducing sedentary time for maintaining health and quality of life. However, it is unclear how changing sedentary behavior may influence executive functions and self-regulatory strategy use, which are vital for the long-term maintenance of a health behavior regimen. The purpose of this cross-sectional study is to examine the estimated self-regulatory and executive functioning effects of substituting 30 min of sedentary behavior with 30 min of light activity, moderate-to-vigorous physical activity (MVPA), or sleep in a sample of older adults. This study reports baseline data collected from low-active healthy older adults (N = 247, mean age 65.4 ± 4.6 years) recruited to participate in a 6 month randomized controlled exercise trial examining the effects of various modes of exercise on brain health and function. Each participant completed assessments of physical activity self-regulatory strategy use (i.e., self-monitoring, goal-setting, social support, reinforcement, time management, and relapse prevention) and executive functioning. Physical activity and sedentary behaviors were measured using accelerometers during waking hours for seven consecutive days at each time point. Isotemporal substitution analyses were conducted to examine the effect on self-regulation and executive functioning should an individual substitute sedentary time with light activity, MVPA, or sleep. The substitution of sedentary time with both sleep and MVPA influenced both self-regulatory strategy use and executive functioning. Sleep was associated with greater self-monitoring (B = .23, p = .02), goal-setting (B = .32, p < .01), and social support (B = .18, p = .01) behaviors. Substitution of sedentary time with MVPA was associated with higher accuracy on 2-item (B = .03, p = .01) and 3-item (B = .02, p = .04) spatial working memory tasks, and with faster reaction times on single (B = -23.12, p = .03) and mixed-repeated task-switching blocks (B = -27.06, p = .04). Substitution of sedentary time with sleep was associated with marginally faster reaction time on mixed-repeated task-switching blocks (B = -12.20, p = .07) and faster reaction time on mixed-switch blocks (B = 17.21, p = .05), as well as reduced global reaction time switch cost (B = -16.86, p = .01). Substitution for light intensity physical activity did not produce significant effects. By replacing sedentary time with sleep and MVPA, individuals may bolster several important domains of self-regulatory behavior and executive functioning. This has important implications for the design of long-lasting health behavior interventions. Trial Registration clinicaltrials.gov identifier NCT00438347.

The effect of age and increasing head-up tilt on pre-oxygenation times in children: a randomised exploratory study.

We conducted a randomised exploratory trial in children aged between one and sixteen years old to establish the time to achieve an end-tidal oxygen fraction ≥ 0.9 in three different positions: supine, and 30 and 45° head up. We recruited 120 children analysed in two age groups: 1-8 years and 9-16 years. The median (IQR [range]) time to reach the end point was 80 (59-114 [41-295]) s in the younger group and 150 (107-211 [44-405]) s in the older group, regardless of position (p = 0.0001). The end point was reached in 90% of children in approximately 160 s in the younger, and 271 s in the older, groups, respectively. There was no statistical difference between the three positions within each age group in the time to reach the endpoint (p = 0.59). Only two patients in the older age group could not reach the end point, due to poorly fitting facemasks. We conclude that pre-oxygenation can therefore be achieved effectively in most children, and that tilting children head up by 30 or 45° does not significantly reduce the time taken to achieve an end-tidal oxygen fraction of ≥ 0.9. The recommended period for pre-oxygenation in both groups should remain at 3 min but it should be noted that this may be insufficient for many older patients.

Decompressive craniectomy and cranioplasty: experience and outcomes in deployed UK military personnel.

OBJECT: In recent conflicts, many UK personnel sustained head injuries requiring damage-control surgery and aeromedical transfer to the UK. This study aims to examine indications, complications and outcomes of UK military casualties undergoing craniectomy and cranioplasty from conflicts in Afghanistan and Iraq. METHODS: The UK military Joint Theatre Trauma Registry (JTTR) was searched for all UK survivors in Afghanistan and Iraq between 2004 and 2014 requiring craniectomy and cranioplasty resulting from trauma. RESULTS: Fourteen decompressive craniectomies and cranioplasties were performed with blast and gunshot wounds equally responsible for head injury. Ten survivors (71%) had an Injury Severity Score (ISS) of 75, normally designated as 'unsurvivable'. Most were operated on the day of injury. Seventy-one percent received a reverse question mark incision and 7% received a bicoronal incision. Seventy-nine percent had bone flaps discarded. Overall infection rate was 43%. Acinetobacter spp was the causative organism in 50% of cases. Median Glasgow Outcome Scale (GOS) at final follow-up was 4. All casualties had a GOS score greater than 3. CONCLUSIONS: Timely neurosurgical intervention is imperative for military personnel given high survival rates in those sustaining what are designated 'un-survivable' injuries. Early decompression facilitates safe aeromedical evacuation of casualties. Excellent outcomes validate the UK military trauma system and the stepwise performance gains throughout recent conflicts however trauma registers most evolving to have specific relevance to military casualties. In high-energy trauma with contamination and soft-tissue destruction, surgery should be conducted with regard for future soft tissue reconstruction. Bone flaps should be discarded and cranioplasty performed according to local preference. Facilities receiving military casualties should have specialist microbiological input mindful of the difficulties treating unusual microbes.

Clinical and microbiological characteristics of Eggerthella lenta bacteremia.

Eggerthella lenta is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with E. lenta bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as E. lenta by both commercially available matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a vanA or vanB gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.

100 Years of British military neurosurgery: on the shoulders of giants.

Death from head injuries has been a feature of conflicts throughout the world for centuries. The burden of mortality has been variously affected by the evolution in weaponry from war-hammers to explosive ordnance, the influence of armour on survivability and the changing likelihood of infection as a complicating factor. Surgery evolved from haphazard trephination to valiant, yet disjointed, neurosurgery by a variety of great historical surgeons until the Crimean War of 1853-1856. However, it was events initiated by the Great War of 1914-1918 that not only marked the development of modern neurosurgical techniques, but our approach to military surgery as a whole. Here the author describes how 100 years of conflict and the input and intertwining relationships between the 20th century's great neurosurgeons established neurosurgery in the United Kingdom and beyond.

Epstein-Barr virus infection in adult renal transplant recipients.

Epstein-Barr virus (EBV) DNAemia in the first year posttransplantation has been studied extensively. There is a paucity of information on prevalence and sequelae of EBV infection in adult renal transplantation beyond the first year. This single-center study examines the relationship between EBV DNAemia and demographic, immunosuppressive, hematologic and infection-related parameters in 499 renal transplant recipients between 1 month and 33 years posttransplant. Participants were tested repeatedly for EBV DNAemia detection over 12 months and clinical progress followed for 3 years. Prevalence of DNAemia at recruitment increased significantly with time from transplant. In multivariate adjusted analyses, variables associated with DNAemia included EBV seronegative status at transplant (p = 0.045), non-White ethnicity (p = 0.014) and previous posttransplant lymphoproliferative disease (PTLD) diagnosis (p = 0.006), while low DNAemia rates were associated with mycophenolate mofetil use (p < 0.0001) and EBV viral capsid antigen positive Epstein-Barr nuclear antigen-1 positive serostatus at transplant (p = 0.044). Patient and graft survival, rate of kidney function decline and patient reported symptoms were not significantly different between EBV DNAemia positive and negative groups. EBV DNAemia is common posttransplant and increases with time from transplantation, but EBV DNAemia detection in low-risk (seropositive) patients has poor specificity as a biomarker for future PTLD risk.

Propensity score analysis of oesophageal cancer treatment with surgery or definitive chemoradiotherapy.

BACKGROUND: The role of treatments involving surgery versus definitive chemoradiotherapy (dCRT) for oesophageal cancer remains controversial. METHODS: Consecutive patients with oesophageal cancer were studied. Those whose treatment involved surgery alone or who received neoadjuvant chemotherapy or chemoradiotherapy were compared with those receiving dCRT. Multiple regression models, including propensity scores, were developed to assess confounding factors associated with undergoing surgery or dCRT, and the risk-adjusted association between treatment and survival. RESULTS: From a total of 727 patients, regression adjustment to control for bias created a cohort of 521 patients available for comparison (277 in the surgery group and 244 in the dCRT group). Local and distant recurrence rates were 10·1 and 22·0 per cent respectively after surgery, compared with 26·2 and 11·9 per cent following dCRT (P < 0·001). Median survival, and 2- and 5-year survival rates after surgery were 27 months, 53·8 and 31·0 per cent respectively, compared with 28 months, 54·2 and 31·9 per cent after dCRT (P = 0·918). On multivariable analysis, disease-free survival was related to endosonographic tumour category (hazard ratio (HR) 0·76, 95 per cent confidence interval 0·10 to 6·04 for T1; HR 1·57, 0·21 to 11·58 for T2; HR 2·12, 0·29 to 15·49 for T3; HR 3·07, 0·41 to 23·16 for T4; P = 0·003, in relation to T0 as reference), lymph node metastasis count (HR 1·10, 1·04 to 1·15; P < 0·001) and total disease length (HR 0·96, 0·93 to 1·00; P = 0·041). CONCLUSION: There was no difference in survival after oesophageal cancer treatment involving surgery or dCRT.

Clostridium difficile as a cause of healthcare-associated diarrhoea among children in Auckland, New Zealand: clinical and molecular epidemiology.

We aimed to determine the incidence of Clostridium difficile infection (CDI), the molecular epidemiology of circulating C. difficile strains and risk factors for CDI among hospitalised children in the Auckland region. A cross-sectional study was undertaken of hospitalised children <15 years of age in two hospitals investigated for healthcare-associated diarrhoea between November 2011 and June 2012. Stool specimens were analysed for the presence of C. difficile using a two-step testing algorithm including polymerase chain reaction (PCR). C. difficile was cultured and PCR ribotyping performed. Demographic data, illness characteristics and risk factors were compared between children with and without CDI. Non-duplicate stool specimens were collected from 320 children with a median age of 1.2 years (range 3 days to 15 years). Forty-six patients (14 %) tested met the definition for CDI. The overall incidence of CDI was 2.0 per 10,000 bed days. The percentage of positive tests among neonates was only 2.6 %. PCR ribotyping showed a range of strains, with ribotype 014 being the most common. Significant risk factors for CDI were treatment with proton pump inhibitors [risk ratio (RR) 1.74, 95 % confidence interval (CI) 1.09-5.59; p = 0.002], presence of underlying malignancy (RR 2.71, 95 % CI 1.65-4.62; p = 0.001), receiving chemotherapy (RR 2.70, 95 % CI 1.41-4.83; p = 0.003) and exposure to antibiotics (RR 1.17, 95 % CI 0.99-1.17; p = 0.03). C. difficile is an important cause of healthcare-associated diarrhoea in this paediatric population. The notion that neonatal populations will always have high rates of colonisation with C. difficile may not be correct. Several risk factors associated with CDI among adults were also found to be significant.

Clinical and molecular epidemiology of community-onset invasive Staphylococcus aureus infection in New Zealand children.

Our aim was to describe the epidemiology and incidence of community-onset invasive S. aureus disease in children presenting to our hospital, and to compare the clonal complexes and virulence genes of S. aureus strains causing invasive and non-invasive disease. The virulence gene repertoire of invasive disease isolates was characterized using DNA microarray and compared with the virulence gene repertoire of non-invasive S. aureus isolates. Over the study period, 163 children had an invasive S. aureus infection. There was no difference in the distribution of clonal complexes or in the prevalence of genes encoding virulence factors between invasive and non-invasive isolates. Future research should include a strong focus on identifying the host and environmental factors that, along with organism virulence factors, are contributing to the patterns of invasive S. aureus disease observed in New Zealand.

N-staging of oesophageal and junctional carcinoma: is there still a role for EUS in patients staged N0 at PET/CT?

AIM: To assess whether separate endoscopic ultrasound (EUS) lymph node (N)-staging is still of prognostic value in those staged node negative (N0) at combined positron-emission tomography/computed tomography (PET/CT) in patients with oesophageal cancer (OC). MATERIALS AND METHODS: One hundred and seventeen consecutive patients [median age 67 years; 88 male; 98 cases of adenocarcinoma, 19 cases of squamous cell carcinoma (SCC)] staged as N0 at PET/CT underwent EUS to record tumour (T)- and N-stage. The patients were subsequently separated into two groups: EUS N0 (n = 78) and EUS N+ (n = 39). Survival analysis using Kaplan-Meier and Cox's proportional hazard methods was performed. Primary outcome was overall survival from diagnosis. RESULTS: EUS N-stage and EUS N0 versus EUS N+ (p = 0.005 and p = 0.001, respectively) were found to be significantly and independently associated with survival in two models of multivariate analysis, in patients staged N0 at PET/CT. EUS T-stage was significantly associated with survival on univariate analysis. CONCLUSION: EUS N-staging still has prognostic value in patients staged N0 at PET/CT. There is a significant difference in survival between EUS N0 and positive nodal EUS status in those staged N0 at PET/CT, suggesting PET/CT is unreliable for local staging. PET/CT and EUS continue to have complimentary roles in OC staging.

Thought disorder in mid-childhood as a predictor of adulthood diagnostic outcome: findings from the New York High-Risk Project.

BACKGROUND: Thought disorder has been proposed as an indicator of schizotypy, which is considered to be necessary but not sufficient for the development of schizophrenia. It is unclear whether thought disorder is an indicator of susceptibility (i.e. an endophenotype) for schizophrenia. The goal of the present study was to elucidate the role of thought disorder in relation to schizotypy by examining its presence in high-risk individuals during mid-childhood. Method The sample consisted of 265 subjects drawn from the New York High-Risk Project. Individuals at high risk for schizophrenia (i.e. offspring of parents with schizophrenia) were compared with individuals at low risk for schizophrenia (i.e. offspring of parents with affective disorder or offspring of psychiatrically normal parents). Videotaped interviews were rated for thought disorder using the Scale for the Assessment of Thought, Language, and Communication (TLC). The same subjects were administered diagnostic interviews in late adolescence/early adulthood. RESULTS: Although positive thought disorder was equally present in subjects with affective and non-affective psychoses, negative thought disorder (namely, poverty of speech and poverty of content of speech) was elevated only in subjects with schizophrenia-related psychosis. Logistic regression analyses revealed that negative thought disorder added to the prediction of schizophrenia-related psychosis outcomes over and above positive thought disorder. CONCLUSIONS: These findings suggest that negative thought disorder may have a specific association with schizotypy, rather than a more general association with psychosis. The findings also support consideration of negative thought disorder as an endophenotypic indicator of a schizophrenia diathesis.

Prognostic significance of 18-FDG PET/CT and EUS-defined tumour characteristics in patients with oesophageal cancer.

AIM: To determine the correlation between 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) defined maximum standardized uptake value (SUVmax) and endoluminal ultrasound-defined tumour volume (EDTV) in patients with oesophageal cancer (OC) and their relative prognostic significance. MATERIALS AND METHODS: One hundred and eighty-five consecutive patients with OC were staged using CT, endoscopic ultrasound (EUS), and PET/CT. The maximum potential EDTV was calculated (πr(2)L, where r = tumour thickness and L = total length of disease including proximal and distal lymph node metastases). Primary outcome measure was survival from diagnosis. RESULTS: Ninety-one percent of patients (168/185) had FDG-avid tumours on PET/CT. SUVmax correlated positively and significantly with EDTV (Spearman's rho = 0.339, p = 0.001). On univariate analysis, survival was inversely related to the PET/CT lymph node metastasis count (LNMC, p = 0.015), EUS N stage (p = 0.002), EDTV (<48 cm(3), p = 0.001), EUS total length of disease (p = 0.001), SUVmax (p = 0.002), PET/CT N stage (p < 0.0001), and EUS LNMC (p < 0.0001). On multivariate analysis two factors were significantly and independently associated with survival: EDTV (HR, 3.118; 95% CI: 1.357-7.167; p = 0.007), and PET/CT N stage (HR, 0.496; 95% CI: 0.084-1.577; p = 0.022). CONCLUSION: EDTV and PET/CT N stage were important predictors of survival and further research is needed to identify critical prognostic values.