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Background Social anxiety disorder (SAD) is a chronic and disabling psychiatric disorder associated with low levels of help-seeking. To date, however, scarce research has examined the epidemiology of SAD in veterans. This study examined the prevalence, comorbidities and incremental burden of SAD in relation to suicidality and functioning in a representative sample of U.S. military veterans. Methods A nationally representative sample of 3,157 U.S. veterans completed a web survey containing measures of SAD symptoms, trauma history, psychiatric history and functioning. Multivariable analyses were conducted to examine associations between SAD and psychiatric comorbidities, suicidality and functioning. Results A total 9.5% (n = 272) of the sample screened positive for lifetime SAD. Veterans with SAD were more likely than those without SAD to be younger, female, single, racial/ethnic minorities and to have experienced childhood abuse. They also had substantially elevated rates of comorbid psychiatric disorders, particularly lifetime major depression (odds ratio [OR]=5.8) and posttraumatic stress disorder (OR=3.1), as well as current suicidal ideation (OR=3.3). Veterans with SAD scored lower on measures of functioning, particularly social, emotional and mental health functioning (d’s=0.21–0.34). Limitations Data were collected cross-sectionally using self-report. Conclusions SAD in U.S. veterans is prevalent and associated with psychiatric comorbidities, functional impairment and a more than 3-fold greater risk for suicidal ideation . Given that SAD is associated with low treatment seeking and engagement, it may be undetected and undertreated relative to other psychiatric morbidities. These results underscore the importance of screening, monitoring and treating SAD in this population along with other prevalent mental disorders.

Background Left-sided cardiac volume overload (LCVO) can cause fluid accumulation in lung tissue changing the distribution of ventilation, which can be evaluated by electrical impedance tomography (EIT). Objectives To describe and compare EIT variables in horses with naturally occurring compensated and decompensated LCVO and compare them to a healthy cohort. Animals Fourteen adult horses, including university teaching horses and clinical cases (healthy: 8; LCVO: 4 compensated, 2 decompensated). Methods In this prospective cohort study, EIT was used in standing, unsedated horses and analyzed for conventional variables, ventilated right (VAR) and left (VAL) lung area, linear-plane distribution variables (avg-max VΔZLine, VΔZLine), global peak flows, inhomogeneity factor, and estimated tidal volume. Horses with decompensated LCVO were assessed before and after administration of furosemide. Variables for healthy and LCVO-affected horses were compared using a Mann-Whitney test or unpaired t-test and observations from compensated and decompensated horses are reported. Results Compared to the healthy horses, the LCVO cohort had significantly less VAL (mean difference 3.02; 95% confidence interval .77-5.2; P = .02), more VAR (−1.13; −2.18 to −.08; P = .04), smaller avg-max VΔZLLine (2.54; 1.07-4.00; P = .003) and VΔZLLine (median difference 5.40; 1.71-9.09; P = .01). Observation of EIT alterations were reflected by clinical signs in horses with decompensated LCVO and after administration of furosemide. Conclusions and Clinical Importance EIT measurements of ventilation distribution showed less ventilation in the left lung of horses with LCVO and might be useful as an objective assessment of the ventilation effects of cardiogenic pulmonary disease in horses.

Background: esophageal cancer is increasingly common and carries a poor prognosis. The optimal treatment modality for locally advanced cancer is unknown, with current guidance recommending either neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) followed by surgery. There is a lack of adequately powered trials comparing CT against CRT. We retrospectively compared CT versus CRT using a propensity score weighting approach.Methods: demographic, disease, treatment and outcome data were retrieved from a local database for patients who received neoadjuvant CT or CRT followed by surgery. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach. Groups were assessed for differences in postoperative outcomes and survival. Kaplan-Meier and non-parametric tests were used to compare survival and outcome data as appropriate.Results: data for 284 patients were retrieved. Following IPTW groups were well matched. No significant differences were seen for postoperative complications (CT 64.9% vs. CRT 63.3%, p=0.807), including major complications (24.0% vs. 23.6%, p=0.943) and anastomotic leak (7.8% vs. 5.6%, p=0.526). Significantly higher rates of clinical regression and complete pathological response were seen following CRT (p=0.002 for both). Rates of R0 resection were higher with CRT, CT 79.1% vs. CRT 93.1%, p=0.006. There was no difference between groups for overall or disease-free survival.Conclusion: this study suggests that the significant improvements in local tumour response seen after neoadjuvant CRT compared to CT may not translate to different survival outcomes. However, it must be stressed that adequately powered prospective trials are sti

Objectives: A review of the literature demonstrates that relatively little is known about acute psychiatric presentations in children (0–12 years), compared with adolescents or young adults (12 years+). This study aims to review psychiatric presentations of children to a CAMHS Liaison Service at Children’s Hospital Ireland (CHI) at Tallaght University Hospital over a 10-year period. Methods: A retrospective study was undertaken of case notes of all children aged 12 years and under who were referred to the CAMHS Liaison Service between January 2009 and December 2018 (n = 318). Data were anonymised and inputted into SPSSv25 for analysis. The relationships between presentations and methods of self-harm over time were measured using Pearson’s correlation. Associations between categorical variables were analysed using chi-squared tests. Results: There was a significant increase in presentations of under-12s over the 10-year period (r(8)=0.66, p = 0.02). There was also a significant increase in children presenting with a disturbance of conduct and/or emotions over time (r(8) = 0.79, p < 0.001). There was a significant association between female gender and ingestion (X2 = 12.73, df = 1, p < 0.05) and between male gender and ligature as a method of self-harm (X2 = 5.54, df = 1, p < 0.05). Over half (53%) of children presented with suicidal thoughts and 22% presented with suicidal behaviours. The reported use of ligature as a method of self-harm emerged only from 2012 among cases studied. Conclusions: Children aged 12 years and under are presenting in increasing numbers with acute mental health difficulties, including suicidal thoughts and behaviours. There is a worrying trend in methods of self-harm, particularly in high lethality behaviours such as attempted strangulation.

Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary of background data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

Background This evidence summary synthesised the evidence relating to pharmacological and non-pharmacological interventions in the community to prevent COVID-19/progression to severe disease. An additional aim was to identify potentially modifiable lifestyle factors associated with reduced risk of infection/progression to severe disease. Methods A systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints was undertaken from 1 January 2020 to 19 April 2021; no language restrictions were applied. All potentially eligible papers were exported to Covidence. Titles/abstracts and full texts were single screened for relevance. Data extraction and quality appraisal of included studies was completed by a single reviewer and checked by a second. Results In total, 50 studies, three randomised controlled trials (RCTs), one non-RCT and 46 cohort studies were included. The four included controlled trials tested variations of the pharmacological intervention, ivermectin. While these controlled trials reported a protective effect for ivermectin use, these trials were of poor quality and had serious risk of bias. Across 46 cohort studies, the modifiable lifestyle risk factors identified were obesity, smoking, vitamin D status, physical activity, alcohol consumption and processed meat consumption. These studies reported mixed results in terms of the association between modifiable lifestyle risk factors and poor COVID-19 outcomes. Conclusions At the time of writing there is no high quality evidence of benefit to support pharmacological interventions to prevent COVID-19. Although there were mixed results for the risk factors identified, maintenance of healthy weight, smoking cessation, engaging in physical activity and moderation of alcohol and processed meat consumption are likely to be beneficial to health and should continue to be encouraged.

To measure time to flap coverage after open tibia fractures and assess whether delays are associated with inpatient complications.Retrospective cohort study.One forty level I and II trauma centers in Canada and the United States.Adult patients (≥16 years) undergoing surgery for (1) an open tibia (including ankle) fracture and (2) a soft-tissue flap during their index admission between January 1, 2012, and December 31, 2015, were eligible for inclusion.Time from hospital arrival to definitive flap coverage (in days).The primary outcome was a composite of the following complications occurring during the index admission: (1) deep infection, (2) osteomyelitis, and/or (3) amputation. The primary analysis compared complications between early and delayed coverage groups (≤7 and7 days, respectively) after matching on propensity scores. We also used logistic regression with time to flap coverage as a continuous variable to examine the impact of the duration of delay on complications.There were 672 patients at 140 centers included. Of these, 412 (61.3%) had delayed coverage (7 days). Delayed coverage was associated with a significant increase in complications during the index admission after matching (16.7% vs. 6.2%, P0.001, number needed to harm = 10). Each additional week of delay was associated with an approximate 40% increased adjusted risk of complications (adjusted odds ratio 1.44, 95% confidence interval 1.13-1.82, for each week coverage was delayed, P = 0.003).This is the first multicenter study of flap coverage for tibia fractures in North America. Complications rose significantly when flap coverage was delayed beyond 7 days, consistent with current guideline recommendations. Because the majority of patients did not have coverage within this timeframe, initiatives are required to improve care for patients with these injuries.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

It is vital that new mothers quickly and accurately recognize their child's facial expressions. There is evidence that during pregnancy women develop enhanced processing of facial features associated with infancy and distress, as these cues signal vulnerability and are therefore biologically salient. In this study, 51 pregnant women at 17-36 weeks gestation watched neutral infant and adult faces gradually morph into either happy or sad expressions. We measured the speed and accuracy with which participants were able to recognize facial affect (happy vs. sad) across facial ages (infant vs. adult). Participants were faster and more accurate at recognizing happy versus sad faces and adult versus infant faces. We discuss how prior exposure to a certain face type may explain faster recognition. We also consider these results in the context of evidence indicating positive affect is recognized more quickly, but associated with slower attention and detection.

Objective: To determine the relationship between body composition (BC), specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients. Background: Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however evidence is lacking in emergency surgery. Methods: An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using pre-operative CT images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modelling. Results: Six hundred and ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs. 45.1%, p = 0.028; 57.5% vs. 42.6%, p = 0.014), 30-day (9.5% vs. 3.6%, p = 0.010; 14.9% vs. 3.4%, p < 0.001), and 1-year mortality (27.4% vs. 11.5%, p < 0.001; 29.7% vs.12.5%, p < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia (OR 2.56 (95%CI 1.12-5.84), p = 0.026) and myosteatosis (OR 4.26 (2.01-9.06), p < 0.001), similarly at 1-year (OR 2.66 (95%CI 1.57-4.52), p < 0.001; OR 2.08 (95%CI 1.26-3.41), p = 0.004). BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95%CI 0.835-0.84). Conclusion: Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.

Aims We aimed to determine the effect of increasing body weight upon right ventricular (RV) volumes, energetics, systolic function, and stress responses using cardiovascular magnetic resonance (CMR). Methods and results We first determined the effects of World Health Organization class III obesity [body mass index (BMI) > 40 kg/m2, n = 54] vs. healthy weight (BMI < 25 kg/m2, n = 49) upon RV volumes, energetics and systolic function using CMR. In less severe obesity (BMI 35 ± 5 kg/m2, n = 18) and healthy weight controls (BMI 21 ± 1 kg/m2, n = 9), we next performed CMR before and during dobutamine to evaluate RV stress response. A subgroup undergoing bariatric surgery (n = 37) were rescanned at median 1 year to determine the effects of weight loss. When compared with healthy weight, class III obesity was associated with adverse RV remodelling (17% RV end-diastolic volume increase, P < 0.0001), impaired cardiac energetics (19% phosphocreatine to adenosine triphosphate ratio reduction, P < 0.001), and reduction in RV ejection fraction (by 3%, P = 0.01), which was related to impaired energetics (R = 0.3, P = 0.04). Participants with less severe obesity had impaired RV diastolic filling at rest and blunted RV systolic and diastolic responses to dobutamine compared with healthy weight. Surgical weight loss (34 ± 15 kg weight loss) was associated with improvement in RV end-diastolic volume (by 8%, P = 0.006) and systolic function (by 2%, P = 0.03). Conclusion Increasing body weight is associated with significant alterations in RV volumes, energetic, systolic function, and stress responses. Adverse RV modelling is mitigated with weight loss. Randomized trials are needed to determine whether intentional weight loss improves symptoms and outcomes in patients with obesity and heart failure.

Background & aims: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs). Methods: Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m 2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group. Results: Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group. Conclusion: One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation. Trial registration: ClinicalTrials.gov Identifier NCT02459561.

STUDY OBJECTIVES: Veterans experience high levels of trauma, psychiatric, and medical conditions that may increase their risk for insomnia. To date, however, no known study has examined the prevalence, risk correlates, and comorbidities of insomnia in a nationally representative sample of veterans. METHODS: A nationally representative sample of 4,069 US military veterans completed a survey assessing insomnia severity; military, trauma, medical, and psychiatric histories; and health and psychosocial functioning. Multivariable analyses examined the association between insomnia severity, psychiatric and medical comorbidities, suicidality, and functioning. RESULTS: A total of 11.4% of veterans screened positive for clinical insomnia and 26.0% for subthreshold insomnia. Greater age and retirement were associated with a lower likelihood of insomnia. Adverse childhood experiences, traumatic life events, lower education and income were associated with greater risk for insomnia. A “dose-response” association was observed for health comorbidities, with increasing levels of insomnia associated with elevated odds of psychiatric and medical conditions (clinical vs no insomnia odds ratio = 1.8–13.4) and greater reductions in health and psychosocial functioning (clinical vs no insomnia Cohen’s d = 0.2–0.4). The prevalence of current suicidal ideation was 3–5 times higher in veterans with clinical and subthreshold insomnia relative to those without insomnia (23.9% and 13.6% vs 4.5%, respectively). CONCLUSIONS: Nearly 2 in 5 US veterans experience clinical or subthreshold insomnia, which is associated with substantial health burden and independent risk for suicidal ideation. Results underscore the importance of assessment, monitoring, and treatment of insomnia in veterans as they transition from the military. CITATION: Byrne SP, McCarthy E, DeViva JC, Southwick SM, Pietrzak RH. Prevalence, risk correlates, and health comorbidities of insomnia in US military veterans: results from the 2019–2020 National Health and Resilience in Veterans Study. J Clin Sleep Med. 2021;17(6):1267–1277.

Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

Introduction: Boerhaave's syndrome is a life-threatening spontaneous perforation of the esophagus associated with significant morbidity and mortality. Historically, thoracotomy has been the mainstay of treatment, but is associated with high morbidity and pain. Minimally invasive approaches provide alternative treatment possibilities. This systematic review together with inclusion of a case series from a tertiary esophagogastric unit assesses current evidence focused on minimally invasive surgical management of this condition. Methods: A systematic review was conducted in line with MOOSE (Meta-analyses Of Observational Studies in Epidemiology) guidelines. Electronic databases PubMed, MEDLINE, and Cochrane Library were searched, and articles focusing on the minimally invasive management of Boerhaave's syndrome were identified and scrutinized. We also report demographics and outcomes for a consecutive case series of patients with acute Boerhaave's syndrome managed via thoracoscopy. Results: Fifteen studies were included comprising 5 retrospective cohort studies and 10 case reports. Management strategies were divided into three categories: thoracoscopic, endoscopic, and laparoscopic. Overall mortality rates for each treatment modality were 2%, 13%, and 33%, and treatment success rates 98%, 38%, and 67%, respectively. Postoperative infective complications were seen in 79% of patients, with only 2 patients requiring salvage thoracotomy. In our local case series, we report 4 consecutive patients managed with thoracoscopy, with a 100% treatment success rate. Conclusion: Minimally invasive approaches in the management of Boerhaave's syndrome are safe and effective. We propose a selective management algorithm involving a minimally invasive approach to management of this life-threatening condition. Registered with local clinical outcomes team as service evaluation. (Approval number sev/0171).

Introduction Trimethylamine N-oxide (TMAO) is formed in the liver from trimethylamine, and is exclusively generated by gut microbiota from the metabolism of dietary carnitine and choline. Elevated plasma levels have been implicated in the pathogenesis of Type 2 Diabetes and cardiovascular disease. The Endobarrier is an endoscopically implanted duodenal jejunal bypass liner (DJBL) designed to mimic the effects of bariatric surgery leading to significant weight loss and improvements in glycaemic control and we present novel data of its effects on the plasma metabolic profile of these patients. Methods The Endobarrier Trial (NCT02459561) is a large multicentre, randomised, controlled trial across two sites in the UK which recruited 170 patients with Type 2 Diabetes and BMI 30–50 kg/m2. Participants were randomised to receive the DJBL (n=85) for one year or conventional medical therapy, diet and exercise (n=85). Plasma samples were collected from all participants at baseline, 6 months and 1 year and analysed using 1H NMR spectroscopy and multivariate statistical analysis to identify key metabolic perturbations between both patient cohorts. Results A total of 112 patients were followed up for one year. 309 plasma samples were processed and then analysed. A typical 1H NMR plasma spectrum is shown in figure 1. Reduction in plasma concentrations of trimethylamine N-oxide (TMAO) were found in the DJBL group at 6 months and 1 year compared with the control group. Conclusions Raised levels of Plasma TMAO have been associated with the development of diabetes and in this study were found to reduce following 6 months and 1 year of DJBL therapy compared with controls. This is the first study of its kind to explore alterations in the metabolic profiles of patients receiving the DJBL by utilising high field 1H nuclear magnetic resonance (NMR) spectroscopy technique. These results may provide a possible insight into the mechanisms of how this device may elicit its effect on weight loss and glycaemic improvement, by reducing plasma TMAO and potentially altering the gut microbial metabolic function.

In esophageal adenocarcinoma (EAC) with apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) debate remains as to whether esophagectomy is required. Recurrence after pCR is not limited to distant metastases outside radiation or resection fields. It is unknown if cancer persists below the lower detection limit of current diagnostic technology. Trials randomising patients with apparent pCR to esophagectomy or active surveillance are currently recruiting in an attempt to spare patients the morbidity of esophagectomy. Methods Single cell (scRNAseq) was performed on fresh tissue taken at surgical resection to determine the transcriptomic profiles of cell populations in 24 EAC tumours and matched normal samples. Five tumour-normal pairs were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to confirm pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three patients was used to compare transcriptomic profiles before and after NAT. Cancer cells were assigned a cancer stem cell module score curated from published gene sets. Results We analysed a total of 22,738 single cells forming 29 different cell states. In two samples with pCR, we repeated the pathological analysis and performed IHC using antibodies to known cancer proteins and identified no residual cancer cells (figure 1A). Bulk tissue RNA (figure 1B) and proteomic analysis did not detect cancer genes or proteins in the pCR samples. ScRNAseq, conversely, revealed small populations of persistent cancer cells in both complete responders (12/978 and 45/774) (figure 1C). Transcriptomic analysis of these residual cells identified upregulation of stem cell markers and high cancer stem cell scores in these remaining cells (figure 1D). Conclusion We have determined the cell states present across multiple different EAC and normal esophageal samples. We have shown cancer cells persisting after NAT, in patients with apparent pCR, beneath the lower detection limit of standard diagnostic approaches. These cells express gene programs consistent with cancer stem cells. Cancer stem cells are a critical subpopulation that drive tumour initiation, growth, and resistance to therapy. Esophagus sparing approaches in pCR may subject patients to risk of progression.

Background Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals. Methods We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semistructured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCP from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24 month) interval risk-based screening. Results Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWD, referral into screening of PWD with diabetic changes regardless of planned interval. For PWD the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCP and PWD that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWD, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system. Conclusions Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.

BackgroundThe EndoBarrier®(GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months.ResultsThere was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98;p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47;p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0;p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48;p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated.ConclusionsThe results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss.Trial registrationCurrent Controlled Trials ISRCTN30845205.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.

Background Trigeminal neuralgia (TGN) is a debilitating disorder, and in patients for whom medical management is not sufficient, there are several therapeutic options. Microvascular decompression (MVD) for TGN has been shown to be highly effective; however, pain does recur after MVD in some patients. Therapeutic options for recurrent TGN are the same as those for primary TGN, including re-exploration of MVD (re-MVD). In this study we review our practice of re-MVD, comparing it with alternative options and assessing its safety and efficacy. Methods Retrospective analysis of prospectively collected data of patients undergoing re-MVD between 2007 and 2016. Results Thirty-two patients underwent re-MVD, all with a Barrow Neurosurgical Institute Pain Index (BNPI) of IV or V. Postoperatively, 87% of patients reported an improvement in their BNPI to III or better, with 50% being BNPI 1 or 2. Eleven patients without distortion or vascular conflict at the time of re-exploration underwent intraoperative neurolysis, and 90% reported improvement in their BNPI. Kaplan-Meier analysis showed a median pain-free period of 36 months after re-MVD. There were no significant complications. Conclusions Re-MVD is a safe and effective method of treating recurrent TGN. Intraoperative neurolysis is an important tool in re-exploration and should be considered when there is no ongoing compression or distortion of the trigeminal nerve.

BACKGROUND: Although a delay of 24 hours for hip fracture repair is associated with medical complications and costs, it is unknown how long patients wait for surgery for hip fracture. We describe novel methods for measuring exact urgent and emergent surgical wait times (in hours) and the factors that influence them. METHODS: Adults aged 45 years and older who underwent surgery for hip fracture (the most common urgently performed procedure) in Ontario, Canada, between 2009 and 2014 were eligible. Validated data from linked health administrative databases were used. The primary outcome was the time elapsed from hospital arrival recorded in the National Ambulatory Care Reporting System until the time of surgery recorded in the Discharge Abstract Database (in hours). The influence of patient, physician and hospital factors on wait times was investigated using 3-level, hierarchical linear regression models. RESULTS: Among 42 230 patients with hip fracture, the mean (SD) wait time for surgery was 38.76 (28.84) hours, and 14 174 (33.5%) patients underwent surgery within 24 hours. Variables strongly associated with delay included time for hospital transfer (adjusted increase of 26.23 h, 95% CI 25.38 to 27.01) and time for preoperative echocardiography (adjusted increase of 18.56 h, 95% CI 17.73 to 19.38). More than half of the hospitals (37 of 72, 51.4%), compared with 4.8% of surgeons and 0.2% of anesthesiologists, showed significant differences in the risk-adjusted likelihood of delayed surgery. INTERPRETATION: Exact wait times for urgent and emergent surgery can be measured using Canada’s administrative data. Only one-third of patients received surgery within the safe time frame (24 h). Wait times varied according to hospital and physician factors; however, hospital factors had a larger impact.

BACKGROUND AND AIMS: Obesity associated with diabetes mellitus is a significant worldwide problem associated with considerable health care costs. Whilst surgical intervention is effective, it is invasive, costly and associated with complications. This study aims to evaluate the safety and efficacy of the EndoBarrier®, a duodenal-jejunal sleeve bypass as an alternative treatment of diabetes mellitus in obese patients. MATERIALS AND METHODS: This was a multi-centre, non-randomised trial recruiting obese patients with type 2 diabetes from three sites in the UK. Eligible participants had a BMI of 30-50 kg/m2and HbA1c levels of 7.5-10%. The study comprised a 12-month period with the EndoBarrier® inserted and a 6-month follow-up period after it had been explanted. The primary study outcomes were weight, BMI, HbA1c levels and fasting insulin and glucose levels. RESULTS: Forty-five patients were recruited and 31 patients (69%) completed the 12-month study period. Significant reductions in weight (95%CI 0.62-29.38; p

Burn-related mortality has decreased significantly over the past several decades. Although often attributed in part to regionalization of burn care, this has not been evaluated at the population level.We conducted a retrospective, population-based cohort study of all patients with 20% or higher total body surface area burn injury in Ontario, Canada. Adult (≥16 years) patients injured between 2003 and 2013 were included. Deaths in the emergency department were excluded. Logistic generalized estimating equations were used to estimate risk-adjusted 30-day mortality. Mortality trends were compared at burn and nonburn centers.Seven hundred seventy-two patients were identified at 84 centers (2 burn, 82 nonburn). Patients were 74% (n = 570) male, of median age 46 (interquartile range [IQR], 35-60) years and median total body surface area 35% (IQR, 25-45). Mortality at 30 days was 19% (n = 149). The proportion of patients treated at a burn center increased from 57% to 71% between 2003 and 2013 (p = 0.07). Average risk-adjusted 30-day mortality rates decreased over time; there were significantly reduced odds of death in 2010 to 2013 compared with 2003 to 2006 (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.25-0.61). Burn centers exhibited significantly reduced mortality from 2003-2006 to 2010-2013 (OR, 0.36; 95% CI, 0.34-0.38) compared with nonburn centers (OR, 0.41; 95% CI, 0.13-1.24).Mortality rates have decreased over time; significant improvements have occurred at burn centers, whereas mortality rates at nonburn centers vary widely. A high proportion of patients continue to receive care outside of burn centers. These data suggest that there are further opportunities to regionalize burn care and in so doing, potentially lower burn-related mortality.Epidemiological study, level III; Therapy, level IV.

BACKGROUND:Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a QuinteT Recruitment Intervention (QRI).PATIENTS/METHODS:The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio-recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization.RESULTS:Recruitment proved to be extremely difficult with only two patients recruited during the first two months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first two months (2/22) to 40% (26/65) in the four months thereafter. Center B, commencing recruitment three months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers.CONCLUSIONS:The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.International Journal of Obesity accepted article preview online, 03 July 2017. doi:10.1038/ijo.2017.153.

This study examined factors influencing parent willingness to use D-Cycloserine (DCS) for treating child anxiety. N = 222 parents were given information about using DCS to treat anxiety. They were then asked to rate their willingness to allow their child to take DCS/antibiotics for mild anxiety, severe anxiety, or an infection. The associations between willingness to use DCS and parental trait anxiety, demographics, as well as specific concerns regarding the medication, were examined. Parents could also provide written responses regarding their attitudes to DCS, which were analysed for themes. Parents reported concerns regarding potential side-effects from DCS. More severe anxiety was associated with more willingness to consent; however, parents were more willing to use antibiotics to treat an infection than DCS to treat their child's anxiety. The degree of perceived benefit from DCS was most strongly associated with parents’ willingness to use it. Overall, parents expressed mixed views, reporting they would consider using DCS to treat their child; however, they had significant concerns about it. Results suggest providing parents with information explaining how DCS works, its risks and potential benefits may increase its acceptability.

YouTube is a global medium used predominantly by young adults (aged 18–49 years). This study examined the quality of YouTube information regarding ACL injury and reconstruction. YouTube was searched on the 13th of June 2015 for “ACL” and “anterior cruciate ligament” with/without associated terms of “injury”, “reconstruction”, and “surgery”. Videos were evaluated by two independent reviewers [EF (Reviewer 1), (Reviewer 2)] using two recognized information scoring systems (Modified DISCERN (MD) 0–5 and JAMA Benchmark 0–4) and an adaptation of a score designed for written ACL information [ACL Specific Score (ASS) 0–25]. The ASS categorized scores as very good (21–25), good (16–20), moderate (11–15), poor (6–10), and very poor (0–5). Number of views/likes/dislikes, animation, and continent of origin and source (e.g., corporate/educational) were recorded. Correlation of video characteristics with number of views was examined using the analysis of variance (ANOVA) model. Agreement between reviewers was assessed by Interclass Correlation Co-efficient (ICC). Following a filtering process of the 964,770 identified videos, 39 videos were retained. The mean MD score was 2.3 (standard deviation (SD) ±0.9) for Reviewer 1 and 2.2 (SD ±0.9) for Reviewer 2 (ICC = 0.7). The mean JAMA score was 2.5(SD ±0.7) for Reviewer 1 and 2.3 (SD ±0.7) for Reviewer 2 (ICC = 0.8). The mean ASS was 6.3 (SD ±3.5) for Reviewer 1 and 4.6 (SD ±2.9) for Reviewer 2 (ICC = 0.9). Five videos achieved moderate score (13%), while 15 (38%) and 19 (49%) scored as poor and very poor, respectively. There was no correlation between number of views and video quality/video source for any scoring system. The majority of videos viewed on YouTube regarding ACL injury and treatment are of low quality.

Pulmonary embolism (PE) is a leading cause of delayed mortality in patients with severe injury. While low-molecular-weight heparin (LMWH) is often favored over unfractionated heparin (UH) for thromboprophylaxis, evidence is lacking to demonstrate an effect on the occurrence of PE. This study compared the effectiveness of LMWH versus UH to prevent PE in patients following major trauma.Data for adults with severe injury who received thromboprophylaxis with LMWH or UH were derived from the American College of Surgeons Trauma Quality Improvement Program (2012-2015). Patients who died or were discharged within 5 days were excluded. Rates of PE were compared between propensity-matched LMWH and UH groups. Subgroup analyses included patients with blunt multisystem injury, penetrating truncal injury, shock, severe traumatic brain injury, and isolated orthopedic injury. A center-level analysis was performed to determine if practices with respect to choice of prophylaxis type influence hospital PE rates.We identified 153,474 patients at 217 trauma centers who received thromboprophylaxis with LMWH or UH. Low-molecular-weight heparin was given in 74% of patients. Pulmonary embolism occurred in 1.8%. Propensity score matching yielded a well-balanced cohort of 75,920 patients. After matching, LMWH was associated with a significantly lower rate of PE compared with UH (1.4% vs. 2.4%; odds ratio, 0.56; 95% confidence interval, 0.50-0.63). This finding was consistent across injury subgroups. Trauma centers in the highest quartile of LMWH utilization (median LMWH use, 95%) reported significantly fewer PE compared with centers in the lowest quartile (median LMWH use, 39%; 1.2% vs. 2.0%; odds ratio, 0.59; 95% confidence interval, 0.48-0.74).Thromboprophylaxis with LMWH (vs. UH) was associated with significantly lower risk of PE. Trauma centers favoring LMWH-based prophylaxis strategies reported lower rates of PE. Low-molecular-weight heparin should be the anticoagulant agent of choice for prevention of PE in patients with major trauma.Therapeutic study, level III.

IntroductionSurgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.Methods and analysisWe will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.Ethics and disseminationThis study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.Trial registration numberNCT10386621.

Background Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20–30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. Methods Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. Results A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal–external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). Conclusion The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients., Early recurrence after surgery for adenocarcinoma of the oesophagus is common. A risk prediction model was derived using modern machine learning methods that accurately predicts risk of early recurrence using postoperative pathology. Machine learning may help

Objectives/aims To explore the burden of neurocognitive impairments in a cohort of Individuals with Korsakoff’s psychosis requiring current long stay psychiatric care. To consider additional therapeutic interventions to target the health care burden potentially created by these comorbidities. Methods As part of a comprehensive systematic review of Korsakoff’s Psychosis, an audit was performed of 114 Individuals currently requiring long-term care in an approved psychiatric facility during the year of 2018. Medical and psychiatric diagnoses as well as pharmacological histories were examined. Alcoholic and non-alcoholic aetiologies were considered, the latter may be underdiagnosed (Nikolakaros et al, 2018). Results Thirteen individuals were identified with a formal diagnosis of Korsakoff’s syndrome (KS) and all continue to require structured Inpatient care due to their levels of neurocognitive impairment and psychiatric presentations. Episodic memory is severely affected, as is the learning of new semantic memories. Patients with Korsakoff’s psychosis are capable of new learning in a calm, structured environment with cued new information (Kopelman et al, 2009). Conclusions Individuals with Korsakoff’s psychosis may have comorbid psychiatric symptoms including mood, anxiety, aggression or psychotic disorders that command therapeutic interventions. Specific memory targeting intervention may not prioritized. Potential therapeutic interventions include Errorless learning (EL) which target levels of competence and independence (Rensen et al, 2017). EL is reported to improve symptoms of psychosis, aggression, apathy or mood disorders. Behavioural Interventions include environmental adaptations and cognitive remediation, which may be combined with pharmacological approaches such as donepezil or memantine to target cognition (Johnson and Fox, 2018). However, these approaches are not identical to those required by Alzheimer’s disease or other dementing disorders. Epidemiological and genomic studies could be preformed to identify those particularly at risk of developing this potentially life-altering condition. References Nikolakaros, G., Kurki, T., Paju, J., Papageorgiou, S.G., Vataja, R., llonen, T. Korsakoff Syndrome in Non-alcoholic Psychiatric Patients Variable Cognitive Presentation and Impaired Frontotemporal Connectivity. Frontiers in Psychiatry 2018;9(204). Kopelman M.D., Thomson, A.D., Guerrini, I., Marshall, E.J. The Korsakoff Syndrome: Clinical Aspects, Psychology and Treatment. Alcohol & Alcoholism 2009;44(2):148–154. Rensen, Y, Egger, J, Westhoff, J., Walvoort, S., Kessels, R. (2017) The effect of errorless learning on quality of life in patients with Korsakoff’s syndrome. Neuropsychiatric Disease and Treatment 2017;13:2867–2873. Johnson, J.M., and Fox, V. Beyond Thiamine: Treatment for Cognitive Impairment in Korsakoff’s Syndrome. Psychosomatics 2018;59(4):311–317.

Motor vehicle crashes (MVCs) are a leading public health concern. Emergency medical service (EMS) response time is a modifiable, system-level factor with the potential to influence trauma patient survival. The relationship between EMS response time and MVC mortality is unknown.To measure the association between EMS response times and MVC mortality at the population level across US counties.This population-based study included MVC-related deaths in 2268 US counties, representing an estimated population of 239 464 121 people, from January 1, 2013, through December 31, 2015. Data were analyzed from October 1, 2017, through April 30, 2018.The median EMS response time to MVCs within each county (county response time), derived from data collected by the National Emergency Medical Service Information System.The county rate of MVC-related death, calculated using crash fatality data recorded in the Fatality Analysis Reporting System of the National Highway Traffic Safety Administration.During the study period, 2 214 480 ambulance responses to MVCs were identified (median, 229 responses per county [interquartile range (IQR), 73-697 responses per county]) in 2268 US counties. The median county response time was 9 minutes (IQR, 7-11) minutes. Longer response times were significantly associated with higher rates of MVC mortality (≥12 vs7 minutes; mortality rate ratio, 1.46; 95% CI, 1.32-1.61) after adjusting for measures of rurality, on-scene and transport times, access to trauma resources, and traffic safety laws. This finding was consistent in both rural/wilderness and urban/suburban settings, where a significant proportion of MVC fatalities (population attributable fraction: rural/wilderness, 9.9%; urban/suburban, 14.1%) were associated with prolonged response times (defined by the median value, ≥10 minutes and ≥7 minutes, respectively).Among 2268 US counties, longer EMS response times were associated with higher rates of MVC mortality. A significant proportion of MVC-related deaths were associated with prolonged response times in both rural/wilderness and urban/suburban settings. These findings suggest that trauma system-level efforts to address regional disparities in MVC mortality should evaluate EMS response times as a potential contributor.

BACKGROUND Emergency medical service (EMS) prehospital times vary between regions, yet the impact of local prehospital times on trauma center (TC) performance is unknown. To inform external benchmarking efforts, we explored the impact of EMS prehospital times on the risk-adjusted rate of emergency department (ED) death and overall hospital mortality at urban TCs across the United States. METHODS We used a novel ecologic study design, linking EMS data from the National EMS Information System to TCs participating in the American College of Surgeons' Trauma Quality Improvement Program (TQIP) by destination zip code. This approach provided EMS times for populations of injured patients transported to TQIP centers. We defined the exposure of interest as the 90th percentile total prehospital time (PHT) for each TC. TCs were then stratified by PHT quartile. Analyses were limited to adult patients with severe blunt or penetrating trauma, transported directly by land to urban TQIP centers. Random-intercept multilevel modeling was used to evaluate the risk-adjusted relationship between PHT quartile and the outcomes of ED death and overall hospital mortality. RESULTS During the study period, 119,740 patients met inclusion criteria at 113 TCs. ED death occurred in 1% of patients, and overall mortality was 7.2%. Across all centers, the median PHT was 61 minutes (interquartile range, 53-71 minutes). After risk adjustment, TCs in regions with the shortest quartile of PHTs (

IMPORTANCE: Adhesive small-bowel obstruction (aSBO) is a potentially chronic, recurring surgical illness. Although guidelines suggest trials of nonoperative management, the long-term association of this approach with recurrence is poorly understood. OBJECTIVE: To compare the incidence of recurrence of aSBO in patients undergoing operative management at their first admission compared with nonoperative management. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, propensity-matched, retrospective cohort study used health administrative data for the province of Ontario, Canada, for patients treated from April 1, 2005, through March 31, 2014. The study population included adults aged 18 to 80 years who were admitted for their first episode of aSBO. Patients with nonadhesive causes of SBO were excluded. A total of 27 904 patients were included and matched 1:1 by their propensity to undergo surgery. Factors used to calculate propensity included patient age, sex, comorbidity burden, socioeconomic status, and rurality of home residence. Data were analyzed from September 10, 2017, through October 4, 2018. EXPOSURES: Operative vs nonoperative management for aSBO. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of recurrence of aSBO among those with operative vs nonoperative management. Time-to-event analyses were used to estimate hazard ratios of recurrence while accounting for the competing risk of death. RESULTS: Of 27 904 patients admitted with their first episode of aSBO, 6186 (22.2%) underwent operative management. Mean (SD) patient age was 61.2 (13.6) years, and 51.1% (14 228 of 27 904) were female. Patients undergoing operative management were younger (mean [SD] age, 60.2 [14.3] vs 61.5 [13.4] years) with fewer comorbidities (low burden, 382 [6.2%] vs 912 [4.2%]). After matching, those with operative management had a lower risk of recurrence (13.0% vs 21.3%; hazard ratio, 0.62; 95% CI, 0.56-0.68; P

Background: There is a growing interest in comparing the effectiveness and costs of alternative forms of bariatric surgery. We aimed to examine the per-patient, procedural costs of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and adjustable gastric banding (AGB) in the United Kingdom.Methods: Multi-centre (two National Health Service; NHS and one private hospital) micro-costing, using a time-and-motion study. Prospective collection of surgery times, staff quantities, equipment, instruments and consumables for 12 patients (four RYGB, five SG, three AGB) from patients’ first surgeon interaction on the day of surgery to departure from the theatre recovery area. Costs were attached to quantities and mean costs compared. Sensitivity and scenario analyses assessed the impact of varying surgery inputs and consideration of additional plausible factors respectively on total costs.Results: Mean procedural costs were £5,002 for RYGB, £4,306 for SG and £2,527 for AGB. Varying staff seniority or altering procedure times had small impacts on costs (±4-6%). Reducing prices of consumables by 20% reduced costs by 10-13%. Accounting for differences in surgical technique by altering the number of staple reloads used impacted costs by ±7-10%. Adjusted total costs from scenario analyses were similar to NHS tariffs for RYGB and SG (difference of £51 and -£119 respectively), but were much lower for AGB (difference of £1,982).Conclusions: These detailed costs will allow for more precise reimbursement of bariatric surgery and support comprehensive assessments of cost-effectiveness. Additional work to investigate costs of post-surgical care, re-operations and life-long support received by patients following surgery is required.

Uncertainty exists about risk:benefit of proximal intestinal exclusion with Endobarrier (EB), a novel endoscopic duodenal jejunal liner device for obesity, both with and without diabetes. In view of this, during 2017, an independent, secure, on-line registry was established under the auspices of the Association of British Clinical Diabetologists, for the collection of safety and efficacy data worldwide. As of December 2017, data had been entered on 403 patients {age 51.3 ± 11.8 year, 62% male, 89% europid, 74% diabetes, BMI 42.6 ± 10.2 kg/m2} from 13 centres in 4 countries: Australia, Austria, Czech Republic and United Kingdom. EB led to many benefits, including: in those with both baseline and explant data, mean ± SD weight fell by 14.5 ± 10.3 kg from 125.3 ± 26.7 to 110.8 ± 26.4 kg (n = 265 p Disclosure R.E.J. Ryder: Other Relationship; Self; AstraZeneca. Speaker's Bureau; Self; Bioquest, Janssen Pharmaceuticals, Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk A/S. L. Munro: None. J.J. McMaster: None. J. Bessell: None. J.M. Bascomb: None. J.E. Collins: None. L. Kow: None. J. Chisholm: None. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc.. P.N. Pferschy: None. J.P. Teare: Research Support; Self; GI Dynamics Inc.. J.C. Mason: None. J.P. Byrne: None. M.C. Wyres: None. M.L. Cull: None. W. Burbridge: Other Relationship; Self; Menarini Group. S.P. Irwin: None. M. Yadagiri: None. E. Fogden: None. M. Anderson: None. P. Sen Gupta: None. M. Benes: None.

Summary Objective The objective of this study was to assess the biomechanical stability of three types of chondral flap repair techniques as well as a hydrogel scaffold implantation on the acetabular articular surface using a physiological human cadaveric model. Methods Chondral flaps were created in the antero-superior zone of the acetabulum in a series of human cadaveric hip joints. The chondral flap was repaired by fibrin glue, cyanoacrylate, suture technique and an agarose hydrogel scaffold sealed with fibrin glue using six hips in each case. After each repair, the specimens were mounted in a validated jig and tested for 1500 gait cycles. In order to determine the stability of the repair, specimens were evaluated arthroscopically at specific intervals. Results The fibrin glue and cyanoacrylate techniques were technically the easiest to perform arthroscopically, all flaps repaired with fibrin were detached at 50 cycles while those repaired with cyanoacrylate lasted for an average of 635 cycles. On the other hand, both the suture repair and scaffold implantation techniques were more technically challenging but were both stable till the endpoint of 1500 cycles. Conclusion Fibrin glue on its own does not provide sufficient fixation to repair chondral flaps on the acetabular surface. Cyanoacrylate repairs universally failed midway through the testing protocol employed here, raising doubts as to the effectiveness of that technique. The suture and hydrogel scaffold technique were the most reliable for chondral repair at any given cycle. The results of this biomechanical study demonstrate the relative effectiveness of chondral repair and fixation techniques.

Background For exposure therapy to be successful, it is essential that fear extinction learning extends beyond the treatment setting. d-Cycloserine (DCS) may facilitate treatment gains by increasing generalization of extinction learning, however, its effects have not been tested in children. We examined whether DCS enhanced generalization of fear extinction learning across different stimuli and contexts among children with specific phobias. Methods The study was a double-blind placebo-controlled randomized controlled trial among dog or spider phobic children aged 6-14. Participants ingested either 50 mg of DCS (n = 18) or placebo (n = 17) before receiving a single prolonged exposure session to their feared stimulus. Return of fear was examined 1 week later to a different stimulus (a different dog or spider), presented in both the original treatment context and an alternate context. Avoidance and fear were measured with Behavior Approach Tests (BATs), where the child was asked to increase proximity to the stimulus while reporting their fear level. Results There were no differences in BAT performance between groups during the exposure session or when a new stimulus was later presented in the treatment context. However, when the new stimulus was presented in a different context, relative to placebo, the DCS group showed less avoidance (P =.03) and less increase in fear (P =.04) with moderate effect sizes. Conclusions DCS enabled children to better retain their fear extinction learning. This new learning generalized to different stimuli and contexts.

Traumatic subarachnoid hemorrhage is a common radiographic finding associated with traumatic brain injury. The objective of this investigation is to evaluate the association between hospital-level ICU admission practices and clinically important outcomes for patients with isolated traumatic subarachnoid hemorrhage and mild clinical traumatic brain injury.Multicenter observational cohort.Trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program spanning January 2012 to March 2014.A total of 14,146 subjects, 16 years old and older, admitted to 215 trauma centers with isolated traumatic subarachnoid hemorrhage and Glasgow Coma Scale score 13 or greater. Patients with concurrent intracranial injuries, severe injury to other body regions, or tests positive for alcohol or illicit substances were excluded.ICU admission.The primary outcome was need for neurosurgical intervention, defined as insertion of an intracranial monitor/drain or craniectomy/craniotomy. Secondary outcomes describing the clinical course included hospital discharge disposition, in-hospital mortality, and length of stay. Admission to ICU was common within the cohort (44.6%), yet the need for neurosurgical intervention was rare (0.24%). Variability was high between centers and remained so after adjusting for differences in case-mix and hospital-level characteristics (median odds ratio, 4.1). No significant differences in neurosurgical interventions, mortality, or discharge disposition to home under self-care were observed between groups of the highest and lowest ICU admitting hospitals. However, those in highest admitting group "stayed" in hospital 1.13 (95% CI, 1.07-1.20; p0.001) times that of the lowest admitting group.Critical care admission for mild traumatic brain injury patients with isolated traumatic subarachnoid hemorrhage is frequent and highly variable despite low probability of requiring neurosurgical intervention. Reevaluation of hospital-level practices may represent an opportunity for resource optimization when managing patients with mild clinical traumatic brain injury and associated isolated traumatic subarachnoid hemorrhage.

Racial disparities in medical treatment for seriously injured patients across the spectrum of care are well established, but racial disparities in end of life decision making practices have not been well described. When time from admission to time to withdrawal of life-sustaining treatment (WLST) increases, so does the potential for ineffective care, health care resource loss, and patient and family suffering. We sought to determine the existence and extent of racial disparities in late WLST after severe injury.We queried the American College of Surgeons' Trauma Quality Improvement Program (2013-2016) for all severely injured patients (Injury Severity Score,15; age,16 years) with a WLST order longer than 24 hours after admission. We defined late WLST as care withdrawn at a time interval beyond the 75th percentile for the entire cohort. Univariate and multivariate analyses were performed using descriptive statistics, and t tests and χ tests where appropriate. Multivariable regression analysis was performed with random effects to account for institutional-level clustering using late WLST as the primary outcome and race as the primary predictor of interest.A total of 13,054 patients from 393 centers were included in the analysis. Median time to WLST was 5.4 days (interquartile range, 2.6-10.3). In our unadjusted analysis, African-American patients (10.1% vs. 7.1%, p0.001) and Hispanic patients (7.8% vs. 6.8%, p0.001) were more likely to have late WLST as compared to early WLST. After adjustment for patient, injury, and institutional characteristics, African-American (odds ratio, 1.42; 95% confidence interval, 1.21-1.67) and Hispanic (odds ratio, 1.23; 95% confidence interval, 1.04-1.46) race were significant predictors of late WLST.African-American and Hispanic race are both significant predictors of late WLST. These findings might be due to patient preference or medical decision making, but speak to the value in assuring a high standard related to identifying goals of care in a culturally sensitive manner.Prognostic and epidemiologic study, level III.

Background Posttraumatic stress disorder (PTSD) is a chronic and often difficult-to-treat condition that is prevalent among military veterans. First-line pharmacotherapy for this population typically involves antidepressants; however, veterans who do not improve are sometimes prescribed antipsychotics such as risperidone. A 2011 randomized controlled trial of adjunctive risperidone versus placebo for veterans with chronic, antidepressant-resistant, military service-related PTSD revealed no difference between groups. Hence, there is a need to examine predictors of nonimprovement for chronic, treatment-resistant PTSD. Methods We examined correlates of nonimprovement and delayed improvement (ie, ≥12 weeks) using data from 267 veterans with chronic, antidepressant-resistant PTSD who were prescribed adjunctive risperidone or a placebo. Veterans received 1 to 4 mg adjunctive risperidone (n = 133; mean dose, 2.74 mg) or a placebo daily (n = 134) in addition to their original treatment regimen over the 24-week trial. Results Greater severity of PTSD symptoms at baseline, specifically reexperiencing (ie, nightmares) and emotional numbing (ie, sense of foreshortened future), was independently associated with nonimprovement. Of the 194 veterans (72.7%) who did improve, 95 (49.0%) showed delayed improvement, taking 12 weeks or longer to demonstrate a 10-point reduction in Clinician-Administered PTSD Scale scores. Emotional difficulties affecting role functioning, as assessed using the Veterans RAND 36-item Health Survey, independently predicted nonimprovement. Conclusions While results are indicative of nonspecific pharmacotherapeutic effects, they suggest that specific PTSD symptom clusters and impairment are associated with variable improvement in veterans with antidepressant-resistant PTSD. They underscore the importance of developing more effective and targeted pharmacotherapies for specific symptom clusters in this population.

Background Mental health disorders are prevalent before and after burn injury. However, the impact of burn injury on risk of subsequent mental health disorders is unknown. Study Design We conducted a population-based, self-matched longitudinal cohort study using administrative data in Ontario, Canada between 2003 and 2011. All adults who survived to discharge after major burn injury were included, and all mental health-related emergency department visits were identified. Rate ratios (RRs) for mental health visits in the 3 years after burn, compared with the 3 years before, were estimated using negative binomial generalized estimating equations. Results Among 1,530 patients with major burn injury, mental health visits were common both before (141 per 1,000 person years) and after (154 per 1,000 person years) injury. Mental health visits were most common in the 12 weeks immediately preceding injury. No significant difference in the overall visit rate was observed after burn (RR 0.97; 95% CI 0.78 to 1.20), although among patients with less than 1 pre-injury visit, mental health visits tripled (RR 3.72; 95% CI 2.70 to 5.14). Self-harm emergencies increased 2-fold (RR 1.95; 95% CI 1.15 to 3.33). Conclusions Mental health emergencies are prevalent among burn-injured patients. Although the overall rate of mental health visits is not increased after burn, the rate increases significantly among patients with one or fewer visits pre-injury. Self-harm risk increases significantly after burn injury, underscoring the need for screening and targeted interventions after discharge. An increased rate immediately before burn suggests an opportunity for injury prevention through mental healthcare.

We set out to compare the incidence of bowel repair and/or resection in a large cohort of patients with adhesive small bowel obstruction (SBO) managed operatively.Laparoscopic lysis of adhesions for adhesive SBO (aSBO) is becoming more common, yet might increase the risk of bowel injury given the distended and/or potentially compromised small bowel.We used administrative discharge data derived from a large geographic region, identifying patients who underwent surgery for their first episode of aSBO during 2005 to 2014. Procedure codes were used to determine the exposure: either an open approach or a laparoscopic approach (including procedures converted to open). The primary outcome was incidence of bowel intervention, defined as intraoperative enterotomy, suture repair of intestine, or bowel resection. We estimated the odds of bowel intervention after adjusting for patient and clinical factors.A total of 8584 patients underwent operation for aSBO. Patients undergoing laparoscopic procedures were younger with fewer comorbid conditions. The rate of laparoscopic approaches increased more than 3-fold during the study period (4.3%-14.3%, P0.0001). The incidence of bowel intervention was 53.5% versus 43.4% in laparoscopic versus open procedures (P0.0001). After adjustment for potential confounders, the odds of bowel intervention among patients treated laparoscopically versus open was 1.6 (95% confidence interval: 1.4-1.9).Laparoscopic procedures for aSBO are associated with a greater likelihood of intervention for bowel injury and/or repair. This increase might be due to challenges inherent with laparoscopic approaches in patients with distended small bowel. Surgeons should approach laparoscopic lysis of adhesions with a higher level of awareness and use strategies to mitigate this risk.

Introduction Obesity is a modern pandemic. One of the major complications of obesity is the development of diabetes which leads to considerable mortality, morbidity and enormous health care costs. 1 The EndoBarrier is an endoscopically implantable duodenal-jejunal sleeve bypass (DJSB); anchored in the duodenum, preventing ingested food from coming into contact with the proximal intestine and induces weight loss and improvement in glycaemic control. The aim of this prospective study was to assess the safety and efficacy of the EndoBarrier in obese patients with type 2 diabetes. Method This was a non-randomised study conducted at three investigational sites (Southampton, London, and Manchester) over an 18 month period with clinical and biochemical assessments carried out at 3 monthly intervals. The device was implanted for 12 months with 6 months follow up. All patients were obese with poorly controlled diabetes. Adverse events were recorded and statistical analysis was performed. Results A total of 45 subjects were enrolled into the study At 12 months following implant: 1) HbA1c significantly reduced from baseline at 0.8% below the mean at baseline (95% CI 0.1–1.6; p 2) Mean weight loss was 15 kg (95% CI 0.62–29.38; p 3) BMI was reduced by 4.9kg/m 2 (95% CI 1.1–8.7; p 14 patients withdrew from the study, 6 required premature EndoBarrier removal. Of these, only 2 patients presented with device related complications (device migration and gastrointestinal bleeding), the others withdrew due to unrelated medical adverse events. Conclusion The EndoBarrier appears to be a safe and effective treatment strategy in those who are overweight and have poor glycaemic control despite medical therapy, or in those who are eligible but decline bariatric surgery. Larger randomised controlled trials with longer follow-up periods post-explant of the device need to be performed to investigate the device’s effects on long term glycaemic control and weight. Reference Control C. f. D. & Prevention. Prevalence of overweight and obesity among adults with diagnosed diabetes-United States, 1988–1994 and 1999–2002. MMWR. Morbidity and mortality weekly report2004;53:1066. Disclosure of Interest None Declared

Background Improvements in survival after burns have resulted in more patients being discharged home after severe injury. However, the postdischarge health care needs of burn survivors are not well understood. We aimed to determine the rate and causes of unplanned presentation to acute care facilities in the 5 years after major burn injury. Methods Data derived from several population-based administrative databases were used to conduct a retrospective cohort study. All patients aged ≥16 years who survived to discharge after a major burn injury in 2003–2013 were followed for 1–5 years. All emergency department visits and unplanned readmissions were identified and classified by cause. Factors associated with emergency department visits were modeled using negative binomial generalized estimating equations. Factors associated with readmission were modeled using multivariable competing risk regression. Results We identified 1,895 patients who survived to discharge; 68% of patients had at least one emergency department visit and 30% had at least one readmission. Five-year mortality was 10%. The most common reason for both emergency department visits and readmissions was traumatic injury. After risk adjustment, patients who received their index care in a burn center experienced significantly less need for subsequent unplanned acute care, fewer emergency department visits (relative risk 0.61, 95% confidence interval, 0.52–0.72), and fewer hospital readmissions (hazard ratio 0.77, 95% confidence interval, 0.65–0.92). Conclusion Acute health care utilization is frequent after burn injury and is most commonly related to traumatic injuries. Burn-related events are uncommon beyond 30 days after discharge, suggesting low rates of burn recidivism. Patients treated at burn centers have significantly reduced unplanned health care utilization after their injury.

Background Enhanced recovery programmes improve outcomes in surgery, but their implementation after upper gastrointestinal resection has been limited. The aim of this study was to compare short-term outcomes for patients undergoing oesophagogastric surgery in an enhanced recovery programme (EROS). Methods EROS was developed after a multidisciplinary meeting by multiple rounds of revision. EROS was applied to all patients undergoing major upper GI resection at a university teaching hospital in the UK from 20/9/13, with data reviewed at 18/09/15. EROS was assessed to identify predictors for compliance. Results One hundred six patients underwent major upper GI resection including 81 oesophagectomies, 24 gastrectomies and 1 colonic interposition graft. Major complications (Clavien Dindo ≥3) occurred in 12 patients with 1 in-hospital death. Thirty-five patients (44%) were discharged on target day 8 of the EROS programme. Age and complications were independently associated with missing this discharge target. Conclusion Enhanced recovery is feasible and safe after major upper gastrointestinal surgery. Electronic supplementary material The online version of this article (doi:10.1007/s11605-017-3363-8) contains supplementary material, which is available to authorized users.

Background The Glasgow Coma Scale (GCS) is the most widely used measure of traumatic brain injury (TBI) severity. Currently, the arrival GCS motor component (mGCS) score is used in risk-adjustment models for external benchmarking of mortality. However, there is evidence that the highest mGCS score in the first 24 hours after injury might be a better predictor of death. Our objective was to evaluate the impact of including the highest mGCS score on the performance of risk-adjustment models and subsequent external benchmarking results. Study Design Data were derived from the Trauma Quality Improvement Program analytic dataset (January 2014 through March 2015) and were limited to the severe TBI cohort (16 years or older, isolated head injury, GCS ≤8). Risk-adjustment models were created that varied in the mGCS covariates only (initial score, highest score, or both initial and highest mGCS scores). Model performance and fit, as well as external benchmarking results, were compared. Results There were 6,553 patients with severe TBI across 231 trauma centers included. Initial and highest mGCS scores were different in 47% of patients (n = 3,097). Model performance and fit improved when both initial and highest mGCS scores were included, as evidenced by improved C-statistic, Akaike Information Criterion, and adjusted R-squared values. Three-quarters of centers changed their adjusted odds ratio decile, 2.6% of centers changed outlier status, and 45% of centers exhibited a ≥0.5-SD change in the odds ratio of death after including highest mGCS score in the model. Conclusions This study supports the concept that additional clinical information has the potential to not only improve the performance of current risk-adjustment models, but can also have a meaningful impact on external benchmarking strategies. Highest mGCS score is a good potential candidate for inclusion in additional models.