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Background: Evidence suggests that physical fitness interventions, mental health support and nutritional advice before surgery (prehabilitation) could reduce hospital stay and improve quality of life of patients with cancer. In this study we captured the opinions of a group of patients with cancer undergoing these interventions after treatment to discover what a prehabilitation programme should encompass., Methods: Patients from the Cancer and Rehabilitation Exercise (CARE) programme based in Nottingham took part in a 26-point online questionnaire about the design of prehabilitation programmes., Results: The questionnaire was completed over a 2-week period in December 2021 by 54 patients from the CARE programme. Their responses were as follows: 44 (81.5%) participants would have participated in prehabilitation had it been available to them and 28 (51.9%) ranked physical exercise as the most important component. Forty (74.1%) participants believed the counselling aspect of prehabilitation would have contributed to a successful outcome and 35 (64.8%) thought dietary advice would have benefitted them before surgery. Thirty-one (57.4%) participants preferred the programme to take place in a fitness centre, rather than at home or hospital and 43 (79.6%) would have liked to have known about prehabilitation from their doctor at the time of diagnosis., Conclusions: Patients are interested in prehabilitation to become more physically fit and mentally prepared for surgery. They expressed the need for a focus on physical exercise, counselling to improve mental health and personalised nutritional advice. Tailoring a prehabilitation programme, with input from patients, could contribute to improving patient outcomes following cancer treatments., (© 2023. The Author(s).)

Objective: The objective of this study was to evaluate the differences between patients who undergo cholecystectomy following index admission for cholecystitis, and those who are managed nonoperatively., Summary Background Data: Index emergency cholecystectomy following acute cholecystitis is widely recommended by national guidelines, but its effect on clinical outcomes remains uncertain., Methods: Data collected routinely from the Hospital Episode Statistics database (all admissions to National Health Service organizations in England and Wales) were extracted between April 1, 2002 and March 31, 2015. Analyses were limited to patients aged over 18 years with a primary diagnosis of cholecystitis. Exclusions included records with missing or invalid datasets, patients who had previously undergone a cholecystectomy, patients who had died without a cholecystectomy, and those undergoing cholecystectomy for malignancy, pancreatitis, or choledocholithiasis. Patients were grouped as either "no cholecystectomy" where they had never undergone a cholecystectomy following discharge, or "cholecystectomy." The latter group was then subdivided as "emergency cholecystectomy" when cholecystectomy was performed during their index emergency admission, or "interval cholecystectomy" when a cholecystectomy was performed within 12 months following a subsequent (emergency or elective) admission. Propensity Score Matching was used to match emergency and interval cholecystectomy groups. Main outcome measures included 1) One-year total length of hospital stay due to biliary causes following an index emergency admission with cholecystitis. 2) One-year mortality; defined as death occurring within 1 year following the index emergency admission with acute cholecystitis., Results: Of the 99,139 patients admitted as an emergency with acute cholecystitis, 51.1% (47,626) did not undergo a cholecystectomy within 1 year of index admission. These patients were older, with more comorbidities (Charlson Comorbidity Score ≥ 5 in 23.5% vs. 8.1%, P < 0.001) when compared to patients who did have a cholecystectomy. While all-cause 1-year mortality was higher in the nonoperated versus the operated group (12.2% vs. 2.0%, P < 0.001), gallbladder-related deaths were significantly lower than all other causes of death in the non-operated group (3.3% vs. 8.9%, P < 0.001). Following matching, 1-year total hospital admission time was significantly higher following emergency compared with interval cholecystectomy (17.7 d vs. 13 d, P < 0.001)., Conclusions: Over 50% of patients in England did not undergo cholecystectomy following index admission for acute cholecystitis. Mortality was higher in the nonoperated group, which was mostly due to non-gallbladder pathologies but total hospital admission time for biliary causes was lower over 12 months. Increasing the numbers of emergency cholecystectomy may risk over-treating patients with acute cholecystitis and increasing their time spent admitted to hospital., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Past studies have highlighted variation in in-hospital mortality rates among hospitals performing emergency laparotomy for large bowel perforation. The aim of this study was to investigate whether failure to rescue (FTR) contributes to this variability., Methods: Patients aged 18 years or over requiring surgery for large bowel perforation between 2013 and 2016 were extracted from the National Emergency Laparotomy Audit (NELA) database. Information on complications were identified using linked Hospital Episode Statistics data and in-hospital deaths from the Office for National Statistics. The FTR rate was defined as the proportion of patients dying in hospital with a recorded complication, and was examined in hospitals grouped as having low, medium or high overall postoperative mortality., Results: Overall, 6413 patients were included with 1029 (16.0 per cent) in-hospital deaths. Some 3533 patients (55.1 per cent) had at least one complication: 1023 surgical (16.0 per cent) and 3332 medical (52.0 per cent) complications. There were 22 in-hospital deaths following a surgical complication alone, 685 deaths following a medical complication alone, 150 deaths following both a surgical and medical complication, and 172 deaths with no recorded complication. The risk of in-hospital death was high among patients who suffered either type of complication (857 deaths in 3533 patients; FTR rate 24.3 per cent): 172 deaths followed a surgical complication (FTR-surgical rate 16.8 per cent) and 835 deaths followed a medical complication (FTR-medical rate of 25.1 per cent). After adjustment for patient characteristics and hospital factors, hospitals grouped as having low, medium or high overall postoperative mortality did not have different FTR rates (P = 0.770)., Conclusion: Among patients having emergency laparotomy for large bowel perforation, efforts to reduce the risk of in-hospital death should focus on reducing avoidable complications. There was no evidence of variation in FTR rates across National Health Service hospitals in England., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: With rapid advancement in the genomics of oesophagogastric (OG) cancer and raised expectations in clinical outcomes from patients and clinicians alike there is a clear need to determine the current research priorities in OG cancer surgery. The aim of our study was to use a modified Delphi process to determine the research priorities among OG cancer surgeons in the United Kingdom., Methods: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high priority research questions. All questions submitted and subsequently ranked were analysed on an anonymised basis., Results: In total, 427 questions were submitted in phase I and 75 with an OG cancer focus were taken forward for prioritisation in phase II. Phase III produced a final list of 12 high priority questions with an emphasis on tailored or personalised treatment strategies in OG cancer surgery., Conclusion: A modified Delphi process produced a list of 12 high priority research questions in OG cancer surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research across multiple centres., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2019 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: The prediction of a difficult cholecystectomy has traditionally been based on certain pre-operative clinical and imaging factors. Most of the previous literature reported small patient cohorts and have not used an objective measure of operative difficulty. The aim of this study was to develop a pre-operative score to predict difficult cholecystectomy, as defined by a validated intra-operative difficulty grading scale., Method: Two cohorts from prospectively maintained databases of patients who underwent laparoscopic cholecystectomy were analysed: the CholeS Study (8755 patients) and a single surgeon series (4089 patients). Factors potentially predictive of difficulty were correlated to the Nassar intra-operative difficulty scale. A multivariable binary logistic regression analysis was then used to identify factors that were independently associated with difficult laparoscopic cholecystectomy, defined as operative difficulty grades 3 to 5. The resulting model was then converted to a risk score, and validated on both internal and external datasets., Result: Increasing age and ASA classification, male gender, diagnosis of CBD stone or cholecystitis, thick-walled gallbladders, CBD dilation, use of pre-operative ERCP and non-elective operations were found to be significant independent predictors of difficult cases. A risk score based on these factors returned an area under the ROC curve of 0.789 (95% CI 0.773-0.806, p < 0.001) on external validation, with 11.0% versus 80.0% of patients classified as low versus high risk having difficult surgeries., Conclusion: We have developed and validated a pre-operative scoring system that uses easily available pre-operative variables to predict difficult laparoscopic cholecystectomies. This scoring system should assist in patient selection for day case surgery, optimising pre-operative surgical planning (e.g. allocation of the procedure to a suitably trained surgeon) and counselling patients during the consent process. The score could also be used to risk adjust outcomes in future research.

Introduction: Surgery is the primary curative treatment for oesophageal cancer, with considerable recent improvements in long-term survival. However, surgery has a long-lasting impact on patient's health-related quality of life (HRQOL). Through a multicentre European study, our research group was able to identify key symptoms that affect patient's HRQOL. These symptoms were combined to produce a tool to identify poor HRQOL following oesophagectomy (LAsting Symptoms after Oesophageal Resection (LASOR) tool). The objective of this multicentre study is to validate a six-symptom clinical tool to identify patients with poor HRQOL for use in everyday clinical practice., Methods and Analysis: Included patients will: (1) be aged 18 years or older, (2) have undergone an oesophagectomy for cancer between 2015 and 2019, and (3) be at least 12 months after the completion of adjuvant oncological treatments. Patients will be given the previously created LASOR questionnaire. Each symptom from the LASOR questionnaire will be graded according to impact on quality of life and frequency of the symptom, with a composite score from 0 to 5. The previously developed LASOR symptom tool will be validated against HRQOL as measured by the European Organisation for Research and Treatment of Cancer QLQC30 and OG25., Sample Size: With a predicted prevalence of poor HRQOL of 45%, based on the previously generated LASOR clinical symptom tool, to validate this tool with a sensitivity and specificity of 80%, respectively, a minimum of 640 patients will need to be recruited to the study., Ethics and Dissemination: NHS Health Research Authority (North East-York Research Ethics Committee) approval was gained 8 November 2019 (REC reference 19/NE/0352). Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility, and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared with wild-type mice, thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Furthermore, we identified the myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced muscle wasting and dysfunction in a preclinical model of pancreatic ductal adenocarcinoma (PDAC). Finally, compared with noncancer control patients, MYOC was significantly reduced in skeletal muscle of patients with PDAC defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of patients with cachectic cancer. SIGNIFICANCE: This work identifies a novel transcriptional mechanism that mediates skeletal muscle wasting in murine models of cancer cachexia that is disrupted in skeletal muscle of patients with cancer exhibiting cachexia., (©2020 American Association for Cancer Research.)

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear., Methods: All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien-Dindo classification (grades 0-V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan-Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination., Results: Some 1100 patients were included, with a median age of 69 (range 28-92) years; 48·1 per cent had stage III disease and cancer recurred in 428 patients (38·9 per cent). Complications of grade III or higher occurred in 244 patients (22·2 per cent). The most common complications were pulmonary (29·9 per cent), with a 13·0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10·0 and 9·6 per cent respectively. Patients with a grade III-IV leak did not have significantly reduced overall survival compared with those who had grade 0-I complications. However, patients with grade III-IV non-leak-related complications had reduced median overall survival (19·7 versus 42·7 months; P < 0·001) and disease-free survival (18·4 versus 36·4 months; P < 0·001). Cox regression analysis identified age, tumour stage, resection margin and grade III-IV non-leak-related complications as independent predictors of poor overall and disease-free survival., Conclusion: Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Several techniques have been described for esophagogastric anastomosis following esophagectomy. This study compared the outcomes of circular stapled anastomoses with semi-mechanical technique using a linear stapler., Methods: Perioperative data were extracted from a contemporaneously collected database of all consecutive esophagectomies for cancer with intrathoracic anastomoses performed in the Trent Oesophago-Gastric Unit between January 2015 and April 2018. Anastomotic techniques: circular stapled versus semi-mechanical, were evaluated and outcomes were compared. The primary outcome was anastomotic leak rate. Secondary outcomes included anastomotic stricture, overall complication rates, length of stay (LOS) and 30 day all-cause mortality., Results: One hundred and fifty-nine consecutive esophagectomies with intrathoracic anastomosis were performed during the study period. There were no significant differences between the two groups in terms of age, American Society of Anaesthesiologists score, Charlson comorbidity index and neoadjuvant therapies received. Circular stapled anastomoses were performed in 85 patients, while 74 patients received a semi-mechanical anastomosis. Clavien-Dindo complications II or more were higher in the circular stapled group (p = 0.02). There were 16 (10%) anastomotic leaks overall, three (4%) in semi-mechanical group versus 13 (15%) in the circular stapled group (p < 0.019). There was no statistically significant difference between the two groups in terms of LOS, 30-day mortality or the need for endoscopic dilatation of the anastomosis at 3 months follow-up., Conclusion: The move from a circular stapled to a semi-mechanical intrathoracic anastomosis has been associated with a reduced postoperative anastomotic leak rate following esophagectomy for esophageal cancer.

Background: Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables., Methods: Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set., Results: Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15-0.23), higher ASA scores (OR 0.19, 95% CI 0.15-0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58-0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48-0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34-0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001)., Conclusions: The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy.

Lack of sarcolemma-localized neuronal nitric oxide synthase mu (nNOSμ) contributes to muscle damage and fatigue in dystrophic muscle. In this study, we examined the effects of compensating for lack of nNOSμ with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice ( mdx ) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T 2 ) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and 31 phosphorus MRS ( 31 P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T 2 was attenuated ( P < 0.05) in treated mdx and wild-type mice compared with untreated mdx . During training, resting T 2 values did not change in wild-type and mdx mice from baseline values; however, the running distance completed during training was greater ( P < 0.05) in treated mdx (>90% of target distance) and wild-type (100%) than untreated mdx (60%). The post-contractile BOLD response was greater ( P < 0.05) in treated mdx that trained than untreated mdx , with no differences in muscle oxidative capacity, as measured by 31 P-MRS. Our findings indicate that PDE5 inhibition reduces muscle damage after a single bout of downhill running and improves performance during endurance training in dystrophic mice, possibly because of enhanced microvascular function. NEW & NOTEWORTHY This study examined the combined effects of PDE5 inhibition and exercise in dystrophic muscle using high-resolution magnetic resonance imaging and spectroscopy. Our findings demonstrated that sildenafil citrate reduces muscle damage after a single bout of downhill running, improves endurance-training performance, and enhances microvascular function in dystrophic muscle. Collectively, the results support the combination of exercise and PDE5 inhibition as a therapeutic approach in muscular dystrophies lacking nNOSμ.

Background: A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets., Methods: Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall's tau for dichotomous variables, or Jonckheere-Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis., Results: A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001)., Conclusion: We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty.

Background: Small bowel obstruction (SBO) is a common indication for emergency laparotomy. There are currently variations in the timing of surgery for patients with SBO and limited evidence on whether delayed surgery affects outcomes. The aim of this study was to evaluate the impact of time to operation on 30-day mortality in patients requiring emergency laparotomy for SBO., Methods: Data were collected from the National Emergency Laparotomy Audit (NELA) on all patients aged 18 years or older who underwent emergency laparotomy for all forms of SBO between December 2013 and November 2015. The primary outcome measure was 30-day mortality, with date of death obtained from the Office for National Statistics. Patients were grouped according to the time from admission to surgery (less than 24 h, 24-72 h and more than 72 h). A multilevel logistic regression model was used to explore the impact of patient factors, primarily delay to surgery, on 30-day mortality., Results: Some 9991 patients underwent emergency laparotomy requiring adhesiolysis or small bowel resection for SBO. The overall mortality rate was 7·2 per cent (722 patients). Within each time group, 30-day mortality rates were significantly worse with increasing age, ASA grade, Portsmouth POSSUM score and level of contamination. Patients undergoing emergency laparotomy more than 72 h after admission had a significantly higher risk-adjusted 30-day mortality rate (odds ratio 1·39, 95 per cent c.i. 1·09 to 1·76)., Conclusion: In patients who require an emergency laparotomy with adhesiolysis or resection for SBO, a delay to surgery of more than 72 h is associated with a higher 30-day postoperative mortality rate., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

The development of therapeutic clinical trials for glycogen storage disorders, including Pompe disease, has called for non-invasive and objective biomarkers. Glycogen accumulation can be measured in vivo with 13 C MRS. However, clinical implementation remains challenging due to low signal-to-noise. On the other hand, the buildup of glycolytic intermediates may be detected with 31 P MRS. We sought to identify new biomarkers of disease progression in muscle using 13 C/ 31 P MRS and 1 H HR-MAS in a mouse model of Pompe disease ( Gaa -/- ). We evaluated the sensitivity of these MR biomarkers in vivo after treatment using an adeno-associated virus vector 2/9 encoding hGAA driven by the desmin promotor. 31 P MRS showed significantly elevated phosphomonoesters (PMEs) in Gaa -/- compared to control at 2 (0.06 ± 0.02 versus 0.03 ± 0.01; p = 0.003), 6, 12, and 18 months of age. Correlative 1 H HR-MAS measures in intact gastrocnemius muscles revealed high glucose-6-phosphate (G-6-P). After intramuscular AAV injections, glycogen, PME, and G-6-P were decreased within normal range. The changes in PME levels likely partly resulted from changes in G-6-P, one of the overlapping phosphomonoesters in the 31 P MR spectra in vivo. Because 31 P MRS is inherently more sensitive than 13 C MRS, PME levels have greater potential as a clinical biomarker and should be considered as a complementary approach for future studies in Pompe patients.

Background: There is a variation in the administration of antibiotics prophylaxis to reduce the perceived risk of SSI in patients undergoing non-emergency cholecystectomy. The aim of this study was to determine the effectiveness of antibiotic prophylaxis following non-emergency cholecystectomy to prevent 30-day superficial surgical site infections (SSIs) using non-selected, nationally collected, prospective data., Methods: Data were extracted from the CholeS study, which examined and independently validated the outcomes on consecutive patients following non-emergency cholecystectomy across 166 hospitals in the UK and Ireland. Patients who received antibiotic prophylaxis were exact matched to those who did not on variables associated with antibiotic prophylaxis. The primary outcome of interest was superficial SSI, and secondary outcomes included deep SSI, readmissions, complications and re-interventions within 30 days., Results: Out of a total of 7327 patients included in the study, 4468 (61%) received antibiotic prophylaxis. These were matched to patients who did not receive antibiotic prophylaxis on a range of demographic and surgical factors, leaving 1269 pairs of patients for analysis. Within this cohort, patients receiving antibiotic prophylaxis had significantly lower rates of superficial SSI (0.7% vs. 2.3%, p = 0.001) and all-cause complications (5.8 vs. 8.0%, p = 0.031), but similar rates of deep SSI (1.0 vs. 1.4%, p = 0.473), readmissions (5.2 vs. 6.2%, p = 0.302) and re-interventions (2.6 vs. 3.7%, p = 0.093). The number needed to treat to prevent one superficial SSI was 45 (95% confidence interval 24-662)., Conclusions: Antibiotics appear effective at reducing SSI after non-emergency cholecystectomy. However, due to the high number needed to treat it is unclear whether they provide a worthwhile clinical benefit to patients.

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Objective: The aim of this study was to compare mortality following emergency laparotomy between populations from New York State and England., Summary of Background Data: Mortality following emergency surgery is a key quality improvement metric in both the United States and UK. Comparison of the all-cause 30-day mortality following emergency laparotomy between populations from New York State and England might identify factors that could improve care., Methods: Patient demographics, in-hospital, and 30-day outcomes data were extracted from Hospital Episode Statistics (HES) in England and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients older than 18 years undergoing laparotomy for emergency open bowel surgery between April 2009 and March 2014. The primary outcome measure was all-cause mortality within 30 days of the index laparotomy. Mixed-effects logistic regression was performed to model independent demographic variables against mortality. A one-to-one propensity score matched dataset was created to compare the odd ratios of mortality between the 2 populations., Results: Overall, 137,869 patient records, 85,286 (61.9%) from England and 52,583 (38.1%) from New York State, were extracted. Crude 30-day mortality for patients was significantly higher in the England compared with New York State [11,604 (13.6%) vs 3633 (6.9%) patients, P < 0.001]. Patients undergoing emergency laparotomy in England had significantly higher risk of mortality compared with those in New York State (odds ratio 2.35, confidence interval 2.24-2.46, P < 0.001)., Conclusion: The risk of mortality at 30 days is higher following emergency laparotomy in England as compared with New York State despite similar patient groups.

Background: To compare selected outcomes (30-day reoperation and total length of hospital stay) following emergency appendectomy between populations from New York State and England., Methods: This retrospective cohort study used demographic and in-hospital outcome data from Hospital Episode Statistics (HES) and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients aged 18+ years undergoing appendectomy between April 2009 and March 2014. Univariate and adjusted multivariable logistic regression were used to test significant factors. A one-to-one propensity score matched dataset was created to compare odd ratios (OR) of reoperations between the two populations., Results: A total of 188,418 patient records, 121,428 (64.4%) from England and 66,990 (35.6%) from NYS, were extracted. Appendectomy was completed laparoscopically in 77.7% of patients in New York State compared to 53.6% in England (P < 0.001). The median lengths of hospital stay for patients undergoing appendectomy were 3 (interquartile range, IQR 2-4) days versus 2 (IQR 1-3) days (P < 0.001) in England and New York State, respectively. All 30-day reoperation rates were higher in England compared to New York State (1.2 vs. 0.6%, P < 0.001), representing nearly a twofold higher risk of 30-day reoperation (OR 1.88, 95% CI 1.64-2.14, P < 0.001). As the proportion of appendectomy completed laparoscopically increased, there was a reduction in the reoperation rate in England (correlation coefficient -0.170, P = 0.036)., Conclusions: Reoperations and total length of hospital stay is significantly higher following appendectomy in England compared to New York State. Increasing the numbers of appendectomy completed laparoscopically may decrease length of stay and reoperations.

Objective: This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach., Summary Background Data: The optimal treatment for resectable esophageal cancer is unknown., Methods: A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival., Results: In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87)., Conclusions: This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.

Assessment of muscle pathology is a key outcome measure to measure the success of clinical trials studying muscular dystrophies; however, few robust minimally invasive measures exist. Indocyanine green (ICG)-enhanced near-infrared (NIR) optical imaging offers an objective, minimally invasive, and longitudinal modality that can quantify pathology within muscle by imaging uptake of ICG into the damaged muscles. Dystrophic mice lacking dystrophin (mdx) or gamma-sarcoglycan (Sgcg -/- ) were compared to control mice by NIR optical imaging and magnetic resonance imaging (MRI). We determined that optical imaging could be used to differentiate control and dystrophic mice, visualize eccentric muscle induced by downhill treadmill running, and restore the membrane integrity in Sgcg -/- mice following adeno-associated virus (AAV) delivery of recombinant human SGCG (desAAV8hSGCG). We conclude that NIR optical imaging is comparable to MRI and can be used to detect muscle damage in dystrophic muscle as compared to unaffected controls, monitor worsening of muscle pathology in muscular dystrophy, and assess regression of pathology following therapeutic intervention in muscular dystrophies.

Background: The optimal timing of cholecystectomy for patients admitted with acute gallbladder pathology is unclear. Some studies have shown that emergency cholecystectomy during the index admission can reduce length of hospital stay with similar rates of conversion to open surgery, complications and mortality compared with a 'delayed' operation following discharge. Others have reported that cholecystectomy during the index acute admission results in higher morbidity, extended length of stay and increased costs. This study examined the cost-effectiveness of emergency versus delayed cholecystectomy for acute benign gallbladder disease., Methods: Using data from a prospective population-based cohort study examining the outcomes of cholecystectomy in the UK and Ireland, a model-based cost-utility analysis was conducted from the perspective of the UK National Health Service, with a 1-year time horizon for costs and outcomes. Probabilistic sensitivity analysis was used to investigate the impact of parameter uncertainty on the results obtained from the model., Results: Emergency cholecystectomy was found to be less costly (£4570 versus £4720; €5484 versus €5664) and more effective (0·8868 versus 0·8662 QALYs) than delayed cholecystectomy. Probabilistic sensitivity analysis showed that the emergency strategy is more than 60 per cent likely to be cost-effective across willingness-to-pay values for the QALY from £0 to £100 000 (€0-120 000)., Conclusion: Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Laparoscopic cholecystectomy is commonly performed, and several factors increase the risk of open conversion, prolonging operating time and hospital stay. Preoperative stratification would improve consent, scheduling and identify appropriate training cases. The aim of this study was to develop a validated risk score for conversion for use in clinical practice., Patients and Methods: Preoperative patient and disease-related variables were identified from a prospective cholecystectomy database (CholeS) of 8820 patients, divided into main and validation sets. Preoperative predictors of conversion were identified by multivariable binary logistic regression. A risk score was developed and validated using a forward stepwise approach., Results: Some 297 procedures (3.4%) were converted. The risk score was derived from six significant predictors: age (p = 0.005), sex (p < 0.001), indication for surgery (p < 0.001), ASA (p < 0.001), thick-walled gallbladder (p = 0.040) and CBD diameter (p = 0.004). Testing the score on the validation set yielded an AUROC = 0.766 (p < 0.001), and a score >6 identified patients at high risk of conversion (7.1% vs. 1.2%)., Conclusion: This validated risk score allows preoperative identification of patients at six-fold increased risk of conversion to open cholecystectomy., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Muscle damage is currently assessed through methods such as muscle biopsy, serum biomarkers, functional testing, and imaging procedures, each with its own inherent limitations, and a pressing need for a safe, repeatable, inexpensive, and noninvasive modality to assess the state of muscle health remains. Our aim was to develop and assess near-infrared (NIR) optical imaging as a novel noninvasive method of detecting and quantifying muscle damage. An immobilization-reambulation model was used for inducing muscle damage and recovery in the lower hindlimbs in mice. Confirmation of muscle damage was obtained using in vivo indocyanine green-enhanced NIR optical imaging, magnetic resonance imaging, and ex vivo tissue analysis. The soleus of the immobilized-reambulated hindlimb was found to have a greater amount of muscle damage compared to that in the contralateral nonimmobilized limb, confirmed by in vivo indocyanine green-enhanced NIR optical imaging (3.86-fold increase in radiant efficiency), magnetic resonance imaging (1.41-fold increase in T2), and an ex vivo spectrophotometric assay of indocyanine green uptake (1.87-fold increase in normalized absorbance). Contrast-enhanced NIR optical imaging provides a sensitive, rapid, and noninvasive screening method that can be used for imaging and quantifying muscle damage and recovery in vivo., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Background: Oral antiseptics reduce nosocomial infections and ventilator-associated pneumonia in critically ill medical and surgical patients intubated for prolonged periods. However, the role of oral antiseptics given before and after planned surgery is not clear. The aim of this systematic review and meta-analysis is to determine the effect of oral antiseptics (chlorhexidine or povidone-iodine) when administered before and after major elective surgery., Methods: Searches were conducted of the MEDLINE, EMBASE and Cochrane databases. The analysis was performed using the random-effects method and the risk ratio (RR) with 95 % confidence interval (CI)., Results: Of 1114 unique identified articles, perioperative chlorhexidine was administered to patients undergoing elective surgery in four studies. This identified 2265 patients undergoing elective cardiac surgery, of whom 1093 (48.3 %) received perioperative chlorhexidine. Postoperative pneumonia and nosocomial infections were observed in 5.3 and 20.2 % who received chlorhexidine compared to 10.4 and 31.3 % who received a control preparation, respectively. Oral perioperative chlorhexidine significantly reduced the risk of postoperative pneumonia (RR = 0.52; 95 % CI 0.39-0.71; p < 0.01) and overall nosocomial infections (RR = 0.65; 95 % CI 0.52-0.81; p < 0.01), with no effect on in-hospital mortality (RR = 1.01; 95 % CI 0.49-2.09; p = 0.98)., Conclusions: Perioperative oral chlorhexidine significantly decreases the incidence of nosocomial infection and postoperative pneumonia in patients undergoing elective cardiac surgery. There are no randomised controlled studies of this simple and cheap intervention in patients undergoing elective non-cardiac surgery., Trial Registration: This systematic review was registered with the International prospective register of systematic reviews (PROSPERO). The registration number is CRD42015016063.

Background: The effectiveness of perioperative antibiotics in reducing surgical-site infection (SSI) and overall nosocomial infections in patients undergoing laparoscopic cholecystectomy for biliary colic and low- and moderate-risk cholecystitis (Tokyo classification) is unclear. A systematic review and meta-analysis was performed to assess this., Methods: Searches were conducted of the MEDLINE, Embase and Cochrane databases. Only randomized clinical trials (RCTs) were included. The analysis was performed using the random-effects method, and the risk ratio (RR) with 95 per cent c.i. was employed., Results: Nineteen RCTs, published between 1997 and 2015, with a total of 5259 participants, of whom 2709 (51·5 per cent) were treated with antibiotics, were included. SSI and overall nosocomial infections were detected in 2·4 and 4·2 per cent respectively of patients given perioperative antibiotics, and in 3·2 and 7·2 per cent of those who received no antibiotics. Antibiotics did not significantly reduce the risk of SSI (RR 0·81, 95 per cent c.i. 0·58 to 1·13; P = 0·21) or overall nosocomial infections (RR 0·64, 0·36 to 1·14; P = 0·13). There was no significant between-study heterogeneity for SSI, but significant between-study heterogeneity in the eight studies that reported nosocomial infections. Analysis of studies considered to be high quality, grouped according to the timing of antibiotics (preoperative only or perioperative) and reporting intention-to-treat analyses, again failed to show a significant reduction in SSI., Conclusion: Antibiotics should not be administered before laparoscopic cholecystectomy in patients with biliary colic and/or low- and moderate-risk cholecystitis., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Introduction: Magnetic resonance imaging (MRI) was used to monitor changes in the transverse relaxation time constant (T2) in lower hindlimb muscles of mdx mice at different ages., Methods: Young (5 weeks), adult (44 weeks), and old mdx (96 weeks), and age-matched control mice were studied. Young mdx mice were imaged longitudinally, whereas adult and old mdx mice were imaged at a single time-point., Results: Mean muscle T2 and percent of pixels with elevated T2 were significantly different between mdx and control mice at all ages. In young mdx mice, mean muscle T2 peaked at 7-8 weeks and declined at 9-11 weeks. In old mdx mice, mean muscle T2 was decreased compared with young and adult mice, which could be attributed to fibrosis., Conclusions: MRI captured longitudinal changes in skeletal muscle integrity of mdx mice. This information will be valuable for pre-clinical testing of potential therapeutic interventions for muscular dystrophy., (© 2015 Wiley Periodicals, Inc.)

Objectives: Ethnicity has complex effects on health and the delivery of health care in part related to language and cultural barriers. This may be important in patients requiring emergency abdominal surgery where delays have profound impact on outcomes. The aim here was to test if variations in outcomes (e.g. in-hospital mortality) exist by ethnic group following emergency abdominal surgery., Study Design: Retrospective cohort study using population-level routinely collected administrative data from England (Hospital Episode Statistics)., Methods: Adult patients undergoing emergency abdominal operations between April 2008 and March 2012 were identified. Operations were divided into: 'major', 'hepatobiliary' or 'appendectomy/minor'. The primary outcome was all cause in-hospital mortality. Univariable and multivariable analysis odds ratios (OR with 95% confidence intervals, CI) adjusting for selected factors were performed., Results: 359,917 patients were identified and 80.7% of patients were White British, 4.7% White (Other), 2.4% Afro-Caribbean, 1.6% Indian, 2.6% Chinese, 3.1% Asian (Other) and 4.9% not known, with crude in-hospital mortality rates of 4.4%, 3.1%, 2.0%, 2.6%, 1.6%, 1.7% and 5.17%, respectively. The majority of patients underwent appendectomy/minor (61.9%) compared to major (20.9%) or hepatobiliary (17.2%) operations (P < 0.001) with an in-hospital mortality of 1.7%, 11.5% and 3.9% respectively. Adjusted mortality was largely similar across ethnic groups except where ethnicity was not recorded (compared to White British patients following major surgery OR 2.05, 95% 1.82-2.31, P < 0.01, hepatobiliary surgery OR 2.78, 95% CI 2.31-3.36, P = 0.01 and appendectomy/minor surgery OR 1.78, 95% 1.52-2.08, P < 0.01)., Conclusions: Ethnicity is not associated with poorer outcomes following emergency abdominal surgery. However, ethnicity is not recorded in 5% of this cohort and this represents an important, yet un-definable, group with significantly poorer outcomes., (Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to investigate whether the increased mortality previously identified for surgery performed on Fridays was apparent following major elective colorectal resections and how this might be affected by case mix., Methods: Patients undergoing elective colorectal resections in England from 2001 to 2011 were identified using Hospital Episode Statistics. Propensity scores were used to match patients having operations on a Friday in a 1 : 1 ratio with those undergoing surgery on other weekdays. Multivariable analyses were used to investigate overall deaths within 1 year of operation., Results: A total of 204,669 records were extracted for patients undergoing major elective colorectal resections. Patients who had surgery on Fridays were more deprived (4780 (17.1 per cent) of 27,920 versus 28,317 (16.0 per cent) of 176,749; P < 0.001), a greater proportion had had an emergency admission in the 3 previous months (7870 (28.2 per cent) of 27,920 versus 48,623 (27.5 per cent) of 176,749; P = 0.019), underwent minimal access surgery (4565 (16.4 per cent) of 27,920 versus 23,783 (13.5 per cent) of 176,749; P < 0.001) and had surgery for benign diagnoses (6502 (23.3 per cent) of 27,920 versus 38,725 (21.9 per cent) of 176,749; P < 0.001) than those who had surgery on Mondays to Thursdays. In a matched analysis the odds ratio for 30-day mortality after colorectal resections performed on Fridays compared with other weekdays was 1.25 (95 per cent c.i. 1.13 to 1.37); odds ratios for 90-day and 1-year mortality were 1.16 (1.07 to 1.25) and 1.10 (1.04 to 1.16) respectively., Conclusion: Patients selected for colorectal resections on Fridays had a higher mortality rate than patients operated on from Monday to Thursday and had different characteristics, suggesting that increased mortality may reflect patient factors rather than hospital variables alone., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Introduction: The evidence for improved prognostic assessment and long-term survival for extended pancreatoduodenectomy (EPD) compared to standard pancreatoduodenectomy (SPD) in patients with carcinoma of the head of the pancreas has not been considered from only randomized controlled trials (RCTs)., Methods: The aim of this study was to conduct a systematic review and meta-analysis of the outcomes comparing SPD and EPD in RCTs. Searches were performed on MEDLINE, Embase and Cochrane databases using MeSH keyword combinations: 'pancreatic cancer', 'pancreaticoduodenectomy', 'extended', 'randomized' and 'lymphadenectomy'. RCTs published up to 2014 were included. Overall post-operative survival, morbidity, 30-day mortality and length of hospital stay were the outcomes assessed., Results: Five eligible RCTs with 546 participants were included (EPD = 276 and SPD = 270). EPD was associated with a significantly higher number of excised lymph nodes (LNs) compared to SPD (mean difference = 15.73, 95% confidence interval (CI) = 9.41-22.04; P < 0.00001; I(2) = 88%). LN metastasis was detected in 58-68 and 55-70% of patients who had EPD and SPD, respectively. EPD did not improve overall survival (hazard ratio (HR) = 0.88, 95% CI = 0.75-1.03; P = 0.11) but did worsen post-operative morbidity compared to SPD (risk ratio (RR) = 1.23; 95% CI = 1.01-1.50; P = 0.004; I(2) = 9%). There were no differences in the 30-day mortality (RR = 0.81; 95% CI = 0.32-2.06; P = 0.66; I(2) = 0%) or length of hospital stay (mean difference = 1.39, 95% CI = -2.31 to 5.09; P = 0.46; I(2) = 67%)., Conclusion: SPD is associated with reduced morbidity, but equivalent long-term benefits compared to patients undergoing EPD.

Introduction: The primary objectives of this study were to evaluate contractile and non-contractile content of lower leg muscles of boys with Duchenne muscular dystrophy (DMD) and determine the relationships between non-contractile content and functional abilities., Methods: Lower leg muscles of thirty-two boys with DMD and sixteen age matched unaffected controls were imaged. Non-contractile content, contractile cross sectional area and non-contractile cross sectional area of lower leg muscles (tibialis anterior, extensor digitorum longus, peroneal, medial gastrocnemius and soleus) were assessed by magnetic resonance imaging (MRI). Muscle strength, timed functional tests and the Brooke lower extremity score were also assessed., Results: Non-contractile content of lower leg muscles (peroneal, medial gastrocnemius, and soleus) was significantly greater than control group (p<0.05). Non-contractile content of lower leg muscles correlated with Brooke score (rs = 0.64-0.84) and 30 feet walk (rs = 0.66-0.80). Dorsiflexor (DF) and plantarflexor (PF) specific torque was significantly different between the groups., Discussion: Overall, non-contractile content of the lower leg muscles was greater in DMD than controls. Furthermore, there was an age dependent increase in contractile content in the medial gastrocnemius of boys with DMD. The findings of this study suggest that T1 weighted MR images can be used to monitor disease progression and provide a quantitative estimate of contractile and non-contractile content of tissue in children with DMD.

Objective: To evaluate this impact on male and female English medical graduates by estimating the total time and amount repaid on loans taken out with the UK's Student Loans Company (SLC)., Setting: UK., Participants: 4286 respondents with a medical degree in the Labour Force Surveys administered by the Office for National Statistics (ONS) between 1997 and 2014., Outcomes: Age-salary profiles were generated to estimate the repayment profiles for different levels of initial graduate debt., Results: 2195 female and 2149 male medical graduates were interviewed by the ONS. Those working full-time (73.1% females and 96.1% males) were analysed in greater depth. Following standardisation to 2014 prices, average full-time male graduates earned up to 35% more than females by the age of 55. The initial graduate debt from tuition fees alone amounts to £39,945.69. Owing to interest charges on this debt the average full-time male graduate repays £57,303 over 20 years, while the average female earns less and so repays £61,809 over 26 years. When additional SLC loans are required for maintenance, the initial graduate debt can be as high as £81,916 and, as SLC debt is written off 30 years after graduation, the average female repays £75,786 while the average male repays £110,644., Conclusions: Medical graduates on an average salary are unlikely to repay their SLC debt in full. This is a consequence of higher university fees and as SLC debt is written off 30 years after graduation. This results in the average female graduate repaying more when debt is low, but a lower amount when debt is high compared to male graduates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The Surgical Safety Checklist (SSC) has been shown to reduce perioperative errors and complications and its implementation is recommended by the World Health Organisation (WHO). However, it is unknown how widely this intervention is used. We investigated attitudes and factors associated with use of WHO SSC in frontline medical professionals across the globe using a survey distributed through social networks., Methods: A survey of usage and opinions regarding the SSC was posted on the Facebook and Twitter pages of a not-for-profit surgical news website for one month (March 2013). Respondents were grouped into four groups based on their country's Gross National Income: high, upper middle, lower middle and low income. Univariate and multivariate analyses were performed to investigate how different factors were associated with the use of the SSC., Results: 6269 medical professionals from 69 countries responded to the survey: most respondents were from lower middle (47.4%) countries, followed by: high (35.0%), upper middle (14.6%), and low (3.0%) income countries. In total, 57.5% reported that they used the WHO SSC perioperatively. Fewer respondents used the WHO SSC in upper middle, lower middle and low income countries (LMICs) compared to high income countries (43.5% vs. 83.5%, p < 0.001). Female (61.3% vs. 56.4% males, p = 0.001), consultant surgeons (59.6% vs. 53.2% interns, p < 0.001) and working in university hospitals (61.4% vs. 53.7% non-university hospitals, p < 0.001) were more likely to use the SSC. Believing the SSC was useful, did not work or caused delays was independently associated with the respondents reported use of the SSC (OR 1.22 95% CI 1.07-1.39; OR 0.47 95% CI 0.36-0.60; OR 0.64 95% CI 0.53-0.77, respectively)., Conclusion: This study suggests the use of the WHO SSC is variable across countries, especially in LMICs where it has the most potential to improve patient safety. Critical appraisal of the documented benefits of the WHO SSC may improve its adoption by those not currently using it.