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Several studies have highlighted poor compliance with surveillance colonoscopy guidelines. The National Health and Medical Research Council (NHMRC) guidelines were revised in 2018 and were more complex than the previous iteration (2011). The aim of this study was to determine the impact of 2018 NHMRC polyp surveillance guidelines on compliance with colonoscopy surveillance intervals.A multicentre retrospective clinical audit was conducted between January 2020 and February 2021. Patients awaiting a colonoscopy for polyp surveillance at two public tertiary care hospitals in South Australia were included. Compliance rates of recommended polyp surveillance colonoscopy intervals after implementation of 2018 NHMRC guidelines were compared with 2011 NHMRC guidelines. The projected impact on colonoscopy bookings of the change in guideline intervals was modelled to 5 and 10 years, factoring in differences in compliance.Of 3996 patients awaiting colonoscopy services at two public hospitals in South Australia, 1984 patients (60% male, median age 61 years) were waitlisted for polyp surveillance. Overall compliance with surveillance guidelines was60%. Implementation of the 2018 NHMRC guidelines significantly reduced compliance from 65.8% (2011 guidelines) to 50.8% (2018) (χThe revised 2018 NHMRC guidelines have resulted in significantly poorer compliance post-implementation, possibly due to their increased complexity. This has potential to increase the surveillance colonoscopy waiting list burden.

Background: Critical care nurses have risked their lives and in some cases their families through hazardous duty during the COVID-19 pandemic and have faced multiple ethical challenges. Research/aim: The purpose of our study was to examine how critical care nurses coped with the sustained multi-faceted pressures of the critical care environment during the unchartered waters of the COVID-19 pandemic. It was anticipated that our study might reveal numerous ethical challenges and decision points. Research design: A qualitative descriptive study, utilizing an interpretivist paradigm. Participants and research setting: Critical care nurses, working in either intensive care units or emergency departments (N = 11) who were primarily from Northern California hospitals. Individual in-depth ZOOM® session interviews, guided by semi-structured questions, were used to collect data. Interviews lasted between 18 and 59 min, with an average length of 33 min. Session interviews were transcribed and analyzed. Ethical considerations: This study was approved by the researchers’ university Institutional Review Board. Findings: Five main themes emerged: Fear of the Unknown, Adapting to Practice Changes and Challenges, Patient Advocacy and Moral Distress, Isolation and the Depersonalization of Care, and Professionalism and a Call to Duty. Discussion and conclusion: Fear of becoming ill or bringing COVID-19 home to their families was a constant source of anxiety for nurses. There were numerous changes in policy and challenges to standard practice protocols, including most notably shortages in personal protective equipment, which nurses navigated resourcefully. Most nurses interviewed were motivated by a sense of professional duty. The nurses experienced some moral distress in their inability to advocate as they might like for their patients, especially at end of life. Infection control requirements for isolation.

Aim: Reviewing outcomes of regorafenib use in metastatic colorectal cancer using real-world data from the South Australian Metastatic Colorectal Cancer Registry. Methods: A retrospective review of the characteristics and outcomes of patients who received regorafenib in the Registry up to December 2018. The registry started in February 2006. Results: Fifty-three patients received regorafenib therapy since approved by the therapeutic goods administration in November 2013. The median age was 66 (range 34–82). 66% were male, 66% had stage IV disease at diagnosis, 53% had liver only involvement, whereas 13% had liver and lung disease and 6% had lung only involvement. 75% had left-sided primary. KRAS was available in 35/53 patients with 49% of them being WT. BRAF status was known in 8/53 with 25% of them having a mutated variant. MSI testing was known in 14 patients in whom 21% of them had MSI-High tumors. Prior lines of treatment received: one line 4%, two 9%, three 23%, four 26%, >four 37%. Prior biological use: bevacizumab 72%, anti-EGFR 100% (for RAS WT). Median survival from diagnosis was 3.3 years (95% CI, 2.8–3.8 years). Median survival from the start of regorafenib was 7.1 months (95% CI, 4.8–9.4 months) and the 12-month survival rate was 28%. Conclusion: The survival outcome for those patients from our population-based registry who access regorafenib is in keeping with reports from large, randomized trials. Thus, clinicians can quote local real world data when discussing efficacy and access to regorafenib therapy for mCRC patients. Refereed/Peer-reviewed

Background Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. Methods This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. Results Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5–4) versus 3 (2–5.5) days; 95 per cent c.i. –1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. Conclusion Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au)

The purpose of this Perspective is to present an application of script-based reasoning to physical therapist education and practice. Illness script–based reasoning has been described as a cognitive strategy for medical practitioners to diagnose and manage health conditions. Analogous to this medical model of patient management, “movement scripts” can be used by physical therapists in clinical reasoning. Movement scripts use features of the human movement system to recognize, categorize, and substantiate clinical problems and can be used to facilitate the development of master adaptive learners across the spectrum of physical therapist education and practice. Movement scripts are also consistent with the concept of the “human body as teacher” as the signature pedagogy proposed by the National Study of Excellence and Innovation in Physical Therapy Education. Movement of the human body, as captured by the concept of the human movement system, is a vehicle for lifelong adaptive learning for the physical therapist. Script-based learning and practice are consistent with other elements of this model, including practice-based learning and the creation of adaptive expertise. As the role of the movement system as a guide to physical therapist practice continues to evolve, movement scripts can provide a structure to facilitate development of clinical reasoning skills for physical therapist practice and education.

Moore, James, Martin J. MacInnis, Jon Dallimore, and Matt Wilkes. The Lake Louise Score: A Critical Assessment of Its Specificity. High Alt Med Biol. 21:237-242, 2020. Introduction: The Lake Louise Score (LLS) has low specificity for diagnosing acute mountain sickness (AMS). As this tool is used for research and clinical decision making, it is important to understand the origins of this poor specificity. We reviewed AMS diagnoses in a population trekking at low altitude ("false positives") to critically assess LLS specificity. Method: We retrospectively analyzed data from a sample of 123 adolescents trekking at low altitude to establish the predominant causes of false-positive AMS diagnoses (1993 LLS criteria), separately removing each LLS component to assess its contribution to the final score. Exploratory factor analysis (EFA) was applied to the data to establish component patterns. Results: Removal of LLS components individually showed fatigue contributed slightly more to false-positive AMS diagnoses than sleep quality in this group. An EFA from morning data highlighted sleep quality as a stand-alone factor in the measurement of AMS. Although of smaller significance, an EFA of the evening data highlighted fatigue and headache as the stand-alone factor. Conclusion: Our findings not only supported the recent removal of sleep quality from the LLS, but also demonstrated that fatigue had an equal part to play in the misdiagnosis of AMS in this population. These data highlighted the poor specificity of the LLS and suggest that the measurement of illness at altitude undergo further review.

Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor that has shown non-inferior efficacy to ritonavir-boosted darunavir, with a superior lipid profile, in adults with HIV who were treatment naive at week 48 in the phase 3 DRIVE-FORWARD trial. Here we present the 96-week data for the study.This randomised, controlled, double-blind, multicentre, non-inferiority, phase 3 study was undertaken at 125 clinical centres in 15 countries. Eligible participants were adults (aged ≥18 years) infected with HIV-1 who were naive to antiretroviral therapy, with a plasma HIV-1 RNA concentration of 1000 copies per mL or higher at screening, and no known resistance to any of the study drugs. Participants were randomly assigned (1:1) using an interactive voice and web response system, stratified by baseline HIV-1 RNA concentration and background nucleoside reverse transcriptase inhibitor therapy, to doravirine (100 mg per day) or ritonavir-boosted darunavir (100 mg ritonavir and 800 mg darunavir per day), both with investigator-selected nucleoside reverse transcriptase inhibitors: emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. Participants and investigators were masked to treatment assignment until week 96. The primary efficacy endpoint was the proportion of participants who had a plasma HIV-1 RNA concentration of less than 50 copies per mL at week 48, which has been reported previously. Here we report the key secondary efficacy endpoint of the proportion of participants who achieved this concentration by week 96, assessed in all participants who received at least one dose of any study drug, regardless of whether it was their randomly assigned treatment. We used a US Food and Drug Administration snapshot approach and a margin of 10 percentage points to define the non-inferiority of doravirine to ritonavir-boosted darunavir at 96 weeks. Key safety endpoints were change in fasting serum lipid concentrations, the incidence of adverse events, and time to discontinuation due to an adverse event, assessed in all participants who received at least one dose of any study medication. This study is registered with ClinicalTrials.gov, NCT02275780, and is closed to accrual.Between Dec 1, 2014, and Oct 20, 2015, 1027 individuals were screened, of whom 769 participants were randomly assigned to doravirine (n=385) or ritonavir-boosted darunavir (n=384), and 383 in both groups were given at least one dose of their allocated treatment. Most participants were male (645 [84%] of 766) and white (560 [73%]), with a mean age of 35·2 years (SD 10·6). 292 participants in the doravirine group and 273 in the darunavir group completed 96 weeks of treatment. At week 96, a higher proportion of the doravirine group (277 [73%] of 383) achieved an HIV-1 RNA concentration of less than 50 copies per mL than did of the darunavir group (248 [66%] of 383; difference 7·1%, 95% CI 0·5-13·7). Responses were similar regardless of baseline characteristics. Treatment-emergent resistance to any study drug occurred in two (1%) of 383 participants in the doravirine group and one (1%) of 383 in the ritonavir-boosted darunavir group. Significant differences were seen between treatment groups in mean changes from baseline in LDL cholesterol (-14·6 mg/dL, 95% CI -18·2 to -11·0) and non-HDL cholesterol (-18·4 mg/dL, -22·5 to -14·3). Frequencies of adverse events were similar between groups. No significant treatment difference (log-rank nominal p=0·063) through week 96 was observed in time to discontinuation due to an adverse event. The most common adverse events (week 0-96) were diarrhoea (65 [17%] in the doravirine group vs 91 [24%] in the ritonavir-boosted darunavir group), nausea (45 [12%] vs 52 [14%]), headache (57 [15%] vs 46 [12%]), and upper respiratory tract infection (51 [13%] vs 30 [8%]). Two participants, one in each group, died during treatment; neither death was considered to be related to study medication.These results through 96 weeks support the efficacy and safety results reported previously for doravirine at 48 weeks, supporting the use of doravirine for the long-term treatment of adults with previously untreated HIV-1 infection.Merck.

The once abundant black abalone, Haliotis cracherodii, is a large, long-lived grazing marine mollusk that inhabits the rocky intertidal along the coast of California. The species has experienced dramatic declines since the mid-1980s largely due to the fatal bacterial disease called withering syndrome, leading to the collapse of an economically important fishery and to its inclusion into the IUCN listing as a critically endangered species. In some places impacted by the disease, populations of black abalone have declined by more than 90%, prompting population crashes associated with very little recruitment of new individuals and changes to intertidal communities. Habitats that were dominated by crustose coralline algae and bare rock have become dominated instead by fleshy algae and sessile invertebrates. Here, we present the first high-quality black abalone reference genome, assembled with PacBio HiFi long-reads and assembled with Dovetail Omni-C data to generate a scaffold-level assembly. The black abalone reference genome will be an essential resource in understanding the evolutionary history of this species as well as for exploring its current levels of genetic diversity and establishing future management and restoration plans.

Background Important incidental pathology requiring further action is commonly found during appendicectomy, macro- and microscopically. We aimed to determine whether the acute surgical unit (ASU) model improved the management and disclosure of these findings. Methods An ASU model was introduced at our institution on 01/08/2012. In this retrospective cohort study, all patients undergoing appendicectomy 2.5 years before (Traditional group) or after (ASU group) this date were compared. The primary outcomes were rates of appropriate management of the incidental findings, and communication of the findings to the patient and to their general practitioner (GP). Results 1,214 patients underwent emergency appendicectomy; 465 in the Traditional group and 749 in the ASU group. 80 (6.6%) patients (25 and 55 in each respective period) had important incidental findings. There were 24 patients with benign polyps, 15 with neuro-endocrine tumour, 11 with endometriosis, 8 with pelvic inflammatory disease, 8 Enterobius vermicularis infection, 7 with low grade mucinous cystadenoma, 3 with inflammatory bowel disease, 2 with diverticulitis, 2 with tubo-ovarian mass, 1 with secondary appendiceal malignancy and none with primary appendiceal adenocarcinoma. One patient had dual pathologies. There was no difference between the Traditional and ASU group with regards to communication of the findings to the patient (p = 0.44) and their GP (p = 0.27), and there was no difference in the rates of appropriate management (p = 0.21). Conclusion The introduction of an ASU model did not change rates of surgeon-to-patient and surgeon-to-GP communication nor affect rates of appropriate management of important incidental pathology during appendectomy.

Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome.Assessment of the specific characteristics and prognostic implications of individual RAS mutation subtypes in patients with metastatic colorectal cancer.Retrospective review of individual RAS mutation types from the South Australian Metastatic Colorectal Registry between 2006 and 2020.Of the 5165 patients entered onto the registry, 2305 (45%) had RAS mutation results available. 772 (33%) had a RAS mutation. The nature of the RAS mutation was available in 668 (87% of those with RAS mutation). Rare mutations (outside codons 12 and 13) made up 12.6% of the total. There were numerical differences in survival between the specific RAS mutation subgroups, with the longest median overall survival (30 months) observed in those with G12S mutations. However, there was no statistical difference in survival when comparing the various RAS mutations, including the comparison of G12C to G12S (p = 0.38). Patients with cancer harbouring rare RAS mutations had a median survival of 30 months.Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ.

Plastics are widely recognized as a pervasive marine pollutant. Microplastics have been garnering increasing attention due to reports documenting their ingestion by animals, including those intended for human consumption. Their accumulation in the marine food chain may also pose a threat to wildlife that consume species that can accumulate microplastic particles. Microplastic contamination in marine ecosystems has thus raised concerns for both human and wildlife health. Our study addresses an unexplored area of research targeting the interaction between plastic and pathogen pollution of coastal waters. We investigated the association of the zoonotic protozoan parasites Toxoplasma gondii, Cryptosporidium parvum, and Giardia enterica with polyethylene microbeads and polyester microfibers. These pathogens were chosen because they have been recognized by the World Health Organization as underestimated causes of illness from shellfish consumption, and due to their persistence in the marine environment. We show that pathogens are capable of associating with microplastics in contaminated seawater, with more parasites adhering to microfiber surfaces as compared with microbeads. Given the global presence of microplastics in fish and shellfish, this study demonstrates a novel pathway by which anthropogenic pollutants may be mediating pathogen transmission in the marine environment, with important ramifications for wildlife and human health.

IntroductionRobust randomised trial data have shown that routine preoperative (pre-op) testing for cataract surgery patients is inappropriate. While guidelines have discouraged testing since 2002, cataract pre-op testing rates have remained unchanged since the 1990s. Given the challenges of reducing low-value care despite strong consensus around the evidence, innovative approaches are needed to promote high-value care. This trial evaluates the impact of an interdisciplinary electronic health record (EHR) intervention that is informed by behavioural economic theory.Methods and analysisThis pragmatic randomised trial is being conducted at UCLA Health between June 2021 and June 2022 with a 12-month follow-up period. We are randomising all UCLA Health physicians who perform pre-op visits during the study period to one of the three nudge arms or usual care. These three nudge alerts address (1) patient harm, (2) increased out-of-pocket costs for patients and (3) psychological harm to the patients related to pre-op testing. The nudges are triggered when a physician starts to order a pre-op test. We hypothesise that receipt of a nudge will be associated with reduced pre-op testing. The primary outcome will be the change in the percentage of patients undergoing pre-op testing at 12 months. Secondary outcomes will include the percentage of patients undergoing specific categories of pre-op tests (labs, EKGs, chest X-rays (CXRs)), the efficacy of each nudge, same-day surgery cancellations and cost savings.Ethics and disseminationThe study protocol was approved by the institutional review board of the University of California, Los Angeles as well as a nominated Data Safety Monitoring Board. If successful, we will have created a tool that can be disseminated rapidly to EHR vendors across the nation to reduce inappropriate testing for the most common low-risk surgical procedures in the country.Trial registration numberClinicalTrials.gov identifier: NCT04104256.

OBJECTIVES This study aims to characterize the material properties of ascending thoracic aortic aneurysmal tissue, using regional biomechanical assessment of both tensile and dissection propagation peel strength. METHODS Thirty-four aneurysm specimens (proximal thoracic aorta) were harvested en-bloc from patients undergoing surgery for aneurysm replacement. Specimens were processed into regional samples of similar shapes covering the whole aneurysm isosurface, according to a structured protocol, in both orientations (longitudinal and circumferential). Thickness mapping, uniaxial tensile and peel tests were conducted, enabling calculation of the following parameters: true stress/strain, tangential modulus, tensile strength, peeling force and dissection energy. Two constitutive material models were used (hyperelastic models of Delfino and Ogden) to fit the data. A circumferential strip of tissue was also obtained for computational histology [regional quantification of (i) elastin, (ii) collagen and (iii) smooth muscle cells]. RESULTS The aortic wall was thinner on the outer curve (2.21, standard deviation (SD) 0.4 mm vs inner curve 2.50, SD 0.12 mm). Advanced patient age and higher pulse wave velocity (externally measured) were predictors of increased aortic wall thickness. Tensile strength was higher in the circumferential versus longitudinal direction when analysed according to anatomical regions. Both peel force (35.5, 22 N/m) and dissection energy (88.5, 69 J/m2) were on average lowest at the outer curve of the aneurysm in the longitudinal orientation. Delfino and Ogden model constants varied throughout anatomical regions, with the outer curve being associated a higher ɑ constant (Delfino) and lower µ1 constant (Ogden) (P 0.05). CONCLUSIONS Our results suggest that the outer aortic curve is more prone to dissection propagation and perhaps less prone to rupture than the inner aortic curve. This strengthens the notion of disease heterogeneity in ascending thoracic aortic aneurysms and has implications for the pathogenesis of aortic dissection.

IntroductionBCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysisThis international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and disseminationEthical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registrationClinicalTrials.gov NCT04327206

BACKGROUND Opioid use disorder (OUD) continues to be a growing and major public health issue in the United States. In an effort to increase OUD treatment access, medication-assisted treatment with buprenorphine via telehealth is emerging as the leading treatment option. OBJECTIVE This study sought to describe the experiences of adults with OUD receiving medication-assisted treatment buprenorphine in a nurse-practitioner-facilitated telehealth program. METHODS Using a descriptive qualitative design, convenience sampling was used to recruit participants who were currently receiving OUD treatment in one telehealth program with locations in California and Michigan. Participants were invited to participate in the study via an email flyer sent to all clients of the telehealth program. Participants completed demographic data and took part in individual, semistructured interviews that were conducted online. RESULTS The study sample included 15 largely White, married, college-educated men (n = 8, 53%) and women (n = 7, 47%). Qualitative content analysis of interview data revealed three overall themes and associated subthemes: (a) improved access to care, (b) isolation, and (c) feeling normal on buprenorphine. CONCLUSION Our findings support a nurse-practitioner-facilitated telehealth treatment program for OUD. However, in a program that offers patient-centered care that does not have a one-size-fits-all approach to service, goals of care must be reevaluated throughout treatment. Moreover, given the increased risk of patients feeling isolated with telehealth appointments and the lack of physical face-to-face interactions, healthcare providers should explore ways to engage patients in meaningful support resources and reduce stigma.

Background Artificial intelligence (AI) is increasingly being used in medical imaging analysis. We aimed to evaluate the diagnostic accuracy of AI models used for detection of lymph node metastasis on pre-operative staging imaging for colorectal cancer. Methods A systematic review was conducted according to PRISMA guidelines using a literature search of PubMed (MEDLINE), EMBASE, IEEE Xplore and the Cochrane Library for studies published from January 2010 to October 2020. Studies reporting on the accuracy of radiomics models and/or deep learning for the detection of lymph node metastasis in colorectal cancer by CT/MRI were included. Conference abstracts and studies reporting accuracy of image segmentation rather than nodal classification were excluded. The quality of the studies was assessed using a modified questionnaire of the QUADAS-2 criteria. Characteristics and diagnostic measures from each study were extracted. Pooling of area under the receiver operating characteristic curve (AUROC) was calculated in a meta-analysis. Results Seventeen eligible studies were identified for inclusion in the systematic review, of which 12 used radiomics models and five used deep learning models. High risk of bias was found in two studies and there was significant heterogeneity among radiomics papers (73.0%). In rectal cancer, there was a per-patient AUROC of 0.808 (0.739–0.876) and 0.917 (0.882–0.952) for radiomics and deep learning models, respectively. Both models performed better than the radiologists who had an AUROC of 0.688 (0.603 to 0.772). Similarly in colorectal cancer, radiomics models with a per-patient AUROC of 0.727 (0.633–0.821) outperformed the radiologist who had an AUROC of 0.676 (0.627–0.725). Conclusion AI models have the potential to predict lymph node metastasis more accurately in rectal and colorectal cancer, however, radiomics studies are heterogeneous and deep learning studies are scarce. Trial registration PROSPERO CRD42020218004.

Background Post-operative ileus (POI) and delayed return of gastrointestinal (GI) function are common complications after colorectal surgery. There is a lack of uniformity in enhanced recovery protocols (ERPs) with regards to interventions used to target these complications. This systematic review aims to categorize and summarize management recommendations available from published ERPs. Methods A systematic search of Ovid MEDLINE, Embase, Cochrane Library and PubMed databases was performed from January 1990 to May 2018. All studies publishing enhanced recovery or fast-track or multimodal pathway protocols for colorectal surgery in their full-text were included. Data on interventions aimed at reducing the duration of POI were extracted, as well as references quoted to support specific interventions. Results Of 481 manuscripts screened, 37 published ERPs were identified from 37 studies (18 cohort, seven historical-control, five guidelines, four randomized controlled trials, one randomized controlled trial protocol, one case series and one narrative review). The most commonly recommended interventions were magnesium-based laxatives (18 of 37, 48.6%), chewing gum (13 of 37, 35.1%), Alvimopan (6 of 37, 16.2%), lactulose (4 of 37, 10.8%), neostigmine (2 of 37, 5.4%) and bisacodyl (2 of 37, 5.4%). Geographical trends were noted for the various interventions, but high-quality evidence was only referenced to support the use of Alvimopan. Conclusion ERP recommendations specific to interventions targeting POI and return of GI function are varied. While laxatives are the most commonly recommended intervention, there is only weak evidence reported to support this practice.

BACKGROUND Few large Australian studies have explored the impact of acute surgical unit (ASU) model in appendicitis. METHODS An ASU model commenced practice at our institution on 1 August 2012. In this retrospective cohort study, patients undergoing appendicectomy 2.5 years before (Traditional group) or after (ASU group) this date were compared. Primary outcomes were median length of stay, median time from emergency department referral to theatre start and proportion of cases performed in-hours. Secondary outcomes were rates of complications, open appendicectomy, consultant scrubbed for procedure, intensive care unit admission and re-presentation to emergency department within 30 days. RESULTS After removing those with incomplete data, 1214 patients were enrolled; 465 in the Traditional group and 749 in the ASU group. There were no significant baseline differences between groups. Compared with the Traditional group, ASU patients had similar length of stay (1.81 versus 1.81 days; P = 0.54) and time to theatre (0.59 versus 0.56 days; P = 0.14), but a greater proportion of in-hours operation (72% versus 79%; P = 0.014). The ASU group also experienced fewer complications (9% versus 6%; P = 0.031), fewer primary open (4% versus 1%; P < 0.0001) or conversion-to-open appendicectomies (6% versus 2%; P < 0.0005) and had superior rates of consultant scrubbed in theatre (21% versus 56%; P < 0.00001). Rates of intensive care unit admission (1% versus 1%; P = 0.72) and re-presentation were unchanged (5% versus 5%; P = 0.46). CONCLUSION In our institution, the introduction of an ASU model was associated with more in-hours operations and safer care for patients undergoing appendicectomy.

AIM Postoperative ileus (POI) is a major problem after colorectal surgery. Acetylcholinesterase inhibitors such as pyridostigmine increase gastrointestinal (GI) motility through a cholinergic anti-inflammatory pathway. The purpose of this phase II pilot study is to determine the safety of oral pyridostigmine after elective colorectal surgery. METHOD This is a Stage 2b safety study (IDEAL framework). All adult patients undergoing elective colorectal resection or formation or reversal of stoma at the Royal Adelaide Hospital between September 2020 and January 2021 were eligible. The primary outcomes were 30-day postoperative complications, reported adverse events and GI-2 - a validated composite outcome measure of recovery of GI function after surgery, defined as the interval from surgery until first passage of stool and tolerance of a solid intake for 24 h (in whole days) in the absence of vomiting. RESULTS Fifteen patients were included in the study. The median age was 58 (range 50-82) years and seven (47%) were men. Most participants had an American Society of Anesthesiologists grade ≥2 (53%) and the median body mass index was 27 (24-35) kg/m2 . There were 13 postoperative complications [seven were Clavien-Dindo (CD) 1, five CD 2 and one CD 3]. None appeared directly related to pyridostigmine administration, and none of the patients had any overt symptoms of excessive parasympathetic activity. Median GI-2 was 2 (1-4) days. CONCLUSION Oral pyridostigmine appears to be safe to use after elective colorectal surgery in a select group of patients. However, considering this is a pilot study with a small sample size, larger controlled studies are needed to confirm this finding and establish efficacy for prevention of POI.

Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Methods During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51–71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration., Highlights • Priority surgeries are being cancelled every week due to the COVID-19 pandemic. • A multicentre surgical referral network was set up as part of an NHS England approach to continuing safe surgery • The referral network consisted of 14 NHS trusts and surgery was performed at a single COVID-19 ‘cold site’. • After 500 surgeries performed, there was a 0% 30-day mortality from COVID-19. • It is safe to continue cancer and priority surgery during the COVID-19 pandemic with appropriate service reconfiguration.

3531 Background: Surgical resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether such benefit is consistently observed for BRAF V600E mutant (MT) and wild type (WT) mCRC. We conducted a retrospective analysis to explore the influence of BRAF mutation status on survival outcomes after metastasectomy. Methods: Data collected from two large prospective population databases in Australia (Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) and South Australian cancer registry). Overall survival (OS) and recurrence free survival (RFS) for BRAF MT and WT mCRC were evaluated by Kaplan-Meier method and compared by log-rank test. Results: 513 patients who had undergone metastasectomy were identified, 6% were BRAF MT. Median age 63. Metastasectomy rate was lower in BRAF MT (13 v 27%). In BRAF WT, 4% underwent resection of metastases (mets) in >1 organ at diagnosis and 5% had 3 or 4 metastasectomies versus none in BRAF MT. Median OS in BRAF MT v WT: 25.7 v 48.5 months (HR 1.95; 1.18-3.22). In a multivariate model adjusting for variables which were significant on univariate analysis, OS differences were not statistically significant. Right primary tumor, intact primary, >1 metastatic sites at diagnosis, non R0 resection, peritoneal mets and synchronous mets were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 v 19 months, p=0.09). Rate of downsizing was higher with triplet chemo than doublet +/- bevacizumab or doublet/EGFR in BRAF WT (50 v 30%) as well as MT (33 v 11%). Conclusions: Median OS was > 2 years in BRAF MT V600E after metastasectomy in this study consistent with an OS benefit. OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Presence of BRAF MT should not impact patient selection for metastasectomy.[Table: see text]

ObjectiveTo test the hypothesis that antidrug antibodies (ADAs) against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining occasional treatment resistance.MethodsRecombinant alemtuzumab single-chain variable fragment antibody with a dual tandem nanoluciferase reporter linker was made and used to detect binding ADAs. Alemtuzumab immunoglobulin G Alexa Fluor 488 conjugate was used in a competitive binding cell-based assay to detect neutralizing ADAs. The assays were used to retrospectively screen, blinded, banked serum samples from people with MS (n = 32) who had received 3 or more cycles of alemtuzumab. Lymphocyte depletion was measured between baseline and about 1 month postinfusion.ResultsThe number of individuals showing limited depletion of lymphocytes increased with the number of treatment cycles. Lack of depletion was also a poor prognostic feature for future disease activity. ADA responses were detected in 29/32 (90.6%) individuals. Neutralizing antibodies occurred before the development of limited depletion in 6/7 individuals (18.8% of the whole sample). Preinfusion, ADA levels predicted limited, postinfusion lymphocyte depletion.ConclusionsAlthough ADAs to alemtuzumab have been portrayed as being of no clinical significance, alemtuzumab-specific antibodies appear to be clinically relevant for some individuals, although causation remains to be established. Monitoring of lymphocyte depletion and the antidrug response may be of practical value in patients requiring additional cycles of alemtuzumab. ADA detection may help to inform on retreatment or switching to another treatment.

The importance of the patient experience is increasingly being recognised. However, there is a dearth of studies regarding factors affecting patient-reported outcomes in emergency general surgery (EGS), including none from the Southern Hemisphere. We aim to prospectively assess factors associated with patient satisfaction in this setting.In this prospective cross-sectional study, all consecutive adult patients admitted to an acute surgical unit over four weeks were invited to complete a validated Patient-Reported Experience Measures questionnaire. These were completed either in person when discharge was imminent or by telephone 4 weeks post-discharge. Responses were used to determine factors associated with overall patient satisfaction.From 146 eligible patients, 100 (68%) completed the questionnaire, with a mean overall satisfaction score of 8.3/10. On multivariate analyses, eight factors were significantly associated with increased overall satisfaction. Five of these were similar to those previously prescribed by other like studies, being patient age 50 years, sufficient analgesia, satisfaction with the level of senior medical staff, important questions answered by nurses and confidence in decisions made about treatment. Three identified factors were new: sufficient privacy in the emergency department, sufficient notice prior to discharge and feeling well looked after in hospital.Factors associated with patient satisfaction were identified at multiple points of the patient journey. While some of these have been reported in similar studies, most differed. Hospitals should assess factors valued by their EGS population prior to implementing initiatives to improve patient satisfaction.

Pre-pregnancy or first trimester biomarkers predicting preterm delivery are lacking. The purpose of this study was to determine whether maternal H-antigen (secretor status) is a potential biomarker for preterm delivery.This cohort study examined maternal saliva samples and birth data gathered by the National Children's Study Vanguard pilot phase (2009-2014) and included 300 women who were ≥18 years old and provided birth data and saliva samples. The maternal secretor status phenotype was determined by quantifying H-antigen in saliva using enzyme-linked immunoassay. Mothers were stratified by secretor status and multivariable analysis estimated adjusted associations with preterm delivery.Maternal lack of H-antigen production was an independent risk factor for preterm delivery after adjusting for known confounders (aOR 4.53; 95% CI: 1.74, 11.81; P = 0.002).Maternal H-antigen may be a biomarker identifying women at-risk for preterm delivery. Prospective cohort studies validating these findings are needed.

Purpose Accurate clinical diagnosis of lymph node metastases is of paramount importance in the treatment of patients with abdominopelvic malignancy. This review assesses the diagnostic performance of deep learning algorithms and radiomics models for lymph node metastases in abdominopelvic malignancies. Methodology Embase (PubMed, MEDLINE), Science Direct and IEEE Xplore databases were searched to identify eligible studies published between January 2009 and March 2019. Studies that reported on the accuracy of deep learning algorithms or radiomics models for abdominopelvic malignancy by CT or MRI were selected. Study characteristics and diagnostic measures were extracted. Estimates were pooled using random-effects meta-analysis. Evaluation of risk of bias was performed using the QUADAS-2 tool. Results In total, 498 potentially eligible studies were identified, of which 21 were included and 17 offered enough information for a quantitative analysis. Studies were heterogeneous and substantial risk of bias was found in 18 studies. Almost all studies employed radiomics models (n = 20). The single published deep-learning model out-performed radiomics models with a higher AUROC (0.912 vs 0.895), but both radiomics and deep-learning models outperformed the radiologist’s interpretation in isolation (0.774). Pooled results for radiomics nomograms amongst tumour subtypes demonstrated the highest AUC 0.895 (95 %CI, 0.810−0.980) for urological malignancy, and the lowest AUC 0.798 (95 %CI, 0.744−0.852) for colorectal malignancy. Conclusion Radiomics models improve the diagnostic accuracy of lymph node staging for abdominopelvic malignancies in comparison with radiologist’s assessment. Deep learning models may further improve on this, but data remain limited.

Background Recovery of gastrointestinal function is often delayed after major abdominal surgery, leading to postoperative ileus (POI). Enhanced recovery protocols recommend laxatives to reduce the duration of POI, but evidence is unclear. This systematic review aimed to assess the safety and efficacy of laxative use after major abdominal surgery. Methods Ovid MEDLINE, Embase, Cochrane Library and PubMed databases were searched from inception to May 2019 to identify eligible RCTs focused on elective open or minimally invasive major abdominal surgery. The primary outcome was time taken to passage of stool. Secondary outcomes were time taken to tolerance of diet, time taken to flatus, length of hospital stay, postoperative complications and readmission to hospital. Results Five RCTs with a total of 416 patients were included. Laxatives reduced the time to passage of stool (mean difference (MD) −0·83 (95 per cent c.i. −1·39 to −0·26) days; P = 0·004), but there was significant heterogeneity between studies for this outcome measure. There was no difference in time to passage of flatus (MD −0·17 (−0·59 to 0·25) days; P = 0·432), time to tolerance of diet (MD −0·01 (−0·12 to 0·10) days; P = 0·865) or length of hospital stay (MD 0·01(−1·36 to 1·38) days; P = 0·992). There were insufficient data available on postoperative complications for meta‐analysis. Conclusion Routine postoperative laxative use after major abdominal surgery may result in earlier passage of stool but does not influence other postoperative recovery parameters. Better data are required for postoperative complications and validated outcome measures., Routine postoperative laxative use after major abdominal surgery may result in earlier passage of stool, but does not influence other postoperative recovery parameters. Better data are required for postoperative complications and validated outcome measures. Laxatives after major abdominal surgery

Objective To systematically review comparative studies on the acute surgical unit (ASU) model. Methods Searches were performed of Cochrane, Embase, Medline and grey literature. Eligible articles were comparative studies of the Acute Surgical Unit (ASU) model published 01/01/2000-12/03/2020. Amongst patients with any diagnosis, primary outcomes were length of stay, after-hours operating, complications and cost. Secondary outcomes were time to surgical review, time to theatre, mortality and re-admission for patients with any diagnosis, and cholecystectomy during index admission for patients with biliary disease. Additional analyses were planned for specific cohorts, such as patients with appendicitis or cholecystitis. Results Searches returned 9,677 results from which 77 eligible publications were identified, representing 150,981 unique patients. Cohorts were adequately homogenous for meta-analysis of all outcomes except cost. For patients with any diagnosis, compared with the Traditional model, the introduction of an ASU model was associated with reduced length of stay (mean difference [MD] 0.68 days; 95% confidence interval [CI] 0.38–0.98), after-hours operating rates (odds ratio [OR] 0.56; 95% CI 0.46–0.69) and complications (OR 0.48, 95% CI 0.33–0.70). Regarding cost, two studies reported savings following ASU introduction, while one found no difference. Amongst secondary outcomes, for patients with any diagnosis, ASU commencement was associated with reduced time to surgical review, time to theatre and mortality. Re-admissions were unchanged. For patients with biliary disease, ASU establishment was associated with superior rates of index cholecystectomy. Conclusion Compared to the Traditional structure, the ASU model is superior for most metrics. ASU introduction should be promoted in policy for widespread benefit.

Anastomotic leak can be a devastating complication, and early prediction is difficult. The aim of this study is to prospectively validate a simple anastomotic leak risk calculator and compare its predictive value with the estimate of the primary operating surgeon. Consecutive patients undergoing elective or emergency colon cancer surgery with a primary anastomosis over a 1-year period were prospectively included. A recently published anastomotic leak risk nomogram was converted to an online calculator ( www.anastomoticleak.com ). The calculator-derived risk of anastomotic leak and the risk estimated by the primary operating surgeon were recorded at the completion of surgery. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve analysis (AUROC) was performed for both risk estimates. A total of 105 patients were screened for inclusion during the study period, of whom 83 met the inclusion criteria. The overall anastomotic leak rate was 9.6%. The anastomotic leak calculator was highly predictive of anastomotic leak (AUROC 0.84, P = 0.002), whereas the surgeon estimate was not predictive (AUROC 0.40, P = 0.243). A simple anastomotic leak risk calculator is significantly better at predicting anastomotic leak than the estimate of the primary surgeon. Further external validation on a larger data set is required.

ObjectiveEmergency general surgery (EGS) patients experience superior outcomes when cared for within an acute surgical unit (ASU) model. EGS structures in most Australian hospitals remain unknown. This study aimed to describe the national spectrum of EGS models. MethodsA cross-sectional study was performed of all Australian public hospitals of medium or greater peer group (>2000 patient separations per annum). The primary outcome was the incidence of each EGS model. Secondary outcomes were the relationship of the EGS model to objective hospital variables, and qualitative reasons for the choice of model. ResultsOf the 120 eligible hospitals, 119 (99%) participated. Sixty-four hospitals reported using an ASU (28%) or hybrid EGS model (26%), whereas the remaining 55 (46%) used a traditional model. ASU implementation was significantly more common among hospitals of greater peer group, bed number, surgeon pool and trauma service sophistication. Leading drivers for ASU commencement were aims to improve patient care and decrease after-hours operating, whereas common barriers against uptake were insufficient EGS patient load or surgeon on-call pool. ConclusionsASU or hybrid models of care may be more widespread than currently reported. The introduction of such structures is heavily dependent on hospital and staff size, trauma subspecialisation and EGS patient throughput. What is known about the topic?Traditionally, general surgical staff were rostered to elective operating and clinic duties, with emergency patients managed on an ad hoc basis. An ASU model, with a surgeon dedicated to EGS patients, has been associated with superior outcomes. However, the Australian uptake of this model is unknown. What does this paper add?This study enrolled 119 of 120 (99%) Australian public hospitals of medium or greater peer group (>2000 patient separations per annum). Uptake of the ASU or hybrid model was more widespread than expected, existing in 64 of 119 (54%) centres. Factors for and against ASU implementation were also assessed. What are the implications for practitioners?Hospitals considering implementing an ASU or hybrid model will be reassured by the common reports of improved patient outcomes and decreased after-hours operating. However, potential hospitals must assess the suitability of the ASU model to their surgeon pool and EGS patient load.

BACKGROUND Few studies have assessed the relationship between different emergency general surgery models and staff satisfaction, operative experience or working hours. The Royal Australasian College of Surgeons recommends maximum on-call frequency of one-in-four for surgeons and registrars. METHODS A cross-sectional study was conducted of all medium- to major-sized Australian public hospitals offering elective general surgery. At each site, an on-call general surgery registrar and senior surgeon were invited to participate. Primary outcomes were staff satisfaction and registrar-perceived operative exposure. Secondary outcomes were working hours. RESULTS Among eligible hospitals, 119/120 (99%) were enrolled. Compared with traditional emergency general surgery models, hybrid or acute surgical unit models were associated with greater surgeon and registrar satisfaction on quantitative (P = 0.012) and qualitative measures. Registrar-perceived operating exposure was unaffected by emergency general surgery model. Longest duration on-duty was higher among traditional structures for both registrars (mean 22 versus 15 h; P = 0.0003) and surgeons (mean 59 versus 41 h; P = 0.020). On-call frequency greater than one-in-four was more common in traditional structures for registrars (51% versus 28%; P = 0.012) but not surgeons (6% versus 0%; P = 0.089). Data on average hours per day off-duty were obtained for registrars only, and were lower in traditional structures (13 versus 15 h; P = 0.00002). CONCLUSION Hybrid or acute surgical unit models may improve staff satisfaction without sacrificing perceived operative exposure. While average maximum duration on-duty exceeded hazardous thresholds for surgeons regardless of model, unsafe working hours for registrars were more common in traditional structures. General surgical departments should review on-call rostering to optimize staff and patient safety.

Background Microsatellite instability (MSI) is the molecular marker for DNA mismatch repair deficiency (dMMR) in colorectal cancer (CRC) and has been associated with better survival outcomes in early stage disease. In metastatic CRC (mCRC), outcomes for patients with MSI are less clear. There is evolving evidence that treatment pathways forMSI CRC should include programmed-death 1 (PD-1) antibodies. Objective An analysis was performed to explore the impact of MSI status on overall survival (OS) in mCRC. Patients and methods South Australian Metastatic CRC Registry data were analysed to assess patient characteristics and survival outcomes, comparing patients with MSI CRC with those whose tumours were microsatellite stable (MSS). Kaplan–Meier survival analysis was used to assess OS. Cox regression analysis was undertaken to assess the independence of MSI as a prognostic factor. Results Of 4359 patients registered on the database, 598 (14%) had been tested for, and 62 (10.1%) of these patients had, demonstrable MSI. There were significantly higher rates of right-sided primary (p < 0.001), poorly differentiated pathology (p = 0.002), and BRAF V600E mutation (p < 0.001) in the MSI group. The MSI group were also less likely to receive chemotherapy (p < 0.001) or to have liver surgery, but more likely to be diagnosed at an early stage. The median overall survival was 9.5 months for those with MSI CRC versus 21.3 months for MSS CRC patients (p =0.052). Cox regression analysis indicated that MSI was not an independent predictor of OS. Independent predictors of better OS included having liver surgery for metastasis, having chemotherapy, and being initially diagnosed at an early stage. Conclusions Only 14% of patients with mCRC were tested for MSI, and 1 in 10 were found to be MSI high. The clinical characteristics of MSI mCRC are in keeping with those previously reported. MSI in this population-based registry was associated with a numerically lower survival which did not attain statistical significance. Refereed/Peer-reviewed

Background: Every year, an estimated 15 million babies are born preterm (Purpose: To identify stress biomarkers that have been studied in preterm infants at different time points in the NICU and as long-term outcome measures. Method/search Strategy: Systematic searches were conducted of PubMed, CINAHL, SCOPUS, and PsychInfo databases. Findings/results: Twenty-one studies met inclusion criteria for this review. Several putative biomarkers were identified, including cortisol levels, epigenetic markers, brain microstructure, markers of oxidative stress, and the brain–gut–microbiome axis. Conclusion: The interaction of disease with therapeutic interventions may inadvertently increase infant allostatic load. In addition to human studies, future research should leverage newly available large data sets to conduct additional analyses.

ObjectivesSome early studies indicated lower survival with longer time from diagnosis to cancer treatment, but others showed the reverse. We investigated time to treatment of colorectal cancer and associations with survival.Setting and participantsClinical registry data for colorectal cancer cases diagnosed in 2000–2010 at four major public hospitals in South Australia and treated by surgery (n=1675), radiotherapy (n=616) and/or systemic therapy (n=1556).DesignA historic cohort design, with rank-order tests for ordinal clinical and sociodemographic predictors and multiple logistic regression for comparing time from diagnosis to treatment. Unadjusted Kaplan-Meier estimates and adjusted Cox proportional hazards regression were used to investigate disease-specific survival by time to treatment.Outcome measuresTime to treatment and survival from diagnosis to death from colorectal cancer.ResultsTreatment (any type) commenced for 87% of surgical cases<60 days of diagnosis, with 80% having surgery within this period. Of those receiving radiotherapy, 59% began this treatment<60 days, and of those receiving systemic therapy, the corresponding proportion was 56%. Adjusted analyses showed treatment delay >60 days was more likely for rectal cancers, 2006–2010 diagnoses, residents of northern than other metropolitan regions and for surgery, younger ages <2 years from diagnosis for time to treatment >30 days. Survival in the 3–10 years postdiagnosis generally did not differ by time to treatment, except for lower survival for any treatment >90 days for surgical cases.ConclusionsThe lower survival<2 years from diagnosis for treatment<30 days of diagnosis is consistent with other studies attributed to preferencing more complicated cases for earlier care. Lower 3–10 years survival for surgical cases first treated >90 days from diagnosis is consistent with previously reported U-shaped relationships.

Background: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy Objective: This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care Design: This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). Settings: This study was conducted at 3 hospital sites in South Australia. Patients: Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. Interventions: Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. Main outcome measures: Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded Results: The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent. Limitations: This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control. Conclusions: We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A698 Refereed/Peer-reviewed

Frequent misdiagnosis of pediatric ankle traumas leads to inappropriate management, which may result in residual pain, instability, slower return to physical activity, and long-term degenerative changes. The purpose of this study was to evaluate the consistency of diagnosis, management, and the treatment of acute lateral pediatric ankle trauma in a tertiary care pediatric hospital. The hypothesis was that the initial diagnosis is often incorrect, and the treatment varies considerably amongst orthopedic surgeons. We conducted a retrospective study of all cases of ankle sprains and Salter–Harris one (SH1) fractures referred to our orthopedic surgery service between May and August 2014. Exclusion criteria included ankle fractures other than SH1 types, and cases where treatment was initially undertaken elsewhere before referral to our service. Primary outcome was the difference between initial and final diagnosis. Among 3047 cases reviewed, 31 matched our inclusion criteria. Initial diagnosis was 20 SH1 fractures, 8 acute ankle sprains, and 3 uncertain, with a change in diagnosis for 48.5% at follow-up. Accurate diagnosis can be difficult in pediatric ankle trauma, with case management and specific treatments varying considerably. This study reinforces the need to evaluate the safety of a general treatment algorithm for all lateral ankle trauma with normal radiographs. Level of evidence III.

PURPOSE The predictive role of biomarkers in colon cancer is still being defined. The aim of this study is to determine the interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival benefit after adjuvant 5-FU based chemotherapy in stage III colon cancer. METHODS We performed a retrospective cohort study including all curatively resected stage III colon cancer cases over a 33-year period. A clinicopathological database was collated (adjuvant chemotherapy, age, gender, obstruction, perforation, tumor location, grade, mucin, nodal stage, extramural vascular, and perineural invasion). BRAF (V600E) mutation testing was performed and MSI status established by immunohistochemistry for mismatch repair proteins and molecular testing for National Cancer Institute panel markers. Patients were categorized into four groups for comparison: MSS and BRAF-ve (termed " traditional"), MSI and BRAF-ve (termed " presumed Lynch"), MSI and BRAF+ve (termed " sporadic MSI"), and MSS and BRAF+ve (termed " other BRAF"). The primary endpoint was cancer specific survival. Interaction testing was conducted to determine whether there were different responses to chemotherapy between groups. RESULTS A total of 686 unselected cases met inclusion criteria and had tissue available, of which 15.7% had BRAF mutation (BRAF+ve) and 13.8% had MSI. Thirty-nine percent received chemotherapy. Overall, adjuvant chemotherapy produced a cancer specific survival benefit (HR 0.66, 95% CI, 0.49-0.88, P

This study aimed to investigate the cancer characteristics,treatments administered and outcomes for nonagenarians and centenarians diagnosed with mCRC using our state-wide population-based mCRC registry to understand the current patterns of care and outcomes in this age subgroup of patients. Refereed/Peer-reviewed

Refereed/Peer-reviewed

Purpose The prognostic significance of biomarkers in colorectal cancer is still being defined. This study aimed to determine the prognostic significance of BRAF mutation alone and in combination with microsatellite instability (MSI), in stage III colon cancer. Methods Curatively resected stage III colon cancers were studied from a 33-year period. Clinicopathological data were collated (adjuvant chemotherapy, age, gender, obstruction, perforation, tumour location, grade, presence of mucin, nodal stage, extramural vascular, and perineural invasion). MSI status was established and molecular testing for BRAF (V600E) was performed. Four mutation categories were examined: "traditional" (microsatellite stable [MSS]/BRAF -ve), "presumed Lynch" (MSI/BRAF -ve), "sporadic MSI" (MSI/BRAF +ve), and "other BRAF" (MSS/BRAF +ve). These factors were correlated with cancer-specific survival. Results In total, 686 unselected cases met our inclusion criteria, of which 15.7% had a BRAF mutation and 13.8% showed MSI. In the adjusted analysis, neither BRAF mutation nor MSI mutation were independently prognostic. On univariate analysis, survival in presumed Lynch cancers was similar to traditional cancers (5-year survival: 62% and 61%, respectively). While there was no difference in cancer-specific survival between sporadic MSI and other BRAF, both these tumour group had poorer outcome when compared to traditional or presumed Lynch cancers. Adjusted analysis of the four groups, however, showed that none of the subgroups were independently prognostic. Conclusion BRAF-mutated cancers demonstrated a trend toward poorer outcomes, however, when adjusted for clinicopathological factors and chemotherapy, BRAF mutation was not found to be an independent prognostic biomarker in stage III colon cancer, even when combined with MSI.

Summary Background Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. Methods In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than −10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. Findings Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI −4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. Interpretation A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. Funding Merck & Co, Inc.

Summary Background Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection. Methods In this randomised, controlled, double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection were screened and enrolled at 125 clinical centres in 15 countries. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy with plasma HIV-1 RNA of at least 1000 copies per mL at screening. Participants who had previously been treated for a viral infection other than HIV-1, those taking immunosuppressive drugs, and individuals with active acute hepatitis were excluded. Participants were randomly assigned (1:1) via an interactive voice and web response system to receive oral doravirine 100 mg or darunavir 800 mg plus ritonavir 100 mg once daily, with two investigator-selected NRTIs (tenofovir and emtricitabine or abacavir and lamivudine) for up to 96 weeks. Randomisation was stratified by HIV-1 RNA measurements at screening (≤100 000 vs >100 000 copies per mL) and the NRTI pair. Study participants, funding institution staff, investigators, and study site personnel were masked to treatment group assignment. The primary efficacy endpoint was the proportion of participants achieving HIV-1 RNA of less than 50 copies per mL at week 48 defined by the US Food and Drug Administration snapshot algorithm, with non-inferiority established if the lower bound of the two-sided 95% CI for the treatment difference (doravirine minus darunavir) was greater than −10 percentage points. All participants who received at least one dose of study drug were included in the primary efficacy and safety analyses. This trial is active, but not recruiting, and is registered with ClinicalTrials.gov, number NCT02275780. Findings Between Dec 1, 2014, and Oct 20, 2015, 1027 participants were screened for eligibility, of whom 769 participants were randomly assigned to treatment (385 with doravirine and 384 with ritonavir-boosted darunavir). 56 participants discontinued treatment in the doravirine group compared with 71 in the darunavir group, mostly due to loss to follow-up. 383 participants who received doravirine and 383 who received darunavir were included in the primary efficacy analyses. At week 48, 321 (84%) participants in the doravirine group and 306 (80%) in the darunavir group achieved plasma HIV-1 RNA of less than 50 copies per mL (difference 3·9%, 95% CI −1·6 to 9·4), indicating non-inferiority of the doravirine regimen. The most common study drug-related adverse events were diarrhoea (21 [5%] of 383 participants in the doravirine group and 49 [13%] of 383 participants in the darunavir group), nausea (25 [7%] vs 29 [8%]), and headache (23 [6%] vs ten [3%]). 18 participants (six [2%] of 383 participants in the doravirine group vs 12 [3%] of 383 participants in the darunavir group) discontinued treatment due to adverse events, which were considered drug-related in four (1%) participants in the doravirine group and 8 (2%) participants in the darunavir group. Serious adverse events occurred in 19 (5%) of 383 participants in the doravirine group and 23 (6%) of 383 in the darunavir roup, and were considered study-drug related in one ( Interpretation In treatment-naive adults with HIV-1 infection, doravirine combined with two NRTIs might offer a valuable treatment option for adults with previously untreated HIV-1 infection. Funding Merck & Co.

Recently published data support the use of a web-based risk calculator ( www.anastomoticleak.com ) for the prediction of anastomotic leak after colectomy. The aim of this study was to externally validate this calculator on a larger dataset. Consecutive adult patients undergoing elective or emergency colectomy for colon cancer at a single institution over a 9-year period were identified using the Binational Colorectal Cancer Audit database. Patients with a rectosigmoid cancer, an R2 resection, or a diverting ostomy were excluded. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve (AUROC) was derived and compared with that of the American College of Surgeons National Surgical Quality Improvement Program® (ACS NSQIP) calculator and the colon leakage score (CLS) calculator for left colectomy. Commercially available artificial intelligence-based analytics software was used to further interrogate the prediction algorithm. A total of 626 patients were identified. Four hundred and fifty-six patients met the inclusion criteria, and 402 had complete data available for all the calculator variables (126 had a left colectomy). Laparoscopic surgery was performed in 39.6% and emergency surgery in 14.7%. The anastomotic leak rate was 7.2%, with 31.0% requiring reoperation. The anastomoticleak.com calculator was significantly predictive of leak and performed better than the ACS NSQIP calculator (AUROC 0.73 vs 0.58) and the CLS calculator (AUROC 0.96 vs 0.80) for left colectomy. Artificial intelligence-predictive analysis supported these findings and identified an improved prediction model. The anastomotic leak risk calculator is significantly predictive of anastomotic leak after colon cancer resection. Wider investigation of artificial intelligence-based analytics for risk prediction is warranted.

Dear SirWhile preparing for our ERASMUS + scheme European placement, we were interested to read “12 Tips for Effective International Clinical Placement” (Balandin et al. 2007). Now in our fifth yea...

In 2010, The Nature Conservancy completed the Mojave Desert Ecoregional Assessment, which characterizes conservation values across nearly 130,000 km2 of the desert Southwest. Since this assessment was completed, several renewable energy facilities have been built in the Mojave Desert, thereby changing the conservation value of these lands. We have completed a new analysis of land use to reassess the conservation value of lands in two locations in the Mojave Desert where renewable energy development has been most intense: Ivanpah Valley, and the Western Mojave. We found that 99 of our 2.59-km2 planning units were impacted by development such that they would now be categorized as having lower conservation value, and most of these downgrades in conservation value were due to solar and wind development. Solar development alone was responsible for a direct development footprint 86.79 km2: 25.81 km2 of this was primarily high conservation value Bureau of Land Management lands in the Ivanpah Valley, and 60.99 km2 was privately owned lands, mostly of lower conservation value, in the Western Mojave. Our analyses allow us to understand patterns in renewable energy development in the mostly rapidly changing regions of the Mojave Desert. Our analyses also provide a baseline that will allow us to assess the effectiveness of the Desert Renewable Energy Conservation Plan in preventing development on lands of high conservation value over the coming decades.

Summary Despite the global financial downturn, millions of people continue to travel abroad each year. Many travel with co-morbidities such as immunosuppression, placing them at greater risk of bacterial, viral and parasitic infections. 1 Leishmaniasis is one of the principal neglected tropical diseases. 2 Although it threatens 350 million people each year 3 it is not an infection that most General Physicians would associate with travel to Southern Europe. A case of visceral leishmaniasis is described in a lady with mild immunosuppression caused by systemic lupus erythematosus, following a holiday in Southern Spain, a destination not normally associated with this leishmaniasis.