Inflammatory cell ratios predict major septic complications following rectal cancer surgery.

INTRODUCTION: The inflammatory response is known to have an important role in tumourigenesis and the response to treatment. Previous studies have demonstrated that inflammatory cell ratios such as the neutrophil-to-lymphocyte ratio (NLR) can predict survival and recurrence following surgery for various cancers. The objective of this study was to demonstrate if pre-operative NLR has a role in predicting post-operative septic complications in patients undergoing rectal cancer surgery. METHODOLOGY: Consecutive patients undergoing scheduled resection for rectal cancer in a tertiary centre from July 2007 to Dec 2015 were included. Data was gathered from a prospectively held database of rectal cancer. Normally distributed data were compared with paired t tests (mean ± standard error in the mean (SEM)), and proportions were compared with Fisher's exact test. A p value of < 0.05 was considered statistically significant. RESULTS: Three hundred fourteen patients were identified in this study. Sixty nine (22.0%) patients had a major septic complication following surgery for rectal cancer, which was associated with a poor survival outcome (p < 0.01) Both pre and post-operative NLR and PLR (platelet lymphocyte ratio) were associated with post-operative septic complications (both p < 0.01). A pre-operative NLR threshold level of 4 was chosen from ROC analysis, and this provided a relatively specific test to predict post-operative septic complications in these patients (specificity = 83.7%, negative predictive value (NPV) = 74.8%). DISCUSSION: In this study, the pre-operative NLR and PLR were both predictive of major post-operative septic complications. A pre-operative NLR of less than 4 was strongly negative predictor of post-operative complications in rectal cancer surgery. It can be regarded as a predictive and prognostic factor for these patients.

The Royal College of Surgeons of England Damage Control Orthopaedic Trauma Skills course (DCOTS): resuscitative knowledge and confidence in surgical skills are reliably maintained at six months post course.

INTRODUCTION: Since 2012, the Damage Control Orthopaedic Trauma Skills course (DCOTS) has trained more than 250 surgeons in the principles and practice of damage control orthopaedics and early appropriate care. This Royal College of Surgeons of England (RCS England) course takes place at the RCS England Partner cadaver laboratory at Brighton and Sussex Medical School. Trauma is a leading cause of morbidity and mortality in the UK, and the course has tried to pass on the lessons of war and conflict from its military faculty and hard-won lessons of "developed world" trauma from its experienced civilian faculty. METHODS: Participating surgeons were invited to score their self-reported confidence before attending the DCOTS course, immediately afterwards and again 6 months later. A modified four-point Likert scale was used, with responses from 1 = No Confidence to 4 = Very Confident. Damage control resuscitation principles with damage control surgery showed the greatest retained increase at 6 months - 100% - which is extremely satisfying. RESULTS: Self-reported confidence in pelvic external fixation was initially 93% dropping to 85%, which is also considered good to excellent. For pelvic packing, confidence was 90% at the end of the course, up from 19% precourse. This dropped to 62%, which was still considered good but low for the high standards of the course. This may relate to UK trainees' lack of familiarity with the concept. CONCLUSIONS: Three of the main skills taught on the DCOTS are effectively retained at 6 months post course.

Altered leucocyte progenitor profile in human bone marrow from patients with major trauma during the recovery phase.

BACKGROUND: Changes in human bone marrow associated with the systemic inflammatory response to injury are little understood. It was hypothesized that major trauma results in an altered bone marrow leucocyte progenitor profile, with either uniform depletion or the balance between multipotent and committed progenitors varying, depending on whether self-renewal is favoured over differentiation. METHODS: Bone marrow aspirate and peripheral blood samples were obtained at definitive surgery in adults with pelvic fractures from blunt trauma (major trauma with Injury Severity Score (ISS) at least 18, or isolated fractures) and control patients undergoing iliac crest bone grafting. ISS, interval to surgery and transfusion in the first 24 h were recorded. Bone marrow aspirate flow cytometry was used to identify haemopoietic progenitor cells (CD34(+) ), multipotent cells (CD34(+) CD45(+) CD38(-) ) and oligopotent cells (CD34(+) CD45(+) CD38(lo/+) and CD34(+) CD45(+) CD38(BRIGHT(++ +)) subsets). Peripheral blood levels of inflammatory markers were measured, and the ratio of immature to mature (CD35(-) /CD35(+) ) granulocytes was determined. RESULTS: The median (range) interval between injury and sampling was 7 (1-21) and 5 (1-21) days in the major trauma and isolated fracture groups respectively. The CD34(+) pool was significantly depleted in the major trauma group (P = 0·017), particularly the CD34(+) CD45(+) CD38(BRIGHT(++ +)) oligopotent pool (P = 0·003). Immature CD35(-) granulocytes increased in bone marrow with increasing injury severity (P = 0·024) and massive transfusion (P = 0·019), and in peripheral blood with increasing interval to surgery (P = 0·005). CONCLUSION: Major blunt trauma resulted in changes in the bone marrow CD34(+) progenitor pool. At the point in recovery when these samples were obtained, oligopotent progenitors were lost from the bone marrow, with continued release of immature cells.

The number of benign moles excised for each malignant melanoma: the number needed to treat.

BACKGROUND: The ratio of benign moles excised for each malignant melanoma (MM) diagnosed, i.e. the number needed to treat (NNT), may be a useful indicator of diagnostic accuracy and the efficient use of healthcare resources, and may have personal implications for the patient. AIM: To assess the NNT for a group of consultant dermatologists serving a population of 600,000, and to compare this with similar studies from other countries. METHODS: This was a retrospective analysis of data on pigmented lesions excised over a 5-year period (2005-2009). The lesions were divided into three groups: benign naevi (BN), dysplastic naevi (DN) and MM. The NNT ratio was calculated as (BN + DN + MM)/MM. RESULTS: In total, 4691 lesions were examined. The overall mean NNT was 6.3, with a range of 4.9-11.3 for each of nine consultant dermatologists. The mean NNT was 7.6 for female and 4.8 for male patients. There were more patients with BN (n = 3534; 75%) than with DN (n = 407; 9%) or MM (n = 750; 16%). The gender representation was similar in the DN and MM groups, but had a disproportionately female bias in the BN group (67% female, 33% male patients). Overall, there were more female patients in all three groups [2962 female patients (63%) and 1729 male patients (37%)]. CONCLUSIONS: The NNT of 6.3 in this study compares favourably with NNT ratios from studies of dermatologists from other countries. This study may encourage other countries and individual doctors to assess their NNT ratios, as it may be an important indicator of the efficient use of resources and the avoidance of unnecessary surgery for patients.

Identifying and prioritising epilepsy treatment uncertainties.

OBJECTIVE: To identify and prioritise uncertainties regarding epilepsy treatment from people with epilepsy, their carers and epilepsy clinicians. BACKGROUND: Failure to acknowledge and address genuine treatment uncertainties has caused unnecessary iatrogenic harm. The authors define an uncertainty as a question that cannot be sufficiently answered by a systematic review of the literature. The database of the uncertainties of the effects of treatment (DUETs) is a collection of 'known unknowns' that enables patient-prioritised research. DESIGN AND PARTICIPANTS: The authors organised five separate focus groups (two consisting of clinicians, three of patients and carers) to garner questions on epilepsy treatment uncertainties; these yielded 398 potential research questions. Participants were asked to rank the questions in terms of importance. The authors then performed a thematic analysis. RESULTS: Patients rated questions concerning cognitive drug side effects, managing the consequences of side effects and improving public awareness about the treatment of epilepsy through improved services as most important. For clinicians, the most important themes were treatment programmes for non-epileptic attack disorder (NEAD), concerns about side effects in utero and uncertainties regarding prescribing in pregnancy. CONCLUSIONS: Patient uncertainties were often focussed on very practical considerations-how to take prescribed medication, access to services and how to minimise drug side effects. Clinicians' questions were also practical but clustered around 'the challenging consultation'-for example, NEAD, sudden unexplained death in epilepsy and prescribing in pregnancy. The authors have published the research questions on NHS Evidence and are working with them to identify those questions which represent genuine uncertainties. The authors encourage other clinicians to seek patient and carers' priorities in order to shape their research agenda.

Novel method of measuring the mental workload of anaesthetists during clinical practice.

BACKGROUND: Cognitive overload has been recognized as a significant cause of error in industries such as aviation and measuring mental workload has become a key method of improving safety. The aim of this study was to pilot the use of a new method of measuring mental workload in the operating theatre using a previously published methodology. METHODS: The mental workload of the anaesthetists was assessed by measuring their response times to a wireless vibrotactile device and the NASA TLX subjective workload score during routine surgical procedures. Primary task workload was inferred from the phase of anaesthesia. RESULTS: Significantly increased response time was associated with the induction phase of anaesthesia compared with maintenance/emergence, non-consultant grade, and during more complex cases. Increased response was also associated with self-reported mental load, physical load, and frustration. These findings are consistent with periods of increased mental workload and with the findings of other studies using similar techniques. CONCLUSIONS: These findings confirm the importance of mental workload to the performance of anaesthetists and suggest that increased mental workload is likely to be a common problem in clinical practice. Although further studies are required, the method described may be useful for the measurement of the mental workload of anaesthetists.

Validation of a novel fibreoptic intubation trainer.

The aim of this study was to validate a novel inexpensive training device as a means of improving the psychomotor skills involved in the manipulation of a fibreoptic endoscope. Seventy-five subjects attempted to pass a fibreoptic endoscope through the device five times, with each attempt timed to the nearest second. Although prior clinical experience of fibreoptic intubation was associated with better performance, all groups showed improvement with each attempt. Qualitative feedback indicated that the device required subjects to use similar skills to those used in clinical practice. This study supports the use of such a device in training and assessment although further studies will be required to determine whether the skills learned on the device can be transferred to the clinical environment.

Comparative Dosimetric Analysis and Normal Tissue Complication Probability Modelling of Four-Dimensional Computed Tomography Planning Scans Within the UK NeoSCOPE Trial.

AIMS: NeoSCOPE is a trial of two different neoadjuvant chemoradiotherapy regimens for resectable oesophageal cancer and was the first multicentre trial in the UK to incorporate four-dimensional computed tomography (4D-CT) into radiotherapy planning. Despite 4D-CT being increasingly accepted as a standard of care for lower third and junctional oesophageal tumours, there is limited evidence of its benefit over standard three-dimensional computed tomography (3D-CT). MATERIALS: Using NeoSCOPE 4D-CT cases, we undertook a dosimetric comparison study of 3D-CT versus 4D-CT plans comparing target volume coverage and dose to organs at risk. We used established normal tissue complication probability models to evaluate the potential toxicity reduction of using 4D-CT plans in oesophageal cancer. RESULTS: 4D-CT resulted in a smaller median absolute PTV volume and lower dose levels for all reported constraints with comparable target volume coverage. NTCP modelling suggests a significant relative risk reduction of cardiac and pulmonary toxicity endpoints with 4D-CT. CONCLUSION: Our work shows that incorporating 4D-CT into treatment planning may significantly reduce the toxicity burden from this treatment.

Using multiple datasets to understand trends in serious road traffic casualties.

Accurate information on the incidence of serious road traffic casualties is needed to plan and evaluate prevention strategies. Traditionally police reported collisions are the only data used. This study investigate the extent to which understanding of trends in serious road traffic injuries is aided by the use of multiple datasets. Health and police datasets covering all or part of Great Britain from 1996-2003 were analysed. There was a significantly decreasing trend in police reported serious casualties but not in the other datasets. Multiple data sources provide a more complete picture of road traffic casualty trends than any single dataset. Increasing availability of electronic health data with developments in anonymised data linkage should provide a better platform for monitoring trends in serious road traffic casualties.

A comparison of two smartphone applications and the validation of smartphone applications as tools for fluid calculation for burns resuscitation.

We conducted a randomised, blinded study to compare the accuracy and perceived usability of two smartphone apps (uBurn(©) and MerseyBurns(©)) and a general purpose electronic calculator for calculating fluid requirements using the Parkland formula. Bespoke software randomly generated simulated clinical data; randomly allocated the sequence of calculation methods; recorded participants' responses and response times; and calculated error magnitude. Participants calculated fluid requirements for nine scenarios (three for each: calculator, uBurn(©), MerseyBurns(©)); then rated ease of use (VAS) and preference (ranking), and made written comments. Data were analysed using ANOVA and qualitative methods. The sample population consisted of 34 volunteers who performed a total of 306 calculations. The three methods showed no significant difference in incidence or magnitude of errors. Mean (SD) response time in seconds for the calculator was 86.7 (50.7), compared to 71.7 (42.9) for uBurn(©) and 69.0 (35.6) for MerseyBurns(©). Both apps were significantly faster than the calculator (p=0.013 and p=0.017 respectively, ANOVA: Tukey's HSD test). All methods showed a learning effect (p<0.001). The participants rated ease of use on a VAS scale with a higher score indicating greater ease of use. The calculator was easiest to use with a mean score (SD) of 12.3 (2.1), followed by MerseyBurns(©) with 11.8 (2.7) and then uBurn(©) with 11.3 (2.7). The differences were not found to be significant at the p=0.05 level after using paired samples t-test and a multiple correction was applied manually. Preference ranking followed a similar trend with mean rankings (SD) of 1.85 (0.17), 1.94 (0.74) and 2.18 (0.90) for the calculator, MerseyBurns(©) and uBurn(©) respectively. Again, none of these differences were significant at the p=0.05 level.

Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.

Genetic toxicology data have traditionally been employed for qualitative, rather than quantitative evaluations of hazard. As a continuation of our earlier report that analyzed ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS) dose-response data (Gollapudi et al., 2013), here we present analyses of 1-ethyl-1-nitrosourea (ENU) and 1-methyl-1-nitrosourea (MNU) dose-response data and additional approaches for the determination of genetic toxicity point-of-departure (PoD) metrics. We previously described methods to determine the no-observed-genotoxic-effect-level (NOGEL), the breakpoint-dose (BPD; previously named Td), and the benchmark dose (BMD10 ) for genetic toxicity endpoints. In this study we employed those methods, along with a new approach, to determine the non-linear slope-transition-dose (STD), and alternative methods to determine the BPD and BMD, for the analyses of nine ENU and 22 MNU datasets across a range of in vitro and in vivo endpoints. The NOGEL, BMDL10 and BMDL1SD PoD metrics could be readily calculated for most gene mutation and chromosomal damage studies; however, BPDs and STDs could not always be derived due to data limitations and constraints of the underlying statistical methods. The BMDL10 values were often lower than the other PoDs, and the distribution of BMDL10 values produced the lowest median PoD. Our observations indicate that, among the methods investigated in this study, the BMD approach is the preferred PoD for quantitatively describing genetic toxicology data. Once genetic toxicology PoDs are calculated via this approach, they can be used to derive reference doses and margin of exposure values that may be useful for evaluating human risk and regulatory decision making.

Intense pulsed light treatment of chronic mid-body Achilles tendinopathy: A double blind randomised placebo-controlled trial.

We conducted a randomised controlled trial to determine whether active intense pulsed light (IPL) is an effective treatment for patients with chronic mid-body Achilles tendinopathy. A total of 47 patients were randomly assigned to three weekly therapeutic or placebo IPL treatments. The primary outcome measure was the Victorian Institute of Sport Assessment - Achilles (VISA-A) score. Secondary outcomes were a visual analogue scale for pain (VAS) and the Lower Extremity Functional Scale (LEFS). Outcomes were recorded at baseline, six weeks and 12 weeks following treatment. Ultrasound assessment of the thickness of the tendon and neovascularisation were also recorded before and after treatment. There was no significant difference between the groups for any of the outcome scores or ultrasound measurements by 12 weeks, showing no measurable benefit from treatment with IPL in patients with Achilles tendinopathy.