Developing an intervention package to optimise the management of vancomycin therapy using theory informed co-design.

BACKGROUND: Optimising the management of vancomycin by achieving target therapeutic concentrations early during therapy has been associated with reduced mortality and morbidity. Despite the availability of guidelines and training, the management of vancomycin remains suboptimal. OBJECTIVES: The primary outcome was the development of interventions and associated implementation strategies to optimise the management of vancomycin therapy. This paper describes how co-design process was used to build a theory informed intervention package, which was implemented across a wide range of in-patient hospital settings in Queensland, Australia. METHODS: This multiple methods study was conducted in four phases: 1) a baseline audit to identify the nature of the problem and associated determinants informed by stakeholder interviews 2) mapping these findings to the Theoretical Domains Framework (TDF) to identify behavioural correlates and modifiers 3) prioritising the behavioural modifiers and associated implementation strategies to inform a protype of the intervention in a series of co-design sessions and 4) implementing and evaluating the intervention package. The study was conducted across the four teaching hospitals in a large Queensland Hospital and Health Service across multiple healthcare disciplines namely nurses, doctors, and pharmacists. This intervention package was subsequently implemented across Queensland Health with the support of the local champions under the guidance of the steering group. RESULTS: Clinicians identified that a multifaceted intervention package and training which can be tailored to the health-care professional disciplines, would be best suited to shift clinician behaviour to align with guidelines. The findings from the co-design process aligned with theory-informed intervention package. Each of the intervention strategies varied in their frequency and popularity of use. CONCLUSIONS: The use of theory-informed and participatory approach assisted with the intervention development process and aligned the intervention content with the priorities of stakeholders. The TDF provided a structured process for developing intervention content which is both acceptable and useful to stakeholders and may improve the management of vancomycin.

Provision of trauma care in asymmetric warfare: a conceptual framework to support the decision to implement frontline care services.

INTRODUCTION: The emerging trends of asymmetric and urban warfare call for a revision of the needs and the way in which frontline trauma care is provided to affected population. However, there is no consensus on the process to decide when and how to provide such lifesaving interventions in form of Trauma Stabilization Point (TSP). METHODS: A three-step Delphi method was used to establish consensus. A focus group discussion was convened to propose a framework and develop the list of twenty-one (21) statements for validation of a group of experts. RESULTS: A panel of twenty-eight (28) experts reviewed the statements and participated to both first and second rounds. Comments and recommendations provided by the FGD and during round 1 were used to analyze the findings of the study. The proposed framework includes five main categories identified as interconnected components that facilitate the decision to implement or not the TSP. A total of sixteen (16) elements distributed across the five categories have been considered as being able to guide the decision to utilize such capability in high-risk security and resource constrained settings. CONCLUSION: The TSP has the potential to prevent death and disability. The proposed framework and categories add a structure to the decision-making process and represents an important step to support emergency and trauma care planning and implementation efforts.

Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

Implementation of podiatry telephone appointments for people with rheumatic and musculoskeletal diseases.

BACKGROUND: Foot health problems are common in the general population, and particularly so in people with rheumatic and musculoskeletal disorders (RMD). Several clinical guidelines state that people with RMDs should have access to foot health services, although service capacity is often limited. The current COVID-19 pandemic has increased the need for alternative ways to provide patient care. The aim of this clinical audit was to review a newly implemented telephone follow-up appointment service conducted within the Rheumatology Podiatry Department in Leeds, UK. METHODS: Fifty-eight patients attending the Rheumatology Podiatry Department at Leeds Teaching Hospitals NHS Trust were contacted by telephone approximately 6-8 weeks following initial intervention. During the telephone consultation, all patients were asked pre-defined questions relating to their symptoms, intervention efficacy, the need for further appointments and their preference for the type of consultation. To assess the cost of the telephone consultation the number of attempts needed in order to make successful contact, the duration of the call and the number of telephone follow-up appointments completed in a working day were also recorded. RESULTS: Twenty-five patients (43%) were successfully contacted within the 6-8 weeks stipulated time frame and were included in the analysis. Of the 25 contacted, twelve (48%) patients were successfully contacted on the first attempt. Ten (40%) were successfully contacted on the second attempt. The remaining three patients (12%) required 3 or more attempts to make successful contact. Telephone consultations were estimated not to last longer than 10 min, including notes screening and documentation. Eleven patients (44%) reported an improvement in their symptoms, thirteen (52%) reported no change and one patient (4%) reported their symptoms to be worse. CONCLUSION: Telephone follow-up consultations may be a potentially cost-effective alternative to face-to-face appointments when implemented in a Rheumatology Podiatry Department, and provide an alternative way of providing care, especially when capacity for face-to-face contact is limited. The potential cost saving and efficiency benefits of this service are likely to be enhanced when telephone consultations are pre-arranged with patients.

Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling.

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor-node-metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP). PATIENTS AND METHODS: A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival. RESULTS: Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival. CONCLUSIONS: We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.

Capturing accelerometer outputs in healthy volunteers under normal and simulated-pathological conditions using ML classifiers.

Wearable devices offer a possible solution for acquiring objective measurements of physical activity. Most current algorithms are derived using data from healthy volunteers. It is unclear whether such algorithms are suitable in specific clinical scenarios, such as when an individual has altered gait. We hypothesized that algorithms trained on healthy population will result in less accurate results when tested in individuals with altered gait. We further hypothesized that algorithms trained on simulated-pathological gait would prove better at classifying abnormal activity. We studied healthy volunteers to assess whether activity classification accuracy differed for those with healthy and simulated-pathological conditions. Healthy participants (n=30) were recruited from the University of Leeds to perform nine predefined activities under healthy and simulated-pathological conditions. Activities were captured using a wrist-worn MOX accelerometer (Maastricht Instruments, NL). Data were analyzed based on the Activity-Recognition-Chain process. We trained a Neural-Network, Random-Forests, k-Nearest-Neighbors (k-NN), Support-Vector-Machines (SVM) and Naive Bayes models to classify activity. Algorithms were trained four times; once with `healthy' data, and once with `simulated-pathological data' for each of activity-type and activity-task classification. In activity-type instances, the SVM provided the best results; the accuracy was 98.4% when the algorithm was trained and then tested with unseen data from the same group of healthy individuals. Accuracy dropped to 52.8% when tested on simulated-pathological data. When the model was retrained with simulated-pathological data, prediction accuracy for the corresponding test set was 96.7%. Algorithms developed on healthy data are less accurate for pathological conditions. When evaluating pathological conditions, classifier algorithms developed using data from a target sub-population can restore accuracy to above 95%.

A calcar collar is protective against early periprosthetic femoral fracture around cementless femoral components in primary total hip arthroplasty: a registry study with biomechanical validation.

AIMS: The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model. MATERIALS AND METHODS: A total of 337 647 primary total hip arthroplasties (THAs) from the United Kingdom National Joint Registry (NJR) were included in a multivariable survival and regression analysis to identify the adjusted hazard of revision for periprosthetic fracture following primary THA using a cementless stem. The effect of a collar in cementless THA on this risk was evaluated in an in vitro model using paired fresh frozen cadaveric femora. RESULTS: The prevalence of early revision for periprosthetic fracture was 0.34% (1180/337 647) and 44.0% (520/1180) occurred within 90 days of surgery. Implant risk factors included: collarless stem, non-grit-blasted finish, and triple-tapered design. In the in vitro model, a medial calcar collar consistently improved the stability and resistance to fracture. CONCLUSION: Analysis of features of stem design in registry data is a useful method of identifying implant characteristics that affect the risk of early periprosthetic fracture around a cementless femoral stem. A collar on the calcar reduced the risk of an early periprosthetic fracture and this was confirmed by biomechanical testing. This approach may be useful in the analysis of other uncommon modes of failure after THA. Cite this article: Bone Joint J 2019;101-B:779-786.

Patient characteristics affect hip contact forces during gait.

OBJECTIVE: To examine hip contact force (HCF), calculated through multibody modelling, in a large total hip replacement (THR) cohort stratified by patient characteristics such as body mass index (BMI), age and function. METHOD: 132 THR patients undertook one motion capture session of gait analysis at a self-selected walking speed. HCFs were then calculated using the AnyBody Modelling System. Patients were stratified into three BMI groups, five age groups, and finally three functional groups determined by their self-selected gait speed. By means of statistical parametric mapping (SPM), statistical analyses of the 1-dimensional time series were performed to separately evaluate the influence of age, BMI and functionality on HCF. RESULTS: The mean predicted HCFs were comparable to HCFs measured with instrumented prostheses reported in the literature. The SPM analysis revealed a statistically significant positive linear correlation between BMI and HCF, indicating that obese patients are more likely to experience higher HCF during most of the stance phase, while a statistically significant negative correlation with age was found only during the late swing-phase. Patients with higher functional ability exhibited significantly increased peak HCF, while patients with lower functional ability demonstrated lower HCFs overall and a pathological flattening of the typical double hump force profile. CONCLUSION: HCFs experienced at the bearing surface are highly dependent on patient characteristics. BMI and functional ability were determined to have the biggest influence on contact forces. Current preclinical testing standards do not reflect this.

Midfoot osteoarthritis: potential phenotypes and their associations with demographic, symptomatic and clinical characteristics.

OBJECTIVE: To investigate the demographic, symptomatic, clinical and structural foot characteristics associated with potential phenotypes of midfoot osteoarthritis (OA). DESIGN: Cross-sectional study of 533 community-dwelling adults aged ≥50 years with foot pain in the past year. Health questionnaires and clinical assessments of symptoms, foot structure and function were undertaken. Potential midfoot OA phenotypes were defined by the pattern of radiographic joint involvement affecting either the medial midfoot (talonavicular, navicular-1st cuneiform, or cuneiform-1st metatarsal joint), central midfoot (2nd cuneiform-metatarsal joint), or both medial and central midfoot joints. Multivariable regression models with generalised estimating equations were used to investigate the associations between patterns of midfoot joint involvement and symptomatic, clinical and structural characteristics compared to those with no or minimal midfoot OA. RESULTS: Of 879 eligible feet, 168 had medial midfoot OA, 103 central midfoot OA, 76 both medial and central midfoot OA and 532 no/minimal OA. Having both medial and central midfoot OA was associated with higher pain scores, dorsally-located midfoot pain (OR 2.54, 95%CI 1.45, 4.45), hallux valgus (OR 1.76, 95%CI 1.02, 3.05), flatter foot posture (ß 0.44, 95%CI 0.12, 0.77), lower medial arch height (ß 0.02, 95%CI 0.01, 0.03) and less subtalar inversion and 1st MTPJ dorsiflexion. Isolated medial midfoot OA and central midfoot OA had few distinguishing clinical characteristics. CONCLUSIONS: Distinct phenotypes of midfoot OA appear challenging to identify, with substantial overlap in symptoms and clinical characteristics. Phenotypic differences in symptoms, foot posture and function were apparent in this study only when both the medial and central midfoot were involved.

Magnetic Resonance Imaging of synovitis in knees of patients with osteoarthritis without injected contrast agents using T1 quantification.

INTRODUCTION: To measure the range of T1 values of synovitis using three Tesla (3 T) magnetic resonance imaging (MRI) in patients with osteoarthritis to assess the potential of T1 mapping for identifying synovitis from other features in the knee on unenhanced magnetic resonance scans. METHODS: After receiving institutional ethical approval, 83 patients who met the American College of Rheumatology criteria for diagnosis of osteoarthritis of the knee were scanned using a 3 T Magnetic Resonance Imaging scanner. T1 maps were calculated from spoiled gradient echo images acquired with five different flip angles of 5°-25°. Mean values for the T1 measurements were calculated and compared to existing data from the published literature for anatomical and pathological structures of the knee. RESULTS: T1 values recorded in patients suffering from osteoarthritis demonstrated that T1 values for synovitis (confirmed on gadolinium enhanced images) fall in a narrow range (849-1277 ms, mean 1005 ms SD 91) delineating this from other structures of the knee such as muscle (T1 value range 1305-2638 ms, mean 1785 ms SD 304) and synovial fluid (T1 value range 3867-4129 ms, mean 3915 SD 899) at 3 T. CONCLUSION: T1 values measured in synovitis in patients with osteoarthritis of the knee demonstrated a range of values distinct to those measured in muscle and synovial fluid at 3 T. This offers potential for the use of T1 maps to delineate or quantify synovitis in patients who are unwilling or unable to receive injectable contrast agents.

Are prehospital deaths from trauma and accidental injury preventable? A direct historical comparison to assess what has changed in two decades.

BACKGROUND & OBJECTIVES: In 1994, Hussain and Redmond revealed that up to 39% of prehospital deaths from accidental injury might have been preventable had basic first aid care been given. Since then there have been significant advances in trauma systems and care. The exclusion of prehospital deaths from the analysis of trauma registries, giv en the high rate of those, is a major limitation in prehospital research on preventable death. We have repeated the 1994 study to identify any changes over the years and potential developments to improve patient outcomes. METHODS: We examined the full Coroner's inquest files for prehospital deaths from trauma and accidental injury over a three-year period in Cheshire. Injuries were scored using the Abbreviated-Injury-Scale (AIS-1990) and Injury Severity Score (ISS), and probability of survival estimated using Bull's probits to match the original protocol. RESULTS: One hundred and thirty-four deaths met our inclusion criteria; 79% were male, average age at death was 53.6 years. Sixty-two were found dead (FD), fifty-eight died at scene (DAS) and fourteen were dead on arrival at hospital (DOA). The predominant mechanism of injury was fall (39%). The median ISS was 29 with 58 deaths (43%) having probability of survival of >50%. Post-mortem evidence of head injury was present in 102 (76%) deaths. A bystander was on scene or present immediately after injury in 45% of cases and prior to the Emergency Medical Services (EMS) in 96%. In 93% of cases a bystander made the call for assistance, in those DAS or DOA, bystander intervention of any kind was 43%. CONCLUSIONS: The number of potentially preventable prehospital deaths remains high and unchanged. First aid intervention of any kind is infrequent. There is a potentially missed window of opportunity for bystander intervention prior to the arrival of the ambulance service, with simple first-aid manoeuvres to open the airway, preventing hypoxic brain injury and cardiac arrest.

Prehospital deaths from trauma: Are injuries survivable and do bystanders help?

BACKGROUND AND OBJECTIVES: Deaths from trauma occurring in the prehospital phase of care are typically excluded from analysis in trauma registries. A direct historical comparison with Hussain and Redmond's study on preventable prehospital trauma deaths has shown that, two decades on, the number of potentially preventable deaths remains high. Using updated methodology, we aimed to determine the current nature, injury severity and survivability of traumatic prehospital deaths and to ascertain the presence of bystanders and their role following the point of injury including the frequency of first-aid delivery. METHODS: We examined the Coroners' inquest files for deaths from trauma, occurring in the prehospital phase, over a three-year period in the Cheshire and Manchester (City), subsequently referred to as Manchester, Coronial jurisdictions. Injuries were scored using the Abbreviated-Injury-Scale (AIS-2008), Injury Severity Score (ISS) calculated and probability of survival estimated using the Trauma Audit and Research Network's outcome prediction model. RESULTS: One hundred and seventy-eight deaths were included in the study (one hundred and thirty-four Cheshire, forty-four Manchester). The World Health Organisation's recommendations consider those with a probability of survival between 25-50% as potentially preventable and those above 50% as preventable. The median ISS was 29 (Cheshire) and 27.5 (Manchester) with sixty-two (46%) and twenty-six (59%) respectively having a probability of survival in the potentially preventable and preventable ranges. Bystander presence during or immediately after the point of injury was 45% (Cheshire) and 39% (Manchester). Bystander intervention of any kind was 25% and 30% respectively. Excluding those found dead and those with a probability of survival less than 25%, bystanders were present immediately after the point of injury or "within minutes" in thirty-three of thirty-five (94%) Cheshire and ten of twelve (83%) Manchester. First aid of any form was attempted in fourteen of thirty-five (40%) and nine of twelve (75%) respectively. CONCLUSIONS: A high number of prehospital deaths from trauma occur with injuries that are potentially survivable, yet first aid intervention is infrequent. Following injury there is a potential window of opportunity for the provision of bystander assistance, particularly in the context of head injury, for simple first-aid manoeuvres to save lives.

A retrospective review of the type of anaesthesia used for LLETZ: proposal for a categorisation audit tool.

BACKGROUND: Large loop excision of the transformation zone (LLETZ) is the most common form of treatment for cervical pre-cancer. The majority of procedures should be performed under local anaesthesia (LA) in an outpatient setting. AIM: To review the reasons behind choice of general anaesthesia (GA) for LLETZ and to devise a categorisation tool for audit purposes. METHODS: Review of the type of anaesthesia and histopathological findings for all cases of LLETZ performed at Wexford General Hospital between January 2010 and June 2013 inclusive. RESULTS: Of the 970 cases reviewed, 829 (85.5 %) were performed under LA and 141 (14.5 %) under GA. In five of the 141 GA cases the indication could not be established. The remaining 136 cases could be classified into three categories based on their indications for choosing GA: Category I: 46 cases (33.8 %) where there was associated pathology requiring treatment under GA. Category II: 56 cases (41.2 %) where the colposcopist anticipated difficulty with the procedure and decided on GA. Category III: 34 remaining cases (25 %), where GA was requested by the patient. During the study period the GA rate decreased significantly from 19.4 to 10 % due to a decrease in category II numbers. Higher rates of complete excision of pre-cancer were not found in the GA group. CONCLUSIONS: The use of GA for LLETZ rarely confers benefits in terms of diagnostic or therapeutic quality indicators. The categorisation we propose is a simple audit tool that could be adopted by all colposcopy units to reduce the rate of GA.

The feasibility of a modified shoe for multi-segment foot motion analysis: a preliminary study.

BACKGROUND: The majority of multi-segment kinematic foot studies have been limited to barefoot conditions, because shod conditions have the potential for confounding surface-mounted markers. The aim of this study was to investigate whether a shoe modified with a webbed upper can accommodate multi-segment foot marker sets without compromising kinematic measurements under barefoot and shod conditions. METHODS: Thirty participants (15 controls and 15 participants with midfoot pain) underwent gait analysis in two conditions; barefoot and wearing a shoe (shod) in a random order. The shod condition employed a modified shoe (rubber plimsoll) with a webbed upper, allowing skin mounted reflective markers to be visualised through slits in the webbed material. Three dimensional foot kinematics were captured using the Oxford multi-segment foot model whilst participants walked at a self-selected speed. RESULTS: The foot pain group showed greater hindfoot eversion and less hindfoot dorsiflexion than controls in the barefoot condition and these differences were maintained when measured in the shod condition. Differences between the foot pain and control participants were also observed for walking speed in the barefoot and in the shod conditions. No significant differences between foot pain and control groups were demonstrated at the forefoot in either condition. CONCLUSIONS: Subtle differences between pain and control groups, which were found during barefoot walking are retained when wearing the modified shoe. The novel properties of the modified shoe offers a potential solution for the use of passive infrared based motion analysis for shod applications, for instance to investigate the kinematic effect of foot orthoses.

Which patellofemoral joint imaging features are associated with patellofemoral pain? Systematic review and meta-analysis.

OBJECTIVES: To review the association between patellofemoral joint (PFJ) imaging features and patellofemoral pain (PFP). DESIGN: A systematic review of the literature from AMED, CiNAHL, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PEDro, EMBASE and SPORTDiscus was undertaken from their inception to September 2014. Studies were eligible if they used magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US) or X-ray (XR) to compare PFJ features between a PFP group and an asymptomatic control group in people <45 years of age. A pooled meta-analysis was conducted and data was interpreted using a best evidence synthesis. RESULTS: Forty studies (all moderate to high quality) describing 1043 people with PFP and 839 controls were included. Two features were deemed to have a large standardised mean difference (SMD) based on meta-analysis: an increased MRI bisect offset at 0° knee flexion under load (0.99; 95% CI: 0.49, 1.49) and an increased CT congruence angle at 15° knee flexion, both under load (1.40 95% CI: 0.04, 2.76) and without load (1.24; 95% CI: 0.37, 2.12). A medium SMD was identified for MRI patella tilt and patellofemoral contact area. Limited evidence was found to support the association of other imaging features with PFP. A sensitivity analysis showed an increase in the SMD for patella bisect offset at 0° knee flexion (1.91; 95% CI: 1.31, 2.52) and patella tilt at 0° knee flexion (0.99; 95% CI: 0.47, 1.52) under full weight bearing. CONCLUSION: Certain PFJ imaging features were associated with PFP. Future interventional strategies may be targeted at these features. PROSPERO REGISTRATION NUMBER: CRD 42014009503.

Daily bread: a novel vehicle for dissemination and evaluation of psychological first aid for families exposed to armed conflict in Syria.

BACKGROUND: Risks to the mental health of children and families exposed to conflict in Syria are of such magnitude that research identifying how best to deliver psychological first aid is urgently required. This study tested the feasibility of a novel approach to large-scale distribution of information and data collection. METHODS: Routine humanitarian deliveries of bread by a bakery run by a non-governmental organisation (NGO) were used to distribute parenting information leaflets and questionnaires to adults looking after children in conflict zones inside Syria. Study materials were emailed to a project worker in Turkey. Leaflets and questionnaires requesting feedback were transported alongside supplies to a bakery in Syria, and then packed with flatbreads. Three thousand bread-packs were distributed, from three distribution points to which questionnaires were returned, and then taken to Turkey and dispatched to the UK. FINDINGS: Notwithstanding delays, 3000 leaflets and questionnaires were successfully distributed over 2 days. Questionnaire return yielded 1783 responses, a 59.5% return rate. Overall ratings of the usefulness of the leaflet were 1060 (59.5%) 'quite a lot' and 339 (19.0%) 'a great deal'. Content analysis was used to code 400 respondent comments. Four themes emerged; positive comments about the leaflet, suggestions for modifications, descriptions of children's needs and the value respondents placed on faith. INTERPRETATION: Findings indicate the willingness of NGO staff and volunteers to assist in research, the remarkable willingness of caregivers to respond and the value of brief advice. It demonstrates the scope for using existing humanitarian routes to distribute information and receive feedback even in high-risk settings.

Prepared for Practice? Interns' Experiences of Undergraduate Clinical Skills Training in Ireland.

BACKGROUND: Many previous studies on internship have reported a lack of preparedness for the role. More recently in Ireland, medical schools have introduced formal clinical skills training programmes. This study sought to evaluate the impact, if any, of formal skills training in the medical training on intern's preparedness for practice. METHODS: The study utilized a survey approach followed by focus group discussions. The aim was to identify the skills that were taught and assessed in medical training and the skills that were actually required in their intern year. RESULTS: Most interns had received skills training in designated skills laboratories. No intern had received training in all skills advised in the European guidelines. Skills taught to all interns were intravenous cannulation, basic life support, and basic suture. Skills required from all interns were intravenous cannulation, phlebotomy, and arterial blood sampling. Removal of peripherally inserted central line (PICC) lines, central lines, and chest drains were commonly requested but not taught. Senior staff underestimated skill abilities and expected failure. CONCLUSION: These findings identify discordance between the skills taught and the skills required in the job. There is a need for standardization in the clinical skills training to ensure that all interns enter practice with equal competencies. Consideration should be given to experiential learning opportunities such as subintern programmes to consolidate learning and improve preparedness. Improvement in communications with senior clinicians is indicated to ensure that expectations are realistic and reflective of actual training.

Genomic interaction between ER and HMGB2 identifies DDX18 as a novel driver of endocrine resistance in breast cancer cells.

Breast cancer resistance to endocrine therapies such as tamoxifen and aromatase inhibitors is a significant clinical problem. Steroid receptor coactivator-1 (SRC-1), a coregulatory protein of the oestrogen receptor (ER), has previously been shown to have a significant role in the progression of breast cancer. The chromatin protein high mobility group box 2 (HMGB2) was identified as an SRC-1 interacting protein in the endocrine-resistant setting. We investigated the expression of HMGB2 in a cohort of 1068 breast cancer patients and found an association with increased disease-free survival time in patients treated with endocrine therapy. However, it was also verified that HMGB2 expression could be switched on in endocrine-resistant tumours from breast cancer patients. To explore the function of this poorly characterized protein, we performed HMGB2 ChIPseq and found distinct binding patterns between the two contexts. In the resistant setting, the HMGB2, SRC-1 and ER complex are enriched at promoter regions of target genes, with bioinformatic analysis indicating a switch in binding partners between the sensitive and resistant phenotypes. Integration of binding and gene expression data reveals a concise set of target genes of this complex including the RNA helicase DDX18. Modulation of DDX18 directly affects growth of tamoxifen-resistant cells, suggesting that it may be a critical downstream effector of the HMGB2:ER complex. This study defines HMGB2 interactions with the ER complex at specific target genes in the tamoxifen-resistant setting.

The impact of surgeon handedness in total hip replacement.

INTRODUCTION: Total hip replacement (THR) is successful and performed commonly. Component placement is a determinant of outcome. Influence of surgeon handedness on component placement has not been considered previously. This study was a radiographic assessment of component positioning with respect to handedness. Early data from 160 patients are reported. METHODS: Overall, 160 primary THRs for osteoarthritis were included. Equal numbers of left and right THRs were performed by four surgeons, two right-handed and two left-handed. Postoperative radiography was assessed for THR component position by measurement of leg length inequality, acetabular inclination and centre of rotation. Surgeons' handedness was assessed using the Edinburgh inventory. RESULTS: For leg length inequality, no significant interaction was seen between hip side and surgeon handedness. Acetabular inclination angles showed a statistically significant difference, however, depending on hand dominance, with higher inclination angles recorded when operating on the dominant side. There was a trend towards greater medialisation of the centre of rotation on the non-dominant side although this did not reach statistical significance. CONCLUSIONS: Surgeon handedness appears to influence acetabular component position during THR but it is one factor of many that interact to achieve a successful outcome.