Search

Electronic institutional review board systems (eIRBs) have become an integral component in ensuring compliance with Human Research Protection Program (HRPP) and IRB requirements. Despite this, few of these systems are configured to administer the single IRB (sIRB) process mandated by the National Institutes of Health (NIH) for multisite research. We interviewed 103 sIRB administrators, chairs, members, and staff members about their experiences with sIRB multisite research review. We observed three main obstacles to adapting existing eIRB systems to accommodate the sIRB process: (1) Existing systems are not designed for sIRBs and are not configured to administer sIRB responsibilities, (2) they are not interoperable, and (3) resources to improve existing systems are lacking. Our findings suggest that IRBs that act as an sIRB will need major changes to their electronic systems in order to accommodate sIRB processes. These difficulties threaten both the ability of IRBs to focus on ethical rather than bureaucratic problems and the efficiency of multisite trials.

A rise in the current trend of corrosive substance attacks have been reported in the UK, causing devastating effects on victims. The optimal management of these patients requires the specialist skills of the burn multidisciplinary team (MDT) to address the resulting physical and psychological trauma experienced. However, burn care must commence in the pre-hospital setting. The public and first responders are invaluable resources in helping to limit the adverse effects of burns. Challenges of burn care outside the Burns Unit are not limited to the treatment of the injured patient and the rehabilitation of survivors. These challenges also encompass better education of the public and allied health professionals, as well as planning strategies to reduce the incidence of acid attacks. Prevention is always better than cure. This paper discusses the broadening of the MDT to improve outcomes in acid attacks by exploring the wider roles of the public, media, emergency services, police, legislation and better education.

Cardiac point-of-care ultrasound (POCUS) is a quick and accurate tool to assess a patient's cardiovascular and hemodynamic status by measuring the E-point septal separation (EPSS) and left ventricular ejection fraction. The case presented here highlights the potential for increased use of POCUS to guide resuscitation in the prehospital setting and during critical care transport. A 56-year-old male presented to a rural emergency department with chest pain and was found to have an inferior STelevation myocardial infarction (STEMI). Local helicopter air ambulance was called to transport the patient to a facility capable of cardiac catheterization. In route, the flight physician performed a cardiac POCUS exam which revealed decreased cardiac perfusion, a hypokinetic inferior wall, and overall decreased contractility. EPSS was measured at 0.77cm, indicating moderate left ventricular ejection fraction (LVEF) reduction. A cardiac left ventriculogram later confirmed a 40% ejection fraction as well as wall motion abnormalities of the inferior wall. The patient was found to have 100% occlusion of the right coronary artery that was revascularized with balloon angioplasty and a drug-eluting stent. He ultimately did well and was discharged home.

Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals.

Summary Aim To investigate the effect of ablative fractional CO2 laser (AFCO2L) on burns scar appearance and dermal architecture at 6 weeks and up to 3-years post-treatment. Methods Twenty adult patients with a burn-related scar were recruited. Inclusion criteria were a minimum scar area of 10 × 10 cm and Vancouver scar scale (VSS) score of >5 and ≥6 months since the time of injury. The region of scar was randomised to treatment/control zones. Treatment zones received 3 standardised laser treatments at 4- to 6-week intervals. All areas of scar received standard scar care. Outcome measures were recorded at baseline, 6-weeks post final treatment and up to 3 years post-treatment. Measures included blinded assessor VSS, Patient Scar Assessment Scale and histological tissue analysis. Results Nineteen and nine patients completed the short- and long-term studies, respectively. Clinical results revealed improvement in all scar areas over time. There was a statistically significant improvement in pain and itch in the treatment zone compared to the control zone at 6 weeks. Histological data revealed a significant increase in medium-sized collagen fibres at 6 weeks relative to the control site. Sub-group analysis according to scar age revealed greater histological improvement following laser treatment in immature scars relative to more mature scar. Conclusions Results demonstrate that 3 treatments of AFCO2L significantly improve scar pain, itch and dermal architecture at 6 weeks post-treatment. Histological results suggest greater potential in treating immature scar. Further investigation into the timing of laser treatment could help assist treatment protocols.

Purpose The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. Methods We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. Results There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. Conclusion People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population.

Introduction Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibodies and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-operative management strategies influence immunological outcome following VCA. Method A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-operative, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis. Result The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients (14.7%) were sensitized prior to reconstructive transplantation with an 80% incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies. Conclusion Currently employed acute management strategies predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. Early appropriate care is warranted in patients with extensive soft tissue loss where the resuscitative needs should be balanced against strategies to mitigate the immunological burden, particularly as reconstructive transplantation becomes a feasible option for future soft tissue coverage. Take-home message Acute resuscitative management may sensitise potential transplant recipients following major soft tissue injury. Early appropriate care is warranted.

Background Clinical genetics is a small specialty with around 70 trainees nationally. New trainees traditionally have a period of observing clinics led by consultants and experienced genetic counsellors before leading their own clinic. This is an important time in which they learn practical and communication skills with respect to approaching a consultation, however, the experience can be variable dependent on the centre. In light of the coronavirus pandemic, knowing that many new trainees would not be able to access this vital induction period, we devised a virtual induction programme. Methods A group of clinical geneticists from three UK centres, including GOSH, worked in collaboration with the GOSH Clinical Simulation Team to devise and deliver a programme that would be accessible to all new trainees. Important topics for discussion were agreed; example consultations were filmed, with the help of actors; and trainee simulations were planned. Results The virtual induction runs live over two days, with homework, in the form of the filmed consultations that can be accessed at any time. The first day has been completed, delivering training to around 20 new trainees. The feedback we have received from both trainees and training programme directors has been overwhelmingly positive. Discussion Given the ongoing impact of the coronavirus pandemic, creative ways of delivering training are flourishing. We have created a bank of videos and presentations, as well as a template for future induction sessions, ensuring a basic level of equity between trainees at different genetics centres. Conclusion Virtual induction tools are a valuable and vital addition to new trainee induction to ensure equity of training, both during the current pandemic and beyond. This approach would work very well on a national level for other small specialties; or on a regional or local level for larger specialties.

Introduction Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody formation and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-transplant management strategies influence immunological outcome following VCA. Methods A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-transplant, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis. Results The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients were sensitised prior to reconstructive transplantation with an 80%%incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies. Conclusions Currently employed acute management strategies may predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. To determine whether association between pre-transplant management and outcomes exists, further refinement of international registries is required.

Aims Dermal preservation during acute burn excision is key to obtaining superior healing/scar outcomes, however, determining the most appropriate excision tool is an ongoing challenge. Novel tool development means the knife is no longer our only option, yet for the majority it remains the gold standard. This systematic review aims to evaluate evidence for burns excision approaches (knife/hydrosurgery/enzymatic). Methods CENTRAL, EMBASE, MEDLINE (1946–2017) were searched with MeSH terms: ‘debridement’, ‘burns’, ‘sharp’, ‘enzymatic’, ‘hydrosurgery’. Relevant randomised control trials (RCTs)/non-randomised controlled case series/trials were extracted/analysed. In vitro/burn non-specific studies were excluded. Main methodological parameters were intervention/excision efficacy. Results Eighteen articles met inclusion criteria (n = 7148): three were RCTs, involving comparator enzymatic (NexoBrid™ (EDNX)) or hydrosurgical (Versajet™) excision to surgical Standard of Care. Both showed statistically significant decreased need for excisional excision and auto-grafting by viable tissue preservation allowing spontaneous healing by epithelialisation. Conclusion Level 1 Evidence comparing excision modalities for acute burns is sparse. Although early excision with a knife is still often considered best practice, there is no tool choice consensus or robust comparison with alternate, possibly superior, tools. EDNX or Versajet™ should be considered alternatively. Further RCTs are indicated, with regards final scar outcomes and to allow consensus within current evidence.

Women who inherit a mutated copy of the BRCA gene have a higher lifetime risk of developing breast cancer. No large epidemiological studies exist looking at BRCA mutation carriers in UK populations. All patients with BRCA1/BRCA2 mutation identified between 1995 and 2015 were included. Individuals were identified from a prospectively gathered data base. Genetics case-notes were obtained and retrospective analysis performed. 581 female BRCA mutation carriers were identified with a median age of 34 (18-81) at the time of testing. Of the 301 women who underwent diagnostic testing (symptomatic) 246 had been diagnosed with breast cancer, 89 with ovarian cancer and 37 had both at time of testing. Median age at diagnostic test was 51 (25-81). 33% of women underwent risk-reducing mastectomies (RRM); median age at surgery 45. This compares with 37% of women in this diagnostic group who underwent Risk-reducing bilateral salpingo-oopherectomies (RRBSO) at a median age of 46. Two hundred and eighty women underwent predictive testing (family history, asymptomatic), median age 36 (18-81). 34% of women in this predictive group underwent RRM, median age 37. There was a 29% uptake of RRBSO (median age 44 years). Fifteen women (5%) developed breast cancer after being tested; none of these had undergone RRS. This unique study of all BRCA mutation carriers in Wales shows considerable variation in uptake of RRS. The decision to undergo RRS is complex and involves a number of factors, including a woman's age and life stage. As BRCA testing becomes more frequent and more gene mutation carriers are identified there will be significant implications for service allocation, screening demands, and provision of risk-reducing surgery for this high-risk patient group.

Early debridement and/or eschar removal is regarded as a significant step in the treatment of deep partial and full thickness burns. It aims to control wound bioburden and allows early wound closure by conservative treatment or skin grafting. Preservation of viable dermis accompanied by early wound closure, is regarded as a necessary step to reduce scar related complication, e.g. functional limitations and/or unaesthetic scar formation. Aside from the classical techniques of surgical excision as tangential excision for eschar removal, hydro-surgery, maggot therapy, laser, enzymatic debridement have been described as additional techniques in the burn surgeon's armamentarium. It is widely accepted that early eschar removal within 72h improves the outcome of burn wound treatment by reducing bacterial wound colonization, infection and length of hospital stay. In contrast, the right technique for eschar removal is still a matter of debate. There is increasing evidence that enzymatic debridement is a powerful tool to remove eschar in burn wounds, reducing blood loss, the need for autologous skin grafting and the number of wounds requiring surgical excision. In order to assess the role and clinical advantages of enzymatic debridement by a mixture of proteolytic enzymes enriched in Bromelain (Nexobrid®) beyond the scope of the literature and in view of users' experience, a European Consensus Meeting was scheduled. The aim was to provide statements for application, based on the mutual experience of applying enzymatic debridement in more than 500 adult and pediatric patients by the consensus panelists. Issues to be addressed were: indications, pain management and anesthesia, timing of application, technique of application, after-intervention care, skin grafting after enzymatic debridement, blood loss, training strategies and learning curve and areas of future research needs. Sixty-eight (68) consensus statements were provided for the use of enzymatic debridement. The degree of consensus was remarkably high, with a unanimous consensus in 88.2% of statements, and lowest degree of consensus of 70% in only 3 statements. This consensus document may serve as preliminary guideline for the use of enzymatic debridement with user-oriented recommendations until further evidence and systematic guidelines are available.

Background Colorectal cancer (CRC) is the most common cancer affecting both men and women. Survivors of CRC often experience various physical and psychological effects arising from CRC and its treatment. These effects may last for many years and adversely affect QoL, and they may not be adequately addressed by standard specialist-based follow-up. Optimal management of these effects should harness the expertise of both primary care and specialist care. Shared models of care (involving both the patient’s primary care physician [PCP] and specialist) have the potential to better support survivors and enhance health system efficiency. Methods/design SCORE (Shared care of Colorectal cancer survivors) is a multisite randomised controlled trial designed to optimise and operationalise a shared care model for survivors of CRC, to evaluate the acceptability of the intervention and study processes, and to collect preliminary data regarding the effects of shared care compared with usual care on a range of patient-reported outcomes. The primary outcome is QoL measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Secondary outcomes are satisfaction with care, unmet needs, continuity of care and health resource use. The shared care model involves replacement of two routine specialist follow-up visits with PCP visits, as well as the provision of a tailored survivorship care plan and a survivorship booklet and DVD for CRC survivors. All consenting patients will be randomised 1:1 to either shared care or usual care and will complete questionnaires at three time points over a 12-month period (baseline and at 6 and 12 months). Health care resource use data will also be collected and used to evaluate costs. Discussion The evaluation and implementation of models of care that are responsive to the holistic needs of cancer survivors while reducing the burden on acute care settings is an international priority. Shared care between specialists and PCPs has the potential to enhance patient care and outcomes for CRC survivors while offering improvements in health care resource efficiency. If the findings of the present study show that the shared care intervention is acceptable and feasible for CRC survivors, the intervention may be readily expanded to other groups of cancer survivors. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12617000004369p. Registered on 3 January 2017; protocol version 4 approved 24 February 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2245-4) contains supplementary material, which is available to authorized users.

Purpose Conflicts of interest (COIs) are important ethical concerns because they may affect scientific decision making, research integrity, and the safety and fairness of studies. No research to date has examined COIs of single institutional review boards (sIRBs), which are now mandated by the National Institutes of Health, and will be by the revised Common Rule in 2020, for all multisite research. This study investigated how different types of sIRBs manage their own COIs by documenting existing processes for and comparing commercial, government, and academic sIRBs. Method One hundred three personnel from 20 commercial, government, or academic sIRBs participated in semistructured interviews about their processes for and experiences with managing COIs when conducting multisite research review. Results Variability in COI management policies exist across types of sIRBs. Commercial sIRBs were aware of their own COIs given their for-profit model, and managed them by using firewalls, relying on external reviewers, and turning down potential clients. Government sIRBs described unique COIs stemming from the same agency funding the sIRB and the research being reviewed. They addressed these by discussing concerns about COIs, using firewalls, relying on nonaffiliated reviewers, and having broad COI policies. In contrast to commercial and government sIRBs, academic sIRBs did not report any specific policies to manage their COIs, which are similar to those of local IRBs. Conclusions As sIRBs become increasingly common, researchers will need to weigh the different COIs inherent to each type of sIRB. Additionally, academic sIRBs may consider implementing specific policies for managing their COIs.

Background In May 2015 the Malawian Ministry of Health (MOH) contacted the German Development Cooperation to seek technical assistance from the P4H Network for Social Health Protection for an “Assessment of the appropriateness and feasibility of National Health Insurance in Malawi” against two alternative options: continuing with a tax (and donor)-funded National Health Service, and introducing a purchaser-provider split without a revenue collection function. Methods A health financing benchmarking matrix was agreed with MOH, with six domains corresponding to six objectives: revenue mobilisation, technical efficiency, equity, financial risk protection, policy coordination, and health outcomes. The assessment comprised key informant interviews with Malawian stakeholders, a review of the relevant literature and datasets, rapid assessments of the Malawi Revenue Authority (MRA) and the Unified Beneficiary Registry (UBR), and projections of the National Health Insurance Scheme’s (NHIS) revenue collection costs and benefits. Results A key finding was that introducing NHIS in Malawi would increase revenues for health, but these would come predominantly from the formal sector and would be unlikely to cover the health sector funding gap. The performance of existing poverty identification and targeting mechanisms was not commensurate with the requirements of a NHIS. Incentives to enrol in NHI are insufficient to reach scale unless service fees be introduced, which would negatively affect equity and financial risk protection. The assessment identified the Purchaser Scenario as the most favourable reform model. Conclusions As ever more countries look towards implementing National Health Insurance, the proposed assessment framework can provide an orientation for evidence-based policy making in the area of health financing. Electronic supplementary material The online version of this article (10.1186/s41256-019-0103-5) contains supplementary material, which is available to authorized users.

Introduction Workforce planning is an essential component of organizing any health service. Centralization of burns services pools expertise, although trainees can struggle to achieve adequate exposure to burns training. We aim to review current staffing levels and predict the future consultant numbers required for UK services to remain staffed with appropriately trained surgeons. Methods We have compiled a database of all UK burns consultants. Basic demographic data, such as age and sex, were collated. Projected UK population data have been used to estimate whether the number of patients under the care of the UK burns network will change in the coming years. Access to burns fellowship training has also been factored in. Results There are 34 burns facilities in the United Kingdom and 86 burns consultants. On average, these consultants are 13 years from retirement age. 22 will reach this age within the next decade. During this time, the UK population is expected to increase by 10%, translating to approximately another 6 consultant posts. Since there are only 2 UK recognized burns fellowships, many of the required consultants will have to seek training abroad. Conclusions Workforce planning is essential to avoid a short fall in the number of upcoming burns consultants. Plans must be in place to anticipate additional workload with a 10% population rise. With the current struggles of NHS funding, a comprehensive review of burns workforce planning should be undertaken to ensure that sufficient numbers of trainees are completing appropriate burns-specific training and are ready to fill these posts.

We demonstrate the use of the near-infrared attenuation coefficient, measured using optical coherence tomography (OCT), in longitudinal assessment of hypertrophic burn scars undergoing fractional laser treatment. The measurement method incorporates blood vessel detection by speckle decorrelation and masking, and a robust regression estimator to produce 2D en face parametric images of the attenuation coefficient of the dermis. Through reliable co-location of the field of view across pre- and post-treatment imaging sessions, the study was able to quantify changes in the attenuation coefficient of the dermis over a period of ~20 weeks in seven patients. Minimal variation was observed in the mean attenuation coefficient of normal skin and control (untreated) mature scars, as expected. However, a significant decrease (13 ± 5%, mean ± standard deviation) was observed in the treated mature scars, resulting in a greater distinction from normal skin in response to localized damage from the laser treatment. By contrast, we observed an increase in the mean attenuation coefficient of treated (31 ± 27%) and control (27 ± 20%) immature scars, with numerical values incrementally approaching normal skin as the healing progressed. This pilot study supports conducting a more extensive investigation of OCT attenuation imaging for quantitative longitudinal monitoring of scars. (Figure presented.) En face 2D OCT attenuation coefficient map of a treated immature scar derived from the pre-treatment (top) and the post-treatment (bottom) scans. (Vasculature (black) is masked out.) The scale bars are 0.5 mm.

Clinical Genetics services provide a diagnostic, counselling and genetic testing service for children and adults affected by, or at risk of, a genetic condition, most of which are rare, and/or genetically heterogeneous. Appropriate triage of referrals is crucial to ensure that the most urgent referrals are seen as quickly as possible, without negatively impacting the waiting times of less urgent cases. We aimed to examine triage practice in six Clinical Genetic centres across the United Kingdom and Ireland. Thirteen simulated referrals were drafted based on common referrals to Clinical Genetics. Copies of each referral were forwarded to each centre, where 10 nominated clinicians were asked to triage each referral. Triaged referrals were returned to the coordinating author for analysis. An electronic questionnaire was contemporaneously completed by clinical leads in each unit to gather local demographic details and local operating procedures relevant to triage. Widespread inconsistencies were noted both within and between units, with respect to the acceptance of referrals to the services, prioritisation and designated clinic type. Referral rates, staffing levels and waiting lists varied widely between units. Inconsistencies observed between units are likely influenced by a number of factors, including staffing levels, referral rates and average family size. Inconsistency within units likely reflects the complex nature of many Clinical Genetic referrals, and triage guidelines should help improve decision-making in this setting.

The new National Institutes of Health (NIH) Policy on the Use of a Single Institutional Review Board (sIRB) for Multi-Site Research was adopted primarily to simplify and speed the review of complex multisite clinical trials. However, speeding review requires overcoming a number of obstacles. Perhaps the most substantial obstacle is the time and effort needed to develop reliance agreements among the participating sites. We conducted 102 semistructured interviews with sIRB personnel, including directors, chairs, reviewers, and staff, from 20 IRBs that acted as sIRBs for multisite research, including 6 commercial/independent sIRBs, and 10 university-based academic and 4 federal sIRBs. Almost without exception, the interviewees agreed that reliance agreements were complex, difficult to develop, and time-consuming. A major problem for relying sites was that different agreements specified different responsibilities for the relying sites. Attitudes differed about whether these problems will be resolved as IRB staff and managers become more experienced with sIRBs. However it is clear that the process of developing reliance agreements must be simplified. Federal assistance in standardizing at least some sections of reliance agreements might reduce the difficulties involved.

This study presents the first in vivo longitudinal assessment of scar vasculature in ablative fractional laser treatment using optical coherence tomography (OCT). A method based on OCT speckle decorrelation was developed to visualize and quantify the scar vasculature over the treatment period. Through reliable co-location of the imaging field of view across multiple imaging sessions, and compensation for motion artifact, the study was able to track the same scar tissue over a period of several months, and quantify changes in the vasculature area density. The results show incidences of occlusion of individual vessels 3 days after the first treatment. The subsequent responses ˜20 weeks after the initial treatment show differences between immature and mature scars. Image analysis showed a distinct decrease (25 ± 13%, mean ± standard deviation) and increase (19 ± 5%) of vasculature area density for the immature and mature scars, respectively. This study establishes the feasibility of OCT imaging for quantitative longitudinal monitoring of vasculature in scar treatment. En face optical coherence tomography vasculature images pre-treatment (top) and ˜20 weeks after the first laser treatment (bottom) of a mature burn scar. Arrows mark the same vessel pattern.

Soft tissue or bony loss to the scalp and forehead present a reconstructive challenge, especially in the young patient. Much literature is available on scalp and forehead reconstruction for primary malignant pathologies, however reconstruction for contact electrical burns is reported infrequently in the literature. This case series looks at two patients with full thickness burns to the scalp and forehead requiring free flap reconstruction over 11 years at the Burns Unit at Royal Perth Hospital in Perth, Western Australia. We describe the flap reconstruction and outcomes of these patients and review the relevant literature. Three free flap reconstructions were performed on the two patients. The first patient had a free gracilis flap which failed five days post-operatively. 25 days post initial injury a free rectus flap was used to cover the predominantly forehead defect. The second patient had a free latissimus dorsi flap completed one week after initial injury. Free flap reconstruction of scalp and forehead following contact electrical burns is complicated and challenging. The outcomes of both of the patients in this case series was positive and both have had satisfactory flap survival at the time of writing. Due to rare nature of this type of burn there is little published evidence outlining the definitive management of this type of injury. Level of Evidence: Level V, therapeutic study

Background\ud Many patients who require an interpreter have difficulty remembering information from their medical consultations. Memory aids such as consultation audio-recordings may be of benefit to these patients. However, there is no established means of measuring patients’ memory of medical information.\ud \ud Objectives\ud This study aimed to develop a method for eliciting and coding recall of medical information in non-English-speaking patients.\ud \ud Design\ud This method, called Patient-Interpreter-Clinician coding (PICcode), was developed in the context of a phase II trial conducted in two outpatient oncology clinics in Melbourne, Australia, and was refined iteratively through consultation with an expert panel and piloting. Between-coder differences in early versions of the coding system were resolved through discussion and consensus resulting in refinements to PICcode.\ud \ud Results\ud The final version of PICcode involved transcribing, translating and coding of audio-recorded consultations and semi-structured interviews (SSI). The SSIs were designed to elicit patients’ free-recall of medical information. Every unit of medical information in the consultation was identified and categorized in a coding tree. SSIs were coded to identify the extent to which information was recalled from the consultation.\ud \ud Discussion\ud The iterative changes involved in developing PICcode assisted in clarifying precise details of the process and produced a widely applicable coding system. PICcode is the most comprehensively described method of determining the amount of information that patients who use an interpreter recall from their medical consultations. PICcode can be adapted for English-speaking patients and other healthcare populations.

Background The abdominal flap can be used in a stacked, double-pedicle configuration for unilateral breast reconstruction. Aided by preoperative mapping, this is a good option when a single-pedicle flap is deemed unsuitable. We present reliable outcomes using the stacked flap and a logical classification system for its use. Methods From 2008 to 2013, 18 patients underwent a stacked abdominal flap for unilateral breast reconstruction. Flaps utilized deep inferior epigastric (D) and superficial inferior epigastric (S) pedicle combinations. Preoperative computed tomography angiogram was performed on all patients. Medical records were reviewed for complications and clinical data, and a thorough clinical evaluation was performed on all patients at follow-up. Flaps were all double-pedicled, with the secondary pedicle anastomosed onto the primary pedicle (type 1 to 3) or onto a second recipient vessel (type 4). Flaps were then classified into groups, based on pedicle dominance and intraflap anastomosis. Results Twelve reconstructions were immediate and six delayed. Mean operative time was 7 hours, the most frequently used configuration being a type 1 DD, that is, secondary pedicle (D) anastomosed end-to-end onto the superior continuation of the primary pedicle (D). Average hospital stay was 6 days. There were no flap losses and minimal complications, and mean follow-up was 20 months. Conclusion Use of this flap poses a greater challenge to the microsurgical breast reconstruction. We demonstrate its reliable use in women deemed unsuitable for a single-pedicle flap. Our structured system clarifies vascular options, and preoperative perforator mapping tools are essential to the success of this technique.

We propose a method to image cutaneous lymphatic vessels in vivo with optical coherence tomography (OCT). Our method segments the transparent lymphatic vessels by thresholding the OCT signal after calibration for systematic variations due to the confocal effect and the sensitivity drop-off, and subsequent compensation for light attenuation with depth. We describe the method and present a pilot demonstration on two human burn scar patients undergoing ablative laser fractionation treatment. The results show visualization of the lymphatic vessels (diameter: ∼30–150 μm) separate from the blood microvasculature network.

Objective: The objective of this study is to evaluate the effectiveness of a self-help coping intervention in reducing intrusive negative thoughts while waiting for cancer genetic risk information. Methods: Between August 2007 and November 2008, 1958 new referrals for cancer genetic risk assessment were invited to participate in a randomised trial. The control group received standard information. The intervention group received this information plus a written self-help coping leaflet. The primary outcome measure was the intrusion subscale of the Impact of Event Scale. Results: The intervention significantly reduced intrusive thoughts during the waiting period in those reporting moderate baseline levels of intrusion (p = 0.03). Following risk provision, those in the intervention group reporting low and moderate intrusive worries at baseline reported less intrusive thoughts than those in the control group (p = 0.04 and p = 0.03, respectively). The intervention had no adverse impact in the sample as a whole. Participants in the intervention group with high baseline avoidance and negative affect scores were significantly more likely to remain in the study than those in the control group (p = 0.05 and p = 0.004). Conclusions: Findings that the intervention both reduced distress in those with moderate levels of distress and had no adverse effects following notification of cancer genetic risk suggest that this simple intervention can be implemented across a range of oncology settings involving periods.

Objective: To gain an ‘in-depth’ understanding of patients’ concerns and their related coping strategies during the genetic risk assessment process. Methods: Participants were the ‘usual care’ arm of a trial of a coping intervention targeted at men and women undergoing assessment of genetic risk for familial cancer. Participants completed questionnaires measuring the degree to which they experienced up to 11 concerns and which of 8 coping strategies they used to respond to each of them at entry into the programme and 1 month subsequently (before they received their risk information). Findings: A majority of participants were at least ‘quite worried’ about all the identified concerns, although the levels of concern fell over the waiting period. Participants used several strategies in response to their varying concerns – although a primary coping strategy for each concern was identifiable. The emotion-focused strategies of acceptance and positive appraisal were generally used in response to concerns they could not change, and seeking social support was used primarily to gain information, but not emotional support from their family. Cluster analysis identified three unique clusters of coping responses. Conclusions: Genetic risk assessment comprises a number of different stressors each of which is coped with using different strategies. Copyright r 2011 John Wiley & Sons, Ltd.

Anticipating future changes in workforce is an essential component of organising any health service. Factors such as changing retirement age, maternity and parental leave, reorganisation of services and population change all impact on the number of staff required to provide a safe and effective service. The UK burns networks provide both emergency and elective services to millions of patients affected by burn-injury every year. With the current struggles of NHS funding, we suggest that a comprehensive review of burns workforce planning is undertaken to ensure that sufficient numbers of trainees are completing appropriate burns-specific training and are ready to fill these posts, ensuring sustainability of our services.

Breast cancer is the commonest cancer affecting women. A family history of breast cancer increases a woman's lifetime risk of developing the disease. Most of the genetic risk is due to low-risk and moderate-risk susceptibility alleles rather than high-penetrance genes such as BRCA1 and BRCA2 . Mutations in these two tumour suppressor genes only account for about 2% of all breast cancers. Female carriers of BRCA gene mutations have a high lifetime risk of developing breast and ovarian cancer and male carriers have an increased risk of prostate and breast cancer. Women with a significant family history of breast cancer should be referred to their local cancer genetics service for a formal cancer genetics risk assessment, discussion of risk management options such as surveillance and risk-reducing surgery and consideration of genetic testing. If a BRCA gene mutation is identified in a family, predictive testing can be offered to unaffected family members to clarify risks and help with risk management decisions. In the future, BRCA mutation carriers are likely to be offered different surgical management and/or first-line chemotherapeutic agents as treatment for cancer and one day chemoprevention agents may also be available.

It is well-recognised that receipt of cancer genetic risk information can evoke a mix of both positive and negative emotional responses. Objective risk itself is not necessarily predictive of emotional response to receipt of risk information and the Cue Adaptive Reasoning Account (CARA; Renner, 2004) suggests that that the degree to which level of risk is consistent with expectations may influence emotional responses. This paper reports a thematic analysis of the free-text data structured around responses to the three risk labels: average, moderate or high. Data is reported from both 123 women and 15 men, including those with a past or current cancer diagnosis. Reactions to risk information appear to be dependent upon participants' pre-conceived expectations about their level of cancer risk. Many average risk respondents questioned the accuracy of their result, whereas high risk information was often expected. Findings are discussed in relation to the CARA model and clinical implications.

Objective: Generic measures of coping fail to capture the process of undergoing specific health processes such as cancer genetic risk assessment. The Genetic Risk Assessment Coping Evaluation (GRACE) has been developed to provide greater specificity of measurement. Method: Based upon previous research findings, the GRACE measures the degree of stress associated with 11 recognised sources of stress for individuals undergoing the early stages of cancer genetic risk assessment, and the use of up to eight coping strategies they may elicit. This paper reports preliminary data from the piloting of the GRACE within a randomised trial of a coping intervention. Results: Of the 265 participants who completed and returned their baseline questionnaire (prior to being informed of their level of genetic risk), 257 completed the GRACE. The most highly endorsed sources of stress involved concerns relating to family members, endorsed by over 60% of respondents, and concerns about how the participants would cope if found to be at increased risk (59%). Participants made use of multiple coping strategies across different sources of stress. The most frequently reported coping strategies were emotion-focused, which may reflect the stage of the assessment process. Conclusion: The completion rates for the matrix and specificity of responses provided suggest that the GRACE may be an acceptable measurement tool. Further data collection and validation is ongoing.

Many individuals receiving genetic counseling are healthy with no need for clinical cancer services. We have recently relocated our cancer genetic clinic to a small house on the outskirts of a hospital site which incorporates many elements proven to be important in creating a "well-being" environment. This study explored participants' perceptions of such an environment. Eleven semi-structured telephone interviews were conducted with women who had attended the new cancer genetic clinic. All were at high risk of familial cancer, five were gene carriers and three had a personal diagnosis of cancer. The new clinic was perceived to be less medical and more relaxing than other clinics, encouraged other family members to attend in support of the attendee and did not appear to impede information comprehension. The importance of not being made to feel like an ill patient was apparent. A desire for a quiet area allowing time for reflection whilst waiting for, and following, counseling was identified. A poorly designed counseling area could reduce the quality of the interaction between patient and counselor. Consideration of specific environmental design features may promote individuals' well-being and make those attending genetic counseling feel less like "patients." Larger studies should seek to explore further the potential associations between factors such as environmental design, psychological well-being and comprehension of risk information.

Women who inherit a mutated copy of the BRCA-1 or BRCA-2 genes have a higher lifetime risk of developing breast cancer. There have been no large epidemiological studies looking at BRCA-positive patients in the UK.

The ethical issues raised by population screening programmes are complex, with implications for individuals, healthcare professionals and society as a whole. While personal autonomy has to be respected in these programmes, especially the need for informed consent, population screening will often be justified on the basis of benevolence. The public health criteria and the ethical considerations applicable to any screening programme are outlined, especially in the context of genetic conditions. The issues raised by some current screening programmes are discussed, and the problems that may arise in the future are considered.

Background With burn injuries involving a large total body surface area (TBSA), the body can enter a state of breakdown, resulting in a condition similar to that seen with severe lack of proper nutrition. In addition, destruction of the effective skin barrier leads to loss of normal body temperature regulation and increased risk of infection and fluid loss. Nutritional support is common in the management of severe burn injury, and the approach of altering immune system activity with specific nutrients is termed immunonutrition. Three potential targets have been identified for immunonutrition: mucosal barrier function, cellular defence and local or systemic inflammation. The nutrients most often used for immunonutrition are glutamine, arginine, branched-chain amino acids (BCAAs), omega-3 (n-3) fatty acids and nucleotides. Objectives To assess the effects of a diet with added immunonutrients (glutamine, arginine, BCAAs, n-3 fatty acids (fish oil), combined immunonutrients or precursors to known immunonutrients) versus an isonitrogenous diet (a diet wherein the overall protein content is held constant, but individual constituents may be changed) on clinical outcomes in patients with severe burn injury. Search methods The search was run on 12 August 2012. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), ISI WOS SCI-EXPANDED & CPCI-S and four other databases. We handsearched relevant journals and conference proceedings, screened reference lists and contacted pharmaceutical companies. We updated this search in October 2014, but the results of this updated search have not yet been incorporated. Selection criteria Randomised controlled trials comparing the addition of immunonutrients to a standard nutritional regimen versus an isonitrogenated diet or another immunonutrient agent. Data collection and analysis Two review authors were responsible for handsearching, reviewing electronic search results and identifying potentially eligible studies. Three review authors retrieved and reviewed independently full reports of these studies for inclusion. They resolved differences by discussion. Two review authors independently extracted and entered data from the included studies. A third review author checked these data. Two review authors independently assessed the risk of bias of each included study and resolved disagreements through discussion or consultation with the third and fourth review authors. Outcome measures of interest were mortality, hospital length of stay, rate of burn wound infection and rate of non-wound infection (bacteraemia, pneumonia and urinary tract infection). Main results We identified 16 trials involving 678 people that met the inclusion criteria. A total of 16 trials contributed data to the analysis. Of note, most studies failed to report on randomisation methods and intention-to-treat principles; therefore study results should be interpreted with caution. Glutamine was the most common immunonutrient and was given in seven of the 16 included studies. Use of glutamine compared with an isonitrogenous control led to a reduction in length of hospital stay (mean stay -5.65 days, 95% confidence interval (CI) -8.09 to -3.22) and reduced mortality (pooled risk ratio (RR) 0.25, 95% CI 0.08 to 0.78). However, because of the small sample size, it is likely that these results reflect a false-positive effect. No study findings suggest that glutamine has an effect on burn wound infection or on non-wound infection. All other agents investigated showed no evidence of an effect on mortality, length of stay or burn wound infection or non-wound infection rates. Authors' conclusions Although we found evidence of an effect of glutamine on mortality reduction, this finding should be taken with care. The number of study participants analysed in this systematic review was not sufficient to permit conclusions that recommend or refute the use of glutamine. Glutamine may be effective in reducing mortality, but larger studies are needed to determine the overall effects of glutamine and other immunonutrition agents.

Testing cancers for mismatch repair (MMR) gene defects assists selection of families for genetic testing for cancer predisposing Lynch syndrome. Performing MMR tumour testing without consent is debated, though little empirical work has been undertaken. We address this by examining the significance of testing for those who have consented without prior genetic counselling, particularly their ‘accounts’ of testing via displays of knowledge and responsibility. Semi-structured interviews were conducted with participants recruited from a UK genetics service. Participants had difficulties in formulating the benefits of testing when consent was facilitated by a relative or by mail. Discourse analysis revealed that in the absence of specific or accurate understandings of tumour testing, participants displayed responsibility towards themselves and others by generalising and diminishing the implications of testing. Within the framework of ‘genetic responsibility’, MMR tumour testing seems less important in participants’ accounts compared to more definitive genetic testing. If facilitating genetic knowledge and responsibility are goals of genetic testing then developing appropriate consent procedures for MMR tumour testing is an important consideration. Further research is required to differentiate whether genetic counselling is a precondition for enacting genetic responsibility or whether intrinsic differences between types of testing make the concept less relevant.

This qualitative interview study focuses on the experiences of a sample of British female BRCA 1/2 carriers who had predictive testing before the age of 30, which is the minimum age for breast screening in the UK. Following appropriate informed consent procedures participants were recruited through the Cancer Genetics Service for Wales. Semi-structured interviews were conducted face-to-face with seven participants, transcribed in full and analyzed using thematic analysis. The motives for testing and perceived advantages described by participants were similar to those identified in previous studies with older participants, such as increased awareness and knowledge and feeling more in control. However some of the perceived disadvantages were specific to younger women, including feeling pressured to make important life decisions earlier than they would have liked, such as about family planning and risk reducing surgery. Participants also reported feeling abandoned or forgotten because of lack of ongoing clinical contact, or feeling “stuck waiting” for screening to begin. However, none felt that these disadvantages were a reason to regret having testing. Findings in this small study suggest that having BRCA 1/2 predictive testing can have positive outcomes for young women even though they may be unable to access interventions such as breast screening. However it may be helpful to encourage young women during pre-test counseling to explore the decisions and choices they may face. These young women could benefit from ongoing support and follow up and increased interaction with healthcare professionals.

A 54 year old man presented with numerous cutaneous schwannomas, cranial nerve lesions, and spinal cord lesions, but no evidence of vestibular nerve involvement. There was no family history of neurocutaneous lesions. To help discriminate between the various possible diagnoses in this patient, molecular analysis of two cutaneous schwannomas was undertaken. An identical point mutation in the NF2 gene in the two anatomically distinct tumours was found, confirming this as a case of NF2 mosaicism.

We present an automated, label-free method for lymphangiography of cutaneous lymphatic vessels in humans in vivo using optical coherence tomography (OCT). This method corrects for the variation in OCT signal due to the confocal function and sensitivity fall-off of a spectral-domain OCT system and utilizes a single-scattering model to compensate for A-scan signal attenuation to enable reliable thresholding of lymphatic vessels. A segment-joining algorithm is then incorporated into the method to mitigate partial-volume effects with small vessels. The lymphatic vessel images are augmented with images of the blood vessel network, acquired from the speckle decorrelation with additional weighting to differentiate blood vessels from the observed high decorrelation in lymphatic vessels. We demonstrate the method with longitudinal scans of human burn scar patients undergoing ablative fractional laser treatment, showing the visualization of the cutaneous lymphatic and blood vessel networks.

Angiogenesis inhibitors may enhance the effects of low dose (metronomic) chemotherapy. However, there is a wide range of novel angiogenesis inhibitors which must be tested in combinations with oral chemotherapy agents to assess the anti-endothelial and anti-cancer effects. This preliminary testing is most suited to high throughput in vitro models, rather than clinical trials. We aimed to establish an in vitro model and test the anti-endothelial and anti-cancer effects of the multi-kinase inhibitor sorafenib when used as a single agent and in combination with oral chemotherapy agents used at low concentrations. Micro-vascular endothelial cells and 3 cancer cell lines were utilised and an extended treatment strategy (96 h) was employed in order to mimic a continuous low dose anti-angiogenic chemotherapy regimen. Sorafenib significantly enhanced the anti-endothelial effect of low dose etoposide, paclitaxel and temozolomide. Sorafenib also significantly enhanced the anti-cancer effect of low dose etoposide, paclitaxel and temozolomide in SK-MEL-2 melanoma cells, producing an additive effect on inhibition of cell growth in all cases. These combinations appear to be the most promising for in vivo pre-clinical studies, with a view to testing in melanoma patients as a continuous dosing strategy, due to the in vitro additive inhibitory effect on growth seen in both endothelial and cancer cells.