The diversity of hypospadias management in North America: a survey of pediatric urologists.

PURPOSE: To determine trends in hypospadias management, including surgical techniques and perioperative care, by pediatric urologists in North America. METHODS: An anonymous online survey was devised to assess approaches to hypospadias repair and management, including anesthetic considerations, catheter placement, choice of dressing, and postoperative antibiotic treatment. The survey was sent to all practicing members of the Societies for Pediatric Urology. RESULTS: The survey was completed by 133 (34.5%) respondents. Hypospadias repair was overwhelmingly recommended between ages 6-12 months (89.5%). A local or regional anesthetic block (caudal, penile, pudendal, spinal) is performed nearly universally (96.2%). The majority of surgeons perform distal repairs outpatient (70.7%), while fewer perform outpatient staged repairs (47.4%) or redo surgery (33.8%). Nearly all respondents preferred either VicrylTM/DexonTM (50.4%) or MaxonTM/PDSTM (48.1%) for urethroplasty. All but one respondent leaves a stent for midshaft to proximal repairs whereas stenting for glanular repairs was split with 53.4% leaving a stent. Most surgeons (60.9-70.9%) prescribe postoperative antibiotics regardless of severity and the majority (72.9%) prescribe narcotics for analgesia. CONCLUSIONS: Approaches to hypospadias repair are extremely varied such that there is a lack of consensus among pediatric urologists regarding most aspects of hypospadias management. Investigations comparing hypospadias practice patterns are necessary to develop a standard of care for this complex pediatric urologic entity.

Cross-sectional quantitative validation of the paediatric Localized Scleroderma Quality of Life Instrument (LoSQI): A disease-specific patient-reported outcome measure.

BACKGROUND: The Localized Scleroderma Quality of Life Instrument (LoSQI) is a disease-specific patient-reported outcome (PRO) measure designed for children and adolescents with localized scleroderma (LS; morphea). This tool was developed using rigorous PRO methods and previously cognitively tested in a sample of paediatric patients with LS. OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of the LoSQI in a clinical setting. METHODS: Cross-sectional data from four specialized clinics in the US and Canada were included in the analysis. Evaluation included reliability of scores, internal structure of the survey, evidence of convergent and divergent validity, and test-retest reliability. RESULTS: One hundred and ten patients with LS (age: 8-20 years) completed the LoSQI. Both exploratory and confirmatory factor analysis supported the use of two sub-scores: Pain and Physical Functioning, and Body Image and Social Support. Correlations with other PRO measures were consistent with pre-specified hypotheses. LIMITATIONS: This study did not evaluate longitudinal validity or responsiveness of scores. CONCLUSION: Results from a representative sample of children and adolescents with LS continue to support the validity of the LoSQI when used in a clinical setting. Future work to evaluate the responsiveness is ongoing.

Perceived social support attenuates increased hostile reactions to traumatic threat.

OBJECTIVE: Extant literature has seldom examined the naturalistic role of reaction to threat on downstream emotional distress while also considering buffers, such as perceived social support, to acute negative mental health outcomes. The present study examined how trauma symptoms, in reaction to a global stressor, predicted increased psychological distress via elevated emotional hostility and whether perceived social support modified such effects. We predicted a priori that increased exposure to trauma would be associated with increased hostility and global psychological distress, but that this path would be attenuated by greater levels of perceived social support, as individuals who report greater support exhibit greater emotional coping. METHODS: We recruited 408 adults from a large university in the Midwestern United States to participate in a survey assessing past-week trauma, hostility, distress, and perceived social support following the initial COVID-19 lockdown. The survey was conducted in March 2020, directly after strict shelter-in-place orders were locally mandated. To test our hypotheses, we employed a moderated mediation analysis approach. RESULTS: Results demonstrate that higher trauma predicted increased hostility, which in turn predicted increased distress, and trauma predicted distress via hostility (an indirect effect). As hypothesized, higher perceived social support attenuated the association between trauma and hostility. CONCLUSION: Results support a hostile emotional pathway that may increase distress in the context of increased traumatic impact; however, social support likely buffers these effects, particularly in the face of new or novel threats and stressors. Findings suggest broad application for understanding the relation between the introduction of stressors, psychological distress, and social support.

Renal replacement and extracorporeal therapies in critical care: current and future directions.

There are a wide number of indications for extracorporeal therapies in the critical care environment. A common indication seen by the acute physician is continuous renal replacement therapy (CRRT) in a proportion of patients with acute kidney injury. It is therefore important that acute physicians have a sound understanding of the principles of CRRT in the acutely unwell patient. This review will outline the indications for its use, commonly used methods and anticoagulation considerations. It will discuss when to start and stop CRRT as well as describing potential treatment complications. This review will also discuss the role of therapeutic plasma exchange in critical care and novel extracorporeal therapies including blood purification in sepsis and carbon dioxide removal in acute respiratory distress syndrome and acute exacerbations of obstructive lung disease. Extracorporeal membrane oxygenation is outside of the scope of this article.

Proficiency and Retention of Five Clinical Veterinary Skills Using Multipurpose Reusable Canine Manikins vs. Live Animals: Model Development and Validation.

Simulation in veterinary education provides a safe and ethical alternative to using live animals, but most simulators are single purpose and unvalidated. In this study, canine training manikins were created using readily available materials to teach fine needle aspiration (FNA) of peripheral lymph nodes, jugular venipuncture, cephalic venipuncture, intravenous catheterization, and cystocentesis. Undergraduate subjects were prospectively enrolled and stratified by veterinary experience prior to randomization into two groups. Students were taught a new skill each week through a written description of the technique, video training, and hands-on practice (live animal vs. manikin). The following week, participants were scored on the performance of the previous week's skill on a live animal using a standardized rubric by reviewers blinded to the training group. Six weeks later, the assessment was repeated for all skills. Scores were compared between groups and time points using repeated-measures ANOVA after logarithmic transformation. p < .05 was significant. There were no significant differences in scores for any of the skills between the groups immediately following or 6 weeks after training. Initial proficiency and short-term retention of clinical skills do not differ for students trained using a manikin vs. a live dog.

Improved preservation of ovarian tissue morphology that is compatible with antigen detection using a fixative mixture of formalin and acetic acid.

STUDY QUESTION: Can ovarian tissue morphology be better preserved whilst enabling histological molecular analyses following fixation with a novel fixative, neutral buffered formalin (NBF) with 5% acetic acid (referred to hereafter as Form-Acetic)? SUMMARY ANSWER: Fixation with Form-Acetic improved ovarian tissue histology compared to NBF in multiple species while still enabling histological molecular analyses. WHAT IS KNOWN ALREADY: NBF fixation results in tissue shrinkage in various tissue types including the ovary. Components of ovarian tissue, notably follicles, are particularly susceptible to NBF-induced morphological alterations and can lead to data misrepresentation. Bouin's solution (which contains 5% acetic acid) better preserves tissue architecture compared to NBF but is limited for immunohistochemical analyses. STUDY DESIGN, SIZE, DURATION: A comparison of routinely used fixatives, NBF and Bouin's, and a new fixative, Form-Acetic was carried out. Ovarian tissue was used from three different species: human (n = 5 patients), sheep (n = 3; 6 ovaries; 3 animals per condition) and mouse (n = 14 mice; 3 ovaries from 3 different animals per condition). PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissue from humans (aged 13 weeks to 32 years), sheep (reproductively young i.e. 3-6 months) and mice (10 weeks old) were obtained and fixed in 2 ml NBF, Bouin's or Form-Acetic for 4, 8, and 24 h at room temperature. Tissues were embedded and sectioned. Five-micron sections were stained with haemotoxylin and eosin (H&E) and the percentage of artefact (clear space as a result of shrinkage) between ovarian structures was calculated. Additional histological staining using Periodic acid-Schiff and Masson's trichrome were performed on 8 and 24 h NBF, Bouin's and Form-Acetic fixed samples to assess the compatibility of the new fixative with stains. On ovarian tissue fixed for both 8 and 24 h in NBF and Form-Acetic, immunohistochemistry (IHC) studies to detect FOXO3a, FoxL2, collagen IV, laminin and anti-Müllerian hormone (AMH) proteins were performed in addition to the terminal deoxynucleotidyl transferase nick end labelling (TUNEL) assay to determine the compatibility of Form-Acetic fixation with types of histological molecular analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fixation in Form-Acetic improved ovarian tissue morphology compared to NBF from all three species and either slightly improved or was comparable to Bouin's for human, mouse and sheep tissues. Form-Acetic was compatible with H&E, Periodic acid-Schiff and Masson's trichrome staining and all proteins (FOXO3a, FoxL2, collagen IV and laminin and AMH) could be detected via IHC. Furthermore, Form-Acetic, unlike NBF, enabled antigen recognition for most of the proteins tested without the need for antigen retrieval. Form-Acetic also enabled the detection of damaged DNA via the TUNEL assay using fluorescence. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, IHC analysis was performed on a select number of protein types in ovarian tissue thus encouraging further studies to confirm the use of Form-Acetic in enabling the detection of a wider range of protein forms in addition to other tissue types. WIDER IMPLICATIONS OF THE FINDINGS: The simplicity in preparation of Form-Acetic and its superior preservative properties whilst enabling forms of histological molecular analyses make it a highly valuable tool for studying ovarian tissue. We, therefore, recommend that Form-Acetic replaces currently used fixatives and encourage others to introduce it into their research workflow. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Oxford Medical Research Council Doctoral Training Programme (Oxford MRC-DTP) grant awarded to B.D.B. (Grant no. MR/N013468/1), the Fondation Hoffmann supporting R.A. and the Petroleum Technology Development Fund (PTDF) awarded to B.V.A.

Ataxia and mobility in children following surgical resection of posterior fossa tumour: A longitudinal cohort study.

PURPOSE: To report the course of ataxia in children up to 2 years post-operatively, following surgical resection of a posterior fossa tumour (PFT). METHODS: Thirty-five children, (median age 9 years, range 4-15) having resection of PFT, were assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Brief Ataxia Rating Scale (BARS) and the mobility domain of the Paediatric Evaluation of Disability Index (PEDI-m) at initial post-operative period (baseline), 3 months, 1 year and 2 years post-operatively. RESULTS: Baseline median scores of the SARA and BARS were 8.5 (range 0-35.5), and 7 (0-25) respectively. Ataxia improved at 3 months (median SARA and BARS reduction 3.5 and 4, respectively). Additional gradual improvements in SARA were recorded at 1 (median reduction 2) and 2 years post-operatively (median reduction 0.5). Median baseline PEDI-m was 54.75 (range 15.2-100) with improvement at 3 months (median increase 36.95) and small improvement at 1 year (median increase 2.5) and 2 years (median increase 5.8). Children with medulloblastoma and midline tumours (median baseline SARA 10 and 11, respectively) demonstrated more severe ataxia than children with low-grade gliomas and unilateral tumours (median baseline SARA 7.5 and 6.5, respectively). CONCLUSION: The largest improvement in ataxia scores and functional mobility scores is demonstrated within the first 3 months post-operatively, but ongoing gradual improvement is observed at 2 years. Children with medulloblastoma and midline tumour demonstrated higher ataxia scores long term.

A novel patient-reported outcome for paediatric localized scleroderma: a qualitative assessment of content validity.

BACKGROUND: According to current standards, no existing patient-reported outcome (PRO) measures have high-quality validity evidence for use with individuals diagnosed with paediatric localized scleroderma (LS). This severely hinders patient-centred LS-focused research, including much needed clinical trials. OBJECTIVES: To develop a valid health-related quality of life measure for individuals with paediatric LS and to qualitatively evaluate its content validity using a patient-centred approach. METHODS: Previously collected qualitative data from youth with LS and their caregivers was used to develop items. The resulting item set was administered in a clinical setting to participants aged 8-18 years old. Cognitive interviews were used to evaluate time to survey completion, readability/understanding of the items, appropriateness of the recall period and construct representation. RESULTS: Seventeen children and adolescents with LS participated in the study. Interviews supported readability, understanding of the items and appropriateness of the recall period in individuals > 10 years old. Revisions were made to simplify the instructions and to be more inclusive of different subtypes of LS. Three items were added to improve content representation. CONCLUSIONS: Content validity was supported by the patient-centred development process of the outcome measure and via direct feedback from individuals with LS and their families. Although an important first step, the resulting PRO, termed the Localized Scleroderma Quality of Life Instrument, should be further evaluated in a larger sample before being implemented. What's already known about this topic? No current health-related quality of life (HRQoL) measures have been created using direct input from children and adolescents with localized scleroderma (LS). When compared with qualitative reports of HRQoL impact in youth with all LS subtypes, no existing patient-reported outcome (PRO) measures have appropriate content validity for individuals with paediatric LS. What does this study add? This study proposes a novel LS-specific PRO and is the first qualitative assessment of content validity for any PRO measure in this population. Results from cognitive interviews with children and adolescents support the content validity of the newly developed item set and its ability to capture HRQoL impact in a clinical context. What are the clinical implications of this work? Incorporating a content-valid PRO of HRQoL impact into clinical practice would allow for the valid, ongoing capture of patient experience in LS. Although content validity is an important and necessary step in the process of evaluating validity, items within this novel measure will undergo additional psychometric evaluation before implementation in research and clinical settings.

STRAWB2 (Stress and Wellbeing After Childbirth): a randomised controlled trial of targeted self-help materials to prevent post-traumatic stress disorder following childbirth.

OBJECTIVES: To test whether providing psychological self-help materials would significantly lower the incidence of post-traumatic stress disorder (PTSD) at 6-12 weeks postnatally. DESIGN: Open-label randomised controlled trial, with blinded outcome assessment. SETTING: Community midwifery services in two National Health Service (NHS) trusts in the North West. SAMPLE: A cohort of 2419 women receiving normal NHS postnatal care. METHODS: Midwives screened women for traumatic birth experience; 678 women who screened positively (28.1%) were randomly allocated to self-help with usual care (n = 336) or to usual care alone (n = 342). The self-help materials were a leaflet and online film designed to prevent the development of PTSD after trauma exposure through explaining how to manage early psychological responses. MAIN OUTCOME MEASURE: The primary outcome was a composite of diagnostic and subdiagnostic PTSD at 6-12 weeks postnatally using the gold-standard Clinician-Administered PTSD Scale (CAPS-5) interview. RESULTS: Of the 678 women correctly randomised plus the nine women randomised in error, 478 (70.5%) were followed up. Diagnostic or subdiagnostic PTSD rates at follow-up did not differ between groups who received self-help (26.7%, 65/243) or usual care alone (26.2%, 64/244) (intention-to-treat analysis: RR 1.02, 95% CI 0.68-1.53). Findings remained consistent in the per-protocol analysis (RR 1.04, 95% CI 0.85-1.27). Women viewed the materials very positively. There were no adverse effects. Health economic micro-costing indicated implementation would be very low cost. CONCLUSIONS: Many women experience a traumatic birth and risk developing PTSD, but self-help strategies without professional support are insufficient and should not be routinely introduced. TWEETABLE ABSTRACT: Self-help information alone does not reduce the number of women developing PTSD after a traumatic childbirth.

Is four-dimensional CT angiography as effective as digital subtraction angiography in the detection of the underlying causes of intracerebral haemorrhage: a systematic review.

PURPOSE: To determine whether the sensitivity and specificity of four-dimensional CTA (4D-CTA) are equivalent to digital subtraction angiography (DSA) in the detection of underlying vascular abnormalities in patients with intracerebral haemorrhage (ICH). METHODS: A systematic review of studies comparing 4D-CTA with DSA in the detection of the underlying structural causes of ICH was performed on the literature published between 1998 and 2019. RESULTS: We identified a total of 237 articles from PubMed, SCOPUS and Web of Science using the following Medical Subject Headings (MeSH) terms: primary intracerebral haemorrhage, 4D-CTA, DSA, cerebral haemorrhage, angiography, digital subtraction, arteriovenous malformations, 4D, CTA, dynamic-CTA and time-resolved CTA. Following the removal of duplicate publications and articles failing to meet our inclusion criteria, there were four articles potentially viable for analysis. Therefore, there were not sufficient studies to provide a statistically meaningful meta-analysis. CONCLUSION: The review of current literature has demonstrated that there are few published studies comparing 4D-CTA with DSA in spontaneous ICH, with only four suitable studies identified for potential analysis. However, due to the restricted number of patients and high sensitivity and specificity of 3 studies (100%), performing a meta-analysis was not meaningful. Qualitative analysis of the data concluded that 4D-CTA has the diagnostic potential to replace invasive DSA in certain cases with vascular abnormalities. However, further research studies directly comparing 4D-CTA with DSA using larger prospective patient cohorts are required to strengthen the evidence base.

British Association of Dermatologists (BAD) National Audit on Non-Melanoma Skin Cancer Excision 2016 in collaboration with the Royal College of Pathologists.

BACKGROUND: We conducted a re-audit of the surgical practice of UK dermatologists for the treatment of nonmelanoma skin cancer and examined changes with reference to our previous audit in 2014. The audit was supplemented by a detailed assessment of completeness of the histopathology reports for each tumour. METHODS: UK dermatologists collected data on 10 consecutive nonmicrographic excisions for basal cell carcinoma (BCC) and 5 for squamous cell carcinoma (SCC). Data were collected on site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins. RESULTS: In total, 222 responses were received from 135 centres, reporting on 3290 excisions. Excisions from the head and neck accounted for 56.7% of cases. Tumour diameter (mean ± SD) was 11.4 ± SD 7.1 mm (maximum size 100 mm) and 97% of cases were primary excisions. BCCs and SCCs respectively accounted for 65.7% and 26.8% of total cases. Of the suspected BCCs and SCCs, 95.8% and 80.4%, respectively, were confirmed histologically. All margins for any tumour were clear in 97.0% of cases, and complication rate in the audit was < 1%. Of the 2864 histology reports evaluated, only 706 (24.6%) contained all core data items; 95% of these were structure (synoptic) reports. Commonly omitted items were level of invasion, risk and T stage, which were absent from 35.7%, 64.2% and 44.1% of reports, respectively. CONCLUSIONS: Diagnostic accuracy and complete excision rates remain high. Complication rates may be under-reported owing to lack of follow-up. Histopathology reporting has a greater chance of being complete if reports are generated on a field-based platform (synoptic reporting).

Correction to: Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

In the published version, the Acknowledgements section was missing a funding note of co-author Dr C Verrill. The corrected version should read as follows.

Attitudes towards child life specialists and their utilization within pediatric urology.

INTRODUCTION: The American Academy of Pediatrics views Certified Child Life Specialists (CCLS) as "an important component of pediatric hospital based care to address the psychosocial concerns that accompany hospitalization." CCLSs help patients and parents navigate the complex medical system in order to minimize psychosocial and emotional stress by implementing age appropriate coping skills. This survey explores the perceptions towards CCLS and their utilization with pediatric urology. MATERIALS AND METHODS: A Survey Monkey questionnaire was developed and distributed to Society for Pediatric Urology members (SPU) (n = 314). Providers were queried about CCLS implementation and their perception regarding CCLS's role in improving health related quality of life (HRQOL). RESULTS: There was a 34.1% response rate (n = 107). Ninety-four providers (87.9%) reported CCLS interaction with their patients and greater than 95% of providers felt CCLS imparted some degree of benefit to their patients' HRQOL. Only 4.7% felt CCLS offered no benefit to the patients. CCLS were consistently used in a minority of inpatient and outpatient settings and never in the radiological setting. They were used at least 50% of the time by the most responders in inpatient and radiological setting and nearly the same in the ambulatory surgery setting. CONCLUSIONS: This survey illuminates that the majority of providers interact with CCLS in clinical settings and believe their involvement is beneficial. However, CCLSs are under-utilized during invasive urological procedures where patient anxiety is high. By understanding perceptions of providers and their practice patterns we can overcome barriers to CCLS use and improve their quality of life.

Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

PURPOSE: This article describes the development of a new reproductive tissue cryopreservation clinical service for children at high risk of infertility in the NHS during times of severe financial constraints in the health service. METHOD: A development plan with two phases was drawn up. Phase 1 restricted the service to childhood cancer patients referred to the Oxford Paediatric Oncology and Haematology Principle Treatment Centre. It was estimated that there would be 10 patients/year and used existing staff and facilities from paediatric oncology, surgery, anaesthetics radiology, pathology, psychology, teenage-young adult gynaecology, and an existing Human Tissue Authority tissue bank with a licence for storage of tissue under a Human Sector Licence. Phase 2 extended the service to include children and young adults across England, Wales and Ireland-patients from Scotland having access to a research programme in Edinburgh. The main challenge in phase 2 being resources and the need for patients to be able to be treated as close to home as safely as possible. RESULTS: The Oxford team developed information resources and eligibility criteria based on published best practice, referral and treatment pathways, multidisciplinary team meetings, a network of third party sites, and a dedicated case management and database. As the programme expanded, the Oxford team was able to justify to management the need for a dedicated theatre list. Patient feedback through questionnaires, qualitative work conducted as part of a Ph.D. thesis as well as direct patient stories and interviews in TV, and radio features underpins the positive impact the programme has on patients and their families. CONCLUSION: The Oxford Reproductive Cryopreservation programme delivers fertility preservation treatment to children and young adults at high risk of infertility safely, effectively and as close to home as possible. The onward view is to apply for national funding for this programme for recognition and sustainability.

Cost-effectiveness of antimicrobial prophylaxis for children in the RIVUR trial.

PURPOSE: We evaluated the cost-effectiveness of antimicrobial prophylaxis to prevent recurrent UTIs in children with vesicoureteral reflux based on the RIVUR trial. MATERIALS AND METHODS: A decision tree model compared strategies of antimicrobial prophylaxis vs. placebo in children with reflux using results from the RIVUR trial. Risk reduction was 50% based on intention to treat analysis. Costs were based on Medicare reimbursement and data in literature. The model incorporated costs of medications, imaging and complications such as pyelonephritis, likelihood of surgery and loss of work. One- and two-way sensitivity analyses were performed evaluating the effect of changing variables on the cost-effectiveness of antibiotic prophylaxis in preventing recurrent UTIs. RESULTS: Mean costs were higher for treatment vs. placebo at $3092 and $2932, respectively, with 12.7 fewer infections per 100 children. One-way sensitivity analyses showed that antibiotics would be cost equivalent if the yearly medical cost was $386, rate of recurrent UTI increased to 32%, antibiotic risk reduction was 63%, or rate of pyelonephritis in the placebo group was 48%. Two-way analyses modifying antibiotic cost, risk reduction of antibiotics and probability of infection showed areas where antibiotics could be more cost-effective than placebo. CONCLUSIONS: Antibiotic prophylaxis is associated with marginally higher costs compared with placebo, but significantly fewer infections. A slight decrease in antibiotic cost or increase in recurrent UTIs on placebo may result in prophylaxis being more cost-effective. We recognize that the marginal overall cost in antibiotics may have a substantial impact on the quality of life for the individual patient and family.

Synchronous, but separate, bladder and vaginal rhabdomyosarcoma: a novel genetic case report.

Embryonal rhabdomyosarcoma is a rare cancer that often requires multimodality therapy to treat; however, these therapies can cause changes in the biology of the tumor. Several reports have documented pathologic changes but only recently have genetic changes been mapped. We present case of two separate synchronous primary rhabdomyosarcomas in a 17-month-old patient and discuss the pathophysiology and genetic changes that occur with treatment. We hypothesize that a genetic field defect arising in development of the urogenital sinus caused the tumors, but that treatment modalities may have caused genetic alterations changing clinical behavior of the tumors and responses to treatment.

Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study.

BACKGROUND: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. PATIENTS AND METHODS: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. RESULTS: Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n = 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and <3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use. CONCLUSIONS: These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.

Ultrasonographic Assessment of Testicular Viability Using Heterogeneity Levels in Torsed Testicles.

PURPOSE: Gross testicular heterogeneity on ultrasound has been associated with testis loss following testicular torsion in children. We aimed to quantify the extent of temporal heterogeneity associated with testis loss in testicular torsion cases using a noninvasive technique to determine a HI (heterogeneity index) on ultrasound images. MATERIALS AND METHODS: We retrospectively studied the records of patients who presented with acute scrotal pain to the Pediatric Emergency Department over a 6-year period. Ultrasound images of the affected testis and the unaffected contralateral testis were examined using a proprietary program to determine the extent of heterogeneity of each image. The difference between the HI of the torsed testis and that of the contralateral normal testis was termed ΔHI. Receiver operating characteristics curve analysis was performed to determine the ΔHI threshold for nonviability. RESULTS: Among 529 patients who presented with acute scrotal pain 147 had testicular torsion based on surgical findings. Of these 147 patients 110 (74.8%) were found to have a viable testis while 37 (25.2%) had a nonviable testis. Using the ΔHI cutoff of 0.394 or greater for nonviability, sensitivity and specificity were 100% and 94.5%, respectively. Positive and negative predictive values were 86% and 100%, respectively. CONCLUSIONS: Our results demonstrate that a quantifiable temporal gradation of heterogeneity exists and the heterogeneity index can be used as an objective parameter to determine the viability of a torsed testicle. By developing the technology to measure the heterogeneity index in real time, we could potentially identify which patients with testicular torsion have a nonviable testicle and, thus, would not require immediate surgical exploration.

The rise of methicillin resistant Staphylococcus aureus: now the dominant cause of skin and soft tissue infection in Central Australia.

This study aimed to examine the epidemiology and treatment outcomes of community-onset purulent staphylococcal skin and soft tissue infections (SSTI) in Central Australia. We performed a prospective observational study of patients hospitalised with community-onset purulent staphylococcal SSTI (n = 160). Indigenous patients accounted for 78% of cases. Patients were predominantly young adults; however, there were high rates of co-morbid disease. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was the dominant phenotype, accounting for 60% of cases. Hospitalisation during the preceding 6 months, and haemodialysis dependence were significant predictors of CA-MRSA infection on univariate analysis. Clinical presentation and treatment outcomes were found to be comparable for methicillin-susceptible S. aureus (MSSA) and methicillin-resistant cases. All MRSA isolates were characterised as non-multi-resistant, with this term used interchangeably with CA-MRSA in this analysis. We did not find an association between receipt of an active antimicrobial agent within the first 48 h, and progression of infection; need for further surgical debridement; unplanned General Practitioner or hospital re-presentation; or need for further antibiotics. At least one adverse outcome was experienced by 39% of patients. Clindamycin resistance was common, while rates of trimethoprim-sulfamethoxazole resistance were low. This study suggested the possibility of healthcare-associated transmission of CA-MRSA. This is the first Australian report of CA-MRSA superseding MSSA as the cause of community onset staphylococcal SSTI.