Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.

BACKGROUND: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. METHODS: In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. RESULTS: The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3" (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). CONCLUSIONS: LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.

Endocrine, immune and renal toxicity in male largemouth bass after chronic exposure to glyphosate and Rodeo®.

Glyphosate is the most used herbicide worldwide, with no historical comparison. It is used for genetically modified crops, and particularly in Florida, it is used as a sugar cane ripener. An aquatic formulation (Rodeo®) is used to treat aquatic weeds in waterbodies and drainage canals. Because of its extended use, glyphosate can run off or be sprayed directly into waterbodies, and chronically expose aquatic wildlife. Exposure in animal models has been associated with kidney and liver damage and glyphosate has been suggested as an endocrine disruptor. We exposed adult male largemouth bass for 21 days to two doses of glyphosate and Rodeo® (chemically equivalent concentration of glyphosate) at 0.5 mg L-1 and 10 mg L-1 and to a clean water control (n=4 fish/tank in quadruplicate). Concentrations during the experiment were corroborated with UHPLC-MS/MS. Total RNA was isolated from the trunk kidney and head kidney. RNA-seq was performed for the high doses compared to controls. Transcripts were analyzed with fish and mammalian pathway analyses software. Transcripts mapped to Zebrafish metabolic pathways using PaintOmics showed steroid hormone biosynthesis in the trunk kidney as the most significantly enriched pathway. Steroid hormones were measured in plasma by UHPLC-MS/MS. Total androgens were significantly reduced at 0.5 mg L-1 of glyphosate and at equivalent concentrations in Rodeo® compared to controls. 11-ketotestosterone and estrone concentrations were significantly reduced in all doses. A gene involved in the conversion of testosterone to 11-ketotestosterone was down-regulated by glyphosate. Using the mammalian pathway analysis algorithm, cellular processes associated with T-cell activation/development and intracellular pH were significantly enriched in the trunk kidney by glyphosate and Rodeo® exposure. Endocrine disruption was corroborated at the hormone and gene expression levels. Rodeo® and glyphosate share gene expression pathways, however, Rodeo® had more pronounced effects in largemouth bass.

Lifetime Prevalence and Correlates of Patient-Perceived Medical Errors Experienced in the U.S. Ambulatory Setting: A Population-Based Study.

Background: The rate of safety harm self-perceived medical errors and harms reported in the U.S. ambulatory system is not well characterized. Objectives: To determine the prevalence of U.S. adult ambulatory care patient self-perceived safety harms and to gauge the degree of association between harms with various patient characteristics and outcomes. Methods: A large U.S. cross-sectional online survey of 9206 ambulatory care adults was assessed for their perception of medical errors and harms during care (misdiagnosis, mistakes in care, and wrong or delayed treatment) and also included patient demographics, health status, comorbidities, insurance status, income, barriers to care (affordability, transportation, and family and social support), number of visits to primary health care services in the past 12 months, and use of urgent or emergency care in the last 12 months. Results: The overall rate of self-perceived medical errors and harms among adult patients in the ambulatory care setting was 36%. Female patients, independent of age, and those with multiple comorbidities or barriers to care, reported the highest number of medical errors. Utilization of multiple providers was associated with a greater number of reported medical errors, often resulting in changing health care providers. Patients who reported having trouble affording health care or navigating the system to receive care also reported higher levels of harm. They were cared for by multiple providers, often switch providers, and their care is associated with greater utilization of health care resources. Patients reporting the highest rates of harm had greater use of hospital and emergency room care. Conclusions: This large U.S. adult ambulatory care study provides evidence that patient self-perceived medical errors and harms reported by patients are common. Patient self-perceived medical errors and harms occur most commonly in women, with poor health, limitation of activities, and who have three or more comorbidities.

Cancer therapy shapes the fitness landscape of clonal hematopoiesis.

Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies.

Gait analysis and hip extensor function early post total hip replacement.

OBJECTIVE: The purpose of this study was to systematically evaluate the sagittal kinematic and kinetic gait patterns in patients in this early post-operative period, to describe them and to better understand the deficiencies in that gait pattern that may help to develop targeted rehabilitation strategies. METHODS: This study evaluated early gait patterns in 10 patients with isolated unilateral hip osteoarthritis who were post-operative for total hip replacement. Kinetic and kinematic assessments - focusing on sagittal plane abnormalities - were performed at 2 weeks pre-operatively and 8 weeks post-operatively. RESULTS: Our results demonstrated that while clinical scoring for pain and functional ability significantly improved post-operatively, as did clinical assessment of range of motion passively, this did not translate to the degree of dynamic improvement in gait. Step length and stride length did not improve significantly. Lack of hip extension in terminal stance associated with excessive anterior pelvic tilt persisted and was associated with a worsening in hip extensor power post-operatively. CONCLUSION: Based on our results, post-operative rehabilitation programmes should include extensor muscle exercises to increase power and to retain the operative gain in passive range of motion, which would help to improve gait patterns.

Services for children with developmental co-ordination disorder: an evaluation against best practice principles.

PURPOSE: The National Health Service in Scotland published a best practice framework to support occupational therapists and physiotherapists to deliver effective services for children with developmental co-ordination disorder (DCD); however, adherence is variable. To highlight areas for development, this study compared the care pathway within a paediatric DCD service against the NHS Scotland framework. METHODS: A partnership of researchers and clinicians based in the United Kingdom conducted a qualitative study with 37 participants (N = 13 interview participants, N = 24 workshop participants). In-depth interviews and/or workshops were used to map the DCD service against the NHS framework. Identified gaps were aligned with four key stages of the care pathway. Qualitative analysis software was used to analyse the data. RESULTS: Core principles to guide future development were identified for each phase of the pathway. These core principles related to the NHS framework and focused on issues such as involving the family, defining clear pathways and enhancing children's participation. Participants identified potential strategies for service improvement such as developing community-based interventions and information provision. CONCLUSION: Challenges when providing services for children with DCD include confusing service pathways and poor partnership working. It is, therefore, important that clinicians utilise collaborative working strategies that support children's participation. IMPLICATIONS FOR REHABILITATION: There are numerous challenges related to the implementation of best practice principles into the provision of therapy services for children with developmental coordination disorder (DCD). It is important that AHPs seek ways of engaging parents and educational professionals at all stages of the care pathway in order to ensure optimum service provision for the child. Addressing participation is an important aspect and community-based strategies may be particularly beneficial, both as a preventative activity and as an intervention approach.

ESTABLISHMENT OF ECHOCARDIOGRAPHIC PARAMETERS OF CLINICALLY HEALTHY FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS).

A standardized echocardiographic technique was recently established for the Florida manatee (Trichechus manatus latirostris). There are no available published data on normal echocardiographic parameters in any Sirenian species. The purpose of this study was to report reference parameters for various echocardiographic measurements. These parameters are intended to serve as a comparison for future research into the prevalence of cardiac diseases in the manatee and to aid in diagnosing animals with suspected cardiac disease in rehabilitation facilities. Annual health assessments of free-ranging manatees in Crystal River National Wildlife Refuge, Florida, and pre-release health assessments of rehabilitated manatees at Tampa's Lowry Park Zoo permitted comparison of echocardiographic measurements in adult (n=14), subadult (n=7), and calf (n=8) animals under manual restraint.

Vocational rehabilitation: facilitating evidence based practice through participatory action research.

BACKGROUND: Improving vocational rehabilitation in line with the current evidence base is an area of considerable interest. Aims To describe the strategies used by a multidisciplinary team in the initial stages of a participatory action research (PAR) approach to improving a vocational rehabilitation service. METHOD: A literature review and PAR process were completed. One hundred and fifteen participants engaged in multifaceted data collection and analysis, building consensus around key principles for a new vocational rehabilitation service. RESULTS: A synthesis of our literature review and PAR process was developed into a set of principles for practice which we plan to implement across the service. CONCLUSIONS: We have developed methodologies in interdisciplinary collaborations spanning statutory and non-statutory services. We have developed a set of principles for practice and detailed plans for implementation are being drawn up to inform provision in the future.

Knee extensor disruption in mild diplegic cerebral palsy: a risk for adolescent athletes.

We report three cases of adolescent boys with mild diplegic cerebral palsy (CP) who suffered disruption of the knee extensor mechanism. Two had fractures of the patella and the third a fracture avulsion of the tibial tubercle combined with an undisplaced fracture of the patella. All three had gait analysis prior to sustaining the fractures and were known to have mild knee crouch. Each participated in sport including football. Each suffered an acute deterioration in gait resulting in a referral for repeat gait analysis, and x-ray of the affected knee. With the increased involvement of children with CP in sporting activities, especially children with mild knee crouch, we caution that knee extensor rupture might be an increasing problem.

Readiness for employment: perceptions of mental health service users.

Work is good for both physical and mental health, and access to work is a basic human right. People with mental health conditions want to work and with the right support can work but are often excluded from the workplace. We explored factors influencing individual's perceptions of their readiness for employment. Participants' narratives focused particularly on personal causation and it's inter-reactions with other aspects of volition, habituation and the environment and highlight a number of key areas, which are discussed in relation to service provision. Sheltered workshops offer support and some structure and routine but may limit an individual's readiness for employment. Services should be evidence based and focused on real work opportunities which fit with individual's interests and values. Occupational therapy theory offers a unique and valuable perspective in understanding perceptions of readiness for employment and occupational therapists offer valid and useful assessments and interventions for vocational rehabilitation.

Hysteroscopy and episiotomy in a rescued, cold-stressed Florida manatee (Trichechus manatus latirostris) for diagnosis and treatment of a retained fetal skeleton.

A rescued female manatee was observed expelling a fetal bone from the vulva. The manatee was anesthetized and diagnosed with uterine retention of a fetal skeleton by ultrasound and hysteroscopy. Episiotomy was performed to gain manual access to the vagina and uterus for removal of the skeleton. Second intention healing of the episiotomy site produced excellent results. Rescued female manatees should receive a thorough reproductive tract evaluation since presence of retained fetal tissues might not be evident in blood or hormone analyses. Retention of a whole or partial dead fetus can be life-threatening to manatees, and retained tissues should be removed as early as possible.

Accuracy of FAST scan in blunt abdominal trauma in a major London trauma centre.

INTRODUCTION: Blunt abdominal trauma (BAT) is a leading cause of morbidity and mortality. Rapid diagnosis and treatment with the Advanced Trauma Life Support guidelines are vital, leading to the development of Focused Assessment with Sonography in Trauma (FAST). METHODS: A retrospective study carried out from January 2007-2008 on all patients who presented with BAT and underwent FAST scan. All patients subsequently had a CT scan within 2 h of admission or a laparotomy within two days. The presence of intra-peritoneal free fluid was interpreted as positive. RESULTS: 100 patients with BAT presented; 71 had complete data. The accuracy of FAST in BAT was 59.2%; in these 31 (43.7%) were confirmed by CT and 11 (15%) by laparotomy. There were 29 (40.8%) inaccurate FAST scans, all confirmed by CT. FAST had a specificity of 94.7% (95% CI: 0.75-0.99) and sensitivity of 46.2% (95% CI: 0.33-0.60). Positive Predictive Value of 0.96 (0.81-0.99) and Negative Predictive Value of 0.39 (0.26-0.54). Fisher's exact test shows positive FAST is significantly associated with Intra-abdominal pathology (p=0.001). Cohen's chance corrected agreement was 0.3. 21 out of 28 who underwent laparotomies had positive FAST results indicating accuracy of 75% (95% CI: 57%-87%). CONCLUSION: Patients with false negative scans, requiring therapeutic laparotomy is concerning. In unstable patients FAST may help in triaging and identifying those requiring laparotomy. Negative FAST scans do not exclude abdominal injury. Further randomised control trials are recommended if the role of FAST is to be better understood.

Image reconstruction for hybrid true-color micro-CT.

X-ray micro-CT is an important imaging tool for biomedical researchers. Our group has recently proposed a hybrid "true-color" micro-CT system to improve contrast resolution with lower system cost and radiation dose. The system incorporates an energy-resolved photon-counting true-color detector into a conventional micro-CT configuration, and can be used for material decomposition. In this paper, we demonstrate an interior color-CT image reconstruction algorithm developed for this hybrid true-color micro-CT system. A compressive sensing-based statistical interior tomography method is employed to reconstruct each channel in the local spectral imaging chain, where the reconstructed global gray-scale image from the conventional imaging chain served as the initial guess. Principal component analysis was used to map the spectral reconstructions into the color space. The proposed algorithm was evaluated by numerical simulations, physical phantom experiments, and animal studies. The results confirm the merits of the proposed algorithm, and demonstrate the feasibility of the hybrid true-color micro-CT system. Additionally, a "color diffusion" phenomenon was observed whereby high-quality true-color images are produced not only inside the region of interest, but also in neighboring regions. It appears harnessing that this phenomenon could potentially reduce the color detector size for a given ROI, further reducing system cost and radiation dose.

Interprofessional learning and virtual communities: an opportunity for the future.

As various agencies increasingly advocate interprofessional care (IPC), it is paramount that the educational implications of this approach are considered. Interprofessional learning (IPL) is necessary for IPC and this paper argues that an emerging educational model, narrative-based virtual communities (VCs), meets this goal. We therefore argue for the fusion of narrative pedagogy with the VC approach to further the IPL agenda. Using stories to teach is not new. Technological innovations now make the possibility of using narrative, a way to enable students to experience greater reality in complex situations. Recently, two multimedia VCs have been developed. Here, we review the use of "The Neighborhood" and "Stilwell", as IPL tools. Early evaluation of these communities has been very positive and they offer a unique and innovative approach to IPL in ways that immerse learners from many professions into the context of the lives of individuals requiring health and social care, and the people who provide that service. Thus, it is possible to more fully realize and teach about collaboration and partnerships among professionals and patients.

Infection after spanning external fixation for high-energy tibial plateau fractures: is pin site-plate overlap a problem?

OBJECTIVES: The purpose of this study was to determine whether overlap between temporary external fixator pins and definitive plate fixation correlates with infection in high-energy tibial plateau fractures. DESIGN: Retrospective chart and radiographic review. SETTING: Academic medical center. PATIENTS: Seventy-nine patients with unilateral high-energy tibial plateau fractures formed the basis of this report. INTERVENTION: Placement of knee-spanning external fixation followed by delayed internal fixation for high-energy tibial plateau fractures treated at our institution between 2000 and 2008. METHODS: Demographic patient information was reviewed. Radiographs were reviewed to assess for the presence of overlap between the temporary external fixator pins and the definitive plate fixation. Fisher exact and t test analyses were performed to compare those patients who had overlap and those who did not and were used to determine whether this was a factor in the development of a postoperative infection. MAIN OUTCOME MEASUREMENTS: Development of infection in those whose external fixation pin sites overlapped with the definitive internal fixation device compared with those whose pin sites did not overlap with definitive plate and screws. RESULTS: Six knees in six patients developed deep infections requiring serial irrigation and débridement and intravenous antibiotics. Of these six infections, three were in patients with closed fractures and three in patients with open fractures. Two of these six infections followed definitive plate fixation that overlapped the external fixator pin sites with an average of 4.2 cm of overlap. In the four patients who developed an infection and had no overlap, the average distance between the tip of the plate to the first external fixator pin was 6.3 cm. There was no correlation seen between infection and distance from pin to plate, pin-plate overlap distance, time in the external fixator, open fracture, classification of fracture, sex of the patient, age of the patient, or healing status of the fracture. CONCLUSION: Fears of definitive fracture fixation site contamination from external fixator pins do not appear to be clinically grounded. When needed, we recommend the use of a temporary external fixation construct with pin placement that provides for the best reduction and stability of the fracture, regardless of plans for future surgery.

Child sexual abuse: a new approach to professional education.

Child sexual abuse is a highly emotive subject and nurses have a key role to play in caring for survivors. Educating students about this role is difficult because a conventional classroom approach does not prepare students adequately or give them sufficient insight into the experiences of victims. The Stilwell virtual simulation model is a radical new approach which aims to assist learning by immersing students in a realistic multimedia simulation of a typical community. This model allows insightful learning about difficult areas such as child sexual abuse. Its use and contribution to learning in this area are discussed.

High sensitivity troponin T concentrations in patients undergoing noncardiac surgery: a prospective cohort study.

OBJECTIVES: To determine the proportion of noncardiac surgery patients exceeding the published 99th percentile or change criteria with the high sensitivity Troponin T (hs-TnT) assay. DESIGN AND METHODS: We measured hs-TnT preoperatively and postoperatively on days 1, 2 and 3 in 325 adults. RESULTS: Postoperatively 45% (95% CI: 39-50%) of patients had hs-TnT≥14ng/L and 22% (95% CI:17-26%) had an elevation (≥14ng/L) and change (>85%) in hs-TnT. CONCLUSION: Further research is needed to inform the optimal hs-TnT threshold and change in this setting.

Key characteristics of knowledge transfer and exchange in healthcare: integrative literature review.

AIM: This paper presents the results of a review of literature relating to knowledge transfer and exchange in healthcare. BACKGROUND: Treatment, planning and policy decisions in contemporary nursing and healthcare should be based on sound evidence wherever possible, but research knowledge remains generally underused. Knowledge transfer and exchange initiatives aim to facilitate the accessibility, application and production of evidence and may provide solutions to this challenge. This review was conducted to help inform the design and implementation of knowledge transfer and exchange activities for a large healthcare organization. DATA SOURCES: Databases: ASSIA, Business Source Premier, CINAHL, PsychInfo, Medline and the Cochrane Database of Systematic Reviews. REVIEW METHODS: An integrative literature review was carried out including an extensive literature search. English language systematic reviews, literature reviews, primary quantitative and qualitative papers and grey literature of high relevance evaluating, describing or discussing knowledge transfer or exchange activities in healthcare were included for review (January 1990-September 2009). FINDINGS: Thirty-three papers were reviewed (four systematic reviews, nine literature reviews, one environmental scan, nine empirical studies and ten case studies). CONCLUSION: Robust research into knowledge transfer and exchange in healthcare is limited. Analysis of a wide range of evidence indicates a number of commonly featured characteristics but further evaluation of these activities would benefit their application in facilitating evidence-based practice in nursing.

Optimization and qualification of a quantitative reversed-phase HPLC method for hemagglutinin in influenza preparations and its comparative evaluation with biochemical assays.

A previously described reversed-phase HPLC (RP-HPLC) method based on fast separations on a non-porous silica stationary phase [1] was optimized and qualified for the quantitative determination of hemagglutinin (HA) in influenza vaccine preparations. Optimization of the gradient elution conditions led to improved separation of the HA1 subunit from other vaccine constituents. The sensitivity of the method was significantly increased by using native fluorescence detection, resulting in an approximately 10-fold increase as compared to UV-vis detection. This enabled the elimination of the concentration step described in the original method and allowed direct analysis of vaccine preparations. The method was qualified for linearity, range, limit of detection, limit of quantitation and precision. Overall, it was found to be linear over the range of 2.5-100 µg HA/mL for all subtypes examined. This range covered 50-150% of the concentration found for individual strains in seasonal influenza vaccines and in the pandemic H1N1 vaccine. The limit of detection and limit of quantitation for each subtype were found to be suitable for the method's intended purpose and compared well to values found by the single radial immunodiffusion (SRID). The repeatability of the method gave RSD values below 5% for both retention time and peak areas. As expected for intermediate precision, larger RSD values for peak area were obtained but were below 10% and deemed acceptable. The RP-HPLC results were compared to Western blot analysis using a HA universal antibody for a set of 15 monovalent A/California H1N1 preparations and showed good correlation. Similarly, the quantitative nature of the RP-HPLC method was assessed in relation to the SRID assay currently used for the determination of the HA content in bulk antigen and final vaccine preparations. Thus, for a series of 23 monovalent A/Brisbane/59/2007 H1N1 bulks, ranging between 12.7 and 15.9 µg HA/mL by SRID, the RP-HPLC values were found to be in very good agreement, ranging between 11.9 and 14.1 µg HA/mL (n=5) for five determinations carried out on 5 different days. During the 2009-10 H1N1 influenza pandemic the quantitative RP-HPLC method was used alongside several other test methods for the analysis of pandemic H1N1 vaccine preparations that included bulk antigen and final vaccines. The HA content of vaccines formulated at 15 or 30 µg/mL was measured by RP-HPLC and SRID and results showed that the HA content determined by RP-HPLC correlated well to that determined by SRID and to values determined by Western blot. Overall, the results provided further evidence of the usefulness of RP-HPLC for the detection and quantitation of the HA content once a reference standard has been established.

Narrative pedagogy and simulation: future directions for nursing education.

Narrative pedagogy has been developed over the last decade in nursing as a means of complementing a conventional content and competency driven pedagogy. It focuses attention on the human experience of health care by deriving shared meanings from interpretation of stories. This allows students to explore the different perspectives of those involved. The emotional experiences of participants can be understood, conventional wisdom challenged and new knowledge emerge as students work together to construct their learning. Individual stories are embedded within the narrative and teachers have successfully used literature and film as narratives to help them explore the meaning of health care with students. Modern technology has opened up a new range of electronic narratives such as virtual simulation. These are considered and rejected as devices for a health care narrative due to their dehumanized and unrealistic nature. However it is argued that a multimedia online simulation of a typical neighbourhood can achieve the goal of providing a suitable narrative. Human actors replace avatars and real world settings replace gaming environments as the stories of people in this community are related and used to support narrative pedagogy. An example of such a narrative developed jointly in the UK and Canada is discussed.