Classification system for primary care provider eConsults about medications for older adults with frailty.

BACKGROUND: Providing primary care for people with frailty can be challenging due to an increased risk of adverse outcomes and use of potentially inappropriate medications which may exacerbate characteristics of frailty. eConsult is a service where primary care providers can receive timely specialist advice for their patients through a secure web-based application. We aimed to develop a classification system to characterize medication-focused eConsult questions for older adults with frailty and assess its usability. METHODS: A classification system was developed and refined over three cycles of improvement through a cross-sectional study of 35 cases categorized as medication-focused from cases submitted in 2019 for patients aged 65 or older with frailty through the Champlain BASE eConsult service (Ontario, Canada). The final classification system was then applied to each case. RESULTS: The classification system contains 5 sections: (1) case descriptives; (2) intent and type of question; (3) medication recommendations and additional information in the response; (4) medication classification; and (5) potentially inappropriate medications. Among the 35 medication-focused cases, the most common specialties consulted were endocrinology (9 cases, 26%) and cardiology (5 cases, 14%). Medication histories were available for 29 cases (83%). Many patients were prescribed potentially inappropriate medications based on explicit tools (AGS Beers Criteria®, STOPPFall, Anticholinergic Cognitive Burden Scale, ThinkCascades) yet few consults inquired about these medications. CONCLUSION: A classification system to describe medication-related eConsult cases for patients experiencing frailty was developed and applied to 35 eConsult cases. It can be applied to more cases to identify professional development opportunities and enhancements for eConsult services.

Spacecraft sample collection and subsurface excavation of asteroid (101955) Bennu.

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

Application of 7T MRS to High-Grade Gliomas.

MRS, including single-voxel spectroscopy and MR spectroscopic imaging, captures metabolites in high-grade gliomas. Emerging evidence indicates that 7T MRS may be more sensitive to aberrant metabolic activity than lower-field strength MRS. However, the literature on the use of 7T MRS to visualize high-grade gliomas has not been summarized. We aimed to identify metabolic information provided by 7T MRS, optimal spectroscopic sequences, and areas for improvement in and new applications for 7T MRS. Literature was found on PubMed using "high-grade glioma," "malignant glioma," "glioblastoma," "anaplastic astrocytoma," "7T," "MR spectroscopy," and "MR spectroscopic imaging." 7T MRS offers higher SNR, modestly improved spatial resolution, and better resolution of overlapping resonances. 7T MRS also yields reduced Cramér-Rao lower bound values. These features help to quantify D-2-hydroxyglutarate in isocitrate dehydrogenase 1 and 2 gliomas and to isolate variable glutamate, increased glutamine, and increased glycine with higher sensitivity and specificity. 7T MRS may better characterize tumor infiltration and treatment effect in high-grade gliomas, though further study is necessary. 7T MRS will benefit from increased sample size; reductions in field inhomogeneity, specific absorption rate, and acquisition time; and advanced editing techniques. These findings suggest that 7T MRS may advance understanding of high-grade glioma metabolism, with reduced Cramér-Rao lower bound values and better measurement of smaller metabolite signals. Nevertheless, 7T is not widely used clinically, and technical improvements are necessary. 7T MRS isolates metabolites that may be valuable therapeutic targets in high-grade gliomas, potentially resulting in wider ranging neuro-oncologic applications.

Radium-223 in the Treatment of Metastatic Castrate-Resistant Prostate Cancer.

Background Radium 223 (Ra-223) has been successfully utilised for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods All men referred to our institution for Ra-223 from September 2016 to March 2019 were included. Patient demographics, treatments received, toxicities and outcomes were recorded. Overall survival (OS) and progression free survival (PFS) were analysed using the Kaplan-Meier method. Results Complete data was available for 54 men. Median age was 75 years (range 61-86 years). The median number of prior systemic treatments for mCRPC was 2 (range 0-4). Median ECOG performance status was 1 at the start of treatment and 2 at completion. The median number of Ra-223 cycles received was 4 with 37%(n=20) completing all 6 planned cycles. The most common treatment-related toxicity was fatigue seen in 52% of patients ( n=28). Improved pain scores were documented in 76% of men requiring opioid analgesia at the start of treatment. The median OS was 7 months. A good ECOG performance status, fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and chemotherapy naivety were associated with improved OS. Conclusions Ra-223 is a moderately well tolerated palliative treatment amongst Irish men with mCRPC.

Episodes of particle ejection from the surface of the active asteroid (101955) Bennu.

Active asteroids are those that show evidence of ongoing mass loss. We report repeated instances of particle ejection from the surface of (101955) Bennu, demonstrating that it is an active asteroid. The ejection events were imaged by the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) spacecraft. For the three largest observed events, we estimated the ejected particle velocities and sizes, event times, source regions, and energies. We also determined the trajectories and photometric properties of several gravitationally bound particles that orbited temporarily in the Bennu environment. We consider multiple hypotheses for the mechanisms that lead to particle ejection for the largest events, including rotational disruption, electrostatic lofting, ice sublimation, phyllosilicate dehydration, meteoroid impacts, thermal stress fracturing, and secondary impacts.

Denosumab utilization among older adults in Ontario: patient characteristics, persistence with therapy, and return to therapy after an extended gap.

We studied 46,797 older adults who initiated denosumab in Ontario, Canada. Patient characteristics remained relatively stable over time and aligned with public reimbursement restrictions. Almost half of patients persisted with therapy for at least 3 years. Fifty-nine percent of patients who discontinued denosumab returned to treatment within 3.6 years. INTRODUCTION: The purpose of this study was to describe the characteristics of patients who initiated denosumab and estimate persistence with therapy. METHODS: We identified older adults (aged ≥ 66 years) in Ontario who initiated denosumab between 2012/02 and 2015/03 and followed them to 2016/03. Patient characteristics were summarized using medical and pharmacy claims in the year before starting denosumab and osteoporosis drug use considered since 1996/10. Persistence with denosumab and return after discontinuation (> 90-day gap) were estimated using Kaplan-Meier curves. Analyses were stratified by community and long-term care (LTC) residence. RESULTS: We identified 46,797 patients (monthly mean = 1263, SD = 187); 97% female, 13% LTC. Community-dwelling patients had a higher prevalence of bone mineral density testing (62% vs. 5%), yet were younger (mean age 78.5 vs. 86.6 years) and had lower prevalence of hip fractures (3% vs. 10%) compared to LTC patients. Eighty-two percent of patients had used osteoporosis medications in the past; 99% of whom took an oral bisphosphonate. Persistence was similar between community-dwelling and LTC patients: 59% persisted ≥ 2 years, 48% ≥ 3 years, and 38% ≥ 4 years, yet a larger proportion of LTC patients returned to denosumab after discontinuation (76% vs. 57%). CONCLUSIONS: Denosumab utilization is increasing at a steady rate in Ontario. However, persistence remains a concern given the highly reversible pharmacokinetic profile of denosumab that results in a rapid increased fracture risk following discontinuation. Over 80% of patients had a history of oral bisphosphonate therapy, which may persist in bone despite discontinuing denosumab. Consequently, better understanding of denosumab safety and effectiveness among real-world users is important.

Next generation sequencing (NGS) to improve the diagnosis and management of patients with disorders of sex development (DSD).

Disorders of sex development (DSDs) are a diverse group of conditions where the chromosomal, gonadal or anatomical sex can be atypical. The highly heterogeneous nature of this group of conditions often makes determining a genetic diagnosis challenging. Prior to next generation sequencing (NGS) technologies, genetic diagnostic tests were only available for a few of the many DSD-associated genes, which consequently had to be tested sequentially. Genetic testing is key in establishing the diagnosis, allowing for personalised management of these patients. Pinpointing the molecular cause of a patient's DSD can significantly impact patient management by informing future development needs, altering management strategies and identifying correct inheritance pattern when counselling family members. We have developed a 30-gene NGS panel, designed to be used as a frontline test for all suspected cases of DSD (both 46,XX and 46,XY cases). We have confirmed a diagnosis in 25 of the 80 patients tested to date. Confirmed diagnoses were linked to mutations in AMH, AMHR2, AR, HSD17B3, HSD3B2, MAMLD1, NR5A1, SRD5A2 and WT1 which have resulted in changes to patient management. The minimum diagnostic yield for patients with 46,XY DSD is 25/73. In 34/80 patients, only benign or likely benign variants were identified, and in 21/80 patients only variants of uncertain significance (VOUS) were identified, resulting in a diagnosis not being confirmed in these individuals. Our data support previous studies that an NGS panel approach is a clinically useful and cost-effective frontline test for patients with DSDs.

Tubulocystic anomalies of the mesonephric duct associated with ipsilateral renal dysgenesis.

INTRODUCTION: Renal agenesis and multicystic dysplastic kidney (MCDK) are usually associated with either an absent or atretic ureter. Occasionally, these renal anomalies may be associated with a dilated tortuous ureter, ureterocele or other cystic malformation of mesonephric duct (MND) remnants. OBJECTIVES: The objective of this study was to identify and classify anatomical variants of tubulocystic remnants of the MND, with a secondary focus on natural history and management outcomes. PATIENTS AND METHODS: A retrospective cohort study of patients seen in the study institution between 2007 and 2014 with a tubulocystic abnormality of MND structures associated with either MCDK or renal agenesis was conducted. Medical imaging and progress notes were reviewed for all patients. Data collected included anatomical information, surgical intervention, histology and outcomes of both conservatively managed and surgically resected MND remnant structures. RESULTS: Nineteen patients were identified, 5 girls and 14 boys. Median age at presentation was 4.6 years. Anomalies of the MND occurred on the left in 9 patients and on the right in 10 patients. Mean follow-up was 3.4 years. Patients fell into 3 distinct anatomical groups: Type I, including orthotopic remnants corresponding to ureteric bud structures (ureter and trigone); Type II, including ectopic MND remnants of ureteric bud structures, and Type III, including complex remnants corresponding to MND structures other than those from ureteric bud (vas, epididymis and seminal vesicles). Anomalies of structures arising from urogenital sinus and paramesonephric ducts were also identified. Most patients were asymptomatic and successfully managed conservatively. Transvesical puncture of trigonal cysts provided effective decompression in 5 patients. Partial or complete MCDK regression was seen in 7 patients, whereas MND cystic anomalies did not regress spontaneously. DISCUSSION: When MND tubulocystic structures persist along with renal agenesis or MCDK, most arise from ureteric bud structures in an orthotopic position as a ureterocele with or without a blind-ending ureter-like structure. Less commonly, ureteric bud structures insert ectopically into the urogenital tract, or tubulocystic structures arising from the remainder of the MND occur. Embryogenesis of other urogenital structures may also be abnormal, and conditions such as Zinner syndrome and obstructed hemivagina and ipsilateral renal agenesis syndrome should be considered. CONCLUSIONS: Complications are uncommon, and surgical intervention should be limited to symptomatic patients. Remnants of metanephric blastema may involute, but MND remnants persist.

Deprescribing antihyperglycemic agents in older persons: evidence-based clinical practice guideline

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper, stop, or switch antihyperglycemic agents in older adults. METHODS: We focused on the highest level of evidence available and sought input from primary care professionals in guideline development, review, and endorsement processes. Seven clinicians (2 family physicians, 3 pharmacists, 1 nurse practitioner, and 1 endocrinologist) and a methodologist comprised the overall team; members disclosed conflicts of interest. We used a rigorous process, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, for guideline development. We conducted a systematic review to assess evidence for the benefits and harms of deprescribing antihyperglycemic agents. We performed a review of reviews of the harms of continued antihyperglycemic medication use, and narrative syntheses of patient preferences and resource implications. We used these syntheses and GRADE quality-of-evidence ratings to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. A decision-support algorithm was developed to accompany the guideline. RECOMMENDATIONS: We recommend deprescribing antihyperglycemic medications known to contribute to hypoglycemia in older adults at risk or in situations where antihyperglycemic medications might be causing other adverse effects, and individualizing targets and deprescribing accordingly for those who are frail, have dementia, or have a limited life expectancy. CONCLUSION: This guideline provides practical recommendations for making decisions about deprescribing antihyperglycemic agents. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Health service changes to address diabetes in pregnancy in a complex setting: perspectives of health professionals.

BACKGROUND: Australian Aboriginal and Torres Strait Islander women have high rates of gestational and pre-existing type 2 diabetes in pregnancy. The Northern Territory (NT) Diabetes in Pregnancy Partnership was established to enhance systems and services to improve health outcomes. It has three arms: a clinical register, developing models of care and a longitudinal birth cohort. This study used a process evaluation to report on health professional's perceptions of models of care and related quality improvement activities since the implementation of the Partnership. METHODS: Changes to models of care were documented according to goals and aims of the Partnership and reviewed annually by the Partnership Steering group. A 'systems assessment tool' was used to guide six focus groups (49 healthcare professionals). Transcripts were coded and analysed according to pre-identified themes of orientation and guidelines, education, communication, logistics and access, and information technology. RESULTS: Key improvements since implementation of the Partnership include: health professional relationships, communication and education; and integration of quality improvement activities. Focus groups with 49 health professionals provided in depth information about how these activities have impacted their practice and models of care for diabetes in pregnancy. Co-ordination of care was reported to have improved, however it was also identified as an opportunity for further development. Recommendations included a central care coordinator, better integration of information technology systems and ongoing comprehensive quality improvement processes. CONCLUSIONS: The Partnership has facilitated quality improvement through supporting the development of improved systems that enhance models of care. Persisting challenges exist for delivering care to a high risk population however improvements in formal processes and structures, as demonstrated in this work thus far, play an important role in work towards improving health outcomes.

E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271.

Multiple myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro. Moreover, an increase in the mRNA levels of genes involved in the generation of E-selectin ligands was associated with inferior progression-free survival in the CoMMpass study. In vivo, E-selectin ligand-enriched cells induced a more aggressive disease and were completely insensitive to Bortezomib. Importantly, this resistance could be reverted by co-administration of GMI-1271, a specific glycomimetic antagonist of E-selectin. Finally, we report that E-selectin ligand-bearing cells are present in primary MM samples from BM and peripheral blood with a higher proportion seen in relapsed patients. This study provides a rationale for targeting E-selectin receptor/ligand interactions to overcome MM metastasis and chemoresistance.

Cystometrogram appearance in PUV is reliably quantified by the shape,wall, reflux and diverticuli (SWRD) score, and presages the need for intervention.

OBJECTIVE: Radiological bladder abnormalities in boys with posterior urethral valves (PUV) are well recognised; however, the assessment is subjective. The shape, wall, reflux and diverticuli (SWRD) score objectively assesses shape, wall, reflux and diverticuli in a simple way. This study was undertaken to demonstrate that the SWRD score is reliable, reproducible and correlates with bladder outcome and videourodynamic (VUD) assessment in boys with PUV. MATERIALS AND METHODS: Three blinded assessors determined the SWRD scores of PUV bladders from cystometrograms taken during VUD from September 2012 to October 2013. The scores were correlated with clinical outcome and VUD pressure measurements. Data were given as median (interquartile range), non-parametric tests used as appropriate (Mann-Whitney U test, or Kruskall-Wallis) and P < 0.05 was taken as significant. RESULTS: A total of 55 boys with PUV underwent VUD assessment, for which 52 cystometrograms were available. The SWRD score for non-operative management was 1.0 (0.1-1.9) vs 2.0 (1.0-3.3) for operative intervention, P = 0.018 (Summary Figure). The SWRD score for compliant bladders was 1.1 (0.6-2.0) vs hypercompliant 1.7 (0.5-2.8) vs non-compliant 3.3 (2.8-5.0), Kruskall-Wallis P = 0.011. The hostile detrusor overactivity (DO) bladders (Pdet >40 cmH2O) had a SWRD score of 2.0 (1.3-3.7) vs 1.0 (0.5-2.5) for low-pressure DO bladders, P < 0.05. DISCUSSION: In this series of patients, increasingly distorted bladder shape was seen to be associated with poor bladder dynamics on VUD. Patients with poorly compliant bladders had a significantly higher SWRD score than normal or megacystis patients. Severe DO was also significantly associated with a high SWRD score. Therefore, the radiological appearance of a hostile bladder represented a marker for high intravesical pressure. VUR and bladder diverticuli may lead to spurious pressure measurements during VUD; however, the SWRD score provided an independent mechanism with which to objectively assess these patients, even in the presence of gross VUR. CONCLUSIONS: The SWRD score is a simple and objective scoring system for the radiological abnormalities of PUV bladders. It correlates with clinical outcome and VUD assessment of compliance and DO, but is independent of pressure measurements and so not confounded by VUR acting as a 'pop-off' mechanism.

British Association of Paediatric Urologists consensus statement on the management of the neuropathic bladder.

INTRODUCTION: A large number of children with spina bifida develop a neuropathic bladder and this group of patients still forms the largest group of children who require urological management. Although there are published guidelines on the management of the neuropathic bladder, they are not specific to children. It is unsurprising, therefore, that the initial investigation, assessment and management of children with spina bifida vary considerably. The 2014 British Association of Paediatric Urologists (BAPU) meeting was devoted to the management of the neuropathic bladder. The aim was to produce a consensus on the appropriate investigation and management of a child with a neuropathic bladder. METHODS AND MATERIALS: A questionnaire was devised and the members were polled on their current practice. Six paediatric urology fellows presented an evidence-based literature review on different aspects of the neuropathic bladder. At the end of the session, the members of the organisation present were polled again using the same questions. RESULTS: The BAPU felt that the use of urodynamics in the neuropathic bladder should be selectively determined by clinical parameters. Regarding CIC, the group was evenly split between universal use or only when poor emptying was established. Oxybutinin was the first-line anticholinergic of choice. Most paediatric urologists routinely used Botox and were happy to use it repeatedly. The surgical intervention most frequently employed was determined to be an ileocystoplasty, with most surgeons deferring the need for surveillance cystoscopy until at least 10 years after surgery. CONCLUSION: It was felt that a consensus statement is not a guideline or a way to establish best practice; however, it serves as a way of surveying current practice and providing a benchmark for clinicians involved in the management of these patients.

Nadir creatinine in posterior urethral valves: How high is low enough?

INTRODUCTION: Large retrospective studies of people with posterior urethral valves (PUV) have reported chronic renal insufficiency (CRI) in up to one third of the participants and end-stage renal failure in up to one quarter of them. Nadir creatinine (lowest creatinine during the first year following diagnosis) is the recognised prognostic indicator for renal outcome in PUV, the most commonly used cut-off being 1 mg/dl (88.4 umol/l). OBJECTIVE: To conduct a statistical analysis of nadir creatinine in PUV patients in order to identify the optimal cut-off level as a prognostic indicator for CRI. STUDY DESIGN: Patients treated by endoscopic valve ablation at the present institution between 1993 and 2004 were reviewed. Chronic renal insufficiency was defined as CKD2 or higher. Statistical methods included receiver operating characteristic (ROC) curve analysis, Fisher exact test and diagnostic utility tests. Statistical significance was defined as P < 0.05. RESULTS AND DISCUSSION: Nadir creatinine was identified in 96 patients. The median follow-up was 9.4 (IQR 7.0, 13.4) years. A total of 29 (30.2%) patients developed CRI, with nine (9.4%) reaching end-stage renal failure. On ROC analysis, Nadir creatinine was highly prognostic for future CRI, with an Area Under the Curve of 0.887 (P < 0.001). Renal insufficiency occurred in all 10 (100%) patients with nadir creatinine >88.4 umol/l compared with 19 of 86 (22.2%) patients with lower nadir creatinine (P < 0.001). As a test for future CRI, a nadir creatinine cut-off of 88.4 umol/l gave a specificity of 100%, but poor sensitivity of 34.5%. Lowering the cut-off to 75 umol/l resulted in improvement in all diagnostic utility tests (Table). All 14 (100%) patients with nadir creatinine >75 umol/l developed CRI, compared with 15 of 82 (18.3%) patients with lower nadir creatinine (P < 0.001). Sensitivity only approached 95% at 35 umol/l, at which level specificity was low (Table). Two out of 36 (5.6%) patients with nadir creatinine <35 umol/l developed CRI. Multivariate analysis found recurrent UTI (OR 4.733; CI 1.297-17.280) and nadir creatinine >75 umol/l (OR 48.988; CI 4.9-490.11) to be independent risk factors for progression to CRI. Using cut-off values of 35 umol/l and 75 umol/l, patients can be stratified into low-, intermediate- and high-risk groups, with development of CRI in 5.3%, 28.3% and 100%, respectively (P <0.001). The stage of CKD was higher in higher risk groups. CONCLUSION: Patients with nadir creatinine >75 umol/l (0.85 mg/dl) should be considered at high risk for CRI, while patients with nadir creatinine ≤35 umol/l (0.4 mg/dl) should be considered low risk. Patients with nadir creatinine between these two values have an intermediate risk of CRI.

A randomised feasibility study to assess a novel strategy to rationalise fluid in patients after cardiac surgery.

BACKGROUND: After cardiac surgery, patients receive large amounts of fluid in the Intensive Care Unit (ICU). We plan to conduct a multi-centre randomised controlled trial, of a conservative fluid regime, in patients after cardiac surgery, and have reported results of a feasibility study that evaluated efficacy and safety of the proposed regime. METHODS: After ethical approval, a single-centre, prospectively randomised interventional study was undertaken. Participants were randomised to either usual care, or to a protocolised algorithm, utilising stroke volume variation, to guide fluid administration to patients who were deemed to have inadequate cardiac output and were likely to be volume responsive. The study protocol lasted from ICU admission to de-sedation or 24 h, whichever occurred first. RESULTS: We randomised 144 subjects over 9 months. Less bolus fluid and less total overall fluid volume was administered in the intervention group (median (IQR) 1620 ml (500-3410) and 2525 ml (1440-5250; P<0.001), compared with the usual care group (2050 ml (910-4280) and 2980 ml (2070-6580; P=0.001), from ICU admission to extubation. There was no significant difference in incidence of acute kidney injury or the average amount of fluid administered to the usual care group at the beginning compared with the end of the study. CONCLUSION: It is both possible and safe to achieve a significant reduction in the amount of fluid administered to patients, allocated to a conservative fluid protocol. These results suggest that a planned multi-centre study is both justified and feasible. CLINICAL TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry www.anzctr.org.au (ACTRN12612000754842).

Genetic diversity and associated pathology of rhabdovirus infections in farmed and wild perch Perca fluviatilis in Ireland.

Rhabdovirus infections are an emerging problem for both wild and farmed freshwater fish in Northern Europe. In October 2005, a clinical outbreak with an approximate mortality rate of 40% occurred in a single batch of juvenile perch on a farm in the Republic of Ireland. Clinical signs developed slowly and were consistent with a perch rhabdovirus infection: signs included haemorrhages at the base of the fins and apparent impairment of the central nervous system (manifested as loss of equilibrium and erratic swimming behaviour). Studies suggest that the infected fish originated from a hatchery within the country which relied on wild fish broodstock to supplement the production of perch juveniles. A related rhabdovirus was subsequently isolated from this hatchery. Virus isolation studies have shown that rhabdoviruses were often isolated from wild fish in the vicinity of the hatchery between 1993 and 2005. All isolates were analysed using a generic primer set specific for the L gene of fish vesiculotype viruses. Phylogenetic analysis revealed that all isolates recovered from perch clustered together with the European lake trout rhabdovirus (903/87) of the genus Perhabdovirus. In addition to this, anguillid rhabdovirus was isolated from eel, and the partial L-gene sequence of a previously reported isolate from tench clustered with the pike fry rhabdoviruses, in the genus Sprivivirus.

Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive" mediastinal nodes in the staging of non-small cell lung cancer.

INTRODUCTION: The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC). METHODS: This was a retrospective, interdisciplinary, per-node analysis study. We included patients with NSCLC and mediastinal nodes with an SUV max in the range of 2.5-4.0 on PET-CT. We hypothesized that the greatest number of false positive cases would occur in this cohort of patients. RESULTS: A total of 92 mediastinal lymph nodes were analyzed in 44 patients. Mediastinal disease (N2/N3) was histologically confirmed in 15 of 44 patients and in 34 of 92 lymph nodes; positive predictive value of 37% and false positive rate of 63%. Lymph node SUV max, tumor size, ratio of node SUV max to tumor SUV max (SUVn/SUVp), and ratio of node SUV max to node size (SUV n/SADn) were significantly higher in true positive cases. Using a threshold of 0.3 for SUV node/tumor and 3 for SUV node/size yielded sensitivities of 91% and 71% and specificities of 71% and 69% respectively for the detection of mediastinal disease. Using both ratios in combination resulted in a sensitivity of 65% and a specificity of 88%. Concurrent benign lung disease was observed significantly more frequently in false-positive cases. CONCLUSION: SUVn/SUVpt and SUVn/SADn may be complimentary to conventional visual interpretation and SUV max measurement in the assessment of mediastinal disease in patients with NSCLC.

A comparison of pre-operative nerve stimulator-guided femoral nerve block and fascia iliaca compartment block in patients with a femoral neck fracture.

We undertook a randomised, controlled trial to compare the analgesic efficacy and opioid sparing effect of nerve stimulator-guided femoral nerve block with fascia iliaca compartment block in patients awaiting surgery for fractured neck of femur. Ten-centimetre visual analogue pain scores were measured before and 2 h after the block and opioid consumption was recorded in the 12-h period after the block. One hundred and ten patients were randomly assigned. Femoral nerve block provided superior pre-operative analgesia for fractured neck of femur compared with fascia iliaca compartment block. The difference in the mean reduction of pain score after the block was 0.9 (95% CI 0-1.8); p = 0.047. Patients receiving a femoral nerve block required less morphine after the block than those receiving fascia iliaca compartment block (p = 0.041).

Automated image analysis of Euglena gracilis Klebs (Euglenophyta) for measuring sublethal effects of three model contaminants.

The short-term impacts of atrazine (herbicide), tributyltin (organometal) and copper on the behaviour of Euglena gracilis Klebs (Euglenophyta) were assessed. First, the ECOTOX automated image analysis system was used, which measured swimming velocity, cell shape, percentage of cells swimming upwards, and randomness of swimming. Next, visual observation by microscopy was used to measure percentage of cell motility and cell shape. Behavioural changes can be used as an indicator of stress in less than 24 h, potentially making them suitable for inclusion in early-warning systems for water quality. Findings indicate that E. gracilis is a very sensitive organism to copper, showing inhibition of motility with visual observation at 0.8 µmol/L within 1 h. The image analysis system was in general less sensitive than visual observation for detecting behavioural changes after incubation in copper. In contrast, after exposure to organic contaminants atrazine and tributyltin, the ECOTOX system detected small changes in the number of cells swimming upwards (antigravitactic behaviour) at higher concentrations.

Health-related quality of life in patients reliant upon mitrofanoff catheterisation.

OBJECTIVE: Aim of the study was determine health care outcomes from the patients' perspective in patients reliant on Mitrofanoff catheterisation for bladder emptying. SUBJECTS/PATIENTS: Patients over the age of 16 dependent on Mitrofanoff catheterisation for bladder emptying were asked to complete a health care outcome questionnaire, the SF-36 (®) Health Survey v2. Quality of life measures for 8 health concepts were compared against published data for the normal population. RESULTS: Out of a total of 25 patients who were eligible for enrolment into our study, we were able to contact 19 patients. The norm-based score for Physical Functioning (PF=50.4), Role Physical (RP=53.8), Bodily Pain (BP=55.6), Vitality (VT=56.9), Social Functioning (SF=51.5), Role Emotional (RE=52.2), and Mental Health (MH=54.6) were all higher than those reported within the normal population (normal=50.0). Physical and mental component summary measures were higher than in the normal population. When compared against age-matched norms our patient group scored higher than the normal population for all measures except Physical Functioning (50.4 vs. 53.4) and physical component summary (51.9 vs. 53.5). The self-reported scores for Vitality, Mental Health and the mental component summary were all statistically significantly better than those seen in the age-matched control population (p<0.01). CONCLUSIONS: Quality of life in patients dependent on Mitrofanoff catheterisation for bladder emptying is good. The SF-36 measures 8 major health care outcomes and in our patients these measures of health were similar to those seen in the general population, rather than the poorer outcomes reported in patients with other chronic medical conditions.