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The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease. NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

BACKGROUND CONTEXT Outcomes of treatment in care of patients with spinal disorders are directly related to patient selection and treatment indications. However, for many disorders, there is absence of consensus for precise indications. With the increasing emphasis on quality and value in spine care, it is essential that treatment recommendations and decisions are optimized. PURPOSE The purpose of the North American Spine Society Appropriate Use Criteria was to determine the appropriate (ie reasonable) multidisciplinary treatment recommendations for patients with degenerative spondylolisthesis across a spectrum of more common clinical scenarios. STUDY DESIGN A Modified Delphi process was used. METHODS The methodology was based on the Appropriate Use Criteria development process established by the Research AND Development Corporation. The topic of degenerative spondylolisthesis was selected by the committee, key modifiers determined, and consensus reached on standard definitions. A literature search and evidence analysis were completed by one work group simultaneously as scenarios were written, reviewed, and finalized by another work group. A separate multidisciplinary rating group was assembled. Based on the literature, provider experience, and group discussion, each scenario was scored on a nine-point scale on two separate occasions, once without discussion and then a second time following discussion based on the initial responses. The median rating for each scenario was then used to determine if indications were rarely appropriate (1 – 3), uncertain (4-6), or appropriate (7-9). Consensus was not mandatory. RESULTS There were 131 discrete scenarios. These addressed questions on bone grafting, imaging, mechanical instability, radiculopathy with or without neurological deficits, obesity, and yellow flags consisting of psychosocial and medical comorbidities. For most of these, appropriateness was established for physical therapy, injections, and various forms of surgical intervention. The diagnosis of spondylolisthesis should be determined by an upright x-ray. Scenarios pertaining to bone grafting suggested that patients should quit smoking prior to surgery, and that use of BMP should be reserved for patients who had risk factors for non-union. Across all clinical scenarios, physical therapy (PT) had an adjusted mean of 7.66, epidural steroid injections 5.76, and surgery 4.52. Physical therapy was appropriate in most scenarios, and most appropriate in patients with back pain and no neurological deficits. Epidural steroid injections were most appropriate in patients with radiculopathy. Surgery was generally more appropriate for patients with neurological deficits, higher disability scores, and dynamic spondylolisthesis. Mechanical back pain and presence of yellow flags tended to be less appropriate, and obesity in general had relatively little influence on decision making. Decompression alone was more strongly considered in the presence of static versus dynamic spondylolisthesis. On average, posterior fusion with or without interbody fusion was similarly appropriate, and generally more appropriate than stand-alone interbody fusion which was in turn more appropriate than interspinous spacers. CONCLUSIONS Multidisciplinary appropriate treatment criteria were generated based on the Research AND Development methodology. While there were consistent and significant differences between surgeons and non-surgeons, these differences were generally very small. This document provides comprehensive evidence-based recommendations for evaluation and treatment of degenerative spondylolisthesis. The document in its entirety will be found on the North American Spine Society website ( https://www.spine.org/Research-Clinical-Care/Quality-Improvement/Appropriate-Use-Criteria) .

Biodiversity underlies ecosystem resilience, ecosystem function, sustainable economies, and human well-being. Understanding how biodiversity sustains ecosystems under anthropogenic stressors and global environmental change will require new ways of deriving and applying biodiversity data. A major challenge is that biodiversity data and knowledge are scattered, biased, collected with numerous methods, and stored in inconsistent ways. The Group on Earth Observations Biodiversity Observation Network (GEO BON) has developed the Essential Biodiversity Variables (EBVs) as fundamental metrics to help aggregate, harmonize, and interpret biodiversity observation data from diverse sources. Mapping and analyzing EBVs can help to evaluate how aspects of biodiversity are distributed geographically and how they change over time. EBVs are also intended to serve as inputs and validation to forecast the status and trends of biodiversity, and to support policy and decision making. Here, we assess the feasibility of implementing Genetic Composition EBVs (Genetic EBVs), which are metrics of within-species genetic variation. We review and bring together numerous areas of the field of genetics and evaluate how each contributes to global and regional genetic biodiversity monitoring with respect to theory, sampling logistics, metadata, archiving, data aggregation, modeling, and technological advances. We propose four Genetic EBVs: (i) Genetic Diversity; (ii) Genetic Differentiation; (iii) Inbreeding; and (iv) Effective Population Size (Ne ). We rank Genetic EBVs according to their relevance, sensitivity to change, generalizability, scalability, feasibility and data availability. We outline the workflow for generating genetic data underlying the Genetic EBVs, and review advances and needs in archiving genetic composition data and metadata. We discuss how Genetic EBVs can be operationalized by visualizing EBVs in space and time across species and by forecasting Genetic EBVs beyond current observations using various modeling approaches. Our review then explores challenges of aggregation, standardization, and costs of operationalizing the Genetic EBVs, as well as future directions and opportunities to maximize their uptake globally in research and policy. The collection, annotation, and availability of genetic data has made major advances in the past decade, each of which contributes to the practical and standardized framework for large-scale genetic observation reporting. Rapid advances in DNA sequencing technology present new opportunities, but also challenges for operationalizing Genetic EBVs for biodiversity monitoring regionally and globally. With these advances, genetic composition monitoring is starting to be integrated into global conservation policy, which can help support the foundation of all biodiversity and species' long-term persistence in the face of environmental change. We conclude with a summary of concrete steps for researchers and policy makers for advancing operationalization of Genetic EBVs. The technical and analytical foundations of Genetic EBVs are well developed, and conservation practitioners should anticipate their increasing application as efforts emerge to scale up genetic biodiversity monitoring regionally and globally. ispartof: BIOLOGICAL REVIEWS vol:97 issue:4 pages:1511-1538 ispartof: location:England status: published

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

TGF-β is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-β blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-β type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer.This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA-IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0-2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/mBetween Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred.The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials.Eli Lilly via ExIST program, The Providence Foundation.

Objective The T-cell receptor β constant region 1 (TRBC1) antibody can identify T-cell clonality and distinguish pathological from normal T cells. This study aims to establish optimal cutpoints for establishing monotypia and validate the diagnostic abilities of the TRBC1 antibody when used as a reflex test in conjunction with an existing T-cell antibody panel. Materials and Methods We used 46 normal peripheral blood specimens and examined 8 patients with reactive lymphoproliferations to determine the normal biological range of TRBC1 on CD4+ and CD8+ T cells. We also evaluated 43 patient specimens that were submitted for investigation of a lymphoproliferative disorder for CD2/CD3/CD4/CD5/CD7/CD8/CD16/CD26/CD45/CD56/TCR αβ/TCR γδ, along with TRBC1 expression. The results were compared to TCR gene rearrangement patterns using polymerase chain reaction (PCR) analysis. Results Statistical analysis established differing cutoff points for establishing monotypia dependent on restricted TRBC1 or TRBC2 usage. Direct comparison with molecular analysis indicated that no specimen identified with the restricted expression of TRBC1 was reported as polyclonal by PCR with a concordance rate of 97% between a clonal PCR result and monotypic TRBC1 expression. Conclusion Incorporation of the TRBC1 antibody using statistically derived cutoff points in a reflex setting for the evaluation of a suspected T-cell neoplasm improves the identification of clonal T-cell populations by flow cytometry and correlates well with molecular methods.

Background Adult neurosurgery in Ireland is carried out in two specialist centres, attached to only two medical schools. This leaves four Irish medical schools with no formal clinical attachment in neurosurgery. We organised a student neurosurgical conference to increase exposure to neurosurgical topics and to evaluate student's experience of undergraduate neurosurgical education. Methods The conference was organised by students from two Irish Universities with assistance from the National Neurosurgical Centre. It was open to students from all medical students in Ireland. Attendees were invited to complete a questionnaire before and after the conference. Questions were either yes or no answer or responses on a Likert scale. Results 95 students attended and all medical schools in Ireland were represented. 22% of attendees have received neurosurgical teaching during their medical education, while only 12% had a clinical rotation in neurosurgery. 40% of students are in a medical school attached to a hospital that performs neurosurgery. 54% of attendees disagreed or strongly disagreed that their medical education has comprehensively covered neurosurgical topics. 92% agreed or strongly agreed that they would like more teaching or clinical exposure in neurosurgery. 96% would attend future neurological study days. Conclusions Undergraduate neurosurgical education in Ireland varies between Irish medical schools. Many students reported their medical education has not adequately covered neurosurgical topics and that they would like more exposure to neurosurgical teaching and clinical attachments. Nearly all students reported they would attend future neurosurgical student conferences and this may be one method of increasing exposure to neurosurgery as a medical student.

The putatively positive association between host genetic diversity and the ability to defend against pathogens has long attracted the attention of evolutionary biologists. Chytridiomycosis, a disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), has emerged in recent decades as a cause of dramatic declines and extinctions across the amphibian clade. Bd susceptibility can vary widely across populations of the same species, but the relationship between standing genetic diversity and susceptibility has remained notably underexplored so far. Here, we focus on a putatively Bd-naive system of two mainland and two island populations of the common toad (Bufo bufo) at the edge of the species’ range, and use controlled infection experiments and dd-RAD sequencing of >10,000 SNPs across 95 individuals to characterise the role of host population identity, genetic variation and individual body mass in mediating host response to the pathogen. We found strong genetic differentiation between populations and marked variation in their susceptibility to Bd. This variation was not, however, governed by isolation-mediated genetic erosion, and individual heterozygosity was even found to be negatively correlated with survival. Individual survival during infection experiments was strongly positively related to body mass, which itself was unrelated to population of origin or heterozygosity. Our findings underscore the general importance of context-dependency when assessing the role of host genetic variation for the ability of defence against pathogens.

Assessments in medical education, with consequent decisions about performance and competence, have both a profound and far-reaching impact on students and their future careers. Physicians who make decisions about students must be confident that these decisions are based on objective, valid and reliable evidence and are thus fair. An increasing use of psychometrics has aimed to minimise measurement bias as a major threat to fairness in testing. Currently, there is substantial literature on psychometric methods and their applications, ranging from basic to advanced, outlining how assessment providers can improve their exams to make them fairer and minimise the errors attached to assessments. Understanding the mathematical models of some of these methods may be difficult for some assessment providers, and in particular clinicians. This guide requires no prior knowledge of mathematics and describes some of the key methods used to improve and develop assessments; essential for those involved in interpreting assessment results. This article aligns each method to the Standards for educational and psychological testing framework, recognised as the gold standard for testing guidance since the 1960s. This helps the reader develop a deeper understanding of how assessors provide evidence for reliability and validity with consideration to test construction, evaluation, fairness, application, and consequences, and provides a platform to better understand the literature in regards other more complex psychometric concepts that are not specifically covered in this article.

Youth accessing mental health care often experience a disruption in care as they attempt to transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS). Few studies have evaluated interventions seeking to improve the experience and outcomes of CAMHS-AMHS transitions, in part due to lack of consensus on what constitutes best practices in intervention success. As such, the aim of this study was to engage patients, caregivers, and clinicians to prioritize core components of successful CAMHS-AMHS transitions which can be used in the design or evaluation of transition interventions. As such, a Delphi study was conducted to determine core components of successful CAMHS-AMHS transitions. Guided by the principles of patient-oriented research, three balanced expert panels consisting of youth, caregivers, and clinicians ranked and provided feedback on the importance and feasibility of core components of CAMHS-AMHS transitions. Components endorsed as feasible or important with ≥ 70% agreement from any panel moved to the next round. As a result, a list of 26 core components of CAMHS-AMHS transitions has been refined which can be used in the design, implementation, or evaluation of interventions intended to improve transition experiences and outcomes for youth in mental health care. Youth and families were engaged in an expert advisory role throughout the research process, contributing their important perspectives to the design and implementation of this study, as well as interpretation of the findings.

We assessed for change in the number of admissions, demographics, mechanism, severity, operative management, length of stay, and in-hospital mortality of Traumatic Brain Injury (TBI) in patients admitted to a Neurosurgical Unit (NSU) in the Republic of Ireland in 2017 compared to 25 years previously.We performed a retrospective cohort study of TBI admissions during 2017 and compared the results with a prospective cohort study covering a one-year period across 1992 and 1993.In 2017, 184 patients (5.78 per 100,000) were admitted, compared to 225 in 1992/1993 (7.31 per 100,000). Mean age increased by 8.5 years. The contribution of road traffic collisions (RTCs) decreased by 62% while sports injuries increased by 300%, led by soccer. Falls replaced RTCs as the leading mechanism of injury. We report a decrease in severe injuries (GCS≤8) of 52% while mild injuries (GCS≥13) increased by 58%. The number undergoing neurosurgery remained comparable (2017: 55%, 1992/1993: 48%), as did in-hospital mortality (13%, 16%). Mean length of stay decreased by four days.There has been a sizable change in the landscape of TBI as seen in the Republic of Ireland's national NSU including in demographics, mechanism of injury, and injury severity.

Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled. Eighteen (18/52; 34.6%) patients reached MRD-negative CR after FCR4 and 29/52 (55.8%) were MRD-negative CR at end of treatment (EOT). Median TTF was 71.1 months (95% CI 61.3-84.1 months), with median overall survival not reached. Mutated immunoglobulin heavy chain gene rearrangements (IGHV) were associated with early MRD-negative remissions, translating into prolonged TTF. Unmutated-IGHV, mutated-SF3B1 and mutated-NOTCH1 were associated with shortened TTF. No TTF difference was observed between patients in MRD-negative CR after four versus six cycles (82.2 versus 85.3 months, p = .6306). Abbreviated FCR therapy is effective for patients achieving early MRD-negative remissions. Interim MRD assessment assists in personalizing therapy and reducing chemotherapy-associated toxicity.

Biclonal lymphoid disorders, when two distinct lymphoproliferative disorders (LPD) co-exist, are rare (incidence of 1.4%) and associated with a poor prognosis. NOTCH1 mutations occur in 10% of CLL at diagnosis, associated with a short disease-free interval and increased risk of Richter's transformation. We hypothesised that the incidence of NOTCH1 mutations in CLL with a second LPD may be increased, because the mutation occurs early in leukaemogenesis, permitting clonal divergence.We identified 19 patients with biclonal LPD at diagnosis: 11 with CLL and a second LPD (group A) and 8 with a second distinct CLL (group B). NOTCH1 mutation analysis was performed and clinical outcome investigated.Ten of 19 (52%) were NOTCH1 mutated: 5 in group A (45%) and 5 in group B (62.5%) with a favourable clinical outcome observed among this cohort with 28.7 (range 1-99) months of follow-up.In conclusion, we identified a significant (52%) incidence of NOTCH1 mutations in CLL in the context of biclonal LPD, associated with an indolent clinical course.

Having used the medical audit form (MAF) on Op TRENTON 4 in South Sudan,[1][1] we would like to raise awareness of this project among your readership and to commend its usefulness. The MAF was developed in preparation for Op GRITROCK with the aim for future clinicians to be able to access details

© FEMS 2017. All rights reserved. Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host-microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology.

Introduction Among youth, the prevalence of mental health and addiction (MHA) disorders is roughly 20%, yet youth are challenged to access evidence-based services in a timely fashion. To address MHA system gaps, this study tests the benefits of an Integrated Collaborative Care Team (ICCT) model for youth with MHA challenges. A rapid, stepped-care approach geared to need in a youth-friendly environment is expected to result in better youth MHA outcomes. Moreover, the ICCT approach is expected to decrease service wait-times, be more youth-friendly and family-friendly, and be more cost-effective, providing substantial public health benefits. Methods and analysis In partnership with four community agencies, four adolescent psychiatry hospital departments, youth and family members with lived experience of MHA service use, and other stakeholders, we have developed an innovative model of collaborative, community-based service provision involving rapid access to needs-based MHA services. A total of 500 youth presenting for hospital-based, outpatient psychiatric service will be randomised to ICCT services or hospital-based treatment as usual, following a pragmatic randomised controlled trial design. The primary outcome variable will be the youth9s functioning, assessed at intake, 6 months and 12 months. Secondary outcomes will include clinical change, youth/family satisfaction and perception of care, empowerment, engagement and the incremental cost-effectiveness ratio (ICER). Intent-to-treat analyses will be used on repeated-measures data, along with cost-effectiveness and cost-utility analyses, to determine intervention effectiveness. Ethics and dissemination Research Ethics Board approval has been received from the Centre for Addiction and Mental Health, as well as institutional ethical approval from participating community sites. This study will be conducted according to Good Clinical Practice guidelines. Participants will provide informed consent prior to study participation and data confidentiality will be ensured. A data safety monitoring panel will monitor the study. Results will be disseminated through community and peer-reviewed academic channels. Trial registration number Clinicaltrials.gov NCT02836080.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of bloodstream infection (BSI), which is declining in many countries, including Ireland. However, it also causes other invasive infections, such as meningitis in neurosurgical patients. It is unclear whether the decline in MRSA BSI is reflected in other invasive infections and in specialist units.To investigate trends in the incidence of MRSA invasive infection in a national neurosurgical centre over a 10-year period.A retrospective review of neurosurgical patients with MRSA recovered from sterile sites and indicating invasive infection, according to internationally agreed definitions was conducted between January 2006 and December 2015. Rates per 10,000 bed days used (BDU) and neurosurgical bed days used (NBDU) were calculated and trends were analysed.Forty-four cases of invasive MRSA infection were identified over the study period. The majority were BSI (26, 59%) followed by ventriculitis (8, 18%). Invasive MRSA infections declined significantly from 0.52 per 10,000 BDU (or 4.65 per 10,000 NBU) in 2006 to 0.22 per 10,000 BDU (or 2.04 per 10,000 NBDU) in 2015, p .01, despite an increase in neurosurgical clinical activity. Half of the infections occurred in patients with no previous history of MRSA colonisation/infection. The mean length-of-stay for neurosurgical patients with invasive MRSA infections was 67 days (median 32.5 days), significantly greater for other neurosurgical patients (p .01).There has been a significant decrease in invasive MRSA infections in neurosurgical patients, reflecting national and international trends for MRSA BSI. This indicates that infection prevention and control measures have been effective in reducing invasive MRSA infections overall, thus contributing to improved patient care.

BackgroundNoninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both ventilation and adherence. We aimed to identify factors associated with effective initiation and ongoing use of NIV in ALS to develop evidence-based guidance and identify areas for further research.MethodsWe searched 11 electronic databases (January 1998 to May 2018) for all types of quantitative and qualitative studies. Supplementary grey literature searches were conducted. Records were screened against eligibility criteria, data were extracted from included studies and risk of bias was assessed. We present findings using a narrative synthesis.ResultsWe screened 2430 unique records and included 52 quantitative and six qualitative papers. Factors reported to be associated with NIV optimisation included coordinated multidisciplinary care, place of initiation, selection of interfaces, ventilator modes and settings appropriate for the individual patient, and adequate secretion management. The literature indicated that patients with significant bulbar dysfunction can still derive considerable benefit from NIV if their needs are met. Research emphasises that obstructive airway events, mask leak and uncontrolled secretions should be addressed by adjustments to the interface and machine settings, and the concomitant use of cough augmentation.ConclusionThis review highlights that NIV optimisation requires an individualised approach to respiratory management tailored to the differing needs of each patient. Ultimately, this should lead to improved survival and quality of life. This review expands on recommendations in current international guidelines for NIV use in ALS and identifies areas for future research.

New efforts and requirements to deposit data in research repositories are necessary to protect privacy interests and comply with the European Union's General Data Protection Regulation. The authors...

You have recently been appointed to be the medical director of an ambulatory surgical center. This center focuses on interventional spine procedures and is used by several independent physician practices in the community. The manager of the center approaches you regarding medication options at the center. Several physicians in the group are requesting that she reorder preservative-free betamethasone phosphate from a compounding pharmacy. They believe strongly that this corticosteroid formulation has the distinct advantage of containing neither particulates nor preservative but is not available from a commercial pharmacy. In contrast, the commercially available form of betamethasone (Celestone Soluspan [Schering Corp, Kenilworth, NJ]), both contains a preservative and is a particulate corticosteroid due to the inclusion of betamethasone acetate in its formulation. The manager of the center is aware of the recent meningitis outbreak and is concerned that allowing any medications from compounding pharmacies is an unacceptable risk to patients. She also believes that using a compounding pharmacy in this setting may be a medicolegal liability to the surgical center. David O’Brien, MD, will argue that physicians should have the ability to use compounding pharmacies and Isaac Cohen, MD, will argue that compounding pharmacies should not be used. Please note the views expressed in this article are for educational purposes only and do not constitute a personal endorsement or necessarily reflect the current practice patterns of the discussants. They also are not intended to establish the standard of care.

Chiari I malformation may be treated with foramen magnum decompression (FMD). We aim to describe the symptoms with which patients initially present, and to determine the number and type of complications occurring after FMD for Chiari I malformation.Retrospective review of medical records for patients who had FMD performed for Chiari I malformation between January 2009 and December 2011. Post-operative outcomes were recorded and analysed. Patient demographic details and other relevant medical conditions were also noted.Between January 2009 and December 2011, 54 FMDs were performed for Chiari I malformation. Among them, 40(74%) patients were female and 14 patients (26%) were male. The majority of patients (42.6%) were aged 16-39 years and 24.07% of patients were children aged16 years. A total of 30(55.6%) patients had documented evidence of a syrinx pre-operatively. 18(33.3%) patients developed complications. Nine of these developed multiple complications while nine had a single problem. One mortality was reported. Ten (18.5%) patients developed hydrocephalus requiring shunting. Two patients developed subdural collections requiring evacuation associated with hydrocephalus. Six (11.1%) patients developed post-operative infections: two CNS infections; one wound infection; and three other infections.FMD for Chiari I malformation is a procedure which carries risk. In particular, the risk of developing post-operative hydrocephalus requiring permanent shunting is relatively high. ICP monitoring prior to FMD may be required to definitively rule out raised intracranial pressure.

Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.

Combined Fludarabine and Cyclophosphamide is now standard first-line therapy in chronic lymphocytic leukaemia (CLL) and the addition of Rituximab improves outcome. We adopted a modified Fludarabine, Cyclophosphamide and Rituximab (FCR) protocol in treating 39 patients (median age 57 years) with progressive or advanced CLL. Depending on CR, treatment was given for four or six cycles. Twenty-six patients were treatment naive and 13 were pre-treated. Twelve patients had progressive Binet stage A, 16 stage B and 11 stage C disease. The overall response rate (ORR) was 100%, with 75% achieving CR. Neutropenia was the major toxicity in 71/187 (38%) of the cycles. There were five deaths, two from infection and three from progressive disease. Twenty-six of 31 patients have maintained their post-treatment disease status for a median of 17 months (2–41). We conclude that FCR is a feasible, well-tolerated and effective treatment for patients with CLL.

Resistance to bevacizumab (BEV) in glioblastoma is believed to occur via activation of molecular networks including the mTOR/PI3K pathway. Using an MR/PET molecular imaging biomarker approach, we investigated the response to combining BEV with the mTOR/PI3K inhibitor BEZ235.Tumours were established by orthotopically implanting U87MG-luc2 cells in mice. Animals were treated with BEZ235 and/or BEV, and imaged using diffusion-weighted-MRI, T2-weighted and T2*-weighted before and after administration of superparamagnetic iron oxide contrast agent. Maps for changes in relaxation rates (ΔR2, ΔR2* and apparent diffusion coefficient) were calculated. Vessel size index and microvessel density index were derived. 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) PET and O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) PET were further performed and tumour endothelium/proliferation markers assessed by immunohistochemistry.Treatment with BEV resulted in a pronounced decrease in tumour volume (T2-weighted MRI). No additive effect on tumour volume was observed with the BEV/BEZ235 combination compared with BEV monotherapy. The Ki67 proliferation index and [(18)F]FLT uptake studies were used to support the observations. Using ΔR2* and ΔR2 values, respectively, the BEV/BEZ235 combination significantly reduced tumour microvessel volume in comparison to BEV alone. Decreased microvessel density index was further observed in animals treated with the combination, supported by von Willebrand factor (vWF) immunohistochemistry. [(18)F]FET uptake was decreased following treatment with BEV alone, but was not further reduced following treatment with the combination. vWF immunohistochemistry analysis showed that the mean tumour vessel size was increased in all cohorts.Assessing MR imaging biomarker parameters together with [(18)F]FET and [(18)F]FLT PET provided information on mechanism of action of the drug combination and clues as to potential clinical responses. Following translation to clinical use, treatment with a BEV/BEZ235 combination could reduce peritumoral oedema obviating the requirement for steroids. The use of hypothesis-driven molecular imaging studies facilitates the preclinical evaluation of drug response. Studies of this kind may more accurately predict the clinical potential of the BEV/BEZ235 combination regimen as a novel therapeutic approach in oncology.

Thoracic aortic disease is an important contributor to arterial disease and therefore, mortality in the UK. It has close associations with hypertension, atherosclerosis and genetic conditions such as Marfan syndrome. The cardiovascular consequences of acute aortic dissection or the rupture of a thoracic aneurysm are life threatening with a 1% increase in mortality per hour with a type A aortic dissection and a high 30-day mortality rate. The clinical diagnosis can be difficult for the general physician as the symptoms can mimic more common conditions such as acute coronary syndrome, pulmonary embolism or acute abdomen. The investigations that carry the highest sensitivity and specificity, CT, transoesophageal echocardiography and MRI are not usually first-line investigations in most patients so a high index of clinical suspicion is key. The management of acute aortic syndromes involves good initial resuscitation and early discussion with the cardiothoracic surgeons. Given the serious consequences of acute aortic syndromes, it is important for all military doctors to be aware of these presentations and to appreciate the difficulties that can be encountered when trying to accurately diagnose them. Routine medicals, particularly entrance medicals, present a unique clinical opportunity to recognise the clinical features that would warrant further investigation and specialist advice.

Epidural corticosteroid injections are a common treatment for radicular pain caused by intervertebral disc herniations, spinal stenosis, and other disorders. Although rare, catastrophic neurologic injuries, including stroke and spinal cord injury, have occurred with these injections.A collaboration was undertaken between the U.S. Food and Drug Administration Safe Use Initiative, an expert multidisciplinary working group, and 13 specialty stakeholder societies. The goal of this collaboration was to review the existing evidence regarding neurologic complications associated with epidural corticosteroid injections and produce consensus procedural clinical considerations aimed at enhancing the safety of these injections. U.S. Food and Drug Administration Safe Use Initiative representatives helped convene and facilitate meetings without actively participating in the deliberations or decision-making process.Seventeen clinical considerations aimed at improving safety were produced by the stakeholder societies. Specific clinical considerations for performing transforaminal and interlaminar injections, including the use of nonparticulate steroid, anatomic considerations, and use of radiographic guidance are given along with the existing scientific evidence for each clinical consideration.Adherence to specific recommended practices when performing epidural corticosteroid injections should lead to a reduction in the incidence of neurologic injuries.

Chronic lymphocytic leukemia (CLL) follows a variable clinical course which is difficult to predict at diagnosis. We assessed somatic mutation (SHM) status, CD38 and ZAP-70 expression in 87 patients (49 male, 38 female) with stage A CLL and known cytogenetic profile to compare their role in predicting disease progression, which was assessed by the treatment free interval (TFI) from diagnosis. Sixty (69%) patients were SHM+, 24 (28%) were CD38+ and ten (12%) were ZAP-70+. The median TFI for: (i) SHM + versus SHM- patients was 124 versus 26 months; hazard ratio (HR) = 3.6 [95% confidence interval (CI) = 1.8 - 7.3; P = 0.001]: (ii) CD38- versus CD38+ patients was 120 versus 34 months; HR = 2.4 (95% CI = 1.4 - 5.3; P = 0.02); and (iii) ZAP70- versus ZAP70+ was 120 versus 16 months; HR = 3.4 (95% CI = 1.4 - 8.7; P = 0.01). SHM status and CD38 retained prognostic significance on multivariate analysis whereas ZAP-70 did not. We conclude that ZAP-70 analysis does not provide additional prognostic information in this group of patients.

Small uncontrolled studies of dialysis-dependent CKD (chronic kidney disease) patients have demonstrated abnormalities of cardiovascular autonomic control and vascular compliance, which may contribute to adverse cardiovascular morbidity in this population. However, there is little information utilizing newer non-invasive techniques in pre-dialysis patients with increasing degrees of uraemia. In the present study, 55 non-dialysis-dependent non-diabetic CKD patients with mean GFR (glomerular filtration rate) of 27 ml x min(-1) x m(-2) were studied. All patients underwent a 10-min period of electrocardiographic and non-invasive blood pressure monitoring. Cardiac BRS (baroreceptor sensitivity) was calculated from the combined alpha-index. PWV (pulse wave velocity) measurement and determination of arterial wave reflexion by applanation tonometry was performed in all patients. Mean (S.D.) cardiac BRS was 10.8 (7.1) ms/mmHg and mean (S.D.) PWV was 8.6 (1.7) m/s. Reduced GFR was correlated with increased PWV and decreased cardiac BRS. On logistic regression analysis with adjustment for clinical significant risk factors, severely impaired renal function (assessed by GFR < 15 ml x min(-1) x m(-2)) was associated with increased large artery stiffness [odds ratio for PWV = 3.14 (95% confidence intervals, 1.03-9.53); P = 0.04] and increased cardiovascular autonomic dysfunction [odds ratio for BRS = 0.87 (95% confidence intervals, 0.75-1.80); P = 0.06]. In conclusion, non-dialysis dependent non-diabetic CKD patients with decreasing GFR have reduced cardiac BRS and increased large artery stiffness. This may have important prognostic and therapeutic consequences for the management of vascular disease in a pre-dialysis population.

Low grade oligodendrogliomas (LGO) are diffusely infiltrating World Health Organization (WHO) grade II gliomas, 20 - 30% of which show contrast enhancement. Seizures are a common presenting feature. It has been suggested that 1p19q co-deletion is associated with occurrence of seizures in adults, however, to date, the relationship of tumor genetics and seizure activity has not been extensively investigated. We sought to assess the influence of 1p19q co-deletion, IDH1-R132H positivity, and radiological variables on seizure activity in LGO patients. Specifically, we examined whether these characteristics were associated with seizure at initial presentation, or if they could predict outcome in terms of seizure free survival. In 62 LGOs, neither tumor location nor tumor enhancement were associated with seizures. 1p19q co-deletion status did not predict seizures when controlled for mutant IDH1-R132H expression, tumor location, or enhancement status (odds ratio (OR) 0.9, 95% confidence interval (CI) 0.1 - 4.3). This study, although of limited statistical power, did not demonstrate an association between 1p19q status and seizure occurrence in LGO's. Replication in a larger cohort would further support our hypothesis that 1p19q status alone cannot be used as a reliable predictor of seizure occurrence in LGO's.

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S. Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S. Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1-99.7; Pless than0.0001). In vitro studies confirmed that plantain NSP (5-10 mg/ml) inhibited adhesion of S. Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64-81); Pless than0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75-90); Pless than0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis.

Two patients with histologically benign pituitary adenomas subsequently underwent resections of a frontal and a cerebellar tumour each of which had histological appearances identical to those of classic pituitary adenomas. The frontal tumour was immunoreactive for prolactin, and the cerebellar metastasis was immunoreactive for thyrotropin and gonadotrophins. There was no evidence of residual or recurrent intrasellar pituitary adenoma, nor was there a connection between the frontal or cerebellar masses and the sella turcica. Extracranial tumours have not developed. Both tumours fulfil criteria for diagnosis of pituitary carcinoma. These rare tumours are reviewed with emphasis on diagnosis and management.

Background Population based data suggest the proportion of patients failing imatinib in chronic myeloid leukaemia (CML) is higher than the reported one-third of patients in clinical trials. Clinical trials have demonstrated second generation tyrosine kinase inhibitors (TKI) dasatinib and nilotinib can restore complete cytogenetic remission (CCR) and major molecular response (MMR) to many patients failing imatinib, but their impact in the general population is not clear. Design and methods We report CML outcome in a population of 2.3 million people in a geographically contiguous area of North West England and North Wales. Results Between 2003 and 2009, 192 new CML cases were diagnosed, of whom 184 were in chronic phase and 160 started on imatinib. The maximal CCR rate was 65% at 24 months and the maximal MMR rate was 50% at 36 months. Patients diagnosed since second generation TKI became available for imatinib failure had a more rapid cumulative CCR and MMR rate and a significantly improved progression free survival ( p = 0.022) than those diagnosed before this time. Conclusion The study indicates that second generation TKI have improved CML outcome in the general population.

Although uncommon, there is significant morbidity and mortality associated with paediatric spinal glioblastoma. The paucity of cases makes treatment options difficult. The current recommended standard of care is biopsy followed by adjuvant chemo-radiotherapy, with emerging data supporting the role of safe gross total resection. The purpose of this paper is to provide a single-institution case study and to discuss current and future therapeutic treatment strategies. A 14-year-old boy presented with a 2-year history of intermittent back pain with recent progressively worsening motor and sensory deficits of the right side. Pre-operative MRI revealed an enhancing intra-medullary tumour extending from C2 to C7. During the operative case, no tumour–cord margin could be identified, and the patient underwent a subtotal excision. Histopathology confirmed glioblastoma. In the subsequent weeks, the patient's clinical condition deteriorated. Adjuvant therapy was declined by the family, and the patient died 9 weeks after initial presentation. Despite major advances in surgical techniques, peri-operative neuro-imaging as well as chemo-radiotherapy, the prognosis of a paediatric intra-medullary high-grade spinal tumour remains poor. Detailed analysis of our understanding of tumour dynamics in this patient group is important in establishing future therapeutic strategies.

A case of an aneurysmal bone cyst of the skull is presented. To date, six cases involving the frontal bone have been reported in the literature. We review the clinicopathological features, investigative procedures and management options of this rare calvarial tumour.

The spectrum of underlying molecular abnormalities of clinically and biologically heterogeneous chronic lymphocytic leukaemia (CLL) and prolymphocytic leukaemia (PLL) has yet to be identified. While whole genome sequencing has identified several genes implicated in the pathogenesis and progression of CLL, the molecular lesions in a substantial proportion of patients remain to be elucidated. The incidence of the BRAF V600E mutation, widely implicated in solid tumours and other B-cell malignancies, was sought in a cohort of patients with CLL and related disorders. One CLL patient and one patient with B-prolymphocytic leukaemia (PLL) were found to harbour this mutation. Although present at a low frequency, the finding of BRAF V600E has biological and clinical implications for CLL and PLL.

A sixteen year old girl presented with a four year history of hip pain followed subsequently by back pain radiating down her left leg, progressive urgency of micturition, urinary incontinence, a feeling of bladder fullness and incomplete bladder emptying, faecal impaction and finally, numbness in both of her buttocks. A diagnosis of Cauda Equina Syndrome was suspected on the history and the clinical examination. A plain X-ray of her lumbar spine revealed evidence of a slow growing mass within the vertebral canal at the level of L3. A Magnetic Resonance Imaging (MRI) scan confirmed an intradural space occupying lesion at the same level. This lesion was surgically removed and histological examination revealed a benign epidermoid cyst.

PURPOSE To evaluate the long-term refractive stability after LASIK for hyperopia with the WaveLight ALLEGRETTO WAVE Excimer Laser System. METHODS All 151 patients enrolled in the 2000-2002 FDA study of the ALLEGRETTO WAVE laser were contacted by the investigators approximately 4 years after study completion to be evaluated for refractive stability. RESULTS A total of 127/290 (43.8%) eyes in 68/151 (45%) patients presented for re-examination. Mean time from the examination taken at the 6-month follow-up stability endpoint in the FDA trial (Stability Exam) to the Post-Approval Exam was 3.9±0.39 years (range: 3.2 to 4.9 years). Stability of the manifest refraction spherical equivalent (MRSE) within ±1.00 D or less was seen in 119/127 (93.7%) eyes. Regression of effect of >1.00 D was seen in 6/127 (4.7%) eyes and progression of effect was seen in 2/127 (1.6%) eyes. Weak correlation of refractive changes with keratometry readings were seen in eyes that underwent >2.00 to 4.00 D treatment (R=0.31) and >4.00 D treatment (R=0.33), implying corneal remodeling may have played a role in the refractive change observed. CONCLUSIONS Refractive stability within ±1.00 D MRSE after hyperopic LASIK with the ALLEGRETTO WAVE excimer laser was seen in 93.7% of eyes at ≥3 years after surgery compared with 6-month follow-up, supporting the conclusion in the FDA trial that refractive stability occurred by 6 months postoperatively. Refractive changes associated with keratometry changes were not significant in eyes that underwent <2.00-D treatment. [J Refract Surg. 2008;24:S431-S438.] ABOUT THE AUTHORS From SurgiVision® Consultants Inc, Scottsdale, Ariz (Kezirian); International Eyecare Laser Vision Center, Houston, Tex, and National Medical Monitor for WaveLight USA (Moore); The Laser Center, Greensboro, NC (Stonecipher). Dr Kezirian is owner of SurgiVision® Consultants Inc, sponsor of the IDE study for the ALLEGRETTO WAVE Excimer Laser System referenced in this article. Dr Moore is a paid consultant for WaveLight AG and is an investigator in the FDA clinical trials for the ALLEGRETTO laser. Dr Stonecipher is an investigator in the FDA clinical trials for the ALLEGRETTO laser. The post-approval data were collected in a voluntary process by the investigator group without compensation. No financial compensation was received by any of the authors for this project. *SurgiVision® Consultants Inc WaveLight Investigator Group: Stephen I.Brint, MD, FACS (Medical Monitor); Thomas Abell, MD; Peter Arrowsmith, MD; Perry Binder, MD; William Bond, MD; Bennett Chotiner, MD; David D. Dulaney, MD; Michael Gordon, MD; and David O’Brien, MD. Correspondence: Guy M. Kezirian, MD, FACS, SurgiVision® Consultants Inc, 28071 N 90th Way, Scottsdale, AZ 85262. Tel: 480.664.1880; Fax: 480.664.1881; E-mail: Guy1000@SurgiVision.net

It is being increasingly recognised that nursing needs to be constructively and critically informed by a body of scientific knowledge, and that practitioners need to develop active and independent learning styles which enable them to access, use and evaluate such knowledge. This approach has led to many teachers reexamining their approaches to teaching and learning, with an increasing emphasis upon cultivating lifelong learning and in providing students with the skills to facilitate this process. It is against this backdrop that the authors developed a comprehensive information skills package for student nurses undertaking an ENB Diploma in Nursing Science/Registered General Nurse Course (ENB Pilot Scheme Course). The package was designed specifically for use within the Newcastle Polytechnic Library though with modifications, it could be used in other venues. This paper explores the rationale and structure of the package and its subsequent implementation and evaluation.

A prominent hospital in Pennsylvania turned to CPOE to help reduce medical errors and improve patient care. Learn what steps hospital officials took to establish a successful CPOE system.

Recent government policies have legitimised the role development of all health care practitioners as a means of improving patient care and service delivery. This study focuses on the professional development of health care assistants (HCAs) and how this relates to patient care. National inconsistencies in training provision and the need to standardise the education of HCAs through registration are discussed. The implications for nursing practice are also examined.

The epilepsy liaison nurse's aim is to achieve a positive outcome in terms of clients' general well-being, social and physical activities, behavioural difficulties and other important issues in their lives. Many clients' problems stem from a lack of adequate information and support. A sound knowledge of the disorder can boost clients' and carers' confidence. They need information on what to do during a seizure, how to ensure that other people know what to do, and to understand the importance of being aware of precipitating factors. Clients and their families should also be encouraged to talk about the condition. This will reveal any misconceptions and anxieties and bring concerns into the open, helping to put them into perspective. Support for carers includes ensuring that clients have the personal care and support they need to improve or maintain a good quality of life. It is important that the person managing the client's epilepsy understands any issues related to learning disabilities and knows how to gain access to health and social care systems. By identifying and addressing the needs of clients and their families, epilepsy liaison nurses can make a positive difference to their lives.

Renal cell carcinomas (RCC) are characterised by a tendency to metastasise widely, often while remaining occult. Intramedullary spinal cord metastases (ISCM) from RCC may be the presenting feature of the disease or present at any time in the disease course. This case report discusses an ISCM from RCC which became manifested at the time of resection of the primary tumour. We review the literature published on ISCM from RCC from 1990 to date comparing disease characteristics and presentations.

There is a prevailing wisdom that the taking and recording of arterial blood pressure is a non-problematic nursing activity. However, closer scrutiny reveals that the practices surrounding blood pressure measurement are subject to rational and ritual actions that have considerable significance for nursing practice.