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Temporary drug treatment cessation might alleviate toxicity without substantially compromising efficacy in patients with cancer. We aimed to determine if a tyrosine kinase inhibitor drug-free interval strategy was non-inferior to a conventional continuation strategy for first-line treatment of advanced clear cell renal cell carcinoma. This open-label, non-inferiority, randomised, controlled, phase 2/3 trial was done at 60 hospital sites in the UK. Eligible patients (aged ≥18 years) had histologically confirmed clear cell renal cell carcinoma, inoperable loco-regional or metastatic disease, no previous systemic therapy for advanced disease, uni-dimensionally assessed Response Evaluation Criteria in Solid Tumours-defined measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) at baseline to a conventional continuation strategy or drug-free interval strategy using a central computer-generated minimisation programme incorporating a random element. Stratification factors were Memorial Sloan Kettering Cancer Center prognostic group risk factor, sex, trial site, age, disease status, tyrosine kinase inhibitor, and previous nephrectomy. All patients received standard dosing schedules of oral sunitinib (50 mg per day) or oral pazopanib (800 mg per day) for 24 weeks before moving into their randomly allocated group. Patients allocated to the drug-free interval strategy group then had a treatment break until disease progression, when treatment was re-instated. Patients in the conventional continuation strategy group continued treatment. Patients, treating clinicians, and the study team were aware of treatment allocation. The co-primary endpoints were overall survival and quality-adjusted life-years (QALYs); non-inferiority was shown if the lower limit of the two-sided 95% CI for the overall survival hazard ratio (HR) was 0·812 or higher and if the lower limit of the two-sided 95% CI of the marginal difference in mean QALYs was -0·156 or higher. The co-primary endpoints were assessed in the intention-to-treat (ITT) population, which included all randomly assigned patients, and the per-protocol population, which excluded patients in the ITT population with major protocol violations and who did not begin their randomisation allocation as per the protocol. Non-inferiority was to be concluded if it was met for both endpoints in both analysis populations. Safety was assessed in all participants who received a tyrosine kinase inhibitor. The trial was registered with ISRCTN, 06473203, and EudraCT, 2011-001098-16. Between Jan 13, 2012, and Sept 12, 2017, 2197 patients were screened for eligibility, of whom 920 were randomly assigned to the conventional continuation strategy (n=461) or the drug-free interval strategy (n=459; 668 [73%] male and 251 [27%] female; 885 [96%] White and 23 [3%] non-White). The median follow-up time was 58 months (IQR 46-73 months) in the ITT population and 58 months (46-72) in the per-protocol population. 488 patients continued on the trial after week 24. For overall survival, non-inferiority was demonstrated in the ITT population only (adjusted HR 0·97 [95% CI 0·83 to 1·12] in the ITT population; 0·94 [0·80 to 1·09] in the per-protocol population). Non-inferiority was demonstrated for QALYs in the ITT population (n=919) and per-protocol (n=871) population (marginal effect difference 0·06 [95% CI -0·11 to 0·23] for the ITT population; 0·04 [-0·14 to 0·21] for the per-protocol population). The most common grade 3 or worse adverse events were hypertension (124 [26%] of 485 patients in the conventional continuation strategy group vs 127 [29%] of 431 patients in the drug-free interval strategy group); hepatotoxicity (55 [11%] vs 48 [11%]); and fatigue (39 [8%] vs 63 [15%]). 192 (21%) of 920 participants had a serious adverse reaction. 12 treatment-related deaths were reported (three patients in the conventional continuation strategy group; nine patients in the drug-free interval strategy group) due to vascular (n=3), cardiac (n=3), hepatobiliary (n=3), gastrointestinal (n=1), or nervous system (n=1) disorders, and from infections and infestations (n=1). Overall, non-inferiority between groups could not be concluded. However, there seemed to be no clinically meaningful reduction in life expectancy between the drug-free interval strategy and conventional continuation strategy groups and treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma. UK National Institute for Health and Care Research.

Background: no phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.Methods: this was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450.Findings: between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2–16·8). Median progression-free survival was 3·0 months (95% CI 2·8–4·1) in the nivolumab group versus 1·8 months (1·4–2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53–0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5–12·1) in the nivolumab group versus 6·9 months (5·0–8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52–0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group.Interpretation: Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy.Funding: Stand up to Cancer–Cancer Research UK and Bristol Myers Squibb.

This project used the Council Health Survey to evaluate the effectiveness of shared governance councils in a children's hospital during the COVID-19 pandemic. A SWOT analysis was performed to assess the organization's strengths, weaknesses, opportunities, and threats regarding council health and to inform strategies to sustain the shared governance environment. The well-established shared governance infrastructure allowed the organization to rapidly pivot council operations to sustain nurse engagement while balancing the unprecedented staffing and resource challenges of the pandemic. Organizations must remain flexible and innovative to maintain an environment supportive of nurse empowerment and shared governance during public health emergencies.

Physicians in training may experience harassment and discrimination fromsupervisors, consultants, colleagues, or patients and families.Instances of discrimination towards students may impact students’ self-esteem, self-efficacy, and ultimately performance.In this particular time, many institutions are looking to enhance their curriculum regarding bias.More tools are needed to help students feel empowered to respond professionally when they encounter challenging situations. This study was designed to assess the impact of a training intervention in addressing biased patient statements.The training was strategically placed prior to clinical interactions. The authors’ intention was to present discriminatory statements by patients as one of the many difficult clinical situations that students are being trained to navigate.The authors developed a clinical rubric for decision-making in flowchart style to mimic the decision trees used in diagnostic or treatment decisions.They then created a workshop to help learners use the flowsheet.The workshop was delivered to third-year medical students as part of “Junior Bootcamp,” a day-long session of events to orient students to the clinical experiences of the M3 year.The workshop was delivered in the summer of 2019. Respondents indicated that they were more likely to be able to appropriately respond to discriminatory comments after completing the workshop.They also felt that they were more likely to be able to engage in respectful dialogue with a patient and to debrief with a faculty member.Fewer participants felt that they were likely to use the flowchart. Findings indicate that the workshop was useful to participants.It may be especially useful to educators dealing with the COVID pandemic because it is scalable and easily delivered remotely.Further studies are needed to determine if introducing this topic in the clinical years of medical school leads to improved skill in addressing instances of bias that come from patients and families.

Ehrlichia canis (Rickettsiales; Anaplasmataceae) is one of the most prevalent tick-borne pathogens of dogs globally. The bacterium infects monocytes and is the aetiological agent of canine monocytic ehrlichiosis. For many decades Australia was thought to be free of the pathogen, but this abruptly changed in May 2020 when E. canis was detected in several dogs from Kununurra, Western Australia. Subsequent surveillance activities found unexpectedly large scale spread of E. canis throughout much of northern Australia. To gain insight into the genetic relationships of the Australian strain and its potential origin, we undertook a genomic analysis of E. canis positive domestic dog and tick (Rhipicephalus linnaei) samples from the north of Western Australia, the far north of South Australia and the Northern Territory, covering thousands of square kilometres. We obtained complete E. canis genomes from each of the three states, plus an additional 16 partial genomes, substantially increasing publicly available E. canis genetic resources. The Australian E. canis genomes were highly conserved across large geographic distances. Outside of Australia, the genomes were most similar to E. canis YZ-1 from China, although few reference sequences were available. We analysed the variable trp36 gene to obtain greater phylogenetic signal, which demonstrated that the Australian E. canis belonged to the Taiwan genotype, comprised of samples from Taiwan, China, Thailand and Turkey. Taken together, our findings suggest that E. canis in Australia may have originated from Asia or the Middle East and spread throughout northern and central Australia following its introduction.

The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.

Beginning from the proposition that doing transdisciplinary child and youth care (CYC) entails an ethic of risk and vulnerability, four graduate students from differing social, spiritual, bodied, a...

Background: –The National Asthma and COPD Audit Programme (NACAP) aims to drive improvements in the quality of care and services provided forRespiratory patients in England and Wales (RCP / BTS 2017) –Part of this programme is the continuous audit of admission to hospital for those patients with COPD –This commenced in April 2017 and currently is scheduled to continue until March 2019 –Best Practice Tariff (BPT) was introduced to improve the proportion of patients who receive specialist respiratory input to their care within 24 hours of admission and completion of a COPD discharge bundle. Aims: –Primary aim was to deliver on the COPD BPT –Secondary aim was to improve the inpatient experience and deliver evidence based care –This would be evidenced by length of stay, readmission rates and inpatient mortality rates Methods: Recruited Associate Practitioners, Registered Nurse and Physiotherapist to into Specialist Practioner Roles. Results: Development of an Inpatient Respiratory Practitioner Team has enabled the Trust to achieve the required 60% for BPT by quarter 3 (Oct-Dec 2017) and thus qualification for the enhanced tariff

BACKGROUND: The transition from an ICU ventilator to a portable home ventilator (PHV) for children requiring long-term mechanical ventilation is a crucial step in preparing for discharge home and may not be successful on the first attempt. A review of this process at our institution revealed that some children required multiple trials before they were able to tolerate a PHV. A protocol was developed to standardize the transition process and reduce the number of failed attempts. Key features of the protocol included a transition readiness assessment and criteria for changing to the PHV. METHODS: A retrospective chart review was completed to evaluate the process of changing to a PHV before and after the protocol was in place during the time period of 2011–2018. Primary outcome measures included the number of transition attempts and the length of time to achieve successful transition. A successful transition attempt was defined as the ability to tolerate a PHV for 14 d. RESULTS: The study included 56 children ≤ 3 y old with a tracheostomy who required long-term ventilator support. The majority of subjects were from the neonatal ICU and had a diagnosis of bronchopulmonary dysplasia. There was a significant decrease in the number of attempts (P = .005) and in the length of time (P = .01) to successfully transition to a PHV for those who underwent the protocol. CONCLUSIONS: The process of changing from an ICU ventilator to a PHV in children requiring long-term mechanical ventilation was improved through the use of a standardized protocol. Both the number of failed attempts and the length of time to achieve successful transition were reduced when the protocol was applied. Further study is needed to evaluate other medical and nonmedical factors that may affect successful transition to a PHV.

In an education system marred by inequity, urban schools in the United States are faced with the challenge of helping students from marginalized groups succeed. While many strategies have been tried, most are built on deficit-based models that blame students and teachers for a lack of achievement and ignore the role of power within the school setting. Building on the body of research on school climate, critical pedagogy, and empowering settings, the present study developed a model of student empowerment using a case study of an ethnically diverse urban high school in the midwestern United States. Participant observation, focus groups, and interviews were utilized to identify classroom and school characteristics related to student empowerment. Students reported equitable teacher–student relationships, integrated student leadership, and shared decision making. Similarly, school staff reported high staff empowerment and sense of community. The Student Empowerment Model is a useful framework for school improvement, adding “power” to the broader literature on school climate and extending the work on empowering settings to schools.

Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications.

Over the past three decades, more and more students are expressing a desire to attend college, yet for many members of disenfranchised groups, this goal is often not attained. While many factors contribute to these disparities, research has shown that students begin adjusting their expectations (what they think they can achieve) for the future in relation to their idealised aspirations (what they would like to achieve). The current study explores this gap among 207 eighth grade students from two urban middle schools. Using the School Attitude Assessment Survey-Revised, three factors were found to predict expectations which matched student aspirations. These factors were academic motivation and self-regulating behaviours, academic self-perception and attitudes towards teachers. Implications for educational interventions and school reform are discussed.

The clinical and histopathological distinctions between inherited versus acquired bone marrow failure and myelodysplastic syndromes are challenging. The identification of inherited bone marrow failure/myelodysplastic syndromes is critical to inform appropriate clinical management. To investigate whether a subset of pediatric and young adults undergoing transplant for aplastic anemia or myelodysplastic syndrome have germline mutations in bone marrow failure/myelodysplastic syndrome genes, we performed a targeted genetic screen of samples obtained between 1990-2012 from children and young adults with aplastic anemia or myelodysplastic syndrome transplanted at the Fred Hutchinson Cancer Research Center. Mutations in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients. While the majority of mutations were constitutional, a RUNX1 mutation present in the peripheral blood at a 51% variant allele fraction was confirmed to be somatically acquired in one myelodysplastic syndrome patient. This highlights the importance of distinguishing germline versus somatic mutations by sequencing DNA from a second tissue or from parents. Pathological mutations were present in DKC1, MPL, and TP53 among the aplastic anemia cohort, and in FANCA, GATA2, MPL, RTEL1, RUNX1, SBDS, TERT, TINF2, and TP53 among the myelodysplastic syndrome cohort. Family history or physical examination failed to reliably predict the presence of germline mutations. This study shows that while any single specific bone marrow failure/myelodysplastic syndrome genetic disorder is rare, screening for these disorders in aggregate identifies a significant subset of patients with inherited bone marrow failure/myelodysplastic syndrome.

Background: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for Disability-adjusted life-years cancer in middle aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium. Methods: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes. Results: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%). Conclusions: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden. © 2016 The Author.

Source: doi: 10.1186/s12916-016-0607-5 Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs. Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking. Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation. Keywords: Smoking Cancer Incidence Mortality Cohort Meta-analysis

Context In surgical and clinical oncology, there is a growing need for patient-centered outcomes that are responsive, meaningful, and fit for purpose. Objectives The aim of this study was to validate physical activity (PA) monitoring as a responsive outcome measure at different stages of disease and treatment, by verifying correlations between PA, performance score, and quality of life (QoL). Methods Daily life PA of 162 cancer patients, monitored by a device that records time sitting/lying, time standing, time walking, number of steps taken, and walking cadence, was compared with 20 healthy volunteers. In a subgroup of patients, functional status and QoL were assessed using the World Health Organization/Eastern Cooperative Oncology Group and the Karnofsky Performance Status scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire. Results The PA of patients with resectable gastrointestinal cancer did not differ significantly from controls. In contrast, patients with advanced cancer took 45% fewer steps and spent an extra 2.8 hours/day lying/sitting (P=0.001). Patients undergoing neoadjuvant chemotherapy and surgery (5–6 weeks after operation) experienced a similar reduction in PA. There were significant correlations between PA and the physical and role domains as well as fatigue subscale of the EORTC QLQ-C30 scale. Conclusion Objective PA scores correlate significantly with disease stage, functional status, and QoL of patients with cancer. Therefore, activity monitoring can make meaningful objective estimates of patient function in response to cancer and its treatment and may provide surrogate outcomes of QoL.

Soft on Sticks is a comprehensive, interdisciplinary, evidence-based practice initiative that was implemented to ensure consistent use of pharmacologic and nonpharmacologic interventions to reduce pain associated with needlestick procedures performed on children. Pre- and postimplementation data from children, parents, and nurses showed positive results from the practice change and identified areas for further improvement.

Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications.

The purpose of the present study was to examine the influence of heat‐induced superaggregation of Amphotericin B (AmB) in the Fungizone® (FZ) formulation on its interaction with human serum components and relate this to reduced toxicity. Whole serum distribution studies showed that a significantly lower percentage of AmB from HFZ was recovered in the high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and triglyceride‐rich lipoprotein (TRL) fractions and a greater percentage recovered in the lipoprotein‐deficient plasma (LPDP), though the majority of both preparations were recovered in LPDP. Circular dichroism (CD) and difference absorption spectroscopy were used to determine the stability of FZ and heat‐treated FZ (HFZ) in the presence of HDL, LDL, serum, and albumin. The CD studies indicate that the "core" aggregate of HFZ is more stable in the presence of HDL and LDL, whereas the FZ is less stable and more dynamic with the core aggregate dissociating to a greater extent in the presence of either purified lipoprotein. Absorption studies with whole serum and purified albumin suggest that FZ aggregates are far less stable in the presence of albumin than HFZ and that interaction with serum albumin is a dominant feature for both drug preparations. HFZ also has a different effect on the cytokine response in vitro . Studies using THP‐1 human monocytes show that HFZ provokes a smaller release of tumor necrosis factor (TNF)‐α than FZ. This cytokine may be associated with the unpleasant side effects of AmB. These findings suggest that heat‐induced superaggregation of AmB alters its interaction with HDL, LDL, serum proteins, and monocytes, and these findings may be important in explaining the reduced toxicity of the superaggregated form of AmB. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:124–133, 2001

Using phenomenological interviewing to preserve students' voices and their lived experiences, researchers at a large public research institution and a midsized comprehensive public institution explored the experiences of student leaders of color. Themes of their experiences included: disdain for the label of leader; the personal costs of holding leadership positions; the different experiences in predominantly White, multiracial, or same-race groups; group loyalty over individual needs; gender differences in leadership experiences; and lack of campus staff and faculty role models

The idea that amphotericin B (AmB) may not require sterols to form ion selective channels has recently been criticized on the grounds that egg phospholipids commonly used in experiments may contain small amounts of sterol which associate with AmB to form AmB/sterol pore channel structures. It was recently shown in this laboratory that modest osmotic stress can enhance the formation of AmB channels in sterol-free egg phosphatidylcholine (eggPC) membranes. We have tested AmB’s ability to form ion channels/defects in synthetic palmitoyl oleoyl (POPC), dieicosenyl (DEPC) and natural eggPC osmotically stressed large unilamellar vesicles (LUV) using pyranine fluorescence detected ion/H a exchange. These sterol-free POPC LUV exhibit greatly increased sensitivity to cation selective AmB channel formation when osmotically stressed ; even more than eggPC. Under these stressed conditions, AmB activity was observed at [AmB]/POPC ratios as low as 3.5U10 34 , corresponding to about 34 AmB molecules/vesicle. DEPC vesicles were almost completely unresponsive, demonstrating a strong bilayer thickness dependence. These results prove conclusively that AmB can form sterol-free channels and do so within therapeutic concentration ranges (s 0.5^10U10 36 M) in a stress-dependent manner. This phenomenon may allow us to use osmotic stress changes in simple model systems to spectroscopically isolate and characterize the thus-far elusive AmB channel forming aggregate. In addition, this stress dependence may be responsible for the potentiation of renal toxicity of AmB in the ascending branch of the loop of Henle which is under greatest osmotic stress. fl 1998 Elsevier Science B.V. All rights reserved.

Although mentoring is an important aspect of implementing evidence-based practice (EBP), few models exist for EBP education. The EBP Academy is an innovative, 6-month educational program designed to develop clinical staff as EBP nurse mentors. Sessions provide protected time for participants to work on their EBP projects with assigned mentors who have EBP expertise and similar clinical or research interests. Participants develop EBP projects focused on improving care in their clinical areas. Evaluation of the EBP Academy is based on a four-level model, including participant feedback about the program, perception of meeting program objectives, ability to apply knowledge to practice through EBP projects, and outcome data measured as a result of implementing the EBP changes. By developing EBP mentors, capacity to move nursing practice to a stronger evidence-based foundation can be enhanced. Positive, professional nursing and patient outcomes have been demonstrated when structured EBP education is provided.

Child and adolescent psychiatric inpatient wards were established because young people with mental illness are often poorly served by admission to general psychiatric wards owing to needs that differ from those adults, different skills needed by staff, and difficulty ensuring young people's safety.1 The admission of young people with mental illness to paediatric wards also raises concerns about safety and the skills of staff. We estimated the number of inappropriate admissions of young people with mental disorder to adult psychiatric wards and paediatric wards. We chose nine health authorities representative of England and Wales in terms of location, population size, deprivation, and provision of child and adolescent psychiatric wards (see table on bmj.com). These health authorities served 1.13 million people aged under 18, representing 9% of the population of England and Wales (1999 projections of 1991 census). We identified all adult psychiatric wards and paediatric wards. Consultant general psychiatrists and paediatricians completed a questionnaire for each eligible patient (patients aged under …

Recently it has been demonstrated that moderate heat treatment of Amphotericin B/deoxycholate solutions (HAmB-DOC ) leads to a therapeutically interesting supramolecular rearrangement that can be observed by significant changes in light scattering, CD, and absorbance. In this study, we continue the investigation of the physical properties of this new form by evaluating the activity and kinetics of dissociation and dispersion of HAmB-DOC and AmB-DOC in saline, serum, and in model mammalian or fungal lipid biomimetic membrane vesicles. Stopped-flow spectrophotometry combined with singular value decomposition (SVD) and global analysis were used to resolve the components of this process. The dissociation kinetics for both states are complex, requiring multi-exponential fits, yet in most cases SVD indicates only two significant changing species representing the monomer and the aggregate. The kinetic mechanism could involve dissociation of monomers from coexisting spectroscopically similar but structurally distinct aggregates or sequential rearrangements in supramolecular structure of aggregates. Rate constants and amplitudes of dissociation from aggregates to monomer in buffer, whole serum, 10% cholesterol, and ergosterol membrane vesicles are generally greater for AmB-DOC, demonstrating its greater kinetic instability. In addition, at comparable low concentrations, HAmB-DOC and AmB-DOC are nearly equally active at promoting cation selective permeability in ergosterol-containing membranes; however, HAmB-DOC is much less active against mammalian mimetic cholesterol-containing vesicles, despite a higher level of self-association, supporting previous observations that there exists a specific "toxic aggregate" structure.

An anonymous self-completion questionnaire on smoking was completed by 2065 (60 per cent) 15-16-year-olds attending secondary schools in Doncaster in 1991. Almost one in four girls (23 per cent) and one in six boys (16 per cent) reported they were regular smokers, an overall increase of 8 per cent since a similar survey in 1988. An increase in smoking was recorded in 12 of the 14 schools which took part in both the 1988 and 1991 surveys. Differences in smoking prevalence were recorded between schools. School-based analysis is likely to be important for the development of effective local intervention. Possible reasons for the overall increase in smoking are discussed, and the need for concerted efforts to influence smoking regulation policy decisions is stressed.

Introduction Although pain and depression co-exist in 36.5% of cancer patients, the precise nature of the relationship between these symptoms requires elucidation. This study aimed to further understanding of the relationship by determining whether improved pain is associated with a significant reduction in depression and increased quality of life in cancer patients. Methods A secondary data analysis of patients enrolled in pain intervention studies (n=123) was undertaken. Pain, depression and quality of life were measured at baseline and endpoint using the Brief Pain Index (BPI), Hospital and Anxiety and Depression Score (HADS) and EuroQol Thermometer assessment tools respectively. The Mann-Whitney U-test and Fisher9s Exact Test were used to statistically analyse score differences between pain response groups. Results Baseline BPI, HADS and EuroQol scores were well matched between the groups. Patients responding to pain interventions had an average 2.95 point decrease in endpoint HADS scores, contrasting with a 0.89 increase in non-responding patients (score range 0–42). There was a statically significant difference in the endpoint total HADS scores between the two groups (p=0.0015). Similar mean changes in EuroQol scores revealed increased quality of life scores occurring in patients with (10.64) and without (12.41) improved pain. Conclusions Improving pain results in reduced depression scores. This supports a unidirectional relationship between pain and depression. Further study is required to establish the presence of a bidirectional relationship. Understanding the relationship between pain and depression allows prioritisation of targeted management of co-existent pain and depression, which may improve the clinical care of cancer patients.