Adaptation of international guidelines on assessment and management of cancer pain for the Australian context

Aim: To develop clinical practice guidelines for screening, assessing and managing cancer pain in Australian adults. Methods: This three phase project utilised the ADAPTE approach to adapt international cancer pain guidelines for the Australian setting. A Working Party was established to define scope, screen guidelines for adaptation, and develop recommendations to support better cancer pain control through screening, assessment, pharmacological and non-pharmacological management, and patient education. Recommendations with limited evidence were referred to Expert Panels for advice before the draft guidelines were opened for public consultation via the Cancer Council Australia Cancer Guidelines Wiki platform in late 2012. All comments were reviewed by the Working Party and the guidelines revised accordingly. Results: Screening resulted in six international guidelines being included for adaptation - those developed by the Scottish Intercollegiate Guidelines Network (2008), National Health Service Quality Improvement Scotland (2009), National Comprehensive Cancer Network (2012), European Society of Medical Oncology (2011), European Association for Palliative Care (2011, 2012) and National Institute of Clinical Excellence (2012). Guideline adaptation resulted in 55 final recommendations. The guidelines were officially launched in November 2013. Conclusion: International guidelines can be efficiently reconfigured for local contexts using the ADAPTE approach. Availability of the guidelines via the Cancer Council Australia Wiki is intended to promote uptake and enable recommendations to be kept up to date. Resources to support implementation will also be made available via the Wiki if found to be effective by a randomised controlled trial commencing in 2015

Defining an epidemic:The body mass index in British and American obesity research 1960-2000

Between the 1970s and the mid‐1990s the body mass index (BMI) became the standard means of assessing obesity both in populations and in individuals, replacing previously diverse and contested definitions of excess body weight. This article draws on theoretical approaches from the sociology of standards and science and technology studies to describe the development of this important new standard and the ways in which its adoption facilitated the development of obesity science, that is, knowledge about the causes, health effects and treatments of excess body weight. Using an analysis of policy and healthcare literatures, I argue that the adoption of the BMI, along with associated standard cut‐off points defining overweight and obesity, was crucial in the framing of obesity as an epidemic. This is because, I suggest, these measures enabled, firstly, the creation of large data sets tracking population‐level changes in average body weight, and, secondly, the construction of visual representations of these changes. The production of these two new techniques of representation made it possible for researchers in this field, and others such as policymakers, to argue credibly that obesity should be described as an epidemic

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

High Reported Rates of Antimicrobial Resistance in Indian Neonatal and Pediatric Blood Stream Infections.

Background.: There is real shortage of national data on antimicrobial resistance rates in Indian neonates and children. A descriptive review was conducted to determine the patterns of antimicrobial resistance in isolates of blood stream infection among hospitalized children in India. Methods.: Published and gray literature on antibiotic resistance in children was searched using "Google Scholar", "Scopus", and "PubMed" databases between January 2000 and July 2015. Studies were included if they were original articles that reported a minimum of 10 pathogenic bacterial isolates from the bloodstream within a pediatric population in India, and studies were excluded if they reported studies done during an outbreak or epidemic. Results.: A total of 1179 studies were screened, and 82 papers were identified as eligible for inclusion. Most studies (78.7%) were reported from neonatal intensive care units. Among a total of 50545 reported blood cultures, 14704 (29.1%) were positive. Staphylococcus aureus (median, 14.7%; IQR, 7.4%-25.6%) and Klebsiella pneumoniae (median, 26%; IQR, 16.7%-35.4%) were the commonest reported Gram-positive and Gram-negative pathogens, respectively. Approximately half of all S aureus isolates were reported as methicillin-resistant S aureus (median, 50%; IQR, 31.4%-65.1%). After age stratification, the median rate of resistance of common Gram-negative pathogens to ampicillin and gentamicin/amikacin were extremely high (K pneumoniae/ampicillin 95.9%; K pneumoniae/gentamicin 75%; Escherichia coli/ampicillin 92.9%; E coli/gentamicin 55.6%). Likewise, the median resistance of common Gram-negative blood stream isolates to cephalosporins were also high (K pneumoniae/cefotaxime 62.6%; E coli/cefotaxime 47.5%). Conclusions.: High rates of resistance to World Health Organization-recommended first-line treatment options for neonates and children have been identified in blood stream infections across India. There is an urgent need to both enhance antibiotic stewardship and infection prevention and control measures and consider urgently how to repurpose older antibiotics back into routine care in India

Circulating 250HD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: The MIDSPAN Family Study

<p>Context: Observational studies relating circulating 25-hydroxyvitamin D (25OHD) and dietary vitamin D intake to cardiovascular disease (CVD) have reported conflicting results.</p> <p>Objective: Our objective was to investigate the association of 25OHD, dietary vitamin D, PTH, and adjusted calcium with CVD and mortality in a Scottish cohort.</p> <p>Design and Setting: TheMIDSPAN Family Study is a prospective study of 1040 men and 1298 women from the West of Scotland recruited in 1996 and followed up for a median 14.4 yr. Participants: Locally resident adult offspring of a general population cohort were recruited from 1972–1976.</p> <p>Main Outcome Measures: CVD events (n = 416) and all-cause mortality (n=100) were evaluated.</p> <p>Results: 25OHD was measured using liquid chromatography-tandem mass spectrometry in available plasma (n=2081). Median plasma 25OHD was 18.6 ng/ml, and median vitamin D intake was 3.2 µ g/d (128 IU/d). Vitamin D deficiency (25OHD<15 ng/ml) was present in 689 participants (33.1%). There was no evidence that dietary vitamin D intake, PTH, or adjusted calcium were associated with CVD events or with mortality. Vitamin D deficiency was not associated with CVD (fully adjusted hazard ratio=1.00; 95% confidence interval=0.77–1.31). Results were similar after excluding patients who reported an activity-limiting longstanding illness at baseline (18.8%) and those taking any vitamin supplements (21.7%). However, there was some evidence vitamin D deficiency was associated with all-cause mortality (fully adjusted hazard ratio=2.02; 95% confidence interval=1.17–3.51).</p> <p>Conclusion: Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD. Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences inmortality outcomes as well as CVD.(J Clin EndocrinolMetab97: 0000 –0000, 2012)</p&gt

Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Background: While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established. We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection. Methods: We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010. We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization. We adjusted for NAI treatment propensity and preadmission antibiotic use, including “study center” as a random intercept to account for differences in baseline hospitalization rate between centers. Results: We included 3376 patients with influenza A(H1N1)pdm09, of whom 3085 (91.4%) had laboratory-confirmed infection. Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%). After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20–0.30). Conclusions: In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission. These data suggest that community patients with severe influenza should receive NAI treatment

Data linkage errors in hospital administrative data when applying a pseudonymisation algorithm to paediatric intensive care records.

OBJECTIVES: Our aim was to estimate the rate of data linkage error in Hospital Episode Statistics (HES) by testing the HESID pseudoanonymisation algorithm against a reference standard, in a national registry of paediatric intensive care records. SETTING: The Paediatric Intensive Care Audit Network (PICANet) database, covering 33 paediatric intensive care units in England, Scotland and Wales. PARTICIPANTS: Data from infants and young people aged 0-19 years admitted between 1 January 2004 and 21 February 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: PICANet admission records were classified as matches (records belonging to the same patient who had been readmitted) or non-matches (records belonging to different patients) after applying the HESID algorithm to PICANet records. False-match and missed-match rates were calculated by comparing results of the HESID algorithm with the reference standard PICANet ID. The effect of linkage errors on readmission rate was evaluated. RESULTS: Of 166,406 admissions, 88,596 were true matches (where the same patient had been readmitted). The HESID pseudonymisation algorithm produced few false matches (n=176/77,810; 0.2%) but a larger proportion of missed matches (n=3609/88,596; 4.1%). The true readmission rate was underestimated by 3.8% due to linkage errors. Patients who were younger, male, from Asian/Black/Other ethnic groups (vs White) were more likely to experience a false match. Missed matches were more common for younger patients, for Asian/Black/Other ethnic groups (vs White) and for patients whose records had missing data. CONCLUSIONS: The deterministic algorithm used to link all episodes of hospital care for the same patient in England has a high missed match rate which underestimates the true readmission rate and will produce biased analyses. To reduce linkage error, pseudoanonymisation algorithms need to be validated against good quality reference standards. Pseudonymisation of data 'at source' does not itself address errors in patient identifiers and the impact these errors have on data linkage.Economic and Social Research Council (ESRC) National Centre for Research Methods (NCRM), grant number ES/F035098/1

Synthesising practice guidelines for the development of community-based exercise programmes after stroke

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Multiple guidelines are often available to inform practice in complex interventions. Guidance implementation may be facilitated if it is tailored to particular clinical issues and contexts. It should also aim to specify all elements of interventions that may mediate and modify effectiveness, including both their content and delivery. We conducted a focused synthesis of recommendations from stroke practice guidelines to produce a structured and comprehensive account to facilitate the development of community-based exercise programmes after stroke.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul

Critical time Intervention for Severely mentally ill Prisoners (CrISP): a randomised controlled trial

Background The transition from prison to community is difficult for prisoners with mental illness. Critical time intervention (CTI) is designed to provide intensive support to meet health, social care and resettlement needs through close working between client and key worker pre, and up to 6 weeks post, release. Objectives To establish whether or not CTI is effective in (1) improving engagement of discharged male prisoners who have mental illness with community mental health teams (CMHTs) and (2) providing practical support with housing, finance and re-establishing social networks. Trial design A multicentre, parallel-group randomised controlled trial, with follow-up at 6 weeks and at 6 and 12 months. A subset of prisoners and case managers participated in a complementary qualitative study. Setting Eight English prisons. Participants One hundred and fifty adult male prisoners, convicted or remanded, cared for by mental health in-reach teams and diagnosed with severe mental illness, with a discharge date within 6 months of the point of recruitment. Intervention Participants were randomised to either the intervention or the control (treatment as usual). The intervention group was assigned a case manager who assessed mental and physical health before and following release, made appropriate links to health, housing and financial services and supported the re-establishment of family/peer contact. Outcome The primary outcome measure was engagement with a CMHT 6 weeks post discharge. Secondary outcomes included contact with mental health services at 6 and 12 months. A health economic evaluation was undertaken using service contact at the follow-up time points. We were unable to assess the intervention’s effect on reoffending and longer-term health-care use because of study delays. Results One hundred and fifty prisoners were recruited: 72 were randomised to the intervention and 78 were randomised to the control. Engagement with teams at 6 weeks was 53% for the intervention group compared with 27% for the control group [95% confidence interval (CI) 0.13% to 0.78%; p = 0.012]. At 6 months’ follow-up, intervention participants showed continued increase in engagement with teams compared with control participants (95% CI 0.12% to 0.89%; p = 0.029); there were no significant differences at 12 months. Increased engagement resulted in higher levels of service use and costs for the intervention than for the control. Qualitative data showed the intervention group reporting better continuity of care and improved access to services. Conclusion The intervention significantly improved contact with services at 6 weeks, although at a higher cost than the control. This is important as, in the days and weeks following release, recently released individuals are at a particularly high risk of suicide and drug overdose. Further research is required to establish how teams can better maintain contact with clients when the intervention ends. Future work Further studies are indicated for groups with different needs, for example women, young prisoners and those in police custody, and at other transition points, for example following arrest and short-term custody, and at points of transition between different mental health services. Trial registration Current Controlled Trials ISRCTN98067793. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 5, No. 8. See the NIHR Journals Library website for further project information

BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial.

BACKGROUND: For human immunodeficiency virus (HIV)-infected adolescents facing lifelong antiretroviral therapy (ART), short-cycle therapy (SCT) with long-acting agents offers the potential for drug-free weekends, less toxicity, better adherence and cost savings. OBJECTIVES: To determine whether or not efavirenz (EFV)-based ART in short cycles of 5 days on and 2 days off is as efficacious (in maintaining virological suppression) as continuous EFV-based ART (continuous therapy; CT). Secondary objectives included the occurrence of new clinical HIV events or death, changes in immunological status, emergence of HIV drug resistance, drug toxicity and changes in therapy. DESIGN: Open, randomised, non-inferiority trial. SETTING: Europe, Thailand, Uganda, Argentina and the USA. PARTICIPANTS: Young people (aged 8-24 years) on EFV plus two nucleoside reverse transcriptase inhibitors and with a HIV-1 ribonucleic acid level [viral load (VL)] of  12 months. INTERVENTIONS: Young people were randomised to continue daily ART (CT) or change to SCT (5 days on, 2 days off ART). MAIN OUTCOME MEASURES: Follow-up was for a minimum of 48 weeks (0, 4 and 12 weeks and then 12-weekly visits). The primary outcome was the difference between arms in the proportion with VL > 50 copies/ml (confirmed) by 48 weeks, estimated using the Kaplan-Meier method (12% non-inferiority margin) adjusted for region and age. RESULTS: In total, 199 young people (11 countries) were randomised (n = 99 SCT group, n = 100 CT group) and followed for a median of 86 weeks. Overall, 53% were male; the median age was 14 years (21% ≥ 18 years); 13% were from the UK, 56% were black, 19% were Asian and 21% were Caucasian; and the median CD4% and CD4 count were 34% and 735 cells/mm(3), respectively. By week 48, only one participant (CT) was lost to follow-up. The SCT arm had a 27% decreased drug exposure as measured by the adherence questionnaire and a MEMSCap(™) Medication Event Monitoring System (MEMSCap Inc., Durham, NC, USA) substudy (median cap openings per week: SCT group, n = 5; CT group, n = 7). By 48 weeks, six participants in the SCT group and seven in the CT group had a confirmed VL > 50 copies/ml [difference -1.2%, 90% confidence interval (CI) -7.3% to 4.9%] and two in the SCT group and four in the CT group had a confirmed VL > 400 copies/ml (difference -2.1%, 90% CI -6.2% to 1.9%). All six participants in the SCT group with a VL > 50 copies/ml resumed daily ART, of whom five were resuppressed, three were on the same regimen and two with a switch; two others on SCT resumed daily ART for other reasons. Overall, three participants in the SCT group and nine in the CT group (p = 0.1) changed ART regimen, five because of toxicity, four for simplification reasons, two because of compliance issues and one because of VL failure. Seven young people (SCT group, n = 2; CT group, n = 5) had major non-nucleoside reverse transcriptase inhibitor mutations at VL failure, of whom two (n = 1 SCT group, n = 1 CT group) had the M184V mutation. Two young people had new Centers for Disease Control B events (SCT group, n = 1; CT group, n = 1). There were no significant differences between SCT and CT in grade 3/4 adverse events (13 vs. 14) or in serious adverse events (7 vs. 6); there were fewer ART-related adverse events in the SCT arm (2 vs. 14; p = 0.02). At week 48 there was no evidence that SCT led to increased inflammation using an extensive panel of markers. Young people expressed a strong preference for SCT in a qualitative substudy and in pre- and post-trial questionnaires. In total, 98% of the young people are taking part in a 2-year follow-up extension of the trial. CONCLUSIONS: Non-inferiority of VL suppression in young people on EFV-based first-line ART with a VL of < 50 copies/ml was demonstrated for SCT compared with CT, with similar resistance, safety and inflammatory marker profiles. The SCT group had fewer ART-related adverse events. Further evaluation of the immunological and virological impact of SCT is ongoing. A limitation of the trial is that the results cannot be generalised to settings where VL monitoring is either not available or infrequent, nor to use of low-dose EFV. Two-year extended follow-up of the trial is ongoing to confirm the durability of the SCT strategy. Further trials of SCT in settings with infrequent VL monitoring and with other antiretroviral drugs such as tenofovir alafenamide, which has a long intracellular half-life, and/or dolutegravir, which has a higher barrier to resistance, are planned. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97755073; EUDRACT 2009-012947-40; and CTA 27505/0005/001-0001. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (projects 08/53/25 and 11/136/108), the European Commission through EuroCoord (FP7/2007/2015), the Economic and Social Research Council, the PENTA Foundation, the Medical Research Council and INSERM SC10-US19, France, and will be published in full in Health Technology Assessment; Vol. 20, No. 49. See the NIHR Journals Library website for further project information