Using simplified peer review processes to fund research: A prospective study

Objective: To prospectively test two simplified peer review processes, estimate the agreement between the simplified and official processes, and compare the costs of peer review. Design, participants and setting: A prospective parallel study of Project Grant proposals submitted in 2013 to the National Health and Medical Research Council (NHMRC) of Australia. The official funding outcomes were compared with two simplified processes using proposals in Public Health and Basic Science. The two simplified processes were: panels of 7 reviewers who met face-to-face and reviewed only the nine-page research proposal and track record (simplified panel); and 2 reviewers who independently reviewed only the nine-page research proposal (journal panel). The official process used panels of 12 reviewers who met face-to-face and reviewed longer proposals of around 100 pages. We compared the funding outcomes of 72 proposals that were peer reviewed by the simplified and official processes. Main outcome measures: Agreement in funding outcomes; costs of peer review based on reviewers’ time and travel costs. Results: The agreement between the simplified and official panels (72%, 95% CI 61% to 82%), and the journal and official panels (74%, 62% to 83%), was just below the acceptable threshold of 75%. Using the simplified processes would save $A2.1–$A4.9 million per year in peer review costs. Conclusions: Using shorter applications and simpler peer review processes gave reasonable agreement with the more complex official process. Simplified processes save time and money that could be reallocated to actual research. Funding agencies should consider streamlining their application processes.

Intravascular device administration sets: Replacement after standard versus prolonged use in hospitalised patients--a study protocol for a randomised controlled trial (The RSVP Trial)

Introduction Vascular access devices (VADs), such as peripheral or central venous catheters, are vital across all medical and surgical specialties. To allow therapy or haemodynamic monitoring, VADs frequently require administration sets (AS) composed of infusion tubing, fluid containers, pressure-monitoring transducers and/or burettes. While VADs are replaced only when necessary, AS are routinely replaced every 3–4 days in the belief that this reduces infectious complications. Strong evidence supports AS use up to 4 days, but there is less evidence for AS use beyond 4 days. AS replacement twice weekly increases hospital costs and workload. Methods and analysis This is a pragmatic, multicentre, randomised controlled trial (RCT) of equivalence design comparing AS replacement at 4 (control) versus 7 (experimental) days. Randomisation is stratified by site and device, centrally allocated and concealed until enrolment. 6554 adult/paediatric patients with a central venous catheter, peripherally inserted central catheter or peripheral arterial catheter will be enrolled over 4 years. The primary outcome is VAD-related bloodstream infection (BSI) and secondary outcomes are VAD colonisation, AS colonisation, all-cause BSI, all-cause mortality, number of AS per patient, VAD time in situ and costs. Relative incidence rates of VAD-BSI per 100 devices and hazard rates per 1000 device days (95% CIs) will summarise the impact of 7-day relative to 4-day AS use and test equivalence. Kaplan-Meier survival curves (with log rank Mantel-Cox test) will compare VAD-BSI over time. Appropriate parametric or non-parametric techniques will be used to compare secondary end points. p Values of <0.05 will be considered significant.

Wikipedia, collective authorship, and the politics of knowledge

This chapter considers the legal ramifications of Wikipedia, and other online media, such as the Encyclopedia of Life. Nathaniel Tkacz (2007) has observed: 'Wikipedia is an ideal entry-point from which to approach the shifting character of knowledge in contemporary society.' He observes: 'Scholarship on Wikipedia from computer science, history, philosophy, pedagogy and media studies has moved beyond speculation regarding its considerable potential, to the task of interpreting - and potentially intervening in - the significance of Wikipedia's impact' (Tkacz 2007). After an introduction, Part II considers the evolution and development of Wikipedia, and the legal troubles that have attended it. It also considers the establishment of rival online encyclopedia - such as Citizendium set up by Larry Sanger, the co-founder of Wikipedia; and Knol, the mysterious new project of Google. Part III explores the use of mass, collaborative authorship in the field of science. In particular, it looks at the development of the Encyclopedia of Life, which seeks to document the world's biodiversity. This chapter expresses concern that Wiki-based software had to develop in a largely hostile and inimical legal environment. It contends that copyright law and related fields of intellectual property need to be reformed in order better to accommodate users of copyright material (Rimmer 2007). This chapter makes a number of recommendations. First, there is a need to acknowledge and recognize forms of mass, collaborative production and consumption - not just individual authorship. Second, the view of a copyright 'work' and other subject matter as a complete and closed piece of cultural production also should be reconceptualised. Third, the defense of fair use should be expanded to accommodate a wide range of amateur, peer-to-peer production activities - not only in the United States, but in other jurisdictions as well. Fourth, the safe harbor protections accorded to Internet intermediaries, such as Wikipedia, should be strengthened. Fifth, there should be a defense in respect of the use of 'orphan works' - especially in cases of large-scale digitization. Sixth, the innovations of open source licensing should be expressly incorporated and entrenched within the formal framework of copyright laws. Finally, courts should craft judicial remedies to take into account concerns about political censorship and freedom of speech.

The role of time pressure and different psychological safety climate referents in the prediction of nurses’ hand hygiene compliance

In this study of 638 Australian nurses, compliance to hand hygiene (HH), as defined by the “five moments” recommended by the World Health Organisation (2009), was examined. Hypotheses focused on the extent to which time pressure reduces compliance and safety climate (operationalised in relation to HH using colleagues, manager, and hospital as referents) increases compliance. It also was proposed that HH climate would interact with time pressure, such that the negative effects of time pressure would be less marked when HH climate is high. The extent to which the three HH climate variables would interact among each other, either in the form of boosting or compensatory effects, was tested in an exploratory manner. A prospective research design was used in which time pressure and the HH climate variables were assessed at Time 1 and compliance was assessed by self-report two weeks later. Compliance was high but varied significantly across the 5 HH Moments, suggesting that nurses make distinctions between inherent and elective HH and also seemed to engage in some implicit rationing of HH. Time pressure dominated the utility of HH climate to have its positive impact on compliance. The most conducive workplace for compliance was one low in time pressure and high in HH climate. Colleagues were very influential in determining compliance, more so than the manager and hospital. Manager and hospital support for HH enhanced the positive effects of colleagues on compliance. Providing training and enhancing knowledge was important, not just for compliance, but for safety climate.

Bayesian refinement of association signals for 14 loci in 3 common diseases

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

Differences in identifying healthcare associated infections using clinical vignettes and the influence of respondent characteristics: A cross-sectional survey of Australian infection prevention staff

Background Australia has commenced public reporting and benchmarking of healthcare associated infections (HAIs), despite not having a standardised national HAI surveillance program. Annual hospital Staphylococcus aureus bloodstream (SAB) infection rates are released online, with other HAIs likely to be reported in the future. Although there are known differences between hospitals in Australian HAI surveillance programs, the effect of these differences on reported HAI rates is not known. Objective To measure the agreement in HAI identification, classification, and calculation of HAI rates, and investigate the influence of differences amongst those undertaking surveillance on these outcomes. Methods A cross-sectional online survey exploring HAI surveillance practices was administered to infection prevention nurses who undertake HAI surveillance. Seven clinical vignettes describing HAI scenarios were included to measure agreement in HAI identification, classification, and calculation of HAI rates. Data on characteristics of respondents was also collected. Three of the vignettes were related to surgical site infection and four to bloodstream infection. Agreement levels for each of the vignettes were calculated. Using the Australian SAB definition, and the National Health and Safety Network definitions for other HAIs, we looked for an association between the proportion of correct answers and the respondents’ characteristics. Results Ninety-two infection prevention nurses responded to the vignettes. One vignette demonstrated 100 % agreement from responders, whilst agreement for the other vignettes varied from 53 to 75 %. Working in a hospital with more than 400 beds, working in a team, and State or Territory was associated with a correct response for two of the vignettes. Those trained in surveillance were more commonly associated with a correct response, whilst those working part-time were less likely to respond correctly. Conclusion These findings reveal the need for further HAI surveillance support for those working part-time and in smaller facilities. It also confirms the need to improve uniformity of HAI surveillance across Australian hospitals, and raises questions on the validity of the current comparing of national HAI SAB rates.

Educational interventions for preventing vascular catheter bloodstream infections in critical care: Evidence map, systematic review and economic evaluation

Background Bloodstream infections resulting from intravascular catheters (catheter-BSI) in critical care increase patients' length of stay, morbidity and mortality, and the management of these infections and their complications has been estimated to cost the NHS annually £19.1–36.2M. Catheter-BSI are thought to be largely preventable using educational interventions, but guidance as to which types of intervention might be most clinically effective is lacking. Objective To assess the effectiveness and cost-effectiveness of educational interventions for preventing catheter-BSI in critical care units in England. Data sources Sixteen electronic bibliographic databases – including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), NHS Economic Evaluation Database (NHS EED), EMBASE and The Cochrane Library databases – were searched from database inception to February 2011, with searches updated in March 2012. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify any additional references. Review methods References were screened independently by two reviewers using a priori selection criteria. A descriptive map was created to summarise the characteristics of relevant studies. Further selection criteria developed in consultation with the project Advisory Group were used to prioritise a subset of studies relevant to NHS practice and policy for systematic review. A decision-analytic economic model was developed to investigate the cost-effectiveness of educational interventions for preventing catheter-BSI. Results Seventy-four studies were included in the descriptive map, of which 24 were prioritised for systematic review. Studies have predominantly been conducted in the USA, using single-cohort before-and-after study designs. Diverse types of educational intervention appear effective at reducing the incidence density of catheter-BSI (risk ratios statistically significantly < 1.0), but single lectures were not effective. The economic model showed that implementing an educational intervention in critical care units in England would be cost-effective and potentially cost-saving, with incremental cost-effectiveness ratios under worst-case sensitivity analyses of < £5000/quality-adjusted life-year. Limitations Low-quality primary studies cannot definitively prove that the planned interventions were responsible for observed changes in catheter-BSI incidence. Poor reporting gave unclear estimates of risk of bias. Some model parameters were sourced from other locations owing to a lack of UK data. Conclusions Our results suggest that it would be cost-effective and may be cost-saving for the NHS to implement educational interventions in critical care units. However, more robust primary studies are needed to exclude the possible influence of secular trends on observed reductions in catheter-BSI.

Costing the Australian National Hand Hygiene Initiative

Background The Australian National Hand Hygiene Initiative (NHHI) is a major patient safety programme co-ordinated by Hand Hygiene Australia (HHA) and funded by the Australian Commission for Safety and Quality in Health Care. The annual costs of running this programme need to be understood to know the cost-effectiveness of a decision to sustain it as part of health services. Aim To estimate the annual health services cost of running the NHHI; the set-up costs are excluded. Methods A health services perspective was adopted for the costing and collected data from the 50 largest public hospitals in Australia that implemented the initiative, covering all states and territories. The costs of HHA, the costs to the state-level infection-prevention groups, the costs incurred by each acute hospital, and the costs for additional alcohol-based hand rub are all included. Findings The programme cost AU$5.56 million each year (US$5.76, £3.63 million). Most of the cost is incurred at the hospital level (65%) and arose from the extra time taken for auditing hand hygiene compliance and doing education and training. On average, each infection control practitioner spent 5 h per week on the NHHI, and the running cost per annum to their hospital was approximately AU$120,000 in 2012 (US$124,000, £78,000). Conclusion Good estimates of the total costs of this programme are fundamental to understanding the cost-effectiveness of implementing the NHHI. This paper reports transparent costing methods, and the results include their uncertainty.

The return to work experiences of middle-aged Australian workers diagnosed with colorectal cancer: a matched cohort study

Background Few studies have been undertaken to understand the employment impact in patients with colorectal cancer and none in middle-aged individuals with cancer. This study described transitions in, and key factors influencing, work participation during the 12 months following a diagnosis of colorectal cancer. Methods We enrolled 239 adults during 2010 and 2011who were employed at the time of their colorectal cancer diagnosis and were prospectively followed over 12 months. They were compared to an age- and gender-matched general population group of 717 adults from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data were collected using telephone and postal surveys. Primary outcomes included work participation at 12 months, changes in hours worked and time to work re-entry. Multivariable logistic and Cox proportional hazards models were undertaken. Results A significantly higher proportion of participants with colorectal cancer (27%) had stopped working at 12 months than participants from the comparison group (8%) (p < 0.001). Participants with cancer who returned to work took a median of 91 days off work (25–75 percentiles: 14–183 days). For participants with cancer, predictors of not working at 12 months included: being older, lower BMI and lower physical well-being. Factors related to delayed work re-entry included not being university-educated, working for an employer with more than 20 employees in a non-professional or managerial role, longer hospital stay, poorer perceived financial status and having or had chemotherapy. Conclusions In middle-adulthood, those working and diagnosed with colorectal cancer can expect to take around three months off work. Individuals treated with chemotherapy, without a university degree and from large employers could be targeted for specific assistance for a more timely work entry.

Living well with diabetes: 24-month outcomes from a randomized trial of telephone-delivered weight loss and physical activity intervention to improve glycemic control

OBJECTIVE: To evaluate the effectiveness of a telephone-delivered behavioral weight loss and physical activity intervention targeting Australian primary care patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Pragmatic randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151). Reported here are 18-month (end-of-intervention) and 24-month (maintenance) primary outcomes of weight, moderate-to-vigorous-intensity physical activity (MVPA; via accelerometer), and HbA1c level. Secondary outcomes include dietary energy intake and diet quality, waist circumference, lipid levels, and blood pressure. Data were analyzed via adjusted linear mixed models with multiple imputation of missing data. RESULTS: Relative to usual-care participants, telephone counseling participants achieved modest, but significant, improvements in weight loss (relative rate [RR] -1.42% of baseline body weight [95% CI -2.54 to -0.30% of baseline body weight]), MVPA (RR 1.42 [95% CI 1.06-1.90]), diet quality (2.72 [95% CI 0.55-4.89]), and waist circumference (-1.84 cm [95% CI -3.16 to -0.51 cm]), but not in HbA1c level (RR 0.99 [95% CI 0.96-1.02]), or other cardio-metabolic markers. None of the outcomes showed a significant change/deterioration over the maintenance period. However, only the intervention effect for MVPA remained statistically significant at 24 months. CONCLUSIONS: The modest improvements in weight loss and behavior change, but the lack of changes in cardio-metabolic markers, may limit the utility, scalability, and sustainability of such an approach.

A randomized trial of fellowships for early career researchers finds a high reliability in funding decisions

Objectives Funding for early career researchers in Australia's largest medical research funding scheme is determined by a competitive peer-review process using a panel of four reviewers. The purpose of this experiment was to appraise the reliability of funding by duplicating applications that were considered by separate grant review panels. Study Design and Methods Sixty duplicate applications were considered by two independent grant review panels that were awarding funding for Australia's National Health and Medical Research Council. Panel members were blinded to which applications were included in the experiment and to whether it was the original or duplicate application. Scores were compared across panels using Bland–Altman plots to determine measures of agreement, including whether agreement would have impacted on actual funding. Results Twenty-three percent of the applicants were funded by both panels and 60 percent were not funded by both, giving an overall agreement of 83 percent [95% confidence interval (CI): 73%, 92%]. The chance-adjusted agreement was 0.75 (95% CI: 0.58, 0.92). Conclusion There was a comparatively high level of agreement when compared with other types of funding schemes. Further experimental research could be used to determine if this higher agreement is due to nature of the application, the composition of the assessment panel, or the characteristics of the applicants.

Study of carotid arterial plaque stress for symptomatic and asymptomatic patients

Stroke is one of the leading causes of death in the world, resulting mostly from the sudden ruptures of atherosclerosis carotid plaques. Until now, the exact plaque rupture mechanism has not been fully understood, and also the plaque rupture risk stratification. The advanced multi-spectral magnetic resonance imaging (MRI) has allowed the plaque components to be visualized in-vivo and reconstructed by computational modeling. In the study, plaque stress analysis using fully coupled fluid structure interaction was applied to 20 patients (12 symptomatic and 8 asymptomatic) reconstructed from in-vivo MRI, followed by a detailed biomechanics analysis, and morphological feature study. The locally extreme stress conditions can be found in the fibrous cap region, 85% at the plaque shoulder based on the present study cases. Local maximum stress values predicted in the plaque region were found to be significantly higher in symptomatic patients than that in asymptomatic patients (200±43. kPa vs. 127±37. kPa, p=0.001). Plaque stress level, defined by excluding 5% highest stress nodes in the fibrous cap region based on the accumulative histogram of stress experienced on the computational nodes in the fibrous cap, was also significantly higher in symptomatic patients than that in asymptomatic patients (154±32. kPa vs. 111±23. kPa, p<0.05). Although there was no significant difference in lipid core size between the two patient groups, symptomatic group normally had a larger lipid core and a significantly thinner fibrous cap based on the reconstructed plaques using 3D interpolation from stacks of 2D contours. Plaques with a higher stenosis were more likely to have extreme stress conditions upstream of plaque throat. The combined analyses of plaque MR image and plaque stress will advance our understanding of plaque rupture, and provide a useful tool on assessing plaque rupture risk.

Stress analysis of carotid atheroma in transient ischemic attack patients: Evidence for extreme stress-induced plaque rupture

Plaque rupture has been considered to be the result of its structural failure. The aim of this study is to suggest a possible link between higher stresses and rupture sites observed from in vivo magnetic resonance imaging (MRI) of transient ischemic attack (TIA) patients, by using stress analysis methods. Three patients, who had recently suffered a TIA, underwent in vivo multi-spectral MR imaging. Based on plaque geometries reconstructed from the post-rupture status, six pre-rupture plaque models were generated for each patient dataset with different reconstructions of rupture sites to bridge the gap of fibrous cap from original MRI images. Stress analysis by fluid structure interaction simulation was performed on the models, followed by analysis of local stress concentration distribution and plaque rupture sites. Furthermore, the sensitivity of stress analysis to the pre-rupture plaque geometry reconstruction was examined. Local stress concentrations were found to be located at the plaque rupture sites for the three subjects studied. In the total of 18 models created, the locations of the stress concentration regions were similar in 17 models in which rupture sites were always associated with high stresses. The local stress concentration region moved from circumferential center to the shoulder region (slightly away from the rupture site) for a case with a thick fibrous cap. Plaque wall stress level in the rupture locations was found to be much higher than the value in non-rupture locations. The good correlation between local stress concentrations and plaque rupture sites, and generally higher plaque wall stress level in rupture locations in the subjects studied could provide indirect evidence for the extreme stress-induced plaque rupture hypothesis. Local stress concentration in the plaque region could be one of the factors contributing to plaque rupture.

Normalized wall index specific and MRI-based stress analysis of atherosclerotic carotid plaques: A study comparing acutely symptomatic and asymptomatic patients

Background: Biomechanical stresses play an important role in determining plaque stability. Quantification of these simulated stresses can be potentially used to assess plaque vulnerability and differentiate different patient groups. Methods and Results: 54 asymptomatic and 45 acutely symptomatic patients underwent in vivo multicontrast magnetic resonance imaging (MRI) of the carotid arteries. Plaque geometry used for finite element analysis was derived from in vivo MRI at the sites of maximum and minimum plaque burden. In total, 198 slices were used for the computational simulations. A pre-shrink technique was used to refine the simulation. Maximum principle stress at the vulnerable plaque sites (ie, critical stress) was extracted for the selected slices and a comparison was performed between the 2 groups. Critical stress in the slice with maximum plaque burden is significantly higher in acutely symptomatic patients as compared to asymptomatic patients (median, inter quartile range: 198.0 kPa (119.8-359.0 kPa) vs 138.4 kPa (83.8-242.6 kPa), P=0.04). No significant difference was found in the slice with minimum plaque burden between the 2 groups (196.7 kPa (133.3-282.7 kPa) vs 182.4 kPa (117.2-310.6 kPa), P=0.82). Conclusions: Acutely symptomatic carotid plaques have significantly high biomechanical stresses than asymptomatic plaques. This might be potentially useful for establishing a biomechanical risk stratification criteria based on plaque burden in future studies.

Arterial luminal curvature and fibrous-cap thickness affect critical stress conditions within atherosclerotic plaque: An in vivo MRI-based 2D finite-element study

High mechanical stress in atherosclerotic plaques at vulnerable sites, called critical stress, contributes to plaque rupture. The site of minimum fibrous cap (FC) thickness (FCMIN) and plaque shoulder are well-documented vulnerable sites. The inherent weakness of the FC material at the thinnest point increases the stress, making it vulnerable, and it is the big curvature of the lumen contour over FC which may result in increased plaque stress. We aimed to assess critical stresses at FCMIN and the maximum lumen curvature over FC (LCMAX) and quantify the difference to see which vulnerable site had the highest critical stress and was, therefore, at highest risk of rupture. One hundred patients underwent high resolution carotid magnetic resonance (MR) imaging. We used 352 MR slices with delineated atherosclerotic components for the simulation study. Stresses at all the integral nodes along the lumen surface were calculated using the finite-element method. FCMIN and LCMAX were identified, and critical stresses at these sites were assessed and compared. Critical stress at FC MIN was significantly lower than that at LCMAX (median: 121.55 kPa; inter quartile range (IQR) = [60.70-180.32] kPa vs. 150.80 kPa; IQR = [91.39-235.75] kPa, p < 0.0001). If critical stress at FCMIN was only used, then the stress condition of 238 of 352 MR slices would be underestimated, while if the critical stress at LCMAX only was used, then 112 out of 352 would be underestimated. Stress analysis at FCMIN and LCMAX should be used for a refined mechanical risk assessment of atherosclerotic plaques, since material failure at either site may result in rupture.