Flying is the safest way to travel

Independent investigations of aviation accidents and incidents have been broadly accepted within the aviation sector throughout its history as a valuable tool to enhance safety. Such investigations enable the sector to learn by establishing the sequence of events that provides a satisfactory explanation of the accident leads to the drafting of recommendations to prevent reoccurrences. In addition, these investigations, which are publicly disseminated, encourage public confidence in the sector. Other transport sectors, including road, rail and water, have been slower in coming to enjoy the same acceptance of independent investigations; here, there is considerable variation amongst nations, and—with the exception of the International Civil Aviation Organization agreement—almost no international consistency. This article examines why aviation has had a different tradition in this regard. Reasons are found in parallel growth of aviation technology and the philosophy of investigative bodies, the inherently international aspect of commercial aviation, and the role of public and political pressure following major accidents. The safety investigative orientation of the aviation sector is gradually expanding to other transport sections and beyond that to other sectors such as fixed site production plants, health care, and management of natural disasters. With the newly installed Safety Investigation Board, the Netherlands has arguably placed itself at the head of this league table

A four-step strategy for handling missing outcome data in randomised trials affected by a pandemic.

BACKGROUND: The coronavirus pandemic (Covid-19) presents a variety of challenges for ongoing clinical trials, including an inevitably higher rate of missing outcome data, with new and non-standard reasons for missingness. International drug trial guidelines recommend trialists review plans for handling missing data in the conduct and statistical analysis, but clear recommendations are lacking. METHODS: We present a four-step strategy for handling missing outcome data in the analysis of randomised trials that are ongoing during a pandemic. We consider handling missing data arising due to (i) participant infection, (ii) treatment disruptions and (iii) loss to follow-up. We consider both settings where treatment effects for a 'pandemic-free world' and 'world including a pandemic' are of interest. RESULTS: In any trial, investigators should; (1) Clarify the treatment estimand of interest with respect to the occurrence of the pandemic; (2) Establish what data are missing for the chosen estimand; (3) Perform primary analysis under the most plausible missing data assumptions followed by; (4) Sensitivity analysis under alternative plausible assumptions. To obtain an estimate of the treatment effect in a 'pandemic-free world', participant data that are clinically affected by the pandemic (directly due to infection or indirectly via treatment disruptions) are not relevant and can be set to missing. For primary analysis, a missing-at-random assumption that conditions on all observed data that are expected to be associated with both the outcome and missingness may be most plausible. For the treatment effect in the 'world including a pandemic', all participant data is relevant and should be included in the analysis. For primary analysis, a missing-at-random assumption - potentially incorporating a pandemic time-period indicator and participant infection status - or a missing-not-at-random assumption with a poorer response may be most relevant, depending on the setting. In all scenarios, sensitivity analysis under credible missing-not-at-random assumptions should be used to evaluate the robustness of results. We highlight controlled multiple imputation as an accessible tool for conducting sensitivity analyses. CONCLUSIONS: Missing data problems will be exacerbated for trials active during the Covid-19 pandemic. This four-step strategy will facilitate clear thinking about the appropriate analysis for relevant questions of interest

Is the involvement of opinion leaders in the implementation of research findings a feasible strategy?

BACKGROUND: There is only limited empirical evidence about the effectiveness of opinion leaders as health care change agents. AIM: To test the feasibility of identifying, and the characteristics of, opinion leaders using a sociometric instrument and a self-designating instrument in different professional groups within the UK National Health Service. DESIGN: Postal questionnaire survey. SETTING AND PARTICIPANTS: All general practitioners, practice nurses and practice managers in two regions of Scotland. All physicians and surgeons (junior hospital doctors and consultants) and medical and surgical nursing staff in two district general hospitals and one teaching hospital in Scotland, as well as all Scottish obstetric and gynaecology, and oncology consultants. RESULTS: Using the sociometric instrument, the extent of social networks and potential coverage of the study population in primary and secondary care was highly idiosyncratic. In contrast, relatively complex networks with good coverage rates were observed in both national specialty groups. Identified opinion leaders were more likely to have the expected characteristics of opinion leaders identified from diffusion and social influence theories. Moreover, opinion leaders appeared to be condition-specific. The self-designating instrument identified more opinion leaders, but it was not possible to estimate the extent and structure of social networks or likely coverage by opinion leaders. There was poor agreement in the responses to the sociometric and self-designating instruments. CONCLUSION: The feasibility of identifying opinion leaders using an off-the-shelf sociometric instrument is variable across different professional groups and settings within the NHS. Whilst it is possible to identify opinion leaders using a self-designating instrument, the effectiveness of such opinion leaders has not been rigorously tested in health care settings. Opinion leaders appear to be monomorphic (different leaders for different issues). Recruitment of opinion leaders is unlikely to be an effective general strategy across all settings and professional groups; the more specialised the group, the more opinion leaders may be a useful strategy

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

BACKGROUND: Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. METHODS AND FINDINGS: We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. CONCLUSIONS: The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. TRIAL REGISTRATION: This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656

Using and Reporting the Delphi Method for Selecting Healthcare Quality Indicators: A Systematic Review

OBJECTIVE: Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice. METHODOLOGY AND MAIN FINDING: Three electronic data bases were searched over a 30 years period (1978-2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility. CONCLUSION: The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Completeness of reporting and risks of overstating impact in cluster randomised trials : a systematic review

Acknowledgments We received no funding specifically for this systematic review. ELT is funded in part by awards R01-AI141444 from the National Institute of Allergy and Infectious Diseases and R01-MH120649 from the US National Institute of Mental Health; both Institutes are part of the National Institutes of Health (NIH). JAG and ACP's support of this project was made possible (in part) by grant number UL1TR002553 from the National Center for Advancing Translational Sciences of the NIH, and the NIH Roadmap for Medical Research. JEM is supported by an Australian National Health and Medical Research Council Career Development Fellowship (APP1143429). SN was supported by an award that is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, and part of the EDCTP2 programme supported by the European Union (grant reference MR/R010161/1). ABF acknowledges funding support from the National Health and Medical Research Council of Australia (grant ID 1183303). KH is funded by a National Institute for Health Research Senior Research Fellowship SRF-2017-10-002. The contents of the research included in this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funders. The research contributed by all authors of this manuscript are independent of their funders. Specifically, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We wish to thank the three reviewers for their insightful comments and constructive feedback.Peer reviewedPublisher PD

Note---On Choosing Between Rev. Bayes and Prof. Von Neumann

In a recent issue of Management Science, Kadane and Larkey [10], [11] debated with Harsanyi [8], [9] on the relative merits of strategic policies derived from game theoretic vs. Bayesian decision-theoretic orientations. While the fact that the two orientations are virtually first cousins gives a Middle Eastern flavor to the discussion, just as the problems of that unfortunate spot on the globe, the two orientations have substantive differences that should be attended to by people faced with managerial decision problems modelled as games.