Comparison of alternative evidence summary and presentation formats in clinical guideline development: a mixed-method study.

BACKGROUND: Best formats for summarising and presenting evidence for use in clinical guideline development remain less well defined. We aimed to assess the effectiveness of different evidence summary formats to address this gap. METHODS: Healthcare professionals attending a one-week Kenyan, national guideline development workshop were randomly allocated to receive evidence packaged in three different formats: systematic reviews (SRs) alone, systematic reviews with summary-of-findings tables, and 'graded-entry' formats (a 'front-end' summary and a contextually framed narrative report plus the SR). The influence of format on the proportion of correct responses to key clinical questions, the primary outcome, was assessed using a written test. The secondary outcome was a composite endpoint, measured on a 5-point scale, of the clarity of presentation and ease of locating the quality of evidence for critical neonatal outcomes. Interviews conducted within two months following completion of trial data collection explored panel members' views on the evidence summary formats and experiences with appraisal and use of research information. RESULTS: 65 (93%) of 70 participants completed questions on the prespecified outcome measures. There were no differences between groups in the odds of correct responses to key clinical questions. 'Graded-entry' formats were associated with a higher mean composite score for clarity and accessibility of information about the quality of evidence for critical neonatal outcomes compared to systematic reviews alone (adjusted mean difference 0.52, 95% CI 0.06 to 0.99). There was no difference in the mean composite score between SR with SoF tables and SR alone. Findings from interviews with 16 panelists indicated that short narrative evidence reports were preferred for the improved clarity of information presentation and ease of use. CONCLUSIONS: Our findings suggest that 'graded-entry' evidence summary formats may improve clarity and accessibility of research evidence in clinical guideline development. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN05154264

From planning to execution to the future: An overview of a concerted effort to enhance biological control in apple, pear, and walnut orchards in the western U.S.

We embarked on a large project designed to help enhance biological control in apple, pear and walnut orchards in the western U.S., where management programs were in the midst of a transition from older organo-phosphate insecticides to mating disruption and newer reduced-risk insecticides. A “pesticide replacement therapy” approach resulted in unstable management programs with unpredictable outbreaks of spider mites and aphids. Our project was designed to provide growers and pest managers with information on the effects of newer pesticide chemistries on a suite of representative natural enemies in both the laboratory and field, potential of new monitoring tools using herbivore-induced plant volatiles and floral volatiles, phenology of the key natural enemy species, economic consequences of using an enhanced biological control program, and value of an outreach program to get project outcomes into the hands of decision-makers. We present an overview of both the successes and failures of the project and of new projects that have spun off from this project to further enhance biological control in our systems in the near future

Theoretical studies of the historical development of the accounting discipline: a review and evidence

Many existing studies of the development of accounting thought have either been atheoretical or have adopted Kuhn's model of scientific growth. The limitations of this 35-year-old model are discussed. Four different general neo-Kuhnian models of scholarly knowledge development are reviewed and compared with reference to an analytical matrix. The models are found to be mutually consistent, with each focusing on a different aspect of development. A composite model is proposed. Based on a hand-crafted database, author co-citation analysis is used to map empirically the entire literature structure of the accounting discipline during two consecutive time periods, 1972–81 and 1982–90. The changing structure of the accounting literature is interpreted using the proposed composite model of scholarly knowledge development

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Sacred turf: the Wimbledon tennis championships and the changing politics of Englishness

© 2015 Taylor & Francis. This article is about ‘Wimbledon’, widely celebrated – not least in its own publicity material – as the world’s premier tennis tournament. It examines ‘Wimbledon’ essentially as a text (hence the inverted commas), viewed politically and historically. In this context, ‘Wimbledon’ is seen as a signifier of a certain kind of Englishness, carefully adapted to meet changing social and economic circumstance. Loose parallels are drawn between the cultural trajectory of ‘Wimbledon’ and that of the British royal family. The transmutations of ‘Wimbledon’ as a tennis championship are also seen as reflecting Britain’s decline as a world power during the twentieth century

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Promoting help-seeking in response to symptoms amongst primary care patients at high risk of lung cancer: a mixed method study

Background: Lung cancer symptoms are vague and difficult to detect. Interventions are needed to promote early diagnosis, however health services are already pressurised. This study explored symptomology and help-seeking behaviours of primary care patients at ‘high-risk’ of lung cancer (≥50 years old, recent smoking history), to inform targeted interventions. Methods: Mixed method study with patients at eight general practitioner (GP) practices across south England. Study incorporated: postal symptom questionnaire; clinical records review of participant consultation behaviour 12 months pre- and post-questionnaire; qualitative participant interviews (n = 38) with a purposive sample. Results: A small, clinically relevant group (n = 61/908, 6.7%) of primary care patients was identified who, despite reporting potential symptoms of lung cancer in questionnaires, had not consulted a GP ≥12 months. Of nine symptoms associated with lung cancer, 53.4% (629/1172) of total respondents reported ≥1, and 35% (411/1172) reported ≥2. Most participants (77.3%, n = 686/908) had comorbid conditions; 47.8%, (n = 414/908) associated with chest and respiratory symptoms. Participant consulting behaviour significantly increased in the 3-month period following questionnaire completion compared with the previous 3-month period (p = .002), indicating questionnaires impacted upon consulting behaviour. Symptomatic non-consulters were predominantly younger, employed, with higher multiple deprivation scores than their GP practice mean. Of symptomatic non-consulters, 30% (18/61) consulted ≤1 month post-questionnaire, with comorbidities subsequently diagnosed for five participants. Interviews (n = 39) indicated three overarching differences between the views of consulting and non-consulting participants: concern over wasting their own as well as GP time; high tolerance threshold for symptoms; a greater tendency to self-manage symptoms. Conclusions: This first study to examine symptoms and consulting behaviour amongst a primary care population at ‘high- risk’ of lung cancer, found symptomatic patients who rarely consult GPs, might respond to a targeted symptom elicitation intervention. Such GP-based interventions may promote early diagnosis of lung cancer or other comorbidities, without burdening already pressurised services

Attitudes and behaviour predict women's intention to drink alcohol during pregnancy: the challenge for health professionals

Background. To explore women's alcohol consumption in pregnancy, and potential predictors of alcohol consumption in pregnancy including: demographic characteristics; and women's knowledge and attitudes regarding alcohol consumption in pregnancy and its effects on the fetus. Methods. We conducted a national cross-sectional survey via computer assisted telephone interview of 1103 Australian women aged 18 to 45 years. Participants were randomly selected from the Electronic White Pages. Pregnant women were not eligible to participate. Quotas were set for age groups and a minimum of 100 participants per state to ensure a national sample reflecting the population. The questionnaire was based on a Health Canada survey with additional questions constructed by the investigators. Descriptive statistics were calculated and logistic regression analyses were used to assess associations of alcohol consumption in pregnancy with participants' characteristics, knowledge and attitudes.Results. The majority of women (89.4%) had consumed alcohol in the last 12 months. During their last pregnancy (n = 700), 34.1% drank alcohol. When asked what they would do if planning a pregnancy (n = 1103), 31.6% said they would consume alcohol and 4.8% would smoke. Intention to consume alcohol in a future pregnancy was associated with: alcohol use in the last pregnancy (adjusted OR (aOR) 43.9; 95% Confidence Interval (CI) 27.0 to 71.4); neutral or positive attitudes towards alcohol use in pregnancy (aOR 5.1; 95% CI 3.6 to 7.1); intention to smoke in a future pregnancy (aOR 4.7; 95% CI 2.5 to 9.0); and more frequent and higher current alcohol consumption. Conclusions. Women's past pregnancy and current drinking behaviour, and attitudes to alcohol use in pregnancy were the strongest predictors of alcohol consumption in pregnancy. Targeted interventions for women at higher risk of alcohol consumption in pregnancy are needed to change women's risk perception and behaviour