Intermittent preventive treatment with sulphadoxine-pyrimethamine but not dihydroartemisinin-piperaquine modulates the relationship between inflammatory markers and adverse pregnancy outcomes in Malawi

Women in malaria-endemic areas receive sulphadoxine-pyrimethamine (SP) as Intermittent Preventive Treatment in Pregnancy (IPTp) to reduce malaria. While dihydroartemisinin-piperaquine (DP) has superior antimalarial properties as IPTp, SP is associated with superior fetal growth. As maternal inflammation influences fetal growth, we investigated whether SP alters the relationship between inflammation and birth outcomes. We measured C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) at enrollment (16–28 gestation weeks (gw)), visit 3 (24–36 gw) and delivery in 1319 Malawian women randomized to receive monthly SP, DP, or DP and single-dose azithromycin (AZ) in the IMPROVE trial (NCT03208179). Logistic regression was used to assess the relationship between adverse outcomes, inflammation, and treatment arm. Elevated AGP at enrollment was associated with adverse birth outcome (aRR 1.40, 95% CI: 1.15, 1.70), with similar associations observed across treatment arms, exceptions being that elevated AGP was associated with low maternal weight gain in SP recipients (aRR 1.94, 95% CI: 1.36, 2.76) and with small for gestational age in DP+AZ recepients (aRR 1.49, 95% CI 1.02, 2.17). At visit 3 there were few associations between inflammation andoutcomes. At delivery, women with elevated AGP receiving either DP or DP+AZ had an increased risk of adverse birth outcomes (aRR 1.60, 95% CI: 1.28, 2.00), including low birth weight, pre-term birth and foetal loss, this was not seen in women receiving SP (aRR 0.82, 95% CI: 0.54, 1.26). The risk of an association between elevated AGP and adverse birth outcome was higher in those receiving DP or DP+AZ compared to those receiving SP (aRR 1.95, 95% CI: 1.21, 3.13). No clear associations between CRP and adverse outcomes were observed. AGP identified women at risk of adverse pregnancy outcomes. SP modifies the relationship between inflammatory biomarkers and adverse outcomes. Our findings provide insights into potential mechanisms by which SP may improve pregnancy outcomes

Sn-W-Critical metals & associated magmatic systems: an international geological conference. Extended abstracts

[From Introduction:] Our world will be a different place by 2040. Electric vehicles will dominate the roads, and clean renewable sources will provide most of our energy needs. The internal combustion engine will be headed for the history books to join the computer floppy disc and the Walkman. Enabling this technological revolution will require steady supplies of specialty metals including tin, tungsten, indium and the rare earth elements. The rare earth elements, indium and tungsten have respectively been ranked first, second and third of the most critical commodities (Skirrow et al, 2013), and according to a study by MIT, tin comes out as the metal to be most impacted by new technology

Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation

The systemic understanding of oncogenic kinase signalling is still limited. Here, the authors combine chemical proteomics with functional screens to assess the impact of oncogenic Src on the expressed kinome and identify SGK1 as a critical mediator of Src-induced cell transformation

Community-onset Escherichia coli infection resistant to expanded- spectrum cephalosporins in low-prevalence countries

Background By global standards the prevalence of community onset expanded-spectrum cephalosporin resistant Escherichia coli (ESC-R-EC) remains low in Australia and New Zealand. Of concern, our countries are in a unique position with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbours with high ESC-R-EC rates. We aim to characterize the risks and dynamics of community onset ESC-R-EC in our low-prevalence region.Methods A case-control methodology was used. Patients with ESC-R-EC or susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary hospitals in Australia and New Zealand. Epidemiological data was prospectively collected and bacteria were retained for analysis.Results In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R amongst E. coli including birth on the Indian subcontinent (OR=11.13, 2.17-56.98, p=0.003), urinary tract infection in the past year (per infection OR=1.430, 1.13-1.82, p=0.003), travel to South East Asia, China, Indian subcontinent, Africa and the Middle East (OR=3.089, 1.29-7.38, p=0.011), prior exposure to trimethoprim+/-sulfamethoxazole &amp;/or an expanded-spectrum cephalosporin (OR=3.665, 1.30-10.35, p=0.014) and healthcare exposure in the previous six months (OR=3.16, 1.54-6.46, p=0.02).Amongst our ESC-R-EC the blaCTX-M ESBLs was dominant (83% of ESC-R-EC), and the worldwide pandemic clone ST-131 was frequent (45% of ESC-R-EC).Conclusion In our low prevalence setting, ESC-R amongst community onset E. coli may be associated with both &lsquo;export&rsquo; from healthcare facilities into the community and direct &lsquo;import&rsquo; into the community from high-prevalence regions.<br /

Transforming Practice: Checklists for Delivering Change

Delivering a revolution in evidence use requires a cultural change across society. For a wide range of groups (practitioners, knowledge brokers, organisations, organisational leaders, policy makers, funders, researchers, journal publishers, the wider conservation community, educators, writers, and journalists), options are described to facilitate a change in practice, and a series of downloadable checklists are provided.publishedVersio

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London