Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Pharmacokinetic study of once-daily formulation of tacrolimus (Advagraf) in stable Chinese kidney transplant recipients

Background/Purpose: The objective of this study is to determine whether tacrolimus trough level is appropriate for therapeutic drug monitoring (TDM) of Advagraf in stable Chinese kidney transplant recipients (KTRs). Methods: In this single-center pharmacokinetic study, stable adult Chinese KTRs on Advagraf were recruited and their blood tacrolimus levels measured at 12 time points within 24 hours. Trough level was defined as predose drug level (C0). The pharmacokinetic parameters were calculated using standardized noncompartmental methods. Drug exposure, defined as 24-hour area under the curve (AUC0–24), was calculated using the linear trapezoidal method. Whole blood tacrolimus level measurement was performed by high-performance liquid chromatography/tandem mass spectrophotometry. Results: Fourteen patients (8 males; mean age, 47.1 ± 9.2 years; mean duration of transplant, 8.3 ± 3.6 years) completed the study. The mean C0 was 4.4 ± 1.9 ng/mL, and the mean AUC0–24 was 143.8 ± 57.0 ng h/mL. The mean maximum concentration (Cmax) was 10.2 ± 3.9 ng/mL, and the median time to Cmax was 2.0 hours (interquartile range, 1.0–3.0 hours). There was a strong correlation between C0 and AUC0–24 (r = 0.90, p < 0.001). Patients receiving diltiazem had higher mean AUC0–24 (153.0 ± 55.3 ng h/mL vs. 110.1 ± 60.1 ng h/mL) despite a lower dose (mean tacrolimus dose, 0.039 ± 0.022 mg/kg/d vs. 0.054 ± 0.021 mg/kg/d), although both differences did not reach statistical significance. Apart from C0, tacrolimus level obtained from 6 hours to 12 hours (C6 to C12) also had good correlation with AUC0–24. Conclusion: Tacrolimus trough level is a good surrogate marker for TDM of Advagraf in stable Chinese KTRs. The role of C6 to C12 in TDM remains to be determined. 背景 / 目的: 本研究旨在調查在病情穩定的華裔腎臟移植接受者 (KTRs) 間,Cmin 是否適用於藥物血中濃度監測 (TDM)。 方法: 在這一項單中心藥物動力學研究中,對象為病情穩定的華裔 KTRs,在 24 小時內 12 個時間點接受了動脈血的取樣,谷值的定義為服藥前藥物濃度 (C0)。藥物動力學參數的計算是採用標準化無房室模式,AUC0–24 的計算採用線性梯形方式。全血 tacrolimus 濃度的測量儀器,則是採用高效能液相色層分析串聯質譜儀 (HPLCMS/MS)。 結果: 本研究共納入 14 位服用 Advagraf® 的病人,平均 C0 為 4.4 ± 1.9 ng/ml,平均 AUC0–24 為 143.8 ± 57.0 ng·h/ml,平均最高濃度 Cmax 為 10.2 ± 3.9 ng/ml,達到 Cmax 的時間中位數 tmax 則為 2.0 小時 (四分位數間距 1.0–3.0 小時);C0 與 AUC0–24 存在明顯的相關性 (r = 0.90、p < 0.001)。在接受 diltiazem 的病人中,平均 AUC0–24 較高 (153.0 ± 55.3 ng·h/ml vs. 110.1 ± 60.1 ng·h/ml),即使他們服用較低的 tacrolimus 劑量 (平均劑量 0.039 ± 0.022 mg/kg/day vs. 0.054 ± 0.021 mg/kg/day);這兩種差異未達統計學意義。除了 C0 之外,6 至 12 小時 (C6 to C12) 之 tacrolimus 濃度亦與 AUC0–24 存在顯著的相關性。 結論: 對於病情穩定的華裔 KTRs,tacrolimus 谷值乃 AUC0–24 的一個良好替代指標;至於 C6 to C12 的角色則仍有待證實

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