The impact of religion on changes in end-of-life practices in European intensive care units: a comparative analysis over 16 years.

PURPOSE: Religious beliefs affect end-of-life practices in intensive care units (ICUs). Changes over time in end-of-life practices were not investigated regarding religions. METHODS: Twenty-two European ICUs (3 regions: Northern, Central, and Southern Europe) participated in both Ethicus-1 (years 1999-2000) and Ethicus-2 studies (years 2015-2016). Data of ICU patients who died or had limitations of life-sustaining therapy were analysed regarding changes in end-of-life practices and patient/physician religious affiliations. Frequencies, timing of decision-making, and religious affiliations of physicians/patients were compared using the same definitions. RESULTS: In total, 4592 adult ICU patients (n = 2807 Ethicus-1, n = 1785 Ethicus-2) were analysed. In both studies, patient and physician religious affiliations were mostly Catholic, Greek Orthodox, Jewish, Protestant, or unknown. Treating physicians (but not patients) commonly reported no religious affiliation (18%). Distribution of end-of-life practices with respect to religion and geographical regions were comparable between the two studies. Withholding [n = 1143 (40.7%) Ethicus-1 and n = 892 (50%) Ethicus-2] and withdrawing [n = 695 (24.8%) Ethicus-1 and n = 692 (38.8%) Ethicus-2] were most commonly decided. No significant changes in end-of-life practices were observed for any religion over 16 years. The number of end-of-life discussions with patients/ families/ physicians increased, while mortality and time until first decision decreased. CONCLUSIONS: Changes in end-of-life practices observed over 16 years appear unrelated to religious affiliations of ICU patients or their treating physicians, but the effects of religiosity and/or culture could not be assessed. Shorter time until decision in the ICU and increased numbers of patient and family discussions may indicate increased awareness of the importance of end-of-life decision-making in the ICU.

Global Comparison of Communication of End-of-Life Decisions in the ICU.

BACKGROUND: Prolonging life in the ICU increasingly is possible, so decisions to limit life-sustaining therapies frequently are made and communicated to patients and families or surrogates. Little is known about worldwide communication practices and influencing factors. RESEARCH QUESTION: Are there regional differences in end-of-life communication practices in ICUs worldwide? STUDY DESIGN AND METHODS: This analysis of data from a prospective, international study specifically addressed end-of-life communications in consecutive patients who died or had limitation of life-sustaining therapy over 6 months in 199 ICUs in 36 countries, grouped regionally. End-of-life decisions were recorded for each patient and ethical practice was assessed retrospectively for each ICU using a 12-point questionnaire developed previously. RESULTS: Of 87,951 patients admitted, 12,850 died or experienced a limitation of therapy (14.6%). Of these, 1,199 patients (9.3%) were known to have an advance directive, and wishes were elicited from 6,456 patients (50.2%). Limitations of life-sustaining therapy were implemented for 10,401 patients (80.9%), 1,970 (19.1%) of whom had mental capacity at the time, and were discussed with 1,507 patients (14.5%) and 8,461 families (81.3%). Where no discussions with patients occurred (n = 8,710), this primarily was because of a lack of mental capacity in 8,114 patients (93.2%), and where none occurred with families (n = 1,622), this primarily was because of unavailability (n = 720 [44.4%]). Regional variation was noted for all end points. In generalized estimating equation (GEE) analyses, the odds for discussions with the patient or family increased by 30% (OR, 1.30; 95% CI, 1.18-1.44; P < .001) for every one-point increase in the Ethical Practice Score and by 92% (OR, 1.92; 95% CI, 1.28-2.89; P = .002) in the presence of an advance directive. INTERPRETATION: End-of-life communication with patients and families or surrogates varies markedly in different global regions. GEE analysis supports the hypothesis that communication may increase with ethical practice and an advance directive. Greater effort is needed to align treatment with patients' wishes.

Drug Content Uniformity: Quantifying Loratadine in Tablets Using a Created Raman Excipient Spectrum.

Raman spectroscopy has proven valuable for determining the composition of manufactured drug products, as well as identifying counterfeit drugs. Here we present a simple method to determine the active pharmaceutical ingredient (API) mass percent in a sample that does not require knowledge of the identities or relative mass percents of the inactive pharmaceutical ingredients (excipients). And further, we demonstrated the ability of the method to pass or fail a manufactured drug product batch based on a calculated acceptance value in accordance with the US Pharmacopeia method for content uniformity. The method was developed by fitting the Raman spectra of 30 Claritin® tablets with weighted percentages of the Raman spectrum of its API, loratadine, and a composite spectrum of the known excipients. The mean loratadine mass of 9.79 ± 40 mg per 100 mg tablet compared favorably to the 10.21 ± 0.63 mg per 100 mg tablet determined using high-performance liquid chromatography, both of which met the acceptance value to pass the 10 mg API product as labelled. The method was then applied to a generic version of the Claritin product that employed different excipients of unknown mass percents. A Raman spectrum representative of all excipients was created by subtracting the API Raman spectrum from the product spectrum. The Raman spectra of the 30 generic tablets were then fit with weighted percents of the pure loratadine spectrum and the created excipient spectrum, and used to determine a mean API mass for the tablets of 10.12 ± 40 mg, again meeting the acceptance value for the 10 mg API product. The data suggest that this simple method could be used to pass or fail manufactured drug product batches in accordance with the US Pharmacopeia method for content uniformity, without knowledge of the excipients.

A practical approach to Events Medicine provision.

In the past three decades, mass casualty incidents have occurred worldwide at multiple sporting events and other mass gatherings. Organisational safety and healthcare provision can consequently be scrutinised post-event. Within the UK, such incidents in the 1980s provided incentives to improve medical services and subsequent high profile UK-based international sporting events (London Olympics and Paralympics 2012, Glasgow Commonwealth Games 2014, Rugby World Cup 2015) added a further catalyst for developing services. Furthermore in the aftermath of the abandoned France versus Germany association football match at the Stade de France (Paris Terrorist Attacks, November 2015) and the 2016 UK report from HM Coroner on the Hillsborough Inquest, medical cover at sporting events is being further reviewed. Doctors providing spectator cover therefore need to have an awareness of their likely roles at sporting venues. Formal guidance exists in many countries for the provision of such cover but remains generic even though Events Medicine is increasingly recognised as a necessary service. The current evidence base is limited with best practice examples often anecdotally cited by acute care specialists (eg, emergency medicine) who provide cover. This article is therefore intended to present an overview for doctors of the knowledge and skills required to treat ill and injured spectators and enable them to adequately risk-assess venues in cooperation with other health and safety providers, including preparation for a major incident. It also gives guidance on how activity can be adequately assessed and how doctors can have management roles in Events Medicine.

Aircraft engine-mounted camera system for long wavelength infrared imaging of in-service thermal barrier coated turbine blades.

This paper announces the implementation of a long wavelength infrared camera to obtain high-speed thermal images of an aircraft engine's in-service thermal barrier coated turbine blades. Long wavelength thermal images were captured of first-stage blades. The achieved temporal and spatial resolutions allowed for the identification of cooling-hole locations. The software and synchronization components of the system allowed for the selection of any blade on the turbine wheel, with tuning capability to image from leading edge to trailing edge. Its first application delivered calibrated thermal images as a function of turbine rotational speed at both steady state conditions and during engine transients. In advance of presenting these data for the purpose of understanding engine operation, this paper focuses on the components of the system, verification of high-speed synchronized operation, and the integration of the system with the commercial jet engine test bed.

A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy.

PURPOSE: Cardiovascular optimization via esophageal Doppler can minimize gastrointestinal hypoperfusion, reducing the risk of multiple organ dysfunction and postoperative complications during major surgery. We assessed the effect of esophageal Doppler guided cardiovascular optimization in patients undergoing radical cystectomy. MATERIALS AND METHODS: We conducted a prospective, randomized, double-blind controlled trial at a United Kingdom teaching hospital between 2006 and 2009. A total of 66 patients were randomized to a control arm (34) and an intervention arm (32). The control group received standard intraoperative fluids. The intervention group received (additional) Doppler guided fluid. Primary outcomes were markers of gastrointestinal morbidity such as ileus, flatus and bowel opening. Secondary outcomes were postoperative nausea and vomiting, wound infection and operative intravenous fluid volumes (total and hourly). RESULTS: There were significant reductions in the control and intervention arms in the incidence of ileus (18 vs 7, p <0.001), flatus (5.36 vs 3.55 days, p <0.01) and bowel opening (9.79 vs 6.53 days, p = 0.02), respectively. Nausea and vomiting were significantly reduced in the study group at 24 and 48 hours postoperatively (11 vs 3, p <0.01 and 13 vs 1, p <0.0001). Wound infection rates were significantly reduced (8 vs 1 superficial, p <0.01 and 10 vs 2 combined, p <0.01). Study patients received significantly higher volumes (ml/kg per minute) of intravenous fluid (0.19 vs 0.23, p <0.01) related to a significantly higher volume (ml/kg) in the first hour of surgery (14.1 vs 21.0, p = 0.0001). CONCLUSIONS: Cardiovascular optimization using esophageal Doppler significantly improved postoperative markers of gastrointestinal function.

Acute renal failure and the critically ill surgical patient.

Acute renal failure can occur following major surgery. Predisposing factors include massive haemorrhage, sepsis, diabetes, hypertension, cardiac disease, peripheral vascular disease, chronic renal impairment and age. Understanding epidemiology, aetiology and pathophysiology can aid effective diagnosis and management. A consensus definition for acute renal failure has recently been developed. It relates to deteriorating urine output, serum creatinine and glomerular filtration rate. In the surgical patient, precipitants are often pre-renal, although intrinsic damage and obstructed urine flow can occur. Worsening renal function results in distal organ damage. Acute renal failure is a marker of disease severity, carrying a poor prognosis if associated with deteriorating respiratory and cardiovascular function. Acute renal failure in the critically ill surgical patient exerts a massive impact on the evolution of complications and prognosis. Management relates to treating life-threatening problems, maintaining effective ventilation and circulation, removal (or reduction) of nephrotoxins and, where appropriate, establishing either renal replacement therapy or palliative care.

The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA.

BACKGROUND: Upon exposure to agents that damage DNA, Saccharomyces cerevisiae undergo widespread reprogramming of gene expression. Such a vast response may be due not only to damage to DNA but also damage to proteins, RNA, and lipids. Here the transcriptional response of S. cerevisiae specifically induced by DNA damage was discerned by exposing S. cerevisiae to a panel of three "radiomimetic" enediyne antibiotics (calicheamicin gamma1I, esperamicin A1 and neocarzinostatin) that bind specifically to DNA and generate varying proportions of single- and double-strand DNA breaks. The genome-wide responses were compared to those induced by the non-selective oxidant gamma-radiation. RESULTS: Given well-controlled exposures that resulted in similar and minimal cell death (~20-25%) across all conditions, the extent of gene expression modulation was markedly different depending on treatment with the enediynes or gamma-radiation. Exposure to gamma-radiation resulted in more extensive transcriptional changes classified both by the number of genes modulated and the magnitude of change. Common biological responses were identified between the enediynes and gamma-radiation, with the induction of DNA repair and stress response genes, and the repression of ribosomal biogenesis genes. Despite these common responses, a fraction of the response induced by gamma radiation was repressed by the enediynes and vise versa, suggesting that the enediyne response is not entirely "radiomimetic." Regression analysis identified 55 transcripts with gene expression induction associated both with double- or single-strand break formation. The S. cerevisiae "DNA damage signature" genes as defined by Gasch et al. 1 were enriched among regulated transcripts associated with single-strand breaks, while genes involved in cell cycle regulation were associated with double-strand breaks. CONCLUSION: Dissection of the transcriptional response in yeast that is specifically signaled by DNA strand breaks has identified that single-strand breaks provide the signal for activation of transcripts encoding proteins involved in the DNA damage signature in S. cerevisiae, and double-strand breaks signal changes in cell cycle regulation genes.