Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

The spiritual organization: critical reflections on the instrumentality of workplace spirituality

Authors' draft of article. Final version published by Routledge in Journal of Management, Spirituality and Religion available online at: http://www.tandf.co.uk/journals/titles/14766086.aspThis paper offers a theoretical contribution to the current debate on workplace spirituality by: (a) providing a selective critical review of scholarship, research and corporate practices which treat workplace spirituality in performative terms, that is, as a resource or means to be manipulated instrumentally and appropriated for economic ends; (b) extending Ezioni’s analysis of complex organizations and proposing a new category, the ‘spiritual organization’, and; (c) positing three alternative positions with respect to workplace spirituality that follow from the preceding critique. The spiritual organization can be taken to represent the development of a trajectory of social technologies that have sought, incrementally, to control the bodies, minds, emotions and souls of employees. Alternatively, it might be employed to conceptualize the way in which employees use the workplace as a site for pursuing their own spiritualities (a reverse instrumentalism). Finally, we consider the possible incommensurability of ‘work organization’ and ‘spirituality’ discourses

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Effect of surgical injury and intraoperative hypothermia on whole body protein metabolism

Whole body protein turnover and urinary nitrogen and 3-methyl-L-histidine (3-MH) excretion were measured before and after cardiac surgery using cardiopulmonary bypass in 20 male patients randomized to an intraoperative blood temperature of 28 or 20 degrees C. Rates of whole body protein synthesis (WBPS) and breakdown (WBPB) were determined from the 15N isotopic enrichment of urinary urea, ammonium, and from a calculated end-product average (EPA) after a primed 24-h infusion of [15N]glycine. In the postoperative period, there was a 40% increase in median nitrogen excretion in the 28 degrees C group (P less than 0.03) and a 22% increase in the 20 degrees C group (P = 0.10). There was a 79% increase in the median postoperative 3-MH excretion in the 28 degrees C group (P = 0.01) and a 66% increase in the median postoperative 3-MH excretion in the 20 degrees C group (P less than 0.01). Postoperatively, there was a 23% fall in the median value of WBPS in the 28 degrees C group (P less than 0.01) and an 11% fall in the 20 degrees C group [not significant (NS)] measured by 15N enrichment of urinary urea. In contrast, when WBPS was measured from isotopic enrichment of urinary ammonium, there was an increase in the median value of the postoperative rates of WBPS in both groups, by 20% in the 28 degrees C group (P = NS) and 29% in the 20 degrees C group (P = 0.03). There was no significant change in the rate of WBPS and WBPB, judged by the postoperative EPA in either group.(ABSTRACT TRUNCATED AT 250 WORDS

Resting and total energy expenditure in patients with ischemic heart disease

Total energy expenditure (TEE) was measured by doubly labeled water in 13 preoperative patients undergoing elective coronary artery surgery and compared to resting energy expenditure (REE) measured by indirect calorimetry (IC) calculated from the Harris-Benedict (HB) formula or from formulas based on midarm circumference and arm muscle circumference. Mean REE measured by IC and calculated from the HB, midarm circumference, arm muscle circumference formulas were 62, 75, 62, and 69%, respectively, of TEE measured by doubly labeled water. REE measured by IC correlated significantly with that predicted by the HB (p = 0.006) but not the anthropometric formulas. The relationship between REE derived from anthropometric predictive formulas and REE measured by IC is altered in ischemic heart disease