Body mass index mortality paradox in chronic kidney disease patients with suspected cardiac chest pain

Background: Chronic kidney disease (CKD) is a silent clinical condition associated with adverse comorbidity and high cardiovascular disease (CVD) risk. An inverse relationship with body mass index (BMI) and mortality has been demonstrated in hemodialysis patients. However, it is unclear if this risk‐factor paradox is evident in non‐dialysis CKD patients. The aims of this study were to explore the relationship between, nutritional status, markers of inflammation, autonomic and cardiac function with BMI. Longitudinal follow‐up explored the relationship between BMI and allcause mortality. Methods: 211‐consecutive CKD patients referred for dobutamine stress echocardiography to detect or exclude myocardial ischemia were recruited. BMI, albumin, C‐reactive protein (CRP) and haemoglobin (Hb) were recorded as markers of nutritional and inflammatory status. Left ventricular ejection fraction (LVEF) and heart rate variability (HRV) as an indicator of cardiac function was recorded. All subjects were followed prospectively until November 2014 and study end‐point was all‐cause mortality. Results: BMI was inversely associated with CKD status. After covariate adjustment, this association remained. During a mean follow‐up period of 3.3±0.9 years there were 35 deaths (17%). BMI was inversely associated with all‐cause mortality (HR 0.81, 95% CI 0.71‐0.9). Other important independent predictors of mortality were heart rate variability (HR 0.98, 95% CI 0.97‐0.99), myocardial ischemia (HR 1.37, 95% CI 1.17‐1.81), and albumin (HR 0.86, 95% CI 0.81‐ 0.92). Conclusions: The presence of a BMI paradox exists in non‐dialysis CKD patients. This risk‐factor paradox was an independent predictor of all‐cause mortality and may have significant clinical implications relevant to screening, assessment and treatment and requires further study

Real world hospital costs following stress echocardiography in the UK: a costing study from the EVAREST/BSE-NSTEP multi-centre study

Background - Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identified key factors that affect costs to help inform future clinical planning and guidelines. Methods - Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level. Results – Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities andhigher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95% CI: 0.65 to 0.93), 0.27 (95% CI: 0.15 to 0.48), 0.99 (95% CI: 0.98 to 0.99) respectively, whereas a prior myocardial infarction, angiotensin receptor blocker medication, and greater operator experience increased accuracy, adjusted odds ratio of 1.77 (95% CI: 1.34 to 2.33), 1.64 (95% CI: 1.22 to 2.22), and 1.06 (95% CI: 1.02 to 1.09) respectively. Average downstream costs were £646 per patient (SD 1796) with significant variation across hospitals. The average downstream costs between the 31 hospitals varied from £384-1730 per patient. False positive and false negative tests were associated with average downstream costs of £1446 (SD £601) and £4192 (SD 3332) respectively, driven by increased non-elective hospital admissions, adjusted odds ratio 2.48 (95% CI: 1.08 to 5.66), 21.06 (95% CI: 10.41 to 42.59) respectively. We estimated that an increase in accuracy by 1 percentage point could save the NHS in the UK £3.2 million annually. Conclusion – This study provides real-world evidence of downstream costs associated with stress echocardiography practice in the UK and estimates how improvements in accuracy could impact healthcare expenditure in the NHS. A real-world downstream costing approach could be adopted more widely in evaluation of imaging tests and interventions to reflect actual value for money and support realistic planning

Prion aggregate structure in yeast cells is determined by the Hsp104-Hsp110 disaggregase machinery

Prions consist of misfolded proteins that have adopted an infectious amyloid conformation. In vivo, prion biogenesis is intimately associated with the protein quality control machinery. Using electron tomography, we probed the effects of the heat shock protein Hsp70 chaperone system on the structure of a model yeast [PSI+] prion in situ. Individual Hsp70 deletions shift the balance between fibril assembly and disassembly, resulting in a variable shell of nonfibrillar, but still immobile, aggregates at the surface of the [PSI+] prion deposits. Both Hsp104 (an Hsp100 disaggregase) and Sse1 (the major yeast form of Hsp110) were localized to this surface shell of [PSI+] deposits in the deletion mutants. Elevation of Hsp104 expression promoted the appearance of this novel, nonfibrillar form of the prion aggregate. Moreover, Sse1 was found to regulate prion fibril length. Our studies reveal a key role for Sse1 (Hsp110), in cooperation with Hsp104, in regulating the length and assembly state of [PSI+] prion fibrils in vivo

Nurses’ experiences of clinical commissioning group boards

The following paper is the first in a series of three papers to highlight current practice among governing body nurses, that is, nurses who hold the statutory role of nurse member on clinical commissioning groups in England. In this paper we present findings from a small pilot study into these nurses’ experiences of Clinical Commissioning Groups. Their roles have emerged at a time of organisational change and in a period following extensive criticism of nursing and nurses in the media. We suggest that nurses’ roles and experiences are affected by these contextual ‘events’ and by the emerging structures and diversity of clinical commissioning groups. We argue that governing body nurses’ effectiveness in leading nurses and nursing on clinical commissioning groups may be affected by their relationships with other nurses, especially senior nurses, within clinical commissioning group localities. We suggest that it is timely to evaluate the effectiveness of statutory nurse member roles in influencing decision making on Clinical Commissioning Groups

The safety of isometric exercise: rethinking the exercise prescription paradigm for those with stage 1 hypertension.

Few studies have investigated the relative safety of prescribing isometric exercise (IE) to reduce resting blood pressure (BP). This study aimed to ascertain the safety of the hemodynamic response during an IE wall squat protocol.Twenty-six hypertensive (BP of 120-139 mm Hg systolic and/or 80-90 mm Hg diastolic) males (45 ± 8 years; 1.78 ± 0.07 m; 89.7 ± 12.3 kg; mean ± SD), visited the laboratory on 2 separate occasions. Heart rate (HR) and BP were measured at rest and continuously throughout exercise. In visit 1, participants completed a continuous incremental isometric wall squat exercise test, starting at 135° of knee flexion, decreasing by 10° every 2 minutes until 95° (final stage). Exercise was terminated upon completion of the test or volitional fatigue. The relationship between knee joint angle and mean HR was used to calculate the participant-specific knee joint angle required to elicit a target HR of 95% HRpeak. This angle was used to determine exercise intensity for a wall squat training session consisting of 4 × 2 minute bouts (visit 2).Systolic BPs during the exercise test and training were 173 ± 21 mm Hg and 171 ± 19 mm Hg, respectively, (P > .05) and were positively related (r = 0.73, P  .05) and were positively related (r = 0.42, P  250 mm Hg. Diastolic BP values > 115 mm Hg were recorded in 12 participants during the incremental test and 6 participants during the training session. Peak rate pressure product was 20681 ± 3911 mm Hg bpm during the IE test and was lower (18074 ± 3209 mm Hg bpm) during the IE session (P = .002). No adverse effects were reported.Based on the current ACSM guidelines for aerobic exercise termination, systolic BP does not reach the upper limit during IE in this population. Diastolic BP exceeds 115 mm Hg in some during the IE protocol, which may suggest the need to individualise IE training prescription in some with suboptimal BP control. Future research is required to ascertain if IE requires modified BP termination guidelines