Cost effectiveness of a 1-hour high-sensitivity troponin-T protocol: an analysis of the RAPID-TnT trial

Background: To understand the economic impact of an accelerated 0/1-hour high-sensitivity troponin-T (hs-cTnT) protocol. Objective: To conduct a patient-level economic analysis of the RAPID-TnT randomised trial in patients presenting with suspected acute coronary syndrome (ACS). Methods: An economic evaluation was conducted with 3265 patients randomised to either the 0/1-hour hs-cTnT protocol (n = 1634) or the conventional 0/3-hour standard-of-care protocol (n = 1631) with costs reported in Australian dollars. The primary clinical outcome was all-cause mortality or new/recurrent myocardial infarction. Results: Over 12-months, mean per patient costs were numerically higher in the 0/1-hour arm compared to the conventional 0/3-hour arm (by $472.49/patient, 95$-1,380.15 to $2,325.13, P = 0.617) with no statistically significant difference in primary outcome (0/1-hour: 62/1634 [3.8$891.22/patient, 95 %CI: $-96.07 to 1,878.50, P = 0.077). Restricting the analysis to patients with hs-cTnT concentrations ≤ 29 ng/L, mean per patient cost remained numerically higher in the 0/1-hour arm (by$152.44/patient, 95 %CI:$-1,793.11 to$2,097.99, P = 0.988), whilst the reduction in ED LOS was more pronounced (by 0.70 h/patient, 95 %CI: 0.45–0.95, P < 0.001). Conclusions: There were no differences in resource utilization between the 0/1-hour hs-cTnT protocol versus the conventional 0/3-hour protocol for the assessment of suspected ACS, despite improved initial ED efficiency. Further refinements in strategies to improve clinical outcomes and subsequent management efficiency are needed.Ming-yu Anthony Chuang Emmanuel S. Gnanamanickam, Jonathan Karnon, Kristina Lambrakis, Matthew Horsfall, Andrew Blyth ... et al

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia

Perceived risk of ischemic and bleeding events in acute coronary syndromes

Background-Acute coronary syndrome registries report the use of incomplete guideline therapies, especially among the highest risk patients. Whether this treatment gap results from misperceptions of risk by physicians is uncertain. Methods and Results-The Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) study was a prospective acute coronary syndrome registry in Australia, China, India, and Russia, involving 58 hospitals between May 2009 and February 2011. In-hospital care and events up to 6 months were assessed. At least 2 clinicians involved in patient care estimated the untreated risk and change in risk with each therapy. Physician risk assessment and objective risk measures (eg, Global Registry of Acute Coronary Events [GRACE] score) for death, death/myocardial infarction, and bleeding events were compared using the c statistic and integrated discrimination improvement. In total, 1542 patients and 4230 patient-specific physician estimates were obtained. Of responding clinicians, 81.9% were cardiovascular specialists (years of practice: mean [SD], 11.5 [7.7] years). The median physician-perceived risk of 6-month death was 25% (interquartile range, 14%-35%). The GRACE score was superior to physician estimation (c statistic: GRACE score, 0.812 [95% confidence interval, 0.772-0.851] versus physician, 0.652 [95% confidence interval, 0.596-0.708];

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial

Aims: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN ™ multi-electrode system. Methods and results: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by -28/10, -27/10 and -26/10 mmHg, respectively (P &amp;lt; 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Conclusion: Renal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension. © The Author 2013

Radon, progeny and health: investigation in different environments in Northamptonshire

The essential findings of this study are that, from a known radium source, radon variability in the environment of the buildings studied is an inevitable consequence of the variability of the prevailing surface boundary layer atmospheric conditions. These influences will be modified by the structural characteristics of the building and will vary directly, relative to the mechanically created variation of the atmospheric conditions inside the building. From the findings, a general hypothesis is postulated. It is probable, that the diurnal variation of radon results from the diurnal variation in ambient water vapour pressure. And that the seasonal variation in radon, arises from the changes in the range of this diurnal variation during the course of a year brought about by changing levels of temperature and barometric pressure. This will be varied to the extent, that wind pressure affects directly both the radon path from source to the building and the level of water vapour pressure. Where mechanically induced air-movement in the building creates overriding pressure and air exchange, then this is likely to determine the pattern of variability; and as a result can be used under some circumstances as a mitigation agent; with levels of concentration anticipated in a predictable way. The current practice of reliance on average radon values derived from time-average radon values of a living room and a bedroom, as being representative of the alpha particle dose delivered to an individual, may well significantly overstate the dose actually delivered to that individual at a particular radon level measured. This would follow potentially from a preponderance of radon transported overnight requiring a lower weighting factor for the amount delivered to above-ground-floor sleepers, and the much reduced level of intake to the respiratory system from reduced breathing rate during the sleep mode. Potentially also, from the mechanism postulated which implies the limitation of the impact of alpha particles, related to an association between water vapour pressure, radon and particulates in the atmosphere. Linkage between elevated radon levels and surface geological was identified; but no positive connection was apparent linking respiratory system cancers relative to radon/geolog

Comparison of three risk stratification rules for predicting patients with acute coronary syndrome presenting to an australian emergency department

Objectives: To compare the predictive ability of three risk stratification tools used to assess patients presenting to the ED with potential acute coronary syndrome. Design: Pre-planned analysis of an observational study. Setting: A single tertiary referral hospital. Participants: 1495 patients presented with chest pain. 948 patients were screened and enrolled. Patients with at least 5. min of chest pain suggestive of ACS were eligible. Interventions: Subjects were risk categorised using the Heart Foundation of Australia/Cardiac Society of Australia and New Zealand guidelines (HFA/CSANZ), the TIMI score and the GRACE score. Three strata of the TIMI and GRACE score were used to compare to the HFA/CSANZ risk categories. Main outcome measurement: 30-Day cardiac event rates including cardiac death, acute myocardial infarction and unstable angina. Results: There were 152 events in 91 patients (9.6%). The discriminatory ability of the scores determined by the AUC was 0.83 (95% CI 0.79-0.87) for the GRACE score, 0.79 (95% CI 0.74-0.83) for TIMI score and 0.75 (95% CI 0.70-0.80) for HFA/CSANZ. The AUCs with three strata of the GRACE and TIMI scores were 0.76 (95% CI 0.72-0.81) and 0.68 (95% CI 0.62-0.73) respectively. Conclusions: All three scores were similar in performance in quantifying risk in ED patients with possible ACS. The GRACE score identified a sizable low risk cohort with high sensitivity and NPV but complexity of this tool may limit its utility. Improved scores are needed to allow early identification of low- and high-risk patients to support improvements in patient flow and ED overcrowding