Rationale and Design of the Cardiac CARE Trial: A Randomized Trial of Troponin-Guided Neurohormonal Blockade for the Prevention of Anthracycline Cardiotoxicity.

BACKGROUND: Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. ß-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. METHODS: The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination ß-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. DISCUSSION: Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.

Assessment of the pollution incident performance of water and sewerage companies in England.

Comparison of the severity, frequency and self-reporting of pollution incidents by water and sewerage companies is made difficult by differences in environmental and operational conditions. In England, the deterioration in pollution incident performance makes it important to investigate common trends that could be addressed to improve pollution management. This study presents the first external analysis of available national pollution incident data, obtained through Environmental Information Regulations 2004 requests to the English Environment Agency. The study aimed to assess and compare the pollution incident performance of water and sewerage companies in England. Results indicated that there were significant variations in numbers of pollution incidents reported and the severity of the impact on the water environment for different asset types (operational property). There were significant positive relationships between the self-reporting percentages and total numbers of reported pollution incidents per 10,000 km sewer length for pumping stations and sewage treatment works. These results indicate that in at least these asset types, an estimated 5% of pollution incidents could go unreported. Pollution events that go unreported can lead to more severe impacts to the water environment, so rapid and consistent reporting of incidents is crucial for limiting damage. The results have significance for the water industry internationally, because the issues presented here are not restricted to England. In the short-term, research should focus on investigating best practice and standardising reporting of pollution incidents, so that an accurate baseline of the number of pollution incidents occurring can be determined.

High sensitive TROponin levels In Patients with Chest pain and kidney disease: A multicenter registry - The TROPIC study.

BACKGROUND: Accuracy of high sensitive troponin (hs-cTn) to detect coronary artery disease (CAD) in patients with renal insufficiency is not established. The aim of this study was to evaluate the prognostic role of hs-cTn T and I in patients with chronic kidney disease (CKD). METHODS: All consecutive patients with chest pain, renal insufficiency (eGFR < 60 mL/min/1.73 m2) and high sensitive troponin level were included. The predictive value of baseline and interval troponin (hs-cTnT and hs-cTnI) for the presence of CAD was assessed. RESULTS: One hundred and thirteen patients with troponin I and 534 with troponin T were included, with 95 (84%) and 463 (87%) diagnosis of CAD respectively. There were no differences in clinical, procedural and outcomes between the two assays. For both, baseline hs-cTn values did not differ be-tween patients with/without CAD showing low area under the curve (AUC). For interval levels, hs-cTnI was significantly higher for patients with CAD (0.2 ± 0.8 vs. 8.9 ± 4.6 ng/mL; p = 0.04) and AUC was more accurate for troponin I than hs-cTnT (AUC 0.85 vs. 0.69). Peak level was greater for hs-cTnI in patients with CAD or thrombus (0.4 ± 0.6 vs. 15 ± 20 ng/mL; p = 0.02; AUC 0.87: 0.79-0.93); no differences were found for troponin T assays (0.8 ± 1.5 vs. 2.2 ± 3.6 ng/mL; p = 1.7), with lower AUC (0.73: 0.69-0.77). Peak troponin levels (both T and I) independently predicted all cause death at 30 days. CONCLUSIONS: Patients with CKD presenting with altered troponin are at high risk of coronary disease. Peak level of both troponin assays predicts events at 30 days, with troponin I being more accurate than troponin T. (Cardiol J 2017; 24, 2: 139-150).

Ecologically relevant measures of the physiological tolerance of light brown apple moth, Epiphyas postvittana, to high temperature extremes.

Invasive ectothermic species are limited in their geographic range expansion primarily by their capacity to withstand temperature extremes. Epiphyas postvittana is a highly polyphagous invasive leafroller that was discovered in California in 2006. To predict its potential range and future response to climate change, high temperature tolerance of this species was determined for all life stages and larval instars. Using the static method to estimate high temperature tolerance with response to probing as an endpoint, the mean time leading to 50% mortality (LT(50)) ranged from 45 to 187h at 32.3°C, 34 to 68h at 36°C, 11 to 21h at 38°C, and 1.2 to 5.6h at 40.4°C. There was no clear pattern in the relative tolerance of the life stages across the range of temperatures tested. For pupae and adults, gender did not influence the LT(50) values at any of the temperatures tested. For the larval instars, LT(50) values increased with increasing larval instar at the highest three temperatures while this trend was reversed for the lowest temperature (32.3°C). An analysis of LT(50) values obtained from acute responses to probing compared to subsequent survival to adult emergence, showed that chronic mortality severely affected all larval instars at three out of the four constant temperatures and resulted in 64-85% reduction in LT(50) values. No difference in acute and chronic mortality was found for exposure of the egg stage to high temperatures. These findings have important implications for predicting thermal limits and range expansions of insect species, since upper thermal tolerance could readily be overestimated from the use of ad hoc rather than ecologically relevant endpoint measurements such as survival to adult emergence.

Cold tolerance of the overwintering larval instars of light brown apple moth Epiphyas postvittana.

The light brown apple moth, Epiphyas postvittana, a leafroller native to southeastern Australia was discovered in California in 2006. The highly polyphagous nature of this pest adds to the importance of being able to predict the potential distribution of this invader across the North American continent. The spread of ectothermic species that lack winter diapause, such as E. postvittana, can be limited by their ability to tolerate cold temperature extremes. In this study we examined the cold hardiness of 4th to 6th instar E. postvittana, the only life stages known to overwinter in California, through a combination of supercooling point (SCP) and mortality at low temperatures. Our results showed that the mean SCP for E. postvittana ranged from -14.1 degrees C for 6th instars to -16.0 degrees C for 4th instars. Lethal time leading to 50% mortality (LT(50)) for the three instars combined were 2.5 h at -10.5 degrees C, 41 h at -6.5 degrees C and 198 h at -0.9 degrees C. At 3 degrees C, the LT(50) of 4th instars was significantly lower at 775 h than that for 5th and 6th instars combined at 1029 h. The cold hardiness characteristics of later-instar E. postvittana larvae were comparable to those of pink bollworm, Pectinophora gossypiella, a diapausing invasive with a geographic distribution restricted to southern California. Slightly greater cold hardiness is shown by the indigenous non-diapausing leafroller Argyrotaenia franciscana, which is restricted to the Pacific Coast of North America. We therefore conclude that the moderate cold hardiness of E. postvittana will substantially limit its spread into northern temperate regions of North America.

A change of heart. Interview by Carol Davis.

One Cambridge nurse has transformed the service for people needing elective cardioversion. Instead of complaints, the hospital now receives plaudits and its success has garnered an award.