Improving the environmental sustainability of paediatric care.

Accelerated global warming is directly related to greenhouse gas (GHG) emissions. In order to achieve international and national set targets on reducing GHG emissions, paediatricians should aim to decrease GHG emissions associated with paediatric care, when this is not in conflict with patient outcomes. In this article, we review literature on practical ways to encourage environmentally sustainable paediatric care and identify areas where more evidence is required. Finally, we introduce readers to the principles of sustainable healthcare which may be used to help guide further efforts to reduce the environmental impact of paediatric care.

A comparison of hospital episode statistics and traditional methods to identify outcomes in a randomized trial; a sub-study of HEAT-PPCI.

BACKGROUND: This study aims to compare information from hospital episode statistics (HES) and traditional direct patient contact to identify readmission and clinical events in the follow-up of a randomized controlled trial (RCT). METHODS: The study followed 1812 patients for 28 days using direct contact (DC). In addition, we obtained HES for this period. We examined medical records for all suspected readmissions and determined confirmed events by adjudication. We compared the ability of the individual DC and HES methods to determine readmission and the occurrence of trial-specific events, confirmed at adjudication. RESULTS: In the ascertainment of readmission, compared to DC, HES demonstrated a trend towards better sensitivity (identifying 153/166 = 92.2% versus 144/166 = 86.7%; difference = 5.4%, 95% CI: 0.1-11.5%) and better specificity (1492/1492 = 100% versus 1426/1492 = 95.5%; difference = 4.4%, 95% CI: 4.2-5.6%).An examination of HES coding does not identify rates for specific events that match those from adjudication, with limitations in both sensitivity and specificity. CONCLUSION: HES is effective in the ascertainment of readmission and is a useful tool in follow-up. Information from HES provides a reflection of a patient's course and associated cost, as perceived by the healthcare system. Future studies could modify outcome definitions to reflect episode coding.

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

BACKGROUND: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS: In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS: Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION: Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Comparison of the antiplatelet and antithrombotic effects of bivalirudin versus unfractionated heparin: A platelet substudy of the HEAT PPCI trial.

In randomised trials, bivalirudin has been associated with higher rates of acute stent thrombosis (AST) compared to unfractionated heparin (UFH), without mechanistic explanation. Furthermore, data are discrepant regards the antiplatelet effects of bivalirudin. This prespecified study, part of a larger HEAT-PPCI Platelet Substudy, aimed to compare the antiplatelet and antithrombotic effects of bivalirudin and UFH using short thrombelastography (s-TEG), an ex vivo whole blood platelet function assay. In HEAT-PPCI, patients were randomised to receive UFH or bivalirudin before angiography. Assay with s-TEG was performed in 184 patients (10.2%) at end of procedure (EOP) and repeated at 24 h. In addition to adenosine diphosphate- (ADP) and arachidonic acid- (AA) mediated platelet aggregation, thrombin-mediated clotting (TMC) was assessed using kaolin with and without heparinase. There were no significant differences between UFH and bivalirudin in ADP- and AA-mediated platelet aggregation at EOP or 24 h. Whilst UFH obliterated TMC at EOP, bivalirudin prolonged R time (19.7 min [15.9-25.4] vs. 8.4 min [7.5-10]; P < 0.0001), K time (2.4 min [1.9-3.4] vs. 2.2 min [1.8-2.7]; P = 0.007) and significantly increased maximum clot strength (MA 62.7 mm [58.7-67.4] vs. 58.6 [55-63]; P = 0.0005), compared to control. In conclusion, there were no significant differences in the antiplatelet effects of UFH and bivalirudin. However, whilst UFH obliterated TMC, bivalirudin prolonged clot initiation but potentiated maximum clot strength. As AST is likely multifactorial in aetiology, in patients treated with bivalirudin, increased clot strength may contribute to this hazard in some individuals and this observation warrants further investigation.

Describing Activity in Primary Percutaneous Coronary Intervention: An Exploration of Denominators. From the HEAT Trial - A Systematic Evaluation of PPCI Activations in Liverpool, Explaining Denominators (HEAT-SEALED).

BACKGROUND: The provision of primary percutaneous coronary intervention (PPCI) in the emergency management of ST-elevation myocardial infarction (STEMI) is expensive and resource intensive. Accurate data collection is essential not only for outcomes analysis but also to characterize activity and performance for regions, centers, and operators. Inconsistency in the use of denominators currently creates problems in data interpretation. OBJECTIVE: To establish a system of denominator groupings, seeking to better describe the range of clinical activity resulting from an unselected series of PPCI activations. METHODS: The HEAT-SEALED pathway designates a key denominator group (n1-n9) to each phase of PPCI activity and identifies a final "destination category" for each patient leaving the pathway. HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention) is a true "all-comers" trial and provides an ideal platform to collect data for prospective validation of the pathway. We report data from all PPCI activation events for the HEAT-PPCI trial. RESULTS: Our findings demonstrate important differences between the sizes of key PPCI denominator groups and hence the potential for variation in reported outcomes depending on the denominator category selected. The main figures are: all activations (n1 = 2490); all suspected MI cases (n4 = 1940; 77.91%); patients in whom angiography was performed (n5 = 1904; 76.46%); cases in which diagnosis was confirmed with a probable culprit lesion (n6 = 1657; 66.54%), and cases with complete PCI success (n9 = 1441; 57.87%). CONCLUSION: The HEAT-SEALED pathway offers a practical and comprehensive solution to the problem of describing denominators in STEMI and PPCI. Routine application would facilitate a more consistent and precise description of activity and outcome.

Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions.

BACKGROUND: The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133+/alpha2beta1hi phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133-/alpha2beta1low) counterparts, resulting in an informative cancer stem cell gene-expression signature. RESULTS: Cell cultures were generated from specimens of human prostate cancers (n = 12) and non-malignant control tissues (n = 7). Affymetrix gene-expression arrays were used to analyze total cell RNA from sorted cell populations, and expression changes were selectively validated by quantitative RT-PCR, flow cytometry and immunocytochemistry. Differential expression of multiple genes associated with inflammation, cellular adhesion, and metastasis was observed. Functional studies, using an inhibitor of nuclear factor kappaB (NF-kappaB), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-kappaB is a major factor controlling the ability of tumor cells to resist apoptosis and provides an attractive target for new chemopreventative and chemotherapeutic approaches. CONCLUSION: We describe an expression signature of 581 genes whose levels are significantly different in prostate cancer stem cells. Functional annotation of this signature identified the JAK-STAT pathway and focal adhesion signaling as key processes in the biology of cancer stem cells.