Field Comparison of Cyclopentanone Versus Carbon Dioxide as an Attractant for Adult Mosquitoes in Southeast Queensland, Australia.

Cyclopentanone is a saturated monoketone typically used as an intermediate in the manufacture of pharmaceuticals, biologicals, insecticides, and rubber chemicals. Recently, it has been demonstrated that cyclopentanone activates the cpA CO2 receptor neuron on the maxillary palp of mosquitoes, suggesting that it may be a viable alternative to CO2 as an attractant for mosquitoes. Furthermore, semifield experiments showed that traps baited with cyclopentanone attract Culex quinquefasciatus Say at a similar rate to those baited with CO2. We evaluated the field efficacy of cyclopentanone as an alternative to CO2 in Centers for Disease Control (CDC) light traps and counterflow geometry (CFG) traps commonly used to collect mosquitoes in surveillance programs. Three pairwise trials and four Latin square trials were conducted across three peri-urban sites, comprising two saltwater sites and one freshwater site, in southeast Queensland, Australia. In all trials, CO2-baited traps outperformed traps baited with cyclopentanone. Carbon dioxide-baited CDC traps collected significantly more total mosquitoes, Aedes vigilax (Skuse), Culex sitiens Weidemann, and Culex annulirostris Skuse, than those baited with ≥99% cyclopentanone in pairwise trials. Similarly, in almost all Latin square trials, CO2-baited CDC and CFG traps collected significantly greater numbers of total mosquitoes, Ae. vigilax, Cx. annulirostris, Culex orbostiensis Dobrotworsky, and Cx. sitiens when compared with CFG traps baited with 20% cyclopentanone. Our trials indicate that cyclopentanone is not effective as a mosquito attractant in the field and cannot be used as a simple substitute for CO2 in commonly used mosquito surveillance traps.

Patient-specific coronary stenoses can be modeled using a combination of OCT and flow velocities to accurately predict hyperemic pressure gradients.

Computational fluid dynamics (CFD) is increasingly being developed for the diagnostics of arterial diseases. Imaging methods such as computed tomography (CT) and angiography are commonly used. However, these have limited spatial resolution and are subject to movement artifact. This study developed a new approach to generate CFD models by combining high-fidelity, patient-specific coronary anatomy models derived from optical coherence tomography (OCT) imaging with patient-specific pressure and velocity phasic data. Additionally, we used a new technique which does not require the catheter to be used to determine the centerline of the vessel. The CFD data were then compared with invasively measured pressure and velocity. Angiography imaging data of 21 vessels collected from 19 patients were fused with OCT visualizations of the same vessels using an algorithm that produces reconstructions inheriting the in-plane (10 µm) and longitudinal (0.2 mm) resolution of OCT. Proximal pressure and distal velocity waveforms ensemble averaged from invasively measured data were used as inlet and outlet boundary conditions, respectively, in CFD simulations. The resulting distal pressure waveform was compared against the measured waveform to test the model. The results followed the shape of the measured waveforms closely (cross-correlation coefficient = 0.898 ± 0.005, ), indicating realistic modeling of flow resistance, the mean of differences between measured and simulated results was -3. 5 mmHg, standard deviation of differences (SDD) = 8.2 mmHg over the cycle and -9.8 mmHg, SDD = 16.4 mmHg at peak flow. Models incorporating phasic velocity in patient-specific models of coronary anatomy derived from high-resolution OCT images show a good correlation with the measured pressure waveforms in all cases, indicating that the model results may be an accurate representation of the measured flow conditions.

Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: a 2-center study.

BACKGROUND: For late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) assessment of atrial scar to guide management and targeting of ablation in atrial fibrillation (AF), an objective, reproducible method of identifying atrial scar is required. OBJECTIVE: To describe an automated method for operator-independent quantification of LGE that correlates with colocated endocardial voltage and clinical outcomes. METHODS: LGE CMR imaging was performed at 2 centers, before and 3 months after pulmonary vein isolation for paroxysmal AF (n = 50). A left atrial (LA) surface scar map was constructed by using automated software, expressing intensity as multiples of standard deviation (SD) above blood pool mean. Twenty-one patients underwent endocardial voltage mapping at the time of pulmonary vein isolation (11 were redo procedures). Scar maps and voltage maps were spatially registered to the same magnetic resonance angiography (MRA) segmentation. RESULTS: The LGE levels of 3, 4, and 5SDs above blood pool mean were associated with progressively lower bipolar voltages compared to the preceding enhancement level (0.85 ± 0.33, 0.50 ± 0.22, and 0.38 ± 0.28 mV; P = .002, P < .001, and P = .048, respectively). The proportion of atrial surface area classified as scar (ie, >3 SD above blood pool mean) on preablation scans was greater in patients with postablation AF recurrence than those without recurrence (6.6% ± 6.7% vs 3.5% ± 3.0%, P = .032). The LA volume >102 mL was associated with a significantly greater proportion of LA scar (6.4% ± 5.9% vs 3.4% ± 2.2%; P = .007). CONCLUSIONS: LA scar quantified automatically by a simple objective method correlates with colocated endocardial voltage. Greater preablation scar is associated with LA dilatation and AF recurrence.

Stent flexibility versus concertina effect: mechanism of an unpleasant trade-off in stent design and its implications for stent selection in the cath-lab.

The "concertina effect", longitudinal deformation of the proximal segments of a deployed stent when force is applied from a guide catheter or other equipment, is a recently recognised problem which seems to particularly affect more recent stent designs. Until now, flexibility and deliverability have been paramount aims in stent design. Developments have focussed on optimising these features which are commonly evaluated by clinicians and demanded by regulatory bodies. Contemporary stent designs now provide high flexibility by reducing the number of connecting links between stent segments and by allowing the connecting links to easily change their length. These design evolutions may, however, simultaneously reduce longitudinal strength and have the unintended effect of inducing some risk of longitudinal compression of the stent (the "concertina effect") during difficult clinical cases. Progress in stent design and elimination of restenosis by drug coating has improved PCI outcome and enabled new applications. Here we discuss design trade-offs that shaped evolution and improvement in stent design, from early bare metal designs to the latest generation of drug eluting stent (DES) platforms. Longitudinal strength was not recognised as a critical parameter by clinicians or regulators until recently. Measurements, only now becoming publically available, seem to confirm vulnerability of some modern designs to longitudinal deformation. Clinicians could be more guarded in their assumption that changes in technology are beneficial in all clinical situations. Sometimes a silent trade-off may have taken place, adopting choices that are favourable for the vast majority of patients but exposing a few patients to unintended hazard.

Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

BACKGROUND: A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. METHOD: We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. RESULTS: Although this study does not seek to compute the price of the final licensed vaccine, the cost of production estimate produced here leads to the conclusion that the vaccine can be made available at a price that most ministries of health in developing countries could afford. This conclusion provides strong encouragement for supporting the development of the vaccine so that, if it proves to be safe and effective, licensure can be achieved soon and the burden of dengue disease can be reduced.

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease.

AIMS/HYPOTHESIS: A high prevalence of diabetes contributes to excess CHD in Indian Asians, but the underlying mechanisms are unclear. Heart rate, heart rate variability (HRV) and baroreflex sensitivity (BRS) are measures of cardiac autonomic function that are disturbed by hyperglycaemia and predict CHD. We compared these measures in Indian Asians and Europeans, and sought explanations for the observed differences. METHODS: A representative sample of 149 Europeans and 151 Indian Asians was recruited from primary care, 66% of them men (aged 35-75 years), 34% women (aged 55-75 years). Heart rate, HRV, BRS and cardio-metabolic profiles were measured over four successive 5 min periods with continuous ECG and blood pressure monitoring. RESULTS: Indian Asians were hyperglycaemic compared with Europeans (HbA(1c) (mean +/- SD) 6.5 +/- 1.2% vs 5.9 +/- 1.0%, p = 0.001). They had shorter mean RR intervals ((mean +/- SE) 969 +/- 13 vs 1,022 +/- 12 ms, p = 0.002), lower total RR interval power ((geometric mean, 95% CI) 925 [796-1075] vs 1,224 [1,064-1,422] ms(2), p = 0.008) and lower BRS ((mean +/- SE) 5.7 +/- 1.0 vs 6.6 +/- 1.0 ms/mmHg, p = 0.01). All measures of cardiac autonomic dysfunction were significantly associated with hyperglycaemia (mean RR interval vs HbA(1c) r = -0.22; p < 0.001). Ethnic differences in cardiac autonomic function persisted after adjustment for age, blood pressure and medication (mean RR interval 973 vs 1,021 ms, p = 0.004), but were attenuated or abolished by adjusting for HbA(1c) (979 vs 1,014 ms, p = 0.06) or other markers of hyperglycaemia. CONCLUSIONS/INTERPRETATION: Indian Asians from the general population have impaired cardiovascular autonomic function compared with Europeans. This is due to greater hyperglycaemia in Indian Asians and may determine their increased CHD risk.

Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) results in chronic right heart failure, which is associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. We investigated the changes in cardiac autonomic nervous activity in relation to disease severity in patients with PAH. In 48 patients with PAH (median World Health Organization class III, pulmonary artery pressure 52+/-14 mmHg, pulmonary vascular resistance 1,202+/-718 dyn x s x cm(-5), cardiac index 2.0+/-0.8 L x min(-1) x m(-2)) and 41 controls, cardiac autonomic nervous activity was evaluated by measurement of heart rate variability (HRV) and baroreflex sensitivity. All patients underwent cardiopulmonary exercise testing (peak oxygen uptake 13.2+/-5.1 mL x kg(-1) x min(-1), minute ventilation/carbon dioxide production slope 47+/-16). In patients with PAH, spectral power of HRV was reduced in the high-frequency (239+/-64 versus 563+/-167 ms2), low-frequency (245+/-58 versus 599+/-219 ms2) and very low-frequency bands (510+/-149 versus 1106+/-598 ms2; all p<0.05). Baroreflex sensitivity was also blunted (5.8+/-0.6 versus 13.9+/-1.2 ms x mmHg(-1); p<0.01). The reduction in high-frequency (r = 0.3, p = 0.04) and low-frequency (r = 0.33, p = 0.02) spectral power and baroreflex sensitivity (r = 0.46, p<0.01) was related to the reduction in peak oxygen uptake. Patients with PAH have a marked alteration in cardiac autonomic control that is related to exercise capacity and may, therefore, serve as an additional marker of disease severity.

Quantifying the paradoxical effect of higher systolic blood pressure on mortality in chronic heart failure.

BACKGROUND: Although higher blood pressures are generally recognised to be an adverse prognostic marker in risk assessment of cardiology patients, its relationship to risk in chronic heart failure (CHF) may be different. OBJECTIVE: To examine systematically published reports on the relationship between blood pressure and mortality in CHF. METHODS: Medline and Embase were used to identify studies that gave a hazard or relative risk ratio for systolic blood pressure in a stable population with CHF. Included studies were analysed to obtain a unified hazard ratio and quantify the degree of confidence. RESULTS: 10 studies met the inclusion criteria, giving a total population of 8088, with 29 222 person-years of follow-up. All studies showed that a higher systolic blood pressure (SBP) was a favourable prognostic marker in CHF, in contrast to the general population where it is an indicator of poorer prognosis. The decrease in mortality rates associated with a 10 mm Hg higher SBP was 13.0% (95% CI 10.6% to 15.4%) in the heart failure population. This was not related to aetiology, ACE inhibitor or beta blocker use. CONCLUSION: SBP is an easily measured, continuous variable that has a remarkably consistent relationship with mortality within the CHF population. The potential of this simple variable in outpatient assessment of patients with CHF should not be neglected. One possible application of this information is in the optimisation of cardiac resynchronisation devices.

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time.

BACKGROUND: Cardiac resynchronisation therapy improves peak oxygen uptake (peak VO(2)) 3-9 months after device implantation. In chronic heart failure, total isovolumic time (t-IVT) is a major determinant of peak VO(2) and of cardiac output at peak dobutamine stress. In selected patients, resynchronisation can instantaneously shorten t-IVT. We sought to determine the acute effect of resynchronisation on exercise performance and determine, with pharmacological stress echocardiography, the mechanism underlying this effect. METHODS AND RESULTS: Twenty-two patients with resynchronisation were studied within 3 months after device implantation. On a single study day, sequential cardiopulmonary exercise tests were performed during native activation (left bundle branch block) and resynchronisation (atrio-biventricular pacing) in random order. Total-IVT and cardiac output (at rest and peak dobutamine stress) were then measured in each activation mode. Resynchronisation acutely increased peak VO(2) by 1.6 (SD 1.5) ml/kg/min (p<0.001) and shortened peak stress t-IVT by 10 (SD 7) s/min (p<0.001), with the effects in individual patients showing a correlation (r = -0.46, p<0.05). Amongst all measurements during native activation, the best predictor of gain in peak VO(2) from resynchronisation was peak stress t-IVT (r = 0.71, p<0.001) with every increment of 5 s/min of peak stress t-IVT during native activation predicting an 8% gain in peak VO(2). No conventional measures during native activation at rest or on stress (including QRS duration, Tei index, tissue Doppler intraventricular delay, and resting t-IVT) added significant additional information. CONCLUSIONS: In eligible patients, resynchronisation can acutely augment peak VO(2), possibly through a mechanism of t-IVT shortening. Under native activation, long t-IVT during peak stress is the single best predictor of acute resynchronisation-mediated increment in peak VO(2).

Accuracy in ECG lead placement among technicians, nurses, general physicians and cardiologists.

The objective of the study was to determine the reliability of ECG precordial electrode placement by doctors and nurses involved in the emergency care of patients admitted with suspected cardiac diseases. A total of 120 subjects were recruited within 2 days from six hospitals. They comprised physicians, nurses and cardiac technicians involved in the clinical assessment and care of patients with suspected cardiac disease. Subjects were asked to complete a questionnaire and marked on two diagrams of the chest wall the positions they would place precordial electrodes V1-V6. This study showed wide inter-individual and inter-group variations in the placement of electrodes. Notably, V1 and V2 were frequently incorrectly positioned in the second intercostal space, especially by physicians. The correct position of V1 in the fourth right intercostal space was identified by 90% of cardiac technicians, 49% of nurses, 31% of physicians (excluding cardiologists) and--most disappointing of all--only 16% of cardiologists (p<0.001 for inter-group differences). V5 and V6 were also often mispositioned, too high on the lateral chest wall. Nurses and doctors (especially cardiologists) do not know the correct positions for ECG electrodes. Because incorrect positioning of the precordial electrodes changes the ECG significantly, patients are at risk of potentially harmful therapeutic procedures. Equally, doctors who are aware of the possibility of lead misplacement may be inclined to ignore some ECG changes that may be genuine evidence of ischaemia. The only safe solution is proper precordial electrode placement, which requires training and an environment supporting precision.

The interaction of interventricular pacing intervals and left ventricular lead position during temporary biventricular pacing evaluated by tissue Doppler imaging.

OBJECTIVE: To determine the effects of interventricular pacing interval and left ventricular (LV) pacing site on ventricular dyssynchrony and function at baseline and during biventricular pacing, using tissue Doppler imaging. METHODS: Using an angioplasty wire to pace the left ventricle, 20 patients with heart failure and left bundle branch block underwent temporary biventricular pacing from lateral (n = 20) and inferior (n = 10) LV sites at five interventricular pacing intervals: +80, +40, synchronous, -40, and -80 ms. RESULTS: LV ejection fraction (EF) increased (mean (SD) from 18 (8)% to 26 (10)% (p = 0.016) and global mechanical dyssynchrony decreased from 187 (91) ms to 97 (63) ms (p = 0.0004) with synchronous biventricular pacing compared to unpaced baseline. Sequential pacing with LV preactivation produced incremental improvements in EF and global mechanical dyssynchrony (p<0.0001 and p = 0.0026, respectively), primarily as a result of reductions in inter-LV-RV dyssynchrony (p = 0.0001) rather than intra-LV dyssynchrony (NS). Results of biventricular pacing from an inferior or lateral LV site were comparable (for example, synchronous biventricular pacing, global mechanical dyssynchrony: lateral LV site, 97 (63) ms; inferior LV site, 104 (41) ms (NS); EF: lateral LV site, 26 (10)%; inferior LV site, 27 (10)% (NS)). ECG morphology was identical during biventricular pacing through an angioplasty wire and a permanent lead. CONCLUSIONS: Sequential biventricular pacing with LV preactivation most often optimises LV synchrony and EF. An inferior LV site offers a good alternative to a lateral site. Pacing through an angioplasty wire may be useful in assessing the acute effects of pacing.

Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay.

OBJECTIVE: To assess the haemodynamic effect of simultaneously adjusting atrioventricular (AV) and interventricular (VV) delays. METHOD: 35 different combinations of AV and VV delay were tested by using digital photoplethysmography (Finometer) with repeated alternations to measure relative change in systolic blood pressure (SBP(rel)) in 15 patients with cardiac resynchronisation devices for heart failure. RESULTS: Changing AV delay had a larger effect than changing VV delay (range of SBP(rel) 21 v 4.2 mm Hg, p < 0.001). Each had a curvilinear effect. The curve of response to AV delay fitted extremely closely to a parabola (average R2 = 0.99, average residual variance 0.8 mm Hg2). The response to VV delay was significantly less curved (quadratic coefficient 67 v 1194 mm Hg/s2, p = 0.003) and therefore, although the residual variance was equally small (0.8 mm Hg2), the R2 value was 0.7. Reproducibility at two months was good, with the SD of the difference between two measurements of SBP(rel) being 2.5 mm Hg for AV delay (2% of mean systolic blood pressure) and 1.5 mm Hg for VV delay (1% of mean systolic blood pressure). CONCLUSIONS: Changing AV and VV delays results in a curvilinear acute blood pressure response. This shape fits very closely to a parabola, which may be valuable information in developing a streamlined clinical protocol. VV delay adjustment provides an additional, albeit smaller, haemodynamic benefit to AV optimisation.

Echocardiographic methods for selecting patients suitable for biventricular pacing therapy.

The large outcome studies of biventricular pacing to date have selected patients using electrocardiogram criteria (prolonged QRS and left bundle branch block morphology). However, 20-30% of patients do not appear to respond clinically, and as a result there has been much interest in developing more specific methods of detecting mechanical dyssynchrony. A number of different echocardiographic techniques have been developed which appear to offer greater sensitivity and specificity than ECG in selecting these patients. This paper reviews the most promising of the echocardiographic techniques and gives guidance for the clinical use of echocardiography in selecting patients for biventricular pacing.

Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH).

OBJECTIVE: To determine the effect of exercise training on survival in patients with heart failure due to left ventricular systolic dysfunction. DESIGN: Collaborative meta-analysis. Inclusion criteria Randomised parallel group controlled trials of exercise training for at least eight weeks with individual patient data on survival for at least three months. Studies reviewed Nine datasets, totalling 801 patients: 395 received exercise training and 406 were controls. MAIN OUTCOME MEASURE: Death from all causes. RESULTS: During a mean (SD) follow up of 705 (729) days there were 88 (22%) deaths in the exercise arm and 105 (26%) in the control arm. Exercise training significantly reduced mortality (hazard ratio 0.65, 95% confidence interval, 0.46 to 0.92; log rank chi(2) = 5.9; P = 0.015). The secondary end point of death or admission to hospital was also reduced (0.72, 0.56 to 0.93; log rank chi(2) = 6.4; P = 0.011). No statistically significant subgroup specific treatment effect was observed. CONCLUSION: Meta-analysis of randomised trials to date gives no evidence that properly supervised medical training programmes for patients with heart failure might be dangerous, and indeed there is clear evidence of an overall reduction in mortality. Further research should focus on optimising exercise programmes and identifying appropriate patient groups to target.

Comparison of medical therapy, pacing and defibrillation in heart failure (COMPANION) trial terminated early; combined biventricular pacemaker-defibrillators reduce all-cause mortality and hospitalization.

The COMPANION trial was terminated prematurely after recruiting 1600 patients, as initial results clearly and for the first time demonstrated survival benefit of resynchronisation and combined device (biventricular pacemaker with defibrillator capacity) therapy in heart failure. The combined primary end-points of all-cause mortality and all-cause hospitalisation in patients with dilated cardiomyopathy and heart failure of poor functional class was reduced by 20% with cardiac resynchronisation therapy (CRT) with or without defibrillator capacity. More importantly, mortality was reduced by 40% (from 19% to 11%) in patients implanted with combined devices, while CRT alone gave an intermediate mortality of 15%.

Viral load test reports: a description of content from a sample of US laboratories.

CONTEXT: Human immunodeficiency virus (HIV) RNA testing (viral load testing) is increasingly important in the care of patients infected with HIV-1 to determine when to initiate, monitor, and change antiretroviral therapy. Patient viral load testing information is communicated to the clinician through the laboratory test report. OBJECTIVES: To examine the format and information used in reporting viral load testing results and determine the clarity of the information provided in these reports. DESIGN: Patient test reports with all personal identifiers removed were requested of viral load testing laboratories participating in a telephone survey of laboratory practices. Hospital, independent, health department, and "other type" laboratories identified as university-associated laboratories participated in the telephone survey. RESULTS: Thirty-seven unique test reports were collected. All laboratories reported results in copies/mL, while 14% also reported results as "log(10) copies/mL." The test kit was identified by only 24% of the laboratories. Reportable ranges were specified by 70% of the laboratories, but there was considerable variation in terminology. One laboratory reported a viral load copy number below the manufacturer's test kit lower limit of sensitivity. The layout and format differed among reports. Some results were expressed in log(10), others contained nonsignificant integers, while others contained exponential numbers. Supplemental information in some reports included previous patient test results and significance of changes from baseline. The format of some reports made it difficult to read the report information and interpret the testing results. CONCLUSION: This study emphasizes the importance of standardizing the reporting of HIV-1 viral load test results to minimize result misinterpretation and incorrect treatment.