Estimating the returns to United Kingdom publicly funded musculoskeletal disease research in terms of net value of improved health outcomes.

BACKGROUND: Building on an approach applied to cardiovascular and cancer research, we estimated the economic returns from United Kingdom public- and charitable-funded musculoskeletal disease (MSD) research that arise from the net value of the improved health outcomes in the United Kingdom. METHODS: To calculate the economic returns from MSD-related research in the United Kingdom, we estimated (1) the public and charitable expenditure on MSD-related research in the United Kingdom between 1970 and 2013; (2) the net monetary benefit (NMB), derived from the health benefit in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of £25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1994 to 2013; (3) the proportion of NMB attributable to United Kingdom research; and (4) the elapsed time between research funding and health gain. The data collected from these four key elements were used to estimate the internal rate of return (IRR) from MSD-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using a one-way sensitivity analysis. RESULTS: Expressed in 2013 prices, total expenditure on MSD-related research from 1970 to 2013 was £3.5 billion, and for the period used to estimate the rate of return, 1978-1997, was £1.4 billion. Over the period 1994-2013 the key interventions analysed produced 871,000 QALYs with a NMB of £16 billion, allowing for the net NHS costs resulting from them and valuing a QALY at £25,000. The proportion of benefit attributable to United Kingdom research was 30% and the elapsed time between funding and impact of MSD treatments was 16 years. Our best estimate of the IRR from MSD-related research was 7%, which is similar to the 9% for CVD and 10% for cancer research. CONCLUSIONS: Our estimate of the IRR from the net health gain to public and charitable funding of MSD-related research in the United Kingdom is substantial, and justifies the research investments made between 1978 and 1997. We also demonstrated the applicability of the approach previously used in assessing the returns from cardiovascular and cancer research. Inevitably, with a study of this kind, there are a number of important assumptions and caveats that we highlight, and these can inform future research.

Randomized trial of the Terumo Capiox FX05 oxygenator with integral arterial filter versus Terumo Capiox Baby RX05 and Terumo Capiox AF02 arterial filter in infants undergoing cardiopulmonary bypass.

UNLABELLED: The purpose of this clinical trial was to evaluate the effect of the Terumo Capiox FX05 oxygenator with integrated arterial filter during cardiopulmonary bypass (CPB) compared with the Terumo Capiox RX05 Baby RX and arterial filter on inflammatory mediators and blood product utilization. Forty patients weighing less than 10 kg who underwent congenital heart surgery utilizing cardiopulmonary bypass were randomized into either oxygenator group. The endpoints included measuring inflammatory markers at six different time points (preoperative baseline, CPB circuit being primed, 15 minutes after CPB initiation, status post protamine administration, prior to transport to intensive care unit, and within 12 to 24 hours post surgery), blood product utilization, extubation time, and days until discharge. The inflammatory mediators showed no significant differences between oxygenators at any time points. However, looking at the inflammatory mediators of both the FX and RX groups combined, a statistically significant difference was seen in interleukin (IL)-6 at 12/24 hour post surgery (p < .001) versus baseline and all other time points. IL-8 at status post protamine (p < .001) and 12/24 hours post surgery (p < .001) demonstrated significant differences versus all other time points, and IL-10 at status post protamine (p < .001) and prior to leaving the operating room (p < .001) were statistically different compared to all other time points. Cardiopulmonary bypass stimulates the systemic inflammatory response through various components of the extracorporeal system. This investigation did not find significant differences in cytokines interferon-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, tumor necrosis factor (TNF)-alpha, and TNF-beta when comparing these two oxygenators. It is well known that various mechanisms contribute to the levels of cytokines circulating in a patient's blood volume and many manipulations throughout cardiac surgery have the ability to demonstrate anti-inflammatory interventions. Further investigation is needed as to how modification of the extracorporeal circuit may minimize increases in inflammatory mediators. KEYWORDS: infant, bypass, cytokines, blood, infant perfusion strategy.

Pump in Parallel-Mechanical Assistance of Partial Cavopulmonary Circulation Using a Conventional Ventricular Assist Device.

Mechanical assistance of systemic single ventricle is effective in pulling blood through a cavopulmonary circuit. In patients with superior cavopulmonary connection, this strategy can lead to arterial desaturation secondary to increased inferior caval flow. We hypothesized that overall augmentation in cardiac output with mechanical assistance compensates for the drop in oxygen saturation thereby maintaining tissue oxygen delivery (DO2). Bidirectional Glenn (BDG) was established in seven swine (25 kg) after a common atrium had been established by balloon septostomy. Mechanical circulatory assistance of the single ventricle was achieved using an axial flow pump with ventricular inflow and aortic outflow. Cardiac output, mean pulmonary artery pressure (PAP), common atrial pressure (left atrial pressure [LAP]), arterial oxygen saturation (SaO2), partial pressure of arterial oxygen (PaO2), and DO2 were compared between assisted and nonassisted circulation. Significant augmentation of cardiac output was achieved with mechanical assistance in BDG circulation (BDG: median [interquartile range {IQR}], 0.8 [0.9-1.15] L/min versus assisted BDG: median [IQR], 1.5 [1.15-1.7] L/min; p = 0.05). Although oxygen saturations and PaO2 trended to be lower with assistance (SaO2; BDG: median [IQR], 43% [32-57%]; assisted BDG: median [IQR], 32% [24-35%]; p = 0.07) (PaO2; BDG: median [IQR], 24 [20-30] mm Hg; assisted BDG: median [IQR], 20 [17-21] mm Hg; p = 0.08), DO2 was unchanged with mechanical assistance (BDG: median [IQR], 94 [35-99] ml/min; assisted BDG: median [IQR], 79 [63-85] ml/min; p = 0.81). No significant change in the LAP or PAP was observed. In the setting of superior cavopulmonary connection/single ventricle, the systemic ventricular assistance with a ventricular assist device (VAD) leads to increase in cardiac output. Arterial oxygen saturations however may be lower with mechanical assistance, without any change in DO2.

Effect of mechanical assistance of the systemic ventricle in single ventricle circulation with cavopulmonary connection.

BACKGROUND: Previous attempts to support single ventricle circulation mechanically have suggested that a custom-built assist device is needed to push, rather than pull, through the pulmonary circulation. We hypothesized that using a conventional ventricular assist device, with or without conversion of a total cavopulmonary connection to a bidirectional Glenn cavopulmonary connection, would allow assistance by pulling blood through the circuit and improve the cardiac index (CI). METHODS: Cavopulmonary connections were established in each of 5 Yorkshire pigs (25 kg) using ePTFE conduits in a Y configuration with appropriate clamping of the limbs of the Y to achieve a total cavopulmonary Fontan connection (TCPC), superior vena cava cavopulmonary connection (SVC Glenn), and inferior vena cava cavopulmonary connection (IVC Glenn). A common atrium had been established previously by balloon septostomy. Mechanical circulatory assistance of the single systemic ventricle was achieved using a centrifugal pump with common atrial inflow and proximal ascending aortic outflow. The CI was calculated using an ultrasonic flow meter placed on the distal ascending aorta and compared between the assisted and nonassisted circulation for 3 conditions: TCPC, SVC Glenn, and IVC Glenn. The mean pulmonary artery pressure, common atrial pressure, arterial oxygen saturation, partial pressure of arterial oxygen, and oxygen delivery were calculated. RESULTS: The unassisted SVC Glenn CI tended to be greater than the TCPC or IVC Glenn CI. Significant augmentation of total CI was achieved with mechanical assistance for SVC Glenn (109% ± 24%, P = .04) and TCPC (130% ± 109%, P = .01). The assisted CI achieved at least a mean baseline biventricular CI for all 3 support modes. Oxygen delivery was greatest for assisted SVC Glenn (1786 ± 1307 mL/L/min) and lowest for TCPC (1146 ± 386 mL/L/min), with a trend toward lower common atrial and pulmonary artery pressures for SVC Glenn. CONCLUSIONS: SVC bidirectional Glenn circulation might allow optimal augmentation of the CI and oxygen delivery in a failing single ventricle using a conventional pediatric ventricular assist device. The results from our model also suggest that the Fontan circulation itself can be supported with systemic ventricular assistance of the single ventricle.