NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand.

Neurally adjusted ventilatory assist (NAVA) is a ventilation assist mode that delivers pressure in proportionality to electrical activity of the diaphragm (Eadi). Compared to pressure support ventilation (PS), it improves patient-ventilator synchrony and should allow a better expression of patient's intrinsic respiratory variability. We hypothesize that NAVA provides better matching in ventilator tidal volume (Vt) to patients inspiratory demand. 22 patients with acute respiratory failure, ventilated with PS were included in the study. A comparative study was carried out between PS and NAVA, with NAVA gain ensuring the same peak airway pressure as PS. Robust coefficients of variation (CVR) for Eadi and Vt were compared for each mode. The integral of Eadi (ʃEadi) was used to represent patient's inspiratory demand. To evaluate tidal volume and patient's demand matching, Range90 = 5-95 % range of the Vt/ʃEadi ratio was calculated, to normalize and compare differences in demand within and between patients and modes. In this study, peak Eadi and ʃEadi are correlated with median correlation of coefficients, R > 0.95. Median ʃEadi, Vt, neural inspiratory time (Ti_ ( Neural )), inspiratory time (Ti) and peak inspiratory pressure (PIP) were similar in PS and NAVA. However, it was found that individual patients have higher or smaller ʃEadi, Vt, Ti_ ( Neural ), Ti and PIP. CVR analysis showed greater Vt variability for NAVA (p < 0.005). Range90 was lower for NAVA than PS for 21 of 22 patients. NAVA provided better matching of Vt to ʃEadi for 21 of 22 patients, and provided greater variability Vt. These results were achieved regardless of differences in ventilatory demand (Eadi) between patients and modes.

Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease.

BACKGROUND: According to recent guidelines, patients with coronary artery disease (CAD) should undergo revascularization if significant myocardial ischemia is present. Both, cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) allow for a reliable ischemia assessment and in combination with anatomical information provided by invasive coronary angiography (CXA), such a work-up sets the basis for a decision to revascularize or not. The cost-effectiveness ratio of these two strategies is compared. METHODS: Strategy 1) CMR to assess ischemia followed by CXA in ischemia-positive patients (CMR + CXA), Strategy 2) CXA followed by FFR in angiographically positive stenoses (CXA + FFR). The costs, evaluated from the third party payer perspective in Switzerland, Germany, the United Kingdom (UK), and the United States (US), included public prices of the different outpatient procedures and costs induced by procedural complications and by diagnostic errors. The effectiveness criterion was the correct identification of hemodynamically significant coronary lesion(s) (= significant CAD) complemented by full anatomical information. Test performances were derived from the published literature. Cost-effectiveness ratios for both strategies were compared for hypothetical cohorts with different pretest likelihood of significant CAD. RESULTS: CMR + CXA and CXA + FFR were equally cost-effective at a pretest likelihood of CAD of 62% in Switzerland, 65% in Germany, 83% in the UK, and 82% in the US with costs of CHF 5'794, euro 1'517, £ 2'680, and $ 2'179 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. CONCLUSIONS: The CMR + CXA strategy is more cost-effective than CXA + FFR below a CAD prevalence of 62%, 65%, 83%, and 82% for the Swiss, the German, the UK, and the US health care systems, respectively. These findings may help to optimize resource utilization in the diagnosis of CAD.

Association Between Long-Term Cognitive Decline in Vietnam Veterans With TBI and Caregiver Attachment Style.

OBJECTIVE: To examine whether a caregiver's attachment style is associated with patient cognitive trajectory after traumatic brain injury (TBI). SETTING: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. PARTICIPANTS: Forty Vietnam War veterans with TBI and their caregivers. MAIN OUTCOME MEASURE: Cognitive performance, measured by the Armed Forces Qualification Test percentile score, completed at 2 time points: preinjury and 40 years postinjury. DESIGN: On the basis of caregivers' attachment style (secure, fearful, preoccupied, dismissing), participants with TBI were grouped into a high or low group. To examine the association between cognitive trajectory of participants with TBI and caregivers' attachment style, we ran four 2 × 2 analysis of covariance on cognitive performances. RESULTS: After controlling for other factors, cognitive decline was more pronounced in participants with TBI with a high fearful caregiver than among those with a low fearful caregiver. Other attachment styles were not associated with decline. CONCLUSION AND IMPLICATION: Caregiver fearful attachment style is associated with a significant decline in cognitive status after TBI. We interpret this result in the context of the neural plasticity and cognitive reserve literatures. Finally, we discuss its impact on patient demand for healthcare services and potential interventions.

Regional consumption of antibiotics : a demand system approach

Through this paper. we have attempted to model the demand for different classes of antibiotics used for respiratory infections in outpatient care in Switzerland using a spatial version of the linear approximate Almost Ideal Demand System (AIDS) model. This model takes spatial dependency into account by means of spatial lags of antibiotic budget shares. We control for the health status of patients and the potential harmful effects of antibiotic use in terms of bacterial resistance. Elasticities to socioeconomic determinants of consumption and own- and cross-price elasticities between different groups of antibiotic have also been computed in this paper. Significant cross-price elasticities are found between newer or more expensive generations and older or less expensive generations of antibiotics. (C) 2009 Elsevier B.V. All rights reserved.

Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks.

Comparativecost-effectivenessanalyses of cardiacmagneticresonanceimaging versus invasive coronary angiography combined with fractional flow reserve testing to diagnose ischemia in coronary artery disease

Introduction: According to guidelines, patients with coronary artery disease (CAD) should undergo revascularization if myocardial ischemia is present. While coronary angiography (CXA) allows the morphological assessment of CAD, the fractional flow reserve (FFR) has proved to be a complementary invasive test to assess the functional significance of CAD, i.e. to detect ischemia. Perfusion Cardiac Magnetic Resonance (CMR) has turned out to be a robust non-invasive technique to assess myocardial ischemia. The objective: is to compare the cost-effectiveness ratio - defined as the costs per patient correctly diagnosed - of two algorithms used to diagnose hemodynamically significant CAD in relation to the pretest likelihood of CAD: 1) aCMRto assess ischemia before referring positive patients to CXA (CMR + CXA), 2) a CXA in all patients combined with a FFR test in patients with angiographically positive stenoses (CXA + FFR). Methods: The costs, evaluated from the health care system perspective in the Swiss, German, the United Kingdom (UK) and the United States (US) contexts, included public prices of the different tests considered as outpatient procedures, complications' costs and costs induced by diagnosis errors (false negative). The effectiveness criterion wasthe ability to accurately identify apatient with significantCAD.Test performancesused in the model were based on the clinical literature. Using a mathematical model, we compared the cost-effectiveness ratio for both algorithms for hypothetical patient cohorts with different pretest likelihood of CAD. Results: The cost-effectiveness ratio decreased hyperbolically with increasing pretest likelihood of CAD for both strategies. CMR + CXA and CXA + FFR were equally costeffective at a pretest likelihood of CAD of 62% in Switzerland, 67% in Germany, 83% in the UK and 84% in the US with costs of CHF 5'794, Euros 1'472, £ 2'685 and $ 2'126 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. Implications for the health care system/professionals/patients/society These results facilitate decision making for the clinical use of new generations of imaging procedures to detect ischemia. They show to what extent the cost-effectiveness to diagnose CAD depends on the prevalence of the disease.

Do Financial Incentives Affect Firms' Demand For Disabled Workers?

A number of OECD countries aim to encourage work integration of disabled persons using quota policies. For instance, Austrian firms must provide at least one job to a disabled worker per 25 nondisabled workers and are subject to a tax if they do not. This "threshold design" provides causal estimates of the noncompliance tax on disabled employment if firms do not manipulate nondisabled employment; a lower and upper bound on the causal effect can be constructed if they do. Results indicate that firms with 25 nondisabled workers employ about 0.04 (or 12%) more disabled workers than without the tax; firms do manipulate employment of nondisabled workers but the lower bound on the employment effect of the quota remains positive; employment effects are stronger in low-wage firms than in high-wage firms; and firms subject to the quota of two disabled workers or more hire 0.08 more disabled workers per additional quota job. Moreover, increasing the noncompliance tax increases excess disabled employment, whereas paying a bonus to overcomplying firms slightly dampens the employment effects of the tax.

Myocardial flow reserve by Rb-82 cardiac PET improves the selection of patients eligible for invasive coronary angiography

Aim: We asked whether myocardial flow reserve (MFR) by Rb-82 cardiac PET improve the selection of patients eligible for invasive coronary angiography (ICA). Material and Methods: We enrolled 26 consecutive patients with suspected or known coronary artery disease who performed dynamic Rb-82 PET/CT and (ICA) within 60 days; 4 patients who underwent revascularization or had any cardiovascular events between PET and ICA were excluded. Myocardial blood flow at rest (rMBF), at stress with adenosine (sMBF) and myocardial flow reserve (MFR=sMBF/rMBF) were estimated using the 1-compartment Lortie model (FlowQuant) for each coronary arteries territories. Stenosis severity was assessed using computer-based automated edge detection (QCA). MFR was divided in 3 groups: G1:MFR<1.5, G2:1.5≤MFR<2 and G3:2≤MFR. Stenosis severity was graded as non-significant (<50% or FFR ≥0.8), intermediate (50%≤stenosis<70%) and severe (≥70%). Correlation between MFR and percentage of stenosis were assessed using a non-parametric Spearman test. Results: In G1 (44 vessels), 17 vessels (39%) had a severe stenosis, 11 (25%) an intermediate one, and 16 (36%) no significant stenosis. In G2 (13 vessels), 2 (15%) vessels presented a severe stenosis, 7 (54%) an intermediate one, and 4 (31%) no significant stenosis. In G3 (9 vessels), 0 vessel presented a severe stenosis, 1 (11%) an intermediate one, and 8 (89%) no significant stenosis. Of note, among 11 patients with 3-vessel low MFR<1.5 (G1), 9/11 (82%) had at least one severe stenosis and 2/11 (18%) had at least one intermediate stenosis. There was a significant inverse correlation between stenosis severity and MFR among all 66 territories analyzed (rho= -0.38, p=0.002). Conclusion: Patients with MFR>2 could avoid ICA. Low MFR (G1, G2) on a vessel-based analysis seems to be a poor predictor of severe stenosis severity. Patients with 3-vessel low MFR would benefit from ICA as they are likely to present a significant stenosis in at least one vessel.

Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

PURPOSE: The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). METHODS: Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with N-ammonia and F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to N-ammonia activity ratios. RESULTS: Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p < 0.001) and to normals (0.63 ± 0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p < 0.05) and stress (p < 0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p < 0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40 ± 0.14 vs 0.90 ± 0.20, p < 0.001) and in nonviable regions (1.13 ± 0.21, p < 0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r =-0.424, p < 0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. CONCLUSION: As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

Rise in plasma lactate concentrations with psychosocial stress: a possible sign of cerebral energy demand.

OBJECTIVE: It is known that exogenous lactate given as an i.v. energy infusion is able to counteract a neuroglycopenic state that developed during psychosocial stress. It is unknown, however, whether the brain under stressful conditions can induce a rise in plasma lactate to satisfy its increased needs during stress. Since lactate is i) an alternative cerebral energy substrate to glucose and ii) its plasmatic concentration is influenced by the sympathetic nervous system, the present study aimed at investigating whether plasma lactate concentrations increase with psychosocial stress in humans. METHODS: 30 healthy young men participated in two sessions (stress induced by the Trier Social Stress Test and a non-stress control session). Blood samples were frequently taken to assess plasma lactate concentrations and stress hormone profiles. RESULTS: Plasma lactate increased 47% during psychosocial stress (from 0.9 ± 0.05 to 1.4 ± 0.1 mmol/l; interaction time × stress intervention: F = 19.7, p < 0.001). This increase in lactate concentrations during stress was associated with an increase in epinephrine (R(2) = 0.221, p = 0.02) and ACTH concentrations (R(2) = 0.460, p < 0.001). CONCLUSION: Plasma lactate concentrations increase during acute psychosocial stress in humans. This finding suggests the existence of a demand mechanism that functions to allocate an additional source of energy from the body towards the brain, which we refer to as 'cerebral lactate demand'.

Less Risk, More Effort : Demand Risk Allocation in Incomplete Contracts

This article investigates the allocation of demand risk within an incomplete contract framework. We consider an incomplete contractual relationship between a public authority and a private provider (i.e. a public-private partnership), in which the latter invests in non-verifiable cost-reducing efforts and the former invests in non-verifiable adaptation efforts to respond to changing consumer demand over time. We show that the party that bears the demand risk has fewer hold-up opportunities and that this leads the other contracting party to make more effort. Thus, in our model, bearing less risk can lead to more effort, which we describe as a new example of âeuro~counter-incentivesâeuro?. We further show that when the benefits of adaptation are important, it is socially preferable to design a contract in which the demand risk remains with the private provider, whereas when the benefits of cost-reducing efforts are important, it is socially preferable to place the demand risk on the public authority. We then apply these results to explain two well-known case studies.