System-level Variation Research Articles

Design and Implementation of a Proof-of-Concept Robotic-Microfluidic Interface to Bridge Spatial Comprehensive Three-Dimensional Liquid Chromatography with Mass Spectrometry.

A proof-of-concept system is presented for the hyphenation of spatial comprehensive three-dimensional liquid chromatography (3D-LC) to mass spectrometry (MS) detection via a robotic-microfluidic interface. A three-dimensional fractal microflow distributor, incorporating 16 parallel RP monolithic capillary columns arranged in a 4 × 4 configuration, was connected to an X-Y-Z robotic system. This setup facilitated the deposition of successive arrays of microdroplets onto an MS target plate. To minimize carryover during droplet deposition, a strategy was implemented in which the distance between the target plate and the capillary was gradually increased during the deposition process. System-level variation in travel time and subsequent flow rates across parallel columns was assessed and translated in retention alignment based on injection of a protein standard. The successful separation of intact proteins was demonstrated through a parallel 4 × 4 column configuration, applying MALDI-MS detection after microdroplet spotting on an MS target plate. Furthermore, the discussion encompasses high-throughput MS imaging detection within the framework of spatial 3D-LC.

System-level variation in evidence-based multidisciplinary cancer care delivery.

11064 Background: Widespread health system integration of hospitals continues to reshape the landscape of U.S. healthcare delivery. While complex cancer care has become centralized to high-volume centers, care for common cancers happens across the spectrum of hospital sizes, with known variation in receipt of evidence-based practice (EBP) based on system affiliation. Strategies are needed to evaluate system performance in order to identify system characteristics and processes that contribute to high-quality cancer care. Methods: Using a novel data linkage between the National Cancer Database and AHRQ Compendium of U.S. Health Systems, adult patients treated for breast, colon, melanoma, and thyroid cancers between 2010 and 2020 at Commission on Cancer (CoC) hospitals were identified. Systems were categorized based on number of CoC hospitals (small, 2-3; medium, 4-9; large, 10+). Eight EBP measures were developed using national multidisciplinary guidelines, and measure-specific cohorts were extracted to calculate system-level EBP performance and within-system variation using mixed effects multivariable logistic regression models. Systems were then ranked across all measures for performance and variation, and average rankings were compared by system size. Results: 3,052,453 patients with breast (60.0%), colon (17.0%), melanoma (14.0%), and thyroid (9.0%) cancers were treated at 866 CoC hospitals in 368 health systems. The 8-measure analytic cohort had 104 systems, most of which were small systems (n=74, 71.2%). Large systems (n=9, 8.7%) had worse average performance rankings compared to medium or small systems, though this was not statistically significant (p=0.1) (Table). A significant increase in within-system variation (as measured by average ranking of variability across EBP measures) was seen with increasing system size (p<0.001). Conclusions: Significant variation in EBP performance for common cancers was noted based on health system size in this large, contemporary cohort, with greater within-system variation as system size increased. Future work will identify modifiable system characteristics associated with performance that could aid system leaders and policy makers to design, measure, and incentivize systems that employ effective cancer care delivery strategies. System rankings from 1 to 104 (best to worst), averaged over all measures; data presented as median (IQR). [Table: see text]

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma

BackgroundExacerbation frequency strongly influences treatment choices in patients with severe asthma. Research QuestionWhat is the extent of the variability of exacerbations rate across countries and its implications in disease management? Study Design and MethodsWe retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥3 days or asthma-related hospitalization/emergency room visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naïve model with country as the only variable, to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. ResultsThe final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (min: 0.04 [Argentina], max:0.88 [Saudi Arabia], interquartile range [IQR]: 0.13–0.54), which remained substantial after adjusting for patient characteristics and sampling variability (IQR: 0.16–0.39). InterpretationIndividuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies. Clinical Trial Registration NumberN/A

Area-level social determinants of health and individual-level social risks: Assessing predictive ability and biases in social risk screening.

Area-level social determinants of health (SDoH) and individual-level social risks are different, yet area-level measures are frequently used as proxies for individual-level social risks. This study assessed whether demographic factors were associated with patients being screened for individual-level social risks, the percentage who screened positive for social risks, and the association between SDoH and patient-reported social risks in a nationwide network of community-based health centers. Electronic health record data from 1,330,201 patients with health center visits in 2021 were analyzed using multilevel logistic regression. Associations between patient characteristics, screening receipt, and screening positive for social risks (e.g., food insecurity, housing instability, transportation insecurity) were assessed. The predictive ability of three commonly used SDoH measures (Area Deprivation Index, Social Deprivation Index, Material Community Deprivation Index) in identifying individual-level social risks was also evaluated. Of 244,155 (18%) patients screened for social risks, 61,414 (25.2%) screened positive. Sex, race/ethnicity, language preference, and payer were associated with both social risk screening and positivity. Significant health system-level variation in both screening and positivity was observed, with an intraclass correlation coefficient of 0.55 for social risk screening and 0.38 for positivity. The three area-level SDoH measures had low accuracy, sensitivity, and area under the curve when used to predict individual social needs. Area-level SDoH measures may provide valuable information about the communities where patients live. However, policymakers, healthcare administrators, and researchers should exercise caution when using area-level adverse SDoH measures to identify individual-level social risks.

CO88 Center-Level Variation in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores in Patients with MS from the Multiple Sclerosis Continuous Quality Improvement (MS-CQI) Research Collaborative Study (2017-2020)

MS-CQI was the first multi-center improvement research collaborative for people with multiple sclerosis (MS) and was a three year study of system-level variation and use quality improvement (QI) methods to improve MS outcomes (2017-2020). Assessing Patient Reported Outcomes (PROs), such as satisfaction to medication treatment, is important in complex, chronic, and costly (“3C”) diseases like MS where people with MS (PwMS) commonly suffer from mental health problems that impact quality of life (QoL) and MS related outcomes.

System-Level Variation in Multiple Sclerosis Disease-Modifying Therapy Utilization: Findings From the Multiple Sclerosis Continuous Quality Improvement Research Collaborative.

The Multiple Sclerosis Continuous Quality Improvement (MS-CQI) Collaborative is the first multicenter improvement research collaborative for multiple sclerosis (MS). The main objective of this study is to describe baseline system-level variation in disease-modifying therapy (DMT) utilization across 4 MS centers participating in MS-CQI. Electronic health record data from the first year of the 3-year MS-CQI study were analyzed. Participants were adults ≥ 18 years with MS presenting to any of the 4 MS-CQI centers. DMT utilization was categorized into oral, infusion, and injection types. Multinomial logistic regression was used to investigate associations between centers and DMT utilization. Overall, 2,029 patients were included in the analysis. Of those patients, 75.1% were female, mean age was 50 years, and 87.4% had relapsing-remitting MS. Overall, 32.7% were on an oral DMT, 23.5% on an infusion DMT, and 43.9% on an injection DMT. Overall, statistically significant differences (p < 0.01) were observed across centers for proportions of patients who received oral, infusion, and no DMTs. There were also overall significant differences (p < 0.01) across MS types for proportions of encounters who received oral, infusion, injection, no DMTs, and mean age varied significantly across centers. System-level effects on MS treatment and outcomes have not been previously studied and our findings contribute initial evidence concerning system-level variation in DMT utilization. Results suggest system-level variation in DMT utilization (ie, after adjusting for individual level factors, MS center or location of care a person with MS engages in care influences DMT treatment choices), resulting in a lack of standardization in DMT management. Continued research and improvement efforts targeting system-level performance could improve outcomes for people with MS.

Cisplatin's potential for type 2 diabetes repositioning by inhibiting CDKN1A, FAS, and SESN1

Cisplatin is a DNA-damaging chemotherapeutic agent used for treating cancer. Based on cDNA dataset analysis, we investigated how cisplatin modified gene expression and observed cisplatin-induced dysregulation and system-level variations relating to insulin resistance and type 2 diabetes mellitus (T2DM). T2DM is a multifactorial disease affecting 462 million people in the world, and drug-induced T2DM is a serious issue. To understand this etiology, we designed an integrative, system-level study to identify associations between cisplatin-induced differentially expressed genes (DEGs) and T2DM. From a list of differential expressed genes, cisplatin downregulated the cyclin-dependent kinase inhibitor 1 (CDKN1A), tumor necrosis factor (FAS), and sestrin-1 (SESN1) genes responsible for modifying signaling pathways, including the p53, JAK-STAT, FOXO, MAPK, mTOR, P13-AKT, Toll-like receptor (TLR), adipocytokine, and insulin signaling pathways. These enriched pathways were expressively associated with the disease. We observed significant gene signatures, including SMAD3, IRS, PDK1, PRKAA1, AKT, SOS, RAS, GRB2, MEK1/2, and ERK, interacting with source genes. This study revealed the value of system genetics for identifying the cisplatin-induced genetic variants responsible for the progression of T2DM. Also, by cross-validating gene expression data for T2DM islets, we found that downregulating IRS and PRK families is critical in insulin and T2DM signaling pathways. Cisplatin, by inhibiting CDKN1A, FAS, and SESN1, promotes IRS and PRK activity in a similar way to rosiglitazone (a popular drug used for T2DM treatment). Our integrative, network-based approach can help in understanding the drug-induced pathophysiological mechanisms of diabetes.

System-Level Variation in Multiple Sclerosis Care Outcomes: Initial Findings from the Multiple Sclerosis Continuous Quality Improvement Research Collaborative.

Multiple sclerosis (MS) is a "3C" (complex, chronic, costly) condition that is a common and disabling neurological illness affecting approximately 1 million adults in the United States. MS has been studied at the basic science, individual, and population levels, but not at the system level to assess small-area variation effects on MS population health outcomes. System-level effects have been observed in other 3C conditions including cystic fibrosis, rheumatoid arthritis, and inflammatory bowel disease. The authors report here on system-level variation findings from the baseline period during the first year of the Multiple Sclerosis Continuous Quality Improvement (MS-CQI) study. Stepwise binary logistic regression analyses were conducted to investigate system-level (small-area variation) effects on MS relapses (exacerbations), disease-modifying therapy (DMT) utilization, and brain MRI utilization, controlling for demographics (age and sex) and other potential confounders. Significant differences were observed in people with MS (PwMS) between centers for a number of demographic and disease characteristics, including sex, age, and MS subtype. Controlling for these factors, significant system-level effects were observed on outcomes, including DMT utilization, MRI utilization, and relapses. Significant relationships also were observed between outcomes and urgent care utilization, including emergency department visits and hospitalizations. This initial study provides evidence establishing the presence of system-level variation effects on MS outcomes in a multicenter population study - where PwMS get their care can influence their outcomes. Results support continued systems-level research and improvement initiatives to optimize MS population health outcomes in this challenging and costly complex chronic condition.

Using Health Systems Engineering Approaches to Prepare for Tailoring of Implementation Interventions.

Implementation of evidence-based practices often requires tailoring implementation strategies to local contextual factors, including available resources, expertise, and cultural norms. Using an exemplar case, we describe how health systems engineering methods can be used to understand system-level variation that must be accounted for prior to broad implementation. Within the context of a single-center quality improvement activity, a multi-disciplinary stakeholder team used health systems engineering methods to describe how pre-endoscopy antithrombotic management was executed, and implemented a redesigned process to improve clinical care. The research team then conducted multiple stakeholder focus groups at four different health-care systems to describe and compare current processes for pre-endoscopy antithrombotic medication management. Detailed work flow maps for each health-care system were developed, analyzed, and integrated to develop an overarching current work flow map, identify key process steps, and describe areas of process variation. Five key process steps were identified across the four health systems: (1) place an endoscopy order, (2) screen for antithrombotic use, (3) coordinate medication management, (4) instruct the patient, and (5) confirm appropriate medication management before procedure. Across health systems, we found a high degree of variation in each step (e.g., who performed, use of technology, systematic vs. ad hoc process). This variation was influenced by two key system-level contextual factors: (1) degree of health system integration and (2) role and training level of available staff. These key steps, areas of variation, and contextual factors were integrated into an assessment tool designed to facilitate tailoring of a future implementation and dissemination strategy. Tools from health systems engineering can be used to identify key work flow process steps, variations in how those steps are executed, and influential contextual factors. This process and the associated assessment tool may facilitate broader implementation tailoring.

Acute mental health service use is increased in rheumatoid arthritis and ankylosing spondylitis: a population-based cohort study.

Background:Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with mental illness. Whether acute mental health (MH) service utilization (i.e. emergency visits or hospitalizations) is increased in RA or AS is not known.Methods:Two population-based cohorts were created where individuals with RA (n = 53,240) or AS (n = 13,964) were each matched by age, sex, and year to unaffected comparators (2002–2016). Incidence rates per 1000 person-years (PY) were calculated for a first MH emergency department (ED) presentation or MH hospitalization. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for demographic, clinical, and health service use variables.Results:Individuals with RA had higher rates of ED visits [6.59/1000 person-years (PY) versus 4.39/1000 PY in comparators] and hospitalizations for MH (3.11/1000 PY versus 1.80/1000 PY in comparators). Higher rates of ED visits (7.92/1000 PY versus 5.62/1000 PY in comparators) and hospitalizations (3.03/1000 PY versus 1.94/1000 PY in comparators) were also observed in AS. Overall, RA was associated with a 34% increased risk for MH hospitalization (HR 1.34, 95% CI 1.22–1.47) and AS was associated with a 36% increased risk of hospitalization (HR 1.36, 95% CI 1.12–1.63). The risk of ED presentation was attenuated, but remained significant, after adjustment in both RA (HR 1.08, 95% CI 1.01–1.15) and AS (HR 1.14, 95% CI 1.02–1.28).Conclusions:RA and AS are both independently associated with a higher rate and risk of acute ED presentations and hospitalizations for mental health conditions. These findings underscore the need for routine evaluation of MH as part of the management of chronic inflammatory arthritis. Additional research is needed to identify the underlying individual characteristics, as well as system-level variation, which may explain these differences, and to help plan interventions to make MH service use more responsive to the needs of individuals living with RA and AS.

System-level variations in treatment delay for nonmetastatic melanoma

System-level variations in treatment delay for nonmetastatic melanoma

It’s not just who you know: System-level variation in the availability of process information

‘Informational lobbying’ is the provision of information to policymakers with the intent of influencing debate and policy. However, influence is more likely when groups make strategic choices about what (relevant and timely) information to provide, when, and to whom. To do this, groups need ‘process information,’ or knowledge about current policymaking. In contrast to extant theories of informational lobbying, I argue that we cannot assume process information is automatically available to groups, nor that access to it is solely dependent on group-level characteristics like resource endowments. Instead, each policymaking system releases process information differently. Using interviews with forestry-related groups in France and Sweden, I show that policymaking systems matter more than group type for these groups’ perceptions of process information. Acknowledging process information as a systemic variable in its own right opens up new avenues of inquiry about lobbying and group behavior.

Mmnet: An R Package for Metagenomics Systems Biology Analysis

The human microbiome plays important roles in human health and disease. Previous microbiome studies focused mainly on single pure species function and overlooked the interactions in the complex communities on system-level. A metagenomic approach introduced recently integrates metagenomic data with community-level metabolic network modeling, but no comprehensive tool was available for such kind of approaches. To facilitate these kinds of studies, we developed an R package, mmnet, to implement community-level metabolic network reconstruction. The package also implements a set of functions for automatic analysis pipeline construction including functional annotation of metagenomic reads, abundance estimation of enzymatic genes, community-level metabolic network reconstruction, and integrated network analysis. The result can be represented in an intuitive way and sent to Cytoscape for further exploration. The package has substantial potentials in metagenomic studies that focus on identifying system-level variations of human microbiome associated with disease.

Managing disruptive patients in health care: Necessary solutions to a difficult problem

We sought to describe the components and processes in a violence risk assessment and management system, including electronic record requirements in the Veterans Health Administration (VA). We present information on system-level variation among program elements and their association with perceived and measured effectiveness. We conducted a cross-sectional survey of Chiefs of Staff (COS) at 140 VA hospitals across the United States about specific disruptive behavior program elements, such as committee processes, patient referrals, and outcome patterns. We assessed COS perceived effectiveness of the processes. We compared COS perceptions with employee-reported assault-related incident rates and workers compensation lost time claim rates for assault-related injuries for 2009 and 2010. We found the violence risk assessment and management system is heavily used, often with guidance to provide police protection for providers. COS respondents were generally satisfied with design and performance of the system. Committee processes and perceptions of effectiveness were associated with reduction in assault-related incident rates. VA's system was considered effective by system owners and users may be effective at reducing assaulted-related injuries.

Accounting for Variation in Technical Quality and Patient Satisfaction

The delivery of healthcare depends on individual providers, coordination within teams, and the structure of the work setting. We analyzed the amount of variation in technical quality and patient satisfaction accounted for at the patient, provider, team, and medical center level. Data abstracted from Veterans Health Administration patient medical records for 2007 were used to calculate measures of technical quality based on adherence to best practice guidelines in 5 domains. Outpatient satisfaction was obtained from a 2007 standardized national mail survey. Hierarchical linear models that accounted for the clustering of patients within providers, providers within teams, and teams within medical centers were used to partition the variation in technical quality and satisfaction across patients and components of the system (ie, providers, teams, and medical centers). Providers accounted for the largest percent of system-level variance for all technical quality domains, ranging from 46.5% to 71.9%. For the single-item measure of patient satisfaction, medical centers, teams, and providers accounted for about the same percent of system-level variance (31%-34%). For the doctor/patient interaction scale providers explained 59.9% of system-level variance, more than double that of teams and medical centers. For all the measures, the residual variance (composed of patient-level and random error) explained the largest proportion of the total variance. Providers explained the greatest amount of system-level variation in technical quality and patient satisfaction. However, in both of these domains, differences between patients were the predominant source of nonrandom variance.

The Macroeconomic Factors Conditioning the Impact of Identity on Attitudes towards the EU

Factors relating to identity and to economics have been shown to be important predictors of attitudes towards the European Union (EU). In this article, we show that the impact of identity is conditional on economic context. First, living in a member state that receives relatively high levels of EU funding acts as a ‘buffer’, diluting the impact of an exclusive national identity on Euroscepticism. Second, living in a relatively wealthy member state, with its associated attractiveness for economic migrants, increases the salience of economic xenophobia as a driver of sceptical attitudes. These results highlight the importance of seeing theories of attitude formation (such as economic and identity theories) not as competitors but rather as complementary, with the predictive strength of one theoretical approach (identity) being a function of system-level variation in factors relating to the other theoretical approach (macro-level economic conditions).

How Do Doctors in Different Countries Manage the Same Patient? Results of a Factorial Experiment

To determine the relative contributions of: (1) patient attributes; (2) provider characteristics; and (3) health care systems to health care disparities in the management of coronary heart disease (CHD) and depression. Primary experimental data were collected in 2001-2 from 256 randomly sampled primary care providers in the U.S. (Massachusetts) and the U.K. (Surrey, Southeast London, and the West Midlands). Two factorial experiments were conducted in which physicians were shown, in random order, two clinically authentic videotapes of "patients" presenting with symptoms strongly suggestive of CHD and depression. "Patient" characteristics (age, gender, race, and socioeconomic status [SES]) were systematically varied, permitting estimation of unconfounded main effects and the interaction of patient, provider, and system-level influences. DATA COLLECTION/DATA EXTRACTION METHODS: Analysis of variance was used to measure provider decision-making outcomes, including diagnosis, information seeking, test ordering, prescribing behavior, lifestyle recommendations, and referrals/follow-ups. There is a high level of consistency in decision making for CHD and depression between the U.S. and the U.K. Most physicians in both countries correctly identified conditions depicted in the vignettes, although U.S. doctors engage in more information seeking, are more likely to prescribe medications, and are more certain of their diagnoses than their U.K. counterparts. The absence of any national differences in test ordering is consistent for both of the medical conditions depicted. U.K. physicians, however, were more likely than U.S. physicians to make lifestyle recommendations for CHD and to refer those patients to other providers. Substantively, these findings point to the importance of patient and provider characteristics in understanding between-country differences in clinical decision making. Methodologically, our use of a factorial experiment highlights the potential of these methods for health services research-especially the estimation of the influence of patient attributes, provider characteristics, and between-country differences in the quality of medical care.

Serum levels of angioregulatory mediators in healthy individuals depend on age and physical activity: Studies of angiogenin, basic fibroblast growth factor, leptin and endostatin

Objective. Angiogenesis is regulated by a wide range of soluble mediators that are released locally or by distant organs that affect local angiogenesis through variations in systemic levels. Serum levels of angioregulatory mediators are important for muscle angiogenesis in response to physical activity; in addition, angioregulation is involved in disease development, and determination of systemic levels may therefore be useful in future clinical practice. The aim of the present study was to investigate whether physical activity alters systemic levels of angioregulatory mediators in healthy individuals. Material and methods. The effects of physical activity on serum levels of pro‐ (angiogenin, basic fibroblast growth factor (bFGF), leptin) and antiangiogenic (endostatin) mediators were investigated. The levels were determined immediately before and after activity for healthy young athletes (all males, age 18 years) and elderly individuals (9 M, 11 F, age 68–88 years). Results. Elderly individuals showed higher pre‐activity levels than the athletes for all mediators. The young athletes showed increased angiogenin and endostatin levels and decreased bFGF levels after 45 min of intensive physical activity, whereas leptin levels were not altered. Elderly individuals showed a similar decrease in bFGF levels after a 3‐h mountain walk, but angiogenin, endostatin and leptin levels were not altered. Conclusions. Serum levels of angioregulatory mediators depend on age, and standardization of physical activity prior to sampling will probably be necessary when evaluating the possible clinical use of these parameters.

Soluble Fas/Apo-1 (CD95) levels during T cell activation in the presence of acute myelogenous leukemia accessory cells; contributions from local release and variations in systemic levels.

Fas (CD95/Apo-1) exists both in membrane-bound and in biologically active soluble (s) forms. Ligation of membrane-expressed Fas can induce apoptosis, and Fas-mediated signaling seems to be involved in T-cell-induced apoptosis of human acute myelogenous leukemia (AML) blasts. The local release of sFas by AML blasts may then function as a protective mechanism by competing with membrane-bound Fas for binding sites on the common Fas ligand (FasL). sFas was released by AML blasts during in vitro culture, and this release was modulated by several cytokines that can be secreted by activated T cells. Increased levels of sFas could be detected during in vitro activation of T cells in the presence of native AML accessory cells, and this was observed both for (i) mitogenic activation of CD4+ and CD8+ T cell clones derived from acute leukemia patients with therapy-induced leukopenia and (ii) allostimulated activation of T cells derived from normal donors. However, local in vivo levels of sFas will also be influenced by variations in systemic levels. High serum levels of sFas were detected in acute leukemia patients during chemotherapy-induced cytopenia, but these levels decreased during complicating bacterial infections. In contrast, serum levels of sFasL were normal in leukopenic patients. The present results support the hypothesis that local release of sFas can function as a protective mechanism against AML-reactive T cells, but the effects of this local release are, in addition, modulated by variations in systemic levels of sFas (but not sFasL).

Use of an Adjustable Tourniquet to Reverse Cyanosis in the Newborn Pig

Background. Previous surgical models of cyanosis have been permanent. Because normal oxygenation was not restored in these models, it is unclear whether the metabolic changes produced by prolonged exposure to hypoxemia are irreversible. We therefore designed an experimental model of cyanosis that is reversible.Methods. The left atrial appendage was anastomosed directly to the main pulmonary artery in 8 piglets, aged 2 to 4 weeks.Results. The oxygen saturation fell from 95.3% ± 0.8% to 72.4% ± 3.9% (p < 0.001). A tourniquet was placed around the anastomosis to produce incremental changes in the level of cyanosis. Complete tourniquet occlusion resulted in obliteration of the right to left shunt, with return of systemic oxygen saturation to baseline levels. Systemic, left atrial, and pulmonary pressures did not change during the study.Conclusions. In this acute preparation, stable hemodynamic conditions were maintained despite substantial variations in systemic levels of oxygenation. Most important, this model allows reversal of cyanosis with the return of normal oxygenation. Application of this experimental design in a chronic model may help to determine whether the metabolic effects of prolonged hypoxemia are potentially reversible.(Ann Thorac Surg 1997;63:456–8)