The Relationships Between BNP and Neurocardiac Injury Severity, Noninvasive Cardiac Output, and Outcomes After Aneurysmal Subarachnoid Hemorrhage

Introduction: Neurocardiac injury, a type of myocardial dysfunction associated with neurological insult to the brain, occurs in 31–48% of aneurysmal subarachnoid hemorrhage (aSAH) patients. Cardiac troponin I (cTnI) is commonly used to diagnose neurocardiac injury. Brain natriuretic peptide (BNP), another cardiac marker, is more often used to evaluate degree of heart failure. The purpose of this study was to examine the relationships between BNP and (a) neurocardiac injury severity according to cTnI, (b) noninvasive continuous cardiac output (NCCO), and (c) outcomes in aSAH patients. Method: This descriptive longitudinal study enrolled 30 adult aSAH patients. Data collected included BNP and cTnI levels and NCCO parameters for 14 days and outcomes (modified Rankin Scale [mRS] and mortality) at discharge and 3 months. Generalized estimating equations were used to evaluate associations between BNP and cTnI, NCCO, and outcomes. Results: BNP was significantly associated with cTnI. For every 1 unit increase in log BNP, cTnI increased by 0.05 ng/ml ( p = .001). Among NCCO parameters, BNP was significantly associated with thoracic fluid content ( p = .0003). On multivariable analyses, significant associations were found between BNP and poor mRS. For every 1 unit increase in log BNP, patients were 3.16 times more likely to have a poor mRS at discharge ( p = .021) and 5.40 times more likely at 3 months ( p < .0001). Conclusion: There were significant relationships between BNP and cTnI and poor outcomes after aSAH. BNP may have utility as a marker of neurocardiac injury and outcomes after aSAH.

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Cardiac troponin I predicts myocardial dysfunction in aneurysmal subarachnoid hemorrhage

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(00)00857-3 ◽

2000 ◽

Vol 36 (4) ◽

pp. 1328-1335 ◽

Cited By ~ 152

Author(s):

Nilesh Parekh ◽

Bala Venkatesh ◽

David Cross ◽

Anne Leditschke ◽

John Atherton ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cardiac Troponin ◽

Troponin I ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Myocardial Dysfunction ◽

Cardiac Troponin I

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Development and Clinical Translation of a Perioperative Nomogram Incorporating Free Fatty Acids to Predict Poor Outcome of Aneurysmal Subarachnoid Hemorrhage Following Endovascular Treatment

Frontiers in Neurology ◽

10.3389/fneur.2021.629997 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yongyi Wang ◽

Yongfan Xie ◽

Houzhong Wang ◽

Jifang Zhang ◽

Chuanfeng Li ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Clinical Application ◽

Endovascular Therapy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Clinical Impact ◽

Poor Outcome ◽

Number Of Patients ◽

Multivariable Analyses ◽

Poor Outcomes ◽

Individualized Prediction

Objective: A reliable prediction of clinical outcome is important for clinicians to set appropriate medical strategies in treating patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aim to establish a perioperative nomogram involving serum lipid signatures for predicting poor outcomes at 3 months in patients with aSAH following endovascular therapy.Methods: Data of patients with aSAH receiving endovascular therapy were collected. Univariable and multivariable analyses were performed to screen independent predictors related to unfavorable outcomes defined by the modified Rankin Scale (mFS) ≥3. A novel nomogram based on these significant features was conducted. The clinical application of this nomogram was assessed by decision curve analysis (DCA) and clinical impact curve.Results: A total number of patients included in this study were 213 (average age 58.9 years, 65.7% female), representing a poor 3-month outcome rate of 48.8%. Free fatty acid (FFA) levels on admission were efficient in predicting poor outcomes compared with other contents in serum lipids. Univariable and multivariable analyses revealed advanced age (P = 0.034), poor Hunt Hess (HH) (odds ratio, OR = 3.7, P < 0.001) and mFS (OR = 6.0, P < 0.001), aneurysms in the posterior circulation (OR = 4.4, P = 0.019), and higher FFA levels on admission (OR = 3.1, P = 0.021) were negative independent predictors of poor 3 months outcome. A novel nomogram composed of these significant features presented a concordance index (C-index) of 0.831 while the practical benefit was validated by DCA and clinical impact curve. An online calculator based on R programming promoted the clinical application of this nomogram.Conclusion: Nomogram involving age, HH grade, mFS, aneurysm location, and serum FFA levels was sufficient to provide an individualized prediction of 3-month poor outcome for each patient with aSAH who underwent endovascular therapy.

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Alanine Aminotransferase Predicts Outcomes in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage

Current Neurovascular Research ◽

10.2174/1567202616666190130094631 ◽

2019 ◽

Vol 16 (1) ◽

pp. 89-95

Author(s):

Jianfeng Zheng ◽

Rui Xu ◽

Zongduo Guo ◽

Xiaochuan Sun

Keyword(s):

Subarachnoid Hemorrhage ◽

Elderly Patients ◽

Clinical Outcomes ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Laboratory Data ◽

Cardiac Complications ◽

World Population ◽

Systemic Complications ◽

Poor Outcome ◽

Poor Outcomes

Objective: With the aging of the world population, the number of elderly patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is gradually growing. We aim to investigate the potential association between plasma ALT level and clinical complications of elderly aSAH patients, and explore its predictive value for clinical outcomes of elderly aSAH patients. Methods: Between January 2013 and March 2018, 152 elderly aSAH patients were analyzed in this study. Clinical information, imaging findings and laboratory data were reviewed. According to the Glasgow Outcome Scale (GOS), clinical outcomes at 3 months were classified into favorable outcomes (GOS 4-5) and poor outcomes (GOS 1-3). Logistic regression analysis was used to assess the indicators associated with poor outcomes, and receiver curves (ROC) and corresponding area under the curve (AUC) were used to detect the accuracy of the indicator. Results: A total of 48 (31.6 %) elderly patients with aSAH had poor outcome at 3 months. In addition to ICH, IVH, Hunt-Hess 4 or 5 Grade and Modified Fisher 3 or 4 Grade, plasma ALT level was also strongly associated with poor outcome of elderly aSAH patients. After adjusting for other covariates, plasma ALT level remained independently associated with pulmonary infection (OR 1.05; 95% CI 1.00–1.09; P = 0.018), cardiac complications (OR 1.05; 95% CI 1.01–1.08; P = 0.014) and urinary infection (OR 1.04; 95% CI 1.00–1.08; P = 0.032). Besides, plasma ALT level had a predictive ability in the occurrence of systemic complications (AUC 0.676; 95% CI: 0.586– 0.766; P<0.001) and poor outcome (AUC 0.689; 95% CI: 0.605–0.773; P<0.001) in elderly aSAH patients. Conclusion: Plasma ALT level of elderly patients with aSAH was significantly associated with systemic complications, and had additional clinical value in predicting outcomes. Given that plasma ALT levels on admission could help to identify high-risk elderly patients with aSAH, these findings are of clinical relevance.

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Predictors of the development of takotsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage and outcomes in patients with intra-aortic balloon pumps

Journal of Neurosurgery ◽

10.3171/2020.5.jns20536 ◽

2020 ◽

pp. 1-6

Author(s):

Joshua S. Catapano ◽

Andrew F. Ducruet ◽

Fabio A. Frisoli ◽

Candice L. Nguyen ◽

Christopher E. Louie ◽

...

Keyword(s):

Risk Factors ◽

Subarachnoid Hemorrhage ◽

Takotsubo Cardiomyopathy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Multivariate Logistic Regression Analysis ◽

High Morbidity ◽

Female Patients ◽

Neurological Outcomes ◽

Poor Outcomes

OBJECTIVETakotsubo cardiomyopathy (TC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Previous studies have shown that female patients presenting with a poor clinical grade are at the greatest risk for developing TC. Intra-aortic balloon pumps (IABPs) are known to support cardiac function in severe cases of TC, and they may aid in the treatment of vasospasm in these patients. In this study, the authors investigated risk factors for developing TC in the setting of aSAH and outcomes among patients requiring IABPs.METHODSThe authors retrospectively reviewed the records of 1096 patients who had presented to their institution with aSAH. Four hundred five of these patients were originally enrolled in the Barrow Ruptured Aneurysm Trial, and an additional 691 patients from a subsequent prospectively maintained aSAH database were analyzed. Medical records were reviewed for the presence of TC according to the modified Mayo Clinic criteria. Outcomes were determined at the last follow-up, with a poor outcome defined as a modified Rankin Scale (mRS) score > 2.RESULTSTC was identified in 26 patients with aSAH. Stepwise multivariate logistic regression analysis identified female sex (OR 8.2, p = 0.005), Hunt and Hess grade > III (OR 7.6, p < 0.001), aneurysm size > 7 mm (OR 3, p = 0.011), and clinical vasospasm (OR 2.9, p = 0.037) as risk factors for developing TC in the setting of aSAH. TC patients, even with IABP placement, had higher rates of poor outcomes (77% vs 47% with an mRS score > 2, p = 0.004) and mortality at the last follow-up (27% vs 11%, p = 0.018) than the non-TC patients. However, aggressive intra-arterial endovascular treatment for vasospasm was associated with good outcomes in the TC patients versus nonaggressive treatment (100% with mRS ≤ 2 at last follow-up vs 53% with mRS > 2, p = 0.040).CONCLUSIONSTC after aSAH tends to occur in female patients with large aneurysms, poor clinical grades, and clinical vasospasm. These patients have significantly higher rates of poor neurological outcomes, even with the placement of an IABP. However, aggressive intra-arterial endovascular therapy in select patients with vasospasm may improve outcome.

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Impact of Hyperoxia and Hypocapnia on Neurological Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study

Critical Care Research and Practice ◽

10.1155/2019/7584573 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Kin Chio Li ◽

Catherine Wing Yan Tam ◽

Hoi-Ping Shum ◽

Wing Wa Yan

Keyword(s):

Subarachnoid Hemorrhage ◽

Critically Ill ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Classification Tree ◽

Tertiary Hospital ◽

Classification Tree Analysis ◽

Radiological Findings ◽

Neurological Outcomes ◽

Poor Outcomes ◽

The Impact

In recent decades, there is increasing evidence suggesting that hyperoxia and hypocapnia are associated with poor outcomes in critically ill patients with cardiac arrest or traumatic brain injury. Yet, the impact of hyperoxia and hypocapnia on neurological outcome in patients with subarachnoid hemorrhage (SAH) has not been well studied. In the present study, we evaluated the impact of hyperoxia and hypocapnia on neurological outcomes in patients with aneurysmal SAH (aSAH). Patients with aSAH who were admitted to the intensive care unit (ICU) of a tertiary hospital in Hong Kong between January 2011 and December 2016 were retrospectively recruited. Patients’ demographics, comorbidities, radiological findings, clinical grades of SAH, PO2, and PCO2 within 24 hours of ICU admission, and Glasgow Outcome Scale (GOS) at 3 months after admission were recorded. Patients with a GOS score of 3 or less were considered having poor neurological outcomes. Among the 244 patients with aSAH, 122 of them (50%) had poor neurological outcomes at 3 months. Early hyperoxia (PO2 > 200 mmHg) and hypercapnia (PCO2 > 45 mmHg) were more common among patients with poor neurological outcomes. Logistic regression analysis indicated that hyperoxia independently predicted poor neurological outcomes (OR 3.788, 95% CI 1.131–12.690, P=0.031). Classification tree analysis revealed that hypocapnia was associated with poor neurological outcomes in patients who were less critically ill (APACHE < 50) and without concomitant intracranial hemorrhage (ICH) or intraventricular hemorrhage (IVH) (adjusted P=0.006, χ2 = 7.452). These findings suggested that hyperoxia and hypocapnia may be associated with poor neurological outcomes in patients with aSAH.

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Impact of smoking on course and outcome of aneurysmal subarachnoid hemorrhage

Acta Neurochirurgica ◽

10.1007/s00701-020-04506-3 ◽

2020 ◽

Vol 162 (12) ◽

pp. 3117-3128

Author(s):

H. Slettebø ◽

T. Karic ◽

A. Sorteberg

Keyword(s):

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Smoking Status ◽

Clinical Grade ◽

Poor Functional Outcome ◽

Related Risk ◽

Poor Outcomes ◽

Subarachnoid Blood ◽

Vertebrobasilar Aneurysms

Abstract Background While the smoking-related risk of experiencing an aneurysmal subarachnoid hemorrhage (aSAH) is well established, it remains unclear whether smoking has an unexpected “protective effect” in aSAH, or if smokers are more at risk for complications and poor outcomes. Methods Prospective, observational study investigating the course and outcome of aSAH in patients admitted during the years 2011 and 2012. Smoking status at admittance, demographic, medical, and radiological variables were registered along with management, complications, and outcome at 1 year in terms of mortality, modified Rankin score, and Glasgow outcome score extended. We compared current smokers with nonsmokers on group level and by paired analysis matched by aSAH severity, age, and severity of vasospasm. Results We included 237 patients, thereof 138 current smokers (58.2%). Seventy-four smoker/nonsmoker pairs were matched. Smokers presented more often in poor clinical grade, had less subarachnoid blood, and were younger than nonsmokers. Ruptured aneurysms were larger, and multiple aneurysms more common in smokers. Severe multi-vessel vasospasm was less frequent in smokers, whereas all other complications occurred at similar rates. Mortality at 30 days was lower in smokers and functional outcome was similar in smokers and nonsmokers. Poor clinical grade, age, cerebral infarction, and vertebrobasilar aneurysms were independent predictors of 1-year mortality and of poor functional outcome. Serious comorbidity was a predictor of 1-year mortality. Smoking did not predict mortality or poor functional outcome. Conclusions Notwithstanding clinically more severe aSAH, smokers developed less frequently severe vasospasm and had better outcome than expected. The risk for complications after aSAH is not increased in smokers.

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20-HETE is Associated with Unfavorable Outcomes in Subarachnoid Hemorrhage Patients

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.75 ◽

2015 ◽

Vol 35 (9) ◽

pp. 1515-1522 ◽

Cited By ~ 19

Author(s):

Mark K Donnelly ◽

Elizabeth A Crago ◽

Yvette P Conley ◽

Jeffery R Balzer ◽

Dianxu Ren ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Medical Center ◽

Delayed Cerebral Ischemia ◽

University Of Pittsburgh ◽

Potential Contributor ◽

Csf Levels ◽

Novel Target ◽

Poor Outcomes

Emerging evidence has suggested that patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) develop vascular dysregulation as a potential contributor to poor outcomes. Preclinical studies have implicated the novel microvascular constrictor, 20-hydroxyeicosatetraenoic acid (20-HETE) in aSAH pathogenesis, yet the translational relevance of 20-HETE in patients with aSAH is largely unknown. The goal of this research was to determine the relationship between 20-HETE cerebrospinal fluid (CSF) levels, gene variants in 20-HETE synthesis, and acute/long-term aSAH outcomes. In all, 363 adult patients (age 18 to 75) with aSAH were prospectively recruited from the University of Pittsburgh Medical Center neurovascular Intensive Care Unit. Patients were genotyped for polymorphic variants and cytochrome P450 (CYP)-eicosanoid CSF levels were measured over 14 days. Outcomes included delayed cerebral ischemia (DCI), clinical neurologic deterioration (CND), and modified Rankin Scores (MRS) at 3 and 12 months. Patients with CND and unfavorable 3-month MRS had 2.2- and 2.7-fold higher mean 20-HETE CSF levels, respectively. Patients in high/moderate 20-HETE trajectory groups (35.7%) were 2.5-, 2.1-, 3.1-, 3.3-, and 2.1-fold more likely to have unfavorable MRS at 3 months, unfavorable MRS at 12 months, mortality at 3 months, mortality at 12 months, and CND, respectively. These results showed that 20-HETE is associated with acute and long-term outcomes and suggest that 20-HETE may be a novel target in aSAH.

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Serum Cortisol as an Early Biomarker of Cardiopulmonary Parameters Within the First 24 Hours After Aneurysmal Subarachnoid Hemorrhage in Intensive Care Unit Patients

Journal of Intensive Care Medicine ◽

10.1177/0885066619837910 ◽

2019 ◽

Vol 35 (11) ◽

pp. 1173-1179

Author(s):

Michael Bender ◽

M. Stein ◽

E. Uhl ◽

M. H. T. Reinges

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Subarachnoid Hemorrhage ◽

Troponin I ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Elevated Serum ◽

Serum Cortisol ◽

Fisher Grade ◽

Gcs Score ◽

Icu Treatment

Objective: Cardiopulmonary complications/stress are well-known phenomena in patients after aneurysmal subarachnoid hemorrhage (aSAH) and might be associated with an elevated serum troponin I (TNI) level. Since the glucocorticoid hormone cortisol is released during stress situations, the present study was conducted to investigate the influence of serum cortisol (SC) on cardiac and pulmonary parameters in patients after aSAH within the first 24 hours of intensive care unit (ICU) treatment. Patients and Methods: We retrospectively analyzed a cohort of 104 patients with aSAH admitted to our emergency department between January 2008 and April 2017. Blood samples were taken to determine SC and TNI. Demographics, initial Glasgow Coma Scale (GCS) score, World Federation of Neurosurgical Societies (WFNS) score, and Fisher grade were evaluated retrospectively. Mean norepinephrine application rate (NAR) in µg/kg/min and mean inspiratory oxygen fraction (OF) within the first 24 hours were defined as cardiopulmonary parameters. Results: An elevated SC value was found in 44 (42%) patients, and 27 (26%) patients showed an increased TNI value. In patients with initially increased SC value, a significant higher NAR ( P = .04) was needed. Furthermore, patients with initially elevated TNI value had a lower GCS score ( P = .0013) and a higher WFNS score ( P = .003) on admission and required a higher NAR ( P = .02) as well as OF ( P = .0008) within the first 24 hours of ICU treatment. Conclusions: In the current study, initially elevated SC values were associated with a higher need of NAR within the first 24 hours of ICU treatment after aSAH. Moreover, patients with initially elevated TNI values required an increased NAR and a higher OF so that these biomarkers could be useful to improve ICU treatment.

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Effect of stress-induced hyperglycemia after non-traumatic non-aneurysmal subarachnoid hemorrhage on clinical complications and functional outcomes

10.21203/rs.3.rs-944631/v1 ◽

2021 ◽

Author(s):

Zeyu Zhang ◽

Yue Zhao ◽

Yibo Liu ◽

Xiaoyu Wang ◽

Houshi Xu ◽

...

Keyword(s):

Risk Factors ◽

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Functional Outcomes ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Complication Rates ◽

Poor Outcome ◽

Clinical Complications ◽

Symptomatic Vasospasm ◽

Poor Outcomes

Abstract Background Despite having an overall benign course, non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH) is still accompanied by a risk of clinical complications and poor outcomes. Risk factors and mechanisms of complications and poor outcomes after naSAH remain unknown. Our aim was to explore the effect of stress-induced hyperglycemia (SIH) on complication rates and functional outcomes in naSAH patients. Methods We retrospectively reviewed patients with naSAH admitted to our institution between 2013 and 2018. SIH was identified according to previous criterion. Symptomatic vasospasm, delayed cerebral infarction, and hydrocephalus were identified as main complications. Outcomes were reviewed using a modified Rankin Scale (mRS) at discharge, 3 months, and 12 months. A statistical analysis of clinical, radiological, and laboratory risk factors of complications and outcomes was conducted. Results 244 naSAH patients were incorporated in the cohort with 74 (30.3%) SIH. After adjusting for age, gender, hypertension, Hunt and Hess (HH) grade, modified Fisher Scale (mFS), intraventricular hemorrhage (IVH), and subarachnoid blood distribution, SIH was significantly associated with symptomatic vasospasm (P < 0.001, 12.176 [4.904–30.231]), delayed cerebral infarction (P < 0.001, 12.434 [3.850-40.161]), hydrocephalus (P = 0.008, 5.771 [1.570-21.222]), and poor outcome at 12 months (P = 0.006, 5.506 [1.632–18.581]), whereas the correlation between SIH and poor outcome at discharge (P = 0.064, 2.409 [0.951-6.100]) or 3 months (P = 0.110, 2.029 [0.852–4.833]) was not significant. Incorporation of SIH increased the area under curve (AUC) of ROC in the combined model for predicting symptomatic vasospasm (P = 0.002), delayed cerebral infarction (P = 0.024), hydrocephalus (P = 0.037), and 12-month poor outcome (P = 0.087). Conclusions SIH is a significant and independent risk factor for symptomatic vasospasm, delayed cerebral infarction, hydrocephalus, and long-term poor outcome in naSAH patients. Identifying SIH early after naSAH is important for decision-making and treatment planning.

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Effect of choice of treatment modality on the incidence of shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2017.9.jns171806 ◽

2019 ◽

Vol 130 (3) ◽

pp. 949-955 ◽

Cited By ~ 2

Author(s):

Masaomi Koyanagi ◽

Hitoshi Fukuda ◽

Masaaki Saiki ◽

Yoshihito Tsuji ◽

Benjamin Lo ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Propensity Score ◽

Endovascular Treatment ◽

Treatment Modality ◽

Propensity Score Analysis ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Endovascular Coiling ◽

Surgical Clipping ◽

Propensity Score Model ◽

Poor Outcomes

OBJECTIVEShunt-dependent hydrocephalus (SDHC) may arise after aneurysmal subarachnoid hemorrhage (aSAH) as CSF resorptive mechanisms are disrupted. Using propensity score analysis, the authors aimed to investigate which treatment modality, surgical clipping or endovascular treatment, is superior in reducing rates of SDHC after aSAH.METHODSThe authors’ multicenter SAH database, comprising 3 stroke centers affiliated with Kyoto University, Japan, was used to identify patients treated between January 2009 and July 2016. Univariate and multivariate analyses were performed to characterize risk factors for SDHC after aSAH. A propensity score model was generated for both treatment groups, incorporating relevant patient covariates to detect any superiority for prevention of SDHC after aSAH.RESULTSA total of 566 patients were enrolled in this study. SDHC developed in 127 patients (22%). On multivariate analysis, age older than 53 years, the presence of intraventricular hematoma, and surgical clipping as opposed to endovascular coiling were independently associated with SDHC after aSAH. After propensity score matching, 136 patients treated with surgical clipping and 136 with endovascular treatment were matched. Propensity score–matched cohorts exhibited a significantly lower incidence of SDHC after endovascular treatment than after surgical clipping (16% vs 30%, p = 0.009; OR 2.2, 95% CI 1.2–4.2). SDHC was independently associated with poor neurological outcomes (modified Rankin Scale score 3–6) at discharge (OR 4.3, 95% CI 2.6–7.3; p < 0.001).CONCLUSIONSSDHC after aSAH occurred significantly more frequently in patients who underwent surgical clipping. Strategies for treatment of ruptured aneurysms should be used to mitigate SDHC and minimize poor outcomes.

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