Patient reported outcomes in an elder-friendly surgical environment: Prospective, controlled before-after study.

INTRODUCTION: The Acute Care for the Elderly (ACE) model has demonstrated clinical benefit, but there is little evidence regarding quality of life after discharge. The Elder-friendly Approaches to the Surgical Environment (EASE) study was conducted to assess implementation of an ACE unit on an acute surgical service. Improved clinical and economic outcomes have been demonstrated, but post-discharge patient reported outcomes have not yet been reported. METHODS: Prospective, concurrently controlled, before-after study at two tertiary care hospitals in Alberta, Canada. The SF-12, EQ-5D, Canadian Malnutrition Screening Tool (CMST) and patient satisfaction were collected from elderly (≥ 65 years old) patients, 6 weeks and 6 months after discharge from an acute care surgical service. A difference-in-difference (DID) method was used to analyze between-site effects. RESULTS: At six weeks, patient satisfaction was high at 68%-86%, with significant improvement Pre-to Post-EASE at the control site (p < 0.001), but not the intervention site (p = 0.06). For the intervention site, within-site adjusted pre-post effects were nonsignificant for all patient reported outcomes [EQ-Index Score ß coefficient (SE): 0.042 (0.022); EQ-Visual Analog Scale: 0.10 (2.14); SF-12 Physical Component Score: -0.57 (0.84); SF-12 Mental Component Score: 1.17 (0.84); CMST Score: -0.39 (0.34)]. DID analyses were also non significant for all outcomes except for SF-12 Mental Component Score (p < 0.001). CONCLUSION: The clinically and economically beneficial EASE interventions do not appear to compromise quality of life, risk for malnutrition, or patient satisfaction in the post-discharge period. Further research with larger sample size is needed with comparisons to pre-intervention and the early post-discharge period.

The impact of delayed mobilization on post-discharge outcomes after emergency abdominal surgery: A prospective cohort study in older patients.

Surgeons are increasingly treating seniors with complex care needs who are at high-risk of readmission and functional decline. Yet, the prognostic importance of post-operative mobilization in older surgical patients is under-investigated and remains unclear. Thus, we evaluated the relationship between post-operative mobilization and events after hospital discharge in older people. Overall, 306 survivors of emergency abdominal surgery aged ≥65y who required help with <3 activities of daily living were prospectively followed at two Canadian tertiary-care hospitals. Time until mobilization after surgery was attained from hospital charts and a priori defined as 'delayed' (≥36h) or 'early' (<36h). Primary outcomes for 30-day and 6-month all-cause readmission/death after discharge were assessed in multivariable logistic regression. Patients had a mean age of 76 ± 7.7 years, 45% were women, 41% were 'vulnerable-to-moderately-frail', according to the Clinical Frailty Scale. Most common reasons for admission were gallstones (23%), intestinal obstructions (21%), and hernia (17%). Median time to post-operative mobilization was 19h (interquartile range 9-35); 74 (24%) patients had delayed mobilization. Delayed mobilization was independently associated with higher risk of 30-day readmission/death (19 [26%] vs. 22 [10%], P<0.001; adjusted odds ratio [aOR] 2.24, 95%CI 0.99-5.06, P = 0.05), but this was not statistically significant at 6-months (38 [51%] vs. 64 [28%], P<0.001; aOR 1.72, 95%CI 0.91-3.25, P = 0.1). One-quarter of older surgical patients stayed in bed for 1.5 days post-operatively. Delayed mobilization was associated with increased risk of short-term readmission/death. As older, more frail patients undergo surgery, mobilization of older surgical patients remains an understudied post-operative factor. Trial registration: clinicaltrials.gov identifier: NCT02233153.

Thigh Ultrasound Used to Identify Frail Elderly Patients with Sarcopenia Undergoing Surgery: A Pilot Study.

BACKGROUND: Computed tomography (CT) scan quantifying skeletal muscle mass is the gold standard tool to identify sarcopenia. Unfortunately, high cost, limited availability, and radiation exposure limit its use. We suggest that ultrasound of the thigh muscle could be an objective, reproducible, portable, and risk-free tool, used as a surrogate to a CT scan, to help identify frail patients with sarcopenia. MATERIALS AND METHODS: We included 49 patients over 64 y old, referred to the acute care surgery service. An ultrasound of thigh muscle thickness was standardized to patient thigh length (U/Swhole/L). CT skeletal muscle index (SMI) was calculated using skeletal muscle surface area of the L3 region divided by height2. Frailty status was assessed using the Canadian Study of Healthy Aging Clinical Frailty Scale. RESULTS: The mean (SD) age was 76 (8) y, and 34% (n = 17) were men. CT-defined sarcopenia was identified in 65% (n = 11) of men and 75% (n = 24) of women. In general, women had longer stay in hospital than men (mean + SD 14 ± 9 versus 7 ± 3 d, P = 0.003). There was a significant positive correlation between thigh U/Swhole/L and CT SMI. There was an inverse correlation between thigh U/Swhole/L and frailty score; a similar relationship was observed between CT SMI and frailty. There was an association between U/Swhole/L and postoperative major complications. CONCLUSIONS: This prospective observational study illustrates that the U/Swhole/L index can be used as a surrogate to CT scan, whereby it can identify elderly frail patients with sarcopenia. Thigh ultrasound should be further tested as an objective tool to assess for stratifying frailty.

Clinical Effectiveness of the Elder-Friendly Approaches to the Surgical Environment Initiative in Emergency General Surgery.

Importance: Older adults, especially those with frailty, have a higher risk for complications and death after emergency surgery. Acute Care for the Elderly models have been successful in medical wards, but little evidence is available for patients in surgical wards. Objectives: To develop and assess the effect of an Elder-Friendly Approaches to the Surgical Environment (EASE) model in an emergency surgical setting. Design, Setting, and Participants: This prospective, nonrandomized, controlled before-and-after study included patients 65 years or older who presented to the emergency general surgery service of 2 tertiary care hospitals in Alberta, Canada. Transfers from other medical services, patients undergoing elective surgery or with trauma, and nursing home residents were excluded. Of 6795 patients screened, a total of 684 (544 in the nonintervention group and 140 in the intervention group) were included. Data were collected from April 14, 2014, to March 28, 2017, and analyzed from November 16, 2018, through May 30, 2019. Interventions: Integration of a geriatric assessment team, optimization of evidence-based elder-friendly practices, promotion of patient-oriented rehabilitation, and early discharge planning. Main Outcomes and Measures: Proportion of participants experiencing a major complication or death (composite) in the hospital, Comprehensive Complication Index, length of hospital stay, and proportion of participants who required an alternative level of care on discharge. Covariate-adjusted, within-site change scores were computed, and the overall between-site, preintervention-postintervention difference-in-differences (DID) were analyzed. Results: A total of 684 patients were included in the analysis (mean [SD] age, 76.0 [7.6] years; 327 women [47.8%] and 357 men [52.2%]), of whom 139 (20.3%) were frail. At the intervention site, in-hospital major complications or death decreased by 19% (51 of 153 [33.3%] vs 19 of 140 [13.6%]; P < .001; DID P = .06), and mean (SE) Comprehensive Complication Index decreased by 12.2 (2.5) points (P < .001; DID P < .001). Median length of stay decreased by 3 days (10 [interquartile range (IQR), 6-17] days to 7 [IQR, 5-14] days; P = .001; DID P = .61), and fewer patients required an alternative level of care at discharge (61 of 153 [39.9%] vs 29 of 140 [20.7%]; P < .001; DID P = .11). Conclusions and Relevance: To our knowledge, this is the first study to examine clinical outcomes associated with a novel elder-friendly surgical care delivery redesign. The findings suggest the clinical effectiveness of such an approach by reducing major complications or death, decreasing hospital stays, and returning patients to their home residence. Trial Registration: ClinicalTrials.gov Identifier: NCT02233153.

Sex differences in the treatment and outcome of emergency general surgery.

BACKGROUND: Sociodemographic characteristics, such as sex, have been shown to influence health care delivery. Acute care surgery models are effective in decreasing mortality and morbidity after emergency surgeries, but sex-based differences in delivery and outcomes have not been explored. Our objective was to explore sex associated differences in the patient characteristics and clinical outcomes of those admitted to emergency general surgery. METHODS: A post-hoc analysis of 512 emergency general surgical patients admitted consecutively to two tertiary care hospitals in Alberta Canada, between April 1, 2014 and July 31, 2015. We measured associations between sex and patient demographics, pre-, intra- and post-operative delivery of care, as well as post-operative outcomes. FINDINGS: Of those excluded from the analysis, older females were more likely to undergo conservative management compared to older men (41% vs 34%, p = 0.03). Overall, there were no differences between sexes for time from admission to surgery, time spent in surgery, overall complication rate, mortality, hospital length of stay, or discharge disposition. Women were more likely to have a cancer diagnosis [OR 4.12 (95% CI: 1.61-10.5), p = 0.003, adjusted for age], while men were more likely to receive hernia surgery [OR 2.33 (95% CI 1.35-4.02), p = 0.002, adjusted for age and Charlson Comorbidity Index]. Finally, men were more likely to have a major respiratory complication [OR 2.73 (95% CI: 1.19-6.24), p = 0.02, adjusted for age]. CONCLUSIONS: Only two differences in peri and post-operative complications between sexes were noted, which suggests sex-based disparity in quality of care is limited once a decision has been made to operate. Future studies with larger databases are needed to corroborate our findings and investigate potential sex biases in surgical versus conservative management.

Incidence and predictors of postoperative delirium in the older acute care surgery population: a prospective study

Background: Among older inpatients, the highest incidence of delirium is within the surgical population. Limited data are available regarding postoperative delirium risk in the acute care surgical population. The purpose of our study was to establish the incidence of and risk factors for delirium in an older acute care surgery population. Methods: Patients aged 65 years or more who had undergone acute care surgery between April 2014 and September 2015 at 2 university-affiliated hospitals in Alberta were followed prospectively and screened for delirium by means of a validated chart review method. Delirium duration was recorded. We used separate multivariable logistic regression models to identify independent predictors for overall delirium and longer episodes of delirium (duration ≥ 48 h). Results: Of the 322 patients included, 73 (22.7%) were identified as having experienced delirium, with 49 (15.2%) experiencing longer episodes of delirium. Postoperative delirium risk factors included Foley catheter use, intestinal surgery, gallbladder surgery, appendix surgery, intensive care unit (ICU) admission and mild to moderate frailty. Risk factors for prolonged postoperative delirium included Foley catheter use and mild to moderate frailty. Surgical approach (open v. laparoscopic) and overall operative time were not found to be significant. Conclusion: In keeping with the literature, our study identified Foley catheter use, frailty and ICU admission as risk factors for delirium in older acute care surgical patients. We also identified an association between delirium risk and the specific surgical procedure performed. Understanding these risk factors can assist in prevention and directed interventions for this high-risk population.

Contexte: Parmi les patients âgés, l'incidence la plus élevée d'épisodes de délire s'observe chez les patients opérés. On dispose de données limitées au sujet du risque de délire postopératoire chez les patients soumis à une chirurgie d'urgence. Le but de notre étude était de connaître l'incidence des épisodes de délire et les facteurs de risque chez la population âgée soumise à une chirurgie d'urgence. Méthodes: Nous avons suivi de façon prospective les patients de 65 ans ou plus soumis à une chirurgie d'urgence entre avril 2014 et septembre 2015 dans 2 centres hospitaliers universitaires de l'Alberta et nous avons recensé les épisodes de délire au moyen d'une méthode validée d'analyse des dossiers. La durée des épisodes de délire a été notée. Nous avons utilisé des modèles séparés d'analyse de régression logistique multivariée pour dégager les prédicteurs indépendants des épisodes globaux de délire et des épisodes plus longs (durée ≥ 48 h). Résultats: Parmi les 322 patients inclus, 73 (22,7 %) ont manifesté un épisode de délire, dont 49 (15,2 %) un épisode plus long. Les facteurs de risque à l'égard des épisodes de délire postopératoire ont inclus : l'emploi d'une sonde Foley, la chirurgie intestinale, la chirurgie de la vésicule biliaire, l'appendicectomie, un séjour à l'unité de soins intensifs (USI) et un état de fragilité léger ou modéré. Les facteurs de risque à l'égard d'un épisode de délire postopératoire prolongé ont inclus : l'emploi d'une sonde Foley et un état de fragilité léger ou modéré. L'approche chirurgicale (ouverte c. laparoscopique) et la durée globale de l'intervention n'ont pas joué un rôle significatif. Conclusion: Faisant écho à la littérature publiée, notre étude a identifié l'emploi de la sonde Foley, l'état de fragilité et le séjour à l'USI comme des facteurs de risque de délire chez les patients âgés soumis à une chirurgie d'urgence. Nous avons aussi observé un lien entre le risque de délire et certains types d'interventions chirurgicales. En comprenant mieux ces facteurs, il sera possible de prévenir ces épisodes et d'orienter les interventions chez cette population à risque élevé.

Development of a reconditioning program for elderly abdominal surgery patients: the Elder-friendly Approaches to the Surgical Environment-BEdside reconditioning for Functional ImprovemenTs (EASE-BE FIT) pilot study.

Background: Elderly individuals who are hospitalized due to emergency abdominal surgery spend over 80% of their recovery time in bed, resulting in early and rapid muscle loss. As these elderly individuals have a lower physiological reserve, the impact of muscle wasting on function may be profound. The objectives of this study are to (1) create an independently led post-surgical reconditioning program and (2) pilot its implementation, while assessing the feasibility and safety of the program. Methods: The BE FIT program was generated with hospital rehabilitation staff to target lower limb strength, balance, and endurance. This pilot study was assessed using a sequential before and after trial, with a cohort of patients aged ≥ 65 years enrolled in the Elder-friendly Approaches to the Surgical Environment (EASE) study. Change in 30-s sit-to-stand performance between postoperative day 2 and discharge was compared between Usual Care pre- and post-BE FIT participants. Results: A total of 66 patients participated in the sub-study, 33 Usual Care and 33 BE FIT. Mean (SD) age was 76.2 (8.78); 44 (67%) were female, with 11 (17%) reporting mild/moderate frailty on the CHSA Clinical Frailty Scale. BE FIT participants had a median of three rehab days and self-reported completing an average of 83% of the exercises. The adjusted between group difference showed that the BE FIT patients were able to complete more stands than the Usual Care (1.9 stands (0.94), p = 0.05). There were no reported adverse events. Conclusion: The reconditioning program was shown to be safe and feasible within the hospital setting for the elderly emergency abdominal surgery patients. More rigorous assessment is needed to confirm this effectiveness and to better assess patient adherence to self-directed exercise. Trial registration: Registration #NCT02233153 through ClinicalTrials.gov. Registered September 8, 2014.

Review of risk assessment tools to predict morbidity and mortality in elderly surgical patients.

BACKGROUND: Informed surgical consent requires accurate estimation of risks and benefits. Multiple risk assessment tools are available; however, most are not widely used or are specific to certain interventions. Assessing surgical risk is especially challenging in elderly patients because of their range of comorbidities, level of frailty, or severity of illness and a number of available surgical interventions. DATA SOURCES: We searched MEDLINE from January 2014 to July 2017 for studies that used risk assessment tools in studies on elderly surgical patients. We then sought the original articles describing each assessment tool and subsequent validation studies. CONCLUSIONS: We identified risk assessment tools that can improve surgical risk assessment in elderly surgical patients. The majority of the identified tools are not commonly used for pre-operative risk assessment. NSQIP-PMP, mFI and SURPAS are promising tools. Age is commonly used to predict risk, but frailty may be a more appropriate measure.

Depressive symptoms are associated with higher rates of readmission or mortality after medical hospitalization: A systematic review and meta-analysis.

Depressive symptoms during a medical hospitalization may be an overlooked prognostic factor for adverse events postdischarge. Our aim was to evaluate whether depressive symptoms predict 30-day readmission or death after medical hospitalization. We conducted a systematic review of studies that compared postdischarge outcomes by in-hospital depressive status. We assessed study quality and pooled published and unpublished data using random effects models. Overall, one-third of 6104 patients discharged from medical wards were depressed (interquartile range, 27%-40%). Compared to inpatients without depression, those discharged with depressive symptoms were more likely to be readmitted (20.4% vs 13.7%, risk ratio [RR]: 1.73, 95% confidence interval [CI]: 1.16-2.58) or die (2.8% vs 1.5%, RR: 2.13, 95% CI: 1.31-3.44) within 30 days. Depressive symptoms were common in medical inpatients and are associated with an increased risk of adverse events postdischarge. Journal of Hospital Medicine 2016;11:373-380. © 2016 The Authors Journal of Hospital Medicine published by Wiley Periodicals, Inc. on behalf of Society of Hospital Medicine.

Self-Reported Outcomes in Individuals Aged 65 and Older Admitted for Treatment to an Acute Care Surgical Service: A 6-Month Prospective Cohort Study.

OBJECTIVES: To examine health-related quality of life (HRQL) and cognitive and functional status before and after emergency surgical care in elderly adults. DESIGN: Six-month prospective cohort study. SETTING: Acute care and emergency surgery service at a single, academic tertiary care center, Edmonton, Alberta, Canada. PARTICIPANTS: Admitted individuals aged 65 and older (mean age 77.8 ± 7.9, 52% female) or their surrogates. MEASUREMENTS: Abbreviated Mental Test Score-4 (AMTS), Barthel Index, Vulnerable Elders Survey (VES-13), and EuroQol-5 Dimensional Scale (EQ-5D) completed by participants or their surrogates within 24 hours of admission to the hospital and 6 months after discharge. Paired t-tests and McNemar tests were used to assess the difference between baseline and 6 months. RESULTS: One hundred fifty-five consecutive individuals (including 16 surrogates) were enrolled. Sixteen (10%) died within 6 months of discharge, and 116 (75%, including 18 surrogates) completed a follow-up assessment 6 months after discharge. Cognitive status improved substantially over 6 months, with 72 (52%) of participants having AMTS scores showing cognitive impairment at baseline and four (4%) having AMTS scores showing cognitive impairment at 6 months (P < .001). There was no statistically significant change from baseline on the Barthel Index, VES-13, or EQ-5D. CONCLUSION: There was significant cognitive improvement in older adults after surgical hospitalization. HRQL improved back to age-matched population norms. These results suggest that elderly adults admitted for emergency surgery have good cognitive, functional, and HRQL outcomes.

Optimizing senior's surgical care - Elder-friendly Approaches to the Surgical Environment (EASE) study: rationale and objectives.

BACKGROUND: It is estimated that seniors (≥65 years old) account for >50% of acute inpatient hospital days and are presenting for surgical evaluation of acute illness in increasing numbers. Unfortunately, conventional acute care models rarely take into account needs of the elderly population. The failure to consider these special needs have resulted in poor outcomes, longer lengths of hospital stay and have likely increased the need for institutional care. Acute Care for the Elderly models on medical wards have demonstrated decreased cost, length of hospital stay, readmissions and improved cognition, function and patient/staff satisfaction. We hypothesize that specific Elder-friendly Approaches to the Surgical Environment (EASE) interventions will similarly improve health outcomes in a cost-effective manner. METHODS/DESIGN: Prospective, before-after study with a concurrent control group. Four cohorts of 140 consecutively-screened older patients (≥65 years old) will be enrolled (560 patients in total). The EASE interventions involves co-locating all older surgical patients on a single unit, involving an interdisciplinary care team (including a geriatric specialist) in the development of individual care plans, implementing evidence-informed elder-friendly practices, use of a reconditioning program, and optimizing discharge planning. Subjects will be followed via chart review for their hospital stay, and will then complete in-person or telephone interviews at 6 weeks and 6 months after discharge. Measured outcomes include clinical (postoperative major in-hospital complication or death [primary composite outcome]; death or readmission within 30-days of initial discharge; length of hospital stay), humanistic (quality of life; functional, cognitive, and nutritional status) and economic (health care resource utilization and costs) endpoints. Within-site mean change scores will be computed for the composite primary outcome and the overall covariate-adjusted between-site pre-post difference will be the dependent variable analyzed using generalized linear mixed model procedures including adjustment for clustering. DISCUSSION: Our findings will generate new knowledge on outcomes from acute surgical care in older patients and validate a novel elder-friendly surgical model including assessment of both clinical and economic benefits. If effective, we expect the EASE initiatives to be generalizable to other surgical centres. TRIAL REGISTRATION: Clinicaltrials.govidentifier: NCT02233153.

Weight loss required by the severely obese to achieve clinically important differences in health-related quality of life: two-year prospective cohort study.

BACKGROUND: Guidelines and experts describe 5% to 10% reductions in body weight as 'clinically important'; however, it is not clear if 5% to 10% weight reductions correspond to clinically important improvements in health-related quality of life (HRQL). Our objective was to calculate the amount of weight loss required to attain established minimal clinically important differences (MCIDs) in HRQL, measured using three validated instruments. METHODS: Data from the Alberta Population-based Prospective Evaluation of Quality of Life Outcomes and Economic Impact of Bariatric Surgery (APPLES) study, a population-based, prospective Canadian cohort including 150 wait-listed, 200 medically managed and 150 surgically treated patients were examined. Two-year changes in weight and HRQL measures (Short-Form (SF)-12 physical (PCS; MCID = 5) and mental (MCS; MCID = 5) component summary score, EQ-5D Index (MCID = 0.03) and Visual Analog Scale (VAS; MCID = 10), Impact of Weight on Quality of Life (IWQOL)-Lite total score (MCID = 12)) were calculated. Separate multivariable linear regression models were constructed within medically and surgically treated patients to determine if weight changes achieved HRQL MCIDs. Pooled analysis in all 500 patients was performed to estimate the weight reductions required to achieve the pre-defined MCID for each HRQL instrument. RESULTS: Mean age was 43.7 (SD 9.6) years, 88% were women, 92% were white, and mean initial body mass index was 47.9 (SD 8.1) kg/m2. In surgically treated patients (two-year weight loss = 16%), HRQL MCIDs were reached for all instruments except the SF-12 MCS. In medically managed patients (two-year weight loss = 3%), MCIDs were attained in the EQ-index but not the other instruments. In all patients, percent weight reductions to achieve MCIDs were: 23% (95% confidence interval (CI): 17.5, 32.5) for PCS, 25% (17.5, 40.2) for MCS, 9% (6.2, 15.0) for EQ-Index, 23% (17.3, 36.1) for EQ-VAS, and 17% (14.1, 20.4) for IWQOL-Lite total score. CONCLUSIONS: Weight reductions to achieve MCIDs for most HRQL instruments are markedly higher than the conventional threshold of 5% to 10%. Surgical, but not medical treatment, consistently led to clinically important improvements in HRQL over two years. TRIAL REGISTRATION: Clinicaltrials.gov NCT00850356.

Predictors of health-related quality of life in 500 severely obese patients.

OBJECTIVE: To characterize health-related quality of life (HRQL) impairment in severely obese subjects, using several validated instruments. METHODS: A cross-sectional analysis of 500 severely obese subjects was completed. Short-Form (SF)-12 [Physical (PCS) and Mental (MCS) component summary scores], EuroQol (EQ)-5D [Index and Visual Analog Scale (VAS)], and Impact of Weight on Quality of Life (IWQOL)-Lite were administered. Multivariable linear regression models were performed to identify independent predictors of HRQL. RESULTS: Increasing BMI was associated with lower PCS (-1.33 points per 5 kg/m(2) heavier; P < 0.001), EQ-index (-0.02; P < 0.001), EQ-VAS (-1.71; P = 0.003), and IWQOL-Lite (-3.72; P = 0.002), but not MCS (P = 0.69). The strongest predictors (all P < 0.005) for impairment in each instrument were: fibromyalgia for PCS (-5.84 points), depression for MCS (-7.49 points), stroke for EQ-index (-0.17 points), less than full-time employment for EQ-VAS (-7.06 points), and coronary disease for IWQOL-Lite (-10.86 points). Chronic pain, depression, and sleep apnea were associated with reduced HRQL using all instruments. CONCLUSION: The clinical impact of BMI on physical and general HRQL was small, and mental health scores were not associated with BMI. Chronic pain, depression, and sleep apnea were consistently associated with lower HRQL.

Failure of deferoxamine, an iron chelator, to improve outcome after collagenase-induced intracerebral hemorrhage in rats.

Intracerebral hemorrhage (ICH) is a devastating stroke with no clinically proven treatment. Deferoxamine (DFX), an iron chelator, is a promising therapy that lessens edema, mitigates peri-hematoma cell death, and improves behavioral recovery after whole-blood-induced ICH in rodents. In this model, blood is directly injected into the brain, usually into the striatum. This mimics many but not all clinical features of ICH (e.g., there is no spontaneous bleed). Thus, we tested whether DFX improves outcome after collagenase-induced striatal ICH in rats. In the first experiment, 3- and 7-day DFX regimens (100 mg/kg twice per day starting 6 h after ICH), similar to those shown effective in the whole-blood model, were compared to saline treatment. Functional recovery was evaluated from 3 to 28 days with several behavioral tests. Except for one instance, DFX failed to lessen ICH-induced behavioral impairments and it did not lessen brain injury, which averaged 43.5 mm(3) at a 28-day survival. In the second experiment, 3 days of DFX treatment were given starting 0 or 6 h after collagenase infusion. Striatal edema occurred, but it was not affected by either DFX treatment (vs. saline treatment). Therefore, in contrast to studies using the whole-blood model, DFX treatment did not improve outcome in the collagenase model. Our findings, when compared to others, suggest that there are critical differences between these ICH models. Perhaps, the current clinical work with DFX will help identify the more clinically predictive model for future neuroprotection studies.