Racial and ethnic variances in preparedness for aging in place among US adults ages 50-80.

OBJECTIVES: To investigate the preparations made by adults to age in place and identify disparities. METHODS: A cross-sectional survey was conducted among U.S. adults ages 50-80 years old (n = 2277). Individual, environmental, social, and community factors influencing readiness for aging in place were examined using chi-square tests and logistic regression. RESULTS: Income, disability status, and household composition, emerged as influential factors, often negatively affecting minority aging. Participants' consideration of aging in place was related to their disability status (OR 1.80 [1.32, 2.45]) and age (OR age 60-69 2.06 [1.54, 2.74], age 70-80 (OR 1.98 [1.46,2.67]), compared with age 50-59). Indigenous and Black older adults reported significantly higher levels of consideration for aging in place than White older adults (Indigenous OR 7.89 [2.35, 26.42], Black OR 1.71 [1.11, 2.64]). CONCLUSION: Aging in place is best facilitated by inclusive communities that prioritize adaptive homes and accessible community services.

Characteristics and Predictors of Sleep Among Spousal Care Dyads Living With Chronic Conditions.

OBJECTIVES: Poor sleep is common among older adults with chronic health conditions and their spousal caregivers. However, dyadic sleep patterns among spouses are underexplored within the literature. This study examines dyadic sleep characteristics and associated contextual factors among spousal care dyads. METHODS: Participants included 462 older adult spousal care dyads from the 2015 National Health and Aging Trends Study and National Study of Caregiving (mean ages of care recipients/caregivers = 79 and 76 years, respectively; 22% of dyads were living with dementia). Self-reported sleep included frequency of (a) trouble falling back asleep among dyads, (b) care-related sleep disturbances among caregivers, and (c) trouble initiating sleep among care recipients. Predictors included between-dyad characteristics such as whether respondents had dementia, care burden and support, relationship quality, neighborhood cohesion, and within-dyad characteristics such as demographics, depression, and positive affect. We conducted multilevel dyadic analysis and actor-partner interdependence modeling. RESULTS: Sleep was correlated more among dyads living with dementia than those with other chronic conditions. Care dyads had poorer sleep if caregivers reported higher care burden; however, better relationship quality marginally ameliorated the association. Depressive symptoms had a partner effect on poorer sleep among care dyads, whereas positive emotions and older age only had an actor effect on better sleep for care recipients and spousal caregivers. Neighborhood cohesion, care support, and other demographic characteristics were not associated with dyadic sleep outcomes. DISCUSSION: Addressing both care recipient- and caregiver-related factors may improve sleep health for both members of the care dyad living with chronic conditions.

Caregiving in the COVID-19 pandemic: Family adaptations following an intensive care unit hospitalisation.

AIM AND OBJECTIVE: To identify how family caregivers adapt to the caregiving role following a relative's COVID-19-related intensive care unit (ICU) hospitalisation. BACKGROUND: Family caregiving is often associated with poor health amongst caregivers which may limit their capacity to effectively support patients. Though severe COVID-19 infection has necessitated increasing numbers of persons who require caregiver support, little is known about these caregivers, the persons they are caring for, or the strategies used to effectively adjust to the caregiving role. DESIGN: A qualitative descriptive study design was adopted, and findings are reported using COREQ. METHODS: A secondary analysis of transcripts from semi-structured interviews conducted with recently discharged ICU patients who had COVID-19 (n = 16) and their family caregivers (n = 16) was completed using thematic analysis. MAXQDA 2020 and Miro were used to organise data and complete coding. Analysis involved a structured process of open and closed coding to identify and confirm themes that elucidated adaptation to family caregiving. RESULTS: Six themes highlight how family caregivers adapt to the caregiving role following an ICU COVID-19-related hospitalisation including (1) engaging the support of family and friends, (2) increased responsibilities to accommodate caregiving, (3) managing emotions, (4) managing infection control, (5) addressing patient independence and (6) engaging support services. These themes were found to be congruent with the Roy adaptation model. CONCLUSIONS: Family caregiving is a stressful transition following a patient's acute hospitalisation. Effective adaptation requires flexibility and sufficient support, beginning with the care team who can adequately prepare the family for the anticipated challenges of recovery. RELEVANCE TO CLINICAL PRACTICE: Clinical teams may improve post-hospitalisation care outcomes of patients by preparing families to effectively adjust to the caregiver role-particularly in identifying sufficient support resources. PATIENT OR PUBLIC CONTRIBUTION: Participation of patients/caregivers in this study was limited to the data provided through participant interviews.

The Association of Nursing Home Characteristics and Quality with Adverse Events After a Hospitalization.

BACKGROUND/OBJECTIVES: We previously found high rates of adverse events (AEs) for long-stay nursing home residents who return to the facility after a hospitalization. Further evidence about the association of AEs with aspects of the facilities and their quality may support quality improvement efforts directed at reducing risk. DESIGN: Prospective cohort analysis. SETTING AND PARTICIPANTS: 32 nursing homes in the New England states. A total of 555 long-stay residents contributed 762 returns from hospitalizations. METHODS: We measured the association between AEs developing in the 45 days following discharge back to long-term care and characteristics of the nursing homes including bed size, ownership, 5-star quality ratings, registered nurse and nursing assistant hours, and the individual Centers for Medicare & Medicaid Services (CMS) quality indicators. We constructed Cox proportional hazards models controlling for individual resident characteristics that were previously found associated with AEs. RESULTS: We found no association of AEs with most nursing home characteristics, including 5-star quality ratings and the composite quality score. Associations with individual quality indicators were inconsistent and frequently not monotonic. Several individual quality indicators were associated with AEs; the highest tertile of percentage of residents with depression (4%-25%) had a hazard ratio (HR) of 1.65 [95% confidence interval (CI) 1.16, 2.35] and the highest tertile of the percentage taking antipsychotic medications (18%-35%) had an HR of 1.58 (CI 1.13, 2.21). The percentage of residents needing increased assistance with activities of daily living was statistically significant but not monotonic; the middle tertile (13% to <20%) had an HR of 1.69 (CI 1.16, 2.47). CONCLUSIONS AND IMPLICATIONS: AEs occurring during transitions between nursing homes and hospitals are not explained by the characteristics of the facilities or summary quality scores. Development of risk reduction approaches requires assessment of processes and quality beyond the current quality measures.

Characteristics of Long-Term Care Residents That Predict Adverse Events after Hospitalization.

BACKGROUND/OBJECTIVES: Adverse events (AEs) occur frequently in long-term care (LTC) residents transitioning from the hospital back to an LTC facility. Measuring the association between resident characteristics and AEs can inform AE risk reduction strategies. DESIGN: Prospective cohort analysis. SETTING: A total of 32 nursing homes from six New England states. PARTICIPANTS: A total of 555 LTC residents contributing 762 transitions from the hospital back to LTC. MEASUREMENTS: We measured the association between all AEs and preventable AEs developing in the 45 days following discharge back to LTC and demographic variables, hospital length of stay (LOS), Charlson Comorbidity Index (CCI) (0-1, 2-3, 4-5 and ≥6), dependency in activities of daily living (ADLs) using the Minimum Data Set Long Form Scale (in quintiles 0-12, 13-15, 16, 17-18, and ≥19), and number of regularly scheduled medications (0-9, 10-13, 14-17, and ≥18). To understand the independent association of each resident characteristic with AEs and preventable AEs, we constructed multiple Cox proportional hazards models. RESULTS: There were 283 discharges with one or more AEs and 212 with preventable AEs. Characteristics independently associated with higher risk of an AE included hospital LOS 9 or more days (hazard ratio [HR] = 1.49; 95% confidence interval [CI] = 1.02-2.17); CCI of 4 to 5 (HR = 1.74; 95% CI = 1.13-2.67) or 6 or higher (HR = 1.58; 95% CI = 1.01-2.46); 18 or more regularly scheduled medications (HR = 1.53; 95% CI = 1.07-2.18); and 19 and above on ADL dependency (HR = 1.78; 95% CI = 1.21-2.62). Results from models with preventable AEs were similar to those with all AEs. CONCLUSION: Increased LOS, higher comorbidity burden, greater dependency in ADLs, and polypharmacy were the resident characteristics most strongly associated with risk of AEs and preventable AEs. We recommend heightened vigilance in the care of LTC residents with these characteristics transitioning back to LTC. We also recommend research to assess strategies to reduce the risk of AEs.

Adverse Events in Long-term Care Residents Transitioning From Hospital Back to Nursing Home.

IMPORTANCE: Transition from hospital to nursing home is a high-risk period for adverse events in long-term care (LTC) residents. Adverse events include harms from medical care, including failure to provide appropriate care. OBJECTIVE: To report the incidence, type, severity, and preventability of adverse events in LTC residents transitioning from hospital back to the same LTC facility. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of LTC residents discharged from hospital back to LTC from March 1, 2016, to December 31, 2017, and followed up for 45 days. In a random sample of 32 nursing homes located in 6 New England states, 555 LTC residents were selected, contributing 762 transitions from hospital back to the same LTC facility. MAIN OUTCOMES AND MEASURES: The main outcome was an adverse event within the 45-day period after transition from hospital back to nursing home. Trained nurse abstractors reviewed nursing home records for the period, and then 2 physicians independently reviewed each potential adverse event to determine whether harm occurred and to characterize the type, severity, and preventability of each event. When reviewers disagreed, they met to reach consensus. RESULTS: Of the 555 individual residents, 365 (65.6%) were female, and the mean (SD) age at the time of discharge was 82.2 (11.5) years. Five hundred twenty (93.7%) were non-Hispanic white, 21 (3.8%) were non-Hispanic black, 9 (1.6%) were Hispanic, and 5 (0.9%) were of other non-Hispanic race/ethnicity. In the cohort, there were 379 adverse events among 762 discharges. One hundred ninety-seven events (52.0%) related to resident care, with pressure ulcers, skin tears, and falls with injury representing the most common types of events in this category. Health care-acquired infections (108 [28.5%]) and adverse drug events (64 [16.9%]) were the next most common. One hundred ninety-eight (52.2%) adverse events were characterized as less serious. However, 145 (38.3%) events were deemed serious, 28 (7.4%) life-threatening, and 8 (2.1%) fatal. In terms of preventability, 267 (70.4%) adverse events were found to be preventable or ameliorable, with less serious events more often considered preventable or ameliorable (146 [73.7%]) compared with more severe events (121 [66.9%]). In addition, resident care-related adverse events such as fall with injury, skin tear, and pressure ulcer were more commonly deemed preventable (173 of 197 [87.8%]) compared with adverse drug events (39 of 64 [60.9%]) or health care-acquired infections (49 of 108 [45.4%]). CONCLUSIONS AND RELEVANCE: Adverse events developed in nearly 4 of 10 of discharges from hospital back to LTC. Most were preventable or ameliorable. Standardized reporting of events and better coordination and information transfer across settings are potential ways to prevent adverse events in LTC residents.

Persistent geographic variations in availability and quality of nursing home care in the United States: 1996 to 2016.

BACKGROUND: Availability of nursing home care has declined and national efforts have been initiated to improve the quality of nursing home care in the U.S. Yet, data are limited on whether there are geographic variations in declines of availability and quality of nursing home care, and whether variations persist over time. We sought to assess geographic variation in availability and quality of nursing home care. METHODS: Retrospective study using Medicaid/Medicare-certified nursing home data from the Centers for Medicare & Medicaid Services, 1996-2016. Outcomes were 1) availability of all nursing home care (1996-2016), measured by the number of Medicaid/Medicare-certified beds for a given county per 100,000 population aged ≥65 years, regardless of nursing home star rating; 2) availability of 5-star nursing home care, measured by the number of Medicaid/Medicare-certified beds provided by 5-star nursing homes; and 3) utilization of nursing home beds, defined as the rate of occupied Medicaid/Medicare-certified beds among the total Medicaid/Medicare-certified beds. RESULTS: From 1999 to 2016, availability of all nursing home care declined from 4882 (standard deviation: 931) to 3480 (912) beds, per 100,000 population aged ≥65 years. Persistent geographic variation in availability of nursing home care was observed; the correlation coefficient of county-specific availabilities from 1996 to 2016 was 0.78 (95% CI 0.77-0.79). From 2011 to 2016, availability of 5-star nursing home beds increased from 658 (303) to 895 (661) per 100,000 population aged ≥65 years. The correlation coefficient for county-specific availabilities from 2011 to 2016 was 0.54 (95% CI 0.51-0.56). Availability and quality of nursing home care were not highly correlated. In 2016, the correlation coefficient for county-specific availabilities between all nursing home and 5-star nursing home beds was 0.33 (95% CI 0.30-0.36). From 1996 to 2016, the utilization of certified beds declined from 78.5 to 72.2%. This decline was consistent across all census divisions, but most pronounced in the Mountain division and less in the South-Atlantic division. CONCLUSION: We observed persistent geographic variations in availability and quality of nursing home care. Availability of all nursing home care declined but availability of 5-star nursing home care increased. Availability and quality of nursing home care were not highly correlated.

Inhibition of IκB Kinase at 24 Hours After Acute Kidney Injury Improves Recovery of Renal Function and Attenuates Fibrosis.

BACKGROUND: Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease. Nuclear factor-κB is a nuclear transcription factor activated post-ischemia, responsible for the transcription of proinflammatory proteins. The role of nuclear factor-κB in the renal fibrosis post-AKI is unknown. METHODS AND RESULTS: We used a rat model of AKI caused by unilateral nephrectomy plus contralateral ischemia (30 minutes) and reperfusion injury (up to 28 days) to show impairment of renal function (peak: 24 hours), activation of nuclear factor-κB (peak: 48 hours), and fibrosis (28 days). In humans, AKI is diagnosed by a rise in serum creatinine. We have discovered that the IκB kinase inhibitor IKK16 (even when given at peak serum creatinine) still improved functional and structural recovery and reduced myofibroblast formation, macrophage infiltration, transforming growth factor-ß expression, and Smad2/3 phosphorylation. AKI resulted in fibrosis within 28 days (Sirius red staining, expression of fibronectin), which was abolished by IKK16. To confirm the efficacy of IKK16 in a more severe model of fibrosis, animals were subject to 14 days of unilateral ureteral obstruction, resulting in tubulointerstitial fibrosis, myofibroblast formation, and macrophage infiltration, all of which were attenuated by IKK16. CONCLUSIONS: Inhibition of IκB kinase at peak creatinine improves functional recovery, reduces further injury, and prevents fibrosis.

Associations between nursing home performance and hospital 30-day readmissions for acute myocardial infarction, heart failure and pneumonia at the healthcare community level in the United States.

OBJECTIVES: To evaluate community-specific nursing home performance with community-specific hospital 30-day readmissions for Medicare patients discharged with acute myocardial infarction, heart failure or pneumonia. DESIGN: Cross-sectional study using 2009-2012 hospital risk-standardised 30-day readmission data for Medicare fee-for-service patients hospitalised for all three conditions and nursing home performance data from the Centers for Medicare & Medicaid Services Five-Star Quality Rating System. SETTING: Medicare-certified nursing homes and acute care hospitals. PARTICIPANTS: 12,542 nursing homes and 3,039 hospitals treating 30 or more Medicare fee-for-service patients for all three conditions across 2,032 hospital service areas in the United States. MEASUREMENTS: Community-specific hospital 30-day risk-standardised readmission rates. Community-specific nursing home performance measures: health inspection, staffing, Registered Nurses and quality performance; and an aggregated performance score. Mixed-effects models evaluated associations between nursing home performance and hospital 30-day risk-standardised readmission rates for all three conditions. RESULTS: The relationship between community-specific hospital risk-standardised readmission rates and community-specific overall nursing home performance was statistically significant for all three conditions. Increasing nursing home performance by one star resulted in decreases of 0.29% point (95% CI: 0.12-0.47), 0.78% point (95% CI: 0.60-0.95) and 0.46% point (95% CI: 0.33-0.59) of risk-standardised readmission rates for AMI, HF and pneumonia, respectively. Among the specific measures, higher performance in nursing home overall staffing and Registered Nurse staffing measures was statistically significantly associated with lower hospital readmission rates for all three conditions. Notable geographic variation in the community-specific nursing home performance was observed. CONCLUSION: Community-specific nursing home performance is associated with community-specific hospital 30-day readmission rates for Medicare fee-for-service patients for acute myocardial infarction, heart failure or pneumonia. IMPLICATIONS FOR PRACTICE: Coordinated care between hospitals and nursing homes is essential to reduce readmissions. Nursing homes can improve performance and reduce readmissions by increasing registered nursing homes. Further, communities can work together to create cross-continuum care teams comprised of hospitals, nursing homes, patients and their families, and other community-based service providers to reduce unplanned readmissions.

Artesunate Protects Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation.

OBJECTIVE: To evaluate the effects of artesunate on organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat. BACKGROUND: HS is still a common cause of death in severely injured patients and is characterized by impairment of organ perfusion, systemic inflammatory response, and multiple organ failure. There is no specific therapy that reduces organ injury/dysfunction. Artesunate exhibits pharmacological actions beyond its antimalarial activity, such as anticancer, antiviral, and anti-inflammatory effects. METHODS: Rats were submitted to HS. Mean arterial pressure was reduced to 30 mm Hg for 90 minutes, followed by resuscitation. Rats were randomly treated with artesunate (2.4 or 4.8 mg/kg i.v.) or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed. RESULTS: Artesunate attenuated the multiple organ injury and dysfunction caused by HS. Pathway analysis of RNA sequencing provided good evidence to support an effect of artesunate on the Akt-survival pathway, leading to downregulation of interleukin-1 receptor-associated kinase 1. Using Western blot analysis, we confirmed that treatment of HS rats with artesunate enhanced the phosphorylation (activation) of Protein kinase B (Akt) and endothelial nitric oxide synthase and the phosphorylation (inhibition) of glycogen synthase kinase-3ß (GSK-3ß). Moreover, artesunate attenuated the HS-induced activation of nuclear factor kappa B and reduced the expression of proinflammatory proteins (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin 6). CONCLUSIONS: Artesunate attenuated the organ injury/dysfunction associated with HS by a mechanism that involves the activation of the Akt-endothelial nitric oxide synthase survival pathway, and the inhibition of glycogen synthase kinase-3ß and nuclear factor kappa B. A phase II clinical trial evaluating the effects of good manufacturing practice-artesunate in patients with trauma and severe hemorrhage is planned.

Use of Indwelling Urinary Catheters in Nursing Homes: Implications for Quality Improvement Efforts.

OBJECTIVES: To describe the epidemiology of indwelling urinary catheter use in nursing homes (NHs). DESIGN: Observational cohort study. SETTING: A purposeful sampling strategy was used to identify a diverse sample of 28 Connecticut NHs, defined in terms of ownership, quality ratings, and bed size. PARTICIPANTS: Long-stay (>100 days) residents of study NHs with an indwelling urinary catheter present at any time over a 1-year period. MEASUREMENTS: Duration of catheter use was determined, and indications for catheter placement were documented. Indications considered appropriate included urinary retention or outlet obstruction, pressure ulcer (Stage 3 or 4 with risk of contamination by urine), hospice care, and need for accurate measurement of input and output. During quarterly follow-up assessments, whether the catheter was still in place or had been removed for any reason other than routine maintenance was determined. RESULTS: The overall rate of any urinary catheter use per 100 resident-beds over a 1-year period was 4.8 (range 1.0-9.9, median 5.1). Of the 228 residents meeting eligibility criteria, a documented indication for the catheter was present in the NH record for 195 (86%). Of those with a documented indication, 99% (n = 193) had one or more indications deemed appropriate, including urinary retention (83%), pressure ulcer (21%), hospice care (10%), and need for accurate measurement of input and output (6%). The urinary catheter was removed at some point during the period of observation in 49% (n = 111) of participants; those with a shorter duration of catheter use before study enrollment were more likely to have the catheter removed during the follow-up period. Of the 111 residents who had the catheter removed, 58 (52.3%) had it reinserted at some point during follow-up. CONCLUSION: These findings suggest that indwelling urinary catheter use in long-stay NH residents is uncommon and generally appropriate and that efforts to improve catheter care and outcomes should extend beyond a singular focus on reducing use.

Inhibition of IκB Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock.

Nuclear factor-kappa B (NF-κB) activation is widely implicated in multiple organ failure (MOF); however, a direct inhibitor of IκB kinase (IKK), which plays a pivotal role in the activation of NF-κB, has not been investigated in shock. Thus, the aim of the present work was to investigate the effects of an IKK inhibitor on the MOF associated with hemorrhagic shock (HS). Therefore, rats were subjected to HS and were resuscitated with the shed blood. Rats were treated with the inhibitor of IKK or vehicle at resuscitation. Four hours later, blood and organs were assessed for organ injury and signaling events involved in the activation of NF-κB. Additionally, survival following serum deprivation was assessed in HK-2 cells treated with the inhibitor of IKK. HS resulted in renal dysfunction, lung, liver and muscular injury, and increases in serum inflammatory cytokines. Kidney and liver tissue from HS rats revealed increases in phosphorylation of IKKαß and IκBα, nuclear translocation of NF-κB and expression of inducible isoform of nitric oxide synthase (iNOS). IKK16 treatment upon resuscitation attenuated NF-κB activation and activated the Akt survival pathway, leading to a significant attenuation of all of the above parameters. Furthermore, IKK16 exhibited cytoprotective effects in human kidney cells. In conclusion, the inhibitor of IKK complex attenuated the MOF associated with HS. This effect may be due to the inhibition of the NF-κB pathway and activation of the survival kinase Akt. Thus, the inhibition of the IKK complex might be an effective strategy for the prevention of MOF associated with HS.

Process Evaluation of a Quality Improvement Project to Decrease Hospital Readmissions From Skilled Nursing Facilities.

OBJECTIVE: To describe and evaluate the impact of quality improvement (QI) support provided to skilled nursing facilities (SNFs) by a Quality Improvement Organization (QIO). DESIGN: Retrospective, mixed-method, process evaluation of a QI project intended to decrease preventable hospital readmissions from SNFs. SETTING: Five SNFs in Connecticut. PARTICIPANTS: SNF Administrators, Directors of Nursing, Assistant Directors of Nursing, Admissions Coordinators, Registered Nurses, Certified Nursing Assistants, Receptionists, QIO Quality Improvement Consultant. INTERVENTION: QIO staff provided training and technical assistance to SNF administrative and clinical staff to establish or enhance QI infrastructure and implement an established set of QI tools [Interventions to Reduce Acute Care Transfers (INTERACT) tools]. MEASUREMENTS: Baseline SNF demographic, staffing, and hospital readmission data; baseline and follow-up SNF QI structure (QI Committee), processes (general and use of INTERACT tools), and outcome (30-day all-cause hospital readmission rates); details of QIO-provided training and technical assistance; QIO-perceived barriers to quality improvement; SNF leadership-perceived barriers, accomplishments, and suggestions for improvement of QIO support. RESULTS: Success occurred in establishing QI Committees and targeting preventable hospital readmissions, as well as implementing INTERACT tools in all SNFs; however, hospital readmission rates decreased in only 2 facilities. QIO staff and SNF leaders noted the ongoing challenge of engaging already busy SNF staff and leadership in QI activities. SNF leaders reported that they appreciated the training and technical assistance that their institutions received, although most noted that additional support was needed to bring about improvement in readmission rates. CONCLUSION: This process evaluation documented mixed clinical results but successfully identified opportunities to improve recruitment of and provision of technical support to participating SNFs. Recommendations are offered for others who wish to conduct similar projects.

Delayed administration of pyroglutamate helix B surface peptide (pHBSP), a novel nonerythropoietic analog of erythropoietin, attenuates acute kidney injury.

In preclinical studies, erythropoietin (EPO) reduces ischemia-reperfusion-associated tissue injury (for example, stroke, myocardial infarction, acute kidney injury, hemorrhagic shock and liver ischemia). It has been proposed that the erythropoietic effects of EPO are mediated by the classic EPO receptor homodimer, whereas the tissue-protective effects are mediated by a hetero-complex between the EPO receptor monomer and the ß-common receptor (termed "tissue-protective receptor"). Here, we investigate the effects of a novel, selective-ligand of the tissue-protective receptor (pyroglutamate helix B surface peptide [pHBSP]) in a rodent model of acute kidney injury/dysfunction. Administration of pHBSP (10 µg/kg intraperitoneally [i.p.] 6 h into reperfusion) or EPO (1,000 IU/kg i.p. 4 h into reperfusion) to rats subjected to 30 min ischemia and 48 h reperfusion resulted in significant attenuation of renal and tubular dysfunction. Both pHBSP and EPO enhanced the phosphorylation of Akt (activation) and glycogen synthase kinase 3ß (inhibition) in the rat kidney after ischemia-reperfusion, resulting in prevention of the activation of nuclear factor-κB (reduction in nuclear translocation of p65). Interestingly, the phosphorylation of endothelial nitric oxide synthase was enhanced by EPO and, to a much lesser extent, by pHBSP, suggesting that the signaling pathways activated by EPO and pHBSP may not be identical.