Measuring the Impact of Medication-Related Interventions on 30-Day Readmission Rates in a Skilled Nursing Facility.

BACKGROUND: There is a lack of published literature that measures the impact of transitional care pharmacist (TCP) medication-related interventions within the skilled nursing facility (SNF) setting. OBJECTIVES: To evaluate the impact of TCP medication-related interventions on 30-day hospital readmissions among SNF patients compared to current standard of care. METHODS: This was a retrospective pilot study. All patients included in the study were discharged from an inpatient facility to a SNF. The control group received transitional services from a care team with no pharmacist. The intervention group received transitional services from a care team plus a pharmacist. RESULTS: The 30-day readmission rates in the intervention group were 14 (12%)/116 compared to the control group, 19 (16%)/116; however, the difference was not statistically significant (P = .35). The median time to readmission was statistically significantly longer in the intervention group, 17.5 days, compared to the control group, 10 days (P = .02). One hundred seventy-four medication-related interventions were performed in the intervention group during the study period. CONCLUSION: This study demonstrates that TCP interventions in an SNF are associated with a significant delay in readmission. A continuation of the pilot program may show a role in reducing all-cause 30-day readmission and ED visit rates.

Polypharmacy, Infectious Diseases, Sexual Behavior, and Psychophysical Health Among Anabolic Steroid-Using Homosexual and Heterosexual Gym Patrons in San Francisco's Castro District.

BACKGROUND: Limited studies based in England and Australia reported misuse of anabolic-androgenic steroids (AAS) among homosexual men to enhance body image. Anecdotally, AAS are also being misused by homosexual men in the United States. Since many AAS and certain performance enhancing drugs (PEDs) are administered via injection, this poses a potential vector for the spread of infectious disease in an already at-risk population. OBJECTIVES: This study compared and contrasted homosexual and heterosexual male gym clients regarding use of AAS and PEDs, use of alcohol and illicit drugs, seroprevalence of infectious disease, engagement in risky injection practices and sexual behaviors, and presence of psychiatric conditions. METHODS: Recruitment and data collection occurred outside four exercise gyms in the San Francisco Castro District area between October 25, 2014 and March 10, 2015. Two hundred and twenty homosexual men and 73 heterosexual men completed the 114-item cross-sectional survey. RESULTS: Ten percent of homosexual men reported lifetime AAS use. Homosexual men had almost four times more sexual partners and were over 14 times more likely to knowingly have unprotected intercourse with a known HIV positive person than heterosexual men. In addition, a quarter of homosexual men who injected drugs admitted to sharing used syringes or needles with another person. Conclusions/Importance: The current study is the first to confirm AAS use among homosexual men in the United States. Homosexual men partook in high-risk sexual behaviors and injection practices which may place them at greater risks for contracting and spreading HIV and other infectious diseases.

Patient and clinical characteristics that heighten risk for heart failure readmission.

BACKGROUND: Within 30 days of hospital discharge, heart failure (HF) readmission rates nationally accumulate to more than 20%. Due to this high rate of unplanned re-hospitalization, predictive models are needed to identify patients who pose the highest readmission risk. OBJECTIVE: To evaluate the diagnosis and timing and to identify patient and clinical characteristics associated with 30 day readmissions among HF patients. METHODS: A retrospective analysis of electronic health records was conducted to study HF admissions during the period October 2008 to November 2014. Patients with a primary discharge diagnosis consistent with HF were included. Descriptive statistics were used to compare the readmitted and non-readmitted cohorts. Logistic regression was used to develop a predictive model to determine patient and clinical variables associated with 30 day readmission. RESULTS: Characteristics of the study cohort (n = 2420) are: a mean age of 72, predominantly male (55%), white (55%), currently not employed (91%), and utilizing Medicare as a payer (68%). Overall, 42% were married. Over the study time period there were 394 (16.3%) 30 day readmissions after 2420 hospitalizations. The 3 most common reasons for readmission were HF (36.0%), renal disorders (8.4%), and other cardiac diseases (6.9%). Analysis showed that 11.9% of patients readmitted during days 0-3, 15.2% during days 4-7, 31.5% during days 8-15, and 41.4% during days 16-30. The final multivariate predictive model included 5 variables that were associated with an increased risk for 30-day readmission: employment status as retired or disabled, > 1 emergency department visit in the past 90 days, length of stay >5 days during index visit, and a BUN value > 45 mg/dL. CONCLUSION: This study provides a deeper understanding of patient and clinical characteristics that are associated with readmission in HF. Evaluation of these characteristics will provide additional information to guide strategies meant to reduce HF readmission rates.

Motivations and Predictors of Cheating in Pharmacy School.

Objective. To assess the prevalence, methods, and motivations for didactic cheating among pharmacy students and to determine predictive factors for cheating in pharmacy colleges and schools. Methods. A 45-item cross-sectional survey was conducted at all four doctor of pharmacy programs in Northern California. For data analysis, t test, Fisher exact test, and logistic regression were used. Results. Overall, 11.8% of students admitted to cheating in pharmacy school. Primary motivations for cheating included fear of failure, procrastination, and stress. In multivariate analysis, the only predictor for cheating in pharmacy school was a history of cheating in undergraduate studies. Conclusion. Cheating occurs in pharmacy schools and is motivated by fear of failure, procrastination, and stress. A history of past cheating predicts pharmacy school cheating. The information presented may help programs better understand their student population and lead to a reassessment of ethical culture, testing procedures, and prevention programs.

Psychosocial Factors Associated with Subclinical Atherosclerosis in South Asians: The MASALA Study.

South Asians have the highest rates of premature atherosclerotic cardiovascular disease amongst all ethnic groups in the world; however this risk cannot be fully explained by traditional risk factors. Participants from the Mediators of Atherosclerosis in South Asians Living in America Study were included in this cross-sectional analysis. The purpose of this study was to investigate the association of psychosocial factors (including anger, anxiety, depressive symptoms, current and chronic stress, and everyday hassles) with carotid intima-media thickness (CIMT). Three multivariate models were examined to evaluate the association between the psychosocial factors and CIMT. Findings suggest that the impact of psychosocial factors on subclinical atherosclerosis is differential for South Asian men and women. For men, anxiety and depression were associated; while for women, stress was associated with common carotid intima media thickness, independent of traditional CVD risk factors, diet and physical activity.

Infectious disease, injection practices, and risky sexual behavior among anabolic steroid users.

Anabolic-androgenic steroids (AAS) and other performance-enhancing drugs (PEDs) are commonly misused to increase muscle size and strength, as well as improve physical appearance. Many AAS and certain PEDs are administered via injection and therefore pose a risk for transmission of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and skin and soft tissue infections (SSTIs). Further, AAS users may be more likely to take part in high-risk sexual behaviors than non-AAS users. This review explores the prevalence of infectious diseases as well as risky injection practices and sexual behaviors of AAS users in the current literature. A comprehensive MEDLINE search (1984-17 April 2015) for English language reports was performed on AAS users. Ten studies analyzed the prevalence of HIV infection, 6 studies analyzed HBV infection, and 6 studies analyzed HCV infection; 20 studies analyzed injection practices and 7 studies analyzed high-risk sexual behaviors of AAS users. HIV, HBV, HCV, and SSTIs have been associated with AAS users. In particular, HIV infection seems much higher among homosexual male AAS users. AAS users also take part in high-risk injection practices but to a much lower extent than intravenous drug users. AAS users are also more likely to engage in high-risk sexual behaviors than the general population. Clinicians and health-policy leaders may utilize these findings to implement strategies to decrease the spread of infectious diseases.

Association of ABC (HbA1c, blood pressure, LDL-cholesterol) goal attainment with depression and health-related quality of life among adults with type 2 diabetes.

AIMS: To determine the relationship between ABC goal attainment, depression, and health-related quality of life (HRQoL) among a national sample of patients with type 2 diabetes (T2DM). METHODS: A retrospective, cross-sectional analysis was performed examining 808 non-pregnant patients ≥20 years old with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. ABC goals were defined as HbA1c<7%, BP<130/80 mm Hg, and LDL-C<100 mg/dL. Patient characteristics associated with ABC goal attainment were examined. RESULTS: Overall, 23.7% of participants achieved simultaneous ABC goals. Severe depression was significantly associated with lower rates of ABC goal attainment compared to those with no depression (5.0% vs. 25.4%, p=0.048). ABC goal attainment rates were lower among females, Hispanic and non-Hispanic black minority groups, and patients with a duration of diabetes over five years, while increased visits with health care professionals were significantly associated with meeting all three ABC goals for patients with T2DM. CONCLUSIONS: The relationship between simultaneous ABC goal attainment, depression and HRQoL is complex. Patients with T2DM unable to meet ABC goals may benefit from increased contact with health care professionals.

Stress, Drugs, and Alcohol Use Among Health Care Professional Students: A Focus on Prescription Stimulants.

OBJECTIVE: To contrast the characteristics of pharmacy, medicine, and physician assistant (PA) students regarding the prevalence of drug, alcohol, and tobacco use and to identify risk factors associated with prescription stimulant use. PARTICIPANTS: Five hundred eighty nine students were recruited to complete a 50-item Web-based survey. MAIN OUTCOME MEASURES: Demographics, nonmedical prescription medication use, illicit drug and alcohol use, Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) psychiatric diagnoses, and perceived stress scale (PSS) scores. RESULTS: Medicine and PA students reported greater nonmedical prescription stimulant use than pharmacy students (10.4% vs 14.0% vs 6.1%; P < .05). Medicine and PA students were more likely to report a history of an anxiety disorder (12.1% vs 18.6% vs 5.9%; P < .05), major depressive disorder (9.4% vs 8.1% vs 3.3%; P < .05), and attention-deficit hyperactivity disorder (ADHD; 4.0% vs 9.3% vs 0.7%; P < .001) than pharmacy students. PSS scores for all 3 groups (21.9-22.3) were roughly twice as high as the general adult population. CONCLUSION: Illicit drug and prescription stimulant use, psychiatric disorders, and elevated stress levels are prevalent among health care professional students. Health care professional programs may wish to use this information to better understand their student population which may lead to a reassessment of student resources and awareness/prevention programs.

Implementation of an accelerated physical examination course in a doctor of pharmacy program.

OBJECTIVE: To describe the implementation of a 1-day accelerated physical examination course for a doctor of pharmacy program and to evaluate pharmacy students' knowledge, attitudes, and confidence in performing physical examination. DESIGN: Using a flipped teaching approach, course coordinators collaborated with a physician faculty member to design and develop the objectives of the course. Knowledge, attitude, and confidence survey questions were administered before and after the practical laboratory. ASSESSMENT: Following the practical laboratory, knowledge improved by 8.3% (p<0.0001). Students' perceived ability and confidence to perform a physical examination significantly improved (p<0.0001). A majority of students responded that reviewing the training video (81.3%) and reading material (67.4%) prior to the practical laboratory was helpful in learning the physical examination. CONCLUSION: An accelerated physical examination course using a flipped teaching approach was successful in improving students' knowledge of, attitudes about, and confidence in using physical examination skills in pharmacy practice.

Factors affecting the unmet demand for pharmacists: state-level analysis.

OBJECTIVE: To describe the relationship between state-level Aggregate Demand Index (ADI) data and market factors reflecting both supply and demand: unemployment rates, pharmacy graduates, community pharmacy prescription growth rates, and Medicare Part D. DESIGN: Cross-sectional time series analysis using state-level data. SETTING: U.S. labor market for pharmacists, from 2001 to 2010. INTERVENTION: Model ADI data for states (dependent variable) against five independent variables: previous year ADI, unemployment rates, pharmacy graduates, prescription growth rates, and Medicare Part D. MAIN OUTCOME MEASURES: Significance and predictive ability of the model, sign of the variables studied, and R2. RESULTS: In the two-way (state and time) fixed-effects model, all variables were significant and R2 was 0.79. Contributions to state-level ADIs were, in rank order, previous year ADI, unemployment rates, pharmacy graduates, and prescription growth rates. The model predicted 2010 ADI values for 44 of 51 states within ±10%. The model depicts the independent contributions of each variable for the short (∼1 year) and longer term. Although the nature of ADI data precludes quantitative predictions about the pharmacist job market, the model results show marketplace directions (up or down) and comparative impacts. CONCLUSION: The model demonstrated that unemployment rates, pharmacy graduates, prescription growth rates, and Medicare Part D contributed significantly to state-level ADIs between 2001 and 2010. The relationships uncovered should be monitored and reexamined as new data emerge in order to anticipate the directions of the pharmacist job market.

Enhancing diabetes care by adding a pharmacist to the primary care team.

PURPOSE: The impact of pharmacist interventions on short-term clinical markers and long-term cardiovascular risk in patients with type 2 diabetes is investigated. METHODS: Selected health outcomes were retrospectively analyzed in 147 adults with type 2 diabetes whose care was managed by a team of providers including a pharmacist (the enhanced care group) and a matched sample of patients (n = 147) managed by a primary care physician only (the control group). All patients received services through the same health maintenance organization (HMO). The primary study endpoints were (1) the changes from baseline to 12-month follow-up in glycosylated hemoglobin (HbA(1c)), low-density lipoprotein cholesterol (LDL-C), and blood pressure (BP) values, (2) rates of attainment of HbA(1c), LDL-C and BP goals, and (3) changes from baseline in predicted 10-year risks of coronary heart disease (CHD) and stroke. RESULTS: During the 12-month study period, the mean HbA(1c) value was decreased from 9.5% to 6.9% in the enhanced care group and from 9.3% to 8.4% in the control group (p < 0.001); patients in the enhanced care group were significantly more likely to attain goals for HbA(1c) (odds ratio [OR], 3.9), LDL-C (OR, 2.0), and BP reduction (OR, 2.0) and three times more likely to attain all three goals (OR, 3.2). The estimated 10-year risk of CHD was decreased from 16.4% to 9.3% with enhanced care versus a reduction from 17.4% to 14.8% with usual care (p < 0.001). CONCLUSION: The addition of a pharmacist to an HMO primary care team improved short-term surrogate markers as well as long-term cardiovascular risk in adult patients with type 2 diabetes.

A Markov model of the cost-effectiveness of pharmacist care for diabetes in prevention of cardiovascular diseases: evidence from Kaiser Permanente Northern California.

BACKGROUND: It has been demonstrated in previous studies that pharmacist management of patients with type 2 diabetes mellitus (T2DM) in the outpatient setting not only improves diabetes-related clinical outcomes such as hemoglobin A1c but also blood pressure (BP), total cholesterol (TC), and quality of life. Improved control of BP and TC has been shown to reduce the risks of cardiovascular disease (CVD), which has placed a heavy economic burden on the health care system. However, no study has evaluated the cost-effectiveness of pharmacist intervention programs with respect to the long-term preventive effects on CVD outcomes among T2DM patients. OBJECTIVES: To (a) quantify the long-term preventive effects of pharmacist intervention on CVD outcomes among T2DM patients using evidence from a matched cohort study in the outpatient primary care setting and (b) assess the relative cost-effectiveness of adding a clinical pharmacist to the primary care team for the management of patients with T2DM based on improvement in CVD risks with the aid of an economic model. METHODS: Clinical data between the periods of June 2007 to February 2010 were collected from electronic medical records at 2 separate clinics at Kaiser Permanente (KP) Northern California, 1 with primary care physicians only (control group) and the other with the addition of a pharmacist (enhanced care group). Patients in the enhanced care group were matched 1:1 with patients in the control group according to baseline characteristics that included age, gender, A1c, and Charlson comorbidity score. The estimated 10-year CVD risk for both groups was calculated by the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine (version 2) based on age, sex, race, smoking status, atrial fibrillation, duration of diabetes, levels of A1c, systolic BP (SBP) and TC, and high-density lipoprotein cholesterol (HDL-C) observed at 12 months. There was no statistical difference in the baseline clinical inputs to the Risk Engine (A1c [P=0.115], SBP [P=0.184], TC [P=0.055], and HDL-C [P=0.475]) between the 2 groups. A Markov model was developed to simulate the estimated CVD outcomes over 10 years and to estimate cost-effectiveness. The final outcomes examined included incremental cost and effectiveness measured by life years and per quality-adjusted life year gained. Both deterministic sensitivity analysis (SA) and probabilistic SA were conducted to examine the robustness of the results. RESULTS: The estimated risks for coronary heart disease (CHD) and stroke (both nonfatal and fatal) at the end of the follow-up were consistently lower in the enhanced care group compared with the control group, even though baseline risks in both groups were similar. The absolute risk reduction (ARR) between the enhanced care and control groups increased over time. For example, the ARR for nonfatal CHD risk in year 1 was 0.5% (1.2% vs. 0.7%), whereas the ARR increased to 5.5% in year 10 (14.8% vs. 9.3%). Similarly, the ARR between the enhanced care and the control groups was calculated as 0.3% for fatal CHD in year 1 and increased to 4.6% in year 10. Results from the Markov model suggest that the enhanced care group was shown to be a dominant strategy (less expensive and more effective) compared with the control group in the 10-year evaluation period in the base-case (average or mean results) scenario. Sensitivity analysis that took into account the uncertainty in all important variables, such as wage of pharmacists, utility weight (the degree of preference individuals have for a particular health state or condition), response rate to pharmacists' care, and uncertainty associated with the estimated 10 years of CVD risk, revealed that the relative value of enhanced care was robust to most of the variations in these parameters. Notably, the level of cost-effectiveness measured by net monetary value depends on the time horizon adopted by the payers and the magnitude of CVD risk reduction. The enhanced care group has a higher chance of being considered as a cost-effective strategy when a longer time horizon such as a minimum of 4 to 5 years is adopted. CONCLUSIONS: Adding pharmacists to the health care management team for diabetic patients improves the long-term CVD risks. The longer-term CVD risk reductions were shown to be more dramatic than the short-term reduction. A longer time horizon adopted by health plans in managing T2DM patients has a higher probability of making the intervention cost-effective.

Depressive symptoms in patients with type 2 diabetes mellitus: do stress and coping matter?

This article examines the relationship among diabetes-related stress, appraisal, coping and depressive symptoms in patients with type 2 diabetes mellitus (T2DM) using the transactional model of stress and coping (TMSC) as the theoretical framework. In this cross-sectional study, a convenience sample of 201 patients with T2DM was recruited from three outpatient clinics. Patients with depressive symptoms reported significantly more diabetes-related stress than patients without depressive symptoms. The results of path analysis suggest that patients who experience greater diabetes-related stress or greater depressive symptoms have a negative appraisal of their diabetes. Negative appraisal is, in turn, associated with greater use of avoidance, passive resignation and diabetes integration coping and lesser use of problem-focused coping. Avoidance, passive resignation and diabetes integration coping are, in turn, related to greater depressive symptoms or greater diabetes-related stress. Overall, the results of this study support the TMSC as a framework to elucidate the relationships among diabetes-related stress, appraisal, coping and depressive symptoms in patients with T2DM. However, given the cross-sectional nature of the study, we are unable to elucidate the directionality of the relationship between stress and depressive symptoms. Implications of the findings and the need for longitudinal studies to evaluate these relationships are discussed.

The pharmacist Aggregate Demand Index to explain changing pharmacist demand over a ten-year period.

OBJECTIVES: To describe Aggregate Demand Index (ADI) trends from 1999-2010; to compare ADI time trends to concurrent data for US unemployment levels, US entry-level pharmacy graduates, and US retail prescription growth rate; and to determine which variables were significant predictors of ADI. METHODS: Annual ADI data (dependent variable) were analyzed against annual unemployment rates, annual number of pharmacy graduates, and annual prescription growth rate (independent variables). RESULTS: ADI data trended toward lower demand levels for pharmacists since late 2006, paralleling the US economic downturn. National ADI data were most highly correlated with unemployment (p < 0.001), then graduates (p < 0.006), then prescription growth rate (p < 0.093). A hierarchical model with the 3 variables was significant (p = 0.019), but only unemployment was a significant ADI predictor. Unemployment and ADI also were significantly related at the regional, division, and state levels. CONCLUSIONS: The ADI is strongly linked to US unemployment rates. The relationship suggests that an improving economy might coincide with increased pharmacist demand. Predictable increases in future graduates and other factors support revisiting the modeling process as new data accumulate.

Visions for required postgraduate year 1 residency training by 2020: a comparison of actual versus projected expansion.

STUDY OBJECTIVE: To explore the feasibility of expanding postgraduate year (PGY) 1 residency training as proposed by the American College of Clinical Pharmacy and American Society of Health-System Pharmacists (ASHP). DESIGN: Prospective survey analysis. DATA SOURCE: The ASHP Online Residency Directory was used to obtain PGY1 residency program data from June 2007-June 2008. A four-item questionnaire was developed to survey future residency growth in identified PGY1 programs. MEASUREMENTS AND MAIN RESULTS: Survey data were aggregated to project future residency growth in the "next few years" (range 2-4 yrs). Estimates of Doctor of Pharmacy (Pharm.D.) graduates to 2020 were used to calculate PGY1 residency positions and average annual growth rates required if 24% (scenario 1), 75% (scenario 2), and 100% (scenario 3) of pharmacy graduates pursue PGY1 residencies. Projected growth from the survey was compared with required growth under the scenarios, as well as with actual PGY1 growth from June 2007-June 2008. A subset analysis of college-affiliated and Veterans Affairs (VA) PGY1 programs was performed. The survey response rate was 57%. The PGY1 positions were projected to increase by 8.3%/year in the next few years or 4193 positions by 2020 if 8.3% growth is sustained. Required average annual growth rates for scenarios 1-3, respectively, were 4.8%, 14.4%, and 17%. Projected growth rates were sufficient to achieve only scenario 1 in which 24% (percentage of pharmacists estimated to practice in health systems) of graduates pursue PGY1 residencies. The actual PGY1 growth rate from 2007-2008 was 9.9%. The VA positions actually grew at 12.5% and college-affiliated positions grew at 8.3% over this period, whereas VA projection for growth was 4.8% and college-affiliated projection was 9.6%. CONCLUSION: Having sufficient PGY1 residency positions available for all Pharm.D. graduates by 2020 would require at least a 17% average annual growth rate, whereas survey respondents predicted 8.3%. Actual residency growth in 2008 (9.9%) exceeded survey projections. Study data suggest that the ASHP aspiration to have all graduates who pursue health-system pharmacy careers complete a PGY1 residency is achievable. Higher percentages, 75% or 100%, are only partially achievable. Continued growth of college-affiliated residencies and sustained growth in the VA system are important to achieving residency growth goals.

Depressive symptoms in patients with type 2 diabetes in the ambulatory care setting: opportunities to improve outcomes in the course of routine care.

OBJECTIVES: To assess the frequency of untreated, self-reported depressive symptoms in a cross section of adult ambulatory patients with type 2 diabetes and to identify demographic and/or clinical characteristics associated with depressive symptoms in study patients. DESIGN: Cross-sectional study. SETTING: Three ambulatory care clinics in the southwestern United States in fall 2005. PATIENTS: 217 primary care patients aged 18 years or older with a diagnosis of type 2 diabetes. INTERVENTION: Administration of the Zung Self-rating Depression Scale (Zung SDS). MAIN OUTCOMES MEASURES: Self-reported data on demographic characteristics and depressive symptoms. Data for insurance, comorbid conditions, and glycosylated hemoglobin (A1C) values were abstracted from patient charts. RESULTS: Depressive symptoms (Zung SDS score > or =50) were identified in 72.1% of patients. Overall, 13% of the patients with a diagnosis of depression (based on patient charts) were not receiving treatment. Factors significantly associated with depressive symptoms were past history of depression (beta= 0.53, P < 0.01), Medicaid insurance (beta= 0.15, P < 0.02), and insulin use (beta= 0.12, P < 0.05). CONCLUSION: The results suggest that possible undetected or untreated depression can be assessed in patients with type 2 diabetes through use of a self-rating scale in the course of routine ambulatory care. Adding the Zung SDS screen to routine care protocols could facilitate improved detection and treatment of comorbid depression in ambulatory patients with type 2 diabetes.

Cofilin mediates ATP depletion-induced endothelial cell actin alterations.

Ischemia and sepsis lead to endothelial cell damage, resulting in compromised microvascular flow in many organs. Much remains to be determined regarding the intracellular structural events that lead to endothelial cell dysfunction. To investigate potential actin cytoskeletal-related mechanisms, ATP depletion was induced in mouse pancreatic microvascular endothelial cells (MS1). Fluorescent imaging and biochemical studies demonstrated a rapid and progressive increase in F-actin along with a decrease in G-actin at 60 min. Confocal microscopic analysis showed ATP depletion resulted in destruction of actin stress fibers and accumulation of F-actin aggregates. We hypothesized these actin alterations were secondary to dephosphorylation/activation of actin-depolymerizing factor (ADF)/cofilin proteins. Cofilin, the predominant isoform expressed in MS1 cells, was rapidly dephosphorylated/activated during ATP depletion. To directly investigate the role of cofilin activation on the actin cytoskeleton during ischemia, MS1 cells were infected with adenoviruses containing the cDNAs for wild-type Xenopus laevis ADF/cofilin green fluorescent protein [XAC(wt)-GFP], GFP, and the constitutively active and inactive isoforms XAC(S3A)-GFP and XAC(S3E)-GFP. The rate and extent of cortical actin destruction and actin aggregate formation were increased in ATP-depleted XAC(wt)-GFP- and XAC(S3A)-GFP-expressing cells, whereas increased actin stress fibers were observed in XAC(S3E)-GFP-expressing cells. To investigate the upstream signaling pathway of ADF/cofilin, LIM kinase 1-GFP (LIMK1-GFP) was expressed in MS1 cells. Cells expressing LIMK1-GFP protein had higher levels of phosphorylated ADF/cofilin, increased stress fibers, and delayed F-actin cytoskeleton destruction during ATP depletion. These results strongly support the importance of cofilin regulation in ischemia-induced endothelial cell actin cytoskeleton alterations leading to cell damage and microvascular dysfunction.