The importance of clinical surveillance in detecting legionnaires' disease outbreaks: a large outbreak in a hospital with a Legionella disinfection system-Pennsylvania, 2011-2012.

BACKGROUND: Healthcare-associated Legionnaires' disease (LD) is a preventable pneumonia with a 30% case fatality rate. The Centers for Disease Control and Prevention guidelines recommend a high index of suspicion for the diagnosis of healthcare-associated LD. We characterized an outbreak and evaluated contributing factors in a hospital using copper-silver ionization for prevention of Legionella growth in water. METHODS: Through medical records review at a large, urban tertiary care hospital in November 2012, we identified patients diagnosed with LD during 2011-2012. Laboratory-confirmed cases were categorized as definite, probable, and not healthcare associated based on time spent in the hospital during the incubation period. We performed an environmental assessment of the hospital, including collection of samples for Legionella culture. Clinical and environmental isolates were compared by genotyping. Copper and silver ion concentrations were measured in 11 water samples. RESULTS: We identified 5 definite and 17 probable healthcare-associated LD cases; 6 case patients died. Of 25 locations (mostly potable water) where environmental samples were obtained for Legionella-specific culture, all but 2 showed Legionella growth; 11 isolates were identical to 3 clinical isolates by sequence-based typing. Mean copper and silver concentrations were at or above the manufacturer's recommended target for Legionella control. Despite this, all samples where copper and silver concentrations were tested showed Legionella growth. CONCLUSIONS: This outbreak was linked to the hospital's potable water system and highlights the importance of maintaining a high index of suspicion for healthcare-associated LD, even in the setting of a long-term disinfection program.

Association of BNP and Troponin Levels with Outcome among Cardiac Resynchronization Therapy Recipients.

BACKGROUND: We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. METHODS: At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. RESULTS: A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). CONCLUSION: Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH.

2-octyl-cyanoacrylate glue for fixation of STSG in genitourinary tissue defects due to Fournier gangrene: a preliminary trial.

BACKGROUND: In these reported cases, we observed the outcomes of skin take and wound healing using 2-octyl-cyanoacrylate glue, which was used as tissue glue in the reconstruction of complex genital skin loss due to fournier gangrene. METHODS: Fifteen patients with Fournier's gangrene were treated in this study. After initial surgical debridement, all defects were repaired using STSG. In this method a thin layer of 2-octyl-cyanoacrylate was dripped on the recipient site immediately before graft application. All wounds were followed up postoperatively and observed for evidence of graft take, seroma or hematoma formation, drainage, and infection. Patient and physician satisfaction were also determined. RESULTS: Grafts were completely accepted in all fifteen patients. None of the patients had wound infection, seroma, hematoma, or other complications. CONCLUSION: Use of 2-octyl-cyanoacrylate glue (Glueseal) for STSG fixation in complex genital skin defects after Fournier gangrene may be an acceptable alternative to conventional surgical closure with a good cosmetic outcome. Further studies are needed to confirm our initial success with this approach.

Assessing the Quality and Performance of Institutional Review Boards: Levels of Initial Reviews.

How well institutional review boards (IRBs) follow Common Rule criteria for levels of initial protocol review has not been systematically evaluated. We compared levels of review as determined using the Office for Human Research Protections (OHRP) human subject regulations decision charts of 313 protocols that had been approved by IRBs. There was a 97.8% agreement between 140 protocols that were reviewed by full board and the levels of review according to OHRP criteria. Likewise, there was a 93.8% agreement between 113 protocols that were reviewed using an expedited review procedure and OHRP criteria. However, there was only 75% agreement for exempt protocols. Specifically, 10 (16.7%) of the 60 exempt protocols were found to require IRB review, that is, six protocols requiring expedited review and four protocols requiring full board review. Conducting non-exempt research without prior IRB approval constitutes serious noncompliance. Our data suggest that exempt protocols need more scrutiny.

Factors associated with the use of preventive care for contrast-induced acute kidney injury.

BACKGROUND: The factors that affect the implementation of preventive care for contrast-induced acute kidney injury (CIAKI) are unknown. OBJECTIVE: To assess patient and provider factors associated with the use of preventive care for CIAKI. DESIGN: Prospective cohort study. PARTICIPANTS: Patients with kidney disease undergoing procedures with intravascular iodinated radiocontrast. MEASUREMENTS: We recorded the use of preventive care defined as the administration of: (1) pre- and post-procedure isotonic intravenous (IV) fluid, (2) N-acetylcysteine, and (3) iso-osmolal radiocontrast. We surveyed patients' providers to assess their knowledge, experience, and training on CIAKI and used multiple logistic regression to assess the independent associations of patient and provider factors with the use of these preventive interventions. RESULTS: We enrolled 660 patients and 87 providers. Patient factors associated with use of IV fluid and N-acetylcysteine were higher baseline serum creatinine (OR 1.5 and 5.0, p < 0.05) and inpatient status (OR 3.0 and 6.3, p < 0.05), while higher baseline serum creatinine was associated with the use of iso-osmolal contrast (OR = 13.4, p < 0.01). The primary provider characteristics associated with the use of IV fluid and N-acetylcysteine were a greater degree of prior training on CIAKI (OR 1.9 and 2.8, p < 0.05) and higher number of prior patients with CIAKI (OR 2.7 and 2.6, p < 0.05). CONCLUSIONS: Patient baseline kidney function and provider training and experience with CIAKI are independently associated with the use of preventive care. Efforts to increase and intensify the training providers receive on CIAKI may help decrease the incidence of this costly iatrogenic condition.

The incidence of clinically significant contrast-induced nephropathy following non-emergent coronary angiography.

OBJECTIVES: The primary aim of this study was to assess the incidence of clinically significant contrast-induced nephropathy (CIN) among patients undergoing non-emergent coronary angiography. BACKGROUND: Although retrospective analyses have emphasized the association of CIN with adverse patient outcomes, the actual incidence of clinically significant CIN following non-emergent coronary angiography is not clear. METHODS: We prospectively identified patients with baseline estimated glomerular filtration rates (eGFR) < 60 ml/min/1.73 m(2) undergoing non-emergent coronary angiography. We measured serum creatinine 48-96 hr following angiography and assessed the incidence of CIN using two definitions, a rise in Scr > or = 25% and > or = 0.5 mg/dl. We tracked the need for dialysis, hospitalization related to kidney injury, and 30-day mortality to examine the association of CIN with these outcomes. RESULTS: We enrolled 181 patients with a median eGFR of 52 ml/min/1.73 m(2). Of the 165 patients (91%) with post-procedure Scr data, the incidence of CIN was 6.1-8.5%. One patient required dialysis (0.55%) and one (0.55%) died within 30 days. Although 38 patients required hospital admission, CIN was not associated with the need for hospitalization. Patients with an increase in Scr > or = 25% demonstrated a trend toward increased risk for 30-day mortality (P = 0.09), whereas those with increments in Scr > or = 0.5 mg/dl had a marginally higher risk for dialysis (P = 0.06) and 30-day mortality (P = 0.06), although these associations failed to meet the level of statistical significance. CONCLUSIONS: Biochemically defined CIN occurs in a small, but notable proportion of patients undergoing non-emergent coronary angiography. However, clinically significant CIN is very uncommon.

Water Cultures Are More Sensitive Than Swab Cultures for the Detection of Environmental Legionella.

Water cultures were significantly more sensitive than concurrently collected swab cultures (n=2,147 each) in detecting Legionella pneumophila within a Veterans Affairs healthcare system. Sensitivity for water versus swab cultures was 90% versus 30% overall, 83% versus 48% during a nosocomial Legionnaires' disease outbreak, and 93% versus 22% post outbreak. Infect Control Hosp Epidemiol 2018;39:108-110.

Impact of blood transfusions in patients presenting with anemia and suspected acute coronary syndrome.

Anemia has been shown to predict adverse events in patients presenting with acute coronary syndromes and non-ST-elevation myocardial infarctions (MIs). Less is known about the value of blood transfusions in this setting. We sought to evaluate the impact of red blood cell transfusions on outcomes. Transfusion in anemic patients admitted with suspected acute coronary syndrome/non-ST-elevation MIs led to a significant increase in 30-day recurrent MI or death (odds ratio 3.05, 95% confidence interval 1.80 to 5.17, p <0.001). This relation persisted after adjusting for significant univariate predictors: hypotension on presentation, pulmonary edema, and increased troponin-I levels (odds ratio 2.57, 95% confidence interval 1.41 to 4.69, p <0.001). In conclusion, the risk versus benefit of transfusion in patients presenting with an acute coronary syndrome needs careful assessment.

Comparison of frequency of new-onset atrial fibrillation or flutter in patients on statins versus not on statins presenting with suspected acute coronary syndrome.

The effect of statins on the incidence of new-onset atrial fibrillation (AF) in patients presenting with suspicion of acute coronary syndrome (ACS) is unknown. Our study population consisted of patients admitted to a tertiary care Veterans Administration hospital with suspicion of ACS between November 2001 and January 2006. All patients had an electrocardiogram on admission that was compared with a previous electrocardiogram to confirm new-onset AF or atrial flutter. Of 1,526 patients, 164 (10.8%) had new-onset AF and 601 (39.4%) were on a statin on admission. Patients with AF were significantly more likely to be older, Caucasian, have renal insufficiency and anemia, and less likely to be diabetic, on a statin or angiotensin-converting enzyme inhibitor on admission, or have chest pain as a presenting complaint. In univariate analysis, patients on statins were significantly less likely to have new-onset AF (odds ratio 0.40, 95% confidence interval 0.33 to 0.69, p <0.01). This relation persisted in the multivariate model (odds ratio 0.57, 95% confidence interval 0.39 to 0.83, p <0.01) after correcting for age, race, diabetes mellitus, chest pain, and use of angiotensin-converting enzyme inhibitor. In conclusion, patients presenting with suspicion of ACS were much less likely to have newonset AF if they were on a statin at time of presentation.

Effect of hyponatremia (<135 mEq/L) on outcome in patients with non-ST-elevation acute coronary syndrome.

Hyponatremia is associated with adverse outcomes in patients with heart failure and ST-elevation myocardial infarction (STEMI). We evaluated the effect of hyponatremia on outcomes in patients with suspected acute coronary syndrome and non-STEMI. All patients had a sodium level determined at time of admission, at 24 and 48 hours, and at discharge. Of 1,478 patients, 341 (23.1%) were hyponatremic (sodium <135 mEq/L) on presentation. Patients who had hyponatremia on admission were significantly more likely to die or have recurrent myocardial infarction in the next 30 days (odds ratio 1.98, 95% confidence interval 1.35 to 2.89, p <0.001). This relation persisted after adjusting for factors such as age, left ventricular ejection fraction, use of diuretics before admission, hypotension on presentation, anemia, chronic renal insufficiency, pulmonary edema, and high troponin levels (odds ratio 1.7, 95% confidence interval 1.1 to 2.5, p = 0.01). In conclusion, hyponatremia on admission is associated with 30-day adverse outcome in patients presenting with suspected acute coronary syndrome/non-STEMI.

Racial variations in treatment and outcomes of black and white patients with high-risk non-ST-elevation acute coronary syndromes: insights from CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines?).

BACKGROUND: Black patients with acute myocardial infarction are less likely than whites to receive coronary interventions. It is unknown whether racial disparities exist for other treatments for non-ST-segment elevation acute coronary syndromes (NSTE ACS) and how different treatments affect outcomes. METHODS AND RESULTS: Using data from 400 US hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines?) National Quality Improvement Initiative, we identified black and white patients with high-risk NSTE ACS (positive cardiac markers and/or ischemic ST-segment changes). After adjustment for demographics and medical comorbidity, we compared the use of therapies recommended by the American College of Cardiology/American Heart Association guidelines for NSTE ACS and outcomes by race. Our study included 37,813 (87.3%) white and 5504 (12.7%) black patients. Black patients were younger; were more likely to have hypertension, diabetes, heart failure, and renal insufficiency; and were less likely to have insurance coverage or primary cardiology care. Black patients had a similar or higher likelihood than whites of receiving older ACS treatments such as aspirin, beta-blockers, or ACE inhibitors but were significantly less likely to receive newer ACS therapies, including acute glycoprotein IIb/IIIa inhibitors, acute and discharge clopidogrel, and statin therapy at discharge. Blacks were also less likely to receive cardiac catheterization, revascularization procedures, or smoking cessation counseling. Acute risk-adjusted outcomes were similar between black and white patients. CONCLUSIONS: Black patients with NSTE ACS were less likely than whites to receive many evidence-based treatments, particularly those that are costly or newer. Longitudinal studies are needed to assess the long-term impact of these treatment disparities on clinical outcomes.

Clinical characteristics, process of care, and outcomes of Hispanic patients presenting with non-ST-segment elevation acute coronary syndromes: results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE).

BACKGROUND: Data regarding the management of non-ST-segment elevation acute coronary syndromes (NSTE ACS) in Hispanic patients, the largest and fastest-growing minority in the United States, are scarce. METHODS: We sought to describe the clinical characteristics, process of care, and outcomes of Hispanics presenting with NSTE ACS at US hospitals. We compared baseline characteristics, resource use, and inhospital mortality among 3936 Hispanics and 90280 non-Hispanic whites with NSTE ACS from the CRUSADE Quality Improvement Initiative. RESULTS: The regional distribution of Hispanics in CRUSADE paralleled that in the US Census. Hispanics were younger (65 vs 70 years, P < .0001) and had less hyperlipidemia (45.4% vs 49.0%, P < .0001) but were more likely to be hypertensive (72.2% vs 67.9%, P < .0001) and diabetic (46.5% vs 30.9%, P < .0001). Hispanics were also more likely to be uninsured (12.5% vs 5.1%, P < .001). During hospitalization, Hispanics were more often managed conservatively, undergoing stress tests more frequently (13.0% vs 10.1%, P < .0001), with less use of cardiac catheterization within 48 hours (48.7% vs 55.5%, P < .0001) or percutaneous coronary intervention (39.6% vs 46.4%, P < .0001) at any time. Hispanics received similar discharge treatments but were less frequently referred for cardiac rehabilitation (38.5% vs 49.2%, P < .0001). Adjusted inhospital mortality was similar in both groups (odds ratio 0.87, 95% CI 0.72-1.05). CONCLUSIONS: Although hispanics have a different risk factor profile and are treated less aggressively during hospitalization when they present with NSTE ACS, these treatment differences do not appear to affect inhospital outcomes. Further research is warranted to explore the long-term consequences of these findings.

Noncardiac surgery and the risk of death and other cardiovascular events in patients with hypertrophic cardiomyopathy.

BACKGROUND: There is a paucity of reports evaluating the perioperative risk of noncardiac surgery in patients with hypertrophic cardiomyopathy (HCM). HYPOTHESIS: The study was undertaken to evaluate the incidence of acute myocardial infarction (MI) and all-cause inhospital mortality following noncardiac surgery in patients with HCM. METHODS: We searched the National Hospital Discharge Survey database for patients with a diagnosis of HCM who had undergone noncardiac surgery. Cases were matched by age, gender, and year of surgery. Death or acute MI were used as endpoints for analysis. RESULTS: From 1996 to 2002, 227 patients with HCM were matched with 554 controls (representing national estimates of 25,874 HCM and 50,326 controls patients). Patients with HCM were more likely than controls to have a history of atrial fibrillation (22.7 vs. 10.6%, p < 0.001) and of congestive heart failure (CHF) (24.2 vs. 14.1%, p < 0.001). The in-hospital incidence of death or MI was higher in patients with HCM than in controls (6.7 vs. 2.5%, p < 0.001 for death and 2.2 vs. 0.3%, p < 0.001 for MI). After correcting for age, gender, race, presence of hypertension, diabetes mellitus, history of coronary artery-disease, history of CHF, atrial fibrillation, and ventricular arrhythmias in a multivariate binary logistic regression model, the presence of HCM increased the odds of death by 61% (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.46-1.77, p < 0.001), and almost tripled the odds of the combined endpoint of death or MI (OR = 2.82, 95% CI 2.59-3.07, p < 0.001). CONCLUSION: The presence of HCM significantly increases the risk of death and MI associated with noncardiac surgery. Patients with HCM undergoing elective procedures may require more careful preoperative assessment and perioperative monitoring. The impact of the severity of HCM on outcomes of noncardiac surgery needs further study.

Racial disparities in outcomes following coronary artery bypass grafting.

More than 12 million people in the United States have coronary heart disease, the second leading cause of hospitalization in the United States. It is known that persons within racial minorities, specifically African Americans, have a higher prevalence of coronary heart disease, yet are much less likely to undergo invasive cardiac treatment interventions. An invasive intervention commonly used to treat coronary heart disease is coronary artery bypass grafting, with over 140,000 operations performed annually in the United States. However, blacks are known to experience higher post-coronary artery bypass graft morbidity and mortality. The causes for racial disparities in post-coronary artery bypass graft outcomes are not well known but may include factors related to the individual, provider, system, and society/environment, either alone or in combination. The purpose of this article is to provide an overview of the literature regarding disparities in the health and healthcare of black patients with coronary heart disease with respect to CABG, and examine potential hypotheses for variant outcomes after surgery.

Improving the Diagnosis of Legionella Pneumonia within a Healthcare System through a Systematic Consultation and Testing Program.

RATIONALE: Legionella testing is not recommended for all patients with pneumonia, but rather for particular patient subgroups. As a result, the overall incidence of Legionella pneumonia may be underestimated. OBJECTIVES: To determine the incidence of Legionella pneumonia in a veteran population in an endemic area after introduction of a systematic infectious diseases consultation and testing program. METHODS: In response to a 2011-2012 outbreak, the VA Pittsburgh Healthcare System mandated infectious diseases consultations and testing for Legionella by urine antigen and sputum culture in all patients with pneumonia. MEASUREMENTS AND MAIN RESULTS: Between January 2013 and December 2015, 1,579 cases of pneumonia were identified. The incidence of pneumonia was 788/100,000 veterans per year, including 352/100,000 veterans per year and 436/100,000 veterans per year with community-associated pneumonia (CAP) and health care-associated pneumonia, respectively. Ninety-eight percent of patients with suspected pneumonia were tested for Legionella by at least one method. Legionella accounted for 1% of pneumonia cases (n = 16), including 1.7% (12/706) and 0.6% (4/873) of CAP and health care-associated pneumonia, respectively. The yearly incidences of Legionella pneumonia and Legionella CAP were 7.99 and 5.99/100,000 veterans, respectively. The sensitivities of urine antigen and sputum culture were 81% and 60%, respectively; the specificity of urine antigen was >99.97%. Urine antigen testing and Legionella cultures increased by 65% and 330%, respectively, after introduction of our program. CONCLUSIONS: Systematic testing of veterans in an endemic area revealed a higher incidence of Legionella pneumonia and CAP than previously reported. Widespread urine antigen testing was not limited by false positivity.

Inflammatory Mediators and Clinical Outcome in Patients With Advanced Heart Failure Receiving Cardiac Resynchronization Therapy.

Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1α, IL-1ß, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome. However, a significant proportion will not respond to this therapy. We conducted this study to assess the association of proinflammatory/fibrotic and/or reparative immune response mediators at baseline with outcome after CRT. In the multicenter RISK study, plasma samples were collected prospectively before CRT implantation. Plasma IL-6, epidermal growth factor, FGF-2, IL-1α, IL-1ß, IL-4, and IL-13 were evaluated by Luminex technology. The primary outcome was predefined as freedom from heart failure hospitalization or death and a decrease in echocardiographic end-systolic volume of >15% at 12 months. To determine associations with the outcome, multivariate logistic regression models including baseline clinical characteristics and the specific cytokines and growth factors were constructed. On multivariate analysis of 257 patients, detectable reparative cytokine IL-13 was significantly associated with the primary outcome (odds ratio 3.79; 95% CI 2.10 to 6.82, p <0.0001). In contrast, detectable proinflammatory/fibrotic growth factor FGF-2 was negatively associated (odds ratio 0.31; 95% CI, 0.14 to 0.68; p = 0.004). In conclusion, in CRT recipients, baseline levels of inflammatory mediators affecting cardiac fibrosis versus repair were associated with subsequent clinical outcome.

Perioperative risk of noncardiac surgery associated with aortic stenosis.

The perioperative risk of noncardiac surgery in patients with aortic stenosis (AS) remains ill-defined, and the few studies published have reported conflicting results. A sample of patients from the National Hospital Discharge Survey database diagnosed with AS who underwent any noncardiac surgical procedure was searched. Patients who underwent any cardiac surgery were excluded. Patients with AS were matched by decile of age and surgical risk for twice as many controls. A discharge diagnosis of acute myocardial infarction (AMI) and death was used as the end points for analysis. From 1996 to 2002, 5,149 patients with a diagnosis of AS had undergone noncardiac surgery and were matched with 10,284 controls. The incidence of AMI was greater in patients with AS than in controls (3.86% vs 2.03%, p <0.001). After correcting for gender and the presence of coronary artery disease, hypertension, and diabetes mellitus in a multivariate logistic regression model, the presence of AS was associated with an increased likelihood of AMI (odds ratio 1.55, 95% confidence interval 1.27 to 1.90, p <0.001). There was no significantly increased risk for death in patients with AS versus controls. In the era of more intense perioperative medical management of patients who undergo noncardiac surgery, the presence of AS increases the risk for perioperative AMI but not overall mortality. The impact of the actual severity of AS on outcomes with noncardiac surgery needs further study.

Effect of both elevated troponin-I and peripheral white blood cell count on prognosis in patients with suspected myocardial injury.

We found a high white blood cell count (>11,000/mul) to be of additive prognostic value to high troponin-I levels in predicting risk of recurrent nonfatal myocardial infarctions and all-cause mortality in patients who present with acute coronary syndromes and non-ST-elevation myocardial infarctions. A high troponin-I level or white blood cell count increased the odds ratio of an event to 2.2 (95% confidence interval 1.0 to 4.73, p = 0.05), but high values for the 2 markers increased the odds ratio to 4.5 (95% confidence interval 1.42 to 14.21, p = 0.01).

Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia.

Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom severity in schizophrenia. The mechanism(s) underlying the clinical effect is not known. Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia and in the mechanism of some antipsychotic agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We examined whether supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA)-modified 5-HT amplified ADP-induced platelet aggregation in patients with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months supplementally to ongoing antipsychotic treatment in 12 patients with chronic schizophrenia, using an open-label design. Red blood cell membrane fatty acids and platelet functions (platelet aggregation and dense granule secretion) were monitored at baseline, 1-, 3- and 6-months. The EPA levels were elevated more than five-fold in RBC membranes of all patients after 3 months supplementation, indicating a high degree of compliance. Consistent with previous reports, there was inhibition of ADP-induced platelet aggregation by EPA supplementation. Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously, we have demonstrated a significant inverse correlation between 5-HT responsivity and psychosis severity in unmedicated patients with schizophrenia. Taken together, the present data support the notion that EPA may be mediating its therapeutic effects in schizophrenia via modulation of the 5-HT2 receptor complex.