Facility-Level Variation in Hospitalization, Mortality, and Costs in the 30 Days After Percutaneous Coronary Intervention: Insights on Short-Term Healthcare Value From the Veterans Affairs Clinical Assessment, Reporting, and Tracking System (VA CART) Program.

BACKGROUND: Policies to reduce unnecessary hospitalizations after percutaneous coronary intervention (PCI) are intended to improve healthcare value by reducing costs while maintaining patient outcomes. Whether facility-level hospitalization rates after PCI are associated with cost of care is unknown. METHODS AND RESULTS: We studied 32,080 patients who received PCI at any 1 of 62 Veterans Affairs hospitals from 2008 to 2011. We identified facility outliers for 30-day risk-standardized hospitalization, mortality, and cost. Compared with the risk-standardized average, 2 hospitals (3.2%) had a lower-than-expected hospitalization rate, and 2 hospitals (3.2%) had a higher-than-expected hospitalization rate. We observed no statistically significant variation in facility-level risk-standardized mortality. The facility-level unadjusted median per patient 30-day total cost was $23,820 (interquartile range, $19,604-$29,958). Compared with the risk-standardized average, 17 hospitals (27.4%) had lower-than-expected costs, and 14 hospitals (22.6%) had higher-than-expected costs. At the facility level, the index PCI accounted for 83.1% of the total cost (range, 60.3%-92.2%), whereas hospitalization after PCI accounted for only 5.8% (range, 2.0%-12.7%) of the 30-day total cost. Facilities with higher hospitalization rates were not more expensive (Spearman ρ=0.16; 95% confidence interval, -0.09 to 0.39; P=0.21). CONCLUSIONS: In this national study, hospitalizations in the 30 day after PCI accounted for only 5.8% of 30-day cost, and facility-level cost was not correlated with hospitalization rates. This challenges the focus on reducing hospitalizations after PCI as an effective means of improving healthcare value. Opportunities remain to improve PCI value by reducing the variation in total cost of PCI without compromising patient outcomes.

Patient access and 1-year outcomes of percutaneous coronary intervention facilities with and without on-site cardiothoracic surgery: insights from the Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking (CART) program.

BACKGROUND: The safety of percutaneous coronary intervention (PCI) at medical facilities without on-site cardiothoracic (CT) surgery has been established in clinical trials. However, the comparative effectiveness of this strategy in real-world practice, including impact on patient access and outcomes, is uncertain. The Veterans Affairs (VA) health care system has used this strategy, with strict quality oversight, since 2005, and can provide insight into this question. METHODS AND RESULTS: Among 24,387 patients receiving PCI at VA facilities between October 2007 and September 2010, 6616 (27.1%) patients underwent PCI at facilities (n=18) without on-site CT surgery. Patient drive time (as a proxy for access), procedural complications, 1-year mortality, myocardial infarction, and rates of subsequent revascularization procedures were compared by facility. Results were stratified by procedural indication (ST-segment-elevation myocardial infarction versus non-ST-segment-elevation myocardial infarction/unstable angina versus elective) and PCI volume. With the inclusion of PCI facilities without on-site CT surgery, median drive time for patients treated at those facilities decreased by 90.8 minutes (P<0.001). Procedural need for emergent coronary artery bypass graft and mortality rates were low and similar between facilities. Adjusted 1-year mortality and myocardial infarction rates were similar between facilities (hazard ratio in PCI facilities without relative to those with on-site CT surgery, 1.02; 95% confidence interval, 0.87-1.2), and not modified by either PCI indication or PCI volume. Subsequent revascularization rates were higher at sites without on-site CT surgery facilities (hazard ratio, 1.21; 95% confidence interval, 1.03-1.42). CONCLUSIONS: This study suggests that providing PCI facilities without on-site CT surgery in an integrated health care system with quality oversight improves patient access without compromising procedural or 1-year outcomes.

The current and future landscape of urinary thromboxane testing to evaluate atherothrombotic risk.

Biomarker testing for efficacy of therapy is an accepted way for clinicians to individualize dosing to genetic and/or environmental factors that may be influencing a treatment regimen. Aspirin is used by nearly 43 million Americans on a regular basis to reduce risks associated with various atherothrombotic diseases. Despite its widespread use, many clinicians are unaware of the link between suboptimal response to aspirin therapy and increased risk for inferior clinical outcomes in several disease states, and biomarker testing for efficacy of aspirin therapy is not performed as routinely as efficacy testing in other therapeutic areas. This article reviews the clinical and laboratory aspects of determining whole-body thromboxane production, particularly as it pertains to efficacy assessment of aspirin responsiveness.

Improving healthcare systems' disclosures of large-scale adverse events: a Department of Veterans Affairs leadership, policymaker, research and stakeholder partnership.

BACKGROUND: The Department of Veterans Affairs (VA) mandates disclosure of large-scale adverse events to patients, even if risk of harm is not clearly present. Concerns about past disclosures warranted further examination of the impact of this policy. OBJECTIVE: Through a collaborative partnership between VA leaders, policymakers, researchers and stakeholders, the objective was to empirically identify critical aspects of disclosure processes as a first step towards improving future disclosures. DESIGN: Semi-structured interviews were conducted with participants at nine VA facilities where recent disclosures took place. PARTICIPANTS: Ninety-seven stakeholders participated in the interviews: 38 employees, 28 leaders (from facilities, regions and national offices), 27 Veteran patients and family members, and four congressional staff members. APPROACH: Facility and regional leaders were interviewed by telephone, followed by a two-day site visit where employees, patients and family members were interviewed face-to-face. National leaders and congressional staff also completed telephone interviews. Interviews were analyzed using rapid qualitative assessment processes. Themes were mapped to the stages of the Crisis and Emergency Risk Communication model: pre-crisis, initial event, maintenance, resolution and evaluation. KEY RESULTS: Many areas for improvement during disclosure were identified, such as preparing facilities better (pre-crisis), creating rapid communications, modifying disclosure language, addressing perceptions of harm, reducing complexity, and seeking assistance from others (initial event), managing communication with other stakeholders (maintenance), minimizing effects on staff and improving trust (resolution), and addressing facilities' needs (evaluation). CONCLUSIONS: Through the partnership, five recommendations to improve disclosures during each stage of communication have been widely disseminated throughout the VA using non-academic strategies. Some improvements have been made; other recommendations will be addressed through implementation of a large-scale adverse event disclosure toolkit. These toolkit strategies will enable leaders to provide timely and transparent information to patients and families, while reducing the burden on employees and the healthcare system during these events.

Feasibility of proactive medical device surveillance: the VA Clinical Assessment Reporting and Tracking (CART) program.

BACKGROUND: Timely identification and reporting of medical device problems is critical to postmarket device surveillance programs to maximize patient safety. Cardiac catheterization laboratories are high-device utilization areas well suited for device surveillance. OBJECTIVE: To demonstrate the feasibility of the national VA Clinical Assessment, Reporting, and Tracking (CART) system, embedded in the electronic health record of all 76 VA cardiac catheterization laboratories, to document unexpected problems with medical devices at the point of care. METHODS: We evaluated 260,258 consecutive cardiac catheterization and/or percutaneous coronary intervention procedures on 175,098 Veterans between August 2006 and February 2012. Unexpected device problems (UDPs) encountered for any equipment used during a procedure were entered by clinicians at the point of care as part of regular care documentation. All UDPs were reviewed in collaboration with the FDA to ascertain the likelihood of a device defect (eg, in manufacture or design) and/or contributing to a procedural complication (level I, unlikely; level II, possibly; level III, likely). RESULTS: Of the 260,258 procedure reports, 974 (0.37%) UDP's were reported by 71 (92.2%) of the 76 VA hospitals. After triage, 739 (75.9%) were deemed level I, 196 (20.1%) level II, and 39 (4.0%) level III. Of the 39 level III reports, 12 (30.7%) are in the submission phase as a FDA MedWatch report. The number of monthly UDP reports increased significantly from 2006 to 2012 (P<0.001). CONCLUSIONS: Leveraging a clinical application embedded in the electronic health record and in collaboration with FDA, a proactive national cardiac device surveillance program has been successfully implemented in the VA.

Commentary: Evidence-Informed Recommendation to Achieve Approximate Parity in the Allowed Number of Doses for Common Psychedelics.

In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for inclusion in those regulations. If "allowable amount" limits are to be written into law to set personal possession limits, then such amounts should be more consistently related to psychedelic doses found to be safe and efficacious in clinical trials, existing data on moderate-high doses commonly used in various naturalistic settings, and the few studies that estimate psychedelic dose equivalence based on the intensity of subjective effects. In this commentary, we provide an evidence-informed table of typical moderate-high doses for seven commonly used psychedelic substances. These estimates of comparable moderate-high doses can be used to inform "allowable amount" values for psychedelic substances. When such limits are written into legislation, the adoption of evidence-informed comparable limits akin to those presented here would be an important first step toward ensuring greater parity and consistency in drug policy, relative to limits that have little or no scientific basis.

Patients with acute heart failure in the emergency department: do they all need to be admitted?

Hospitalization for acute heart failure (AHF) is associated with a high rate of postdischarge mortality and readmissions, as well as high financial costs. Reducing 30-day readmissions after AHF hospitalization is a major national quality goal intended to both improve patient outcomes and reduce costs. Although the decision threshold for the vast majority of hospitalized AHF patients lies in the emergency department (ED), the role of the ED in reducing preventable admissions has largely been ignored. While admissions for AHF also originate from outpatient clinics, the greatest opportunity to reduce inpatient admissions lies with the cohort of patients who present to the ED with AHF. Safe discharge mandates interdisciplinary collaboration, close follow-up, careful scrutiny of psychosocial and socioeconomic factors, and a shared definition of risk stratification. Although additional research is needed, strategies for lower risk patients can and should be initiated to safely discharge AHF patients from the ED.

Strategies from a nationwide health information technology implementation: the VA CART story.

The VA Cardiovascular Assessment, Reporting, and Tracking (CART) system is a customized electronic medical record system which provides standardized report generation for cardiac catheterization procedures, serves as a national data repository, and is the centerpiece of a national quality improvement program. Like many health information technology projects, CART implementation did not proceed without some barriers and resistance. We describe the nationwide implementation of CART at the 77 VA hospitals which perform cardiac catheterizations in three phases: (1) strategic collaborations; (2) installation; and (3) adoption. Throughout implementation, success required a careful balance of technical, clinical, and organizational factors. We offer strategies developed through CART implementation which are broadly applicable to technology projects aimed at improving the quality, reliability, and efficiency of health care.

Declining mortality following acute myocardial infarction in the Department of Veterans Affairs Health Care System.

BACKGROUND: Mortality from acute myocardial infarction (AMI) is declining worldwide. We sought to determine if mortality in the Veterans Health Administration (VHA) has also been declining. METHODS: We calculated 30-day mortality rates between 2004 and 2006 using data from the VHA External Peer Review Program (EPRP), which entails detailed abstraction of records of all patients with AMI. To compare trends within VHA with other systems of care, we estimated relative mortality rates between 2000 and 2005 for all males 65 years and older with a primary diagnosis of AMI using administrative data from the VHA Patient Treatment File and the Medicare Provider Analysis and Review (MedPAR) files. RESULTS: Using EPRP data on 11,609 patients, we observed a statistically significant decline in adjusted 30-day mortality following AMI in VHA from 16.3% in 2004 to 13.9% in 2006, a relative decrease of 15% and a decrease in the odds of dying of 10% per year (p = .011). Similar declines were found for in-hospital and 90-day mortality.Based on administrative data on 27,494 VHA patients age 65 years and older and 789,400 Medicare patients, 30-day mortality following AMI declined from 16.0% during 2000-2001 to 15.7% during 2004-June 2005 in VHA and from 16.7% to 15.5% in private sector hospitals. After adjusting for patient characteristics and hospital effects, the overall relative odds of death were similar for VHA and Medicare (odds ratio 1.02, 95% C.I. 0.96-1.08). CONCLUSION: Mortality following AMI within VHA has declined significantly since 2003 at a rate that parallels that in Medicare-funded hospitals.

Mortality based on the presenting electrocardiogram in patients with myocardial infarction in the troponin era.

BACKGROUND: Studies reporting short-term mortality in patients with myocardial infarction (MI) based on the initial electrocardiogram (ECG) are often limited by requiring an ischemic ECG for inclusion. Because few patients with normal or nonspecific findings were included, outcomes in these patients are less clear, especially in the troponin era. METHODS: Consecutive patients diagnosed as having MI using troponin I (TnI) over a 6-year period were included and classified into 8 mutually exclusive groups based on the initial ECG using standard criteria. Patients were included in only 1 group. The MI size was estimated using multiples of peak creatine kinase-MB (CK-MB), and 30-day mortality rate was assessed. RESULTS: Among 1641 patients with MI, patients with ST elevation represented only 22% of all MIs. Patients with ST elevation had the largest MI size, with 2 of 3 having a peak CK-MB greater than 10 times normal. In contrast, most of the patients representing all the other ECG groups had a peak CK-MB less than 5 times normal, with approximately 1 of 3 having no CK-MB elevation and were diagnosed by TnI elevation alone. Patients could be separated into a high-risk group (ST elevation, ischemia, other, or left bundle-branch block), in which mortality rate exceeded 9% (mean, 14%), and a lower-risk group (prior MI, left ventricular hypertrophy, nonspecific changes, and normal), in which the 30-day mortality rate averaged 6% (P < .001; range, 5.23%-7.1%). CONCLUSIONS: Specific ECG findings other than ischemia portend poor outcomes in patients with MI. Once MI is diagnosed, patients are no longer low risk.

Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome.

CONTEXT: Prior mechanistic studies reported that omeprazole decreases the platelet inhibitory effects of clopidogrel, yet the clinical significance of these findings is not clear. OBJECTIVE: To assess outcomes of patients taking clopidogrel with or without a proton pump inhibitor (PPI) after hospitalization for acute coronary syndrome (ACS). DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 8205 patients with ACS taking clopidogrel after discharge from 127 Veterans Affairs hospitals between October 1, 2003, and January 31, 2006. Vital status information was available for all patients through September 30, 2006. MAIN OUTCOME MEASURES: All-cause mortality or rehospitalization for ACS. RESULTS: Of 8205 patients taking clopidogrel after discharge, 63.9% (n = 5244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI (adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11-1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5244), periods of use of clopidogrel plus PPI (compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10-1.46). In analyses of secondary outcomes, patients taking clopidogrel plus PPI had a higher risk of hospitalizations for recurrent ACS compared with patients taking clopidogrel without PPI (14.6% vs 6.9%; AOR, 1.86 [95% CI, 1.57-2.20]) and revascularization procedures (15.5% vs 11.9%; AOR, 1.49 [95% CI, 1.30-1.71]), but not for all-cause mortality (19.9% vs 16.6%; AOR, 0.91 [95% CI, 0.80-1.05]). The association between use of clopidogrel plus PPI and increased risk of adverse outcomes also was consistent using a nested case-control study design (AOR, 1.32; 95% CI, 1.14-1.54). In addition, use of PPI without clopidogrel was not associated with death or rehospitalization for ACS among patients not taking clopidogrel after hospital discharge (n = 6450) (AOR, 0.98; 95% CI, 0.85-1.13). CONCLUSION: Concomitant use of clopidogrel and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS.

Survey of subjective "God encounter experiences": Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT.

Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose "God" as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose "Ultimate Reality." Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.

Predictive power of systolic function and congestive heart failure in patients with patients admitted for chest pain without ST elevation in the troponin era.

BACKGROUND: Impaired systolic function and congestive heart failure (CHF) are powerful predictors of adverse outcomes in patients with myocardial infarction (MI). However, there are little data in which both of these variables were assessed in heterogenous patients admitted from the emergency department for exclusion of ischemia. METHODS: Consecutive patients admitted for MI exclusion who had ejection fraction (EF) measured were included. Systolic dysfunction was defined as EF <40%. Congestive heart failure was diagnosed based on clinical or x-ray evidence in the first 24 hours. Multivariate analysis was used to determine predictors of 30-day and 1-year mortality. RESULTS: Of the 4,343 consecutive patients admitted, 3,682 (85%) had EF assessed (including 97% of the troponin I [TnI]-positive patients) and were included. One-year unadjusted mortality was 9.5%, but in the presence of systolic dysfunction or CHF, it increased to 22% and 26%, respectively. The most important multivariate predictors of 30-day and 1-year mortality were similar and included CHF (OR for 1-year mortality 2.5, 95% CI 1.9-3.4), TnI elevations (OR 2.0, 95% CI 1.5-2.6), and severe renal failure (OR 5.2, 95% CI 3.7-7.2). Systolic dysfunction was predictive of 1 year (OR 1.9, 95% CI 1.4-2.5) but not 30-day mortality. Results were similar in the 3,018 patients who were troponin-negative. CONCLUSIONS: Congestive heart failure is an independent predictor of both short- and long-term mortality in patients admitted for MI exclusion. In contrast, systolic dysfunction predicts long-term but not short-term mortality. One cannot be used as a surrogate for the other.

Comparison of the modification of diet in renal disease and the Cockcroft-Gault equations for predicting mortality in patients admitted for exclusion of myocardial ischemia.

Renal dysfunction is an important predictor of mortality in patients with acute coronary syndrome. Until recently, the Cockcroft-Gault (C-G) equation has been most commonly used to estimate renal function, although the Modification of Diet in Renal Disease (MDRD) equation is now recommended. Which equation better predicts mortality is unclear. Consecutive patients without ST elevation on the initial electrocardiogram admitted for exclusion of myocardial ischemia were included. Admission creatinine was used to estimate renal function, and 30-day and 1-year mortality were compared after classifying patients as having no (estimated glomerular filtration rate [eGFR] > or =60 ml/min/m(2)), moderate (eGFR 30 to 59 ml/min/ m(2)), or severe (eGFR <30 ml/min/m(2)) renal dysfunction using the 2 equations. Of the 4,343 patients (49% women, 64% African-American) included, 16% had troponin I elevations consistent with myocardial infarction, and 1-year mortality was 10%. Agreement between the 2 equations was high (r = 0.87 p <0.001, concordance 86%). Mortality was similar in the 2 renal function classifications, with no significant differences based on race or troponin I status at 30 days or 1 year. However, the area of the receiver operator characteristic curve was significantly larger for predicting 1-year mortality with the C-G equation (0.75 [0.72 to 0.77] vs 0.71 [0.68 to 0.73]; p <0.01); both were superior to creatinine alone (0.68 [0.66 to 0.71]; p <0.01 for both C-G and MDRD). Results for 30-day mortality were similar. In conclusion, the C-G equation appears to be superior to the MDRD equation for predicting short- and long-term mortality in patients admitted for exclusion of ischemia, although differences are minor.

Value of simultaneous functional assessment in association with acute rest perfusion imaging for predicting short- and long-term outcomes in emergency department patients with chest pain.

BACKGROUND: Rest tomographic myocardial perfusion imaging (MPI) has significant utility for clinical decision making in emergency department chest pain patients. The role of functional data, commonly acquired with perfusion, has not been systematically evaluated. METHODS AND RESULTS: Low- to moderate-risk patients undergoing rest MPI for risk stratification were included. The patients' MPI findings were classified as normal (normal perfusion or function), abnormal (perfusion defect with abnormal regional function), or discordant (perfusion defect with normal regional function). Ejection fraction was determined from the gated MPI studies. Events based on perfusion classifications and ejection fraction were evaluated. A total of 2,826 consecutive patients (abnormal MPI results in 40%, normal in 32%, and discordant in 27%) were studied. Outcomes were similar for those with normal MPI results versus those with discordant MPI results (myocardial infarction [MI] based on troponin I [TnI], 3.5% vs 4.0%; MI based on creatine kinase-MB, 1.5% vs 1.7%; revascularization, 5.2% vs 5.5%; and MI/revascularization based on TnI, 7.9% vs 8.1%) (P = not significant for all). Both groups had significantly fewer events (P < .001 for all) when compared with patients with abnormal MPI studies (MI based on TnI, 15%; MI based on creatine kinase-MB, 10%; revascularization, 17%; MI based on TnI or revascularization, 24%). The mortality rate was not different among the 3 groups. Multivariate analysis showed that mild/moderate and severe systolic dysfunction were independent predictors of 30-day and 1-year mortality rates (P = .001). CONCLUSIONS: The concurrent evaluation of perfusion and function (regional and global) with MPI provides significant risk/outcome predictive power.

Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome.

CONTEXT: It is unknown whether patients are at increased short-term risk for adverse events following clopidogrel cessation. OBJECTIVE: To assess the rates of adverse events after stopping treatment with clopidogrel in a national sample of patients with acute coronary syndrome (ACS). DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 3137 patients with ACS discharged from 127 Veterans Affairs hospitals between October 1, 2003, and March 31, 2005, with posthospital treatment with clopidogrel. MAIN OUTCOME MEASURE: Rate of all-cause mortality or acute myocardial infarction (AMI) after stopping treatment with clopidogrel. RESULTS: Mean (SD) follow-up after stopping treatment with clopidogrel was 196 (152) days for medically treated patients with ACS without stents (n = 1568) and 203 (148) days for patients with ACS treated with percutaneous coronary intervention (PCI) (n = 1569). Among medically treated patients, mean (SD) duration of clopidogrel treatment was 278 [corrected] (169) [corrected] days and death or AMI occurred in 17.1% (n = 268) of patients, with 60.8% (n = 163) of events occurring during 0 to 90 days, 21.3% (n = 57) during 91 to 180 days, and 9.7% (n = 26) during 181 to 270 days after stopping treatment with clopidogrel. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90-day interval after stopping treatment with clopidogrel was associated with a significantly higher risk of adverse events (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.46-2.69 vs the interval of 91-180 days). Similarly, among PCI-treated patients with ACS, mean (SD) duration of clopidogrel treatment was 302 [corrected] (151) [corrected] days and death or AMI occurred in 7.9% (n = 124) of patients, with 58.9% (n = 73) of events occurring during 0 to 90 days, 23.4% (n = 29) during 91 to 180 days, and 6.5% (n = 8) during 181 to 270 days after stopping clopidogrel treatment. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90-day interval after stopping clopidogrel treatment was associated with a significantly higher risk of adverse events (IRR, 1.82; 95% CI, 1.17-2.83). CONCLUSIONS: We observed a clustering of adverse events in the initial 90 days after stopping clopidogrel among both medically treated and PCI-treated patients with ACS, supporting the possibility of a clopidogrel rebound effect. Additional studies are needed to confirm the clustering of events after stopping clopidogrel, including associations with cardiovascular mortality and reasons for stopping clopidogrel, as well as to determine the mechanism of this phenomenon, and to identify strategies to reduce early events after clopidogrel cessation.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.