Monique L. Anderson

Compliance with Results Reporting at ClinicalTrials.gov

BACKGROUND The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. METHODS Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. RESULTS From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. CONCLUSIONS Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).

Association of Bystander and First-Responder Intervention With Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010-2013

IMPORTANCE Out-of-hospital cardiac arrest is associated with low survival, but early cardiopulmonary resuscitation (CPR) and defibrillation can improve outcomes if more widely adopted. OBJECTIVE To examine temporal changes in bystander and first-responder resuscitation efforts before arrival of the emergency medical services (EMS) following statewide initiatives to improve bystander and first-responder efforts in North Carolina from 2010-2013 and to examine the association between bystander and first-responder resuscitation efforts and survival and neurological outcome. DESIGN, SETTINGS, AND PARTICIPANTS We studied 4961 patients with out-of-hospital cardiac arrest for whom resuscitation was attempted and who were identified through the Cardiac Arrest Registry to Enhance Survival (2010-2013). First responders were dispatched police officers, firefighters, rescue squad, or life-saving crew trained to perform basic life support until arrival of the EMS. EXPOSURES Statewide initiatives to improve bystander and first-responder interventions included training members of the general population in CPR and in use of automated external defibrillators (AEDs), training first responders in team-based CPR including AED use and high-performance CPR, and training dispatch centers in recognition of cardiac arrest. MAIN OUTCOMES AND MEASURES The proportion of bystander and first-responder resuscitation efforts, including the combination of efforts between bystanders and first responders, from 2010 through 2013 and the association between these resuscitation efforts and survival and neurological outcome. RESULTS The combination of bystander CPR and first-responder defibrillation increased from 14.1% (51 of 362; 95% CI, 10.9%-18.1%) in 2010 to 23.1% (104 of 451; 95% CI, 19.4%-27.2%) in 2013 (P < .01). Survival with favorable neurological outcome increased from 7.1% (82 of 1149; 95% CI, 5.8%-8.8%) in 2010 to 9.7% (129 of 1334; 95% CI, 8.2%-11.4%) in 2013 (P = .02) and was associated with bystander-initiated CPR. Adjusting for age and sex, bystander and first-responder interventions were associated with higher survival to hospital discharge. Survival following EMS-initiated CPR and defibrillation was 15.2% (30 of 198; 95% CI, 10.8%-20.9%) compared with 33.6% (38 of 113; 95% CI, 25.5%-42.9%) following bystander-initiated CPR and defibrillation (odds ratio [OR], 3.12; 95% CI, 1.78-5.46); 24.2% (83 of 343; 95% CI, 20.0%-29.0%) following bystander CPR and first-responder defibrillation (OR, 1.70; 95% CI, 1.06-2.71); and 25.2% (109 of 432; 95% CI, 21.4%-29.6%) following first-responder CPR and defibrillation (OR, 1.77; 95% CI, 1.13-2.77). CONCLUSIONS AND RELEVANCE Following a statewide educational intervention on rescusitation training, the proportion of patients receiving bystander-initiated CPR and defibrillation by first responders increased and was associated with greater likelihood of survival. Bystander-initiated CPR was associated with greater likelihood of survival with favorable neurological outcome.

Part 6: Alternative Techniques and Ancillary Devices for Cardiopulmonary Resuscitation 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

Conventional cardiopulmonary resuscitation (CPR) consisting of manual chest compressions with rescue breaths is inherently inefficient with respect to generating cardiac output. A variety of alternatives and adjuncts to conventional CPR have been developed, with the aim of enhancing perfusion during resuscitation from cardiac arrest. Since the publication of the 2010 American Heart Association (AHA) Guidelines for CPR and Emergency Cardiovascular Care (ECC),1 a number of clinical trials have provided additional data on the effectiveness of these alternatives and adjuncts. Compared with conventional CPR, many of these techniques and devices require specialized equipment and training. Some have only been tested in highly selected subgroups of cardiac arrest patients; this context must be considered when rescuers or healthcare systems are considering implementation. ### Methodology The recommendations in this 2015 AHA Guidelines Update for CPR and ECC are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) after the publication of the ILCOR 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 2,3 and was completed in February 2015.4,5 In this in-depth evidence review process, the ILCOR Advanced Life Support (ALS) Task Force examined topics and then generated a prioritized list of questions for systematic review. Questions were first formulated in PICO (population, intervention, comparator, outcome) format,6 search strategies and criteria for inclusion and exclusion of articles were defined, and then a search for relevant articles was performed. The evidence was evaluated by the ILCOR ALS Task Force by using the standardized methodological approach proposed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group.7 The quality of the evidence was categorized based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and …

Regional Variation in Out-of-Hospital Cardiac Arrest Survival in the United States

Background— Although previous studies have shown marked variation in out-of-hospital cardiac arrest survival across US regions, factors underlying this survival variation remain incompletely explained. Methods and Results— Using data from the Cardiac Arrest Registry to Enhance Survival, we identified 96 662 adult patients with out-of-hospital cardiac arrest in 132 US counties. We used hierarchical regression models to examine county-level variation in rates of survival and survival with functional recovery (defined as Cerebral Performance Category score of 1 or 2) and examined the contribution of demographics, cardiac arrest characteristics, bystander cardiopulmonary resuscitation, automated external defibrillator use, and county-level sociodemographic factors in survival variation across counties. A total of 9317 (9.6%) patients survived to discharge, and 7176 (7.4%) achieved functional recovery. At a county level, there was marked variation in rates of survival to discharge (range, 3.4%–22.0%; median odds ratio, 1.40; 95% confidence interval, 1.32–1.46) and survival with functional recovery (range, 0.8%–21.0%; median odds ratio, 1.53; 95% confidence interval, 1.43–1.62). County-level rates of bystander cardiopulmonary resuscitation and automated external defibrillator use were positively correlated with both outcomes (P<0.0001 for all). Patient demographic and cardiac arrest characteristics explained 4.8% and 27.7% of the county-level variation in survival, respectively. Additional adjustment of bystander cardiopulmonary resuscitation and automated external defibrillator explained 41% of the survival variation, and this increased to 50.4% after adjustment of county-level sociodemographic factors. Similar findings were noted in analyses of survival with functional recovery. Conclusions— Although out-of-hospital cardiac arrest survival varies significantly across US counties, a substantial proportion of the variation is attributable to differences in bystander response across communities.

Rates of cardiopulmonary resuscitation training in the United States.

IMPORTANCE Prompt bystander cardiopulmonary resuscitation (CPR) improves the likelihood of surviving an out-of-hospital cardiac arrest. Large regional variations in survival after an out-of-hospital cardiac arrest have been noted. OBJECTIVES To determine whether regional variations in county-level rates of CPR training exist across the United States and the factors associated with low rates in US counties. DESIGN, SETTING, AND PARTICIPANTS We used a cross-sectional ecologic study design to analyze county-level rates of CPR training in all US counties from July 1, 2010, through June 30, 2011. We used CPR training data from the American Heart Association, the American Red Cross, and the Health & Safety Institute. Using multivariable logistic regression models, we examined the association of annual rates of adult CPR training of citizens by these 3 organizations (categorized as tertiles) with a countys geographic, population, and health care characteristics. EXPOSURE Completion of CPR training. MAIN OUTCOME AND MEASURES Rate of CPR training measured as CPR course completion cards distributed and CPR training products sold by the American Heart Association, persons trained in CPR by the American Red Cross, and product sales data from the Health & Safety Institute. RESULTS During the study period, 13.1 million persons in 3143 US counties received CPR training. Rates of county training ranged from 0.00% to less than 1.29% (median, 0.51%) in the lower tertile, 1.29% to 4.07% (median, 2.39%) in the middle tertile, and greater than 4.07% or greater (median, 6.81%) in the upper tertile. Counties with rates of CPR training in the lower tertile were more likely to have a higher proportion of rural areas (adjusted odds ratio, 1.12 [95% CI, 1.10-1.15] per 5-percentage point [PP] change), higher proportions of black (1.09 [1.06-1.13] per 5-PP change) and Hispanic (1.06 [1.02-1.11] per 5-PP change) residents, a lower median household income (1.18 [1.04-1.34] per

Short- and Long-Term Outcomes of Coronary Stenting in Women Versus MenClinical Perspective

10 000 decrease), and a higher median age (1.28 [1.04-1.58] per 10-year change). Counties in the South, Midwest, and West were more likely to have rates of CPR training in the lower tertile compared with the Northeast (adjusted odds ratios, 7.78 [95% CI, 3.66-16.53], 5.56 [2.63-11.75], and 5.39 [2.48-11.72], respectively). CONCLUSIONS AND RELEVANCE Annual rates of US CPR training are low and vary widely across communities. Counties located in the South, those with higher proportions of rural areas and of black and Hispanic residents, and those with lower median household incomes have lower rates of CPR training than their counterparts. These data contribute to known geographic disparities in survival of cardiac arrest and offer opportunities for future community interventions.

Short- and Long-Term Outcomes of Coronary Stenting in Women Versus Men Results From the National Cardiovascular Data Registry Centers for Medicare & Medicaid Services Cohort

Background— Conflicting evidence exists on sex-based outcomes after coronary stenting. Methods and Results— Data on 426 996 patients ≥65 years old (42.3% women) from the National Cardiovascular Data Registry CathPCI Registry (2004–2008) were linked to Medicare inpatient claims to compare in-hospital outcomes by sex and long-term outcomes by sex and stent type. In-hospital complications were more frequent in women than in men: death (3869 [2.2%] versus 3737 [1.6%]; adjusted odds ratio, 1.41; 95% confidence interval [CI], 1.33–1.49), myocardial infarction (2365 [1.3%] versus 2858 [1.2%]; odds ratio, 1.19; 95% CI, 1.11–1.27), bleeding (7860 [4.4%] versus 5627 [2.3%]; odds ratio, 1.86; 95% CI, 1.79–1.93), and vascular complications (2381 [1.3%] versus 1648 [0.7%]; odds ratio, 1.85; 95% CI, 1.73–1.99). At 20.4 months, women had a lower adjusted risk of death (hazard ratio [HR], 0.92; 95% CI, 0.90–0.94) but similar rates of myocardial infarction, revascularization, and bleeding. Relative to bare metal stent use, drug-eluting stent use was associated with similar improved long-term outcomes in both sexes: death (women: adjusted HR, 0.78; 95% CI, 0.76–0.81; men: HR, 0.77; 95% CI, 0.74–0.79), myocardial infarction (women: HR, 0.79; 95% CI, 0.74–0.84; men: HR, 0.81; 95% CI, 0.77–0.85), and revascularization (women: HR, 0.93; 95% CI, 0.90–0.97; men: HR, 0.91; 95% CI, 0.88–0.94). There was no interaction between sex and stent type for long-term outcomes. Conclusions— In contemporary coronary stenting, women have a slightly higher procedural risk than men but have better long-term survival. In both sexes, use of a drug-eluting stent is associated with lower long-term likelihood for death, myocardial infarction, and revascularization.

Differences in the Profile, Treatment, and Prognosis of Patients With Cardiogenic Shock by Myocardial Infarction Classification A Report From NCDR

BACKGROUND Conflicting evidence exists on sex-based outcomes after coronary stenting. METHODS AND RESULTS Data on 426 996 patients ≥65 years old (42.3% women) from the National Cardiovascular Data Registry CathPCI Registry (2004-2008) were linked to Medicare inpatient claims to compare in-hospital outcomes by sex and long-term outcomes by sex and stent type. In-hospital complications were more frequent in women than in men: death (3869 [2.2%] versus 3737 [1.6%]; adjusted odds ratio, 1.41; 95% confidence interval [CI], 1.33-1.49), myocardial infarction (2365 [1.3%] versus 2858 [1.2%]; odds ratio, 1.19; 95% CI, 1.11-1.27), bleeding (7860 [4.4%] versus 5627 [2.3%]; odds ratio, 1.86; 95% CI, 1.79-1.93), and vascular complications (2381 [1.3%] versus 1648 [0.7%]; odds ratio, 1.85; 95% CI, 1.73-1.99). At 20.4 months, women had a lower adjusted risk of death (hazard ratio [HR], 0.92; 95% CI, 0.90-0.94) but similar rates of myocardial infarction, revascularization, and bleeding. Relative to bare metal stent use, drug-eluting stent use was associated with similar improved long-term outcomes in both sexes: death (women: adjusted HR, 0.78; 95% CI, 0.76-0.81; men: HR, 0.77; 95% CI, 0.74-0.79), myocardial infarction (women: HR, 0.79; 95% CI, 0.74-0.84; men: HR, 0.81; 95% CI, 0.77-0.85), and revascularization (women: HR, 0.93; 95% CI, 0.90-0.97; men: HR, 0.91; 95% CI, 0.88-0.94). There was no interaction between sex and stent type for long-term outcomes. CONCLUSIONS In contemporary coronary stenting, women have a slightly higher procedural risk than men but have better long-term survival. In both sexes, use of a drug-eluting stent is associated with lower long-term likelihood for death, myocardial infarction, and revascularization.

Association between hospital post-resuscitative performance and clinical outcomes after out-of-hospital cardiac arrest

Background— Cardiogenic shock is a deadly complication of an acute myocardial infarction (MI). We sought to characterize differences in patient features, treatments, and outcomes of cardiogenic shock by MI classification: ST–segment-elevation MI (STEMI) versus non–ST-segment elevation MI (NSTEMI). Methods and Results— We compared differences in care by the shock status of 235 541 patients with STEMI and NSTEMI treated at 392 US hospitals from 2007 to 2011. Cardiogenic shock occurred in 12.2% of patients with STEMI versus 4.3% of patients with NSTEMI. Compared with STEMI shock, NSTEMI shock was more likely in patients who were older and predominantly women; had diabetes mellitus, hypertension, previous heart failure, MI, or peripheral arterial disease; and who received coronary artery bypass grafting (11.6% versus 21.2%; P<0.0001) but less likely to have received percutaneous coronary intervention (84.2% versus 35.3%; P<0.0001). Compared with patients with STEMI presenting with shock at admission, patients with NSTEMI presenting with shock had longer delays to percutaneous coronary intervention (1.2 versus 3.2 hours) and coronary artery bypass grafting (7.9 versus 55.9 hours). Cardiogenic shock in patients with STEMI was associated with a lower mortality risk (33.1% shock versus 2.0% no shock; adjusted odds ratio, 14.1; 95% confidence interval, 13.0–15.4; interaction P value <0.0001) compared with patients with NSTEMI (40.8% shock versus 2.3% no shock, odds ratio, 19.0; 95% confidence interval, 17.1–21.2). Conclusions— Cardiogenic shock is associated with high mortality in patients with STEMI and NSTEMI. However, urgent revascularization is more commonly pursued in patients with STEMI presenting with shock than in patients with NSTEMI. More research is needed to improve the outcomes for patients with MI presenting with shock, particularly those presenting with NSTEMI.

Association of neighborhood characteristics with incidence of out-of-hospital cardiac arrest and rates of bystander-initiated CPR: Implications for community-based education intervention

BACKGROUND Survival varies among those resuscitated from out-of-hospital cardiac arrest (OHCA). Evidence-based performance measures have been used to describe hospital quality of care in conditions such as acute coronary syndrome and major trauma. It remains unclear if adherence to performance measures is associated with better outcome in patients hospitalized after OHCA. OBJECTIVES To assess whether a composite performance score based on evidence-based guidelines for care of patients resuscitated from OHCA was independently associated with clinical outcomes. METHODS Included were 3252 patients with OHCA who received care at 111 U.S. and Canadian hospitals participating in the Resuscitation Outcomes Consortium (ROC-PRIMED) study between June 2007 and October 2009. We calculated composite performance scores for all patients, aggregated these at the hospital level, then associated them with patient mortality and favorable neurological status at discharge. RESULTS Composite performance scores varied widely (median [IQR] scores from lowest to highest hospital quartiles, 21% [20%, 25%] vs. 59% [55%, 64%]. Adjusted survival to discharge increased with each quartile of performance score (from lowest to highest: 16.2%, 20.8%, 28.5%, 34.8%, P<0.01), with similar findings for adjusted rates of good neurologic status. Hospital score was significantly associated with outcome after risk adjustment for established baseline factors (highest vs. lowest adherence quartile: adjusted OR of survival 1.64; 95% CI 1.13, 2.38). CONCLUSIONS Greater survival and favorable neurologic status at discharge were associated with greater adherence to recommended hospital based post-resuscitative care guidelines. Consideration should be given to measuring, reporting and improving hospital adherence to guideline-based performance measures, which could improve outcomes following OHCA.