3D Capsule Networks for Brain Image Segmentation.

BACKGROUND AND PURPOSE: Current autosegmentation models such as UNets and nnUNets have limitations, including the inability to segment images that are not represented during training and lack of computational efficiency. 3D capsule networks have the potential to address these limitations. MATERIALS AND METHODS: We used 3430 brain MRIs, acquired in a multi-institutional study, to train and validate our models. We compared our capsule network with standard alternatives, UNets and nnUNets, on the basis of segmentation efficacy (Dice scores), segmentation performance when the image is not well-represented in the training data, performance when the training data are limited, and computational efficiency including required memory and computational speed. RESULTS: The capsule network segmented the third ventricle, thalamus, and hippocampus with Dice scores of 95%, 94%, and 92%, respectively, which were within 1% of the Dice scores of UNets and nnUNets. The capsule network significantly outperformed UNets in segmenting images that were not well-represented in the training data, with Dice scores 30% higher. The computational memory required for the capsule network is less than one-tenth of the memory required for UNets or nnUNets. The capsule network is also >25% faster to train compared with UNet and nnUNet. CONCLUSIONS: We developed and validated a capsule network that is effective in segmenting brain images, can segment images that are not well-represented in the training data, and is computationally efficient compared with alternatives.

Digitizing clinical trials.

Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.

What are covering doctors told about their patients? Analysis of sign-out among internal medicine house staff.

OBJECTIVES: To characterise and assess sign-out practices among internal medicine house staff, and to identify contributing factors to sign-out quality. DESIGN: Prospective audiotape study. SETTING: Medical wards of an acute teaching hospital. PARTICIPANTS: Eight internal medicine house staff teams. MEASUREMENTS: Quantitative and qualitative assessments of sign-out content, clarity of language, environment, and factors affecting quality and comprehensiveness of oral sign-out. RESULTS: Sign-out sessions (n = 88) contained 503 patient sign-outs. Complete written sign-outs accompanying 50/88 sign-out sessions (57%) were collected. The median duration of sign-out was 35 s (IQR 19-62) per patient. The combined oral and written sign-outs described clinical condition, hospital course and whether or not there was a task to be completed for 184/298 (62%) of patients. The least commonly conveyed was the patient's current clinical condition, described in 249/503 (50%) of oral sign-outs and 117/306 (38%) of written sign-outs. Most patient sign-outs (298/503, 59%) included no questions from the sign-out recipient (median 0, IQR 0-1). Five factors were associated with a higher rate of oral content inclusion: familiarity with the patient, sense of responsibility for the patient, only one sign-out per day, presence of a senior resident and a comprehensive written sign-out. Omissions and mischaracterisations of data were present in 22% of sign-outs repeated in a single day. CONCLUSIONS: Sign-outs are not uniformly comprehensive and include few questions. The findings suggest that several changes may be required to improve sign-out quality, including standardising key content, minimising sign-outs that do not involve the primary team, templating written sign-outs, emphasising the role of sign-out in maintaining patient safety and fostering a sense of direct responsibility for patients among covering staff.

Ischaemic symptoms, quality of care and mortality during myocardial infarction.

OBJECTIVE: To study in myocardial infarction (MI) whether documentation of ischaemic symptoms is associated with quality of care and outcomes, and to compare patient reports of ischaemic symptoms during interviews with chart documentation. DESIGN: Observational acute MI study from 2003 to 2004 (Prospective Registry Evaluating Myocardial Infarction: Event and Recovery). SETTING: 19 diverse US hospitals. PATIENTS: 2094 consecutive patients with MI (10 911 patients screened; 3953 patients were eligible and enrolled) with both positive cardiac enzymes and other evidence of infarction (eg, symptoms, electrocardiographic changes). Transferred patients and those with confounding non-cardiac comorbidity were not included (n = 1859). MAIN OUTCOME MEASURES: Quality of care indicators and adjusted in-hospital survival. RESULTS: The records of 10% of all patients with MI (217/2094) contained no documented ischaemic symptoms at presentation. Patients without documented symptoms were less likely (p<0.05) to receive aspirin (89% vs 96%) or beta-blockers (77% vs 90%) within 24 hours, reperfusion therapy for ST-elevation MI (7% vs 58%) or to survive their hospitalisation (adjusted odds ratio = 3.2, 95% CI 1.8 to 5.8). Survivors without documented symptoms were also less likely (p<0.05) to be discharged with aspirin (87% vs 93%), beta-blockers (81% vs 91%), ACE/ARB (67% vs 80%), or smoking cessation counselling (46% vs 66%). In the subset of 1356 (65%) interviewed patients, most of those without documented ischaemic symptoms (75%) reported presenting symptoms consistent with ischaemia. CONCLUSIONS: Failure to document patients' presenting MI symptoms is associated with poorer quality of care from admission to discharge, and higher in-hospital mortality. Symptom recognition may represent an important opportunity to improve the quality of MI care.

The impact of late career job loss on myocardial infarction and stroke: a 10 year follow up using the health and retirement survey.

BACKGROUND: Involuntary job loss is a major life event associated with social, economic, behavioural, and health outcomes, for which older workers are at elevated risk. OBJECTIVE: To assess the 10 year risk of myocardial infarction (MI) and stroke associated with involuntary job loss among workers over 50 years of age. METHODS: Analysing data from the nationally representative US Health and Retirement Survey (HRS), Cox proportional hazards analysis was used to estimate whether workers who suffered involuntary job loss were at higher risk for subsequent MI and stroke than individuals who continued to work. The sample included 4301 individuals who were employed at the 1992 study baseline. RESULTS: Over the 10 year study frame, 582 individuals (13.5% of the sample) experienced involuntary job loss. After controlling for established predictors of the outcomes, displaced workers had a more than twofold increase in the risk of subsequent MI (hazard ratio (HR) = 2.48; 95% confidence interval (CI) = 1.49 to 4.14) and stroke (HR = 2.43; 95% CI = 1.18 to 4.98) relative to working persons. CONCLUSION: Results suggest that the true costs of late career unemployment exceed financial deprivation, and include substantial health consequences. Physicians who treat individuals who lose jobs as they near retirement should consider the loss of employment a potential risk factor for adverse vascular health changes. Policy makers and programme planners should also be aware of the risks of job loss, so that programmatic interventions can be designed and implemented to ease the multiple burdens of joblessness.

Knowledge of blood pressure levels and targets in patients with coronary artery disease in the USA.

Little is known about patient awareness of nationally recommended blood pressure targets, especially among patients with cardiac disease. To examine this issue, we interviewed 738 patients hospitalized with coronary artery disease to assess their knowledge of their systolic and diastolic blood pressure levels as well as corresponding national targets. We used bivariate and multivariate analyses to determine if any patient demographic or clinical characteristics were associated with blood pressure knowledge. Only 66.1% of patients could recall their own systolic and diastolic blood pressure levels. Only 48.9% of all patients could correctly name targets for these values. Knowledge of target blood pressure levels was particularly poor among patients who were female (odds ratio (OR) 0.69; 95% confidence interval (CI) 0.49-0.98), aged > or =60 years (OR 0.70, CI 0.51-0.97), without any college education (OR 0.48, CI 0.35-0.65), without a documented history of hypertension (OR 0.57, CI 0.39-0.84), and with known diabetes (OR 0.46, CI 0.33-0.66). Patients in the highest risk group, according to Joint National Committee guidelines stratification, were no more knowledgeable about their blood pressure levels and targets than lower risk patients. A significant proportion of patients hospitalized with coronary artery disease do not know their own blood pressure levels or targets. Current blood pressure education efforts appear inadequate, particularly for certain patient subgroups in which hypertension is an important modifiable risk factor.

Impact of managed care on cancer trial enrollment.

PURPOSE: To determine the relationship between managed care market activity and cancer trial enrollment. METHODS: Trial participant data were obtained from the National Cancer Institute. Participants in cooperative group trials of breast, colorectal, lung, or prostate cancer during the years 1996 through 2001 were assigned to counties based on their zip code of residence. Linear regression was used to determine the relationship between county enrollment rate and two measures of county managed care activity (penetration and index of competition [IOC]), adjusting for other county characteristics. RESULTS: In bivariate analysis, there was a strong inverse correlation between trial enrollment rate and IOC (r = -0.23; P < .001) as well as the proportion of the population uninsured (-0.31; P < .001) and the percentage below poverty (-0.16; P < .001). In the multivariate model, greater county managed care competition (IOC) was inversely related to trial enrollment rate (P < .008 for comparison of each quartile v lowest quartile) after accounting for managed care penetration, proportion uninsured, and other county characteristics. Counties in the lowest quartile of managed care penetration tended to have lower enrollment rates than the remaining counties (r = -0.05; P = .048), while counties in the second, third, and fourth quartiles of penetration all had similar enrollment rates to one another. CONCLUSION: Cancer trial enrollment rates were suboptimal across all counties, and counties with higher levels of managed care competition had significantly lower enrollment rates. The relationship between managed care penetration and trial enrollment was less consistent. Future efforts to enhance trial participation should address the potential negative influence of market factors.

Cancer trial enrollment after state-mandated reimbursement.

BACKGROUND: Recruitment of patients into cancer research studies is exceedingly difficult, particularly for early phase trials. Payer reimbursement policies are a frequently cited barrier. We examined whether state policies that ensure coverage of routine medical care costs for cancer trial participants are associated with an increase in clinical trial enrollment. METHODS: We used logistic Poisson regressions to analyze enrollment in National Cancer Institute phase II and phase III Clinical Trials Cooperative Group trials and compared changes in trial enrollment rates between 1996 and 2001 of privately insured cancer patients who resided in the four states that enacted coverage policies in 1999 with enrollment rates in states without such policies. All statistical tests were two-sided. RESULTS: Trial enrollment rates increased in the coverage and noncoverage states by 24.9% (95% confidence interval [CI] = 22.8% to 27.0%) and 28.8% (95% CI = 27.7% to 29.8%) per year, respectively, from 1996 through 2001. After implementation of the coverage policies in 1999 in four states, there was a 21.7% (95% CI = 3.8% to 42.6%) annual increase in phase II trial enrollment in coverage states, compared with a 15.6% (95% CI = 8.8% to 21.8%) annual decrease in noncoverage states (P<.001). After accounting for secular trend, cancer type, and race in multivariable analyses, the odds ratio (OR) for a phase II trial participant residing in a coverage versus a noncoverage state after 1999 was 1.59 per year (95% CI = 1.22 to 2.07; P =.001). In a multivariable analysis of phase III trial participation, there was a decrease in the odds of residing in a coverage state after 1999 (OR = 0.90, 95% CI = 0.84 to 0.98; P =.011). CONCLUSION: State coverage policies were associated with a statistically significant increase in phase II cancer trial participation and did not increase phase III cancer trial enrollment.

Data feedback efforts in quality improvement: lessons learned from US hospitals.

BACKGROUND: Data feedback is a fundamental component of quality improvement efforts, but previous studies provide mixed results on its effectiveness. This study illustrates the diversity of hospital based efforts at data feedback and highlights successful strategies and common pitfalls in designing and implementing data feedback to support performance improvement. METHODS: Open ended interviews with 45 clinical and administrative staff in eight US hospitals in 2000 concerning their perceptions about the effectiveness of data feedback in supporting performance improvement efforts were analysed. The hospitals were chosen to represent a range of sizes, geographical regions, and beta blocker improvement rates over a 3 year period. Data were organized and analyzed in NUD-IST 4 using the constant comparative method of qualitative data analysis. RESULTS: Although the data feedback efforts at the hospitals were diverse, the interviews suggested that seven key themes may be important: (1) data must be perceived by physicians as valid to motivate change; (2) it takes time to develop the credibility of data within a hospital; (3) the source and timeliness of data are critical to perceived validity; (4) benchmarking improves the meaningfulness of data feedback; (5) physician leaders can enhance the effectiveness of data feedback; (6) data feedback that profiles an individual physician's practices can be effective but may be perceived as punitive; (7) data feedback must persist to sustain improved performance. Embedded in several themes was the view that the effectiveness of data feedback depends not only on the quality and timeliness of the data, but also on the organizational context in which such efforts are implemented. CONCLUSIONS: Data feedback is a complex and textured concept. Data feedback strategies that might be most effective are suggested, as well as potential pitfalls in using data to promote performance improvement.

Overestimation of genetic risks owing to small sample sizes in cardiovascular studies.

We sought evidence of publication bias to explain conflicting findings in studies of angiotensin-converting enzyme deletion polymorphism (ACE D) and glycoprotein IIIa PlA2 (PLA2) polymorphism and the risk of myocardial infarction. Factor 5 Leiden (F5L), a well-established thrombotic risk factor, served as an internal comparison. We conducted systematic reviews of published studies involving ACE D, PLA2, F5L and relevant outcomes, searching medline (January 1990 through February, 2001), bibliographies, and meta-analyses. Random effects pooled odds ratios (95% confidence interval) for cardiovascular outcomes were as follows: PLA2 (n = 13,167 subjects): 1.13 (1.02, 1.26); ACE D (n = 42,140 subjects): 1.22 (1.11, 1.35); and F5L (n = 27,277 subjects): 4.43 (3.65, 5.38). However, funnel plots of ACE D and PLA2, but not F5L, showed an inverse relationship between sample size and odds ratios for ACE D (p = 0.02) and PLA2 (p = 0.04) but not F5L (p = 0.65) by Egger's test for potential publication bias. Despite research-based genotyping of over 50,000 subjects, the overall risk for myocardial infarction as a result of PLA2 and ACE D remains doubtful. Our study provides a clear example of how publication of underpowered studies can spuriously implicate polymorphisms as genetic risk factors.

Sex differences in cardiac catheterization: the role of physician gender.

CONTEXT: Many studies indicate that women are less likely than men to undergo cardiac procedures after an acute myocardial infarction (AMI), raising concerns of sexual bias in clinical care. However, no data exist regarding the relationship between patient sex, physician sex, and use of cardiac procedures. OBJECTIVE: To determine whether sex differences in cardiac catheterization after AMI were greater when patients were treated by male attending physicians compared with female attending physicians. DESIGN, SETTING, AND PATIENTS: Analysis of data from the Cooperative Cardiovascular Project, a retrospective medical record review. A total of 104 >231 Medicare fee-for-service beneficiaries who were hospitalized in US acute care hospitals for an AMI between January 1994 and February 1995. MAIN OUTCOME MEASURE: Use of cardiac catheterization within 60 days of admission, compared between the 4 groups of patient sex-physician sex combinations. RESULTS: Women underwent fewer cardiac catheterizations than men when treated by either male physicians (38.6% vs 50.8%; P =.001) or female physicians (34.8% vs 45.8%; P =.001). Sex differences in procedure use were not greater when a patient and physician were of different sexes (P for interaction =.85). After potential confounders in multivariable analysis were accounted for, women were less likely to undergo cardiac catheterization (risk ratio, 0.90 [95% confidence interval (CI), 0.88-0.92]), regardless of the treating physician's sex. Patients treated by male physicians were more likely to undergo cardiac catheterization (risk ratio, 1.06 [95%CI, 1.02-1.10]) than those treated by female physicians, regardless of patient sex. CONCLUSIONS: Women who have had an AMI undergo a cardiac catheterization less often than men, whether treated by a male or female physician. These results suggest that factors other than sexual bias by male physicians toward women account for sex differences in cardiac procedure use.

The Connecticut Cardiovascular Consortium: a unique, state-wide research collaboration to advance clinical outcomes in patients with heart disease.

The establishment of "best clinical practices" founded upon evidence-based medicine has become an increasingly important priority. Frequently, management guidelines are derived from published research data and disseminated among practitioners to help optimize patient care. The ultimate clinical impact of these guidelines in the "real world," however, is often clouded by an incomplete assessment of patient outcomes throughout the continuum of health-care delivery models. In order to address this gap in clinical outcome assessment, we propose to establish the Connecticut Cardiovascular Consortium. The Consortium will consist of a collaborative partnership among all 31 Connecticut hospitals working in concert with Connecticut Office of Health Care Access (OHCA). The primary objective of the Consortium will be to assess, compare, and optimize clinical outcomes among Connecticut residents with cardiovascular disease. As an initial goal for the Consortium, we further propose to undertake a prospective, observational study of Connecticut residents who present with ST Segment Elevation Acute Myocardial Infarction (STEMI). Recent advances in pharmacologic and mechanical reperfusion for STEMI have resulted in a need to define the optimal use of these therapies in the community at large. The primary purpose of this study will be to determine the relative merits of different treatment patterns for STEMI with regard to the use of fibrinolytic therapy and percutaneous coronary intervention (PCI). Particular emphasis will be placed on assessing the relative benefits of urgent mechanical revascularization performed at the state's seven tertiary facilities with PCI capability compared to all other treatment modalities. Successful completion of this unique collaborative endeavor is expected to have significant impact on improved patient care and on current health-care policy for medical resource allocation. Moreover, continued collaboration of health-care providers within the Connecticut Cardiovascular Consortium infrastructure should serve as a useful mechanism for ongoing improvements in evidence-based cardiovascular medicine and clinical research in the state of Connecticut.

Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program.

Pulse pressure has been related to higher risk of cardiovascular events in older persons. Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure. Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure. Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension, and the influence of treatment on the pulse pressure effect. We assessed the relation between pulse pressure, measured throughout the follow-up period, and the incidence of coronary heart disease (CHD), heart failure (HF), and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program, a 5-year randomized, placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults. In the treatment group, a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32% increase in risk of HF and a 24% increase in risk of stroke after controlling for systolic blood pressure and other known risk factors, as well as with a 23% increase in risk of HF and a 19% increase in risk of stroke after controlling for diastolic blood pressure and other risk factors. Pulse pressure was not significantly associated with HF or stroke in the placebo group, nor with incidence of CHD in either the placebo or treatment group. These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension.

The association between white blood cell count and acute myocardial infarction mortality in patients > or =65 years of age: findings from the cooperative cardiovascular project.

OBJECTIVES: The purpose of the study was to examine the association between white blood cell (WBC) count on admission and 30-day mortality in patients with acute myocardial infarction (AMI). BACKGROUND: Elevations in WBC count have been associated with the development of AMI and with long-term mortality in patients with coronary artery disease. However, the relationship between WBC count and prognosis following AMI is less clear. METHODS: Using the Cooperative Cardiovascular Project database, we evaluated 153,213 patients > or = 65 years of age admitted with AMI. RESULTS: An increasing WBC count is associated with a significantly higher risk of in-hospital events, in-hospital mortality and 30-day mortality. Relative to those patients in the lowest quintile, patients in the highest quintile were three times more likely to die at 30 days (10.3% vs. 32.3%; p < 0.001). After adjustment for confounding factors, WBC count was found to be a strong independent predictor of 30-day mortality (odds ratio = 2.37; 95% confidence interval 2.25 to 2.49, p = 0.0001 for the highest quintile of WBC count). CONCLUSIONS: White blood cell count within 24 h of admission for an AMI is a strong and independent predictor of in-hospital and 30-day mortality as well as in-hospital clinical events. Although the mechanism of the association remains speculative, the results of this study have important clinical implications for risk-stratifying patients with AMI.

Blood transfusion in elderly patients with acute myocardial infarction.

BACKGROUND: Anemia may have adverse effects in patients with coronary artery disease. However, the benefit of blood transfusion in elderly patients with acute myocardial infarction and various degrees of anemia is uncertain. METHODS: We conducted a retrospective study of data on 78,974 Medicare beneficiaries 65 years old or older who were hospitalized with acute myocardial infarction. Patients were categorized according to the hematocrit on admission (5.0 to 24.0 percent, 24.1 to 27.0 percent, 27.1 to 30.0 percent, 30.1 to 33.0 percent, 33.1 to 36.0 percent, 36.1 to 39.0 percent, or 39.1 to 48.0 percent), and data were evaluated to determine whether there was an association between the use of transfusion and 30-day mortality. RESULTS: Patients with lower hematocrit values on admission had higher 30-day mortality rates. Blood transfusion was associated with a reduction in 30-day mortality among patients whose hematocrit on admission fell into the categories ranging from 5.0 to 24.0 percent (adjusted odds ratio, 0.22; 95 percent confidence interval, 0.11 to 0.45) to 30.1 to 33.0 percent (adjusted odds ratio, 0.69; 95 percent confidence interval, 0.53 to 0.89). It was not associated with a reduction in 30-day mortality among those whose hematocrit values fell in the higher ranges. In one of seven subgroup analyses (among patients who survived at least two days), transfusion was not associated with a reduction in mortality for patients with hematocrit values of 30.1 percent or higher. CONCLUSIONS: Blood transfusion is associated with a lower short-term mortality rate among elderly patients with acute myocardial infarction if the hematocrit on admission is 30.0 percent or lower and may be effective in patients with a hematocrit as high as 33.0 percent on admission.

The case for comprehensive quality indicator reliability assessment.

To demonstrate the importance of evaluating overall quality indicator reliability, in addition to component or variable level reliability, a comparison of interrater agreement on four chart-abstracted pneumonia-related processes of care was conducted. The hospital medical records of 356 Medicare patients' recent discharges for pneumonia were independently abstracted by different abstractors. Kappa, prevalence and bias-adjusted kappa, P(pos), P(neg), and the Bias Index were used to assess reliability of composite quality indicators and their components. The adjusted kappas for the data elements used to determine eligibility to receive as well as to derive the pneumonia-related processes of care ranged from 0.68 to 1.0. The adjusted kappa associated with overall eligibility to receive the pneumonia-related processes of care was 0.63. The kappa statistics for determining if processes of care were provided ranged from 0.56 to 0.83 and increased to 0.65 and 0.85 upon adjustment for the prevalence effect. Kappas for the composite quality indicators were lower, but improved with adjustment for the prevalence effect. The composite quality indicator with the highest adjusted kappa value was oxygenation assessment (0.93); the composite quality indicator with the lowest adjusted kappa value was antibiotic administration within 8 hours of hospital arrival (0.74). This study establishes the reliability of pneumonia indicators and underscores the need for reliability assessment at the quality indicator level, as well as at the component level.

Symptom predictors of acute coronary syndromes in younger and older patients.

BACKGROUND: Symptoms, a key element in the patient's decision to seek care, are critical to appropriate triage, and influence decisions to pursue further evaluation and initiation of treatment. Although many studies have described symptoms associated with acute coronary syndromes (ACS), few, if any, have examined symptom predictors of ACS and whether they differ by patients' age. OBJECTIVES: To explore symptom predictors of ACS in younger (< 70 years) and older (> or = 70 years) patients. To test the hypothesis that typical symptoms are predictive of ACS in younger patients, but are less predictive in older patients. METHOD: Secondary analysis of observational data gathered on 531 patients presenting to the emergency department of a regional cardiac referral center in New England with symptoms suggestive of ACS. RESULTS: Bivariate analyses revealed no symptoms significantly (p < .01) associated with ACS in older patients. In younger patients presence of chest symptoms and the total number of typical symptoms reported were significantly (p < .01) associated with ACS. After adjustment for age and gender, typical symptoms that were positive predictors of ACS in younger patients included chest symptoms (OR 2.37, 95% CI 1.32-4.27, p = .004) and arm pain (OR 1.78, 95% CI 1.03-3.09, p = .040). Additionally, the total number of typical symptoms reported (OR 1.68, 95% CI 1.31-2.15, p < .001) was a positive predictor of ACS in younger patients. The atypical symptom of fatigue (OR 2.52, 95% CI 1.10-5.81, p = .029) was a significant positive predictor of ACS, whereas dizziness/faintness (OR .50, 95% CI .26-.91, p = .024) was a significant negative predictor of ACS in younger patients. Logistic regression analysis using the entire sample revealed an interaction between age and number of typical symptoms indicating that younger patients had a 36% greater odds for ACS for each additional typical symptom present compared with older patients (OR 1.36, 95% CI 1.02-1.83, p = .038 for interaction between age and number of typical symptoms reported). The model with the interaction between age and chest symptoms revealed a borderline association (p = .10 for the interaction between age and chest symptoms), with younger patients being more likely than older patients to report chest symptoms. CONCLUSIONS: Typical symptoms are predictive of ACS in younger patients and less predictive in older patients.