Radial Scars Without Atypia Diagnosed at Percutaneous Core Needle Breast Biopsy: Support for Imaging Surveillance.

Objective: Radial scar (RS) is a low-risk breast lesion that can be associated with or mimic malignancy. Management guidelines remain controversial for patients with RS without atypia on core needle biopsy (CNB). The aim was to evaluate the upgrade rate of these lesions and factors associated with malignancy risk and excision rate to more definitively guide management. Materials and Methods: In this retrospective study, 123 patients with RS without atypia, diagnosed with CNB between January 2008 to December 2014 who were either referred for surgical excision or followed-up with imaging, were reviewed. The differences in clinical presentation, imaging features, and biopsy technique among the benign RS patients and those upgraded, as well as the excised versus the observed patients were compared. Results: Of 123 RS reviewed, 93 cases of RS without atypia as the highest-grade lesion in the ipsilateral breast and with either 24-month imaging follow-up or surgical correlation were included. Seventy-four (79.6%) lesions were surgically excised and 19 (20.4%) were followed-up for at least 24 months. A single upgrade to malignancy (1%) and 15 upgrades to high-risk lesions (16%) were found. There was no association of any upgraded lesion with presenting symptoms or imaging features. The use of vacuum-assistance and larger biopsy needles, along with obtaining a higher number of samples, was associated with fewer upgrades and lower surgical excision rates. Conclusion: The upgrade rate of RS without atypia in our population was low, regardless of the imaging features and biopsy technique utilized. Close imaging surveillance is an acceptable alternative to surgical excision in these patients.

Common genetic variation impacts stress response in the brain.

To explain why individuals exposed to identical stressors experience divergent clinical outcomes, we determine how molecular encoding of stress modifies genetic risk for brain disorders. Analysis of post-mortem brain (n=304) revealed 8557 stress-interactive expression quantitative trait loci (eQTLs) that dysregulate expression of 915 eGenes in response to stress, and lie in stress-related transcription factor binding sites. Response to stress is robust across experimental paradigms: up to 50% of stress-interactive eGenes validate in glucocorticoid treated hiPSC-derived neurons (n=39 donors). Stress-interactive eGenes show brain region- and cell type-specificity, and, in post-mortem brain, implicate glial and endothelial mechanisms. Stress dysregulates long-term expression of disorder risk genes in a genotype-dependent manner; stress-interactive transcriptomic imputation uncovered 139 novel genes conferring brain disorder risk only in the context of traumatic stress. Molecular stress-encoding explains individualized responses to traumatic stress; incorporating trauma into genomic studies of brain disorders is likely to improve diagnosis, prognosis, and drug discovery.

Federally Qualified Health Center Penetration Associated With Reduced Community COVID-19 Mortality in Four United States Cities.

BACKGROUND: The COVID-19 pandemic has had significant impacts on health care access and delivery, with disparate effects across social and racial lines. Federally Qualified Health Centers (FQHCs) provide critical primary care services to the nation's most underserved populations, including many communities hardest hit by COVID-19. METHODS: We conducted an ecological analysis that aimed to examine FQHC penetration, COVID-19 mortality, and socio-demographic factors in 4 major United States cities: New York, New York; Chicago, Illinois; Detroit, Michigan; and Seattle, Washington. RESULTS: We found the distribution of COVID-19 cases and mortality varied spatially and in magnitude by city. COVID-19 mortality was significantly higher in communities with higher percentages of low-income residents and higher percentages of racial/ethnic minority residents. FQHC penetration was protective against increased COVID-19 mortality, after model adjustment. CONCLUSIONS: Our study underpins the critical role of safety-net health care and policymakers must ensure investment in long-term sustainability of FQHCs, through strategic deployment of capital, workforce development, and reimbursement reform.

Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression.

Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains. We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD. These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.

Age and Sex Differences and Temporal Trends in the Use of Invasive and Noninvasive Procedures in Patients Hospitalized With Acute Myocardial Infarction.

Background Few studies have examined age and sex differences in the receipt of cardiac diagnostic and interventional procedures in patients hospitalized with acute myocardial infarction and trends in these possible differences during recent years. Methods and Results Data from patients hospitalized with a first acute myocardial infarction at the major medical centers in the Worcester, Massachusetts, metropolitan area were utilized for this study. Logistic regression analysis was used to examine age (<55, 55-64, 65-74, and ≥75 years) and sex differences in the receipt of echocardiography, exercise stress testing, coronary angiography, percutaneous coronary interventions, and coronary artery bypass graft surgery, and trends in the use of those procedures during patients' acute hospitalization, between 2005 and 2018, while adjusting for important confounding factors. The study population consisted of 1681 men and 1154 women with an initial acute myocardial infarction who were hospitalized on an approximate biennial basis between 2005 and 2018. A smaller proportion of women underwent cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery, while there were no sex differences in the receipt of echocardiography and exercise stress testing. Patients aged ≥75 years were less likely to undergo cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery, but were more likely to receive echocardiography compared with younger patients. Between 2005 and 2018, the use of echocardiography and coronary artery bypass graft surgery nonsignificantly increased among all age groups and both sexes, while the use of cardiac catheterization and percutaneous coronary intervention increased nonsignificantly faster in women and older patients. Conclusions We observed a continued lower receipt of invasive cardiac procedures in women and patients aged ≥75 years with acute myocardial infarction, but age and sex gaps associated with these procedures have narrowed during recent years.

Integrating deep learning and unbiased automated high-content screening to identify complex disease signatures in human fibroblasts.

Drug discovery for diseases such as Parkinson's disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinson's disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes. We use fixed weights from a convolutional deep neural network trained on ImageNet to generate deep embeddings from each image and train machine learning models to detect morphological disease phenotypes. Our platform's robustness and sensitivity allow the detection of individual-specific variation with high fidelity across batches and plate layouts. Lastly, our models confidently separate LRRK2 and sporadic Parkinson's disease lines from healthy controls (receiver operating characteristic area under curve 0.79 (0.08 standard deviation)), supporting the capacity of this platform for complex disease modeling and drug screening applications.

Patient Commitment to Health (PACT-Health) in the Heart Failure Population: A Focus Group Study of an Active Communication Framework for Patient-Centered Health Behavior Change.

BACKGROUND: Over 6 million Americans have heart failure, and 1 in 8 deaths included heart failure as a contributing cause in 2016. Lifestyle changes and adherence to diet and exercise regimens are important in limiting disease progression. Health coaching and public commitment are two interactive communication strategies that may improve self-management of heart failure. OBJECTIVE: This study aimed to conduct patient focus groups to gain insight into how best to implement health coaching and public commitment strategies within the heart failure population. METHODS: Focus groups were conducted in two locations. We studied 2 patients in Oakland, California, and 5 patients in Los Angeles, California. Patients were referred by local cardiologists and had to have a diagnosis of chronic heart failure. We used a semistructured interview tool to explore several patient-centered themes including medication adherence, exercise habits, dietary habits, goals, accountability, and rewards. We coded focus group data using the a priori coding criteria for these domains. RESULTS: Medication adherence barriers included regimen complexity, forgetfulness, and difficulty coping with side effects. Participants reported that they receive little instruction from care providers on appropriate exercise and dietary habits. They also reported personal and social obstacles to achieving these objectives. Participants were in favor of structured goal setting, use of online social networks, and financial rewards as a means of promoting health lifestyles. Peers were viewed as better motivating agents than family members. CONCLUSIONS: An active communication framework involving dissemination of diet- and exercise-related health information, structured goal setting, peer accountability, and financial rewards appears promising in the management of heart failure.

A Historical Perspective on Presentations of Hypertensive Acute Heart Failure.

BACKGROUND: The initial systolic blood pressure (SBP) in patients presenting to the hospital with acute heart failure (AHF) informs prognosis, diagnosis, and guides initial treatment. However, over time AHF presentations with elevated SBP appear to have declined. The present study examined whether the frequency of AHF presentations with systolic hypertension (SBP >160 mmHg) declined over a nearly two-decade time interval. METHODS: This study compares four historical, cross-sectional cohorts with AHF who were admitted to tertiary care medical centres in the North-eastern USA in 1995, 2000, 2006, and 2011-13. The main outcome was the proportion of AHF patients presenting with an initial SBP >160 mmHg. RESULTS: 2,366 patients comprised the study sample. The average age was 77 years, 55% were female, 94% white, and 75% had prior heart failure. In 1995, 34% of AHF patients presented with an initial SBP >160 mmHg compared to 20% in 2011-2013 (p<0.01). Multivariate logistic regression demonstrated reduced odds of presenting with a SBP >160 mmHg in 2006 (0.64, 95% CI 0.42-0.96) and 2011-13 (0.46, 95% CI 0.28-0.74) compared with patients in 1995. CONCLUSION: The proportion of patients with AHF and initial SBP >160 mmHg significantly declined over the study time period. There are several potential reasons for this observation and these findings highlight the need for ongoing surveillance of patients with AHF as changing clinical characteristics can impact early treatment decisions.

Academic physicians' views on low-value services and the choosing wisely campaign: A qualitative study.

BACKGROUND: In 2012, the American Board of Internal Medicine (ABIM) Foundation launched a campaign called Choosing Wisely which was intended to start a national dialogue on services that are not medically necessary. More research is needed on the in-depth reasons why doctors overuse low-value services, their views on Choosing Wisely specifically, and ways to help them change their practice patterns. METHODS: We performed a qualitative study of focus groups with physicians to explore their views on the problem of overuse of low-value services, the reasons why they overuse, and ways that they think could be effective at curbing overuse. Participants were attendings in the fields of emergency medicine, internal medicine, hospital medicine, and cardiology. RESULTS: All physicians felt that overuse of low-value services was a significant problem. Physicians frequently cited that patient expectations drove the use of low-value services and lack of time was the most cited reason why behavior change was difficult. Facilitators that could promote behavior change included decision support through the electronic medical record, motivation to maintain their reputation among their colleagues, internal motivation to be a good doctor, objective data showing their rates of overuse, alignment of institutional goals, and forums to discuss evidence and new research. CONCLUSIONS AND IMPLICATIONS: In focus groups with physicians, we found that physicians perceived that overuse of low-value services was a problem. Participants cited many barriers to behavior change. Methods that help address patient expectations, physician time, and social norms may help physicians reduce their use of low-value services.

Engagement in health and wellness: An online incentive-based program.

Increasingly, corporate health promotion programs are implementing wellness programs integrating principles of behavioral economics. Employees of a large firm were provided a customized online incentive program to design their own commitments to meet health goals. This study examines patterns of program participation and engagement in health promotion activities. Subjects were US-based employees of a large, nondurable goods manufacturing firm who were enrolled in corporate health benefits in 2010 and 2011. We assessed measures of engagement with the workplace health promotion program (e.g., incentive points earned, weight loss). To further examine behaviors indicating engagement in health promotion activities, we constructed an aggregate, employee-level engagement index. Regression models were employed to assess the association between employee characteristics and the engagement index, and the engagement index and spending. 4220 employees utilized the online program and made 25,716 commitments. Male employees age 18-34 had the highest level of engagement, and male employees age 55-64 had the lowest level of engagement overall. Prior year health status and prior year spending did not show a significant association with the level of engagement with the program (p > 0.05). Flexible, incentive-based behavioral health and lifestyle programs may reach the broader workforce including those with chronic conditions and higher levels of health spending.

Blood pressure abnormalities in children with sickle cell anemia.

BACKGROUND: Kidney disease is an important cause of morbidity and mortality in patients with sickle cell anemia (SCA). The factors that affect progression of renal disease are unknown, especially in children and adolescents. Alterations in blood pressure, including hypertension and lack of the normal nocturnal dip in blood pressure, are important determinants of diabetic nephropathy and other renal diseases and may play a role in sickle cell nephropathy. Our primary hypothesis was that children with SCA who have microalbuminuria will demonstrate less nocturnal dipping of blood pressure compared to patients without microalbuminuria. We also investigated other potential factors associated with microalbuminuria. PROCEDURE: This prospective study of 52 adolescents with SCA followed in the Children's Medical Center Dallas Comprehensive Sickle Cell Center characterized 24-hour ambulatory blood pressure profiles and presence of microalbuminuria. Stepwise logistic regression was performed to identify significant independent factors that are associated with microalbuminuria. RESULTS: Thirty-five percent of patients were identified as having previously unrecognized hypertension, and 17% had pre-hypertension (blood pressure greater than the 90th percentile but less than the 95th percentile). Fifty-six percent of patients lacked the normal nocturnal dip in blood pressure. In addition, 21% had microalbuminuria, and their percent nocturnal dip was significantly less than those without microalbuminuria (P = 0.01). CONCLUSIONS: Blood pressure abnormalities are common in adolescents with SCA and are a possible modifiable risk factor in the progression of sickle cell nephropathy.

Recent trends in the characteristics and prognosis of patients hospitalized with acute heart failure.

BACKGROUND: Despite the magnitude and impact of heart failure (HF) in the United States, relatively little data are available that describe the prognosis associated with acute HF, especially from the perspective of a population-based investigation. The purpose of this nonconcurrent prospective study was to describe the overall, and changing trends therein, prognosis of 4228 patients discharged from all eleven greater Worcester (MA) medical centers after a documented episode of acute HF and factors associated with an increased risk of dying after hospital discharge. METHODS: The study population consisted of residents of the Worcester metropolitan area discharged after being hospitalized for acute HF at all greater Worcester medical centers during 1995 (n = 1783) and 2000 (n = 2445). RESULTS: The 3-month (20% versus 18%), 1-year (41% versus 38%), and 5-year (84% versus 82%) death rates were lower in patients discharged from all metropolitan Worcester hospitals in 2000 versus 1995, respectively. Improving long-term survival rates for patients discharged in 2000 as compared with 1995 were magnified after controlling for several confounding demographic and clinical factors of prognostic importance. A number of potentially modifiable demographic, medical history, and clinical factors were associated with an increased risk of dying during the first year after hospital discharge for acute HF. CONCLUSION: The results of this community-wide observational study suggest improving trends in the long-term prognosis after acute HF. Despite these encouraging trends, the long-term prognosis for patients with acute HF remains poor, and several at-risk groups can be identified for early intervention and increased monitoring efforts.

Delays in seeking medical care in hospitalized patients with decompensated heart failure.

PURPOSE: The magnitude of, and factors associated with, prolonged delay in seeking medical care in patients with acute myocardial infarction has been well described. It is unknown, however, what the extent of, and factors associated with, prehospital delay are in patients hospitalized with acute heart failure. The purpose of this study was to examine patterns of prehospital delay, and factors associated with delay in seeking medical care, in patients hospitalized with acute heart failure at all 11 medical centers in the Worcester, Massachusetts metropolitan area. METHODS: The medical records of 2587 greater Worcester residents with decompensated heart failure who were hospitalized in 2000 were reviewed for the collection of information about prehospital delay and demographic and clinical factors associated with extent of delay. RESULTS: Information about acute symptom onset and duration of delay in seeking medical care was available in only 44% of the hospital charts of patients with heart failure. The average delay time was 13.3 hours, while the median was 2.0 hours. Male sex, multiple presenting symptoms, absence of a history of heart failure, and seeking medical care between midnight and 6:00 am were associated with prolonged prehospital delay. CONCLUSIONS: The results of this study in residents of a large New England metropolitan area suggest that patients hospitalized with acute heart failure exhibit considerable delays in seeking medical care. Several demographic and clinical characteristics were associated with prolonged delay. More research is needed to better understand the reasons why patients with this serious and increasingly prevalent clinical syndrome delay seeking medical care in a timely fashion.

A community-wide perspective into changing trends in the utilization of diagnostic and interventional procedures in patients hospitalized with acute myocardial infarction.

BACKGROUND: Limited data are available describing contemporary trends in the utilization of diagnostic and interventional procedures in patients hospitalized with acute myocardial infarction (AMI). The objectives of our population-based investigation were to examine long-term trends (1986-2003) in the utilization of cardiac catheterization, percutaneous coronary interventions (PCI), and coronary artery bypass graft surgery (CABG) in a community sample of patients hospitalized with AMI. We examined the demographic and clinical characteristics of patients who received these diagnostic and interventional procedures and determined whether the profile of patients undergoing these procedures had changed over time. METHODS: The study sample consisted of 9422 greater Worcester (MA) residents hospitalized with confirmed AMI at all metropolitan Worcester medical centers in 10 annual periods between 1986 and 2003. Information on patient demographics, clinical course, and treatment practices was obtained through the review of hospital medical records. RESULTS: Marked increases were observed in the utilization of cardiac catheterization (18.4% to 55.8%) and PCI (2.0% to 42.1%) between 1986 and 2003, respectively. Utilization of CABG showed modest increases in the early 1990s, whereas its use was relatively stable thereafter. Several demographic and clinical characteristics were associated with the receipt of these diagnostic and interventional procedures. CONCLUSIONS: The results of this study of patients hospitalized with AMI in a large New England community suggest evolving trends in the use of cardiac catheterization, PCI, and CABG. Despite these changing patterns, our findings suggest that there remains room for improvement in the therapeutic management of patients hospitalized with AMI, including certain high-risk groups.