Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity

Churn, Baby, Churn: Strategic Dynamics Among Dominant and Fringe Firms in a Segmented Industry

This paper integrates and extends the literatures on industry evolution and dominant firms to develop a dynamic theory of dominant and fringe competitive interaction in a segmented industry. It argues that a dominant firm, seeing contraction of growth in its current segment(s), enters new segments in which it can exploit its technological strengths, but that are sufficiently distant to avoid cannibalization. The dominant firm acts as a low-cost Stackelberg leader, driving down prices and triggering a sales takeoff in the new segment. We identify a “churn” effect associated with dominant firm entry: fringe firms that precede the dominant firm into the segment tend to exit the segment, while new fringe firms enter, causing a net increase in the number of firms in the segment. As the segment matures and sales decline in the segment, the process repeats itself. We examine the predictions of the theory with a study of price, quantity, entry, and exit across 24 product classes in the desktop laser printer industry from 1984 to 1996. Using descriptive statistics, hazard rate models, and panel data methods, we find empirical support for the theoretical predictions

Primary Care Appointment Availability and Preventive Care Utilization: Evidence From an Audit Study

Insurance expansions under the Affordable Care Act raise concerns about primary care access in communities with large numbers of newly insured. We linked individual-level, cross-sectional data on adult preventive care utilization from the 2011-2012 Behavioral Risk Factor Surveillance System to novel county-level measures of primary care appointment availability collected from an experimental audit study conducted in 10 states in 2012-2013 and other county-level health service and demographic measures. In multivariate regressions, we found higher county-level appointment availability for privately-insured adults was associated with significantly lower preventive care utilization among adults likely to have private insurance. Estimates were attenuated after controlling for county-level uninsurance, poverty, and unemployment. By contrast, greater availability of Medicaid appointments was associated with higher, but not statistically significant, preventive care utilization for likely Medicaid enrollees. Our study highlights that the relationship between preventive care utilization and primary care access in small areas likely differs by insurance status

A Qualitative Evaluation of Advances in Emergency Department Opioid Use Disorder Care in Michigan

The United States opioid epidemic claims the lives of tens of thousands of Americans each year due to opioid overdose. Hospital emergency departments (EDs) have been essential in combatting the crisis by stabilizing patients who are experiencing an overdose and other symptoms of their opioid use disorders (OUD). Over time, EDs have also become more involved in providing other addiction treatment services, such as prescribing and administering medications for opioid use disorder (MOUD) and referring their patients to outpatient behavioral health care providers for follow-up treatment. Policymakers have been essential in driving EDs to expand the scope of their addiction medicine services and referrals by creating specialized programs that provide incentivizes to participating hospitals.The following report summarizes advances in opioid use disorder care within EDs in 19 hospitals across 8 health systems in Michigan. These hospitals participated in an initiative created by the Community Foundation for Southeast Michigan (CFSEM) in collaboration with the Michigan Opioid Partnership (MOP), a public-private collaborative with a mission to reduce opioid overdoses in Michigan by improving the access and quality of prevention, treatment, harm reduction, and recovery services. The initiative was supported by State Opioid Response grants from the Michigan Department of Health and Human Services. Vital Strategies, a global public health organization that helps governments strengthen public health, provided support, technical assistance, and resources to improve hospital coordination and designed the evaluation. Specifically, hospitals were provided funding by CFSEM to improve OUD care training, coordination, delivery, and quality in their EDs. Hospitals and health systems funded by CFSEM included the University of Michigan Health System (Michigan Medicine hospital), Trinity Health (Mercy Health Muskegon, Mercy Health St. Mary, St. Joseph Mercy - Ann Arbor, St. Joseph Mercy Chelsea, St. Joseph Mercy Livingston, St. Joseph Mercy Oakland), Henry Ford Health Systems (Henry Ford – Main, Henry Ford - Wynadotte/ Brownstown), Beaumont Health Systems (Beaumont - Royal Oak, Beaumont – Troy, Beaumont – Wayne), Ascension (Ascension St. John Hospital, Ascension Genesys Hospital), Munson Healthcare (Munson Medical Center - Traverse City, Sparrow Health System (Sparrow Hospital - Lansing), Spectrum Health (Spectrum Health Butterworth), War Memorial, and Hurley Medical Center. After receiving funding, hospitals created work plans related to improving opioid use disorder care in their EDs, including by increasing their number of employed X-waivered providers, integrating clinical tracking and support tools into electronic medical records, and connecting patients with behavioral health care providers in the community to establish treatment continuity (i.e., "warm handoffs"). Researchers with the Bloomberg Overdose Prevention Initiative at the Johns Hopkins Bloomberg School of Public Health evaluated hospital improvement in these areas using surveys and qualitative interviews with participants

Primary Care Access for new Patients on the eve of Health Care Reform

Importance: Current measures of access to care have intrinsic limitations and may not accurately reflect the capacity of the primary care system to absorb new patients. Objective: To assess primary care appointment availability by state and insurance status. Design, Setting, and Particpants: We conducted a simulated patient study. Trained field staff, randomly assigned to private insurance, Medicaid, or uninsured, called primary care offices requesting the first available appointment for either routine care or an urgent health concern. The study included a stratified random sample of primary care practices treating nonelderly adults within each of 10 states (Arkansas, Georgia, Illinois, Iowa, Massachusetts, Montana, New Jersey, Oregon, Pennsylvania, and Texas), selected for diversity along numerous dimensions. Collectively, these states comprise almost one-third of the US nonelderly, Medicaid, and currently uninsured populations. Sampling was based on enrollment by insurance type by county. Analyses were weighted to obtain population-based estimates for each state. Main Outcomes and Measures: The ability to schedule an appointment and number of days to the appointment. We also examined cost and payment required at the visit for the uninsured. Results: Between November 13, 2012, and April 4, 2013, we made 12,907 calls to 7788 primary care practices requesting new patient appointments. Across the 10 states, 84.7% (95% CI, 82.6%-86.8%) of privately insured and 57.9% (95% CI, 54.8%-61.0%) of Medicaid callers received an appointment. Appointment rates were 78.8% (95% CI, 75.6%-82.0%) for uninsured patients with full cash payment but only 15.4% (95% CI, 13.2%-17.6%) if payment required at the time of the visit was restricted to $75 or less. Conditional on getting an appointment, median wait times were typically less than 1 week (2 weeks in Massachusetts), with no differences by insurance status or urgency of health concern. Conclusions and Relevance: Although most primary care physicians are accepting new patients, access varies widely across states and insurance status. Navigator programs are needed, not only to help patients enroll but also to identify practices accepting new patients within each plan\u27s network. Tracking new patient appointment availability over time can inform policies designed to strengthen primary care capacity and enhance the effectiveness of the coverage expansions with the Patient Protection and Affordable Care Act

Carotid plaque imaging and the risk of atherosclerotic cardiovascular disease

Carotid artery plaque is a measure of atherosclerosis and is associated with future risk of atherosclerotic cardiovascular disease (ASCVD), which encompasses coronary, cerebrovascular, and peripheral arterial diseases. With advanced imaging techniques, computerized tomography (CT) and magnetic resonance imaging (MRI) have shown their potential superiority to routine ultrasound to detect features of carotid plaque vulnerability, such as intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC), and calcification. The correlation between imaging features and histological changes of carotid plaques has been investigated. Imaging of carotid features has been used to predict the risk of cardiovascular events. Other techniques such as nuclear imaging and intra-vascular ultrasound (IVUS) have also been proposed to better understand the vulnerable carotid plaque features. In this article, we review the studies of imaging specific carotid plaque components and their correlation with risk scores

Moderating role of physical activity on hippocampal iron deposition and memory outcomes in typically aging older adults

Physical activity (PA) is linked to better cognitive and brain health, though its mechanisms are unknown. While brain iron is essential for normal function, levels increase with age and, when excessive, can cause detrimental neural effects. We examined how objectively measured PA relates to cerebral iron deposition and memory functioning in normal older adults. Sixty-eight cognitively unimpaired older adults from the UCSF Memory and Aging Center completed neuropsychological testing and brain magnetic resonance imaging, followed by 30-day Fitbit monitoring. Magnetic resonance imaging quantitative susceptibility mapping (QSM) quantified iron deposition. PA was operationalized as average daily steps. Linear regression models examined memory as a function of hippocampal QSM, PA, and their interaction. Higher bilateral hippocampal iron deposition correlated with worse memory but was not strongly related to PA. Covarying for demographics, PA moderated the relationship between bilateral hippocampal iron deposition and memory such that the negative effect of hippocampal QSM on memory performances was no longer significant above 9120 daily steps. PA may mitigate adverse iron-related pathways for memory health