Persistent mortality and heart failure burden of anterior ST-segment elevation myocardial infarction following primary percutaneous coronary intervention: real-world evidence from the US Medicare Data Set.

OBJECTIVES: We sought to compare the temporal trends in the incidence of death and rehospitalisation for congestive heart failure (CHF) following anterior ST-elevation myocardial infarction (STEMI) in a Medicare cohort of beneficiaries treated with primary percutaneous coronary intervention (PCI) in 2005 (n=1479) with those treated in 2016 through quarter (Q) 2 of 2017 (n=22 432). DESIGN: This retrospective analysis examined outcomes using both descriptive and regression analysis to control for differences in patient clinical characteristics over time. PRIMARY OUTCOME MEASURES: The primary outcomes are 1 year and 2 year rates of mortality and re-hospitalisation for CHF. RESULTS: The 1 year mortality rate was numerically higher in the 2016 cohort at 10.3% (95% CI 9.9 to 10.7) versus 8.9% (CI 7.4 to 10.3; p=0.068). The 2 year mortality rate was significantly higher in the 2016 cohort at 14.5% (CI 13.9 to 15.1) versus 11.4% (CI 9.2 to 13.6; p<0.01). The 1 year rehospitalisation for CHF was lower in the 2016 cohort at 10.6% (CI 10.0 to 11.2) versus 16.7% (CI 14.0 to 19.4; p<0.001), but the 2 year rate was not significantly different at 19.3% (CI 17.7 to 20.9) versus 20.7% (CI 16.4 to 24.9; p=0.55). After adjustment for covariates with two models, the 1 year mortality increased by 2.3% (CI 0.8 to 3.7; p<0.01) and 4.1% (CI 2.6 to 5.6; p<0.001) in the 2016 cohort. The 2 year adjusted mortality also increased by 4.2% (CI 2.0 to 6.4; p<0.001) and 6.5% (CI 4.2 to 8.7; p<0.001) in the 2016 cohort. The risk adjusted trends for rehospitalisation for CHF were similar to the unadjusted findings. CONCLUSIONS: Despite prior improvements in STEMI outcomes in the reperfusion era related to the broad adoption of timely PCI, there is a persistent high mortality and CHF burden in Medicare beneficiaries with anterior STEMI. New strategies that address reperfusion injury and enhance myocardial salvage are needed.

Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease.

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia.

Public knowledge and assessment of child mental health problems: findings from the National Stigma Study-Children.

OBJECTIVE: Child and adolescent psychiatry confronts help-seeking delays and low treatment use and adherence. Although lack of knowledge has been cited as an underlying reason, we aim to provide data on public recognition of, and beliefs about, problems and sources of help. METHOD: The National Stigma Study-Children is the first nationally representative study of public response to child mental health problems. A face-to-face survey of 1,393 adults (response rate 70.1%, margin of error +/-3.5%) used vignettes consistent with diagnoses of attention-deficit/hyperactivity disorder (ADHD) and depression. Descriptive and multivariate analyses provide estimates of the levels and correlates of recognition, labeling, and treatment recommendations. RESULTS: Respondents do differentiate "daily troubles" from mental health problems. For the cases that meet diagnostic criteria, 58.5% correctly identify depression and 41.9% correctly identify ADHD. However, respondents are less likely to see ADHD as serious, as a mental illness, or needing treatment compared with depression. Moreover, a substantial group who correctly identifies each disorder rejects its mental illness label (ADHD 19.1%, depression 12.8%). Although women are more knowledgeable, the influence of other sociodemographic characteristics, particularly race, is complex and inconsistent. More respondents see general practitioners, mental health professionals, and teachers as suitable sources of advice than psychiatrists. Behaviors and perceived severity seem to drive public responses. CONCLUSIONS: Americans have clear and consistent views of children's mental health problems. Mental health specialists face challenges in gaining family participation. Unless systematically addressed, the public's lack of knowledge, skepticism, and misinformed beliefs signal continuing problems for providers, as well as for caregivers and children seeking treatment.

Under the influence of genetics: how transdisciplinarity leads us to rethink social pathways to illness.

This article describes both sociological and genetic theories of illness causation and derives propositions expected under each and under a transdisciplinary theoretical frame. The authors draw propositions from three theories -- fundamental causes, social stress processes, and social safety net theories -- and tailor hypotheses to the case of alcohol dependence. Analyses of a later wave of the Collaborative Study on the Genetics of Alcoholism reveal a complex interplay of the GABRA2 gene with social structural factors to produce cases meeting DSM/ICD diagnoses. Only modest evidence suggests that genetic influence works through social conditions and experiences. Further, women are largely unaffected in their risk for alcohol dependence by allele status at this candidate gene; family support attenuates genetic influence; and childhood deprivation exacerbates genetic predispositions. These findings highlight the essential intradisciplinary tension in the role of proximal and distal influences in social processes and point to the promise of focusing directly on dynamic, networked sequences that produce different pathways to health and illness.

Problem drinking patterns among African Americans: the impacts of reports of discrimination, perceptions of prejudice, and "risky" coping strategies.

This research builds on a series of recent studies that have reported independent effects of personal experiences of racial discrimination on poor mental health outcomes. We suggest that for one mental health outcome, problem drinking, discrimination experiences have an impact not only via abridged socioeconomic attainment and the frustrations associated with institutionally limited opportunity structures, but also by directly increasing the likelihood of problem drinking. Moreover, we argue that personal experiences with discrimination help to foster a set of beliefs about the utility of drinking as a means of reducing stress that in the alcohol literature is referred to as "escapist" drinking. Escapist drinking is proposed as an intervening mechanism that is associated with a higher probability of alcohol-related mental health problems. Using data from the 1999-2000 National Survey of Black Workers, we find that, independent of socioeconomic attainment, personal reports of discriminatory experiences have direct influences on problem drinking. Consistent with our hypotheses, we also find that the effects of personal reports of discrimination are at least partially mediated by the endorsement of beliefs that drinking provides an effective coping mechanism. We conclude that racial impacts on mental health outcomes reflect more than the "simple" effects of constrained socioeconomic attainment.

American attitudes toward and willingness to use psychiatric medications.

Despite recent advances in treatment, many Americans decline to take prescribed psychiatric medication. This study explores the role of attitudes regarding the effectiveness of and potential problems associated with psychiatric medications on Americans' willingness to use them. Face-to-face interviews of a US household population sample were done with 1387 volunteers. The 1998 General Social Survey's (response rate, 76.4%) included questions about efficacy, problems, and potential use. Most Americans agree that psychiatric medications are effective, and fewer than half had concerns regarding potential problems. However, the majority of respondents would not be willing to take them. Willingness to use is influenced by these attitudes and other factors, including health status and past use of mental health treatments. Although Americans perceive psychiatric medications to be effective, and this influences their willingness to take them, many still are not willing to take them.