Publications

The original version of this article unfortunately contained a mistake in Fig. 1. The figure was incorrectly presented with the results of an additional path model for forgotten antiretroviral therapy (ART) doses that was dropped from the primary analyses.

Viral suppression, a critical component of HIV care, is more likely when individuals initiate antiretroviral therapy (ART) early in disease progression and maintain optimal levels of adherence to ART regimens. Although several studies have documented the negative association of depressive symptoms with ART adherence, less is known about how depressed mood relates to intentional versus unintentional lapses in adherence as well as the mechanisms underlying this association. The purpose of the current study was to examine the association of depressive symptoms with ART adherence, assessed as a multidimensional construct. Secondarily, this study conducted preliminary indirect path models to determine if medication self-efficacy could explain the depressed mood-adherence relationship. Depressive symptoms were not associated with 95% ART taken, self-reported viral load, deliberate adjustments to ART regimens or skipped ART doses. However, the indirect association of depressive symptoms via decrements in medication self-efficacy was significant for 95% ART taken, self-reported viral load and skipped ART doses, but not deliberate changes to ART regimens. In this sample of HIV-positive outpatients, there is evidence to support medication self-efficacy as a potential mechanism underlying the association between depressive symptoms and ART adherence. Additional longitudinal studies are needed to formally examine medication taking self-efficacy as a mediator.

Importance

Overuse of medical tests and treatments is an increasingly recognized problem across health systems; best practices for reducing overuse are not clear. Framing the problem in terms of the spectrum of potential patient harm is likely to be an effective strategy for clinician and patient engagement in efforts to reduce overuse, but the scope of negative consequences of overuse for patients has not been well described.

Observations

We sought to generate a comprehensive conceptual map documenting the processes through which overused tests and treatments lead to multiple domains of negative consequences for patients. For map development, an iterative consensus process was informed by structured review of the literature on overuse using PubMed and input from a panel of 6 international experts. For map verification, a systematic review was performed of case reports involving overused services, identified through literature review and manual review of relevant article collections. The conceptual map documents that overused tests and treatments and resultant downstream services generate 6 domains of negative consequences for patients: physical, psychological, social, financial, treatment burden, and dissatisfaction with health care. Negative consequences can result from overused services and from downstream services; they can also trigger further downstream services that in turn can lead to more negative consequences, in an ongoing feedback loop. Case reports on overuse confirmed the processes and domains of the conceptual map. Cases also revealed strengths and weaknesses in published communication about overuse: they were dominated by physical harms, with other negative consequences receiving far less attention.

Conclusions and Relevance

This evidence-based conceptual map clarifies the processes by which overused tests and treatments result in negative consequences for patients; it also documents multiple domains of negative consequences experienced by patients. The map will be useful for facilitating comprehensive communication about overuse, estimating harms and costs associated with overused services, and informing health system efforts to reduce overuse.

Optimal right ventricular (RV) function in pulmonary hypertension (PH) requires structural and functional coupling between the RV cardiomyocyte and its adjacent capillary network. Prior investigations have indicated that RV vascular rarefaction occurs in PH, which could contribute to RV failure by reduced delivery of oxygen or other metabolic substrates. However, it has not been determined if rarefaction results from relative underproliferation in the setting of tissue hypertrophy or from actual loss of vessels. It is also unknown if rarefaction results in inadequate substrate delivery to the RV tissue. In the present study, PH was induced in rats by SU5416-hypoxia-normoxia exposure. The vasculature in the RV free wall was assessed using stereology. Steady-state metabolomics of the RV tissue was performed by mass spectrometry. Complementary studies were performed in hypoxia-exposed mice and rats. Rats with severe PH had evidence of RV failure by decreased cardiac output and systemic hypotension. By stereology, there was significant RV hypertrophy and increased total vascular length in the RV free wall in close proportion, with evidence of vessel proliferation but no evidence of endothelial cell apoptosis. There was a modest increase in the radius of tissue served per vessel, with decreased arterial delivery of metabolic substrates. Metabolomics revealed major metabolic alterations and metabolic reprogramming; however, metabolic substrate delivery was functionally preserved, without evidence of either tissue hypoxia or depletion of key metabolic substrates. Hypoxia-treated rats and mice had similar but milder alterations. There is significant homeostatic vascular adaptation in the right ventricle of rodents with PH.