Objective. A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths

The paper focuses on the biology of stress and resilience and their biomarkers in humans from the system science perspective. A stressor pushes the physiological system away from its baseline state toward a lower utility state. The physiological system may return toward the original state in one attractor basin but may be shifted to a state in another, lower utility attractor basin. While some physiological changes induced by stressors may benefit health, there is often a chronic wear and tear cost due to implementing changes to enable the return of the system to its baseline state and maintain itself in the high utility baseline attractor basin following repeated perturbations. This cost, also called allostatic load, is the utility reduction associated with both a change in state and with alterations in the attractor basin that affect system responses following future perturbations. This added cost can increase the time course of the return to baseline or the likelihood of moving into a different attractor basin following a perturbation. Opposite to this is the system's resilience which influences its ability to return to the high utility attractor basin following a perturbation by increasing the likelihood and/or speed of returning to the baseline state following a stressor. This review paper is a qualitative systematic review; it covers areas most relevant for moving the stress and resilience field forward from a more quantitative and neuroscientific perspective.

Traumatic brain injury (TBI) has been called “the most complicated disease of the most complex organ of the body,” and is an increasingly high-profile public health issue. Many patients report long-term impairments following a concussion, but reliable criteria for diagnosis and prognosis are lacking. Every clinical trial for TBI treatment to date has failed to demonstrate reliable and safe improvement in outcomes, and the existing body of literature is insufficient to support the creation of a new classification system. Concussion is a highly heterogeneous phenomenon and numerous factors interact dynamically to influence an individual’s recovery trajectory. Many of the obstacles faced in research and clinical practice related to TBI and concussion, including observed heterogeneity, arguably stem from the complexity of the condition itself. To improve understanding of this complexity, we review the current state of research through the lens provided by the interdisciplinary field of systems science, which has been increasingly applied to biomedical issues in recent years. The review was conducted iteratively, through multiple phases of literature review, expert interviews, and systems diagramming, and represents the first phase in an effort to develop systems models of concussion. The primary focus of this work was to examine concepts and ways of thinking about concussion that currently impede research design and block advancements in care of TBI. Results are presented in the form of a multi-scale conceptual framework intended to synthesize knowledge across disciplines, improve research design, and provide a broader, multi-scale model for understanding concussion pathophysiology, classification, and treatment.

Despite increasing public awareness and a growing body of literature on the subject of concussion, or mild traumatic brain injury, an urgent need still exists for reliable diagnostic measures, clinical care guidelines, and effective treatments for the condition. Complexity and heterogeneity complicate research efforts and indicate the need for innovative approaches to synthesize current knowledge in order to improve clinical outcomes. Methods from the interdisciplinary field of systems science, including models of complex systems, have been increasingly applied to biomedical applications and show promise for generating insight for traumatic brain injury. The current study uses causal-loop diagramming to visualize relationships between factors influencing the pathophysiology and recovery trajectories of concussive injury, including persistence of symptoms and deficits. The primary output is a series of preliminary systems maps detailing feedback loops, intrinsic dynamics, exogenous drivers, and hubs across several scales, from micro-level cellular processes to social influences. Key system features, such as the role of specific restorative feedback processes and cross-scale connections, are examined and discussed in the context of recovery trajectories. This systems approach integrates research findings across disciplines and allows components to be considered in relation to larger system influences, which enables the identification of research gaps, supports classification efforts, and provides a framework for interdisciplinary collaboration and communication—all strides that would benefit diagnosis, prognosis, and treatment in the clinic.

Significance: The opioid crisis remains one of the greatest public health challenges in the United States. The crisis is complex, with long delays and feedbacks between policy actions and their effects, which creates a risk of unintended consequences and complicates policy decision-making. We present SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), an operationally detailed national-level model of the opioid crisis, intended to enhance understanding of the crisis and guide policy decisions. Drawing on multiple data sources, SOURCE replicates how risks of opioid misuse initiation and overdose have evolved over time in response to behavioral and other changes and suggests how those risks may evolve in the future, providing a basis for projecting and analyzing potential policy impacts and solutions.

Opioid overdose deaths remain a major public health crisis. We used a system dynamics simulation model of the U.S. opioid-using population age 12 and older to explore the impacts of 11 strategies on the prevalence of opioid use disorder (OUD) and fatal opioid overdoses from 2022 to 2032. These strategies spanned opioid misuse and OUD prevention, buprenorphine capacity, recovery support, and overdose harm reduction. By 2032, three strategies saved the most lives: (i) reducing the risk of opioid overdose involving fentanyl use, which may be achieved through fentanyl-focused harm reduction services; (ii) increasing naloxone distribution to people who use opioids; and (iii) recovery support for people in remission, which reduced deaths by reducing OUD. Increasing buprenorphine providers’ capacity to treat more people decreased fatal overdose, but only in the short term. Our analysis provides insight into the kinds of multifaceted approaches needed to save lives.