Toward safer opioid prescribing: effects of the TOWER intervention on HIV care providers.

ABSTRACTRates of opioid use disorder and associated deaths remain alarmingly high. Measures to address the epidemic have included reductions in opioid prescribing, in part guided by the Centers for Disease Control Opioid Prescribing Guideline (CDCG). While reductions in over-prescribing have occurred, these measures have also resulted in decreased access and adverse outcomes for some stable opioid-treated chronic pain patients. The TOWard SafER Opioid Prescribing (TOWER) intervention was designed to support HIV primary care providers in use of the CDCG and in decision-making and patient-provider communication regarding safe opioid prescribing. Eleven HIV primary care providers and 40 of their patients were randomized into intervention and control groups. Transcripts from 21 patient visits were analyzed, focusing on opioid and pain-related communications. Findings from this research indicate greater alignment with the CDCG among visits carried out with providers in the TOWER intervention group. However, control group visits were notably consistent with guideline recommendations in several key areas. Differences observed between the intervention and control group visits demonstrate intervention strengths, as well as areas where additional work needs to be done to ensure prescribing and communication consistent with the CDCG.

Validation of the Safer Opioid Prescribing Evaluation Tool (SOPET) for Assessing Adherence to the Centers for Disease Control Opioid Prescribing Guidelines.

OBJECTIVE: In response to the opioid epidemic, the Centers for Disease Control and Prevention issued guidelines (CDCG) in 2016 for the prescription of opioids for chronic pain. To facilitate research into whether CDCG implementation will lead to reductions in opioid prescribing and improved patient safety, we sought to validate a tool that quantifies CDCG adherence based on clinical documentation. DESIGN: The Safe Opioid Prescribing Evaluation Tool (SOPET) was developed in four phases as part of a study to improve the implementation of the CDCG in the clinical setting. Four raters with varying levels of clinical experience and expertise were trained to use the SOPET and then used it to evaluate 21 baseline patient encounters. Intraclass correlation coefficient (ICC) estimates and their 95% confident intervals (CIs) were calculated for the total SOPET score based on a mean-rating (k = 4), absolute-agreement, two-way random-effects model. For intrarater reliability, two-way mixed-effect models were used. RESULTS: Inter-rater reliability was good, with an average-measures ICC of 0.82 (95% CI = 0.63-0.92). Intrarater reliability was excellent for the three raters, who were MDs, with average-measures ICCs as follows: 0.92 (95% CI = 0.81-0.97), 0.97 (95% CI = 0.92-0.99), 0.99 (95% CI = 0.99-0.99). However, the intrarater reliability for the non-MD rater was lower 0.69 (95% CI = 0.22-0.88). CONCLUSIONS: Overall, the SOPET is useful for evaluating implementation of the CDCG in clinical documentation. It is an important first step in the design of future studies assessing whether adherence to the CDCG improves patient safety outcomes.

The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV.

Background and Objectives: Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. The relevance of these pathways to the development of inflammatory disorders in humans remains unknown. We hypothesized that a comprehensive examination of the ANS-immune network in patients with HIV, would reveal that the type and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics. Methods: This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10). Results: Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman's rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017). Discussion: Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.

Gastrointestinal Dysmotility, Autonomic Function and Small Intestinal Bacterial Overgrowth Among People with Well-Controlled HIV.

Introduction: Gastrointestinal dysfunction, including microbiome changes and increased translocation across a compromised gastrointestinal barrier plays a role in the chronic inflammation experienced by people with HIV (PWH). It is unknown whether autonomic neuropathy (AN) may contribute to these mechanisms by altering gastrointestinal motility. Methods: This is a cross-sectional study of 100 PWH and 89 controls. All participants underwent assessment of gastrointestinal transit times using a wireless motility capsule (WMC). All PWH and a subset of controls also underwent: a standardized battery of autonomic function tests summarized as the Modified Composite Autonomic Severity Score (MCASS) and its adrenergic, cardiovagal and sudomotor sub-scores, breath testing for small intestinal bacterial overgrowth (SIBO), and the Patient Assessment of Upper Gastrointestinal Disorders Symptoms (PAGI-SYM) and Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaires. Results: PWH displayed shorter gastric emptying times (GET) and longer small bowel and colonic transit times (SBTT, CTT) compared to controls. Among PWH, GET was associated with PAGI-SYM score. The MCASS and its sudomotor sub-score (reflecting peripheral sympathetic function) were associated with SBTT but not GET or CTT. PWH with prolonged SBTT (>6h) were more likely to have SIBO. Conclusion: Gastrointestinal motility is altered in PWH. This study provides preliminary evidence that changes in autonomic function may influence SBTT in PWH and that prolonged SBTT may contribute to the development of SIBO. Future studies are needed to more fully elucidate the pathophysiologic links between HIV-associated AN, altered gastrointestinal motility, the gastrointestinal microbiome, chronic inflammation, and resulting morbidity and mortality among PWH.

Toward Safer Opioid Prescribing in HIV care (TOWER): a mixed-methods, cluster-randomized trial.

BACKGROUND: The 2016 U.S. Centers for Disease Control Opioid Prescribing Guideline (CDC Guideline) is currently being revised amid concern that it may be harmful to people with chronic pain on long-term opioid therapy (CP-LTOT). However, a methodology to faithfully implement the CDC guideline, measure prescriber adherence, and systematically test its effect on patient and public health outcomes is lacking. We developed and tested a CDC Guideline implementation strategy (termed TOWER), focusing on an outpatient HIV-focused primary care setting. METHODS: TOWER was developed in a stakeholder-engaged, multi-step iterative process within an Information, Motivation and Behavioral Skills (IMB) framework of behavior change. TOWER consists of: 1) a patient-facing opioid management app (OM-App); 2) a progress note template (OM-Note) to guide the office visit; and 3) a primary care provider (PCP) training. TOWER was evaluated in a 9-month, randomized-controlled trial of HIV-PCPs (N = 11) and their patients with HIV and CP-LTOT (N = 40). The primary outcome was CDC Guideline adherence based on electronic health record (EHR) documentation and measured by the validated Safer Opioid Prescribing Evaluation Tool (SOPET). Qualitative data including one-on-one PCP interviews were collected. We also piloted patient-reported outcome measures (PROMs) reflective of domains identified as important by stakeholders (pain intensity and function; mood; substance use; medication use and adherence; relationship with provider; stigma and discrimination). RESULTS: PCPs randomized to TOWER were 48% more CDC Guideline adherent (p < 0.0001) with significant improvements in use of: non-pharmacologic treatments, functional treatment goals, opioid agreements, prescription drug monitoring programs (PDMPs), opioid benefit/harm assessment, and naloxone prescribing. Qualitative data demonstrated high levels of confidence in conducting these care processes among intervention providers, and that OM-Note supported these efforts while experience with OM-App was mixed. There were no intervention-associated safety concerns (defined as worsening of any of the PROMs). CONCLUSIONS: CDC-guideline adherence can be promoted and measured, and is not associated with worsening of outcomes for people with HIV receiving LTOT for CP. Future work would be needed to document scalability of these results and to determine whether CDC-guideline adherence results in a positive effect on public health. Trial registration https://clinicaltrials.gov/ct2/show/NCT03669939 . Registration date: 9/13/2018.

Decreasing risk among HIV patients on opioid therapy for chronic pain: Development of the TOWER intervention for HIV care providers.

Many people with HIV (PWH) experience chronic pain that limits daily function and quality of life. PWH with chronic pain have commonly been prescribed opioids, sometimes for many years, and it is unclear if and how the management of these legacy patients should change in light of the current US opioid epidemic. Guidelines, such as the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain (CDCG), provide recommendations for the management of such patients but have yet to be translated into easily implementable interventions; there is also a lack of strong evidence that adhering to these recommendations improves patient outcomes such as amount of opioid use and pain levels. Herein we describe the development and preliminary testing of a theory-based intervention, called TOWER (TOWard SafER Opioid Prescribing), designed to support HIV primary care providers in CDCG-adherent opioid prescribing practices with PWH who are already prescribed opioids for chronic pain. TOWER incorporates the content of the CDCG into the theoretical and operational framework of the Information Motivation and Behavioral Skills (IMB) model of health-related behavior. The development process included elicitation research and incorporation of feedback from providers and PWH; testing is being conducted via an adaptive feasibility clinical trial. The results of this process will form the basis of a large, well-powered clinical trial to test the effectiveness of TOWER in promoting CDCG-adherent opioid prescribing practices and improving outcomes for PWH with chronic pain.