Opioids and Infectious Disease: Immunosuppression, Prescribing Disparities, and Integrated Care

Abstract

Introduction The US opioid epidemic converges with several other public health crises. This dissertation explores three issues that are related to that convergence: (1) the US national frequency of outpatient prescribing of certain opioids that have known immunosuppressive properties but unknown clinical implications; (2) the racial/ethnic disparity of opioid prescribing in US emergency departments (EDs); and (3) the integration of care for substance use disorder (SUD), tuberculosis, and HIV, which is a primary strategy of the World Health Organization for mitigating the harms of these comorbidities. Aim 1 Methods: Publicly available datasets from the National Center for Health Statistics (NCHS) were analyzed to estimate US national frequencies of: (1) outpatient prescribing of immunosuppressive opioids (ISOs) to patients who are likely to be immunocompromised; as well as (2) concurrent prescribing of ISOs alongside anti-infective medications. Results: During the most recent 5-year periods of NAMCS (2012-2016) and NHAMCS-ED (2014-2018), ISOs were prescribed annually during nearly 11.6 million visits to outpatient physician offices and 11.1 million visits to EDs. In both care settings, patients with underlying conditions associated with immunosuppression were prescribed ISOs, including chronic conditions such as cancer, CKD, COPD, diabetes, ESRD, and HIV. Discussion: Until further research is conducted on the clinical relevance of these opioids’ immunosuppressive properties, their use to treat immunocompromised patients represent prescribing patterns that have unknown implications for patient outcomes. Aim 2 Methods: A conceptual framework of effect modification was used to analyze NHAMCS-ED datasets (years 2014-2018) and assess how demographic and socioeconomic variables modify the association between patient race/ethnicity and visits when ≥1 opioid was prescribed during an ED visit. Data analysis followed a priori assumptions that were expressed as causal diagrams (i.e., directed acyclic graphs). Logistic regression and tabular analyses (i.e., contingency tables) were used to compute odds ratios and 95% confidence intervals. Results: Patients who represent racial/ethnic minority groups, ages 18 to 64 years, had lower odds of receiving an opioid during an ED-visit that required urgent or semi-urgent care, relative to non-Hispanic White adults of similar age and immediacy of care. Discussion: The magnitude of racial/ethnic prescribing disparity appears to be modified by select patient characteristics, particularly age and the immediacy of care required during an ED-visit. Prescribing disparities may occur more intensely among visits that are triaged for urgent or semi-urgent care, rather than non-urgent or critical care situations. Aim 3 Methods: A scoping review was conducted to evaluate publications that are available on Embase, PubMed, CINAHL, and PsycINFO databases which pertain to the prevention or treatment of tuberculosis or HIV-associated tuberculosis among PWUD. This review followed Arksey and O’Malley’s methodology framework, as well as the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Results: The initial search identified 676 records that were deduplicated, screened and reviewed for eligibility. Seventeen studies were included for final data charting. Most of these studies evaluated drug dependency treatment programs that offered co-located TB prevention and SUD treatment services. No models of completely integrated TB, HIV, and SUD care were identified. Discussion: Outside the context of palliative care, opioid pharmaceuticals have been infrequently studied in the context of TB and HIV, which are both major priorities for Global Health. The ideal of completely integrated care for TB, HIV, and SUD may be unfeasible in most settings. Future literature reviews on this topic could focus on interventions or models of care that deliver the WHO’s comprehensive package of harm reduction for PWUD. Conclusion To our knowledge, this dissertation includes the first study to examine frequencies of prescribing immunosuppressive opioids in US outpatient care settings. ISOs are prescribed annually during >11 million visits in each outpatient setting, and both individual and population-level implications remain unclear. Additionally, this dissertation makes a novel contribution by identifying emergency severity and age as strong modifiers of the association between patient race/ethnicity and opioid prescribing. This work also affirms that few studies have been conducted on opioid pharmaceuticals and infectious diseases that are high-priority for Global Health, particularly TB and HIV. Future research could focus on the WHO’s comprehensive package of harm-reduction for PWUD.