Acceptability of a Fentanyl Vaccine to Prevent Opioid Overdose and Need for Personalized Decision-Making.

BACKGROUND: The opioid epidemic worsened during the coronavirus disease 2019 (COVID-19) pandemic. Synthetic opioids (primarily fentanyl) comprise the most common drugs involved in overdose (OD) death. A vaccine that blocks fentanyl from reaching the brain to prevent OD is under development, and insight is needed into its acceptability. METHODS: Using a semi-structured interview guide, persons with opioid use disorder (OUD), family, professionals, and the public were interviewed about attitudes and concerns regarding a fentanyl vaccine. Reactions to fictional clinical vignettes of persons at risk of OUD because of pain and/or substance use histories were collected, analyzed, and quantified for favorability. Interviews were transcribed, coded, and analyzed thematically. RESULTS: Among N = 64 participants, (70.3% female, average age 32.4 years), attitudes were favorable toward a fentanyl vaccine, with preference for lifelong durability (76% of n = 55 asked). Perceived benefits centered on the potential for a life-saving intervention, suffering averted, healthcare dollars saved, and the utility of a passive harm reduction strategy. Concerns centered on uncertainty regarding vaccine safety, questions about efficacy, worry about implications for future pain management, stigma, and need for supportive counseling and guidance to personalize decision making. Reactions to vignettes revealed complex attitudes toward fentanyl vaccination when considering recipient age, health history, and future risks for addiction and pain. CONCLUSIONS: Positive responses to a fentanyl vaccine were found along with appreciation for the complexity of a vaccine strategy to prevent OD in the setting of pain and uncertain durability. Further research is needed to elucidate operational, ethical, and communications strategies to advance the model.

Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs.

BACKGROUND: The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. METHODS: The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copies/ml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copies/ml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed. DISCUSSION: The T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05208697. Trial registry name: Tele-Harm Reduction. Registration date: January 26, 2022.

Using nominal group technique to identify barriers and facilitators to preventing HIV using combination same-day pre-exposure prophylaxis and medications for opioid use disorder.

BACKGROUND: Preventing HIV transmission among people who inject drugs (PWID) is a key element of the US Ending the HIV Epidemic strategy and includes both pre-exposure prophylaxis (PrEP) and medications for opioid use disorder (MOUD). While both lead to decreases in HIV transmission, MOUD has other social and health benefits; meanwhile, PrEP has additional HIV prevention advantages from sexual risk and the injection of stimulants. However, these medications are often prescribed in different settings and require multiple visits before initiation. Strategies to integrate these services (i.e., co-prescription) and offer same-day prescriptions may reduce demands on patients who could benefit from them. METHODS: Nominal group technique, a consensus method that rapidly generates and ranks responses, was used to ascertain barriers and solutions for same-day delivery of PrEP and MOUD as an integrated approach among PWID (n = 14) and clinical (n = 9) stakeholders. The qualitative portion of the discussion generated themes for analysis, and the ranks of the proposed barriers and solutions to the program are presented. RESULTS: The top three barriers among PWID to getting a same-day prescription for both PrEP and MOUD were (1) instability of insurance (e.g., insurance lapses); (2) access to a local prescriber; and (3) client-level implementation factors, such as lack of personal motivation. Among clinical stakeholders, the three greatest challenges were (1) time constraints on providers; (2) logistics (e.g., coordination between providers and labs); and (3) availability of providers who can prescribe both medications. Potential solutions identified by both stakeholders included pharmacy delivery of the medications, coordinated care between providers and health care systems (e.g., case management), and efficiencies in clinical care (e.g., clinical checklists), among others. CONCLUSIONS: Implementing and sustaining a combined PrEP and MOUD strategy will require co-training providers on both medications while creating efficiencies in systems of care and innovations that encourage and retain PWID in care. Pilot testing the co-prescribing of PrEP and MOUD with quality performance improvement is a step toward new practice models.

Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US.

The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).

Impact of Cannabis Use, Substance Use Disorders, and Psychiatric Diagnoses on COVID-19 Outcomes: A Retrospective Cohort Study.

Objective: While psychiatric disorders have been recognized as a risk factor for COVID-19 outcomes, the impact of substance use disorders (SUD) on COVID-19 outcomes has not, to date, been examined in a systematic manner. We examined the association between SUD (cannabis, cocaine, alcohol, opioid, and benzodiazepine) as well as psychiatric diagnoses (schizophrenia, mood disorders, anxiety disorders) and COVID-19 outcomes in a large, retrospective cohort study.Methods: COVID-19-positive patients admitted to a large health care system in the US between January and December 2020 were included in this study. SUD and psychiatric diagnoses were identified from urine toxicology reports and ICD-10 diagnosis codes in the electronic medical record, respectively. Multivariable logistic regression was performed controlling for potential confounders such as age, race, sex, smoking status, and medical comorbidities. COVID-19-relevant outcomes included mortality, need for intensive care unit (ICU) admission, need for ventilatory support, length of hospitalization, and number of hospitalizations.Results: Among COVID-19 patients (N = 6,291), those with SUD were more likely to require ICU admission (adjusted odds ratio [AOR] = 1.46, P = .003) and ventilatory support (AOR = 1.49, P = .01). The association between SUD and ICU admission was driven by alcohol use disorder (AUD), whereas that between SUD and ventilatory support was driven by both AUD and opioid use disorder (OUD). Patients with SUD were more likely to have a longer mean maximum length of hospitalization (11.32 vs 8.62 days, P < .0001) and a greater mean number of hospital admissions in 2020 (2.96 vs 2.33, P < .0001). These associations were significant for cannabis use disorder, AUD, OUD, and benzodiazepine use disorder. The association with greater number of admissions was also significant for cocaine use disorder. Patients with psychiatric diagnoses were also more likely to have a greater maximum length of hospitalization (11.93 vs 8.39 days, P < .0001) and hospital admissions (2.72 vs 2.31, P < .0001). These associations were significant for schizophrenia, mood disorders, and anxiety disorders.Conclusions: COVID-19 patients with SUD had greater likelihood of requiring critical interventions, such as ICU admission and ventilatory support. SUD and psychiatric diagnoses were also associated with a longer duration of hospitalization and greater number of hospital admissions. These findings identify COVID-19 patients with SUD and psychiatric comorbidities as a high-risk group.

Reduced Opioid Use and Prescribing in a Same Day Discharge Pilot Enhanced Recovery Program for Elective Minimally Invasive Colorectal Surgical Procedures During the COVID-19 Pandemic.

PURPOSE: Enhanced recovery pathways (ERPs) are associated with reduced complications and length of stay. The validation of the I-FEED scoring system, advances in perioperative anesthesia, multimodal analgesia, and telehealth remote monitoring have resulted in further evolution of ERPs setting the stage for same day discharge (SDD). Pioneers and early adopters have demonstrated the safety and feasibility of SDD programs. The aim of this study is to evaluate the impact of a pilot SDD ERP on patient self-reported pain scoring and narcotic usage. METHODS: A quality improvement pilot program was conducted to assess the impact of a SDD ERP on post-operative pain score reporting and opioid use in healthy patients undergoing elective colorectal surgery as an alternative to post-operative hospitalization during the COVID-19 pandemic (May 2020-December 2021). Patients were monitored remotely with daily telephone visits on POD 1-7 assessing the following variables: I-FEED score, pain score, pain management, bowel function, dietary advancement, any complications, and/or re-admissions. RESULTS: Thirty-seven patients met the highly selective eligibility criteria for "healthy patient, healthy anastomosis." SDD occurred in 70%. The remaining 30% were discharged on POD 1. Mean total narcotic usage was 5.2 tablets of 5 mg oxycodone despite relatively high reported pain scores. CONCLUSIONS: In our initial experience, SDD is associated with significantly lower patient narcotic utilization for postoperative pain management than hypothesized. This pilot SDD program resulted in a change in clinical practice with reduction of prescribed discharge oxycodone 5 mg quantity from #40 to #10 tablets.

When Management of Cancer-Related Pain Is Complicated by Coexisting Opioid Use Disorder: A Case Review.

Patients with cancer are living longer, and many experience pain secondary to tumor invasion or as a consequence of cancer-directed therapies. Opioid use disorders and associated morbidity and mortality have increased with dramatic rise during the SARS-CoV-2 pandemic. National and international stakeholders have developed clinical practice guidelines in an effort to curb opioid misuse and overdose-related death. However, to ensure that patients with cancer do not experience barriers to adequate pain management, most of these guidelines are not intended for patients with cancer-related pain or for those receiving palliative or hospice care. Oncology, palliative, and hospice care providers are increasingly tasked with the management of severe disease-related pain in the setting of coexisting opioid use disorder without research on the most effective risk and harm reduction strategies to guide care. Clinicians should be familiar with addiction medicine and chronic pain literature and be able to incorporate some of these best practices. This case study reviews the management of severe cancer-related pain in a patient with co-occurring opioid use disorder, utilizing many of the best practices in available clinical practice guidelines for the management of chronic non-cancer-related pain.

Opioids and Acute Kidney Injury.

Opioid use and misuse in the United States has been at epidemic proportions and is predicted to increase further in the setting of the Coronavirus disease 19 pandemic. Acute kidney injury is a condition associated with significant morbidity and increased mortality. We review the literature on the effect of opioids on kidney function and critically examine the association between opioid use and acute kidney injury and identify at-risk populations in whom opioids should be used with caution. We also discuss the role of biomarkers in elucidating this condition and propose preventive measures, novel therapeutic options, and research directions.

The Effects of opioids on female fertility, pregnancy and the breastfeeding mother-infant dyad: A Review.

Opioids cover a broad class of natural, synthetic and semi-synthetic drugs that act on opioid receptors to produce powerful analgesic effects. Rates of opioid use and opioid agonist maintenance treatment have increased substantially in recent years, particularly among women. Trends and outcomes of opioids use on fertility, pregnancy and breastfeeding, and longer-term child developmental outcomes have not been well-described. Here, we review the existing literature on the health effects of opioid use on female fertility, pregnancy, breastmilk and the exposed infant. We find that the current literature is primarily concentrated on the impact of opioid use in pregnancy and neonatal outcomes, with little exploration of effects on fertility. Studies are limited in number, some with small sample sizes, and many are hampered by methodological challenges related to confounding and other potential biases. Opioid use is becoming more prevalent due to environmental pressures such as COVID-19. More research is needed to better elucidate its effects on reproductive health among younger women and support the development of evidence-based recommendations for safe prescription practices and public health messaging.

The impact of long-term opioid use on the risk and severity of COVID-19.

Based on evidence of the immunosuppressive effects of chronic opioids, long-term users of prescription and illicit opioids comprise an unrecognized but growing population of Americans with compromised immune function and respiratory depression who may be at high risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)-related hospitalization, prolonged ICU stay, adverse events, and death. This perspective is of broad clinical and public health importance because the US has the highest population of long-term users of prescription opioids, a sequel of a decade-long practice of opioid overprescribing in the US. For long-term opioid users who are hospitalized for COVID-19, clinicians face clinical challenges arising from the suppressive effects of opioids on the respiratory and immune functions, as well as the potential for adverse drug-drug interaction when opioids have to be continued in long-term users. More research is needed to further understand the association of long-term opioid use and susceptibility to COVID-19 and other emerging infections.

Countermeasures for Preventing and Treating Opioid Overdose.

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic "nanosponge" decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

Update: COVID-19 Upends Progress on Opioid Crisis.

The pandemic has stretched resources and complicated the delivery of care.

Opioid Use Disorder and COVID-19: Biological Plausibility for Worsened Outcomes.

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.

Opioid use disorder and the COVID 19 pandemic: A call to sustain regulatory easements and further expand access to treatment.

We highlight the critical roles that pharmacists have related to sustaining and advancing the changes being made in the face of the current COVID-19 pandemic to ensure that patients have more seamless and less complex access to treatment. Discussed herein is how the current COVID-19 pandemic is impacting persons with substance use disorders, barriers that persist, and the opportunities that arise as regulations around treatments for this population are eased.