Opioid Injection Research Articles

The tale of two Badakhshans: Determinants of access and utilization of HIV preventive services along the Afghan-Tajik border.

Injection of opioids has contributed to growing HIV epidemics in Tajikistan and Afghanistan. This qualitative study explored determinants of access to primary prevention and screening for HIV among people who inject drugs (PWID) residing in border communities of Gorno-Badakhshan, Tajikistan and Badakhshan, Afghanistan. Semi-structured interviews were conducted with PWID, community leaders, and healthcare workers. The social-ecological model was used to inform a thematic analysis of determinants of access. There were no preventive or screening services for HIV in the border districts of Afghanistan. Barriers to accessing HIV-related services in Tajikistan, and to accessing general health services in Afghanistan, included: lack of knowledge about HIV, inaccessible communities with poor infrastructure, discrimination and violence against women, and stigmatization of PWID and people living with HIV. Access to HIV-related and other health services by PWID was facilitated by community leader support, family support, outreach services, and linkage of harm reduction services with HIV testing and care. Urgent interventions are needed to stem the escalating HIV epidemic in Afghanistan and enhance existing services in Tajik border communities. This qualitative study offers insights into barriers and facilitators for accessing HIV prevention and screening services among PWID, suggesting potential interventions.

Exploration of weekly variation in naloxone possession and carriage among people who use opioids in New York City before, during, and after the COVID-19 pandemic.

Naloxone is critical for reversing opioid-related overdoses. However, there is a dearth of research examining how naloxone possession and carriage are impacted by time-varying individual and social determinants, and if this differed during the height of the COVID-related mitigation measures (e.g., shutdowns). We utilized weekly ecological momentary assessments (EMA) to measure factors associated with naloxone possession and carriage among 40 people who use illicit opioids in New York City, for 24 months. Descriptive statistics were used to explore the frequency of weeks with consistent naloxone possession and carriage. Mixed effects binary and multivariable logistic regression was used to test for the impact of time-varying EMA- and baseline-level factors on each outcome. Approximately 70% of weekly EMAs were associated with consistent naloxone possession or carriage. In multivariable models, compared to during the height of the COVID-related shutdowns (March 12, 2020-May 19, 2021), the time before was associated with lower odds of consistent possession (Odds Ratio (OR) = 0.05, 95% Confidence Interval (CI) = 0.01-0.15) and consistent carriage (OR = 0.06, CI = 0.01-0.25). Additionally, being female (OR = 11.15, CI = 2.85-43.42), being White versus being Black or Hispanic/Latinx (OR = 8.05, CI = 1.96-33.06), and lifetime overdose (OR = 1.96, CI = 1.16-19.80) were associated with higher odds of consistent possession. Recent opioid injection (OR = 3.66, CI = 1.34-9.94), being female (OR = 7.91, CI = 3.91-8.23), and being White (OR = 5.77, CI = 1.35-24.55) were associated with higher odds of consistent carriage. Not wanting to be perceived as a drug user was reported in nearly one third (29.0%; 190/656) of EMAs where inconsistent possession was reported. Our findings paint a relatively positive picture of possession and carriage during COVID-related shutdowns, particularly among white and female participants, and highlight the importance of capturing time-varying factors to understand naloxone-related behavior. To curb growing disparities, outreach to equip Black and Hispanic/Latinx people with naloxone is needed as well as interventions to reduce stigma as a barrier to naloxone engagement.

S135 - Differences in Hepatitis C Virus (HCV) Testing and Treatment by Opioid, Stimulant, and Polysubstance Injection Among People who Inject Drugs (PWID) in Rural U.S. Communities

S135 - Differences in Hepatitis C Virus (HCV) Testing and Treatment by Opioid, Stimulant, and Polysubstance Injection Among People who Inject Drugs (PWID) in Rural U.S. Communities

Longitudinal trends in service utilisation of Alcohol and Other Drugs Services (AODS) during COVID-19: A Scoping Review

Background: COVID-19 has affected service delivery and utilization of AODS worldwide with a potential negative impact on service users and staff. Objectives: To understand the trends of service utilization of AODS, identify knowledge gaps, and provide directions for future research and planning. Methods: Medline, Embase, CINAHL, PubMed and PsycINFO were searched for original articles published in English since 2019, with quantitative analysis of service utilization of AODS. Of the 1546 initial search results, 938 were screened after de-duplication and 43 underwent full-text review. Data extracted from 30 studies informed this review. Results: Of the studies, 29 were from high-income countries and 15 focused on medication for opioid use disorders (MOUD). An initial reduction of service utilization followed by gradual improvement was seen in most treatment types, with most disruptions in residential programs, outreach services, home visits, group therapy and needle syringe programs and fewer disruptions in individual counselling and MOUD. Treatment initiations decreased, while treatment adherence improved during COVID-19. The use of telehealth and treatment-related policy changes were associated with improved service utilization. Telehealth was associated with catchment expansion and broadening of service-user profiles. An increased tendency to use the opioid long-acting injection was reported in Australia. Conclusions: The impact of COVID-19 on AODS changed over time and according to, the drug/treatment type and geographical remoteness. Main contributors to minimizing disruptions in service utilization included treatment-related policy changes, telehealth, and newer treatment modalities. Longitudinal studies beyond 2021 and studies on regional/rural AODS and AOD workforce are recommended.

Belonephilia as a model for interpretation of some relapsing features in chronic substance addiction and needle fixation

ABSTRACT Objective The purpose of this article is to illustrate how a peculiar behavior, skin puncture-seeking based on “philia,” may support the propensity to recidivism in subjects diagnosed with addictive disorders during treatment. Method Sixty-eight patients were interviewed about their behavior concerning the use of needles for the almost exclusive injection of opioids. Their opinions were examined according to the presence or absence of similar behaviors, irrespective of drug injection. The findings were organized and statistically elaborated. For the period of one year, every patient visited for evaluation and for control was asked to discuss the following: 31 surely suffered from this form; 29 did not but were sure of its existence; 8 denied its existence. Results The existence of needle fixation was largely confirmed. About half of patients with relapsing intravenous administrations of addictive disorder suffered or had suffered from this form. The results showed that this condition did not significantly increase the risk of relapse or reduce the duration of remission with the same duration of illness. This finding was unexpected because statistical significance was reached only in the difference between the group of “those who know but do not have” and the group of “those who deny.” Every other comparison produced no statistical significance. Conclusions Suffering from this form has a non-increased risk compared with not suffering from it. Similarly, having the problem is not riskier than denying its existence. The issue is that those who know about needle fixation, but do not suffer from it, have a significant increase in the risk of relapse and a significant reduction in the number of days of remission in the same illness duration and with the same treatment.

Comparison of sequential and mixture injections of opioids and hyperbaric bupivacaine for subarachnoid block for lower segment caesarean section: a randomised controlled study.

Opioids are commonly added to local anaesthetic for subarachnoid block for caesarean section due to their synergistic effects. The physiochemical characteristics of opioids suggest premixing with hyperbaric bupivacaine may limit their distribution within the CSF. We studied the effect of a separate injection with a combination of bupivacaine, morphine and fentanyl on block characteristics, haemodynamic changes, postoperative pain and patient satisfaction. Following ethical approval and informed consent, a prospective double-blinded randomised controlled trial was performed in a university hospital. A total of 126 patients undergoing caesarean section were randomised to two groups. In group M, the premixed group, patients received 12mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 100 mcg of morphine injected as a single mixture. In group S, the separate injection group, patients received the same drugs in separate injections. Measurements included haemodynamics, block distribution, intra- and postoperative pain, as well as patient satisfaction. Patients in both groups had similar block height, time to maximum sensory block, time to block regression and motor block. However, haemodynamics were different between the groups. The proportion of systolic hypotension episodes was greater in group S [159/1320 (12.05%)] than group M [113/1452 (7.78%)], with P = 0.0002. Moreover, a greater amount of ephedrine was administered in group S than group M, with values 12.09 (8.1) and 9.09 (8.5) mg respectively (P = 0.001). Additionally, postoperative pain, as measured by the Visual Analogue Scale (VAS), was greater in group M, with a VAS of 4.6 (1.7), vs. group S, which recorded a VAS of 3.8 (2.0) (P = 0.017). Sequential injection of intrathecal opioids and hyperbaric bupivacaine resulted in greater early haemodynamic instability and slightly better postoperative analgesia without any difference in block height or patient satisfaction. NCT04403724.

“I'm just searching to get better”: Constructions of treatment citizenship on injectable opioid agonist treatment

BackgroundAs part of the response to Canada's worsening overdose crisis driven by a toxic, adulterated drug supply, there has been increased attention to and expansion of drug treatment, options, including injectable opioid agonist treatment (iOAT). iOAT typically involves the, witnessed daily injection of opioids under healthcare provider supervision. There is a robust, evidence base on iOAT; however, there has been less focus on how people engage with this; treatment outside of clinical trials. This paper examines how people engage with iOAT programs, in expanded treatment settings in Canada, focusing on how the broader socio-structural context, shapes patient subjectivities in treatment. MethodsThis study draws on critical ethnographic and community-based research approaches, conducted with people accessing four iOAT programs in Vancouver's Downtown Eastside; neighbourhood from May 2018 to November 2019. Data included in-depth baseline and followup, interviews and approximately 50 h of observation fieldwork conducted in one iOAT, program and with a subsample of participants in the surrounding neighbourhood. Analysis, leveraged the concepts of biological citizenship and structural vulnerability. ResultsThis analysis characterized three narrative frames—regular long-term engagers, pain, patients, and sporadic and short-term engagers—through in-depth case presentations of participants with distinct types of engagement with iOAT programs. Participants within these, narrative frames described a dominant form of iOAT citizenship, an autonomous patient who, regularly engages in treatment and avoids pleasure. However, structural vulnerabilities, including, homelessness and housing instability, entrenched poverty, criminal-legal system engagement, and unmanaged pain, shaped the ability of participants to make claims to this normative model of citizenship. ConclusionThis study examined how structural vulnerabilities impact people's construction and ability to make iOAT citizenship claims. Findings point to the need for changes within and outside of iOAT programs, such as lower threshold treatment models, improved social services (e.g., secure housing), and pain management support.

Relationship between opioid cross-tolerance during buprenorphine stabilization and return to opioid use during buprenorphine dose tapering.

Opioid injection drug use (IDU) has been linked to a more severe pattern of use (e.g. tolerance, overdose risk) and shorter retention in treatment, which may undermine abstinence attempts. This secondary data analysis of four human laboratory studies investigated whether current opioid IDU modulates subjective abuse liability responses to high-dose hydromorphone during intermediate-dose buprenorphine stabilization (designed to suppress withdrawal but allow surmountable agonist effects), and whether hydromorphone response magnitude predicts latency of return to opioid use during buprenorphine dose-tapering. Regular heroin users not currently seeking treatment (n = 54; 29 current injectors, 25 non-injectors) were stabilized on 8-mg/day sublingual buprenorphine and assessed for subjective responses (e.g. 'liking', craving) to hydromorphone 24-mg intramuscular challenge (administered 16-hr post-buprenorphine) under randomized, double-blinded, controlled conditions. A subgroup (n = 35) subsequently completed a standardized 3-week outpatient buprenorphine dose-taper, paired with opioid-abstinent contingent reinforcement, and were assessed for return to opioid use based on thrice-weekly urinalysis and self-report. During buprenorphine stabilization, IDU reported lower 'liking' of buprenorphine and post-hydromorphone peak 'liking', 'good effect' and 'high' compared to non-IDU. Less hydromorphone peak increase-from-baseline in 'liking' (which correlated with less hydromorphone-induced craving suppression) predicted significantly faster return to opioid use during buprenorphine dose-tapering. In these buprenorphine-stabilized regular heroin users, IDU is associated with attenuated 'liking' response (more cross-tolerance) to buprenorphine and to high-dose hydromorphone challenge and, in turn, this cross-tolerance (but not IDU) predicts faster return to opioid use. Further research should examine mechanisms that link cross-tolerance to treatment response.

Investigating Patients’ Satisfaction With Patient-controlled Analgesia Versus Intrathecal Opioid Injection After Cesarean Section

Background: This study compares patients’ satisfaction with patient-controlled analgesia versus intrathecal opioid injection after cesarean section in Shariati and Khalij Fars hospitals in Bandar Abbas City, Iran, from 2016 to 2017. Methods: This double-blind, randomized clinical trial included 60 women with term pregnancies scheduled for elective cesarean section in Shariati and Khalij Fars hospitals in Bandar Abbas City, Iran, from 2017 to 2018. The patients were randomized into two groups: One group received patient-controlled analgesia (PCA), and the other group received intrathecal opioid injection. A numerical rating scale was used to assess pain and patient satisfaction. The patients also reported nausea, vomiting, and pruritus. The data were analyzed using the SPSS software, version 25. Results: Nausea and or vomiting did not differ significantly between the groups (P=0.46). The highest frequency of pruritus was observed in the PCA group at 1 (P=0.44), 4 (P=1.00), and 24 (P=0.24) h after surgery. Patient satisfaction was higher in the intrathecal opioid group (9.23±1.22) compared to the PCA group (8.84±1.22); however, the difference between groups was not statistically significant (P=0.08). Discussion: The results of the current study showed that despite the novelty of PCA, this method is not superior to conventional methods such as intrathecal opioid injection for pain relief. Also, patient satisfaction was lower with PCA compared to intrathecal opioids.

Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine

BackgroundThe efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. MethodsIn this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. ResultsA total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. ConclusionAdherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.

Binge Drug Injection in a Cohort of People Who Inject Drugs in Montreal: Characterizing the Substances and Social Contexts Involved

AbstractWe describe binge drug injection in a longitudinal cohort study of people who inject drugs (PWID) in Montreal, Canada (eligibility: age ≥ 18, past-6-month injection drug use; follow-up: 3-monthly interviews). Bingeing was defined as injecting large quantities of drugs over a limited period, until participants ran out or were unable to continue, in the past 3 months. We recorded substances and circumstances typically involved in binge episodes. Eight hundred five participants (82% male, median age 41) provided 8158 observations (2011–2020). Thirty-six per cent reported bingeing throughout follow-up. Binges involved a diverse range of substances and social contexts. Cocaine was involved in a majority of recent binges (73% of visits). Injection of multiple drug classes (24% of visits) and use of non-injection drugs (63% of visits) were common, as were opioid injection (42%) and injecting alone (41%). Binge drug use may thus be an important yet overlooked trigger of overdose and other harms among PWID. This understudied high-risk behavior warrants further research and public health attention.

Associations of hepatitis C virus (HCV) antibody positivity with opioid, stimulant, and polysubstance injection among people who inject drugs (PWID) in rural U.S. communities.

People who inject drugs (PWID) in the rural U.S. often inject stimulants, alone or with opioids. The impact of these substance use patterns may influence HCV risk behaviors. This analysis examines the associations of HCV antibody positivity with injecting only opioids, only stimulants (methamphetamine/cocaine), and opioids and stimulants together among rural PWID. The Rural Opioid Initiative (ROI) consists of eight research sites that enrolled people who use drugs in rural communities in ten U.S. states from 2018 to 2020. This cross-sectional analysis included adult participants who resided in a study area and injected any drug in the past 30 days. The primary outcome was HCV antibody positivity. The exposure of interest was injection drug use classified as only opioids, only stimulants, separate injections of opioids and stimulants, and same-syringe injection of both in the past 30 days. We used multivariable log-binomial regression with generalized linear mixed models to generate prevalence ratios (P.R.) adjusted for demographics, injection history, health insurance, and substance use treatment. Among 3,084 participants enrolled in the ROI, 1,982 met inclusion criteria. Most participants injected opioids and stimulants in the same syringe (34%) or separately (21%), followed by injecting only stimulants (26%), and injecting only opioids (19%). Half (51%) were HCV antibody positive. Compared to people who injected only stimulants, HCV antibody positivity was more prevalent among people who injected opioids alone (aPR=1.62, 95% CI:(1.29-2.03)), injected both opioids and stimulants separately (aPR=1.61, 95% CI:(1.32-1.95)), and in the same syringe (aPR=1.54, 95% CI:(1.28-1.85)). HCV antibody positivity, indicating prior exposure, was highest among those who had recently injected opioids, alone or with stimulants. Additional nucleic acid testing is necessary to confirm active infection. More research is needed to determine the underlying causes of HCV antibody positivity by injection use.

Treatment of Refractory Low Back Pain Using Passive Recharge Burst in Patients Without Options for Corrective Surgery: Findings and Results From the DISTINCT Study, a Prospective Randomized Multicenter Controlled Trial

ObjectiveSpinal cord stimulation (SCS) is effective for relieving chronic intractable pain conditions. The Dorsal spInal cord STImulatioN vs mediCal management for the Treatment of low back pain study evaluates the effectiveness of SCS compared with conventional medical management (CMM) in the treatment of chronic low back pain in patients who had not undergone and were not candidates for lumbar spine surgery. Methods and MaterialsPatients were randomized to passive recharge burst therapy (n = 162) or CMM (n = 107). They reported severe pain and disability for more than a decade and had failed a multitude of therapies. Common diagnoses included degenerative disc disease, spondylosis, stenosis, and scoliosis—yet not to a degree amenable to surgery. The six-month primary end point compared responder rates, defined by a 50% reduction in pain. Hierarchical analyses of seven secondary end points were performed in the following order: composite responder rate (numerical rating scale [NRS] or Oswestry Disability Index [ODI]), NRS, ODI, Pain Catastrophizing Scale responder rate, Patient Global Impression of Change (PGIC) responder rate, and Patient-Reported Outcome Measure Information System-29 in pain interference and physical function. ResultsIntention-to-treat analysis showed a significant difference in pain responders on NRS between SCS (72.6%) and CMM (7.1%) arms (p < 0.0001). Of note, 85.2% of those who received six months of therapy responded on NRS compared with 6.2% of those with CMM (p < 0.0001). All secondary end points indicated the superiority of burst therapy over CMM. A composite measure on function or pain relief showed 91% of subjects with SCS improved, compared with 16% of subjects with CMM. A substantial improvement of 30 points was observed on ODI compared with a <one-point change in the CMM arm. Three serious and 14 non–serious device- or procedure-related events were reported. ConclusionsThis study found substantial improvement at six months in back pain, back pain-related disability, pain-related emotional suffering, PGIC, pain interference, and physical function in a population with severe, debilitating back pain for more than a decade. These improvements were reported in conjunction with reduced opioid use, injection, and ablation therapy. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT04479787.

Do Intrathecal Opioids Improve Surgical Outcomes After Coronary Artery Bypass Grafting? A Systematic Review and Analysis

BACKGROUND: Intrathecal opioids have long been used as analgesia for intractable cancer pain or as part of spinal anesthesia during obstetric operations. More recently, they have been used preoperatively as a pain management adjuvant for open cardiac and thoracic procedures. OBJECTIVE: This study aims to analyze the impact of administering intrathecal opioids before cardiac and thoracic surgeries on postoperative pain and mechanical ventilation. STUDY DESIGN: Systematic review and meta-analysis. SETTING: University, School of Medicine, and several university-affiliated hospitals. METHODS: Five outcomes were studied, including the primary outcome of time to extubation, secondary outcomes of analgesia requirements at 24 and 48 hours, resting pain scores at 1 and 24 hours post-extubation, ICU length of stay in hours, and hospital length of stay in days. A search of multiple databases provided 28 studies reporting 4,000 total patients. Outcomes were measured using continuous mean difference with a 95% confidence interval, and the studies were examined for heterogeneity and sensitivity analysis. RESULTS: The primary outcome analysis suggested that time to extubation was 42 minutes shorter in the intrathecal opioid group (ranging from 82 to 1 minute, P = 0.04). There was also a decrease in postoperative analgesia requirements at both 24 hours (mean difference (MD) = -8.95 mg morphine equivalent doses (MED) [-9.4, -8.5], P &lt; 0.001) and 48 hours (MD = -17.7 mg MED [-23.1, -12.4], P &lt; 0.001) with I2 of 94% and 85% respectively, an improvement of pain scores at both 1 hour (MD = -2.24 [-3.16, -1.32], P &lt; 0.001) and 24-hours (MD = -1.64 [-2.48, -0.80], P =&lt; 0.001) I2 of 94% and 85%, no change in both ICU length of stay (MD = -0.27 hours [-0.55, 0.01], P = 0.06) I2 = 77% and hospital length of stay (MD = -0.30 days [-0.66, 0.06], P = 0.11) I2 = 32%. LIMITATIONS: The major limitation of this meta-analysis was the inconsistent dosages of intrathecal opioids utilized. Some used the same dose for each patient, while other studies used weight-based doses. The differences in the outcomes observed may then be a result of the different amounts of opioids administered rather than the technique itself. Another limitation was the inconsistent timing of reports for pain scores and postoperative analgesic requirements. Further studies were analyzed at the 2 time periods for both secondary outcomes, making it difficult to attribute the 2 effects solely to the intervention. CONCLUSIONS: We conclude that preoperative injection of intrathecal opioids is significantly associated with decreased time to extubation, decreased postoperative analgesia requirement, and improved pain scores. In controlled conditions with adequate staff education, this method of analgesia may make it possible to extubate the patients after the surgery in the operating room and fast-track their discharge from the hospital. KEY WORDS: Analgesia, cardiac surgery, extubation, fast-tracking, hospital stay, spinal

High levels of interest in access to free safer smoking equipment to reduce injection frequency among people who inject drugs in Seattle, Washington

BackgroundDrug use route transition interventions promote safer consumption by facilitating a switch from injection to safer routes such as smoking or oral consumption. MethodsWe performed a descriptive analysis using data from questions about “free, clean equipment for smoking” heroin, methamphetamine and/or crack from the Seattle 2018 National HIV Behavioral Surveillance survey of people who inject drugs (N = 555). We estimated the proportion of respondents with access to free safer smoking equipment, and among these participants, the proportion who reported that this access reduced their injection frequency. Among respondents without access to free safer smoking equipment, we described the proportion who were interested in getting access, and whether they thought this access would reduce their injection frequency. ResultsAmong participants who reported prior year heroin (n = 495), methamphetamine (n = 372), or crack (n = 88) injection, 11%, 11% and 12% reported access to free safer smoking equipment, respectively. Of those with access, the proportion that reported that access reduced their injection frequency ranged from 12% to 44%. Among participants without access, 28% who used heroin, 45% who used methamphetamine, and 49% who used crack were interested in access. Of interested participants, a majority reported that they thought this access would reduce their frequency of injection. ConclusionsAccess to free safer smoking equipment was limited. Many participants were interested in getting free safer smoking equipment and reported that this access may reduce their injection frequency. Safer smoking equipment is a harm reduction strategy that should be available to reduce risks from opioid and stimulant injection.

Buprenorphine treatment receipt characteristics and retention among people who inject drugs at Integrated Care Centers in India

BackgroundIndia is facing overlapping opioid injection and HIV epidemics among people who inject drugs (PWID) in several cities. Integrated Care Centers (ICCs) provide single-venue HIV and substance use services to PWID. We evaluated PWID engagement in daily observed buprenorphine treatment at 7 ICCs to inform interventions. MethodsWe analyzed 1-year follow-up data for PWID initiating buprenorphine between 1 January – 31 December 2018, evaluating receipt frequency, treatment interruptions (no buprenorphine receipt for 60 consecutive days with subsequent re-engagement), and drop-out (no buprenorphine receipt for 60 consecutive days without re-engagement). Using descriptive statistics, we explored differences between ICCs in the opioid-endemic Northeast region and ICCs in the emerging opioid epidemic North/Central region. We used a multivariable logistic regression model to determine predictors of treatment drop-out by 6 months. Results1312 PWID initiated buprenorphine (76% North/Central ICCs vs. 24% Northeast ICCs). 31% of PWID in North/Central, and 25% in Northeast ICCs experienced ≥ 1 treatment interruption in 1 year. Over 6 months, 48% of PWID in North/Central vs. 60% in Northeast ICCs received buprenorphine ≤ 2 times/week (p < 0.0001). A third of PWID in North/Central vs. half in Northeast ICCs experienced treatment drop-out by 6 months (p < 0.001). In the multivariable model, living in Northeast cities was associated with increased odds of drop-out while counseling receipt was associated with decreased odds. ConclusionsRetention among PWID initiating buprenorphine at ICCs was comparable to global reports. However, regional heterogeneity in retention, and low daily buprenorphine receipt suggest patient-centered interventions adapted to regional contexts are urgently needed.

Effect of intravenous magnesium on post-operative pain following Latarjet shoulder reconstruction.

Single injection ropivacaine interscalene anesthesia (ISA) is frequently used in Latarjet reconstruction to enhance post-operative analgesia. A potential limitation is the occurrence of severe rebound pain on block resolution. We investigated the effect of intravenous magnesium on post-operative pain, particularly at the transition of block resolution to multimodal analgesia. Elective patients (n = 40) having Latarjet open shoulder reconstruction were randomised to receive either intravenous magnesium sulphate 50 mg/kg (M) or normal saline (S) before induction. Post-operatively, a standardised analgesic regimen was used, and post-operative pain was recorded using a verbal numerical rating assessment (VNRA) score. Requirement for injected opioid analgesia was recorded. ISA provided longstanding analgesia in all patients with block duration slightly prolonged in the magnesium group (16.7(1.0) (S), 17.8(1.3) h (M), p = 0.049). Magnesium resulted in less rebound pain following ISA resolution (VNRA 4.0 (0.6) M, 6.2 (0.8) S, p = 0.03) and lower pain intensity at 24 h. Four patients had nausea and two required rescue opioid injection. Magnesium before Latarjet surgery results in less rebound pain following ropivacaine block and improves post-operative analgesia. Magnesium may be indicated in major upper limb surgery, where significant pain intensity is anticipated. Treatment study; Randomised blinded; Level 2.

Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences

The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.

Men who inject opioids exhibit altered tRNA-Gly-GCC isoforms in semen.

In addition to their role in protein translation, tRNAs can be cleaved into shorter, biologically active fragments called tRNA fragments (tRFs). Specific tRFs from spermatocytes can propagate metabolic disorders in second generations of mice. Thus, tRFs in germline cells are a mechanism of epigenetic inheritance. It has also been shown that stress and toxins can cause alterations in tRF patterns. We were therefore interested in whether injecting illicit drugs, a major stressor, impacts tRFs in germline cells. We sequenced RNA from spermatocytes and from semen-derived exosomes from people who inject illicit drugs (PWID) and from non-drug using controls, both groups of unknown fertility status. All PWID injected opioids daily, but most also used other illicit drugs. The tRF cleavage products from Gly-GCC tRNA were markedly different between spermatocytes from PWID compared to controls. Over 90% of reads in controls mapped to shorter Gly-GCC tRFs, while in PWID only 45% did. In contrast, only 4.1% of reads in controls mapped to a longer tRFs versus 45.6% in PWID. The long/short tRF ratio was significantly higher in PWID than controls (0.23 versus 0.16, P = 0.0128). We also report differential expression of a group of small nucleolar RNAs (snoRNAs) in semen-derived exosomes, including, among others, ACA14a, U19, and U3-3. Thus, PWID exhibited an altered cleavage pattern of tRNA-Gly-GCC in spermatocytes and an altered cargo of snoRNAs in semen-derived exosomes. Participants were not exclusively using opioids and were not matched with controls in terms of diet, chronic disease, or other stressors, so our finding are not conclusively linked to opioid use. However, all individuals in the PWID group did inject heroin daily. Our study indicates a potential for opioid injection and/or its associated multi-drug use habits and lifestyle changes to influence epigenetic inheritance.

Sexual HIV transmission risk behaviors associated with stimulant drug injection among people who non-medically use gabapentin and opioids

ABSTRACT Background Recent research shows that co-use of stimulants and opioids appears to be increasing and injection of opioids and stimulants carries a risk for HIV transmission. This study examined stimulant injection and sexual HIV risk behaviors among individuals who reported nonmedical use of gabapentin and opioids (n = 62). Methods Comparisons of people who injected stimulants to those who did not were conducted using chi-square and t-tests. Results Compared to those who did not, people who injected stimulants, were less likely to be African American/Black (p < 0.05) and more likely to report sex with another person who injects drugs (p < 0.01), recent injections of prescription and/or illicit opioids (p < .000), and hepatitis C infection (p < 0.01). Condomless intercourse during group sex was more prevalent among stimulant injectors, significant at the trend level (p < 0.1). Conclusions Given the documented association between the use of opioids and nonmedical use of gabapentin and the growing trend of opioid-stimulant co-use, future research must examine whether nonmedical use of gabapentin is an indicator of substance use disorder severity and/or a risk factor for injection drug use. Education and intervention opportunities that address group sex and other sexual risk behaviors are warranted.