Faculty Bibliography

OBJECTIVES:This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18-34, 35-64, and 65-75 years), sex, and race, and ethnicity. METHOD:VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups. RESULTS:Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups. DISCUSSION:The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time.

BACKGROUND/UNASSIGNED:The risk for cannabis use disorder (CUD) is elevated among U.S. adults with chronic pain, and CUD rates are disproportionately increasing in this group. Little is known about the role of medical cannabis laws (MCL) and recreational cannabis laws (RCL) in these increases. Among U.S. Veterans Health Administration (VHA) patients, we examined whether MCL and RCL effects on CUD prevalence differed between patients with and without chronic pain. METHODS/UNASSIGNED:Patients with ≥1 primary care, emergency, or mental health visit to the VHA and no hospice/palliative care within a given calendar year, 2005-2019 (yearly n=3,234,382 to 4,579,994) were analyzed using VHA electronic health record (EHR) data. To estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed CUD and whether this differed between patients with and without chronic pain, staggered-adoption difference-in-difference analyses were used, fitting a linear binomial regression model with fixed effects for state, categorical year, time-varying cannabis law status, state-level sociodemographic covariates, a chronic pain indicator, and patient covariates (age group [18-34, 35-64; 65-75], sex, and race and ethnicity). Pain was categorized using an American Pain Society taxonomy of painful medical conditions. OUTCOMES/UNASSIGNED:In patients with chronic pain, enacting MCL led to a 0·14% (95% CI=0·12%-0·15%) absolute increase in CUD prevalence, with 8·4% of the total increase in CUD prevalence in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·19% (95%CI: 0·16%, 0·22%) absolute increase in CUD prevalence, with 11·5% of the total increase in CUD prevalence in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in CUD prevalence (MCL: 0·037% [95%CI: 0·03, 0·05]; RCL: 0·042% [95%CI: 0·02, 0·06]), with 5·7% and 6·0% of the increases in CUD prevalence attributable to MCL and RCL. Overall, MCL and RCL effects were significantly greater in patients with than without chronic pain. By age, MCL and RCL effects were negligible in patients age 18-34 with and without pain. In patients age 35-64 with and without pain, MCL and RCL effects were significant (p<0.001) but small. In patients age 65-75 with pain, absolute increases were 0·10% in MCL-only states and 0·22% in MCL/RCL states, with 9·3% of the increase in CUD prevalence in MCL-only states attributable to MCL, and 19.4% of the increase in RCL states attributable to RCL. In patients age 35-64 and 65-75, MCL and RCL effects were significantly greater in patients with pain. INTERPRETATION/UNASSIGNED:In patients age 35-75, the role of MCL and RCL in the increasing prevalence of CUD was greater in patients with chronic pain than in those without chronic pain, with particularly pronounced effects in patients with chronic pain age 65-75. Although the VHA offers extensive behavioral and non-opioid pharmaceutical treatments for pain, cannabis may seem a more appealing option given media enthusiasm about cannabis, cannabis commercialization activities, and widespread public beliefs about cannabis efficacy. Cannabis does not have the risk/mortality profile of opioids, but CUD is a clinical condition with considerable impairment and comorbidity. Because cannabis legalization in the U.S. is likely to further increase, increasing CUD prevalence among patients with chronic pain following state legalization is a public health concern. The risk of chronic pain increases as individuals age, and the average age of VHA patients and the U.S. general population is increasing. Therefore, clinical monitoring of cannabis use and discussion of the risk of CUD among patients with chronic pain is warranted, especially among older patients. RESEARCH IN CONTEXT/UNASSIGNED:

BACKGROUND:Cannabis use disorder is associated with considerable comorbidity and impairment in functioning, and prevalence is increasing among adults with chronic pain. We aimed to assess the effect of introduction of medical cannabis laws (MCL) and recreational cannabis laws (RCL) on the increase in cannabis use disorder among patients in the US Veterans Health Administration (VHA). METHODS:Data from patients with one or more primary care, emergency, or mental health visit to the VHA in 2005-19 were analysed using 15 repeated cross-sectional VHA electronic health record datasets (ie, one dataset per year). Patients in hospice or palliative care were excluded. Patients were stratified as having chronic pain or not using an American Pain Society taxonomy of painful medical conditions. We used staggered-adoption difference-in-difference analyses to estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed cannabis use disorder and associations with presence of chronic pain, accounting for the year that state laws were enacted. We did this by fitting a linear binomial regression model stratified by pain, with time-varying cannabis law status, fixed effects for state, categorical year, time-varying state-level sociodemographic covariates, and patient covariates (age group [18-34 years, 35-64 years, and 65-75 years], sex, and race and ethnicity). FINDINGS:Between 2005 and 2019, 3 234 382-4 579 994 patients were included per year. Among patients without pain in 2005, 5·1% were female, mean age was 58·3 (SD 12·6) years, and 75·7%, 15·6%, and 3·6% were White, Black, and Hispanic or Latino, respectively. In 2019, 9·3% were female, mean age was 56·7 (SD 15·2) years, and 68·1%, 18·2%, and 6·5% were White, Black, and Hispanic or Latino, respectively. Among patients with pain in 2005, 7·1% were female, mean age was 57·2 (SD 11·4) years, and 74·0%, 17·8%, and 3·9% were White, Black, and Hispanic or Latino, respectively. In 2019, 12·4% were female, mean age was 57·2 (SD 13·8) years, and 65·3%, 21·9%, and 7·0% were White, Black, and Hispanic or Latino, respectively. Among patients with chronic pain, enacting MCL led to a 0·135% (95% CI 0·118-0·153) absolute increase in cannabis use disorder prevalence, with 8·4% of the total increase in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·188% (0·160-0·217) absolute increase in cannabis use disorder prevalence, with 11·5% of the total increase in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in cannabis use disorder prevalence (MCL: 0·037% [0·027-0·048], 5·7% attributable to MCL; RCL: 0·042% [0·023-0·060], 6·0% attributable to RCL). Overall, associations of MCL and RCL with cannabis use disorder were greater in patients with chronic pain than in patients without chronic pain. INTERPRETATION:Increasing cannabis use disorder prevalence among patients with chronic pain following state legalisation is a public health concern, especially among older age groups. Given cannabis commercialisation and widespread public beliefs about its efficacy, clinical monitoring of cannabis use and discussion of the risk of cannabis use disorder among patients with chronic pain is warranted. FUNDING:NIDA grant R01DA048860, New York State Psychiatric Institute, and the VA Centers of Excellence in Substance Addiction Treatment and Education.

For 5 decades, US federal regulations have segregated methadone treatment for opioid use disorder from the rest of the health care system, confining its availability to specialty treatment programs that are highly regulated. These regulations have led to severe shortages in the availability of methadone and grave underutilization of this lifesaving medication despite a worsening overdose crisis. In this commentary, we discuss current barriers to methadone in the US opioid treatment system and how recent changes to federal regulations fall short of the reforms needed to significantly expand access to this treatment. Instead, we propose the urgent need to expand methadone to mainstream health care settings by allowing for office-based prescribing and pharmacy dispensing of methadone, the norm in many other developed countries.

Evaluating causal effects in the presence of interference is challenging in network-based studies of hard-to-reach populations. Like many such populations, people who inject drugs (PWID) are embedded in social networks and often exert influence on others in their network. In our setting, the study design is observational with a non-randomized network-based HIV prevention intervention. Information is available on each participant and their connections that confer possible HIV risk through injection and sexual behaviors. We considered two inverse probability weighted (IPW) estimators to quantify the population-level spillover effects of non-randomized interventions on subsequent health outcomes. We demonstrated that these two IPW estimators are consistent, asymptotically normal, and derived a closed-form estimator for the asymptotic variance, while allowing for overlapping interference sets (groups of individuals in which the interference is assumed possible). A simulation study was conducted to evaluate the finite-sample performance of the estimators. We analyzed data from the Transmission Reduction Intervention Project, which ascertained a network of PWID and their contacts in Athens, Greece, from 2013 to 2015. We evaluated the effects of community alerts on subsequent HIV risk behavior in this observed network, where the connections or links between participants were defined by using substances or having unprotected sex together. In the study, community alerts were distributed to inform people of recent HIV infections among individuals in close proximity in the observed network. The estimates of the risk differences for spillover using either IPW estimator demonstrated a protective effect. The results suggest that HIV risk behavior could be mitigated by exposure to a community alert when an increased risk of HIV is detected in the network.

BACKGROUND:In the United States, methadone treatment for opioid use disorder is only available at opioid treatment programs (OTPs). In addition to federal regulations, states can enact laws which shape access to OTPs. We aimed to define classes of states according to restrictiveness of state OTP laws and examine population characteristics associated with class membership. METHODS:A set of laws was extracted from a database of statutes and regulations governing OTPs in 49 states and the District of Columbia as of June 2021. Latent class analysis of laws was used to estimate the probability of class membership for each state. Class-weighted multinomial logistic regression analysis assessed state-level correlates of class membership and adjusted Relative Risk Ratio (aRRR) and 95% confidence intervals (95%CI) were generated. RESULTS:States (n = 50) were assigned to three classes; Class 1) High restrictiveness on patient experience, low restrictiveness on access to service (n = 13); Class 2) Medium restrictiveness on patient experience, high restrictiveness on access to service (n = 14); Class 3) Low restrictiveness on patient experience, low restrictiveness on access to service (n = 23). States with a higher probability of membership in Classes with higher restrictiveness had higher rates of unemployment (Class 1 vs Class 3, aRRR:1.24; 95%CI:1.06-1.45), and Black residents (Class 2 vs Class 3, aRRR:1.10; 95%CI:1.04-1.15), and lower likelihood of Medicaid coverage of methadone (Class 1 vs Class 3, aRRR:0.25; 95%CI:0.07-0.88). States with a higher probability of membership in Classes with higher restrictiveness also had higher rates of potential indicators for opioid use disorder treatment need, including rates of opioid dispensing (Class 1 vs Class 3, aRRR:1.06; 95%CI:1.02-1.10, Class 2 vs Class 3, aRRR:1.07; 95%CI:1.03-1.11) and HIV diagnoses attributed to injection (Class 1 vs Class 3, aRRR:3.92; 95%CI:1.25-12.22). CONCLUSIONS:States with indicators of greater potential need for opioid use disorder treatment have the most restrictions, raising concerns about unmet treatment need.

Locating undiagnosed HIV infections is important for limiting transmission. However, there is limited evidence about how best to do so. In South Africa, men have been particularly challenging to reach for HIV testing due, in part, to stigma. We pilot-tested two versions of a network-based case-finding and care-linkage intervention. The first, TRIP, asked "seeds" (original participants) to recruit their sexual and/or injection partners. The second, TRIPLE, aimed to circumvent some stigma-related issues by asking seeds to recruit anyone they know who might be at risk of being HIV-positive-unaware. We recruited 11 (18% male) newly diagnosed HIV-positive (NDP) seeds from two clinics in KwaZulu-Natal, South Africa and randomly assigned them to either TRIP or TRIPLE. Network members were recruited two steps from each seed. The TRIP arm recruited 12 network members; the TRIPLE arm recruited 62. Both arms recruited NDPs at higher rates than local clinic testing, with TRIP (50.0%) outperforming (p = 0.012) TRIPLE (14.5%). However, TRIPLE (53.2%) was far superior to clinics (27.8%) and to TRIP (25.0%) at recruiting men. Given challenges around testing and treating men for HIV in this context, these findings suggest that the TRIPLE expanded network-tracing approach should be tested formally among larger samples in multiple settings.

Buprenorphine is a highly effective treatment for opioid use disorder (OUD) and a critical tool for addressing the worsening US overdose crisis. However, multiple barriers to treatment-including stringent federal regulations-have historically made this medication hard to reach for many who need it. In 2020, under the COVID-19 public health emergency, federal regulators substantially changed access to buprenorphine by allowing prescribers to initiate patients on buprenorphine via telehealth without first evaluating them in person. As the public health emergency has been set to expire in May of 2023, Congress and federal agencies can leverage extensive evidence from studies conducted during the wake of the pandemic to make evidence-based decisions on the regulation of buprenorphine going forward. To aid policy makers, this narrative review synthesizes and interprets peer-reviewed research on the effect of buprenorphine flexibilities on the uptake and implementation of telehealth, and its impact on OUD patient and prescriber experiences, access to treatment, and health outcomes. Overall, our review finds that many prescribers and patients took advantage of telehealth, including the audio-only option, with a wide range of benefits and few downsides. As a result, federal regulators-including agencies and Congress-should continue nonrestricted use of telehealth for buprenorphine initiation.

BACKGROUND/UNASSIGNED:Approximately 1800 opioid treatment programs (OTPs) in the US dispense methadone to upwards of 400,000 patients with opioid use disorder (OUD) annually, operating under longstanding highly restrictive guidelines. OTPs were granted novel flexibilities beginning March 15, 2020, allowing for reduced visit frequency and extended take-home doses to minimize COVID exposure with great variation across states and sites. We sought to use electronic health records to compare retention in treatment, opioid use, and adverse events among patients newly entering methadone maintenance in the post-reform period in comparison with year-ago, unexposed, controls. METHODS/UNASSIGNED:Retrospective observational cohort study across 9 OTPs, geographically dispersed, in the National Institute of Drug Abuse (NIDA) Clinical Trials Network. Newly enrolled patients between April 15 and October 14, 2020 (post-COVID, reform period) v. March 15-September 14, 2019 (pre-COVID, control period) were assessed. The primary outcome was 6-month retention. Secondary outcomes were opioid use and adverse events including emergency department visits, hospitalizations, and overdose. FINDINGS/UNASSIGNED: INTERPRETATION/UNASSIGNED:Policies allowing for extended take-home schedules were not associated with worse retention or adverse events despite slightly elevated rates of measured opioid use while in care. Relaxed guidelines were not associated with measurable increased harms and findings could inform future studies with prospective trials. FUNDING/UNASSIGNED:USDHHSNIDACTNUG1DA013035-15.