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Walter Ling,1 Steve Shoptaw,1 David Goodman-Meza2 1UCLA Department of Family Medicine, Center for Behavioral and Addiction Medicine, Los Angeles, CA, USA; 2UCLA Department of Medicine, Division of Infectious Diseases, Los Angeles, CA, USACorrespondence: Walter Ling Email lwalter@ucla.eduAbstract: Buprenorphine has pharmacologic advantages over methadone, especially buprenorphine’s better safety profile. The true significance of buprenorphine’s introduction lies in returning the care of those suffering from opioid use disorder (OUD) to the hands of the physician. The clinical success of buprenorphine has been meager, in part because most physicians have not been exposed to treating these patients. For physicians inclined to treat OUD, the barriers to buprenorphine’s implementation have been onerous and largely counter to the norms of medical practice. Some notable concerns pertain to buprenorphine’s clinical pharmacology like street diversion, unintended use and accidental poisoning. Recently, injectable buprenorphine preparations have been introduced to mitigate these latter shortcomings. Yet, the injectable preparations’ clinical and commercial success has fallen far short of expectation. Here, we review the clinical pharmacology of these products and their expected clinical advantages for the manufacturers, clinicians, policy makers and patients, and offer our perspective, as clinicians and researchers, on how things can improve. Questions remain whether clinicians are willing to overcome barriers to treat OUD using these medications.Keywords: opioid use disorder, injectable buprenorphine, treatment barriers, stakeholders

Ling W, Shoptaw S, Goodman-Meza D. Subst Abuse Rehabil. 2019;10:69–78.The authors of this paper have advised that Table 1 is incorrect. The authors advised that they had listed values for Cmax and Ctrough after a single dose of Brixadi (CAM2038) and not steady state, as it was provided for Sublocade. The new Table 1 reflects the Brixadi steady state concentrations for a more direct comparison with Sublocade.Read the original article

Since April 2019, CA Bridge has worked with emergency departments (EDs) in diverse geographic and emergency care settings across California to scale up low-threshold buprenorphine access, patient navigation programs, harm reduction services, and take-home naloxone. Between April 2019 and June 2023, 268 (81.0%) of 331 acute care hospitals in California received funding and technical assistance from CA Bridge and completed data reporting. These hospitals provided navigation services during 279 025 patient encounters and gave patients buprenorphine in 89 549 ED visits. ( Am J Public Health . 2024;114(9):874-878. https://doi.org/10.2105/AJPH.2024.307710).

People with substance use disorder (SUD) face barriers to prevention and treatment services, increasing risk for hospitalization and death. Injection drug use (IDU) can lead to an increased risk of overdose and infections. However, identifying people who inject drugs (PWID) within healthcare systems is challenging. International Classification of Disease (ICD-10) codes are used for billing and tracking healthcare utilization. In this commentary, experts in the field weigh the benefits and risks of creating an IDU-specific ICD-10 code. Potential benefits include earlier identification, better access to health services, and improved systems of resource allocation. Potential risks include further stigmatization of PWID and, if not tied to financial reimbursement, low rates of code utilization. As the current systems of identifying PWID are lacking, we feel that a guided operationalization of an ICD code to identify PWID could improve quantitative and epidemiological research accuracy and, therefore, support the health and well-being of PWID., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sandra A Springer reports a relationship with Indivior PLC that includes: non-financial support. Sandra A Springer reports a relationship with Alkermes Inc. that includes: consulting or advisory and non-financial support. Ellen F Eaton reports a relationship with Prime Healthcare Services Inc. that includes: consulting or advisory. Ellen F Eaton reports a relationship with IAS-USA that includes: consulting or advisory. Ellen F Eaton reports a relationship with Integritas Communications LLC that includes: consulting or advisory. Ellen F Eaton reports a relationship with Gilead Sciences that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder., Methods: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles., Discussion: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022., (© 2024. The Author(s).)

Background: HIV burden in the US among people who inject drugs (PWID) is driven by overlapping syndemic factors such as co-occurring health needs and environmental factors that synergize to produce worse health outcomes among PWID. This includes stigma, poverty, and limited healthcare access (e.g. medication to treat/prevent HIV and for opioid use disorder [MOUD]). Health services to address these complex needs, when they exist, are rarely located in proximity to each other or to the PWID who need them. Given the shifting drug use landscapes and geographic heterogeneity in the US, we evaluate a data-driven approach to guide the delivery of such services to PWID in local communities., Methods: We used a hybrid, type I, embedded, mixed method, data-driven approach to identify and characterize viable implementation neighborhoods for the HPTN 094 complex intervention, delivering integrated MOUD and HIV treatment/prevention through a mobile unit to PWID across five US cities. Applying the PRISM framework, we triangulated geographic and observational pre-implementation phase data (epidemiological overdose and HIV surveillance data) with two years of implementation phase data (weekly ecological assessments, study protocol meetings) to characterize environmental factors that affected the viability of implementation neighborhoods over time and across diverse settings., Results: Neighborhood-level drug use and geographic diversity alongside shifting socio-political factors (policing, surveillance, gentrification) differentially affected the utility of epidemiological data in identifying viable implementation neighborhoods across sites. In sites where PWID are more geographically dispersed, proximity to structural factors such as public transportation and spaces where PWID reside played a role in determining suitable implementation sites. The utility of leveraging additional data from local overdose and housing response systems to identify viable implementation neighborhoods was mixed., Conclusions: Our findings suggest that data-driven approaches provide a contextually relevant pragmatic strategy to guide the real-time implementation of integrated care models to better meet the needs of PWID and help inform the scale-up of such complex interventions. This work highlights the utility of implementation science methods that attend to the impact of local community environmental factors on the implementation of complex interventions to PWID across diverse drug use, sociopolitical, and geographic landscapes in the US., Trial Registration: ClincalTrials.gov, Registration Number: NCT04804072 . Registered 18 February 2021., (© 2024. The Author(s).)

Problem: Stigma in health care toward people who inject drugs (PWID) is a well-described, significant barrier to quality care, resulting in poor health outcomes. Harm reduction offers a person-centered counter-framework for minimizing harm for people who use drugs. Despite the evidence in support of harm reduction, medical students typically receive minimal training on harm reduction and the care of PWID., Approach: To fill this gap, medical students at the University of California, Los Angeles organized around the principles of harm reduction to improve the medical school curriculum related to PWID. Students screened lectures for stigmatizing language and collaborated with faculty to improve lecture materials. They partnered with a community organizer and hosted a mandatory 1-hour lecture and 30-minute discussion introducing the principles of harm reduction within an overdose prevention, recognition, and response training for first-year medical students during medical school orientation in August 2022. An anonymous online pretest and posttest survey, assessing student attitudes toward PWID, was used to evaluate the effects of the training., Outcomes: A total of 156 students completed the pretest survey, and 107 students completed the pretest and posttest survey (68.5% response rate). The overall posttest mean stigma score was 1.8 (standard deviation [SD] = 0.5) and was significantly lower than the pretest mean of 2.1 (SD = 0.7; P < .0001), indicating a reduction in stigma among medical student attitudes after the course. There was statistically significant improvement in attitudes for 7 of 13 component measures., Next Steps: This analysis demonstrated that the mandatory class has the capacity to improve medical student attitudes toward PWID. The authors plan to further evaluate the program's effectiveness through measuring and reporting outcomes for future student cohorts. The authors are working with curriculum directors to further incorporate harm reduction principles into other lectures and problem-based learning exercises., (Copyright © 2024 the Association of American Medical Colleges.)

Background: The United States (US) is an extreme global outlier for drug-related death rates. However, data describing drug-related deaths are generally available only on an 8-13-month lag. Furthermore, granular details about substance-involvement are often not available, which particularly stymies efforts to track fatal polysubstance and novel psychoactive substance use. Detailed medical examiner records provide a powerful source of information for drug-related death surveillance, but have been underutilized., Methods: We pooled medical examiner data from five US states and 14 counties that together comprise 18% of the US population to examine demographic, geographic, and drug-specific trends in polysubstance drug-related deaths. We employed mixed effects logistic regression to identify demographic factors associated with polysubstance rather than single substance drug-related deaths. We assessed the correlations between drug classes and described geographic variation in the prevalence of specific drugs and the presence of novel and emerging psychoactive substances., Results: Our sample included 73,077 drug-related deaths from 2012 through early 2022. Nearly two-thirds of drug-related deaths were polysubstance-involved, with the number and percentage growing annually. High percentages of polysubstance drug-related deaths were observed in both urban and rural jurisdictions. After adjusting for year and jurisdiction, female, American Indian and Alaska Native, and White individuals had the most elevated odds of polysubstance drug-related deaths. Drug-related deaths involving benzodiazepines or opioids, whether pharmaceutical or illicit, and other pharmaceutical drugs were most likely to have polysubstance involvement, while methamphetamine-involved deaths were least likely to involve multiple substances. Strong correlations were observed between prescription opioids and prescription benzodiazepines, fentanyl and xylazine, and designer benzodiazepines and novel synthetic opioids., Conclusions: Analysis of detailed medical examiner records reveals the breadth and complexity of polysubstance drug-related deaths in the US. Future efforts to use this unique resource can improve population-based surveillance of drug-related deaths to better tailor interventions and solutions to this critical health crisis., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations., Methods: HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization., Discussion: This trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care., Trial Registration: ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021., (© 2024. The Author(s).)

Introduction: Initiation of medications for opioid use disorder (MOUD) within the hospital setting may improve outcomes for people who inject drugs (PWID) hospitalized because of an infection. Many studies used International Classification of Diseases (ICD) codes to identify PWID, although these may be misclassified and thus, inaccurate. We hypothesized that bias from misclassification of PWID using ICD codes may impact analyses of MOUD outcomes., Methods: We analyzed a cohort of 36 868 cases of patients diagnosed with Staphylococcus aureus bacteremia at 124 US Veterans Health Administration hospitals between 2003 and 2014. To identify PWID, we implemented an ICD code-based algorithm and a natural language processing (NLP) algorithm for classification of admission notes. We analyzed outcomes of prescribing MOUD as an inpatient using both approaches. Our primary outcome was 365-day all-cause mortality. We fit mixed-effects Cox regression models with receipt or not of MOUD during the index hospitalization as the primary predictor and 365-day mortality as the outcome., Results: NLP identified 2389 cases as PWID, whereas ICD codes identified 6804 cases as PWID. In the cohort identified by NLP, receipt of inpatient MOUD was associated with a protective effect on 365-day survival (adjusted hazard ratio, 0.48; 95% confidence interval, .29-.81; P < .01) compared with those not receiving MOUD. There was no significant effect of MOUD receipt in the cohort identified by ICD codes (adjusted hazard ratio, 1.00; 95% confidence interval, .77-1.30; P = .99)., Conclusions: MOUD was protective of all-cause mortality when NLP was used to identify PWID, but not significant when ICD codes were used to identify the analytic subjects., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Despite national goals to eliminate Hepatitis C (HCV) and the advancement of curative, well-tolerated direct-acting antiviral (DAAs) regimens, rates of HCV treatment have declined nationally since 2015. Current HCV guidelines encourage treatment of HCV by primary care providers (PCPs). Payors have reduced restrictions to access DAAs nationally and in California however it remains unclear if the removal of these restrictions has impacted the proportion of PCPs prescribing DAAs at a health system level. Our objective was to examine the proportion of DAAs prescribed by PCPs and specialists and to describe the population receiving treatment in a single health system from 2015 to 2022., Methods: We examined the proportion of DAAs prescribed by PCPs and specialists and the population receiving treatment through a retrospective analysis of claims data in the University of California, Los Angeles (UCLA) Health System from 2015 to 2022. We described number of prescriptions for HCV medication prescribed by PCPs and specialists by year, medication type, and physician specialty. We also described numbers of prescriptions by patient demographics and comorbidities., Results: A total of 1515 adult patients received a prescription for HCV medication through the UCLA Health System between 2015 and 2022. The proportion of patients receiving prescriptions for PCPs peaked at 19% in 2016, yet decreased to 5.7% in 2022, an average of 13% across all years. Median age of patients receiving treatment was 60 years old, and 56% of patients receiving HCV treatment had commercial insurance as their primary payer., Conclusions: HCV treatment declined from 2015 to 2022 among specialists and PCPs in our health system. Older patients comprised the majority of patients receiving treatment, suggesting a need for novel approaches to reach patients under 40, an age group with significant increases in HCV transmission., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Saab is on the speaker bureau for and receives honorarium from Gilead Sciences and AbbVie Pharmaceuticals. Dr. Bhattacharya reports grants from Gilead Sciences outside of the submitted work. Dr. Goodman-Meza reports grants from NIH-NIDA outside of the submitted work.

Background: Fentanyl- and methamphetamine-based counterfeit prescription drugs have driven escalating overdose death rates in the US, however their presence in Mexico has not been assessed. Our ethnographic team has conducted longitudinal research focused on illicit drug markets in Northern Mexico since 2018. In 2021-2022, study participants described the arrival of new, unusually potent tablets sold as ostensibly controlled substances, without a prescription, directly from pharmacies that cater to US tourists., Aims: To characterize the availability of counterfeit and authentic controlled substances at pharmacies in Northern Mexico available to English-speaking tourists without a prescription., Methods: We employed an iterative, exploratory, mixed methods design. Longitudinal ethnographic data was used to characterize tourist-oriented micro-neighborhoods and guide the selection of n=40 pharmacies in n=4 cities in Northern Mexico. In each pharmacy, samples of "oxycodone", "Xanax", and "Adderall" were sought as single pills, during English-language encounters, after which detailed ethnographic accounts were recorded. We employed immunoassay-based testing strips to check each pill for the presence of fentanyls, benzodiazepines, amphetamines, and methamphetamines. We used Fourier-Transform Infrared Spectroscopy to further characterize drug contents., Results: Of n=40 pharmacies, one or more of the requested controlled substances could be obtained with no prescription (as single pills or in bottles) at 28 (70.0%) and as single pills at 19 (47.5%). Counterfeit pills were obtained at 11 pharmacies (27.5%). Of n=45 samples sold as one-off controlled substances, 18 were counterfeit. 7 of 11 (63.6%) samples sold as "Adderall" contained methamphetamine, 8 of 27 (29.6%) samples sold as "Oxycodone" contained fentanyl, and 3 "Oxycodone" samples contained heroin. Pharmacies providing counterfeit drugs were uniformly located in tourist-serving micro-neighborhoods, and generally featured English-language advertisements for erectile dysfunction medications and "painkillers". Pharmacy employees occasionally expressed concern about overdose risk and provided harm reduction guidance., Discussion: The availability of fentanyl-, heroin-, and methamphetamine-based counterfeit medications in tourist-oriented independent pharmacies in Northern Mexico represents a public health risk, and occurs in the context of 1) the normalization of medical tourism as a response to rising unaffordability of healthcare in the US, 2) plummeting rates of opioid prescription in the US, affecting both chronic pain patients and the availability of legitimate pharmaceuticals on the unregulated market, 3) the rise of fentanyl-based counterfeit opioids as a key driver of the fourth, and deadliest-to-date, wave of the opioid crisis. It was not possible to distinguish counterfeit medications based on appearance of pills or geography of pharmacies, because identically-appearing authentic and counterfeit versions were often sold in close geographic proximity. Nevertheless, people who consume drugs may be more trusting of controlled substances purchased directly from pharmacies. Due to Mexico's limited opioid overdose surveillance infrastructure, the current death rate from these substances remains unknown., Competing Interests: Declaration of Competing Interest Authors declare to disclosures or competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: We conducted a population-based observational study of all medical examiner cases in Los Angeles County from January 2012 through June 2021 in which methamphetamine was listed as a cause of or contributing factor to death (n = 6125). We aimed to characterize demographics, comorbidities, and co-involved substances in methamphetamine-related deaths longitudinally in Los Angeles County, California., Methods: We used detailed death record data to manually classify fatalities by involvement of each organ system, opioids, alcohol, cocaine, other drugs or medications, and external/traumatic causes. Primary outcomes included: the number of methamphetamine-involved deaths, demographics of decedents, percentage of methamphetamine deaths also involving other drugs, and percentage of methamphetamine deaths involving different organ systems. We performed Mann Kendall tests of trends to identify statistically significant longitudinal changes., Results: During the study period, the percentage of methamphetamine-related deaths involving opioids significantly increased from 16 % in 2012 to 54 % in 2021 (p < 0.001). Concurrently, the percentage involving cardiovascular causes significantly decreased from 47 % to 26 % (p < 0.05). Methamphetamine-related deaths in LAC increasingly affected people experiencing homelessness, for whom the percentage tripled from 13 % in 2012 to 35 % in 2021. The share of decedents under 40 years old increased from 33 % to 41 %. The percentage of Black or African American decedents increased over five-fold from 3 % to 17 %., Conclusions: Methamphetamine-related deaths involving opioids more than tripled in Los Angeles County from 2012 to 2021, reflecting the drug supply's shift to illicit fentanyl. More than a quarter involved cardiovascular causes. These findings have implications for treatment and prevention, including scaling up contingency management, distributing naloxone to people who primarily use stimulants, and including cardiovascular care alongside these interventions directly targeted to reduce harms of methamphetamine use., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: Research on women who inject drugs is scarce in low- and middle-income countries. Women experience unique harms such as sexism and sexual violence which translate into negative health outcomes. The present work aims to provide insight into the experiences of women who inject drugs at the US-Mexico border to identify social and health-related risk factors for overdose to guide harm reduction interventions across the Global South., Methods: We recruited 25 women ≥ 18 years of age accessing harm reduction and sexual health services at a non-governmental harm reduction organization, "Verter", in Mexicali, Mexico. We employed purposeful sampling to recruit women who inject drugs who met eligibility criteria. We collected quantitative survey data and in-depth interview data. Analyses of both data sources involved the examination of descriptive statistics and thematic analysis, respectively, and were guided by the syndemic and continuum of overdose risk frameworks., Results: Survey data demonstrated reports of initiating injection drug use at a young age, experiencing homelessness, engaging in sex work, being rejected by family members, experiencing physical violence, injecting in public spaces, and experiencing repeated overdose events. Interview data provided evidence of stigma and discrimination toward women, a lack of safe spaces and support systems, risk of overdose-related harms, sexual violence, and the overall need for harm reduction services., Conclusion: Women who inject drugs in Mexicali describe experiences of violence, overdose, and public injecting. Women are particularly vulnerable in the Mexicali context, as this area faces a noticeable lack of health and social services. Evidenced-based harm reduction strategies such as safe consumption sites and overdose prevention strategies (e.g., naloxone distribution and training) may benefit this population. Evidence from local organizations could help close the gap in service provision in low-resource settings like Mexico, where government action is almost nonexistent., (© 2023. The Author(s).)

The public health crisis due to opioid overdose is worsening in Mexico's northern region due to the introduction of illicitly manufactured fentanyl into the local drug supply. Though there is an increase in overdose deaths, there is no accurate report of overdoses by Mexican government agencies and no comprehensive opioid overdose prevention strategy. There is currently only an anti-drug marketing strategy which is likely insufficient to mitigate the growing epidemic. In order to address the growing opioid overdose crisis in the country, it is necessary to create and implement a decentralized prevention strategy, that includes naloxone distribution, expanded treatment services in regions most in need, and create active dialogue with community organisations already implementing harm reduction actions. Decisive action must be taken by the Mexican government to ensure the health and wellbeing of the Mexican citizens, especially those at high risk for opioid overdose., Competing Interests: The authors declare they have no competing interests., (© 2023 Published by Elsevier Ltd.)

Competing Interests: Authors declare no conflicts of interest.

Background: Historically, overdose mortality rates among Hispanics have been lower than non-Hispanics. The purpose of this analysis was to characterize the U.S. overdose crisis among Hispanics compared to non-Hispanics., Methods: We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (WONDER) platform to obtain drug overdose mortality rates per 100,000 population between 2010 and 2021 for Hispanics and non-Hispanics. We examined the relative percent change and specific drug involvement (2010-2021) and state-level disparities (2010-2020) among Hispanics versus non-Hispanics. We calculated rate ratios by state and annual percent change in total and for each specific drug. Statistical analyses were performed using R software version 4.0.3 (R Project for Statistical Computing)., Results: Nationally, from 2010 to 2021, Hispanic overdose rates rose from 5.6 to 21.7 per 100,000, an increase of 287.5 % compared to 13.5-35.1 per 100,000, an increase of 160 % among non-Hispanics. The average annual percent change was 12 % for Hispanics and 9 % for non-Hispanics. The three most common drug classes involved in overdose deaths among both groups included: Fentanyls and synthetic opioids; cocaine; and prescription opioids. Hispanic overdose rates were higher than non-Hispanic rates in New Mexico, Colorado, Massachusetts, and Pennsylvania in 2020, versus only Michigan in 2010., Conclusions: We observed disparities in overdose mortality growth among Hispanics compared to non-Hispanics from 2010 to 2021. These disparities highlight the urgency to develop community-centered solutions that take into consideration the social and structural inequalities that exacerbate the effects of the opioid overdose crisis on Hispanic communities., Competing Interests: Conflict of interest No conflict declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Long-acting injectable antiretroviral medications are new to HIV treatment. People with HIV may benefit from a treatment option that better aligns with their preferences, but could also face new challenges and barriers. Authors from the fields of HIV, substance use treatment, and mental health collaborated on this commentary on the issues surrounding equitable implementation and uptake of LAI ART by drawing lessons from all three fields. We employ a socio-ecological framework beginning at the policy level and moving through the community, organizational, interpersonal, and patient levels. We look at extant literature on the topic as well as draw from the direct experience of our clinician-authors., (© 2022. The Author(s).)

We observed a higher rate of blood-culture contamination during the COVID-19 pandemic at our institution compared to a prepandemic period. Given the potential implications of blood contamination in antibiotic and diagnostic test utilization as well as added cost, it is imperative to continue efforts to minimize these episodes during the pandemic.

Background: Improving the identification of people who inject drugs (PWID) in electronic medical records can improve clinical decision making, risk assessment and mitigation, and health service research. Identification of PWID currently consists of heterogeneous, nonspecific International Classification of Diseases ( ICD ) codes as proxies. Natural language processing (NLP) and machine learning (ML) methods may have better diagnostic metrics than nonspecific ICD codes for identifying PWID., Methods: We manually reviewed 1000 records of patients diagnosed with Staphylococcus aureus bacteremia admitted to Veterans Health Administration hospitals from 2003 through 2014. The manual review was the reference standard. We developed and trained NLP/ML algorithms with and without regular expression filters for negation (NegEx) and compared these with 11 proxy combinations of ICD codes to identify PWID. Data were split 70% for training and 30% for testing. We calculated diagnostic metrics and estimated 95% confidence intervals (CIs) by bootstrapping the hold-out test set. Best models were determined by best F-score, a summary of sensitivity and positive predictive value., Results: Random forest with and without NegEx were the best-performing NLP/ML algorithms in the training set. Random forest with NegEx outperformed all ICD -based algorithms. F-score for the best NLP/ML algorithm was 0.905 (95% CI, .786-.967) and 0.592 (95% CI, .550-.632) for the best ICD -based algorithm. The NLP/ML algorithm had a sensitivity of 92.6% and specificity of 95.4%., Conclusions: NLP/ML outperformed ICD -based coding algorithms at identifying PWID in electronic health records. NLP/ML models should be considered in identifying cohorts of PWID to improve clinical decision making, health services research, and administrative surveillance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Importance: Overdose is one of the leading causes of death in the US; however, surveillance data lag considerably from medical examiner determination of the death to reporting in national surveillance reports., Objective: To automate the classification of deaths related to substances in medical examiner data using natural language processing (NLP) and machine learning (ML)., Design, Setting, and Participants: Diagnostic study comparing different natural language processing and machine learning algorithms to identify substances related to overdose in 10 health jurisdictions in the US from January 1, 2020, to December 31, 2020. Unstructured text from 35 433 medical examiner and coroners' death records was examined., Exposures: Text from each case was manually classified to a substance that was related to the death. Three feature representation methods were used and compared: text frequency-inverse document frequency (TF-IDF), global vectors for word representations (GloVe), and concept unique identifier (CUI) embeddings. Several ML algorithms were trained and best models were selected based on F-scores. The best models were tested on a hold-out test set and results were reported with 95% CIs., Main Outcomes and Measures: Text data from death certificates were classified as any opioid, fentanyl, alcohol, cocaine, methamphetamine, heroin, prescription opioid, and an aggregate of other substances. Diagnostic metrics and 95% CIs were calculated for each combination of feature extraction method and machine learning classifier., Results: Of 35 433 death records analyzed (decedent median age, 58 years [IQR, 41-72 years]; 24 449 [69%] were male), the most common substances related to deaths included any opioid (5739 [16%]), fentanyl (4758 [13%]), alcohol (2866 [8%]), cocaine (2247 [6%]), methamphetamine (1876 [5%]), heroin (1613 [5%]), prescription opioids (1197 [3%]), and any benzodiazepine (1076 [3%]). The CUI embeddings had similar or better diagnostic metrics compared with word embeddings and TF-IDF for all substances except alcohol. ML classifiers had perfect or near perfect performance in classifying deaths related to any opioids, heroin, fentanyl, prescription opioids, methamphetamine, cocaine, and alcohol. Classification of benzodiazepines was suboptimal using all 3 feature extraction methods., Conclusions and Relevance: In this diagnostic study, NLP/ML algorithms demonstrated excellent diagnostic performance at classifying substances related to overdoses. These algorithms should be integrated into workflows to decrease the lag time in reporting overdose surveillance data.

Background: Fentanyl has led to an increased number of overdose deaths in North America. Testing substances for fentanyl may be a harm reduction strategy to prevent overdose. Little is known about behavior change after fentanyl testing and the attitudes around fentanyl knowledge and testing along the US-Mexico border in the context of a safe consumption site., Methods: This was a pilot quantitative and qualitative study with 30 women who use drugs at an unsanctioned safe consumption site in Mexicali, Mexico. Women participated in a quantitative survey, a semi-structured interview, and fentanyl testing of substances. Injection behavior was observed after fentanyl testing results were provided. Qualitative data were collected to explore the meanings participants attributed to fentanyl and fentanyl testing., Results: Half of the substances tested positive for fentanyl (n=15, 50%), and all of them were in samples of black tar heroin. Among those participants who tested positive for fentanyl, 7 (47%) subsequently used less of the intended substance, 1 did not use the intended substance, and 7 (47%) did not change their behavior (i.e., used as originally intended). In qualitative interviews, a predominant theme was a description of fentanyl as dangerous and deadly and fentanyl testing as being helpful for modifying drug use behaviors. However, participants recognized that there could be no change in behavior following a positive fentanyl test in the context of not being able to find substances free of fentanyl., Conclusion: We observed mixed results related to behavior change after women's intended substance for use tested positive for fentanyl. Fentanyl testing was acceptable to women, but behavior change was hampered by the inability to find substances free of fentanyl. Further research is needed to maximize the potential of fentanyl testing as a harm reduction tool especially in the context of a changing drug supply., Competing Interests: Declarations of Interest The authors declared that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the impact of the COVID-19 pandemic along the U.S.-Mexico border region and evaluate the relationship of COVID-19 related mortality, socioeconomic status, and vaccination., Methods: We used indirect standardization to age-adjust mortality rates and calculate standardized mortality ratios [SMR] in both countries. To examine the impact of socioeconomic factors, we calculated the Human Development Index (HDI) by county/municipality. We performed linear regression to understand the relationship between mortality, vaccination, and HDI. We used choropleth maps to visualize the trends seen in the region., Results: Between January 22nd, 2020 and December 1st, 2021, surges of cases and deaths were similar in dyad cities along the U.S.-Mexico border visualizing the interconnectedness of the region. Mortality was higher in U.S. counties along the border compared to the national average (SMR 1.17, 95% CI 1.15-1.19). In Mexico, border counties had a slightly lower mortality to the national average (SMR 0.94, 95% CI 0.93-0.95). In U.S. border states, SMR was shown to negatively correlate with human development index (HDI), a socioeconomic proxy, resulting in a higher SMR in the border region compared to the rest of the counties. Conversely in Mexican border states, there was no association between SMR and HDI. Related to vaccination, U.S. counties along the border were vaccinated at a greater percentage than non-border counties and vaccination was negatively correlated with HDI. In Mexico, states along the border had a higher ratio of vaccinations per person than non-border states., Conclusions: The U.S.-Mexico border is a divide of incredible importance not only to immigration but as a region with unique social, economic, environmental, and epidemiological factors that impact disease transmission. We investigated how the COVID-19 pandemic followed trends of previously studied diseases in the corridor such as tuberculosis, HIV, and influenza H1N1. These data state how targeted intervention along the U.S.-Mexico border region is a necessity when confronting COVID-19 and have implications for future control of infectious diseases in the region., (© 2022. The Author(s).)

Background: Sharp exacerbations of the US overdose crisis are linked to polysubstance use of synthetic compounds. Xylazine is a veterinary tranquilizer, long noted in the street opioid supply of Puerto Rico, and more recently Philadelphia. Yet its national trends, geographic distribution, and health risks are poorly characterized., Methods: In this sequential mixed-methods study, xylazine was increasingly observed by ethnographers in Philadelphia among drug-sellers and people who inject drugs (PWID). Subsequently, we systematically searched for records describing xylazine-present overdose mortality across the US and assessed time trends and overlap with other drugs., Results: In 10 jurisdictions - representing all four US Census Regions - xylazine was increasingly present in overdose deaths, rising from 0.36% of deaths in 015m 6.7% in 2020. The highest xylazine prevalence data was observed in Philadelphia, (25.8% of deaths), followed by Maryland (19.3%) and Connecticut (10.2%). Illicitly-manufactured-fentanyls were present in 98.4% of xylazine-present-overdose-deaths - suggesting a strong ecological link - as well as cocaine (45.4%), benzodiazepines (28.4%), heroin (23.3%), and alcohol (19.7%). PWID in Philadelphia described xylazine as a sought-after adulterant that lengthens the short duration of fentanyl injections. They also linked it to increased risk of soft tissue infection and naloxone-resistant overdose., Conclusions: Xylazine is increasingly present in overdose deaths, linked to the proliferation of illicitly-manufactured-fentanyls. Ethnographic accounts associate it with profound risks for PWID. Nevertheless, many jurisdictions do not routinely test for xylazine, and it is not comprehensively tracked nationally. Further efforts are needed to provide PWID with services that can help minimize additional risks associated with a shifting drug supply., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study tested the hypothesis that reported frequency of methamphetamine use is significantly associated with measures of social adversity, sexual risk behaviors, chronic health conditions, bacterial STIs and HIV-related factors among diverse men who have sex with men (MSM)., Methods: Data were 2428 visits from 515 mSTUDY participants (261 people living with HIV; 254 HIV-negative). mSTUDY is an ongoing longitudinal study of racially/ethnically diverse MSM in Los Angeles County. Logistic regression with random intercepts modeled associations between self-reported past 6-month methamphetamine use (none, monthly or less, weekly or more) with reported adverse social outcomes (unemployment, housing instability, intimate partner violence), sexual risk behaviors, chronic health conditions, and biomarkers of bacterial STIs (chlamydia, gonorrhea, or syphilis) and detectable HIV viral load (among HIV-positive). Models controlled for confirmed HIV-serostatus., Results: Prevalence of reported monthly or less methamphetamine use was 19%; weekly or more use was 18%. Multivariable models showed escalating odds of adverse social outcomes and sexual risk behaviors (p's < 0.001) with increased methamphetamine use frequency. Frequency of methamphetamine use associated with increased odds of a positive bacterial STI test (p < .001), detectable viral load (in HIV-positive participants) (p < .001), renal condition (p = .047), neurological condition (p = .008), and psychological condition (p = .001)., Conclusions: Findings show cross-sectional links between reported methamphetamine use frequency and adverse social and health outcomes among MSM in Los Angeles and suggest there may be fewer social and physical health harms corresponding to less frequent use of methamphetamine in this group., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Long-acting injectable (LAI) antiretroviral therapy (ART) is a novel HIV treatment option for people with HIV. The first LAI ART regimen for HIV treatment received regulatory approval in the United States in January 2021. In February 2020, we collected qualitative data from 18 consumers and 23 clinical and non-clinical stakeholders to catalog anticipated individual-consumer, healthcare system, and structural levels barriers and facilitators to LAI ART implementation in Los Angeles County, California. Thematic analysis was guided by the CFIR implementation science model. CFIR constructs of intervention characteristics, individual characteristics, outer and inner setting, intervention characteristics, and implementation process emerged in analysis. Under intervention characteristics, anticipated facilitators included the relative advantage of LAI ART over pills for adherence and reduced treatment management burden and related anxiety; anticipated barriers included non-adherence to injection appointments, concerns of developing HIV resistance, discomfort with injection and cost. Anticipated facilitators based on individual characteristics included overall acceptability based on knowledge and positive beliefs about LAI ART. Participant noted several characteristics of the outer setting that could negatively impact implementation, such as medical mistrust, external policies, and LAI ART eligibility (i.e., to be virally suppressed prior to initiation). Participants were optimistic about the potential to decrease stigma but expressed that provider willingness for adoption could be hindered by challenges in organizational inner setting related to payment authorizations, increased staffing needs, medication procurement and storage, and provider and healthcare system readiness. Results from this pre-implementation study may inform rollout and scale-up of LAI ART in Los Angeles County., Competing Interests: One author, Raphael Landovitz has declared competing interest, because he served as a consultant to Gilead, Merck, Janssen, and Cepheid. The other authors have declared no competing interests

Background: Drug overdoses are prevalent in low- and middle-income countries but are scarcely reported in the literature. We report on an opioid overdose reversal and naloxone distribution program that was instituted at the first safe consumption site in Latin America., Methods: A cross-sectional analysis of witnessed drug overdoses and naloxone distribution between 1 June 2019 and 31 May 2021 in Mexicali, Mexico. Case report forms were entered in an electronic database. Trends in overdose and naloxone distribution were described. Comparisons were made before and after the COVID-19 pandemic was declared in the city. Maps were created to represent the geographic distribution of overdose in the city., Results: During the study period 1,534 doses of naloxone were distributed throughout the community. In addition, there were 464 overdoses reported during this period, of which 4 were fatal. There was a 30% increase in reported overdoses from the period before the COVID-19 pandemic to the period after the pandemic was declared ( p  = 0.03). Most common substance reported included heroin (93%), sedatives (21%), methamphetamine (16%) and fentanyl (14%). Naloxone was given in 96% of cases (median 1 dose, IQR 1-2 doses) and emergency services were called in 20% of cases., Conclusions: An opioid overdose reversal program in Mexicali, Mexico was able to distribute naloxone and register drug overdoses between 2019 and 2021 as a harm reduction strategy. This adds to the growing body of literature on the impact of community-based programs on preventing fatal overdoses and the potential for implementation in low-resource settings., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Background: Leronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19)., Methods: Twenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records., Results: Mean age was 69.5 ± 14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died., Conclusions: Leronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Study Objective: We retrospectively evaluated the implementation of low-threshold emergency department (ED) buprenorphine treatment at 52 hospitals participating in the CA Bridge Program using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework., Methods: The CA Bridge model included low-threshold buprenorphine, connection to outpatient care, and harm reduction. Implementation began in March 2019. Participating hospitals reported aggregated clinical data monthly after program initiation. Outcomes included identification of opioid use disorder, buprenorphine administration, and linkage to outpatient addiction treatment. Multivariable models assessed associations between hospital location (rural versus urban) and teaching status (clinical teaching hospital versus community hospital) and outcomes in adopting the CA Bridge Program., Results: Reach: A diverse and geographically distributed group of 52 California hospitals were enrolled in 2 phases (March and August 2019); 12 (23%) were rural and 13 (25%) were teaching hospitals. Effectiveness: Over a 14-month implementation period, 12,009 opioid use disorder patient encounters were identified, including 7,179 (59.7%) where buprenorphine was administered and 4,818 (40.1%) where follow-up visits were attended. Adoption: In multivariable analysis, adoption did not differ significantly between rural and urban or teaching and nonteaching hospitals., Implementation: By program completion, all 52 (100%) hospitals treated opioid use disorder with buprenorphine; 45 (86.5%) administered buprenorphine after naloxone reversal; 41 (84.6%) offered buprenorphine for inpatients; 48 (92.3%) initiated buprenorphine in pregnant women; and 29 (55.8%) offered take-home naloxone. Maintenance: At 8-month follow-up, all 52 sites reported continued buprenorphine treatment., Conclusion: Low-threshold ED buprenorphine treatment implemented with a harm reduction approach and active navigation to outpatient addiction treatment was successful in achieving buprenorphine treatment for opioid use disorder in diverse California communities., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: To highlight geographic differences and the socio-structural determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity within Los Angeles County (LAC)., Methods: A geographic information system was used to integrate, map, and analyze SARS-CoV-2 testing data reported by the LAC Department of Public Health and data from the American Community Survey. Structural determinants included race/ethnicity, poverty, insurance status, education, and population and household density. We examined which factors were associated with positivity rates, using a 5% test positivity threshold, with spatial analysis and spatial regression., Results: Between 1 March and 30 June 2020 there were 843 440 SARS-CoV-2 tests and 86 383 diagnoses reported, for an overall positivity rate of 10.2% within the study area. Communities with high proportions of Latino/a residents, those living below the federal poverty line, and with high household densities had higher crude positivity rates. Age- adjusted diagnosis rates were significantly associated with the proportion of Latino/as, individuals living below the poverty line, and population and household density., Conclusions: There are significant local variations in test positivity within LAC and several socio-structural determinants contribute to ongoing disparities. Public health interventions, beyond shelter in place, are needed to address and target such disparities., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Tijuana, Mexico, has a concentrated HIV epidemic among overlapping key populations (KPs) including people who inject drugs (PWID), female sex workers (FSW), their male clients, and men who have sex with men (MSM). We developed a dynamic HIV transmission model among these KPs to determine the extent to which their unmet prevention and treatment needs is driving HIV transmission. Over 2020-2029 we estimated the proportion of new infections acquired in each KP, and the proportion due to their unprotected risk behaviours. We estimate that 43.7% and 55.3% of new infections are among MSM and PWID, respectively, with FSW and their clients making-up < 10% of new infections. Projections suggest 93.8% of new infections over 2020-2029 will be due to unprotected sex between MSM or unsafe injecting drug use. Prioritizing interventions addressing sexual and injecting risks among MSM and PWID are critical to controlling HIV in Tijuana., (© 2021. The Author(s).)

Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield ∼95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-naı̈ve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-naı̈ve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-naı̈ve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of ∼90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-naı̈ve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

Background: Medication for opioid use disorder (MOUD) using buprenorphine in primary or specialty care settings is accessed primarily by persons with private health insurance, stable housing, and no polysubstance use. This paper applies Social Cognitive Theory to frame links between social factors and treatment outcomes among patients with social and economic disadvantages who are seeking MOUD at California Bridge Program (CA Bridge) hospitals., Methods: Electronic medical records for patients identified with OUD between January-April, 2020 receiving care at CA Bridge hospitals defined outcomes: hospital-administered buprenorphine; provision of buprenorphine prescription at discharge. Multi-level models assessed whether social factors-housing status, insurance type, and co-methamphetamine use-predicted outcomes while accounting for group-level effects of treating hospital and controlling for age, race/ethnicity, and gender., Results: 15 CA Bridge hospitals yielded 845 patient records. Most patients received hospital-administered buprenorphine (58 %) and/or a buprenorphine prescription (55 %); 26 % received neither treatment. Patients with unstable housing had greater odds of hospital-administered buprenorphine compared to patients with stable housing. Patients with Medicaid had greater odds of receiving a buprenorphine prescription compared to patients with other insurance. Co-methamphetamine use was not associated with outcomes., Conclusions: Patients with OUD are successful in accessing same-day MOUD in CA Bridge hospital settings over a significant period. Importantly, access to MOUD in these settings was facilitated for patients traditionally not treated using buprenorphine, i.e., those with housing instability, Medicaid insurance, and co-methamphetamine use. Findings suggest barriers to MOUD for patients with social and economic disadvantages can be lowered by changing treatment delivery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: As the SARS-CoV-2 pandemic continues, little guidance is available on clinical indicators for safely discharging patients with severe COVID-19., Objective: To describe the clinical courses of adult patients admitted for COVID-19 and identify associations between inpatient clinical features and post-discharge need for acute care., Design: Retrospective chart reviews were performed to record laboratory values, temperature, and oxygen requirements of 99 adult inpatients with COVID-19. Those variables were used to predict emergency department (ED) visit or readmission within 30 days post-discharge., Patients (or Participants): Age ≥ 18 years, first hospitalization for COVID-19, admitted between March 1 and May 2, 2020, at University of California, Los Angeles (UCLA) Medical Center, managed by an inpatient medicine service., Main Measures: Ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, procalcitonin, white blood cell count, absolute lymphocyte count, temperature, and oxygen requirement were noted., Key Results: Of 99 patients, five required ED admission within 30 days, and another five required readmission. Fever within 24 h of discharge, oxygen requirement, and laboratory abnormalities were not associated with need for ED visit or readmission within 30 days of discharge after admission for COVID-19., Conclusion: Our data suggest that neither persistent fever, oxygen requirement, nor laboratory marker derangement was associated with need for acute care in the 30-day period after discharge for severe COVID-19. These findings suggest that physicians need not await the normalization of laboratory markers, resolution of fever, or discontinuation of oxygen prior to discharging a stable or improving patient with COVID-19.

The California Bridge Program supports expansion of medications for opioid use disorder (MOUD) in emergency departments (EDs) and hospital inpatient units across the state. Here, we describe the change in activity before and after the coronavirus disease 2019 (COVID-19) California statewide shutdown. Of the 70 participating hospitals regionally distributed across California, 52 report MOUD-related activity monthly. We analyzed data on outcomes of OUD care and treatment: identification of OUD, acceptance of referral, receipt of buprenorphine prescription, administration of buprenorphine, and follow-up linkage to outpatient OUD treatment, from May 2019 to April 2020. In estimating the expected number of patients who met each outcome in April 2020, we found decreases in the expected to observed number of patients across all outcomes (all p-values<0.002): 37% (from 1053 to 667) decrease in the number of patients identified with OUD, 34% (from 632 to 420) decrease in the number of patients who accepted a referral, 48% (from 521 to 272) decrease in the number of patients who were prescribed buprenorphine, 53% (from 501 to 234) decrease in the number of patients who were administered buprenorphine, and 33% (from 416 to 277) decrease in the number of patients who attended at least one follow-up visit for addiction treatment. The COVID-19 California statewide shutdown was associated with an abrupt and large decrease in the progress toward expanded access to OUD treatment., (Copyright © 2020. Published by Elsevier Inc.)

Background: In 2015, Mexico implemented regulatory changes and an electronic system to improve access to prescription opioids. We aimed to investigate trends in opioid dispensing after the implementation of these changes and assess how opioid dispensing varied geographically and by socioeconomic status., Methods: In this retrospective analysis of prescription medication surveillance data, we analysed dispensing data for group 1 medications (all opioids, including morphine, methadone, hydromorphone, oxycodone, tapentadol, fentanyl, sufentanil, and remifentanil) obtained from the Federal Commission for the Protection against Sanitary Risk database for 32 states and six large metropolitan areas in Mexico. We calculated crude annual opioid prescriptions per 10 000 people at the national, state, and municipal levels. Adapting methods from the report of the Lancet Commission on Palliative Care and Pain Relief, we calculated the need for palliative opioids by state, and then assessed the observed opioid dispensing rates as a percentage of expected need by geographical socioeconomic status. Within the six major metropolitan areas, we mapped the geocoded location of opioid prescriptions and assessed the association between opioid dispensing and socioeconomic status as well as the association between opioid dispensing and time to US border crossing for areas on the US-Mexico border., Findings: Between June 25, 2015, and Oct 7, 2019, opioid dispensing rates increased by an average of 13% (95% CI 6·8-19·6) per quarter (3 months). The overall national opioid dispensing rate during the study period was 26·3 prescriptions per 10 000 inhabitants. States with a higher socioeconomic status had higher opioid dispensing rates than states with lower socioeconomic status (rate ratio [RR] 1·88, 95% CI 1·33-2·58, p=0·00016) after controlling for the estimated opioid requirement per state, the presence of methadone clinics, and the presence of tertiary hospitals and cancer centres. The same association between opioid dispensing and socioeconomic status was observed in the metropolitan areas, and in those metropolitan areas on the US-Mexico border a 20% decrease (RR 0·80, 95% CI 0·75-0·86) in opioid dispensation was observed per each SD increase (SD 17·1 min) in travel time to the border., Interpretation: Measures introduced by the Mexican federal Government to increase opioid access for patients with palliative care needs were only marginally successful in raising opioid prescription rates. Opioid access should be improved for patients with palliative care needs who live in geographical areas of lower socioeconomic status., Funding: US National Institutes of Health., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The coronavirus disease (COVID-19) pandemic has impacted patients receiving methadone maintenance treatment (MMT) through opioid treatment programs (OTPs), especially because of the unique challenges of the care delivery model. Previously, documentation of patient experiences during emergencies often comes years after the fact, in part because there is a substantial data void in real-time. Methods: We extracted 308 posts that mention COVID-19 keywords on r/methadone, an online community for patients receiving MMT to share information, on Reddit occurring between January 31, 2020 and September 30, 2020. 215 of these posts self-report an impact to their MMT. Using qualitative content analysis, we characterized the impacts described in these posts and identified four emergent themes describing patients' experience of impacts to MMT during COVID-19. Results: The themes included (1) 54.4% of posts reporting impediments to accessing their methadone, (2) 28.4% reporting impediments to accessing physicial OTPs, (3) 19.5% reporting having to self-manage their care, and (4) 4.7% reporting impediments to accessing OTP providers and staff. Conclusions: Patients described unanticipated consequences to one-size-fits-all policies that are unevenly applied resulting in suboptimal dosing, increased perceived risk of acquiring COVID-19 at OTPs, and reduced interaction with OTP providers and staff. While preliminary, these results are formative for follow-up surveillance metrics for patients of OTPs as well as digitally-mediated resource needs for this online community. This study serves as a model of how social media can be employed during and after emergencies to hear the lived experiences of patients for informed emergency preparedness and response.

Purpose: To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV)., Materials and Methods: A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV., Results: Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis., Conclusions: Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SYC consults for PureTech on their deupirfenidone in COVID study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To determine the diagnostic yield of repeat testing for SARS-CoV-2., Methods: A retrospective analysis was performed of all SARS-CoV-2 test results within the UCLA Health System between March 9th and April 29th, 2020. All patients with repeat test results were identified and those with discordant results were reviewed., Results: Between March 9th and April 29th there were 10,165 SARS-CoV-2 test results, of which 630 (6.2%) were positive. Among the 904 patients with repeat test results, 808 (89.4%) were initially negative and 96 (10.6%) were initially positive. Among the 808 patients with an initial negative test, 15 (1.9%) subsequently tested positive. Eleven cases with an initial negative SARS-CoV-2 test and without a known prior positive SARS-CoV-2 test were reviewed; 6 were employed as healthcare workers and 10 were positive on the second test., Conclusions: We found a low diagnostic yield of repeat testing for SARS-CoV-2 in our health system. Repeat testing might prove useful in certain clinical scenarios, such as in healthcare workers, when symptoms develop after a negative test, and in hospitalized patients with a high clinical suspicion for COVID-19., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Worldwide, testing capacity for SARS-CoV-2 is limited and bottlenecks in the scale up of polymerase chain reaction (PCR-based testing exist. Our aim was to develop and evaluate a machine learning algorithm to diagnose COVID-19 in the inpatient setting. The algorithm was based on basic demographic and laboratory features to serve as a screening tool at hospitals where testing is scarce or unavailable. We used retrospectively collected data from the UCLA Health System in Los Angeles, California. We included all emergency room or inpatient cases receiving SARS-CoV-2 PCR testing who also had a set of ancillary laboratory features (n = 1,455) between 1 March 2020 and 24 May 2020. We tested seven machine learning models and used a combination of those models for the final diagnostic classification. In the test set (n = 392), our combined model had an area under the receiver operator curve of 0.91 (95% confidence interval 0.87-0.96). The model achieved a sensitivity of 0.93 (95% CI 0.85-0.98), specificity of 0.64 (95% CI 0.58-0.69). We found that our machine learning algorithm had excellent diagnostic metrics compared to SARS-CoV-2 PCR. This ensemble machine learning algorithm to diagnose COVID-19 has the potential to be used as a screening tool in hospital settings where PCR testing is scarce or unavailable., Competing Interests: No authors have competing interests.

Introduction: Marijuana use is common among persons living with HIV, but whether it's use increases the risk of type 2 diabetes in this population has not been explored., Objective: To determine whether self-reported marijuana use is associated with incident type 2 diabetes in women and men living with and at risk for HIV., Methods: We analyzed data from the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), between 2000-2017 (WIHS) and 1999-2017 MACS. The association between self-reported marijuana use and incident type 2 diabetes was analyzed using time-dependent Cox regression models among 3578 and 2682 participants in the WIHS and MACS respectively., Results: Over the follow-up period, 452 (WIHS) and 326 (MACS) incident type 2 diabetes cases occurred. In multivariable models, the hazard ratios, collectively indicate a reduced risk of type 2 diabetes, in marijuana users compared to none users, although all associations were not statistically significant. The results were similar for HIV-positive and HIV-negative participants in both cohorts., Conclusions: In this prospective analysis of nearly 20 years of data for women and men with and at risk for HIV in the WIHS and MACS, although we found a pattern of reduced risk of type 2 diabetes among self-reported marijuana users, the associations were not statistically significant. To better inform clinical decisions and legal policy regarding marijuana use in this population, further longitudinal investigations that biologically quantify marijuana use to assess risk for incident diabetes is warranted., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: In recent years, the number of infective endocarditis (IE) cases associated with injection drug use has increased. Clinical guidelines suggest deferring surgery for IE in people who inject drugs (PWID) due to a concern for worse outcomes in comparison to non-injectors (non-PWID). We performed a systematic review and meta-analysis of long-term outcomes in PWID who underwent cardiac surgery and compared these outcomes to non-PWID., Methods: We systematically searched for studies reported between 1965 and 2018. We used an algorithm to estimate individual patient data (eIPD) from Kaplan-Meier (KM) curves and combined it with published individual patient data (IPD) to analyze long-term outcomes after cardiac surgery for IE in PWID. Our primary outcome was survival. Secondary outcomes were reoperation and mortality at 30-days, one-, five-, and 10-years. Random effects Cox regression was used for estimating survival., Results: We included 27 studies in the systematic review and 19 provided data (KM or IPD) for the meta-analysis. PWID were younger and more likely to have S. aureus than non-PWID. Survival at 30-days, one-, five-, and 10-years was 94.3, 81.0, 62.1, and 56.6% in PWID, respectively; and 96.4, 85.0, 70.3, and 63.4% in non-PWID. PWID had 47% greater hazard of death (HR 1.47, 95% CI, 1.05-2.05) and more than twice the hazard of reoperation (HR 2.37, 95% CI, 1.25-4.50) than non-PWID., Conclusion: PWID had shorter survival that non-PWID. Implementing evidence-based interventions and testing new modalities are urgently needed to improve outcomes in PWID after cardiac surgery.