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Background: The etiology of nongonococcal urethritis (NGU) is incompletely understood. We sought to determine if genitourinary bacterial diversity or specific taxa were associated with incident NGU., Methods: From August 2014-July 2018, men who have sex with women attending a sexual health clinic were clinically evaluated, including Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) testing, at enrollment and six monthly visits. New cases of NGU (≥5 PMNs/HPF in urethral exudates plus either symptoms or visible discharge) and their visit preceding NGU diagnosis were matched 1:1 to two sequential visits without NGU (controls). We determined associations with incident NGU and applied broad-range 16S rRNA gene polymerase chain reaction and sequencing to urine samples from each visit. We used conditional logistic regression to evaluate the association of Shannon Diversity Index (SDI), species richness, Haemophilus influenzae, Fannyhessea vaginae, Lactobacillus iners, and Streptococcus mitis group with incident non-CT-non-MG-NGU (NCNM-NGU)., Results: Of 62 matched case-control pairs, median age was 32. Higher SDI the previous month was associated with higher odds of incident NCNM-NGU (adjusted odds ratio [aOR] = 2.8 per unit increase; 95% CI = 1.03-7.47), as was F. vaginae at NGU diagnosis (aOR = 5.1; 95% CI = 1.28-20.15), F. vaginae acquisition (aOR = 13.8; 95% CI = 1.96-97.33) and consistent carriage of F. vaginae (aOR = 16.1; 95% CI = 1.66-156.29). Odds of NCNM-NGU were higher when L. iners cleared between visits (aOR = 18.0; 95% CI = 1.08-299.24). Neither H. influenzae nor S. mitis group were associated with incident NCNM-NGU., Conclusions: F. vaginae acquisition/detection and L. iners clearance were associated with urethritis. This merits investigation in larger longitudinal studies using species-specific detection methods., Competing Interests: Conflicts of Interest: LEM has received consulting fees from Health Advances, speaker’s fees from MedConnect, research funding and materials from Hologic, Inc. and Nabriva Therapeutics, and travel support from Hologic, Inc. DNF and TLF receive a royalty from BD for intellectual property around molecular diagnosis of bacterial vaginosis. CMK has received research supplies from Hologic, Inc. and research support from Gilead Sciences., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Emergency department (ED) visits are an opportunity to provide prevention services to people at high risk of overdose. Considering patients' resources to initiate and sustain recovery ("recovery capital") may be useful for tailoring ED services, although its relevance in this population is unknown., Methods: This secondary analysis used data from ED patients at high risk of opioid overdose enrolled in a randomized controlled trial in Rhode Island (2018-2021). We assessed baseline recovery capital using the Brief Assessment of Recovery Capital (BARC-10), dichotomized as a total score <47 versus ≥47. Post-discharge addiction treatment engagement within 30 days and non-fatal opioid overdose and fatal overdose within 18 months were assessed using statewide administrative data. We used modified Poisson regression and Cox proportional hazards models to estimate the association between recovery capital and (1) treatment engagement and (2) overdose risk, respectively, adjusting for potential confounders., Results: Among 543 participants, 32.2% had a baseline BARC-10 total score of ≥47, 32.6% engaged in treatment within 30 days, and 25.6% had a non-fatal opioid overdose and 4.2% had a fatal overdose within 18 months. BARC-10 total score was not associated with treatment engagement within 30 days (adjusted relative risk = 0.79, 95% confidence interval [CI] = 0.60-1.05) or non-fatal opioid overdose (adjusted hazard ratio [aHR] = 0.83, 95%CI = 0.57-1.20) or fatal overdose (aHR = 0.45, 95%CI = 0.14-1.40) within 18 months., Conclusion: The majority of ED patients at high risk of opioid overdose had a BARC-10 total score of <47, suggesting low recovery capital. BARC-10 total score was not associated with post-discharge treatment engagement or overdose risk.

Background and Aims: Emergency departments (EDs) provide an opportunity to identify people at risk of overdose and reduce the risk. We evaluated the effect of an ED behavioral intervention delivered by peer recovery support specialists (PRSSs) on non-fatal opioid overdose., Design: Two-arm, randomized trial., Setting: Two EDs in Rhode Island, USA., Participants: ED patients presenting with an opioid overdose, complications of opioid use disorder or a recent history of opioid overdose (November 2018-May 2021). Among 648 participants, the mean age was 36.9 years, 68.2% were male and 68.5% were White., Intervention and Comparator: Participants were randomized to receive a behavioral intervention from a PRSS (n = 323) or a licensed clinical social worker (LICSW) (n = 325). PRSS and LICSW used evidence-based interviewing and intervention techniques, informed by their lived experience (PRSS) or clinical theory and practice (LICSW)., Measurements: We identified non-fatal opioid overdoses in the 18 months following the ED visit through linkage to statewide emergency medical services data using a validated case definition. The primary outcome was any non-fatal opioid overdose during the 18-month follow-up period., Findings: Among 323 participants randomized to the PRSS arm, 81 (25.1%) had a non-fatal opioid overdose during follow-up, compared with 95 (29.2%) of 325 participants randomized to the LICSW arm (P = 0.24). There was no statistically significant difference in the effectiveness of randomization to the PRSS arm versus the LICSW arm on the risk of non-fatal opioid overdose, adjusting for the history of previous overdose (relative risk = 0.86, 95% confidence interval = 0.67-1.11)., Conclusions: In Rhode Island, USA, over one-in-four emergency department patients at high risk of overdose experience a non-fatal opioid overdose in the 18 months post-discharge. We found no evidence that the risk of non-fatal opioid overdose differs for emergency department patients receiving a behavioral intervention from a peer recovery support specialist versus a licensed clinical social worker., (© 2024 Society for the Study of Addiction.)

Introduction: Buprenorphine is a highly effective treatment for opioid use disorder (OUD). However, provider observations and preliminary research suggest that the current standard maintenance dose may be insufficient for suppressing withdrawal and preventing cravings among people who use or have used fentanyl. Buprenorphine dosing guidelines were based on studies among people who use heroin and have not been formally re-evaluated since fentanyl became predominant in the unregulated drug supply. We aim to compare the effectiveness of a high (24 mg) vs standard (16 mg) maintenance daily dose of buprenorphine for improving retention in treatment, decreasing the use of non-prescribed opioids, preventing cravings and reducing opioid overdose risk in patients., Methods and Analysis: Adults who are initiating or continuing buprenorphine for moderate to severe OUD and have a recent history of fentanyl use (n=250) will be recruited at four outpatient substance use treatment clinics in Rhode Island. Patients continuing buprenorphine must be on doses of 16 mg or less and have ongoing fentanyl use to be eligible. Participants will be randomly assigned 1:1 to receive either a high (24 mg) or standard (16 mg) maintenance daily dose, each with usual care, and followed for 12 months to evaluate outcomes. Providers will determine the buprenorphine initiation strategy, with the requirement that participants reach the study maintenance dose within 7 days of randomisation. Providers may adjust the maintenance dose, if clinically needed, for participant safety. The primary study outcome is retention in buprenorphine treatment at 6 months postrandomisation, measured using clinical and statewide administrative data. Other outcomes include non-prescribed opioid use and opioid cravings (secondary), as well as non-fatal or fatal opioid overdose (exploratory)., Ethics and Dissemination: This protocol was approved by the Brown Institutional Review Board (STUDY00000075). Results will be presented at conferences and published in peer-reviewed journals., Trial Registration Number: NCT06316830., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Certified peer recovery specialists (CPRS) and licensed clinical social workers (LCSWs) can facilitate substance use disorder (SUD) treatment engagement for emergency department (ED) patients at risk for overdose. Predictors of treatment engagement after such behavioral services are unknown., Methods: This secondary analysis included Rhode Island ED patients at high risk for opioid overdose participating in a randomized controlled trial comparing the effectiveness of CPRS and LCSWs services (2018-2021). SUD treatment engagement within 90 days post-discharge was identified using statewide administrative data. Potential predictors were obtained from baseline questionnaires. Classification and regression trees (CART) were used to identify predictors of treatment engagement., Results: In the ED, 323 and 325 participants received CPRS and LCSWs services, respectively, among whom 141 (43.7 %) and 137 (42.2 %) engaged in SUD treatment within 90 days post-discharge. For the CPRS group, predictors of treatment engagement included unhealthy alcohol use, prescription opioid or benzodiazepine use in past 6 months, and lifetime history of: unstable housing, barriers to treatment, bipolar disorder diagnosis, addiction treatment, and recovery services. In the LCSW group, predictors included health insurance, current pain, opioid overdose in past year, and lifetime history of anxiety disorder diagnosis and mental illness treatment. However, CART had low predictive accuracy (CPRS: 60.9 %, LCSW: 54.8 %)., Conclusions: Among ED patients at high risk of opioid overdose receiving behavioral services, 90-day SUD treatment engagement was high. Sociobehavioral and clinical patient characteristics did not accurately predict treatment engagement. Behavioral services should be offered to all ED patients at high risk of opioid overdose., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brandon Marshall reports financial support was provided by Arnold Ventures LLC. Brandon Marshall reports financial support was provided by Cigna Foundation. Dr. Brandon Marshall was partially supported by the National Institute of General Medical Sciences of the NIH [grant number: P20GM125507] and the National Institute on Allergy and Infectious Disease of the NIH [grant number: 3P30AI042853]. 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., (© 2024 The Author(s).)

Objectives. To determine whether geographic prioritization of limited COVID-19 vaccine supply was effective for reducing geographic disparities in case rates. Methods. Rhode Island allocated a portion of the initial COVID-19 vaccine supply to residents of Central Falls, a community already affected by structural policies and inadequate systems that perpetuate health inequities and experiencing disproportionately high COVID-19 morbidity and mortality. The policy was implemented with a culturally and linguistically appropriate community engagement plan and was intended to reduce observed disparities. Using a Bayesian causal analysis with population surveillance data, we evaluated the impact of this prioritization policy on recorded cases over the subsequent 16 weeks. Results. Early geographic prioritization of Central Falls accelerated vaccine uptake, averting an estimated 520 cases (95% confidence interval = 22, 1418) over 16 weeks and reducing cases by approximately 34% during this period (520 averted vs 1519 expected without early prioritization). Conclusions. Early geographic prioritization increased vaccine uptake and reduced cases in Central Falls, thereby reducing geographic disparities. Public Health Implications. Public health institutions should consider geographic prioritization of limited vaccine supply to reduce geographic disparities in case rates. ( Am J Public Health . 2024;114(S7):S580-S589. https://doi.org/10.2105/AJPH.2024.307741).

Background: Overdose remains a pressing public health concern in the United States, particularly with the emergence of fentanyl and other potent synthetic opioids in the drug supply. We evaluated trends in recurrent overdose and opioid use disorder (OUD) treatment initiation following emergency department (ED) visits for opioid overdose to inform response efforts., Methods: This retrospective cohort study used electronic health record and statewide administrative data from Rhode Island residents who visited EDs for opioid overdose between July 1, 2016, and June 30, 2021, a period with fentanyl predominance in the local drug supply. The primary outcome was recurrent overdose in the 365 days following the initial ED visit. OUD treatment initiation within 180 days following the initial ED visit was considered as a secondary outcome. Trends in study outcomes were summarized by year of the initial ED visit., Results: Among 1745 patients attending EDs for opioid overdose, 20 % (n=352) experienced a recurrent overdose within 365 days, and this percentage was similar by year (p=0.12). Among patients who experienced any recurrent overdose, the median time to first recurrent overdose was 88 days (interquartile range=23-208), with 85 % (n=299/352) being non-fatal. Among patients not engaged in OUD treatment at their initial ED visit, 33 % (n=448/1370) initiated treatment within 180 days; this was similar by year (p=0.98)., Conclusions: Following ED visits for opioid overdose in Rhode Island from 2016-2021, the one-year risk of recurrent overdose and six-month treatment initiation rate remained stable over time. Innovative prevention strategies and improved treatment access are needed., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Little is known about how best to reach people with social marketing messages promoting use of clinical HIV and sexually transmitted infection (STI) services., Objective: We evaluated a multiplatform, digital social marketing campaign intended to increase use of HIV/STI testing, treatment, and prevention services among gay, bisexual, and other men who have sex with men (MSM) at an LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and/or questioning) community health center., Methods: We evaluated engagement with a social marketing campaign launched by Open Door Health, the only LGBTQ+ community health center in Rhode Island, during the first 8 months of implementation (April to November 2021). Three types of advertisements encouraging use of HIV/STI services were developed and implemented on Google Search, Google Display, Grindr, and Facebook. Platforms tracked the number of times that an advertisement was displayed to a user (impressions), that a user clicked through to a landing page that facilitated scheduling (clicks), and that a user requested a call to schedule an appointment from the landing page (conversions). We calculated the click-through rate (clicks per impression), conversion rate (conversions per click), and the dollar amount spent per 1000 impressions and per click and conversion., Results: Overall, Google Search yielded the highest click-through rate (7.1%) and conversion rate (7.0%) compared to Google Display, Grindr, and Facebook (click-through rates=0.4%-3.3%; conversion rates=0%-0.03%). Although the spend per 1000 impressions and per click was higher for Google Search compared to other platforms, the spend per conversion-which measures the number of people intending to attend the clinic for services-was substantially lower for Google Search (US $48.19 vs US $3120.42-US $3436.03)., Conclusions: Campaigns using the Google Search platform may yield the greatest return on investment for engaging MSM in HIV/STI services at community health clinics. Future studies are needed to measure clinical outcomes among those who present to the clinic for services after viewing campaign advertisements and to compare the return on investment with use of social marketing campaigns relative to other approaches., (© Laura C Chambers, Yelena Malyuta, William C Goedel, Philip A Chan, Cassandra Sutten Coats, Ken Allen, Amy S Nunn. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Objective: This study examined if emergency department (ED) operational metrics, such as wait time or length of stay, are associated with interest in substance use disorder (SUD) treatment referral among patients at high risk of opioid overdose., Methods: In this observational study, 648 ED patients at high risk of opioid overdose completed a baseline questionnaire. Operational metrics were summarized using electronic health record data. The association between operational metrics and treatment interest was estimated with multivariable logistic regression., Results: Longer time to room (adjusted odds ratio [AOR]=1.12, 95% confidence interval [CI]=1.01-1.25) and length of stay (AOR=1.02, 95% CI=1.00-1.05) were associated with treatment referral interest. Time to provider and number of treating providers showed no significant association., Conclusion: Longer rooming wait times and longer ED visits were associated with increased SUD treatment referral interest. This suggests patients who wait for longer periods may be motivated for treatment and warrant further resource investment.

Partner notification services (PNS) offers opportunities to discuss HIV pre-exposure prophylaxis (PrEP) and provide referrals. We evaluated the PrEP care cascade among men who have sex with men (MSM) engaging in PNS within a sexually transmitted infections clinic. Among 121 MSM eligible for PrEP during PNS, 21% subsequently initiated PrEP.

Background: The COVID-19 pandemic negatively affected adolescent mental health due to school closures, isolation, family loss/hardships, and reduced health care access., Methods: We compared adolescent mental health in Rhode Island before versus during the pandemic, separately among middle and high schoolers. This serial cross-sectional study used Youth Risk Behavior Survey data from 2019 and 2021 (N = 7403). Multivariable logistic regression models estimated the association between year and mental health status, adjusting for sociodemographics., Results: Middle schoolers in 2021 had higher odds of ever seriously considering suicide (22.6% vs 16.7%) and ever attempting suicide (9.3% vs 6.1%) compared to 2019. Among high schoolers, those in 2021 had higher odds of experiencing persistent sadness/hopelessness in the past year (37.4% vs 32.0%). However, high schoolers in 2019 and 2021 had similar odds of considering suicide in the past year, while those in 2021 had lower odds of having attempted suicide in the past year (8.5% vs 14.6%)., Conclusion: The COVID-19 pandemic may have worsened multiple aspects of adolescent mental health in Rhode Island, particularly among middle schoolers., Implications for School Health Policy, Practice, and Equity: Promoting school connectedness, creating supportive environments, and diversifying the mental health workforce may help overcome adverse pandemic effects., (© 2023, American School Health Association.)

Background: Sexual behavior may influence the composition of the male urethral microbiota, but this hypothesis has not been tested in longitudinal studies of men who have sex with men (MSM)., Methods: From December 2014 to July 2018, we enrolled MSM with nongonococcal urethritis (NGU) attending a sexual health clinic. Men attended 5 in-clinic visits at 3-week intervals, collected weekly urine specimens at home, and reported daily antibiotics and sexual activity on weekly diaries. We applied broad-range 16S rRNA gene sequencing to urine. We used generalized estimating equations to estimate the association between urethral sexual exposures in the prior 7 days (insertive oral sex [IOS] only, condomless insertive anal intercourse [CIAI] only, IOS with CIAI [IOS + CIAI], or none) and Shannon index, number of species (observed, oral indicator, and rectal indicator), and specific taxa, adjusting for recent antibiotics, age, race/ethnicity, HIV, and preexposure prophylaxis., Results: Ninety-six of 108 MSM with NGU attended ≥1 follow-up visit. They contributed 1140 person-weeks of behavioral data and 1006 urine specimens. Compared with those with no urethral sexual exposures, those with IOS only had higher Shannon index ( P = 0.03 ) but similar number of species and presence of specific taxa considered, adjusting for confounders; the exception was an association with Haemophilus parainfluenzae . CIAI only was not associated with measured aspects of the urethral microbiota. IOS + CIAI was only associated with presence of H. parainfluenzae and Haemophilus ., Conclusions: Among MSM after NGU, IOS and CIAI did not seem to have a substantial influence on measured aspects of the composition of the urethral microbiota., Competing Interests: Conflict of Interest of Sources of Funding: This work was supported by the National Institutes of Health (grant number U19 AI113173). L.C.C. was supported by the National Institutes of Health (grant number TL1 TR002318 trainee support). K.A.T. was supported by the University of Washington/Fred Hutch Center for AIDS Research, a program funded by the National Institutes of Health (grant number P30 AI027757). Study data were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at the University of Washington Institute of Translational Health Sciences and supported by the National Institutes of Health (grant number UL1 TR002319). C.M.K. has received donations of test kits and reagents from Hologic, Inc. M.R.G. has conducted studies unrelated to this work supported by grants from Hologic, Inc. L.E.M. has received research support and honoraria from Hologic, Inc., and Nabriva Therapeutics. All other authors declare that they have no conflict of interest., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Objectives: PNS is critical to prevent the spread of STIs. We evaluated the feasibility of integrating PNS into an STI clinic focused on MSM., Design/methods: The RI STI Clinic, in partnership with the RIDOH, implemented a PNS program in 2019. Interviews with patients diagnosed with gonorrhea/ syphilis were conducted. RIDOH attempted outreach to partners identified. We utilized interview data among MSM diagnosed with gonorrhea/syphilis in clinic from 1/1/19-12/31/2021. Bivariate analyses/multivariable logistic regression were conducted., Results: 341 MSM were diagnosed with gonorrhea/syphilis during the three-year period, and 233 (68%) interviews were completed. Partner information was provided in 173 (74%) interviews. At least one workable partner was provided in 110 (47%) interviews. No statistically significant associations between provision of workable partners and index patient age/race/ethnicity were found., Conclusions: PNS at an STI clinic was successful, but challenges led to suboptimal information. Research is needed to identify barriers to integrate/optimize PNS in STI clinics.

Introduction: Chronic pain and serious mental illness increase risk of opioid use, and opioid use can exacerbate both conditions. Substance use disorder (SUD) treatment can be lifesaving, but chronic pain and serious mental illness may make recovery challenging. We evaluated the association between current chronic pain and prior hospitalization for mental illness and 90-day SUD treatment engagement, among emergency department (ED) patients at high risk of opioid overdose., Methods: We conducted a cohort analysis of 648 ED patients enrolled in a randomized controlled trial in Rhode Island. We linked baseline study data on chronic pain and prior hospitalization for mental illness to statewide administrative data on state-licensed treatment programs (including methadone) and buprenorphine treatment via prescription. We defined treatment engagement as initiation of a state-licensed treatment program, transfer between state-licensed programs/providers, or a buprenorphine prescription (re-)fill. We used modified Poisson models to estimate the association between each baseline comorbidity and treatment engagement within 90 days following the ED visit, adjusted for a priori potential confounders. In an exploratory analysis, models were stratified by baseline treatment status., Results: The mean age of participants was 37 years; 439 (68 %) were male, and 446 (69 %) had been recently unhoused. Overall, 278 participants (43 %) engaged in treatment within 90 days of the ED visit. Participants with prior hospitalization for mental illness were more likely to engage in treatment than those without (adjusted risk ratio [ARR] = 1.24, 95 % confidence interval [CI] = 1.01-1.53), although this association was only among those already accessing treatment at baseline (ARR = 1.58, 95 % CI = 1.10-2.27). Chronic pain was not associated with 90-day treatment engagement overall (ARR = 1.12, 95 % CI = 0.91-1.38) or within baseline treatment subgroups., Conclusions: Among ED patients at high risk of opioid overdose and accessing treatment at baseline, those with prior hospitalization for mental illness (but not chronic pain) were more likely to engage in treatment following the ED visit, which may reflect disproportionate initiation of additional treatment programs, transfer between programs/providers, or ongoing buprenorphine treatment. Touchpoints within the medical system should be leveraged to ensure that everyone, including those with serious mental illness, can access high-quality SUD treatment at the desired intensity level., Competing Interests: Declaration of competing interest Dr. Beaudoin received grants from the National Institutes of Health, Centers for Disease Control and Prevention, and Institute for Clinical and Economic Review outside the submitted work. Dr. Marshall received grants from the National Institutes of Health outside of the submitted work. All other authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To help understand whether decreased emergency medical services (EMS) utilization due to the COVID-19 pandemic contributed to increased accidental fatal drug overdoses, we characterized recent EMS utilization history among people who had an accidental opioid-involved fatal drug overdose in Rhode Island., Methods: We identified accidental opioid-involved fatal drug overdoses among Rhode Island residents that occurred from January 1, 2018, through December 31, 2020. We linked decedents by name and date of birth to the Rhode Island EMS Information System to obtain EMS utilization history., Results: Among 763 people who had an accidental opioid-involved fatal overdose, 51% had any EMS run and 16% had any opioid overdose-related EMS run in the 2 years before death. Non-Hispanic White decedents were significantly more likely than decedents of other races and ethnicities to have any EMS run ( P < .001) and any opioid overdose-related EMS run ( P = .05) in the 2 years before death. Despite a 31% increase in fatal overdoses from 2019 through 2020, corresponding with the onset of the COVID-19 pandemic, EMS utilization in the prior 2 years, prior 180 days, or prior 90 days did not vary by time frame of death., Conclusion: In Rhode Island, decreased EMS utilization because of the COVID-19 pandemic was not a driving force behind the increase in overdose fatalities observed in 2020. However, with half of people who had an accidental opioid-involved fatal drug overdose having an EMS run in the 2 years before death, emergency care is a potential opportunity to link people to health care and social services., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although viral infections, including SARS-CoV-2, can cause persistent symptoms and functional limitations, the impact of post-viral syndromes on workplaces is uncertain., Methods: We conducted a cross-sectional study of workplaces in Rhode Island in the D&B Hoovers database (September-October 2022). Eligible workplaces had ≥1 contact with a valid email address and ≥2 paid employees. Participants completed a survey on the impact of Long COVID (post-viral syndrome of SARS-CoV-2) on their workplace., Results: Of 6,149 eligible workplaces, 484 (8%) participated. Awareness of Long COVID among workplace leaders was limited. Overall, 28% of workplaces had any employees report having Long COVID. Of those, 14% had ≥1 employee discontinue employment, 45% had ≥1 employee reduce their workload, and 22% had ≥1 employee request an accommodation due to having Long COVID; 80% of employers reported improvement in employee productivity with accommodations., Conclusion: Pandemic preparations for the long-term impacts of post-viral syndromes should consider workplace settings.

Objectives: To estimate excess health care costs in the 12 months following COVID-19 diagnosis., Study Design: Retrospective cohort study using Blue Cross Blue Shield of Rhode Island claims incurred from January 1, 2019, to March 31, 2022, among commercial and Medicare Advantage members., Methods: Difference-in-differences analyses were used to compare changes in health care spend between the 12 months before (baseline period) and the 12 months after (post period) COVID-19 diagnosis for COVID-19 cases and contemporaneous matched controls without COVID-19., Results: Overall, there were 7224 commercial and 1630 Medicare Advantage members with a COVID-19 diagnosis on/before March 31, 2021, each with a matched control, yielding a sample of 14,448 commercial and 3260 Medicare Advantage members. Among commercial members, 51.9% were aged 25 to 54 years and 54.0% were female. Among Medicare Advantage members, 94.2% were 65 years or older and 62.0% were female. Among commercial members, from the baseline period to the post period, total health care spend increased $41.61 (7.7%) per member per month (PMPM) more among COVID-19 cases compared with their matched controls. Among Medicare Advantage members, the difference-in-differences was greater, with spend increasing $97.30 (13.1%) PMPM more among cases compared with controls. The difference-in-differences was greatest for outpatient and professional services (both populations) and prescription services (Medicare Advantage only)., Conclusions: COVID-19 diagnosis was associated with excess health care spend PMPM over the subsequent 12 months, highlighting the importance of societal preparations to support individuals' long-term health care needs following COVID-19 and as a part of future pandemic preparedness.

Background: Curcumin is a commonly used herbal supplement with anti-inflammatory and anti-fibrotic properties. Animal studies and small human trials suggest that curcumin reduces albuminuria in patients with chronic kidney disease (CKD). Micro-particle curcumin is a new, more bioavailable formulation of curcumin., Methods: To determine whether micro-particle curcumin versus placebo slows the progression of albuminuric CKD we conducted a randomized, double-blind, placebo-controlled trial with 6-month follow-up. We included adults with albuminuria [a random urine albumin-to-creatinine ratio >30 mg/mmol (265 mg/g) or a 24-h urine collection with more than 300 mg of protein] and an estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 within the 3 months before randomization. We randomly allocated participants 1:1 to receive micro-particle curcumin capsules (90 mg/day) or matching placebo for 6 months. After randomization, the co-primary outcomes were the changes in albuminuria and the eGFR., Results: We enrolled 533 participants, but 4/265 participants in the curcumin group and 15/268 in the placebo group withdrew consent or became ineligible. The 6-month change in albuminuria did not differ significantly between the curcumin and placebo groups [geometric mean ratio 0.94, 97.5% confidence interval (CI) 0.82 to 1.08, P = .32]. Similarly, the 6-month change in eGFR did not differ between groups (mean between-group difference -0.22 mL/min/1.73 m2, 97.5% CI -1.38 to 0.95, P = .68)., Conclusions: Ninety milligrams of micro-particle curcumin daily did not slow the progression of albuminuric CKD over 6 months., Trial Registration: ClinicalTrials.gov Identifier: NCT02369549., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Importance: Buprenorphine treatment for opioid use disorder (OUD) has more than doubled since 2009. However, current US Food and Drug Administration buprenorphine dosing guidelines are based on studies among people using heroin, prior to the emergence of fentanyl in the illicit drug supply., Objective: To estimate the association between buprenorphine dose and time to treatment discontinuation during a period of widespread fentanyl availability., Design, Setting, and Participants: This retrospective cohort study used statewide Rhode Island Prescription Drug Monitoring Program data. Participants were Rhode Island residents initiating buprenorphine treatment for OUD between October 1, 2016, and September 30, 2020. Data analysis was performed from December 9, 2022, to August 10, 2023., Exposure: Daily dose of buprenorphine (16 mg and 24 mg) defined starting on the day of initiation based on total quantity and days' supply dispensed. Patients were censored on any dose change., Main Outcomes and Measures: Buprenorphine treatment discontinuation in the 180 days following initiation, defined as a gap in treatment of more than 27 days based on prescription fill dates and days' supply. Kaplan-Meier and Cox regression survival analyses were conducted to estimate the association between buprenorphine dose and time to treatment discontinuation, controlling for potential informative censoring and measured potential confounders., Results: Among 6499 patients initiating buprenorphine treatment for OUD, most were aged 25 to 44 years (57%; n = 3682), were male (61%; n = 3950), and had private (47%; n = 3025) or Medicaid (33%; n = 2153) insurance. More than half of patients were prescribed a daily dose of interest at initiation (16 mg: 50%; n = 3264; 24 mg: 10%; n = 668). In Kaplan-Meier analyses, 58% of patients discontinued buprenorphine treatment within 180 days (16 mg: 59% vs 24 mg: 53%; log-rank test P = .005). In Cox regression analyses, patients prescribed a dose of 16 mg had a greater risk of treatment discontinuation than those prescribed 24 mg (adjusted hazard ratio, 1.20; 95% CI, 1.06-1.37)., Conclusions and Relevance: In this cohort study of patients initiating buprenorphine treatment from 2016 to 2020, patients prescribed a 24 mg dose of buprenorphine remained in treatment longer than those prescribed 16 mg. The value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.

Background: Substance use patterns are diverse, and multiple substances are often involved in fatal and nonfatal overdoses. Additionally, polysubstance use is associated with greater difficulty accessing and remaining in substance use disorder (SUD) treatment. The aim of this study was to identify substance use patterns and determine their association with SUD treatment engagement among emergency department (ED) patients at risk of opioid overdose., Methods: This was a sub-analysis of a randomized controlled trial comparing two behavioral interventions for individuals at two EDs in Rhode Island from 2018 to 2021. Past six-month substance use frequency for eight substances plus injection drug use was self-reported at trial enrollment, and SUD treatment engagement within 90 days after enrollment was obtained using administrative data linkages. Latent class analysis identified substance use patterns and multivariable log-binomial models estimated the association with SUD treatment engagement., Results: Among 607 participants, there were four substance use patterns: 1) low reported use (n = 295), 2) frequent injection and heroin use (n = 131), 3) high frequency broad polysubstance use (n = 62), and 4) low frequency broad polysubstance use (n = 119). Compared to participants with the low reported use pattern, those with the frequent injection and heroin pattern had a greater likelihood of SUD treatment engagement (adjusted risk ratio = 1.28; 95% confidence interval = 1.02-1.61)., Conclusions: Distinct and meaningful polysubstance use patterns showed differential SUD treatment engagement after ED discharge. Nuanced relationships between substance use patterns and treatment highlight the necessity for tailored harm reduction, treatment, and recovery services., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objectives: Bacterial vaginosis-associated bacterium 2 (BVAB2), Mageeibacillus indolicus and Sneathia spp are highly predictive of bacterial vaginosis (BV) in cisgender women. They have been associated with non-gonococcal urethritis (NGU) in cisgender men in some but not all populations. We evaluated this association in a cross-sectional study of cisgender men who have sex with women only (MSW)., Methods: MSW without gonorrhoea attending a sexual health clinic (SHC) from 2014 to 2018 completed a computer-assisted self-interview, clinical interview and examination. NGU was defined as ≥5 polymorphonuclear leucocytes/high-power field in urethral exudates plus either urethral symptoms or visible discharge. Urine was tested for Chlamydia trachomatis and Mycoplasma genitalium using Aptima (Hologic) and for BVAB2, M. indolicus , Sneathia spp, Trichomonas vaginalis , Ureaplasma urealyticum , Haemophilus influenzae , herpes simplex virus and adenovirus using quantitative PCR., Results: Of 317 MSW age 17-71, 67 (21.1%) had Sneathia spp, 36 (11.4%) had BVAB2, and 17 (5.4%) had M. indolicus at enrolment. Having ≥3 partners in the past 2 months was the only characteristic that was more common among MSW with than those without these bacteria (BVAB2: 47% vs 23%, M. indolicus : 53% vs 24%, Sneathia spp: 42% vs 22%; p≤0.03 for all). One-hundred seventeen men (37%) were diagnosed with NGU at enrolment. There was no significant association of BVAB2, M. indolicus or Sneathia spp with NGU (adjusted OR=0.59, 95% CI 0.14 to 2.43; aOR=3.40, 95% CI 0.68 to 17.06; aOR=0.46, 95% CI 0.16 to 1.27). Of 109 MSW with monthly samples, 34 (31.2%) had one of the bacteria at one or more follow-up visits, 22 of which were co-colonised with >1. Median persistence over 6 months did not differ significantly (BVAB2=30.5 days, IQR=28-87; M. indolicus =87 days, IQR=60-126; Sneathia spp=70 days, IQR=30-135; p≥0.20 for each comparison)., Conclusions: Neither BVAB2, M. indolicus nor Sneathia spp were associated with increased risk of prevalent NGU in MSW attending an SHC., Competing Interests: Competing interests: LEM has received research support and honoraria from Hologic and Nabriva Therapeutics., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Photoisomerization of chromophores usually shows significantly less efficiency in solid polymers than in solution as strong intermolecular interactions lock their conformation. Herein, we establish the impact of macromolecular architecture on the isomerization efficiency of main-chain-incorporated chromophores (i.e., α-bisimine) in both solution and the solid state. We demonstrate that branched architectures deliver the highest isomerization efficiency for the main-chain chromophore in the solid state─remarkably as high as 70% compared to solution. The macromolecular design principles established herein for efficient solid-state photoisomerization can serve as a blueprint for enhancing the solid-state isomerization efficiency for other polymer systems, such as those based on azobenzenes.

Background: Monoclonal antibody (MAB) treatments for COVID-19 received Emergency Use Authorization in the United States., Methods: We used surveillance data from Rhode Island to conduct a retrospective, statewide cohort study to estimate the effectiveness of MABs for preventing hospitalization and death during periods when Alpha and Delta variants were predominant., Results: From 1/17/2021-10/26/2021, 285 long-term congregate care (LTCC) residents and 3,113 non-congregate patients met our eligibility criteria and received MAB; they were matched to 285 and 6,226 controls, respectively. Among LTCC residents, 8.8% (25/285) of patients who received MAB were hospitalized or died compared to 25.3% (72/285) of those who did not receive MAB (adjusted difference=16.7%, 95% confidence interval CI=11.0-22.3%). Among non-congregate patients, 4.5% (140/3,113) of patients who received MAB were hospitalized or died compared to 11.8% (737/6,226) of those who did not receive MAB (adjusted difference=7.2%, 95% CI=6.0-8.4%)., Conclusions: Administration of MABs led to an absolute reduction in hospitalization or death during periods when Alpha and Delta variants were predominant.

Importance: Health departments have used a variety of methods for overdose surveillance, and the Centers for Disease Control and Prevention (CDC) is implementing a standardized case definition to improve overdose surveillance nationally. The comparative accuracy of the CDC opioid overdose case definition vs existing state opioid overdose surveillance systems is unknown., Objective: To evaluate the accuracy of the CDC opioid overdose case definition and existing Rhode Island Department of Health (RIDOH) state opioid overdose surveillance system., Design, Setting, and Participants: This cross-sectional study of ED opioid overdose visits was conducted at 2 EDs in Providence, Rhode Island, at the state's largest health system from January to May 2021. Electronic health records (EHRs) were reviewed for opioid overdoses identified by the CDC case definition and opioid overdoses reported to the RIDOH state surveillance system. Included patients were those at study EDs whose visit met the CDC case definition, was reported to the state surveillance system, or both. True overdose cases were confirmed by EHR review using a standard case definition; 61 of 460 EHRs (13.3%) were double reviewed to estimate classification accuracy. Data were analyzed from January through May 2021., Main Outcome and Measure: Accurate identification of an opioid overdose was assessed by estimating the positive predictive value of the CDC case definition and state surveillance system using results from the EHR review., Results: Among 460 ED visits that met the CDC opioid overdose case definition, were reported to the RIDOH opioid overdose surveillance system, or both (mean [SD] age, 39.7 [13.5] years; 313 males [68.0%]; 61 Black [13.3%], 308 White [67.0%], and 91 other race [19.8%]; and 97 Hispanic or Latinx [21.1%] among each patient visit), 359 visits (78.0%) were true opioid overdoses. For these visits, the CDC case definition and RIDOH surveillance system agreed that 169 visits (36.7%) were opioid overdoses. Of 318 visits meeting the CDC opioid overdose case definition, 289 visits (90.8%; 95% CI, 87.2%-93.8%) were true opioid overdoses. Of 311 visits reported to the RIDOH surveillance system, 235 visits (75.6%; 95% CI, 70.4%-80.2%) were true opioid overdoses., Conclusions and Relevance: This cross-sectional study found that the CDC opioid overdose case definition more often identified true opioid overdoses compared with the Rhode Island overdose surveillance system. This finding suggests that using the CDC case definition for opioid overdose surveillance may be associated with improved data efficiency and uniformity.

Background: Antiretroviral therapy (ART) is recommended for people with HIV (PWH), irrespective of CD4 cell count, to improve their health and reduce the risk of transmission to sexual partners through long-term viral suppression. We identified risk factors for viral rebound among patients with a period of stable viral suppression to inform counseling and monitoring., Methods: We conducted a multisite, retrospective study of PWH with a 2-year period of sustained viral suppression in the United States using the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We used multivariable logistic regression to identify characteristics independently associated with any viral rebound (viral load [VL] ≥200 copies/mL) and sustained viral rebound (VL ≥200 copies/mL followed by a VL that was also ≥200 copies/mL within 6 months), within 2 years of follow-up., Results: Among 3496 eligible patients with a 2-year period of sustained viral suppression, most (90%) continued to have viral suppression over 2 additional years; 10% experienced viral rebound, and 4% experienced sustained viral rebound. In multivariable analyses, Black race, current smoking, integrase strand transfer inhibitor use, and 5- to 9-year duration of ART were positively associated, and being age ≥50 years was negatively associated, with any viral rebound. Only current smoking and 5- to 9-year (vs 2- to 4-year) duration of ART were positively associated, and being age ≥60 years was negatively associated, with sustained viral rebound., Conclusions: Most people retained in clinical care and with HIV viral suppression on ART will have persistent viral suppression. However, some patients may benefit from additional treatment adherence support., Competing Interests: Potential conflicts of interest. E.R.C. received unrestricted research funds paid to UC Regents from Gilead Sciences, Inc., and Merck for unrelated research topics and served on advisory boards for Gilead Sciences, Inc., and Theratechnologies on unrelated medical topics. K.C. served as a medical advisory board member for Gilead Sciences, Inc. K.H.M. received unrestricted research grants from Gilead Sciences, Inc., and Merck. A.R. received research funding from Merck on an unrelated research topic. C.G.B. received research funding from Gilead Sciences, Inc., for unrelated research topics. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Hypertension is a leading modifiable risk factor for cerebral small vessel disease. Our laboratory has shown that endothelium-dependent dilation in cerebral parenchymal arterioles (PAs) is dependent on transient receptor potential vanilloid 4 (TRPV4) activation, and this pathway is impaired in hypertension. This impaired dilation is associated with cognitive deficits and neuroinflammation. Epidemiological evidence suggests that women with midlife hypertension have an increased dementia risk that does not exist in age-matched men, though the mechanisms responsible for this are unclear. This study aimed to determine the sex differences in young, hypertensive mice to serve as a foundation for future determination of sex differences at midlife. We tested the hypothesis that young hypertensive female mice would be protected from the impaired TRPV4-mediated PA dilation and cognitive dysfunction observed in male mice. Angiotensin II (ANG II)-filled osmotic minipumps (800 ng/kg/min, 4 wk) were implanted in 16- to 19-wk-old male C56BL/6 mice. Age-matched female mice received either 800 ng/kg/min or 1,200 ng/kg/min ANG II. Sham-operated mice served as controls. Systolic blood pressure was elevated in ANG II-treated male mice and in 1,200 ng ANG II-treated female mice versus sex-matched shams. PA dilation in response to the TRPV4 agonist GSK1016790A (10 -9 -10 -5 M) was impaired in hypertensive male mice, which was associated with cognitive dysfunction and neuroinflammation, reproducing our previous findings. Hypertensive female mice exhibited normal TRPV4-mediated PA dilation and were cognitively intact. Female mice also showed fewer signs of neuroinflammation than male mice. Determining the sex differences in cerebrovascular health in hypertension is critical for developing effective therapeutic strategies for women. NEW & NOTEWORTHY Vascular dementia is a significant public health concern, and the effect of biological sex on dementia development is not well understood. TRPV4 channels are essential regulators of cerebral parenchymal arteriolar function and cognition. Hypertension impairs TRPV4-mediated dilation and memory in male rodents. Data presented here suggest female sex protects against impaired TRPV4 dilation and cognitive dysfunction during hypertension. These data advance our understanding of the influence of biological sex on cerebrovascular health in hypertension.

In 2017, Rhode Island responded to rising overdose deaths by establishing statewide emergency department (ED) treatment standards for opioid overdose and opioid use disorder. One requirement of the policy is that providers prescribe or provide take-home naloxone to anyone presenting to EDs with opioid overdose. Among adults presenting to EDs with opioid overdose from 2018 to 2019, approximately half received take-home naloxone. Receipt of naloxone was associated with administration of naloxone before ED presentation, ED policy certification level, and regional overdose frequency. ( Am J Public Health . 2023;113(4):372-377. https://doi.org/10.2105/AJPH.2022.307213).

Objective: To evaluate the impact of a statewide treatment standards policy for post-overdose emergency department (ED) care on services provided and subsequent treatment engagement., Methods: This pre-/post-study used electronic health record data and surveillance data from Rhode Island. Outcomes were compared for patients attending EDs for opioid overdose before (03/1/2015-02/28/2017) and after (04/01/2017-03/31/2021) policy release., Results: Overall, 2,134 patients attended 2,891 ED visits for opioid overdose. Compared to pre-policy, visits post-policy more often included initiation of buprenorphine in or from the ED (<1% vs. 3%, p<0.01), provision of a take-home naloxone kit or prescription (41% vs. 58%, p<0.01), and referral to treatment (0% vs. 34%, p<0.01). Provision of behavioral counseling in the ED and initiation of treatment within 30 days of the visit were similar during the two periods., Conclusions: Statewide post-overdose treatment standards may improve provision of some ED services. Additional strategies are needed to improve subsequent treatment engagement.

Although nuanced parameterization of sexual behavior may improve estimates from mathematical models of human immunodeficiency virus and sexually transmitted infection transmission, prospective estimates of the incidence of specific sexual behaviors among men who have sex with men (MSM) are limited. From December 2014 to July 2018, MSM with and without nongonococcal urethritis (NGU) completed weekly diaries over 3-12 weeks. Incidence rates of any sex, receptive anal sex, insertive anal sex, insertive oral sex, receptive rimming, and receptive hand-penile contact were 1.19, 0.28, 0.66, 0.90, 0.24, and 0.85 episodes per person-week, respectively, among 104 MSM with NGU at baseline, and 1.33, 0.54, 0.32, 0.95, 0.44, and 0.88 episodes per person-week, respectively, among 25 MSM without NGU at baseline. Most receptive anal sex (NGU + 83%, NGU - 86%) and insertive anal sex (NGU + 85%, NGU - 76%) episodes were condomless. MSM engaged in sex just over once per week, and condom use was infrequent. Insertive oral sex and receptive hand-penile contact were the most common behaviors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The objective of this study was to estimate the association between receipt of specific post-overdose care services in the emergency department (ED) and subsequent engagement in treatment for opioid use disorder (OUD) after discharge., Methods: This was a retrospective cohort study of Rhode Island residents treated at 1 of 4 EDs for opioid overdose who were not engaged in OUD treatment and were discharged home (May 2016-April 2021). Electronic health record data were used to identify ED services received, and state administrative data were used to define subsequent engagement in OUD treatment within 30 days. Multivariable conditional logistic regression was used to estimate the association between ED services received and subsequent treatment engagement., Results: Overall, 1008 people not engaged in OUD treatment were treated at study EDs for opioid overdose and discharged home, of whom 146 (14%) subsequently engaged in OUD treatment within 30 days. Most patients were aged 25 to 44 years (59%) and non-Hispanic White (69%). Receipt of behavioral counseling in the ED (adjusted odds ratio [aOR] = 1.79, 95% confidence interval [CI] = 1.18-2.71) and initiation of buprenorphine treatment in/from the ED (aOR = 5.86, 95% CI = 2.70-12.71) were associated with treatment engagement. Receipt of a take-home naloxone kit or naloxone prescription and referral to treatment at discharge were not associated with treatment engagement. Overall, 49% of patients received behavioral counseling in the ED, and 3% initiated buprenorphine in/from the ED., Conclusion: Strategies for increasing provision of behavioral counseling and initiation of buprenorphine in the ED may be useful for improving subsequent engagement in OUD treatment after discharge., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Rates of psychostimulant use, misuse, and hospitalization have increased markedly over the past decade. The objective of this study was to estimate the association between receipt of a psychostimulant prescription in the past year and fatal, unintentional psychostimulant-involved overdose. Methods: We conducted a population-based case-control study using linked, state-level databases from the Rhode Island Department of Health. Cases were defined as Rhode Island residents who experienced a fatal, unintentional drug overdose involving a psychostimulant, and controls included non-psychostimulant involved fatal overdoses occurring between May 1, 2017 and May 31, 2020 The primary exposure of interest was receipt of a psychostimulant prescription within 12 months prior to death, ascertained through linkage to the state's prescription drug monitoring program. Conditional logistic regression was used to estimate unadjusted and adjusted odds ratios. Results: Of 894 eligible overdose fatalities, the majority were white/non-Hispanic (72%), mean age was 43 years, and most resided in Providence County (69%). A total of 39 (4%) involved a psychostimulant. After adjusting for year of death and matching by sex, age, and county of residence, cases had 4.1 (95% confidence interval: 1.6, 10.6) times the odds of receiving a prescription stimulant in the past year compared to controls. Conclusions: Our findings suggest that there is a strong, positive association between prescription psychostimulant receipt and psychostimulant-involved fatal overdose. In response to an evolving polysubstance use landscape, current harm reductions measures, including naloxone training, fentanyl test strip distribution, and overdose education, should be expanded to include patients who receive psychostimulant prescriptions.

Background and Aims: Partial opioid agonist medications for opioid use disorder reduce mortality and morbidity, however long-term retention in treatment is challenging. The objective of this study was to identify patient and prescription characteristics associated with long-term buprenorphine treatment retention., Methods: We used data from the Rhode Island prescription drug monitoring program to identify residents who initiated buprenorphine treatment and determine if they were retained in long-term buprenorphine treatment 12-months after treatment initiation. Multivariable logistic regression models were used to identify sociodemographic and prescription characteristics associated with long-term buprenorphine retention., Findings: During the study period 4898 unique Rhode Island residents initiated buprenorphine treatment, of whom 37.8 % were retained in treatment at 12-months. Demographic factors associated with a higher odds of long-term buprenorphine retention included older age, female sex, Medicaid insurance (vs private), and living closer to the pharmacy where the prescription was filled. Individuals who were prescribed the tablet formulation (aOR: 0.82 [95 % CI 0.72, 0.93]) or received a non-buprenorphine opioid during the follow-up window (aOR: 0.37 [95 % CI 0.31, 0.44]) had lower odds of long-term treatment at 12-months. Individuals who received at least one day of overlapping benzodiazepine and buprenorphine prescriptions (aOR: 2.00 [95 % CI 1.70, 2.34]) and those given a longer days supply (aOR: 1.26 [95 % CI 1.01, 1.56]) had higher odds of long-term treatment at 12-months. Findings were similar for treatment retention at 6-months in sensitivity analyses., Conclusions: These findings highlight several modifiable prescribing practices associated with long-term buprenorphine retention, suggesting that clinicians and public health practitioners can help remove barriers to long-term retention., Competing Interests: Conflicts of interest All authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Overdose deaths have increased dramatically in the United States, including in Rhode Island. In July 2021, the Rhode Island government passed legislation supporting a two-year pilot program authorizing supervised consumption sites (SCSs) in response to this crisis. We estimated the costs and benefits of a hypothetical SCS in Providence, Rhode Island., Methods: We utilized a decision analytic mathematical model to compare costs and outcomes for people who inject drugs under two scenarios: (1) a SCS that includes syringe services provision, and (2) a syringe service program only (i.e., status quo). We assumed 0.95% of injections result in overdose, the SCS would serve 400 clients monthly and have a net cost of $783,899 annually, 46% of overdoses occurring outside of the SCS result in an ambulance run and 43% result in an emergency department (ED) visit, 0.79% of overdoses occurring within the SCS result in an ambulance run and ED visit, and the SCS would lead to a 25.7% reduction in fatal overdoses near the site. The model was developed from a modified societal perspective with a one-year time horizon., Results: A hypothetical SCS in Providence would prevent approximately 2 overdose deaths, 261 ambulance runs, 244 ED visits, and 117 inpatient hospitalizations for emergency overdose care annually compared to a scenario that includes a syringe service program only. The SCS would save $1,104,454 annually compared to the syringe service program only, accounting only for facility costs and short-term costs of emergency overdose care and ignoring savings associated with averted deaths. Influential parameters included the percentage of injections resulting in overdose, the total annual injections at the SCS, and the percentage of overdoses outside of the SCS that result in an ED visit., Conclusion: A SCS in would result in substantial cost savings due to prevention of costly emergency overdose care., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Potential conflicts of interest: LCC conducts research unrelated to this work funded by the Hassenfeld Family Foundation. All other authors declare that they have no potential conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: In a model of secondary hypertension, mineralocorticoid receptor (MR) antagonism during the development of hypertension prevents the impairment of transient receptor potential vanilloid 4 (TRPV4) activation in parenchymal arterioles (PAs) and cognitive impairment. However, it is unknown whether MR antagonism can improve these impairments when treatment begins after the onset of essential hypertension. We tested the hypothesis that MR activation in stroke-prone spontaneously hypertensive rats (SHRSP) leads to impaired TRPV4-mediated dilation in PAs that is associated with cognitive dysfunction and neuroinflammation., Methods: 20-22-week-old male SHRSP ± eplerenone (EPL; 100 mg/kg daily for 4 weeks) were compared to normotensive Sprague-Dawley (SD) rats. Pressure myography was used to assess PA function. Cognition was tested using Y-maze. Neuroinflammation was assessed using immunofluorescence and qRT-PCR., Results: Carbachol-mediated endothelium-dependent dilation was impaired in SHRSP, and MR antagonism improved this without affecting myogenic tone. Dilation to TRPV4 agonist GSK1016790A was impaired in SHRSP, and ELP treatment restored this. Intermediate conductance potassium channel (IKCa)/small conductance potassium channel (SKCa)-mediated dilation was impaired by hypertension and unaffected by EPL treatment. TRPV4 and IKCa/SKCa channel mRNA expression were reduced in PAs from hypertensive rats, and EPL did not improve this. Impairments in PA dilation in SHRSP were associated with cognitive decline, microglial activation, reactive astrogliosis, and neuroinflammation; cognitive and inflammatory changes were improved with MR blockade., Conclusions: These data advance our understanding of the effects of hypertension on cerebral arterioles using a clinically relevant model and treatment paradigm. Our studies suggest TRPV4 and the MR are potential therapeutic targets to improve cerebrovascular function and cognition during hypertension., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

More than 2 million people are incarcerated in the United States with many millions more processed through correctional facilities annually. Communities impacted by incarceration are also disproportionately impacted by the HIV and sexually transmitted infection (STI) epidemics. However, relatively little is known about the behaviors that place individuals with a history of incarceration at risk for HIV/STI acquisition. We utilized clinical data from patients presenting to an STI clinic located in Providence, Rhode Island. A latent class analysis was conducted on reported HIV acquisition risk behavior and STI testing results on a total of 1129 encounters where a history of incarceration was reported. A total of three classes were identified. Class 1 ( N  = 187, 11%), more frequently reported 10+ sexual partners (45%), an STI diagnosis (48%) and sex while intoxicated (86%) in the past year as well as identifying as a man who has sex with other men (60%). Class 2 ( N  = 57, 5%) was more likely to report giving (53%) and receiving (44%) money/drugs for sex in the past year as well as a history of injecting drugs (61%) and using methamphetamine (60%). Class 3 ( N  = 885, 78%) most frequently reported 0-2 sexual partners (48%), identified as Black (27%), Hispanic/Latino (69%) and a man who only has sex with women (80%). Class 1 had significantly higher odds ratio (1.8, 95% confidence interval = 1.3-2.5) of testing HIV/STI positive. The results provide important insights into risk subgroups for those with a history of incarceration at risk of HIV/STI acquisition.

Importance: The benefit of vaccination for preventing reinfection among individuals who have been previously infected with SARS-CoV-2 is largely unknown., Objective: To obtain population-based estimates of the probability of SARS-CoV-2 reinfection and the effectiveness associated with vaccination after recovery from COVID-19., Design, Setting, and Participants: This cohort study used Rhode Island statewide surveillance data from March 1, 2020, to December 9, 2021, on COVID-19 vaccinations, laboratory-confirmed cases, hospitalizations, and fatalities to conduct a population-based, retrospective study during periods when wild type, Alpha, and Delta strains of SARS-CoV-2 were predominant. Participants included Rhode Island residents aged 12 years and older who were previously diagnosed with COVID-19 and unvaccinated at the time of first infection, stratified into 3 subpopulations: long-term congregate care (LTCC) residents, LTCC employees, and the general population (ie, individuals not associated with congregate settings). Data were analyzed from October 2021 to January 2022., Exposures: Completion of the primary vaccination series, defined as 14 days after the second dose of an mRNA vaccine or 1 dose of vector virus vaccine., Main Outcomes and Measures: The main outcome was SARS-CoV-2 reinfection, defined as a laboratory-confirmed positive result on a polymerase chain reaction (PCR) or antigen test at least 90 days after the first laboratory-confirmed positive result on a PCR or antigen test., Results: Overall, 3124 LTCC residents (median [IQR] age, 81 [71-89]; 1675 [53.6%] females), 2877 LTCC employees (median [IQR] age, 41 [30-53]; 2186 [76.0%] females), and 94 516 members of the general population (median [IQR] age, 35 [24-52] years; 45 030 [47.6%] females) met eligibility criteria. Probability of reinfection at 9 months for those who remained unvaccinated after recovery from prior COVID-19 was 13.0% (95% CI, 12.0%-14.0%) among LTCC residents, 10.0% (95% CI, 8.8%-11.5%) among LTCC employees, and 1.9% (95% CI, 1.8%-2.0%) among the general population. Completion of the primary vaccination series after infection was associated with 49% (95% CI, 27%-65%) protection among LTCC residents, 47% (95% CI, 19%-65%) protection among LTCC employees, and 62% (95% CI, 56%-68%) protection in the general population against reinfection, adjusting for potential sociodemographic and clinical confounders and temporal variation in infection rates., Conclusions and Relevance: These findings suggest that risk of SARS-CoV-2 reinfection after recovery from COVID-19 was relatively high among individuals who remained unvaccinated. Vaccination after recovery from COVID-19 was associated with reducing risk of reinfection by approximately half.

Endothelial cells form the innermost layer of all blood vessels and are the only vascular component that remains throughout all vascular segments. The cerebral vasculature has several unique properties not found in the peripheral circulation; this requires that the cerebral endothelium be considered as a unique entity. Cerebral endothelial cells perform several functions vital for brain health. The cerebral vasculature is responsible for protecting the brain from external threats carried in the blood. The endothelial cells are central to this requirement as they form the basis of the blood-brain barrier. The endothelium also regulates fibrinolysis, thrombosis, platelet activation, vascular permeability, metabolism, catabolism, inflammation, and white cell trafficking. Endothelial cells regulate the changes in vascular structure caused by angiogenesis and artery remodeling. Further, the endothelium contributes to vascular tone, allowing proper perfusion of the brain which has high energy demands and no energy stores. In this article, we discuss the basic anatomy and physiology of the cerebral endothelium. Where appropriate, we discuss the detrimental effects of high blood pressure on the cerebral endothelium and the contribution of cerebrovascular disease endothelial dysfunction and dementia. © 2022 American Physiological Society. Compr Physiol 12:3449-3508, 2022., (Copyright © 2022 American Physiological Society. All rights reserved.)

Objective: Understanding and identifying disparities in COVID-19 testing outcomes can help allocate resources to where they are most needed. The objective of this study was to estimate the association between lesbian, gay, bisexual, transgender, and queer (LGBTQ+) identity and SARS-CoV-2 test positivity., Methods: Data were from the Rhode Island SARS-CoV-2 surveillance database and included tests scheduled from June 8, 2020, through January 15, 2021. We used multivariable generalized estimating equations accounting for repeat testing to estimate the odds of receiving a positive test result for SARS-CoV-2 by LGBTQ+ identity and race/ethnicity, adjusting for sociodemographic and temporal confounders., Results: In multivariable analysis of 232 025 tests, LGBTQ+ people had lower odds of receiving a positive test result than cisgender heterosexual people (5.4% vs 8.7%; adjusted odds ratio [aOR] = 0.63; 95% CI, 0.59-0.68). Compared with cisgender heterosexual White people, LGBTQ+ White people were significantly less likely (aOR = 0.67; 95% CI, 0.61-0.73) and cisgender heterosexual people of color were significantly more likely (aOR = 1.71; 95% CI, 1.64-1.78) to receive a positive test result. LGBTQ+ people of color had similar test positivity (aOR = 0.90; 95% CI, 0.79-1.02) as cisgender heterosexual White people. People in sexual minority groups were significantly less likely than heterosexual people to receive a positive test result, but we found no significant differences in test results among cisgender, transgender, and gender nonconforming people., Conclusions: LGBTQ+ people may be less likely than heterosexual people to receive a positive test result for SARS-CoV-2, potentially related to protective health practices and greater social isolation. Addressing racial and ethnic disparities among both LGBTQ+ people and cisgender heterosexual people should be a priority of the public health workforce.

We explore a cross-linked polymer network based on a visible light photodynamic [2 + 2] cycloaddition driven by styrylpyrene chemistry. Based on a polymer backbone with pendent styrylpyrene units, the network can be formed by using λ = 450 nm irradiation. Upon irradiation with λ = 340 nm, a photostationary state is generated within the network with ∼17% of the styrylpyrene units open compared to close to 2% in the visible light cured state. The limited fraction of open [2 + 2] couples is caused by their proximity and is in sharp contrast to solution experiments on the photoreactive moiety. Thus, the polymer network retains its mechanical properties even at the photostationary point. We hypothesize that the application of an additional stimulus could serve as a second gate for inducing network disintegration by spacing the [2 + 2] units during ultraviolet irradiation.

Objective: To identify initial diagnoses associated with elevated risk of chronic prescription opioid use., Design: Population-based, retrospective cohort study., Setting: State of Rhode Island., Participants: Rhode Island residents with an initial opioid prescription dispensed between 1 April 2019 and 31 March 2020., Primary Outcome Measure: Subsequent chronic prescription opioid use, defined as receiving 60 or more days' supply of opioids in the 90 days following an initial opioid prescription., Results: Among the 87 055 patients with an initial opioid prescription, 3199 (3.7%) subsequently became chronic users. Patients who become chronic users tended to receive a longer days' supply, greater quantity dispensed, but a lower morphine milligram equivalents on the initial opioid prescription. Patients prescribed an initial opioid prescription for diseases of the musculoskeletal system and connective tissue (adjusted OR (aOR): 5.9, 95% CI: 4.7 to 7.6), diseases of the nervous system (aOR: 6.3, 95% CI: 4.9 to 8.0) and neoplasms (aOR: 5.6, 95% CI: 4.2 to 7.5) had higher odds of subsequent chronic prescription opioid use, compared with a referent group that included all diagnosis types with fewer than 15 chronic opioid users, after adjusting for confounders., Conclusions: By focusing interventions and prescribing guidelines on specific types of diagnoses that carry a high risk of chronic prescription opioid use and diagnoses that would benefit equally or more from alternative management approaches, states and healthcare organisations may more efficiently decrease inappropriate opioid prescribing while improving the quality of patient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Accidental opioid-involved overdose deaths are increasing nationally in the wake of the COVID-19 pandemic, but it is unclear if this reflects a change in populations most at risk. Objective: To determine whether the demographic characteristics and controlled substance prescription history of accidental opioid-involved drug overdose decedents in 2020 differed from prior years. Methods: We identified accidental opioid-involved overdose decedents using Rhode Island (RI) State Medical Examiner's Office data. Decedents were linked to the RI Prescription Drug Monitoring Program database. We compared demographic characteristics and prescription history by year of death. Results: From 2018 to 2020, 763 RI residents died from accidental opioid-involved overdose in RI. From 2018 to 2019, deaths decreased by 7%, but then increased by 31% from 2019 to 2020. Demographic characteristics were similar by year of death (all p  > 0.05). The percentage of decedents with a prior opioid prescription and a prior benzodiazepine prescription declined from 2018 to 2020 ( p  < 0.01 and p  = 0.03). Conclusions: We found that opioid-involved overdose deaths in RI are increasing overall, but without significant changes in demographics. While prior exposure to some controlled substances did decline over time, it is not clear if these changes reflect more responsible prescribing practices, or a more concerning pattern such as patient abandonment or decreased healthcare access. More studies are needed to better describe the current trend of increasing opioid-involved deaths while also pursuing current evidence-based interventions.

Objective: No case definition exists that allows public health authorities to accurately identify opioid overdoses using emergency medical services (EMS) data. We developed and evaluated a case definition for suspected nonfatal opioid overdoses in EMS data., Methods: To identify suspected opioid overdose-related EMS runs, in 2019 the Rhode Island Department of Health (RIDOH) developed a case definition using the primary impression, secondary impression, selection of naloxone in the dropdown field for medication given, indication of medication response in a dropdown field, and keyword search of the report narrative. We developed the case definition with input from EMS personnel and validated it using an iterative process of random medical record review. We used naloxone administration in consideration with other factors to avoid misclassification of opioid overdoses., Results: In 2018, naloxone was administered during 2513 EMS runs in Rhode Island, of which 1501 met our case definition of a nonfatal opioid overdose. Based on a review of 400 randomly selected EMS runs in which naloxone was administered, the RIDOH case definition accurately identified 90.0% of opioid overdoses and accurately excluded 83.3% of non-opioid overdose-related EMS runs. Use of the case definition enabled analyses that identified key patterns in overdose locations, people who experienced repeat overdoses, and the creation of hotspot maps to inform outbreak detection and response., Practice Implications: EMS data can be an effective tool for monitoring overdoses in real time and informing public health practice. To accurately identify opioid overdose-related EMS runs, the use of a comprehensive case definition is essential.

The Rhode Island Department of Health (RIDOH) uses emergency department data to monitor nonfatal opioid overdoses in Rhode Island. In April 2019, RIDOH detected an increase in nonfatal opioid overdoses in Woonsocket, Rhode Island, and sent an alert to state and local partners (eg, fire departments, emergency departments, faith leaders) with guidance on how to respond. To guide community-level, strategic response efforts, RIDOH analyzed surveillance data to identify overdose patterns, populations, and geographic areas most affected. During April-June 2019, nonfatal opioid overdoses in Woonsocket increased 463% (from 13 to 73) when compared with the previous 3 months. Because of the sustained increase in nonfatal opioid overdoses, RIDOH brought together community partners at a meeting in June 2019 to discuss RIDOH opioid overdose data and coordinate next steps. Data analyses were essential to framing the discussion and allowed community partners at the event to identify an unexpected increase in cocaine-involved nonfatal opioid overdoses in Woonsocket. Many patients with cocaine-involved nonfatal overdoses also had fentanyl in their system, and input from community partners suggested that many patients were unaware of using fentanyl. Community response actions included targeting harm reduction services (eg, distribution of naloxone, mobile needle exchange); deploying peer recovery support specialists to overdose hotspots to connect people to treatment and recovery resources; placing harm reduction messaging in high-traffic areas; and targeted social media messaging. After the meeting, nonfatal opioid overdoses returned to pre-outbreak levels. This case study provides an example of how timely opioid overdose data can be effectively used to detect a spike in nonfatal opioid overdoses and inform a strategic, community-level response.

Background: Nongonococcal urethritis (NGU) is a common syndrome with no known etiology in ≤50% of cases. We estimated associations between urethral bacteria and NGU in men who have sex with men (MSM) and men who have sex with women (MSW)., Methods: Urine was collected from NGU cases (129 MSM, 121 MSW) and controls (70 MSM, 114 MSW) attending a Seattle STD clinic. Cases had ≥5 polymorphonuclear leukocytes on Gram stain plus symptoms or discharge; controls had <5 PMNs, no symptoms, no discharge. NGU was considered idiopathic when Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenovirus, and herpes simplex virus were absent. The urethral microbiota was characterized using 16S rRNA gene sequencing. Compositional lasso analysis was conducted to identify associations between bacterial taxa and NGU and to select bacteria for targeted qPCR., Results: Among NGU cases, 45.2% were idiopathic. Based on compositional lasso analysis, we selected Haemophilus influenzae (HI) and Mycoplasma penetrans (MP) for targeted qPCR. Compared with 182 men without NGU, the 249 men with NGU were more likely to have HI (14% vs 2%) and MP (21% vs 1%) (both P ≤ .001). In stratified analyses, detection of HI was associated with NGU among MSM (12% vs 3%, P = .036) and MSW (17% vs 1%, P < .001), but MP was associated with NGU only among MSM (13% vs 1%, P = .004). Associations were stronger in men with idiopathic NGU., Conclusions: HI and MP are potential causes of male urethritis. MP was more often detected among MSM than MSW with urethritis., (© 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.)

To guide intervention efforts, we identified the proportion of individuals previously engaged in opioid agonist therapy among people who died of an accidental opioid-involved overdose. Most individuals (60.9%) had never received any prior buprenorphine or methadone treatment. Individuals who died of an overdose in 2020 had a similar demographic profile and treatment history compared with prior years. To prevent additional accidental opioid-involved overdose deaths, efforts should be directed toward linking individuals to care.

We demonstrate the light-induced, crosslinker mediated collapse of linear polymer chains into single-chain nanoparticles (SCNPs) capable of self-reporting their unfolding. The crosslinker entails a phenyloxalate motif allowing for the targeted degradation of the SCNPs via addition of hydrogen peroxide that triggers chemiluminescence (CL). The time-dependant CL emission can serve as a guide to follow the time dependent unfolding of the SCNPs, allowing for a qualitative assessment of the underlying mechanism.

Background: Incidence and risk factors for nongonococcal urethritis (NGU) remain poorly defined. We conducted a cohort study to estimate the incidence of NGU and identify risk factors in men who have sex with women., Methods: We enrolled cisgender male sexually transmitted disease clinic attendees 16 years or older who reported exclusively female partners. At enrollment and 6 monthly follow-up visits, men underwent a clinical examination, provided urethral swab and urine specimens, completed a sexual behavior survey and biweekly diaries, and were tested for Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) using Aptima assays (Hologic, Inc). Nongonococcal urethritis was defined as ≥5 polymorphonuclear leukocytes per high-power field plus either urethral symptoms or visible discharge. We estimated the incidence of NGU overall, asymptomatic and symptomatic NGU, non-CT/non-MG NGU, and CT/MG-associated NGU using Poisson regression for clustered outcomes. We performed relative risk binomial regression for clustered data to identify characteristics associated with incident NGU., Results: From August 2014 to July 2018, 307 participants at risk for NGU contributed 109.4 person-years. Median age was 32 years, and 52% were White. At enrollment, 107 men had NGU; of these, 88% were symptomatic, 27% had CT, and 22% had MG. Fifty men had 60 cases of incident NGU (incidence rate, 56 per 100 person-years; 95% confidence interval, 43-74). Unlike prevalent NGU at enrollment, CT/MG-associated incident NGU was rare (incidence rate, 7; 95% confidence interval [CI], 4-15), and most (78%) incident NGU was asymptomatic. Risk factors for incident NGU were ≤ high school education (adjusted rate ratio [ARR], 2.45; 95% CI, 1.19-5.00), history of CT (ARR, 2.15; 95% CI, 1.08-4.27), history of NGU (ARR, 2.67; 95% CI, 1.27-5.62), and NGU at enrollment (ARR, 2.03; 95% CI, 1.04-3.98). Neither condom use nor having a new partner was associated with incident NGU; Black race was only associated with incident symptomatic and non-CT/non-MG NGU., Conclusions: Incidence of NGU was high, predominantly non-CT/non-MG and asymptomatic. Future studies should investigate the etiology and clinical significance of asymptomatic NGU., Competing Interests: Conflict of Interest and Sources of Funding: L.E.M. has received honoraria, reagents, and test kits for diagnostic assays from Hologic, Inc. L.C.C. and E.R. have received trainee support from the Institute of Translational Health Sciences (grant number TL1 TR002318). M.R.G. has received grants from the National Institutes of Health, Hologic, and GSK. All other authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the article have been disclosed., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

Remdesivir is one of few FDA-approved treatments for severe cases of Coronavirus Disease 2019 (COVID-19). To better assess its efficacy and safety, we conducted a meta-analysis to systematically identify and synthesize existing findings. We conducted a comprehensive literature search among six electronic databases and unpublished studies. Random-effects meta-analyses were performed to summarize the risk ratio (RR) and rate estimates from eligible studies. Funnel plots, the Egger test, and the trim and fill analysis were used to detect publication bias. Thirteen eligible studies were included in this meta-analysis, giving a pooled sample size of 10,002 COVID-19 hospitalized patients (5068 administered remdesivir; 4934 control). Among patients on remdesivir, we synthesized mortality (15%, 95% confidence interval [CI]: 9%, 22%), clinical improvement (64%, 95% CI: 51%, 78%), recovery (70%, 95% CI: 57%, 83%), hospital discharge (74%, 95% CI: 60%, 87%), serious adverse effect (SAE) (21%, 95% CI:13%, 29%), and Grade 3 or 4 adverse effect (AE) (30%, 95% CI: 12%, 48%). Patients on remdesivir were 17% (RR: 0.83, 95% CI: 0.65, 1.06) less likely to die than those within the control group. Additionally, remdesivir had favorable outcomes in terms of clinical improvement, recovery, and hospital discharge. Lastly, non-mechanically ventilated patients had better overall clinical outcomes than mechanically ventilated patients. Remdesivir shows a moderate-favorable treatment efficacy among hospitalized COVID-19 patients with disproportionate impact among non-mechanically ventilated patients; however, a substantial proportion of COVID-19 patients may suffer from SAE or Grade 3 or 4 AE during the treatment course., Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-021-01014-y., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021.)