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Purpose: To describe healthcare experiences and health outcomes among rural LGBTQ + individuals., Design: 2022 cross-sectional survey., Setting: Southern Illinois., Sample: 85 individuals., Measures: Demographics, sexual orientation and gender identity, healthcare experiences, health outcomes., Analysis: Experiences and outcomes were assessed vs orientation and identity. Distribution comparison was by t -test and chi-square, risk prediction by logistic regression, and significance assumed at P < .050., Results: By orientation, participants were: 35.3% gay, 16.5% lesbian, and 45.8% bisexual plus; and by identity they were: 49.4% cisgender, 25.9% transgender, and 24.8% other identity. Survey item responses ranged from 95%-99%. Compared to gay men, lesbians and bisexual plus individuals more frequently reported medical bill payment difficulty (58.3% and 57.9% vs 25.0%; P = .020) and more past month days of poor mental health (19.4 and 15.8 vs 10.6; P = .018). Compared to heterosexual and other identity, transgender individuals less frequently reported having a routine medical provider (72.7% vs 92.7% and 95.0%; P = .037) and more frequently reported past healthcare denial (45.5% vs 17.5% and 18.8%; P = .042). Current health was associated with medical bill payment ability (OR = .33, 95% CI = .13-.86) and respectful treatment by healthcare administrators (OR = 3.90, 95% CI = 1.34-11.35) and clinicians (OR = 3.82, 95% CI = 1.39-10.47). Significance of some findings likely limited due to sample size., Conclusions: Our data describes healthcare experience and health outcome disparities among rural lesbian, gay, bisexual, transgender, queer and other sexual and gender minority individuals, and indicate that clinical experiences directly influence health outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The United States' (US) opioid overdose epidemic has evolved into a combined stimulant/opioid epidemic, a pattern driven in part by mitigating opioid overdose risk, variable substance availability, and personal preferences. This study aimed to investigate the association between self-reported substance preference (heroin or methamphetamine) and behavioral/health outcomes among individuals who used both heroin and methamphetamine in the rural US., Methods: The Rural Opioid Initiative is a consortium of 8 research cohorts from 10 states and 65 rural counties that recruited individuals reporting past 30-day injection of any substance or opioid substance use by any route from 1/2018 to 3/2020. Analyses were restricted to participants ⩾18 years, who self-reported either heroin or methamphetamine as their preferred substance and past 30-day use of both heroin and methamphetamine. We examined cross-sectional associations between preferred substance (heroin versus methamphetamine) and behavioral and health outcomes using random effects meta-analysis with adjusted regression models., Results: Among 1239 participants, 61% (n = 752) reported heroin as their preferred substance. Adjusting for age, sex, and race/ethnicity, methamphetamine preference was associated with lower prevalence ratios for current naloxone possession (adjusted prevalence ratio [aPR] = 0.68; 95% Confidence Interval [95% CI] = 0.59-0.78; P -value ⩽ .001), of ever being told they had the hepatitis C virus (HCV; aPR = 0.72; 95% CI: 0.61-0.85; P -value ⩽ .001) and a personal history of overdose (aPR = 0.81; 95% CI = 0.73-0.90; P -value ⩽ .001)., Conclusion: In our study analyzing associations between preferred substance and various behavioral and health outcomes amongst people who use both heroin and methamphetamine, a majority of participants preferred heroin. Methamphetamine preference was associated with lower prevalence of naloxone possession, ever being told they had HCV, and prior history of an overdose. This study underscores the need for targeted harm reduction services for people who prefer methamphetamine in rural areas., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes the depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results in death, typically before fifteen years of age. Histopathological features of CLN1 include aggregation of lysosomal autofluorescent storage material (AFSM), as well as profound gliosis. The current management of CLN1 is relegated to palliative care. Here, we examine the therapeutic potential of a small molecule PPT1 mimetic, N-tert-butyl hydroxylamine (NtBuHA), in a Cln1 -/- mouse model. Treatment with NtBuHA reduced AFSM accumulation both in vitro and in vivo. Importantly, NtBuHA treatment in Cln1 -/- mice reduced neuroinflammation, mitigated epileptic episodes, and normalized motor function. Live cell imaging of Cln1 -/- primary cortical neurons treated with NtBuHA partially rescued aberrant synaptic calcium dynamics, suggesting a potential mechanism contributing to the therapeutic effects of NtBuHA in vivo. Taken together, our findings provide supporting evidence for NtBuHA as a potential treatment for CLN1 Batten Disease., Competing Interests: Declaration of competing interest AIS and DW have stock in Circumvent. NAN, CH, PR and RJ all receive compensation for their time and expertise from Circumvent., (Copyright © 2024. Published by Elsevier Inc.)

Sexual and gender minorities (SGM) frequently experience depression and health care-related stigma. Health care satisfaction is important for seeking care, but little is known about SGM health care satisfaction, and especially as it relates to depression among rural SGM. From May 25 to July 2, 2021, we surveyed rural Illinois (IL) individuals aged ≥18 years on the topics of demographics, depression, health care satisfaction, past health care experiences, internalized stigma, and victimization. Among the 398 respondents, the gender identity distribution included cisgender males and females (171 and 203, respectively) and transgender males and females (8 and 7, respectively), while sexual orientation included heterosexuals (114), gay/lesbians (143), and other orientations (141). Analyses were conducted with respect to both identity and orientation (and their interaction). In univariate analysis, transgender individuals were more likely than cisgender to screen positive for depression and less likely to report feeling accepted by their medical provider. Compared to heterosexual respondents, gay/lesbians and other orientations were more likely to screen positive for depression. In logistic regression, factors associated with increased risk of depression included nonheterosexual orientation and past poor health care experiences. In linear regression, factors most commonly associated with the seven satisfaction subscales include: sexual orientation, past poor experiences, and employment. There were significant differences in depression across both sexual orientation and gender identity, and in health care satisfaction by sexual orientation. Rural SGMs are more vulnerable to depression and less likely to report satisfactory care. As health care engagement is critical for screening and care adherence, engaging rural SGM in a routine and satisfactory fashion is needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Anthropogenic stressors threaten large whales globally. Effective management requires an understanding of where, when, and why threats are occurring. Strandings data provide key information on geographic hotspots of risk and the relative importance of various threats. There is currently considerable public interest in the increased frequency of large whale strandings occurring along the US East Coast of the United States since 2016. Interest is accentuated due to a purported link with offshore wind energy development. We reviewed spatiotemporal patterns of strandings, mortalities, and serious injuries of humpback whales (Megaptera novaeangliae), the species most frequently involved, for which the US government has declared an "unusual mortality event" (UME). Our analysis highlights the role of vessel strikes, exacerbated by recent changes in humpback whale distribution and vessel traffic.  Humpback whales have expanded into new foraging grounds in recent years. Mortalities due to vessel strikes have increased significantly in these newly occupied regions, which show high vessel traffic that also increased markedly during the UME. Surface feeding and feeding in shallow waters may have been contributing factors. We found no evidence that offshore wind development contributed to strandings or mortalities. This work highlights the need to consider behavioral, ecological, and anthropogenic factors to determine the drivers of mortality and serious injury in large whales and to provide informed guidance to decision-makers., (© 2024 The Author(s). Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Background: Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated., Methods: RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses., Results: Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach., Conclusions: RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations., (© 2024. The Author(s).)

Background: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs., Methods: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose., Results: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14)., Conclusions: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk., (© 2024. The Author(s).)

The Rural Opioid Initiative surveyed 2693 people who inject drugs (PWID) in eight rural U.S. areas in 2018-2020 about self-reported HIV testing in the past 6 months. Correlates of interest included receipt of any drug-related services, incarceration history, and structural barriers to care (e.g., lack of insurance, proximity to syringe service programs [SSP]). Overall, 20% of participants reported receiving an HIV test within the past 6 months. Multivariable generalized estimating equations showed that attending substance use disorder (SUD) treatment (OR 2.11, 95%CI [1.58, 2.82]), having health insurance (OR 1.42, 95%CI [1.01, 2.00]) and recent incarceration (OR 1.49, 95%CI [1.08, 2.04]) were positively associated with HIV testing, while experiencing a resource barrier to healthcare (inability to pay, lack of transportation, inconvenient hours, or lack of child care) had inverse (OR 0.73, 95%CI [0.56, 0.94]) association with HIV testing. We found that the prevalence of HIV testing among rural PWID is low, indicating an unmet need for testing. While SUD treatment or incarceration may increase chances for HIV testing for rural PWID, other avenues for expanding HIV testing, such as SSP, need to be explored., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The acoustic ecology of sei whales (Balaenoptera borealis) is poorly understood due to limited direct observation of the behavioral context of sound production and individual behavior. Suction cup-attached acoustic recording tags were deployed on sei whales to unambiguously assign call types and explore the acoustic behavior of this endangered species. Twelve tag deployments resulted in ∼173 h of acoustic data and 1030 calls. Sound types included downsweeps and three previously undescribed call types. Knocks were short duration (<1 s), with an average peak frequency of 330 Hz. Pulse type 1 and pulse type 2 calls, typically produced in sequences, were short in duration (0.08 and 0.28 s) and low in average peak frequency (50 and 26 Hz), with relatively high received levels. Average call rates for all call types combined were three calls per hour, but increased during twilight. Sex differences in call type usage included a higher use of pulses by females and knocks by males. Calls were almost exclusively produced at depths <10 m, although whales rarely dove deeper in this study. These data provide a more comprehensive picture of the acoustic and behavioral ecology of sei whales than previously possible, which can inform future conservation efforts for this endangered species., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Background: Research conducted in urban areas has highlighted the impact of housing instability on people who inject drugs (PWID), revealing that it exacerbates vulnerability to drug-related harms and impedes syringe service program (SSP) use. However, few studies have explored the effects of houselessness on SSP use among rural PWID. This study examines the relationship between houselessness and SSP utilization among PWID in eight rural areas across 10 states., Methods: PWID were recruited using respondent-driven sampling for a cross-sectional survey that queried self-reported drug use and SSP utilization in the prior 30 days, houselessness in the prior 6 months and sociodemographic characteristics. Using binomial logistic regression, we examined the relationship between experiencing houselessness and any SSP use. To assess the relationship between houselessness and the frequency of SSP use, we conducted multinomial logistic regression analyses among participants reporting any past 30-day SSP use., Results: Among 2394 rural PWID, 56.5% had experienced houselessness in the prior 6 months, and 43.5% reported past 30-day SSP use. PWID who had experienced houselessness were more likely to report using an SSP compared to their housed counterparts (adjusted odds ratio [aOR] = 1.24 [95% confidence intervals [CI] 1.01, 1.52]). Among those who had used an SSP at least once (n = 972), those who experienced houselessness were just as likely to report SSP use two (aOR = 0.90 [95% CI 0.60, 1.36]) and three times (aOR = 1.18 [95% CI 0.77, 1.98]) compared to once. However, they were less likely to visit an SSP four or more times compared to once in the prior 30 days (aOR = 0.59 [95% CI 0.40, 0.85])., Conclusion: This study provides evidence that rural PWID who experience houselessness utilize SSPs at similar or higher rates as their housed counterparts. However, housing instability may pose barriers to more frequent SSP use. These findings are significant as people who experience houselessness are at increased risk for drug-related harms and encounter additional challenges when attempting to access SSPs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Multiple rural states and communities experience elevated rates of human immunodeficiency virus (HIV), often associated with diminished healthcare access and increased drug use. Though a substantial proportion of rural populations are sexual and gender minorities (SGM), little is known of this group regarding substance use, healthcare utilization, and HIV transmission behaviors. During May-July 2021, we surveyed 398 individuals across 22 rural Illinois counties. Participants included cisgender heterosexual males (CHm) and females (CHf) ( n  = 110); cisgender non-heterosexual males and females (C-MSM and C-WSW; n  = 264); and transgender individuals (TG; n  = 24). C-MSM participants were more likely to report daily-to-weekly alcohol and illicit drug use prescription medication misuse (versus CHf; aOR = 5.64 [2.37-13.41], 4.42 [1.56-12.53], and 29.13 [3.80-223.20], respectively), and C-MSM participants more frequently reported traveling to meet with romantic/sex partners. Further, more C-MSM and TG than C-WSW reported healthcare avoidance and denial due to their orientation/identity ( p  < 0.001 and p  = 0.011, respectively); 47.6% of C-MSM and 58.3% of TG had not informed their provider about their orientation/identity; and only 8.6% of C-MSM reported ever receiving a pre-exposure prophylaxis (PrEP) recommendation. More work is needed to explore the substance use and sexual behaviors of rural SGM, as well as their healthcare interactions, to better target health and PrEP engagement campaigns.

Purpose: To evaluate how technology access affected substance use disorder (SUD) treatment prior to COVID-19 for people who use drugs in rural areas., Methods: The Rural Opioid Initiative (January 2018-March 2020) was a cross-sectional study of people with prior 30-day injection drug or nonprescribed opioid use from rural areas of 10 states. Using multivariable mixed-effect regression models, we examined associations between participant technology access and SUD treatment., Findings: Of 3,026 participants, 71% used heroin and 76% used methamphetamine. Thirty-five percent had no cell phone and 10% had no prior 30-day internet use. Having both a cell phone and the internet was associated with increased days of medication for opioid use disorder (MOUD) use (aIRR 1.29 [95% CI 1.11-1.52]) and a higher likelihood of SUD counseling in the prior 30 days (aOR 1.28 [95% CI 1.05-1.57]). Lack of cell phone was associated with decreased days of MOUD (aIRR 0.77 [95% CI 0.66-0.91]) and a lower likelihood of prior 30-day SUD counseling (aOR 0.77 [95% CI 0.62-0.94])., Conclusions: Expanding US rural SUD treatment engagement via telemedicine may require increased cell phone and mobile network access., (© 2022 National Rural Health Association.)

Background: Methamphetamine use is common among persons with opioid use disorder. This study evaluated associations between methamphetamine use and treatment with agonist medications for opioid use disorder (MOUD, specifically buprenorphine, and/or methadone) in U.S. rural communities., Methods: The Rural Opioid Initiative (ROI) is a consortium spanning 10 states and 65 rural counties that included persons who reported past 30-day use of opioids and/or injection drug use between 1/2018 and 3/2020. Analyses were restricted to participants who had ever used opioids and had data on past 30-day methamphetamine use. Multivariable models examined the relationship between methamphetamine use and utilization of agonist MOUD., Results: Among 2899 participants, 2179 (75.2%) also reported recent methamphetamine use. Persons with methamphetamine use compared to those without were younger, more likely to have injected drugs, be unhoused, criminal justice involved, and less likely to have health insurance. Adjusted for age, sex, race, and study site, recent methamphetamine use was associated with lower relative odds of past 30-day methadone treatment (aOR=0.66; 95% CI: 0.45-0.99) and fewer methadone treatment days (aIRR=0.76; 0.57-0.99), but not past 30-day buprenorphine receipt (aOR=0.90; 0.67-1.20), buprenorphine treatment days in past 6 months: aIRR=0.88; 0.69-1.12) or perceived inability to access buprenorphine (aOR=1.12; 0.87-1.44) or methadone (aOR=1.06; 0.76-1.48)., Conclusion: Methamphetamine use is common among persons who use opioids in rural U.S. areas and negatively associated with current treatment and retention on methadone but not buprenorphine. Future studies should examine reasons for this disparity and reduce barriers to methadone for persons who use opioids and methamphetamine., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: High-contact structured diabetes prevention programs are effective in lowering weight and HbA1cs, yet their intensity level can create barriers to participation. Peer support programs improve clinical outcomes among adults with Type 2 diabetes, but their effectiveness in diabetes prevention is unknown. This study examined whether a low-intensity peer support program improved outcomes more than enhanced usual care in a diverse population with prediabetes., Study Design: The intervention was tested in a pragmatic 2-arm RCT., Setting/participants: Participants were adults with prediabetes at three healthcare centers., Intervention: Participants randomized to the enhanced usual care arm received educational materials. Participants in the Using Peer Support to Aid in Prevention and Treatment in Prediabetes arm were matched with a peer supporter: another patient who had made healthy lifestyle changes and was trained in autonomy-supportive action planning. Peer supporters were instructed to provide weekly telephone support to their peers on specific action steps toward behavioral goals for 6 months, then monthly support for 6 months., Main Outcome Measures: Changes in primary outcomes of weight and HbA1c and secondary outcomes of enrollment in formal diabetes prevention programs, self-reported diet, physical activity, health-specific social support, self-efficacy, motivation, and activation at 6 and 12 months were examined., Results: Data collection occurred from October 2018 to March 2022, with analyses completed in September 2022. Among 355 randomized patients, in intention-to-treat analyses, there were no between-group differences in HbA1c or weight changes at 6 and 12 months. Using Peer Support to Aid in Prevention and Treatment in Prediabetes participants were more likely to enroll in structured programs at 6 (AOR=2.45, p=0.009) and 12 (AOR=2.21, p=0.016) months and to report eating whole grains at 6 (4.49, p=0.026) and 12 (4.22, p=0.034) months. They reported greater improvements in perceived social support for diabetes prevention behaviors at 6 (6.39, p<0.001) and 12 (5.48, p<0.001) months, with no differences in other measures., Conclusions: A stand-alone, low-intensity peer support program improved social support and participation in formal diabetes prevention programs but not weight or HbA1c. It will be important to examine whether peer support could effectively complement higher-intensity, structured diabetes prevention programs., Trial Registration: This trial is registered at ClinicalTrials.gov, NCT03689530. Full protocol available at https://clinicaltrials.gov/ct2/show/NCT03689530., (Copyright © 2023. Published by Elsevier Inc.)

Importance: People who use drugs (PWUD) continue to be at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within various rural communities is poorly understood., Objective: To examine the association of characteristics of rural PWUD with HIV transmission behaviors., Design, Setting, and Participants: In this cross-sectional study, surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin) were collected January 2018 through March 2020 and analyzed August through December 2022. A chain-referral sampling strategy identified convenience sample seeds who referred others who used drugs. Rural PWUD who reported any past 30-day injection drug use or noninjection opioid use "to get high" were included., Exposures: Individual characteristics, including age, race, gender identity, sexual orientation, partnership status, drug of choice, and location, were collected., Main Outcomes and Measures: Past 30-day frequency of behaviors associated with HIV transmission, including drug injection, syringe sharing, opposite- and same-gender partners, transactional sex, and condomless sex, was assessed., Results: Of 3048 rural PWUD (mean [SD] age, 36.1 [10.3] years; 225 American Indian [7.4%], 96 Black [3.2%], and 2576 White [84.5%] among 3045 with responses; and 1737 men [57.0%] among 3046 with responses), most participants were heterosexual (1771 individuals [86.8%] among 2040 with responses) and single (1974 individuals [68.6%] among 2879 with responses). Opioids and stimulants were reported as drug of choice by 1636 individuals (53.9%) and 1258 individuals (41.5%), respectively, among 3033 individuals with responses. Most participants reported recent injection (2587 of 3046 individuals [84.9%] with responses) and condomless sex (1406 of 1757 individuals [80.0%] with responses), among whom 904 of 1391 individuals (65.0%) with responses indicated that it occurred with people who inject drugs. Syringe sharing (1016 of 2433 individuals [41.8%] with responses) and transactional sex (230 of 1799 individuals [12.8%] with responses) were reported less frequently. All characteristics and behaviors, except the number of men partners reported by women, varied significantly across locations (eg, mean [SD] age ranged from 34.5 [10.0] years in Wisconsin to 39.7 [11.0] years in Illinois; P < .001). In multivariable modeling, younger age (adjusted odds ratio [aOR] for ages 15-33 vs ≥34 years, 1.36; 95% CI, 1.08-1.72) and being single (aOR, 1.37; 95% CI, 1.08-1.74) were associated with recent injection; younger age (aOR, 1.49; 95% CI, 1.20-1.85) and bisexual orientation (aOR vs heterosexual orientation, 2.27; 95% CI, 1.60-3.23) with syringe sharing; gender identity as a woman (aOR vs gender identity as a man, 1.46; 95% CI, 1.01-2.12), bisexual orientation (aOR vs heterosexual orientation, 2.59; 95% CI, 1.67-4.03), and being single (aOR, 1.71; 95% CI, 1.15-2.55) with transactional sex; and bisexual orientation (aOR vs heterosexual orientation, 1.60; 95% CI, 1.04-2.46) and stimulants as the drug of choice (aOR vs opioids, 1.45; 95 CI, 1.09-1.93) with condomless sex with someone who injects drugs., Conclusions and Relevance: This study found that behaviors associated with HIV transmission were common and varied across communities. These findings suggest that interventions to reduce HIV risk among rural PWUD may need to be tailored to locally relevant factors.

Introduction Homelessness contributes to worsening health and increased health care costs. There is little published research that leverages rich electronic health record (EHR) data to predict future homelessness risk and inform interventions to address it. The authors' objective was to develop a model for predicting future homelessness using individual EHR and geographic data covariates. Methods This retrospective cohort study included 2,543,504 adult members (≥ 18 years old) from Kaiser Permanente Northern California and evaluated which covariates predicted a composite outcome of homelessness status (hospital discharge documentation of a homeless patient, medical diagnosis of homelessness, approved medical financial assistance application for homelessness, and/or "homeless/shelter" in address name). The predictors were measured in 2018-2019 and included prior diagnoses and demographic and geographic data. The outcome was measured in 2020. The cohort was split (70:30) into a derivation and validation set, and logistic regression was used to model the outcome. Results Homelessness prevalence was 0.35% in the overall sample. The final logistic regression model included 26 prior diagnoses, demographic, and geographic-level predictors. The regression model using the validation set had moderate sensitivity (80.4%) and specificity (83.2%) for predicting future cases of homelessness and achieved excellent classification properties (area under the curve of 0.891 [95% confidence interval = 0.884-0.897]). Discussion This prediction model can be used as an initial triage step to enhance screening and referral tools for identifying and addressing homelessness, which can improve health and reduce health care costs. Conclusions EHR data can be used to predict chance of homelessness at a population health level.

Rationale: Optimal systemic oxygenation targets in pediatric critical illness are unknown. A U-shaped relationship exists between blood oxygen levels and PICU mortality. Redox stress or iatrogenic injury from intensive treatments are potential mechanisms of harm from hyperoxia., Objectives: To measure biomarkers of oxidative status in children admitted to PICU and randomized to conservative (oxygen-hemoglobin saturation [Sp o2 ] 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation targets., Design: Mechanistic substudy nested within the Oxygen in PICU (Oxy-PICU) pilot randomized feasibility clinical trial ( ClinicalTrials.gov : NCT03040570)., Setting: Three U.K. mixed medical and surgical PICUs in university hospitals., Patients: Seventy-five eligible patients randomized to the Oxy-PICU randomized feasibility clinical trial., Interventions: Randomization to a conservative (Sp o2 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation target., Measurements and Main Results: Blood and urine samples were collected at two timepoints: less than 24 hours and up to 72 hours from randomization in trial participants (March 2017 to July 2017). Plasma was analyzed for markers of ischemic/oxidative response, namely thiobarbituric acid-reactive substances (TBARS; lipid peroxidation marker) and ischemia-modified albumin (protein oxidation marker). Total urinary nitrate/nitrite was measured as a marker of reactive oxygen and nitrogen species (RONS). Blood hypoxia-inducible factor (HIF)-1a messenger RNA (mRNA) expression (hypoxia response gene) was measured by reverse transcription- polymerase chain reaction. Total urinary nitrate/nitrite levels were greater in the liberal compared with conservative oxygenation group at 72 hours (median difference 32.6 μmol/mmol of creatinine [95% CI 13.7-93.6]; p < 0.002, Mann-Whitney test). HIF-1a mRNA expression was increased in the conservative group compared with liberal in less than 24-hour samples (6.0-fold [95% CI 1.3-24.0]; p = 0.032). There were no significant differences in TBARS or ischemia-modified albumin., Conclusions: On comparing liberal with conservative oxygenation targets, we show, first, significant redox response (increase in urinary markers of RONS), but no changes in markers of lipid or protein oxidation. We also show what appears to be an early hypoxic response (increase in HIF-1a gene expression) in subjects exposed to conservative rather than liberal oxygenation targets., Competing Interests: The remaining authors have disclosed that they do not have any potential conflicts of interest. Drs. Jones’, Eaton’s, Ray’s, Harrison’s, and Peters’ institutions received funding from the Great Ormond Street Hospital Children’s Charity. Drs. Jones’ and Harrison’s institutions received funding from the U.K. National Institute for Health Research (NIHR). Dr. Jones was funded by the National Institute for Health Research Academic Clinical Fellowship scheme. Dr. Eaton’s institution received funding from Vitaflo; he disclosed that he is an inventor on a patent licensed to Vitaflo and University College London. Dr. Ray received support for article research from the NIHR Great Ormond Street Hospital Biomedical Research Centre; he disclosed consultancy work with La Roche Ltd. Dr. Grocott disclosed that he is a coinvestigator of the Intensive Care Unit Randomized Trial Comparing Two Approaches to OXygen Therapy (UK-ROX) in critically ill adults. Dr. Griksaitis is part funded though the National Institute for Health Research (NIHR) Senior Investigator scheme and via Southampton NIHR Biomedical Research Centre. Drs. Mouncey’s and Rowan’s institutions received funding from the U.K. NIHR Health Technology Assessment program. Dr. Mouncey received support for article research from the U.K. NIHR. Dr. Peters’ institution received funding from the Pediatric Critical Care Society; he received funding from the U.K. NIHR Health Technology Assessment Program. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Purpose: Comparison of anal pre-cancer screening strategies in men who have sex with men (MSM)., Methods: MSM in the Multicenter AIDS Cohort Study underwent repeated anal cytology (aCyt), oncogenic human papillomavirus (oncHPV) testing. A subset received High-Resolution Anoscopy (HRA). We evaluated three screening strategies for their ability to predict anal histological High-Grade Squamous Intraepithelial lesion (HSIL): single aCyt, sequential aCyt, and oncHPV co-testing. Multivariable logistic regression models evaluated risk of HSIL among participants undergoing HRA within 5 years of screening. Sensitivity and specificity were estimated among participants with HRA, and results corrected for verification bias using weighted generalized estimating equations., Results: There were 1426 MSM with aCyt screening (48% people with HIV [PWH]) and 428 that underwent HRA. Median age was 57 years, 14% of PWH had CD4< 350 cells/mm 3 . HSIL probability was higher in MSM with one (39%, p < 0.01) or two abnormal aCyt results (46%, p < 0.01), versus those with normal aCyt (23-24%). Among men with abnormal aCyt, men with oncHPV+ had significantly higher risk than those who were oncHPV- (47% vs. 16%, p < 0.01). Specificity was modest with single aCyt+ (50%) but increased with sequential aCyt+ (79%) or oncHPV+ (67%). Sensitivity was high with single oncHPV+ (88%), moderate with single aCyt+ (66%) and oncHPV+ co-testing (61%), and low with sequential aCyt+ (39%). After correcting for potential verification bias, specificity increased and sensitivity decreased, but inferences were similar., Conclusion: None of the screening strategies evaluated had both sufficient specificity and sensitivity to warrant routine widespread use.

Metal-organic frameworks (MOFs) with Brønsted acidity are an alternative solid acid catalyst for many important chemical and fuel processes. However, the nature of the Brønsted acidity on the MOF's metal cluster or center is underexplored. To design and optimize the acid strength and density in these MOFs, it is important to understand the origin of their acidity at the molecular level. In the present work, isoreticular MOFs, ZrNDI and HfNDI (NDI = N , N '-bis(5-isophthalate)naphthalenediimide), were prepared as a prototypical system to unravel and compare their Brønsted and Lewis acid sites through an array of spectroscopic, computational, and catalytic characterization techniques. With the aid of solid-state nuclear magnetic resonance and density functional calculations, Hf 6 oxo-clusters on HfNDI are quantitatively proved to possess a higher density Brønsted acid site, while ZrNDI-based MOFs display stronger and higher-population Lewis acidity. HfNDI-based MOFs exhibit a superior catalytic performance in activating dihydroxyacetone (DHA) and converting DHA to ethyl lactate, with 71.1% selectivity at 54.7% conversion after 6 h. The turnover frequency of BAS-dominated Hf-MOF in DHA conversion is over 50 times higher than that of ZSM-5, a strong BAS-based zeolite. It is worth noting that HfNDI is reported for the first time in the literature, which is an alternative platform catalyst for biorefining and green chemistry. The present study furthermore highlights the uniqueness of Hf-based MOFs in this important biomass-to-chemical transformation., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Given increasing social interest in health and wellness, rising cultural trends toward sobriety and moderating alcohol intake, and improvements in brewing technology, low(er) alcohol beer is a rising segment in the beer industry for both craft and larger-scale producers. In this paper, we assess the representation of low(er) alcohol beer among craft brewers in the United States. Using a novel quantitatively-informed qualitative analytical approach, we surveyed a randomized, non-representative sample of 400 craft brewery websites in the United States to assess the relative presence of low(er) alcohol beers as well as how these brews are represented by the breweries themselves. To do so, we recorded, both numerically and via website screenshots, the lowest ABV beverage on offer and noted the beer type, the beer name, and the ABV. Ales were the most prominent style of beer on offer, accounting for 62% of the low(er) ABV beers identified. Only 15.5% of the breweries surveyed in this study offered a beer with an ABV of less than 4%; however, an additional 67.9% offered a beer with an ABV of less than 5%. The representations of these low(er) alcohol products focused mostly on taste, health, and demographic indicators.

Background: Chronic health conditions associated with long-term drug use may pose additional risks to people who use drugs (PWUD) when coupled with COVID-19 infection. Despite this, PWUD, especially those living in rural areas, may be less likely to seek out health services. Previous research has highlighted the increased disease burden of COVID-19 among PWUD. Our manuscript supplements this literature by exploring unique attitudes of PWUD living in rural areas toward the pandemic, COVID-19 vaccination, and the role of harm reduction (HR) organizations in raising health awareness among PWUD., Methods: Semi-structured interviews were conducted with 20 PWUD living in rural southern Illinois. Audio recordings were professionally transcribed. A preliminary codebook was created based on interview domains. Two trained coders conducted iterative coding of the transcripts, and new codes were added through line-by-line coding and thematic grouping., Results: Twenty participants (45% female, mean age of 38) completed interviews between June and November 2021. Participants reported negative impacts of the pandemic on mental health, financial wellbeing, and drug quality. However, the health impacts of COVID-19 were often described as less concerning than its impacts on these other aspects of life. Many expressed doubt in the severity of COVID-19 infection. Among the 16 unvaccinated participants who reported receiving most of their information from the internet or word of mouth, uncertainty about vaccine contents and distrust of healthcare and government institutions engendered wariness of the vaccination. Distrust of healthcare providers was related to past stigmatization and judgement, but did not extend to the local HR organization, which was unanimously endorsed as a positive institution. Among participants who did not access services directly from the HR organization, secondary distribution of HR supplies by other PWUD was a universally cited form of health maintenance. Participants expressed interest in low-threshold healthcare, including COVID-19 vaccination, should it be offered in the local HR organization's office and mobile units., Conclusion: COVID-19 and related public health measures have affected this community in numerous ways. Integrating healthcare services into harm reduction infrastructures and mobilizing secondary distributors of supplies may promote greater engagement with vaccination programs and other healthcare services., Trial Number: NCT04427202., (© 2022. The Author(s).)

Importance: Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities., Objective: To estimate the prevalence of methamphetamine use and its correlates among people who use drugs (PWUD) in rural US communities and to determine whether methamphetamine use is associated with increased nonfatal overdoses., Design, Setting, and Participants: From January 2018 through March 2020, the National Rural Opioid Initiative conducted cross-sectional surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin). Participants included rural PWUD who reported any past-30-day injection drug use or noninjection opioid use to get high. A modified chain-referral sampling strategy identified seeds who referred others using drugs. Data analysis was performed from May 2021 to January 2022., Exposures: Use of methamphetamine alone, opioids alone, or both., Main Outcomes and Measures: Unweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses., Results: Among the 3048 participants, 1737 (57%) were male, 2576 (85%) were White, and 225 (7.4%) were American Indian; the mean (SD) age was 36 (10) years. Most participants (1878 of 2970 participants with any opioid or methamphetamine use [63%]) reported co-use of methamphetamine and opioids, followed by opioids alone (702 participants [24%]), and methamphetamine alone (390 participants [13%]). The estimated unweighted prevalence of methamphetamine use was 80% (95% CI, 64%-90%), and the estimated weighted prevalence was 79% (95% CI, 57%-91%). Nonfatal overdose was greatest in people using both methamphetamine and opioids (395 of 2854 participants with nonmissing overdose data [22%]) vs opioids alone (99 participants [14%]) or methamphetamine alone (23 participants [6%]). Co-use of methamphetamine and opioids was associated with greater nonfatal overdose compared with opioid use alone (adjusted odds ratio, 1.45; 95% CI, 1.08-1.94; P = .01) and methamphetamine use alone (adjusted odds ratio, 3.26; 95% CI, 2.06-5.14; P < .001). Those with co-use had a mean (SD) of 2.4 (4.2) (median [IQR], 1 [0-3]) lifetime overdoses compared with 1.7 (3.5) (median [IQR], 0 [0-2]) among those using opioids alone (adjusted rate ratio, 1.20; 95% CI, 1.01-1.43; P = .04), and 1.1 (2.9) (median [IQR], 0 [0-1]) among those using methamphetamine alone (adjusted rate ratio, 1.81; 95% CI, 1.45-2.27; P < .001). Participants with co-use most often reported having tried and failed to access substance use treatment: 827 participants (44%) for both, 117 participants (30%) for methamphetamine alone, and 252 participants (36%) for opioids alone (χ22 = 33.8; P < .001). Only 66 participants (17%) using methamphetamine alone had naloxone., Conclusions and Relevance: These findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.

Objective: To characterize and address the opioid crisis disproportionately impacting rural U.S. regions., Methods: The Rural Opioid Initiative (ROI) is a two-phase project to collect and harmonize quantitative and qualitative data and develop tailored interventions to address rural opioid use. The baseline quantitative survey data from people who use drugs (PWUD) characterizes the current opioid epidemic (2018-2020) in eight geographically diverse regions., Results: Among 3,084 PWUD, 92% reported ever injecting drugs, 86% reported using opioids (most often heroin) and 74% reported using methamphetamine to get high in the past 30 days; 53% experienced homelessness in the prior 6 months; and 49% had ever overdosed. Syringe service program use varied by region and 53% had ever received an overdose kit or naloxone prescription. Less than half (48%) ever received medication for opioid use disorder (MOUD)., Conclusions: The ROI combines data across eight rural regions to better understand drug use including drivers and potential interventions in rural areas with limited resources. Baseline ROI data demonstrate extensive overlap between opioid and methamphetamine use, high homelessness rates, inadequate access to MOUD, and other unmet needs among PWUD in the rural U.S. By combining data across studies, the ROI provides much greater statistical power to address research questions and better understand the syndemic of infectious diseases and drug use in rural settings including unmet treatment needs., (© 2022. The Author(s).)

Background: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking., Methods: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer., Results: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test)., Conclusions: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada., Methods: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness., Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values., Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Attention-Deficit/Hyperactivity Disorder (ADHD) is often misdiagnosed or mistreated in adults because it is often thought of as a childhood problem. If a child is diagnosed and treated for the disorder, it often persists into adulthood. In adult ADHD, the symptoms may be comorbid or mimic other conditions making diagnosis and treatment difficult. Adults with ADHD require an in-depth assessment for proper diagnosis and treatment. The presentation and treatment of adults with ADHD can be complex and often requires interdisciplinary care. Mental health and non-mental health providers often overlook the disorder or feel uncomfortable treating adults with ADHD. The purpose of this manuscript is to discuss the diagnosis and management of adults with ADHD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rural cancer disparities are associated with lesser healthcare access and screening adherence. The opioid epidemic may increase disparities as people who use drugs (PWUD) frequently experience healthcare-associated stigmatizing experiences which discourage seeking routine care. Rural PWUD were recruited to complete surveys and interviews exploring cancer (cervical, breast, colorectal, lung) risk, screening history, and healthcare experiences. From July 2020-July 2021 we collected 37 surveys and 8 interviews. Participants were 24.3% male, 86.5% White race, and had a mean age of 44.8 years. Females were less likely to report seeing a primary care provider on a regular basis, and more likely to report stigmatizing healthcare experiences. A majority of females reporting receiving recommendations and screens for cervical and breast cancer, but only a minority were adherent. Similarly, only a minority of males and females reported receiving screening tests for colorectal and lung cancer. Screening rates for all cancers were substantially below those for the US generally and rural areas specifically. Interviews confirmed stigmatizing healthcare experiences and suggested screening barriers and possible solutions. The opioid epidemic involves millions of individuals and is disproportionately experienced in rural communities. To avoid exacerbating existing rural cancer disparities, methods to engage PWUD in cancer screening need to be developed.

Background: The COVID-19 pandemic has worsened the opioid overdose crisis in the US. Rural communities have been disproportionately affected by opioid use and people who use drugs in these settings may be acutely vulnerable to pandemic-related disruptions due to high rates of poverty, social isolation, and pervasive resource limitations., Methods: We performed a mixed-methods study to assess the impact of the pandemic in a convenience sample of people who use drugs in rural Illinois. We conducted 50 surveys capturing demographics, drug availability, drug use, sharing practices, and mental health symptoms. In total, 19 qualitative interviews were performed to further explore COVID-19 knowledge, impact on personal and community life, drug acquisition and use, overdose, and protective substance use adaptations., Results: Drug use increased during the pandemic, including the use of fentanyl products such as gel encapsulated "beans" and "buttons". Disruptions in supply, including the decreased availability of heroin, increased methamphetamine costs and a concomitant rise in local methamphetamine production, and possible fentanyl contamination of methamphetamine was reported. Participants reported increased drug use alone, experience and/or witness of overdose, depression, anxiety, and loneliness. Consistent access to harm reduction services, including naloxone and fentanyl test strips, was highlighted as a source of hope and community resiliency., Conclusions: The COVID-19 pandemic period was characterized by changing drug availability, increased overdose risk, and other drug-related harms faced by people who use drugs in rural areas. Our findings emphasize the importance of ensuring access to harm reduction services, including overdose prevention and drug checking for this vulnerable population.

This analysis was designed to determine if there existed differences by race in seeking sexually transmitted disease (STD) care in an emergency department (ED)., Methods: Data were collected from 4,138 patients attending 26 STD clinics across the United States (U.S.). The questionnaire asked where the patient would have sought care if the STD clinic had not been available that day. Responses were stratified by race and differences were tested for statistical significance., Results: Black/African American patients chose hospital emergency room as an alternative for STD clinic care at a rate approximately 2.5 times that of White patients (15.5% v. 5.8%, p &lt; .05). This difference persisted among Black/African American patients after controlling for demographic variables (adjusted OR 2.91; 2.21-3.82 95% CI)., Discussion: Receiving appropriate care is key to stemming the increases in sexually transmitted infections in the U.S. These findings suggest that disparities in access to STD care exist for Black/African American people.

Background: Although rural areas contain approximately 19% of the US population, little research has explored sexually transmitted infection (STI) risk and how urban-developed interventions may be suitable in more population-thin areas. Although STI rates vary across rural areas, these areas share diminishing access to screening and limited rural-specific testing of STI interventions., Methods: This narrative review uses a political ecology model of health and explores 4 domains influencing STI risk and screening: epidemiology, health services, political and economic, and social. Articles describing aspects of rural STI epidemiology, screening access and use, and intervention utility within these domains were found by a search of PubMed., Results: Epidemiology contributes to risk via multiple means, such as the presence of increased-risk populations and the at-times disproportionate impact of the opioid/drug use epidemic. Rural health services are diminishing in quantity, often have lesser accessibility, and may be stigmatizing to those needing services. Local political and economic influences include funding decisions, variable enforcement of laws/statutes, and systemic prevention of harm reduction services. Social norms such as stigma and discrimination can prevent individuals from seeking appropriate care, and also lessen individual self-efficacy to reduce personal risk., Conclusions: Sexually transmitted infection in rural areas is significant in scope and facing diminished prevention opportunities and resources. Although many STI interventions have been developed and piloted, few have been tested to scale or operationalized in rural areas. By considering rural STI risk reduction within a holistic model, purposeful exploration of interventions tailored to rural environments may be explored., Competing Interests: Conflict of Interest and Sources of Funding: The authors state they have no conflicts of interest., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

Soccer participation in the United States (U.S.) has increased over time, and injuries as well as interest to prevent injuries has become more common. This study described Emergency Department (ED) visits related to concussions, intracranial injuries (ICI), and all-other injuries attributed to soccer play; described healthcare cost and length of hospital stay of soccer-related injuries; and determined independent predictors of concussions, ICI, and all-other soccer injuries leading to ED visits. The study examined soccer-related weighted discharge data from the Nationwide Emergency Department Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Weighted tabular analysis of univariate and bivariate analyses and weighted and adjusted logistic regression models were conducted. A total of 480,580 of U.S. ED visits related to soccer injuries were available for analysis between 2010 to 2013. Generally, 98% of soccer-related ED visits resulted in routine (treat-and-release) visits. However, the odds of transfer to a short-term hospital following ED evaluation and treatment was more than 37-fold higher for soccer-injured youth and adults diagnosed with ICI when compared to all-other soccer injuries; additionally, these patients showed 28-fold higher odds of being admitted for inpatient care at the ED-affiliated hospital. For concussion, soccer-injured patients with concussion showed nearly 1.5-fold higher odds of being transferred to a short-term hospital than did those with any other soccer injury. Soccer-related ED visits cost more than 700 million in U.S. dollars from 2010 to 2013. Notable differences were noted between concussions, ICI, and all-other soccer injuries presenting to U.S. ED. Albeit underestimated given that this study excludes other forms of health care and treatment for injuries, such as outpatient clinics, over the counter medications and treatment, and rehabilitation, healthcare cost associated with soccer-related injuries presenting to ED is high, and remarkably costly in those with an ICI diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

Lesser health care access and utilization in rural areas are associated with ruralurban health outcome disparities. While some work has examined similar disparities by sexual orientation, little has explicitly explored the combined influences of rural residence and lesbian, gay, and bisexual (LGB) status. This study aims to explore literature specific to rural LGB health care access and utilization, identify gaps, and suggest future research. Several databases were searched to identify studies specific to LGB health care access and utilization, and 18 articles were identified and divided into two categories: barriers and facilitators to health care access. Barriers included provider training, discrimination, distance and physical access, and fewer social supports. The data also indicated that sexual orientation disclosure is associated with better health care. Rural sexual minority individuals undergo health care access and utilization inequities, even in excess of their heterosexual rural peers that may be addressed with training and social interventions. Further research is warranted.

Background: Mail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence., Objective: To assess an intervention to encourage MOP services to increase its use and medication adherence., Design: Randomized encouragement trial., Patients: 63,012 diabetes patients from three health care systems: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Hawaii (KPHI), and Harvard Pilgrim Health Care (HPHC) who were poorly adherent to at least one class of cardiometabolic medications and had not used MOP in the prior 12 months., Intervention: Patients were randomized to receive either usual care (control arm) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use (intervention arm). HPHC intervention patients received the letter only., Measurements: We compared the percentages of patients that began using MOP and that became adherent to cardiometabolic medication classes during a 12-month follow-up period. We also conducted a race/ethnicity-stratified analysis., Results: During follow-up, 10.6% of intervention patients began using MOP vs. 9.3% of controls (p < 0.01); the percent of cardiometabolic medication delivered via mail was 42.1% vs. 39.8% (p < 0.01). Metformin adherence improved in the intervention arm relative to control at the two KP sites (52% vs. 49%, p < 0.01). Stratified analyses suggested a significant positive effect of the intervention in White (RR: 1.12, 95% CI: 1.03, 1.22) and Asian (RR: 1.30, 95% CI: 1.17, 1.45) patients., Conclusion: This pragmatic trial showed that simple outreach to encourage MOP modestly increased its use and improved adherence measured by refills to a key class of diabetes medications in some settings. Given its minimal cost, clinicians and health systems should consider outreach interventions to actively promote MOP use among diabetes patients., Trial Registration: ClinicalTrials.gov registration number: NCT02621476.

Stigma is a known barrier to treating substance use disorders and dramatically diminishes the quality of life of people who use drugs (PWUD) nonmedically. Stigma against PWUD may be especially pronounced in rural areas due to their decreased anonymity and residents' limited access, or resistance, to "neutralizing" information on factors associated with drug use. Stigma often manifests in the attitudes of professionals whom stigmatized individuals regularly interact with and often materially impact. We analyzed interviews conducted between July 2018 and February 2019 with professional stakeholders in rural southern Illinois who interact with PWUD, specifically those who use opioids nonmedically or who inject drugs (n = 30). We further analyzed interview data from a complementary PWUD sample (n = 22). Interviews addressed perspectives around nonmedical drug use and treatment/harm reduction, with analysis centered around the Framework Integrating Normative Influences on Stigma and its focus on micro, meso and macro level stigmatization processes. Stakeholder participants included professionals from local law enforcement, courts, healthcare organizations, emergency management services, and faith-based and social services organizations. Most stakeholders, particularly law enforcement, negatively perceived PWUD and nonmedical drug use in general, questioned the character, agency and extrinsic value of PWUD, and used labels (e.g. "addict," "abuser," etc.) that may be regarded as stigmatizing. Further, most respondents, including PWUD, characterized their communities as largely unaware or dismissive of the bio-medical and sociocultural explanations for opioid use, drug injection and towards harm reduction services (e.g., syringe exchanges) and naloxone, which were frequently framed as undeserved usages of taxpayer funds. In conclusion, rural stigma against PWUD manifested and was framed as a substantial issue, notably activating at micro, meso and macro levels. Stigma prevention efforts in these communities should aim to improve public knowledge on the intricate factors contributing to opioid use and drug injection and harm reduction programming's moral and fiscal value., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited., Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19., Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020., Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108)., Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%)., Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively., Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions., Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Objective: People who use drugs (PWUD) face increased risk of exposure to COVID-19, but also elevated risk associated from injection drug use. We describe factors underlying their increased risk and identify mechanisms for reducing or minimizing rates of COVID-19 transmission and other health outcomes., Methods: Our commentary draws upon empirical data, governmental and other reports, and field-based unpublished data from our own studies to inform our conclusion and recommendations., Results: Co-morbid health conditions (eg, diabetes), structural challenges (eg, homelessness, criminal justice involvement), stigma (eg, social devaluation, discrediting), and syndemic clustering of of overdose, HCV, and HIV among PWUD are exacerbated by COVID-19., Conclusions: Beyond the many challenges all people face to remain safe and healthy during the COVID-19 pandemic, PWUD face additional barriers to remaining safe not only from COVID-19 but from negative health outcomes associated with their living environments, socioeconomic positions, and injection drug use. Collaborative efforts among governmental agencies, health providers, SSPs, CBOs, and other agencies providing services to PWUD is essential to the development of programs and services to meet the many needs of PWUD, which have been particularly accentuated during the COVID-19 pandemic., Competing Interests: CONFLICT OF INTEREST DISCLOSURE STATEMENT None of the authors have any conflicts of interest.

Purpose: Although few studies have examined screening uptake among sexual minorities (lesbian, gay, bisexual, queer), almost none have examined it in the specific context of rural populations. Therefore, our objective was to assess how cancer screening utilization varies by residence and sexual orientation., Methods: Publicly available population-level data from the 2014 and 2016 Behavioral Risk Factor Surveillance System were utilized. Study outcomes included recommended recent receipt of breast, cervical, and colorectal cancer screening. Independent variables of interest were residence (rural/urban) and sexual orientation (heterosexual/gay or lesbian/bisexual). Weighted proportions and multivariable logistic regressions were used to assess the association between the independent variables and the outcomes, adjusting for demographic, socioeconomic, and healthcare utilization factors., Results: Rates for all three cancer screenings were lowest in rural areas and among sexual minority populations (cervical: rural lesbians at 64.8% vs. urban heterosexual at 84.6%; breast: rural lesbians at 66.8% vs. urban heterosexual at 80.0%; colorectal for males: rural bisexuals at 52.4% vs. urban bisexuals at 81.3%; and colorectal for females: rural heterosexuals at 67.2% vs. rural lesbians at 74.4%). In the multivariate analyses for colorectal screening, compared to urban heterosexual males, both rural gay and rural heterosexual males were less likely to receive screening (aOR = 0.45; 95% = 0.24-0.73 and aOR = 0.79; 95% = 0.72-0.87, respectively) as were rural heterosexual females (aOR = 0.87; 95% = 0.80-0.94) compared to urban heterosexual females. For cervical screening, lesbians were less likely to receive screening (aOR = 0.62; 95% = 0.41-0.94) than heterosexuals, and there were no differences for breast screening., Conclusion: We found that rural sexual minorities may experience disparities in cancer screening utilization associated with the compounding barriers of rural residence and sexual minority status, after adjusting for demographic, socioeconomic, and healthcare utilization factors. Further work is needed to identify factors influencing these disparities and how they might be addressed.

Background: There is an urgent need to develop and evaluate effective and scalable interventions to prevent or delay the onset of type 2 diabetes mellitus (T2DM)., Methods: In this randomized controlled pragmatic trial, 296 adults with prediabetes will be randomized to either a peer support arm or enhanced usual care. Participants in the peer support arm meet face-to-face initially with a trained peer coach who also is a patient at the same health center to receive information on locally available wellness and diabetes prevention programs, discuss behavioral goals related to diabetes prevention, and develop an action plan for the next week to meet their goals. Over six months, peer coaches call their assigned participants weekly to provide support for weekly action steps. In the final 6 months, coaches call participants at least once monthly. Participants in the enhanced usual care arm receive information on local resources and periodic updates on available diabetes prevention programs and resources. Changes in A1c, weight, waist circumference and other patient-centered outcomes and mediators and moderators of intervention effects will be assessed., Results: At least 296 participants and approximately 75 peer supporters will be enrolled., Discussion: Despite evidence that healthy lifestyle interventions can improve health behaviors and reduce risk for T2DM, engagement in recommended behavior change is low. This is especially true among racial and ethnic minority and low-income adults. Regular outreach and ongoing support from a peer coach may help participants to initiate and sustain healthy behavior changes to reduce their risk of diabetes., Trial Registration: The ClinicalTrials.gov registration number is NCT03689530., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: As the number of cancer survivors in the United States increases, quantifying the risks and burden of second primary cancers (SPCs) among cancer survivors will help develop long-term prevention and surveillance strategies. We describe the risk of developing a SPC among survivors of 10 cancer sites with the highest survival rates in the United States., Methods: Adult patients diagnosed with an index smoking-related (urinary bladder, kidney and renal pelvis, uterine cervix, oral cavity and pharynx, and colon and rectum) and index non-smoking-related (prostate, thyroid, breast, corpus and uterus, and non-Hodgkin lymphoma) cancers were identified from Surveillance, Epidemiology, and End Results (2000-2015). SPC risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR)., Results: A cohort of 2,903,241 patients was identified and 259,685 (8.9%) developed SPC (7.6% of women and 10.3% of men). All index cancer sites (except prostate) were associated with a significant increase in SPC risk for women and men. Patients diagnosed with smoking-related index cancers (SIR range 1.20-2.16 for women and 1.12-1.91 for men) had a higher increased risk of SPC than patients with non-smoking-related index cancers (SIR range 1.08-1.39 for women and 1.23-1.38 for men) relative to the general population., Conclusion: We found that 1-in-11 cancer survivors developed a SPC. Given the increasing number of cancer survivors and the importance of SPC as a cause of cancer death, there is a need for increased screening for and prevention of SPC.

Objective: Despite its established benefits, palliative care (PC) is not well known among patients and family/caregivers. From a nationally representative survey, we sought to assess the following associated with PC: knowledge, knowledge sources, and beliefs., Methods: Data were drawn from the Health Information National Trends Study (HINTS 5 Cycle 2), a cross-sectional, survey of non-institutionalized adults aged 18+ years in the USA. Data were weighted and assessed by proportional comparison and multivariable logistic regression., Results: A total of 3504 respondents were identified, and approximately 29% knew about PC. In the adjusted model, less PC knowledge was associated with: lower age (those aged <50), male gender, lower education (

Importance: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown., Objective: To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis., Design, Setting, and Participants: Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital., Interventions: Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs)., Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay., Results: Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group., Conclusions and Relevance: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication., Trial Registration: anzctr.org.au Identifier: ACTRN12616000481471.

The epidemiology of sexually transmitted infections (STI) is constantly evolving, and the mechanisms of infection risk in the oral cavity (OC) are poorly characterized. Evidence indicates that microbial community (microbiota) compositions vary widely between the OC, genitalia and the intestinal and rectal mucosa, and microbiome-associated STI susceptibility may also similarly vary. The opioid misuse epidemic is at an epidemic scale, with >11 million US residents misusing in the past 30 days. Opioids can substantially influence HIV progression, microbiota composition and immune function, and these three factors are all mutually influential via direct and indirect pathways. While many of these pathways have been explored independently, the supporting data are mostly derived from studies of gut and vaginal microbiotas and non-STI infectious agents. Our purpose is to describe what is known about the combination of these pathways, how they may influence microbiome composition, and how resultant oral STI susceptibility may change. A better understanding of how opioid misuse influences oral microbiomes and STI risk may inform better mechanisms for oral STI screening and intervention. Further, the principles of interaction described may well be applied to other aspects of disease risk of other health conditions which may be impacted by the opioid epidemic.

Purpose: This study's purpose was to evaluate the effective dose (E) and equivalent dose ( H T ) of exposing a pediatric phantom to the extraoral bitewing programs of the Planmeca ProMax 2D S3 (ProMax) and Instrumentarium Orthopantomograph OP30 (OP30) and compare these results with dosimetry associated with the intraoral bitewing and panoramic radiograph. Methods: Dosimetry was acquired by placing 24 dosimeters in tissues of interest in a 10-year-old phantom. Manufacturer child settings were used for all scans. Repeat exposures of 20 scans were utilized. The average values of E and H T were calculated. Results: The E for the ProMax and OP30 units, respectively, were 16.84 μSv and 5.82 μSv. The highest E for both units was delivered to the thyroid, remainder tissues, and salivary glands. The highest HT for both units was delivered to the oral mucosa, salivary glands, extrathoracic airway, and thyroid. The mean differences between units were statistically significant (P<0.05). Conclusions: The average effective dose of the ProMax was higher than for the OP30. The effective dose of the pediatric extraoral bitewing is three to 11 times higher than that of the intraoral bitewing and comparable to the traditional panoramic radiograph of a pediatric phantom. Pediatric extraoral bitewing radiation protection guidelines are recommended.

Prescription and illicit opioids were involved in over 42,000 deaths in the USA in 2016. Rural counties experience higher rates of opioid prescribing and, although opioid prescribing rates have fallen in recent years, the rate of decline is less in rural areas. The sociocultural context of rural life may impact opioid misuse in important ways; however, little research directly explores this possibility. We performed a systematic review of English-language manuscripts in U.S. context to determine what is known about social networks, norms, and stigma in relation to rural opioid misuse. Of nine articles identified and reviewed, two had only primary findings associated with social networks, norms, or stigma, five had only secondary findings, and two had both primary and secondary findings. The normalization of prescription opioid use along with environmental factors likely impacts the prevalence of opioid misuse in rural communities. Discordant findings exist regarding the extent to which social networks facilitate or protect against nonmedical opioid use. Lastly, isolation, lack of treatment options, social norms, and stigma create barriers to substance use treatment for rural residents. Although we were able to identify important themes across multiple studies, discordant findings exist and, in some cases, findings rely on single studies. The paucity of research examining the role of social networks, norms, and stigma in relation to nonmedical opioid use in rural communities is evident in this review. Scholarship aimed at exploring the relationship and impact of rurality on nonmedical opioid use is warranted., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sand lances of the genus Ammodytes are keystone forage fish in coastal ecosystems across the northern hemisphere. Because they directly support populations of higher trophic organisms such as whales, seabirds or tuna, the current lack of empirical data and, therefore, understanding about the climate sensitivity of sand lances represent a serious knowledge gap. Sand lances could be particularly susceptible to ocean warming and acidification because, in contrast to other tested fish species, they reproduce during boreal winter months, and their offspring develop slowly under relatively low and stable p CO 2 conditions. Over the course of 2 years, we conducted factorial p CO 2  × temperature exposure experiments on offspring of the northern sand lance Ammodytes dubius , a key forage species on the northwest Atlantic shelf. Wild, spawning-ripe adults were collected from Stellwagen Bank National Marine Sanctuary (Cape Cod, USA), and fertilized embryos were reared at three p CO 2 conditions (400, 1000 and 2100 μatm) crossed with three temperatures (5, 7 and 10 ˚C). Exposure to future p CO 2 conditions consistently resulted in severely reduced embryo survival. Sensitivity to elevated p CO 2 was highest at 10 ˚C, resulting in up to an 89% reduction in hatching success between control and predicted end-of-century p CO 2 conditions. Moreover, elevated p CO 2 conditions delayed hatching, reduced remaining endogenous energy reserves at hatch and reduced embryonic growth. Our results suggest that the northern sand lance is exceptionally CO 2 -sensitive compared to other fish species. Whether other sand lance species with similar life history characteristics are equally CO 2 -sensitive is currently unknown. But the possibility is a conservation concern, because many boreal shelf ecosystems rely on sand lances and might therefore be more vulnerable to climate change than currently recognized. Our findings indicate that life history, spawning habitat, phenology and developmental rates mediate the divergent early life CO 2 sensitivities among fish species., (© The Author(s) 2019. Published by Oxford University Press and the Society for Experimental Biology.)

Introduction: Chlamydia and gonorrhea are the most commonly reported notifiable infections in the U.S., with direct medical costs for the treatment of these infections exceeding $700 million annually. Medicaid currently covers approximately 80 million low-income Americans, including a high percentage of racial and ethnic minorities. Studies have shown that racial and ethnic minority populations, particularly those with low SES, are at an increased risk of acquiring a sexually transmitted disease. Therefore, as Medicaid expands, there will likely be a greater demand for sexually transmitted disease services in community-based physician offices. To determine demand for these services among Medicaid enrollees, this study examined how often Medicaid was used to pay for sexually transmitted disease services received in this setting., Methods: This study combined 2014 and 2015 data from the National Ambulatory Medical Care Survey and tested for differences in the proportion of visits with an expected payment source of Medicaid when sexually transmitted disease services were and were not provided. All analyses were conducted in October 2018., Results: During 2014-2015, an estimated 25 million visits received a sexually transmitted disease service. Medicaid paid for a greater percentage of sexually transmitted disease visits (35.5%, 95% CI=22.5%, 51.1%) compared with non-sexually transmitted disease visits (12.1%, 95% CI=10.8%, 13.6%). Logistic regression modeling, controlling for age, sex, and race of the patient, showed that visits covered by Medicaid had increased odds of paying for a sexually transmitted disease service visit (OR=1.97, 95% CI=1.12, 3.46), compared with other expected payment sources., Conclusions: Focusing sexually transmitted disease prevention in Medicaid populations could reduce sexually transmitted disease incidence and resulting morbidity and costs., (Copyright © 2019. Published by Elsevier Inc.)