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Background Emergency Departments (EDs) have served as critical surveillance sites for infectious diseases. We sought to determine the prevalence and temporal trends of acute (by PCR) and convalescent (by antibody [Ab]) SARS-CoV-2 infection during the earliest phase of the pandemic among patients in an urban ED in Baltimore City. Methods We tested remnant blood samples from 3255 unique ED patients, collected between March 16th and May 31st 2020 for SARS-CoV-2 Ab. PCR for acute SARS-CoV-2 infection from nasopharyngeal swabs was obtained on any patients based on clinical suspicion. Hospital records were abstracted and factors associated with SARS-CoV-2 infection were assessed. Results Of 3255 ED patients, 8.2% (95%CI: 7.3%, 9.2%) individuals had evidence of SARS-CoV-2 infection; 155 PCR+, 78 Ab+, and 35 who were both PCR+ and Ab+. Prevalence of disease increased throughout the study period, ranging from 3.2% (95%CI: 1.8%, 5.2%) PCR+ and 0.6% (95%CI: 0.1%, 1.8%) Ab+ in March, to 6.2% (95%CI: 5.1%, 7.4%) PCR+ and 4.2% (95%CI: 3.3%, 5.3%) Ab+ in May. The highest SARS-CoV-2 prevalence was found in Hispanic individuals who made up 8.4% (95%CI: 7.4%, 9.4%) of individuals screened, but 35% (95%CI: 29%, 41%) of infections (PCR and/or Ab+). Demographic and clinical factors independently associated with acute infection included Hispanic ethnicity, loss of smell or taste, subjective fever, cough, muscle ache and fever. Factors independently associated with convalescent infection were Hispanic ethnicity and low oxygen saturation. Conclusions The burden of COVID-19 in Baltimore City increased dramatically over the 11-week study period and was disproportionately higher among Hispanic individuals. ED-based surveillance methods are important for identifying both acute and convalescent SARS-CoV-2 infections and provides important information regarding demographic and clinical correlates of disease in the local community.

BACKGROUND: The intersecting epidemics of opioid misuse, injection drug use, and HIV/HCV have resulted in record overdose deaths and sustained high levels of HIV/HCV transmissions. Literature on social networks suggests opportunities to connect people who use drugs (PWUD) and their peers to HIV/HCV and opioid overdose prevention services. However, little evidence exists on how to design such peer referral interventions in emergency department (ED) settings. METHODS: A mixed-method study was conducted to assess the feasibility of an mHealth-facilitated ‘patient to peer social network referral program’ for PWUD. In-depth interviews (IDIs) and quantitative surveys were conducted with urban ED patients (n=15), along with 3 focus group discussions (FGDs) (n=19). RESULTS: Overall, 34 participants were enrolled (71% males, 53% Black). 13/15 IDI participants reported a history of opioid overdose; all had witnessed overdose events; all received HIV/HCV testing. From survey responses, most would invite their peers for HIV/HCV testing and naloxone training; and anticipated peers to accept referrals (HIV: 60%, HCV: 73%, naloxone: 93%). Qualitative data showed PWUD shared health-related information with each other but preferred word of mouth rather than text messages. Participants used smartphones regularly and suggested using Internet advertising for prevention services. Participants expressed enthusiasm for ED-based peer mHealth referral platform to prevention services, as well as referring their peers to proposed services, with monetary incentives. CONCLUSION: ED-based peer referral intervention to HIV/HCV testing and naloxone training was viewed favorably by PWUD. Frequent smartphone use among PWUD suggests that the medium could be a promising mode for peer referral.

Importance Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, setting, and participants Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main outcomes and measures The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and relevance Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial registration ClinicalTrials.gov Identifier: NCT03509350.

Introduction Few large studies describe quality control procedures and reproducibility findings in cardiovascular ultrasound, particularly in novel techniques such as speckle tracking echocardiography (STE). We evaluate the echocardiography assessment performance in the Coronary Artery Risk Development in Young Adults (CARDIA) study Year 25 (Y25) examination (2010–2011) and report findings from a quality control and reproducibility program conducted to assess Field Center image acquisition and reading center (RC) accuracy. Methods The CARDIA Y25 examination had 3475 echocardiograms performed in 4 US Field Centers and analyzed in a RC, assessing standard echocardiography (LA dimension, aortic root, LV mass, LV end-diastolic volume [LVEDV], ejection fraction [LVEF]), and STE (two- and four-chamber longitudinal, circumferential, and radial strains). Reproducibility was assessed using intraclass correlation coefficients (ICC), coefficients of variation (CV), and Bland–Altman plots. Results For standard echocardiography reproducibility, LV mass and LVEDV consistently had CV above 10% and aortic root below 6%. Intra-sonographer aortic root and LV mass had the most robust values of ICC in standard echocardiography. For STE, the number of properly tracking segments was above 80% in short-axis and four-chamber and 58% in two-chamber views. Longitudinal strain parameters were the most robust and radial strain showed the highest variation. Comparing Field Centers with echocardiography RC STE readings, mean differences ranged from 0.4% to 4.1% and ICC from 0.37 to 0.66, with robust results for longitudinal strains. Conclusion Echocardiography image acquisition and reading processes in the CARDIA study were highly reproducible, including robust results for STE analysis. Consistent quality control may increase the reliability of echocardiography measurements in large cohort studies.

Background Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies. Methods The PACE study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow–derived ALDH br stem cells. The primary MRI end points of the study are as follows: (1) total collateral count, (2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and (3) peak hyperemic popliteal flow by phase-contrast MRI (PC-MRI). Results The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8% vs 5.6%) and peak hyperemic popliteal flow (4.1 vs 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization. Conclusions Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.

Aims The aim of this study was to examine the effect of a case management intervention on retention in opiate agonist therapy among injection drug users (IDUs) referred from a needle exchange program (NEP). Design, intervention, participants, and setting A randomized trial of a strengths-based case management intervention versus passive referral (control) was conducted among NEP attendees requesting and receiving referrals to subsidized, publicly funded opiate agonist treatment programs in Baltimore, MD. Measurements Multivariable Cox regression models were used to identify predictors of treatment retention using an ecological model approach, taking into account factors at the individual, social, and environmental level. Findings Of 245 IDUs, 127 (51.8%) entered opiate agonist treatment, for whom median retention was 7.9 months. The intervention was not associated with longer retention (p = .91). Individual-level factors predictive of shorter retention included being employed and greater levels of psychiatric distress. Participants who had prior treatment experience and multiple treatment requests were retained significantly longer. Social factors adversely affecting treatment retention included unstable housing and buying drugs for others. Living further away from the treatment site was an environmental barrier that negatively affected treatment retention. Conclusions Multilevel interventions that address individual, social, and environmental factors are necessary to improve substance abuse treatment retention and treatment outcomes among IDUs referred from NEP.

Background: Iron deficiency is common among female injection drug users, but it is unclear whether iron supplementation can reduce anemia and improve iron status without increasing plasma hepatitis C virus (HCV) or HIV RNA levels. Methods: We conducted a phase 3, double-blind, randomized, controlled clinical trial of daily micronutrients with 18 mg of iron (iron group) versus micronutrients without iron (control group) for 12 months among hepatitis C-positive female injection drug users in Baltimore, Maryland. The main outcome measures were hemoglobin, markers of iron status, plasma HCV RNA, plasma HIV RNA, and liver enzymes at 6 and 12 months of follow-up. Results: Four hundred fifty-eight women (320 HIV-negative and 138 HIV-positive) enrolled in the trial. There were no significant differences in the proportion of women with anemia, ferritin

Background: Most studies of hypothalamic-pituitary-gonadal (HPG) function in illicit drug users either focus on men or do not consider the impact of HIV. Objective: This study investigated the relationships between cocaine and/or opiate use, HIV status, and HPG function in both men and women. Methods: Men and women between 18 and 50 years of age were stratified by sex, drug use, and HIV status. Information on demographics, HIV disease and treatment, and illicit drug use patterns was collected. To determine potential effects on HPG function, free testosterone (free T), estradiol, and gonadotropin concentrations were measured. Results: In a total of 197 men and women, free T concentrations were lower in men who used cocaine and/or opiates and in women infected with HIV Gonadotropin concentrations were elevated in seropositive men only. In women who received highly active antiretroviral therapy, HIV infection and illicit drug use had an additive or synergistic impact on free T concentrations. Conclusions: Our data reveal the importance of considering the independent effects of illicit drug use and HIV status for both men and women, so that risks may be identified and potential treatments designed for HPG dysfunction in these groups.

Physical activity is beneficial for persons with HIV infection but little is known about the relationships between physical activity, HIV treatment and injection drug use (IDU). This study compared physical activity levels between HIV-negative and HIV-positive injection drug users (IDUs) and between HIV-positive participants not on any treatment and participants on highly active antiretroviral therapy (HAART). Anthropometric measurements were obtained and an interviewer-administered modified Paffenbarger physical activity questionnaire was administered to 324 participants in a sub-study of the AIDS Linked to Intravenous Experiences (ALIVE) cohort, an ongoing study of HIV-negative and HIV-positive IDUs. Generalized linear models were used to obtain univariate means and to adjust for confounding (age, gender, employment and recent IDU). Vigorous activity was lower among HAART participants than HIV-positive participants not on treatment (p=0.0025) and somewhat lower than HIV-negative participants (p=0.11). Injection drug use and viral load were not associated with vigorous activity. Energy expenditure in vigorous activity was also lower among HAART participants than both HIV-negative and HIV-positive participants not on treatment. Thus, HIV-positive participants on HAART spend less time on vigorous activity independent of recent IDU. More research is needed into the reasons and mechanism for the lack of vigorous activities, including behavioral, psychological and physiological reasons.

We evaluated a case management intervention to increase treatment entry among injecting drug users referred from a needle exchange program (NEP). A randomized trial of a strengths based case management (intervention) versus passive referral (control) was conducted among NEP attenders requesting and receiving referrals to subsidized, publicly funded opiate agonist treatment programs in Baltimore, MD. Logistic regression identified predictors of treatment entry within 7 days, confirmed through treatment program records. Of 247 potential subjects, 245 (99%) participated. HIV prevalence was 19%. Overall, 34% entered treatment within 7 days (intervention: 40% versus control: 26%, p = 0.03). In a multivariate “intention to treat’ model (i.e., ignoring the amount of case management actually received), those randomized to case management were more likely to enter treatment within 7 days. Additional ‘as treated’ analyses revealed that participants who received 30 min or more of case management within 7 days were 33% more likely to enter treatment and the active ingredient of case management activities was provision of transportation. These findings demonstrate the combined value of offering dedicated treatment referrals from NEP, case management and transportation in facilitating entry into drug abuse treatment. Such initiatives could be implemented at more than 140 needle exchange programs currently operating in the United States. These data also support the need for more accessible programs such as mobile or office-based drug abuse treatment.

Injection drug use is a growing but understudied problem in Tijuana, a city situated on the northwestern Mexico-U.S border. The authors studied factors associated with receptive needle sharing in an effort to inform prevention activities. In 2003, street-recruited injection drug users (IDUs) in Tijuana underwent interviews on injection risk behaviors and rapid HIV antibody tests. Logistic regression was used to identify correlates of receptive needle sharing at the last injection episode. Of 402 IDUs, 87.6% were male; the median age was 34. HIV prevalence was 4.01% (95% CI: 2.29-6.51). One third reported receptive needle sharing at last injection. Factors independently associated with receptive needle sharing were years living in Tijuana (Adjusted Odds Ratio [AdjOR]= 0.97 per year, 95% CI: 0.96-0.99), being bisexual/homosexual (AdjOR=2.12; 95% CI: 1.30 - 3.44), unemployed (AdjOR=2.5; 95% CI: 1.52-4.10), never having an HIV test (AOR: 4.02; 95% CI: 2.44-6.60), having friends who placed importance on avoiding HIV (AdjOR: 0.36; 95% CI: 0.19-0.68) and last injecting in a shooting gallery (AdjOR=1.98; 95% CI: 1.21-3.24). These results underscore the need to increase access to voluntary HIV testing and counseling to IDUs and migrants in Tijuana, as well as expand access to sterile syringes in an effort to avert widespread HIV transmission.

Smoking worsens quality of life among HIV-infected individuals, but it remains unclear if this association is related simply to smoking or to chronic obstructive pulmonary disease (COPD), the end-organ disease caused by smoking.Using cross-sectional data from the AIDS Linked to the Intravenous Experience study, we determined the independent effects of smoking, HIV and COPD assessed using the Medical Outcome Studies-HIV questionnaire.Of 973 participants, 287 (29.5%) were HIV infected and 151 (15.5%) had spirometry-defined obstruction. Eight hundred and thirty-four (85.7%) were current smokers with 23.3 mean pack-years history. HIV infection was independently associated with reduced physical and mental health. COPD was associated with a trend toward worse physical health (-1.48 units; 95%CI -3.33 to 0.38; p = 0.12) and was independently associated with worse mental health (-2.43 units; 95%CI -4.22 to -0.64; p0.01). After accounting for COPD and other covariates, smoking was not associated with changes in physical or mental health.The presence of COPD, rather than smoking, is associated with worse quality of life independent of HIV infection. Diagnosis and management of COPD in former or current smokers with or at risk for HIV may further improve quality of life.

Lead toxicity has been associated with behavioral handicaps, reading disability, antisocial and hyperactive behavior, juvenile delinquency, and impaired cognition. In addition, preclinical studies suggest an association with drug addiction; e.g., animals treated with lead either pre- or postnatally self-administer opiates at a much higher rate than untreated animals. Iron deficiency further increases the risk of lead toxicity through enhanced absorption of lead in the gastrointestinal tract. Female injection drug users have a high prevalence of iron deficiency, although the question remains as to whether this relationship is either a partial function of high lead exposure or heroin use. Specific aims were to preliminarily determine whether female injection heroin users have high tibial lead concentrations, a marker for cumulative lead exposure, compared with normal reference populations, and whether cognitive deficits potentiated the relationship between lead exposure and frequency of heroin use. Tibial lead concentrations were measured via 109Cd-based K-shell X-ray fluorescence. In 26 female injection heroin users, mean (standard deviation (SD)) tibial lead concentration was 14.5 (6.8) μg/(g bone mineral), which was 1.8 times higher than the tibial lead concentration found among age-adjusted normal community-dwelling women. Interaction effects of tibial lead concentration and selected cognitive functions on frequency with which heroin was used were significant. Further research is warranted to determine whether a history of lead exposure is associated with increased proclivity to drug addiction.

This study examined the relationship between lifetime abuse and suicidal ideation in a sample of 245 injection drug users (IDUs) who attended the Baltimore Needle Exchange Program and received a referral for opiate agonist therapy. Data were obtained from baseline interviews and HIV antibody tests. The sample mean age was 42.2 (SD = 8.1 ); 77% were African American; 69% were male. Overall, 27% reported thoughts of suicide in the last six months, and lifetime emotional, physical and sexual abuse was reported by 17%, 12% and 10%, respectively. In bivariate analyses, recent suicidal ideation was associated with emotional (odds ratio [OR] = 3.2; p = 0.001), physical (OR = 2.5; p = 0.026), and sexual abuse (OR = 5.0; p < 0.001). In multiple logistic regression models controlling for HIV status and Center for Epidemiological Studies Depression (CES-D) score, individuals who experienced emotional abuse were more than twice as likely to report recent suicidal ideation (adjusted odds ratio [AOR] = 2.6; p = 0.011); those who experienced sexual abuse were four times more likely to report suicidal ideation (AOR = 4.0; p = 0.004). These findings suggest that emotional and sexual abuse might be risk factors for suicidality among IDUs and also might suggest that suicide prevention should be an integral part of drug treatment for treatment-seeking IDUs.

Adherence and retention of female injection drug users (IDUs) in clinical trials are not well known and were evaluated among 458 female IDUs in a clinical trial in Baltimore. Of all, 62.9% were adherent to visits (attendedor = 80% of visits). Of women withor = 1 visit after enrollment, 76% were adherent to treatment (tookor = 80% of pills); 27.7% were lost to follow-up (missedor = 3 consecutive visits). Women nonadherent to visits were younger and less likely to be on methadone. Women lost to follow-up were younger, more often white, not on methadone, and injecting drugs daily. Fair-moderate adherence to visits and treatment occurs among female IDUs in a clinical trial.

We examined the effect of a case management intervention on drug treatment entry among injection drug users (IDUs) with and without comorbid antisocial personality disorder (ASPD). Injection drug users attending the Baltimore Needle Exchange Program who sought and were granted referrals to opioid agonist treatment were randomized to receive a strengths-based case management intervention or passive referral. Of 162 IDUs, 22.8% met the DSM-IV criteria for ASPD. Compared to those without ASPD, IDUs with comorbid ASPD who spent 25 or more minutes with their case manager prior to their treatment entry date were 3.51 times more likely to enter treatment than those receiving less than 5 min, adjusting for intervention status, race, and treatment site (95% confidence interval 1.04–11.89). Providing case management services to IDUs with comorbid ASPD may facilitate treatment entry and reduce the negative consequences of drug abuse.

We tested hypotheses that social living arrangement and drug use in one's network are independently associated with entry into opiate agonist treatment modalities. Injection drug users (IDUs) attending the Baltimore Needle Exchange Program who received a referral for drug abuse treatment were studied. Baseline interviews, HIV testing, and the Addiction Severity Index (ASI) were administered. Agency records were used to confirm entry into a treatment program offering opiate agonist maintenance therapy within 30 days of the baseline interview. Logistic regression was used to identify predictors of treatment entry. To date, of 245 IDUs, 39% entered such a program. Multivariate logistic regression models controlling for age and intervention status revealed that compared to individuals who lived alone, in a controlled, or nonstable environment (e.g., streets, abandoned house, transitional housing program, or boarding house), individuals who lived with a sexual partner were 3 times more likely to enter treatment (adjusted Odds Ratio [aOR]=3.04; p=0.013) and those who lived with family or friends were almost 3 times more likely to enter treatment (aOR=2.72; p=0.016). In the bivariate analyses, a marginal association was observed between being responsible for children or others and entry into treatment (p=0.066); however, this association was not significant in the multivariate model. Findings from this study suggest that supportive living environments may facilitate entry into treatment and may be helpful in devising appropriate and targeted interventions to encourage drug treatment entry.

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.

Background Injection drug use is associated with an increased risk of human immunodeficiency virus (HIV) infection and with obstructive lung diseases (OLD). Understanding how HIV and OLD may impact respiratory symptoms among injection drug users (IDUs) is important to adequately care for this high-risk population. We characterized the independent and joint effects of HIV and OLD on respiratory symptoms of a cohort of inner-city IDUs. Methods Demographics, risk behavior and spirometric measurements were collected from a cross-sectional analysis of the Acquired Immunodeficiency Syndrome Link to the IntraVenous Experience study, an observational cohort of IDUs followed in Baltimore, MD since 1988. Participants completed a modified American Thoracic Society respiratory questionnaire and the Medical Research Council (MRC) dyspnea score to assess respiratory symptoms of cough, phlegm, wheezing and dyspnea. Results Of 974 participants, 835 (86%) were current smokers and 288 (29.6%) were HIV-infected. The prevalence of OLD (FEV1/FVC ≤ 0.70) was 15.5%, and did not differ by HIV status. OLD, but not HIV, was associated with increased frequency of reported respiratory symptoms. There was a combined effect of OLD and HIV on worsening of MRC scores. OLD and HIV were independently associated with an increased odds of reporting an MRC ≥ 2 (OR 1.83 [95%CI 1.23-2.73] and 1.50 [95%CI 1.08-2.09], respectively). COPD, but not HIV, was independently associated with reporting an MRC ≥ 3 (OR 2.25 [95%CI 1.43-3.54] and 1.29 [95%CI 0.87-1.91], respectively). Conclusions While HIV does not worsen cough, phlegm or wheezing, HIV significantly increases moderate but not severe dyspnea in individuals of similar OLD status. Incorporating the MRC score into routine evaluation of IDUs at risk for OLD and HIV provides better assessment than cough, phlegm and wheezing alone.