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Background and aimsThe individual-level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established but there is less evidence on population-level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in community and prison on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation.DesignDynamic modeling.Setting and participantsA cohort of 49,359 individuals who ever received OAT in NSW from 2001-2018.MeasurementsReceipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1-9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1-12 months ago. The model incorporated elevated mortality post-release from prison, and OAT impact on reducing mortality and incarceration.FindingsAmong the cohort, mortality was 0.9 per 100 person-years, OAT coverage and retention remained high (>50%, 1.74 years/episode). Over 2001-2020, we estimate OAT provision reduced overdose and other cause mortality among the cohort by 53% [95% credible interval: 49%-56%] and 27% [22%-30%], respectively. We estimate 1.2 deaths averted and 9.7 life-years gained per 100 person-years on OAT. Prison OAT with post-release OAT-linkage accounted for 12% [11%-13%] of all deaths averted by the OAT program, primarily through preventing deaths in the first month post-release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% [1%-2%] and 3% [2%-5%] of deaths, respectively.ConclusionThe community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population-level overdose and all-cause mortality in the past 20 years, partially due to high retention.

New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from

Background To assess differences in platelet inhibition during ticagrelor monotherapy (TIC) or dual therapy with ticagrelor and aspirin (TIC+ASP) in patients after percutaneous coronary intervention using a comprehensive panel of functional tests. Methods and Results In a single‐center parallel group, open label, randomized controlled trial, 110 participants were randomized to receive either TIC (n=55) or TIC+ASP (n=55) for 4 weeks. The primary outcome was the platelet aggregation response with 10 μmol/L thrombin receptor activation peptide‐6 (TRAP‐6). The secondary outcomes were platelet aggregation responses and binding of surface activation markers with a panel of other activators. The mean percentage aggregation for 10 μmol/L TRAP‐6 was similar for the TIC and TIC+ASP groups (mean difference+4.29; 95% CI, −0.87 to +9.46). Aggregation was higher in the TIC group compared with the TIC+ASP group with 1 μg/mL (+6.47; +2.04 to +10.90) and 0.5 μg/mL (+14.00; +7.63 to +20.39) collagen related peptide. Aggregation responses with 5 μmol/L TRAP‐6, 5 μmol/L or 2.5 μmol/L thromboxane A2 receptor agonist and surface activation marker binding with 5 μmol/L TRAP‐6 or 0.5 μg/mL collagen related peptide were the same between the treatment groups. Conclusions Patients with PCI show similar levels of inhibition of most platelet activation pathways with TIC compared with dual therapy with TIC + ASP. However, the greater aggregation response with collagen related peptide during TIC indicates incomplete inhibition of glycoprotein VI (collagen) receptor‐mediated platelet activation. This difference in pharmacodynamic response to anti‐platelet medication may contribute to the lower bleeding rates observed with TIC compared with dual antiplatelet therapy in recent clinical trials. Registration Information URL: https://www.isrctn.com; Unique Identifier ISRCTN84335288.

Objectives The aim of the study was to identify possible causes of pancreatic insufficiency in patients with HIV infection. Methods A retrospective analysis of 233 HIV-positive patients for whom faecal elastase measurement was available was performed to investigate potential associations with core demographic data, HIV infection characteristics, degree of immunosuppresion, exposure to antiretroviral therapy ( ART), alcohol misuse, diabetes, hepatitis C virus ( HCV) infection, triglyceride and cholesterol levels and symptomatology. The response to pancreatic enzyme replacement for patients with evidence of insufficiency was also evaluated. Results Of 233 patients, 104 (45%) had evidence of pancreatic exocrine insufficiency (faecal elastase < 200 mcg/g). A positive association with exocrine pancreatic insufficiency was found for HCV infection ( P = 0.007), previous or current HCV treatment ( P = 0.003), alcohol misuse history ( P = 0.006) and the presence of steatorrhoea ( P = 0.03). There was no demonstrated association between exocrine pancreatic insufficiency and didanosine ( ddI) exposure ( P = 0.43) or stavudine ( d4T) exposure ( P = 0.62). Seventy-seven per cent of patients who were treated with pancreatic enzymatic supplementation reported a subjective improvement in symptoms. Conclusions Faecal elastase sampling should form part of the routine work-up for HIV-positive patients with chronic diarrhoea even in the absence of 'traditional' risk factors such as ddI exposure. In particular, if the patient has steatorrhoea, a history of alcohol exposure or their HCV serology is positive, they should be considered for investigation. Treatment with pancreatic enzyme supplementation appears to be effective in the treatment of chronic diarrhoea caused by pancreatic insufficiency in the majority of patients. [ABSTRACT FROM AUTHOR]

Background: A recent systematic review observed that HIV prevalence amongst injectors is negligible (<1%) below a threshold HCV prevalence of 30%, but thereafter increases with HCV prevalence. We explore whether a model can reproduce these trends, what determines different epidemiological profiles and how this affects intervention impact.Methods: An HIV/HCV transmission model was developed. Univariate sensitivity analyses determined whether the model projected a HCV prevalence threshold below which HIV is negligible, and how different behavioural and epidemiological factors affect the threshold. Multivariate uncertainty analyses considered whether the model could reproduce the observed breadth of HIV/HCV epidemics, how specific behavioural patterns produce different epidemic profiles, and how this affects an intervention's impact (reduces injecting risk by 30%).Results: The model projected a HCV prevalence threshold, which varied depending on the heterogeneity in risk, mixing, and injecting duration in a setting. Multivariate uncertainty analyses showed the model could produce the same range of observed HIV/HCV epidemics. Variability in injecting transmission risk, degree of heterogeneity and injecting duration mainly determined different epidemic profiles. The intervention resulted in 50%/28% reduction in HIV incidence/prevalence and 37%/10% reduction in HCV incidence/prevalence over five years. For either infection, greater impact occurred in settings with lower prevalence of that infection and higher prevalence of the other infection.Discussion: There are threshold levels of HCV prevalence below which HIV risk is negligible but these thresholds are likely to vary by setting. A setting's HIV and HCV prevalence may give insights into IDU risk behaviour and intervention impact. [ABSTRACT FROM AUTHOR]

Background: Supervised consumption sites (SCS) have been shown to reduce receptive syringe sharing among people who inject drugs (PWID) in the United States and elsewhere, which can prevent HIV and hepatitis C virus (HCV) transmission. PWID are at risk of disease transmission and may benefit from SCS, however legislation has yet to support their implementation. This study aims to determine the potential impact of SCS implementation on HIV and HCV incidence among PWID in three California counties., Methods: A dynamic HIV and HCV joint transmission model among PWID (sexual and injecting transmission of HIV, injecting transmission of HCV) was calibrated to epidemiological data for three counties: San Francisco, Los Angeles, and San Diego. The model incorporated HIV and HCV disease stages and HIV and HCV treatment. Based on United States data, we assumed access to SCS reduced receptive syringe sharing by a relative risk of 0.17 (95 % CI: 0.04-1.03). This model examined scaling-up SCS coverage from 0 % to 20 % of the PWID population within the respective counties and assessed its impact on HIV and HCV incidence rates after 10 years., Results: By increasing SCS from 0 % to 20 % coverage among PWID, 21.8 % (95 % CI: -1.2-32.9 %) of new HIV infections and 28.3 % (95 % CI: -2.0-34.5 %) of new HCV infections among PWID in San Francisco County, 17.7 % (95 % CI: -1.0-30.8 %) of new HIV infections and 29.8 % (95 % CI: -2.1-36.1 %) of new HCV infections in Los Angeles County, and 32.1 % (95 % CI: -2.8-41.5 %) of new HIV infections and 24.3 % (95 % CI: -1.6-29.0 %) of new HCV infections in San Diego County could be prevented over ten years., Conclusion: Our models suggest that SCS is an important intervention to enable HCV elimination and could help end the HIV epidemic among PWID in California. It could also have additional benefits such facilitating pathways into drug treatment programs and preventing fatal overdose., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NM has received unrestricted research grants paid to her university from Gilead unrelated to this work. Unrelated to this work, JK was employed as a contractor for the US Department of Defense and by CommonSpirit Health in a lab has several NIH, DOD and Michael J Fox Foundation grants, but she is not funded under these grants and they were unrelated to this work., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature., Methods: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms., Results: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively., Conclusion: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition., (© 2024. The Author(s).)

Introduction: Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates., Methods: The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented., Results: A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm 3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis., Conclusions: High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts hepatitis C virus (HCV) and human immunodeficiency virus (HIV) incidence among a cohort of people who inject drugs (PWID) in San Diego, California and Tijuana, Mexico., Methods: PWID were recruited during 2020-2022, undergoing semi-annual interviewer-administered surveys and HIV and HCV serological rapid tests through 2024. Cox regression was conducted to examine predictors of seroconversion considering self-reported IMF use as a 6-month lagged, time-dependent covariate., Results: Of 398 PWID at baseline, 67% resided in San Diego, 70% were male, median age was 43 years, 42% reported receptive needle sharing, and 25% reported using IMF. HCV incidence was 14.26 per 100 person-years (95% confidence interval [CI]: 11.49-17.02), and HIV incidence was 1.29 (95% CI: .49-2.10). IMF was associated with HCV seroconversion, with a univariable hazard ratio (HR) of 1.64 (95% CI: 1.09-2.40), and multivariable HR of 1.57 (95% CI: 1.03-2.40). The direction of the relationship with HIV was similar, albeit not significant (HR 2.39; 95% CI: .66-8.64)., Conclusions: We document a novel association between IMF and HCV seroconversion among PWID in Tijuana-San Diego. Few HIV seroconversions (n = 10) precluded our ability to assess if a similar relationship held for HIV. IMF's short half-life may destabilize PWID-increasing the need for repeat dosing and sharing smoking materials and syringes. New preventive care approaches may reduce HCV transmission in the fentanyl era., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Alcohol use is a major contributor to mortality and morbidity worldwide. Uganda has a high level of alcohol use per capita. Compared to men, women are less likely to consume alcohol globally; however, women who drink have increased risks for co-occurring conditions, including depression, intimate partner violence, and HIV. This study assessed the prevalence of alcohol use and correlates of harmful alcohol use by gender and HIV status in rural Uganda., Methods: We used cross-sectional data from a study among women and men aged 15-59 residing in rural, central Uganda and accepting home-based HIV testing (Nov 2017 to Dec 2020). We estimated the prevalence of levels of alcohol use (categorized as no alcohol use (score 0), low (score 1-3 for men; 1-2 for women), medium (score 4-5 for men; 3-5 for women), high (score 6-7), and very-high (score 8-12) use with the AUDIT-C), stratified by gender and HIV status. We assessed correlates of harmful alcohol use using multivariable logistic regression models for women and men., Results: Among 18,460 participants, 67% (95% CI: 66-67%) reported no alcohol use, 16% (95% CI: 16-17%) reported low, 5% (95% CI: 4.8-5%) reported medium, 5% (95% CI: 4-5%) reported high, and 3% (95% CI: 2.8-3) reported very high alcohol use. Compared to women, men were more likely to report alcohol use (Chi-squared p-value<0.0001). People diagnosed with HIV (both newly diagnosed and previously aware of their status prior to home-based HIV testing) were more likely to report low, medium, high, and very high alcohol use compared to those who were HIV negative (Chi-squared p-value<0.0001). Among women, those who were newly diagnosed were more likely report alcohol use, compared to those who were HIV negative. In multivariable models, being newly diagnosed with HIV (compared to HIV negative) increased the odds of harmful alcohol use among women, but not men., Conclusion: While alcohol use was higher among men and people living with HIV, being newly diagnosed with HIV had a stronger relationship with harmful alcohol use among women than men. More research is needed to understand how alcohol use may increase the risks of HIV acquisition among women and to identify gender-responsive services to address harmful alcohol use and increase access to HIV testing and linkage to care for women who use harmful levels of alcohol., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wynn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Alcohol use among people living with HIV (PWH) is common and may negatively affect engagement in HIV care. We evaluated the relationships between alcohol use, ART use, and viral suppression among PWH in Uganda. PATH/Ekkubo was a trial evaluating a linkage to HIV care intervention in four Ugandan districts, Nov 2015-Sept 2021. Our analytical sample included: (1) baseline data from individuals not enrolled in the intervention trial (previously diagnosed HIV+); and 12-month follow-up data from the control group (newly diagnosed or previously diagnosed, but not in care). Level of alcohol use was categorized using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C): none (AUDIT-C = 0), low (women = 1-2, men = 1-3), medium (women = 3-5, men = 4-5), high/very high (6-12). Multivariable logistic regression models evaluated associations between alcohol use, ART use and viral suppression (a viral load of < 20); we also stratified by gender. Among 931 PWH, medium (OR: 0.43 [95% CI 0.25-0.72]) and high/very high (OR: 0.22 [95% CI 0.11-0.42]) levels of alcohol use were associated with lower odds of being on ART. In a sub-sample of 664, medium use (OR: 0.63 [95% CI 0.41-0.97]) was associated with lower odds of viral suppression. However, this association was not statistically significant when restricting to those on ART, suggesting the relationship between alcohol use and viral suppression is explained by ART use. Among men, high/very high, and among women, medium alcohol use levels were associated with lower odds of being on ART and being virally suppressed. Interventions for PWH who use higher levels of alcohol may be needed to optimize the benefits of Uganda's Universal Test and Treat strategy., (© 2024. The Author(s).)

Background: Opioid overdose and related diseases remain a growing public health crisis in the USA. Identifying sociostructural and other contextual factors associated with adverse health outcomes is needed to improve prediction models to inform policy and interventions. We aimed to identify high-risk communities for targeted delivery of screening and prevention interventions for opioid use disorder and hepatitis C virus (HCV)., Methods: In this ecological and modelling study, we fit mixed-effects negative binomial regression models to identify factors associated with, and predict, opioid-related and HCV-related hospitalisations for ZIP code tabulation areas (ZCTAs) in South Carolina, USA. All individuals aged 18 years or older living in South Carolina from Jan 1, 2016, to Dec 31, 2021, were included. Data on opioid-related and HCV-related hospitalisations, as well as data on additional individual-level variables, were collected from medical claims records, which were obtained from the South Carolina Revenue and Fiscal Affairs Office. Demographic and socioeconomic variables were obtained from the United States Census Bureau (American Community Survey, 2021) with additional structural health-care barrier data obtained from South Carolina's Center for Rural and Primary Health Care, and the American Hospital Directory., Findings: Between Jan 1, 2016, and Dec 31, 2021, 41 691 individuals were hospitalised for opioid misuse and 26 860 were hospitalised for HCV. There were a median of 80 (IQR 24-213) opioid-related hospitalisations and 61 (21-196) HCV-related hospitalisations per ZCTA. A standard deviation increase in ZCTA-level uninsured rate (relative risk 1·24 [95% CI 1·17-1·31]), poverty rate (1·24 [1·17-1·31]), mortality (1·18 [1·12-1·25]), and social vulnerability index (1·17 [1·10-1·24]) was significantly associated with increased combined opioid-related and HCV-related hospitalisation rates. A standard deviation increase in ZCTA-level income (0·79 [0·75-0·84]) and unemployment rate (0·87 [0·82-0·93]) was significantly associated with decreased combined opioid-related and HCV-related hospitalisations. Using 2016-20 hospitalisations as training data, our models predicted ZCTA-level opioid-related hospitalisations in 2021 with a median of 80·4% (IQR 66·8-91·1) accuracy and HCV-related hospitalisations in 2021 with a median of 75·2% (61·2-87·7) accuracy. Several underserved high-risk ZCTAs were identified for delivery of targeted interventions., Interpretation: Our results suggest that individuals from economically disadvantaged and medically under-resourced communities are more likely to have an opioid-related or HCV-related hospitalisation. In conjunction with hospitalisation forecasts, our results could be used to identify and prioritise high-risk, underserved communities for delivery of field-level interventions., Funding: South Carolina Center for Rural and Primary Healthcare, National Institute on Drug Abuse, and National Library of Medicine., Competing Interests: Declaration of interests FG, AHL, and LR received salary support from South Carolina Center for Rural and Primary Healthcare (SCCRPH2015593). FG, AHL, LR, and NKM received salary support from the National Institute on Drug Abuse (R61DA059892) and the National Library of Medicine (R01 LM014193) during this study. LR and AHL received support from the Health Resources and Services Administration (HRSA HB1RH47075-01-00) during this study. KAH declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Investigate the role of the Ryan White HIV/AIDS Program (RWHAP) - which funds services for vulnerable and historically disadvantaged populations with HIV - in reducing health inequities among people with HIV over a 10-year horizon., Design: We use an agent-based microsimulation model to incorporate the complexity of the program and long-time horizon., Methods: We use a composite measure (the Theil index) to evaluate the health equity implications of the RWHAP for each of four subgroups (based on race and ethnicity, age, gender, and HIV transmission category) and two outcomes (probability of being in care and treatment and probability of being virally suppressed). We compare results with the RWHAP fully funded versus a counterfactual scenario, in which the medical and support services funded by the RWHAP are not available., Results: The model indicates the RWHAP will improve health equity across all demographic subgroups and outcomes over a 10-year horizon. In Year 10, the Theil index for race and ethnicity is 99% lower for both outcomes under the RWHAP compared to the non-RWHAP scenario; 71-93% lower across HIV transmission categories; 31-44% lower for age; and 73-75% lower for gender., Conclusion: Given the large number of people served by the RWHAP and our findings on its impact on equity, the RWHAP represents an important vehicle for achieving the health equity goals of the National HIV/AIDS Strategy (2022-2025) and the Ending the HIV Epidemic Initiative goal of reducing new infections by 90% by 2030., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Standard-of-care nucleic acid amplification tests (routine NAATs) for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can take several days to result and therefore delay treatment. Rapid point-of-care GC/CT NAAT (rapid NAAT) could reduce the time to treatment and therefore onward transmission. This study evaluated the incremental cost per infectious day averted and overall cost of implementation associated with rapid compared with routine NAAT., Methods: Prospective sexually transmitted infection (STI) treatment data from men who have sex with men and transgender women in San Diego who received rapid NAAT between November 2018 and February 2021 were evaluated. Historical time from testing to treatment for routine NAAT was abstracted from the literature. Costs per test for rapid and routine NAAT were calculated using a micro-costing approach. The incremental cost per infectious day averted comparing rapid to routine NAAT and the costs of rapid GC/CT NAAT implementation in San Diego Public Health STI clinics were calculated., Results: Overall, 2333 individuals underwent rapid NAAT with a median time from sample collection to treatment of 2 days compared with 7 to 14 days for routine NAAT equating to a reduction of 5 to 12 days. The cost of rapid and routine GC/CT NAAT was $57.86 and $18.38 per test, respectively, with a cost-effectiveness of between $2.43 and $5.82 per infectious day averted. The incremental cost of rapid NAAT improved when at least 2000 tests were performed annually., Conclusions: Although rapid GC/CT NAAT is more expensive than routine testing, the reduction of infectious days between testing and treatment may reduce transmission and provide improved STI treatment services to patients., Competing Interests: Conflict of Interest and Sources of Funding: S.J.L. has received funding from Gilead Sciences paid to her institution and donation of medications from Gilead Sciences. E.W., T.C.S.M., N.K.M., and W.T. have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states., Methods: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID., Results: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks., Conclusions: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population., Competing Interests: Potential conflicts of interest . N. M. reports research grants paid to their institution unrelated to this work from the NIH (National Institute on Drug Abuse and NIAID) and Gilead and an unpaid board position on the International Network on Health and Hepatitis in Substance Users. R. G. reports grant funding from the Department of State Bureau of Educational and Cultural Affairs unrelated to this work. C. D. reports research grants paid to their institution unrelated to this work from the UK Medical Research Council and UK Foreign, Commonwealth, and Development office; coauthorship book royalties from Cambridge University Press and Chapman & Hall/CRC Press; consulting fees from UK Defra via the UK Animal and Plant Health Agency; honoraria for lectures at the London School of Hygiene and Tropical Medicine; unpaid trustee roles in the Council of the Royal Society; role as vice-president for the External Affairs of the Royal Statistical Society; membership of the St. Peter's College Oxford Governing Body (part of University position); unpaid work developing and evaluating possible vaccine effectiveness studies for the World Health Organization (WHO) R&D Blueprint; payment for grant proposal review from the Science Foundation Ireland; and payment for Dengue Expert Advisory Panel participation from the Singapore National Environmental Agency. N.C. L. reports consulting fees from the WHO for work related to guidelines on neglected tropical diseases, which are unrelated to this work. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

US regulations mandate annual N95 mask fit testing for healthcare workers, but the optimal testing interval is unknown. In our study using data from 12,565 healthcare workers, the probability of survival free from fit-test failure after 3 years was 99.4%, suggesting that less frequent fit testing every 3 years would be safe.

Background: Incarceration is associated with drug-related harms among people who inject drugs (PWID). We trained >1800 police officers in Tijuana, Mexico on occupational safety and HIV/HCV, harm reduction, and decriminalization reforms (Proyecto Escudo). We evaluated its effect on incarceration, population impact and cost-effectiveness on HIV and fatal overdose among PWID., Methods: We assessed self-reported recent incarceration in a longitudinal cohort of PWID before and after Escudo. Segmented regression was used to compare linear trends in log risk of incarceration among PWID pre-Escudo (2012-2015) and post-Escudo (2016-2018). We estimated population impact using a dynamic model of HIV transmission and fatal overdose among PWID, with incarceration associated with syringe sharing and fatal overdose. The model was calibrated to HIV and incarceration patterns in Tijuana. We compared a scenario with Escudo (observed incarceration declines for 2 years post-Escudo among PWID from the segmented regression) compared to a counterfactual of no Escudo (continuation of stable pre-Escudo trends), assessing cost-effectiveness from a societal perspective. Using a 2-year intervention effect and 50-year time horizon, we determined the incremental cost-effectiveness ratio (ICER, in 2022 USD per disability-adjusted life years [DALYs] averted)., Findings: Compared to stable incarceration pre-Escudo, for every three-month interval in the post-Escudo period, recent incarceration among PWID declined by 21% (adjusted relative risk = 0.79, 95% CI: 0.68-0.91). Based on these declines, we estimated 1.7% [95% interval: 0.7%-3.5%] of new HIV cases and 12.2% [4.5%-26.6%] of fatal overdoses among PWID were averted in the 2 years post-Escudo, compared to a counterfactual without Escudo. Escudo was cost-effective (ICER USD 3746/DALY averted compared to a willingness-to-pay threshold of $4842-$13,557)., Interpretation: Escudo is a cost-effective structural intervention that aligned policing practices and human-rights-based public health practices, which could serve as a model for other settings where policing constitutes structural HIV and overdose risk among PWID., Funding: National Institute on Drug Abuse, UC MEXUS CONACyT, and the San Diego Center for AIDS Research (SD CFAR)., Competing Interests: JAC and SS report research grants from NIH. NM reports research grants from NIH and unrestricted research grants from Gilead and Abbvie unrelated to this work; and Leadership or fiduciary role for the International Network on Health and Hepatitis in Substance Users. All other authors declare no interests., (© 2024 The Author(s).)

Background: Reinfection after successful treatment with direct-acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct-acting antivirals, and the proportion of all incident cases attributable to reinfection., Methods: We pooled individual-level data on HCV reinfection in people with HIV after spontaneous or treatment-induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment-induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct-acting antiviral access periods (pre-direct-acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year., Findings: Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person-years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct-acting antivirals (pre-introduction period; 4·1 cases per 100 person-years, 95% CI 2·8-6·0). Compared with the pre-introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0·96, 95% CI 0·78-1·19), and 28% lower during the period of broad access (0·72, 0·60-0·86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1·02 cases per 100 person-years (95% CI 0·96-1·07) in 2015 to 0·67 cases per 100 person-years (95% CI 0·59-0·75) in 2019., Interpretation: HCV reinfection incidence and combined incidence declined in people with HIV following direct-acting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct-acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests MK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead; consulting fees from ViiV Healthcare, AbbVie, and Gilead, all outside the submitted work; and is supported by a Tier I Canada Research Chair. AR reports support to his institution for advisory boards or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator initiated trial grant from Gilead Sciences; all remuneration to AR was paid to his home institution, and all remuneration was provided outside the submitted work. KL reports honoraria for advice or public speaking from Gilead, MSD, and ViiV Healthcare; support for attending meetings or travel expenses from Gilead and MSD; and a leadership or fiduciary role in other board, society, committee or advocacy groups, paid or unpaid, from Spikmm. FB reports grants from Gilead and honoraria from Gilead, ViiV Healthcare, and MSD. NKM received research grants from Gilead and the US National Institutes of Health unrelated to this work. TS reports consulting fees from Biogen for serving on advisory boards and scientific leadership committees. JSD reports investigator-initiated research funding to his institution from Gilead Sciences; investigator-initiated and company sponsored research funding to his institution from AbbVie; and consulting fees unrelated to this work to his institution from AbbVie. GVM reports grants or contracts from Gilead, AbbVie, ViiV Healthcare, and Janssen to her institution; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events; and support for attending meetings or travel expenses from Gilead; and participation on a data safety monitoring board or advisory board for Gilead, ViiV Healthcare, and AstraZeneca. IJ reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Gilead Sciences, ViiV Healthcare, and GESIDA; and payment for expert testimony and support for attending meetings or travel expenses from Gilead Sciences. AB reports speakers fees from Gilead Sciences; and participation on a data safety monitoring board for Amsterdam University Medical Centers and an advisory board for ANRS Emerging Infectious Diseases. MvdV reports grants or contracts and consulting fees from Gilead, ViiV Healthcare, and MSD to his institution. MH reports investigator-initiated research grants from Gilead Sciences and AbbVie. MS reports investigator-initiated research grants from Gilead Sciences and AbbVie. M-BR reports funding from SIDACTION for the duration of her PhD. RG reports funding from Cepheid and SpeeDex towards the Australian Research Council Industrial Transformation Research Program Hub to Combat Antimicrobial Resistance grant (IH190100021). Cepheid has also contributed in-kind study equipment (cartridges, machines) to the project Scaling up infectious disease point-of-care testing for Indigenous people (RARUR000080) funded by the Medical Research Future Fund Rapid Applied Research Translation grant. RS-D, DKvS, CS, OL, MP, LW, JY, AS, and JB declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP-C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3-6 months (October-2014 to November-2019). Participants eligible for this analysis included those at-risk of HCV primary infection (anti-HCV negative) or re-infection (anti-HCV positive, HCV RNA negative) with follow-up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person-years of follow-up). Overall HCV incidence was 6.11/100 person-years (95%CI: 5.07-7.35), with higher rate of re-infection (9.34/100 person-years; 95%CI: 7.15-12.19) than primary infection (4.60/100 person-years; 95%CI: 3.56-5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison [vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88-18.92), and those who were released and re-incarcerated during follow-up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03-2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high-dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02-0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35-15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High-dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required., (© 2023 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation., Competing Interests: Declaration of interests K.G.A. has received consulting fees on SARS-CoV-2 and the COVID-19 pandemic., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study demonstrated that scaling up of direct-acting antiviral (DAA) treatment reduced hepatitis C virus (HCV) transmission. We evaluated the cost-effectiveness of scaling up HCV treatment in statewide prison services incorporating long-term outcomes across custodial and community settings., Methods: A dynamic model of incarceration and HCV transmission among people who inject drugs (PWID) in New South Wales, Australia, was extended to include former PWID and those with long-term HCV progression. Using Australian costing data, we estimated the cost-effectiveness of scaling up HCV treatment in prisons by 44% (as achieved by the SToP-C study) for 10 years (2021-2030) before reducing to baseline levels, compared to a status quo scenario. The mean incremental cost-effectiveness ratio (ICER) was estimated by comparing the differences in costs and quality-adjusted life-years (QALYs) between the scale-up and status quo scenarios over 40 years (2021-2060) discounted at 5% per annum. Univariate and probabilistic sensitivity analyses were performed., Results: Scaling up HCV treatment in the statewide prison service is projected to be cost-effective with a mean ICER of A$12 968/QALY gained. The base-case scenario gains 275 QALYs over 40 years at a net incremental cost of A$3.6 million. Excluding DAA pharmaceutical costs, the mean ICER is reduced to A$6 054/QALY. At the willingness-to-pay threshold of A$50 000/QALY, 100% of simulations are cost-effective at various discount rates, time horizons, and changes of treatment levels in prison and community., Conclusions: Scaling up HCV testing and treatment in prisons is highly cost-effective and should be considered a priority in the national elimination strategy., Clinical Trials Registration: NCT02064049., Competing Interests: Potential conflicts of interest. G. J. D. is a consultant/advisor for and has received research grants from Gilead, AbbVie, Merck, Bristol-Myers Squibb, and Cepheid. A. R. L. has received investigator-initiated research grants from Gilead, AbbVie, Merck, and Bristol-Myers Squibb. J. G. is a consultant/advisor and has received research grants from Gilead, AbbVie, Merck, and Cepheid. P. V. has received investigator-initiated untied grants from Gilead and honoraria from Gilead and Merck. N. K. M. has received unrestricted research grants from Gilead and Merck. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Needle and syringe programs (NSPs) are effective at preventing HIV and hepatitis C virus (HCV) among people who inject drugs (PWID), yet global coverage is low, partly because governments lack data on the cost and cost-effectiveness of NSP in their countries to plan and fund their responses. We conducted a global systematic review of unit costs of NSP provision to inform estimation of cost drivers and extrapolated costs to other countries., Methods: We conducted a systematic review to extract data on the cost per syringe distributed and its cost drivers. We estimated the impact of country-level and program-level variables on the cost per syringe distributed using linear mixed-effects models. These models were used to predict unit costs of NSP provision, with the best performing model used to extrapolate the cost per syringe distributed for 137 countries. The total cost for a comprehensive NSP (200 syringes per PWID/year) was also estimated for 68 countries with PWID population size estimates., Results: We identified 55 estimates of the unit cost per syringe distributed from 14 countries. Unit costs were extrapolated for 137 countries, ranging from $0.08 to $20.77 (2020 USD) per syringe distributed. The total estimated spend for a high-coverage, comprehensive NSP across 68 countries with PWID size estimates is $5 035 902 000 for 10 887 500 PWID, 2.1-times higher than current spend., Conclusion: Our review identified cost estimates from high-income, upper-middle-income, and lower-middle-income countries. Regression models may be useful for estimating NSP costs in countries without data to inform HIV/HCV prevention programming and policy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We aimed to evaluate factors associated with HRQoL among a cohort of PWID in Australia., Methods: Participants were enrolled in an observational cohort study (the LiveRLife Study) between 2014 and 2018 at 15 sites in Australia. They provided fingerstick whole-blood samples for point-of-care HCV RNA testing and underwent transient elastography to assess liver disease. Participants completed the EQ-5D-3L survey at enrolment. Regression models were used to assess the impact of clinical and socioeconomic characteristics on the EQ-5D-3L scores., Results: Among 751 participants (median age, 43 years; 67% male), 63% reported injection drug use in the past month, 43% had current HCV infection, and 68% had no/mild liver fibrosis (F0/F1). The mean EQ-5D-3L and EQ-VAS scores were 0.67 and 62, respectively, for the overall study population. There was no significant difference in the EQ-5D-3L scores among people with and without recent injecting drug use (mean: 0.66 vs. 0.68, median: 0.73 vs. 0.78, P = 0.405), and among people receiving and not receiving opioid agonist therapy (mean: 0.66 vs. 0.68, median: 0.73 vs. 0.76, P = 0.215). Participants who were employed were found to have the highest mean EQ-5D-3L (0.83) and EQ-VAS scores (77). The presence of current HCV infection, liver fibrosis stage, and high-risk alcohol consumption had little impact on HRQoL., Conclusions: The study findings provide important HRQoL data for economic evaluations, useful for guiding the allocation of resources for HCV elimination strategies and interventions among PWID., (© 2023. The Author(s).)

In the context of historic reckoning with the role of the criminal-legal system as a structural driver of health harms, there is mounting evidence that punitive drug policies have failed to prevent problematic drug use while fueling societal harms. In this explainer article, we discuss how simulation modeling provides a methodological framework to explore the potential outcomes (beneficial and harmful) of various drug policy alternatives, from incremental to radical. We discuss potential simulation modeling opportunities while calling for a more active role of simulation modeling in visioning and operationalizing transformative change., Highlights: This article discusses opportunities for simulation modeling in projecting health and economic impacts (beneficial and harmful) of drug-related criminal justice reforms.We call on modelers to explore radical interventions to reduce drug-related harm and model grand alternative futures in addition to more probable scenarios, with a goal of opening up policy discourse to these options., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the follo wing financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided entirely by a grant from the National Institute on Drug Abuse, R13DA052198. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report., (© The Author(s) 2023.)

Background and Aims: Criminalization of drug use and punitive policing are key structural drivers of hepatitis C virus (HCV) risk among people who inject drugs (PWID). A police education program (Proyecto Escudo) delivering training on occupational safety together with drug law content was implemented between 2015 and 2016 in Tijuana, Mexico, to underpin drug law reform implementation. We used data from a longitudinal cohort of PWID in Tijuana to inform epidemic modeling and assess the long-term impact of Escudo on HCV transmission and burden among PWID in Tijuana., Methods: We developed a dynamic, compartmental model of HCV transmission and incarceration among PWID and tracked liver disease progression among current and former PWID. The model was calibrated to data from Tijuana, Mexico, with 90% HCV seroprevalence. We used segmented regression analysis to estimate impact of Escudo on recent incarceration among an observational cohort of PWID. By simulating the observed incarceration trends, we estimated the potential impact of the implemented (2-year reduction in incarceration) and an extended (10-year reduction in incarceration) police education program over a 50-year follow-up (2016-2066) on HCV outcomes (incidence, cirrhosis, HCV-related deaths and disability adjusted life-years averted) compared with no intervention., Results: Over the 2-year follow-up, Proyecto Escudo reduced HCV incidence among PWID from 21.5 per 100 person years (/100py) (95% uncertainty interval [UI] = 15.3-29.7/100py) in 2016 to 21.1/100py (UI = 15.0-29.1/100py) in 2018. If continued for 10 years, Escudo could reduce HCV incidence to 20.0/100py (14.0-27.8/100py) by 2026 and avert 186 (32-389) new infections, 76 (UI = 12-160) cases of cirrhosis and 32 (5-73) deaths per 10 000 PWID compared with no intervention over a 50-year time horizon., Conclusions: In Tijuana, Mexico, implementation of a police education program delivering training on occupational safety and drug law content appears to have reduced hepatitis C virus incidence among people who inject drugs., (© 2023 Society for the Study of Addiction.)

Introduction: It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site., Areas Covered: In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant., Expert Opinion: Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.