Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. METHODS: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. RESULTS: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days. CONCLUSIONS: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. IMPACT AND IMPLICATIONS: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. CLINICAL TRIAL NUMBER: NCT02824640.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study.

BACKGROUND: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold. METHODS: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold. RESULTS: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis. CONCLUSIONS: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

Cryopreservation of sperm from the gudgeon, Microphysogobio rapidus (Cyprinidae): Effects of cryoprotectant, diluents, and dilution ratio.

We investigated methods for cryopreserving sperm from the endangered gudgeon, Microphysogobio rapidus, by examining the effects of cryoprotective agent (CPA) concentration, diluent, and dilution ratio on post-thaw sperm quality. The quality of frozen sperm was evaluated in terms of motility and kinematic parameters, viability, DNA damage, and fertilization rate. We evaluated methanol, glycerol, dimethyl sulfoxide (DMSO), and ethylene glycol as CPAs. Sperm motility, velocity, and viability were significantly higher when methanol was used as the CPA (p < 0.05). The diluents tested were Ringer's solution, Kurokura's Extender, Common Carp Sperm Extender (CCSE), and buffered sperm motility-inhibiting saline solution (BSMIS); post-thaw motility was highest when Ringer's solution was used as the diluent. Next, various quantities of methanol were combined with Ringer's solution to identify the optimal dose of methanol. The dilution ratios tested ranged from 1:1 to 1:7. Cryopreserved sperm was thawed at 20 °C for 15 s. The use of 10% methanol with Ringer's solution at a dilution ratio of 1:5 resulted in the highest post-thaw sperm motility, viability, and velocity including VAP, VCL, and VSL. Post-thaw sperm showed significantly greater DNA damage than the control (fresh sperm) (p < 0.05). The fertilization rate was highest with fresh sperm (p < 0.05), followed by sperm frozen with 10% methanol + Ringer's solution. We recommend that the best way to preserve sperm in the studied species is to use a combination of Ringer's solution and 10% methanol at a 1:5 dilution ratio. Our findings will facilitate the artificial fertilization of M. rapidus.

Reducing Opioid Analgesic Prescribing in Dentistry Through Prescribing Defaults: A Cluster-Randomized Controlled Trial.

OBJECTIVE: To determine the effect of a uniform, reduced, default dispense quantity for new opioid analgesic prescriptions on the quantity of opioids prescribed in dentistry practices. METHODS: We conducted a cluster-randomized controlled trial within a health system in the Bronx, NY, USA. We randomly assigned three dentistry sites to a 10-tablet default, a 5-tablet default, or no change (control). The primary outcome was the quantity of opioid analgesics prescribed in the new prescription. Secondary outcomes were opioid analgesic reorders and health service utilization within 30 days after the new prescription. We analyzed outcomes from 6 months before implementation through 18 months after implementation. RESULTS: Overall, 6,309 patients received a new prescription. Compared with the control site, patients at the 10-tablet-default site had a significantly larger change in prescriptions for 10 tablets or fewer (38.7 percentage points; confidence interval [CI]: 11.5 to 66.0), lower number of tablets prescribed (-3.3 tablets; CI: -5.9 to -0.7), and lower morphine milligram equivalents (MME) prescribed (-14.1 MME; CI: -27.8 to -0.4), which persisted in the 30 days after the new prescription despite a higher percentage of reorders (3.3 percentage points; CI: 0.2 to 6.4). Compared with the control site, patients at the 5-tablet-default site did not have a significant difference in any outcomes except for a significantly higher percentage of reorders (2.6 percentage points; CI: 0.2 to 4.9). CONCLUSIONS: Our findings further support the efficacy of strategies that lower default dispense quantities, although they indicate that caution is warranted in the selection of the default. TRIAL REGISTRATION: ClinicalTrials.org ID: NCT03030469.

Discrimination and Adverse Perinatal Health Outcomes: A Latent Class Analysis.

INTRODUCTION: An intersectionality framework recognizes individuals as simultaneously inhabiting multiple intersecting social identities embedded within systems of disadvantage and privilege. Previous research links perceived discrimination with worsened health outcomes yet is limited by a focus on racial discrimination in isolation. We applied an intersectional approach to the study of discrimination to examine the association with adverse perinatal health outcomes. METHODS: We analyzed data from a cohort of 2,286 pregnant participants (Black, n = 933; Hispanic, n = 471; White, n = 853; and Other, n = 29) from the Centering and Racial Disparities trial. Perceived discrimination was assessed via the Everyday Discrimination Scale (EDS) and perinatal health outcomes collected via electronic medical record review. Latent class analysis was used to identify subgroups of discrimination based on EDS item response and the rate of adverse perinatal health outcomes compared between subgroups using a Bolck, Croon and Hagenaars 3-step approach. RESULTS: Four discrimination subgroups were identified: no discrimination, general discrimination, discrimination attributed to one or several social identities, and discrimination attributed to most or all social identities. Experiencing general discrimination was associated with postpartum depression symptoms when compared with experiencing no discrimination among Black (9% vs 5%, P = .04) and White participants (18% vs 9%, P = .01). White participants experiencing general discrimination gave birth to low birthweight infants at a higher rate than those experiencing no discrimination (11% vs 6%, P = .04). No significant subgroup differences were observed among Hispanic participants. CONCLUSION: Perceived discrimination may play an influential role in shaping perinatal health. More research applying an intersectional lens to the study of discrimination and perinatal health outcomes is needed.

Changes in Health-related Quality of Life for Hepatitis C Virus-Infected People Who Inject Drugs While on Opioid Agonist Treatment Following Sustained Virologic Response.

BACKGROUND: Although efforts to treat hepatitis C virus (HCV) in people who inject drugs (PWID) yield high rates of sustained virologic response (SVR), the relationship between successful HCV treatment and health-related quality of life (HRQOL) among PWID is poorly understood. We examined HRQOL changes throughout HCV treatment and post-treatment for PWID achieving SVR. METHODS: Participants included 141 PWID who achieved SVR following HCV treatment onsite at 3 opioid agonist treatment (OAT) clinics in the Bronx, New York. EQ-5D-3L assesses 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), producing an index of HRQOL ranging from 0 to 1. EQ-5D-3L was measured at baseline; 4, 8, and 12 weeks during treatment; and 12 and 24 weeks post-treatment. Linear mixed effects regression models assessed changes in the mean EQ-5D-3L index over time. RESULTS: Mean EQ-5D-3L index baseline was 0.66 (standard error [SE] = 0.02). While over half the population reported no baseline problems with self-care (85.1%), usual activities (56.0%), and mobility (52.5%), at least two-thirds reported problems with pain/discomfort (78.0%) and anxiety/depression (66.0%). Twenty-four weeks post-treatment, proportions reporting pain/discomfort and anxiety/depression decreased by 25.7% and 24.0%, respectively. Mean EQ-5D-3L index significantly improved during treatment (P < .0001), and improvement was sustained following treatment completion, with mean EQ-5D-3L index of 0.77 (SE = 0.02) 12 weeks post-SVR. CONCLUSIONS: HCV treatment led to sustained improvement in HRQOL for PWID on OAT who achieved SVR. Future research is necessary to determine whether improvements in HRQOL can be sustained beyond 12 weeks post-SVR.

Pediatrician Adherence to Guidelines for Diagnosis and Management of High Blood Pressure.

OBJECTIVES: To assess pediatrician adherence to the 2017 American Academy of Pediatrics' clinical practice guideline for high blood pressure (BP). STUDY DESIGN: Pediatric primary care practices (n = 59) participating in a quality improvement collaborative submitted data for patients with high BP measured between November 2018 and January 2019. Baseline data included patient demographics, BP, body mass index (BMI), and actions taken. Logistic regression was used to test associations between patient BP level and BMI with provider adherence to guidelines (BP measurement, counseling, follow-up, evaluation). RESULTS: A total of 2677 patient charts were entered for analysis. Only 2% of patients had all BP measurement steps completed correctly, with fewer undergoing 3-limb and ambulatory BP measurement. Overall, 46% of patients received appropriate weight, nutrition, and lifestyle counseling. Follow-up for high BP was recommended or scheduled in 10% of encounters, and scheduled at the appropriate interval in 5%. For patients presenting with their third high BP measurement, 10% had an appropriate diagnosis documented, 2% had appropriate screening laboratory tests conducted, and none had a renal ultrasound performed. BMI was independently associated with increased odds of counseling, but higher BP was associated with lower odds of counseling. Higher BP was independently associated with an increased likelihood of documentation of hypertension. CONCLUSIONS: In this multisite study, adherence to the 2017 American Academy of Pediatrics' guideline for high BP was low. Given the long-term health implications of high BP in childhood, it is important to improve primary care provider recognition and management. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03783650.

Changes in alcohol use during hepatitis C treatment in persons who inject drugs.

People who inject drugs (PWID) are a vulnerable population at high risk for acquiring hepatitis C virus (HCV) and frequently suffer from comorbid alcohol use. This study examines the characteristics and correlates of alcohol use among study participants, the association between alcohol consumption and sustained virologic response (SVR) in patients receiving HCV treatment, changes in drinking behaviours during HCV treatment and associations of drinking over time with specific models of HCV treatment. Participants were 150 PWID with HCV who were receiving opioid agonist therapy (OAT) and enrolled in a randomized clinical trial exploring the effectiveness of three models of care for HCV treatment. The addiction severity index was the primary measure of alcohol consumption. Days of alcohol intake were evaluated longitudinally and across three treatment groups. At baseline, 31% (47/150) reported having at least one drink in the last 30 days including 24% (36/150) who reported drinking to intoxication in the last 30 days. There was no difference in SVR rates between groups. There was a significant decrease in overall days of drinking from baseline (7.78 ± 7.86) to follow-up at Week 24 (5.78 ± 8.83) (p = 0.041), but there were no significant changes among those who drank to intoxication; modified directly observed therapy (mDOT) was the only group with a significant decline in days of alcohol consumption (p = 0.041). In this cohort of PWID on OAT, baseline alcohol consumption did not affect SVR rates. HCV treatment was overall associated with decreased alcohol consumption. In particular, mDOT was associated with decreased alcohol consumption. Given the additive effect of alcohol and HCV on the development of cirrhosis, studies should be done to investigate the complimentary effects of the mDOT model of care on alcohol cessation.

Group vs traditional prenatal care for improving racial equity in preterm birth and low birthweight: the Centering and Racial Disparities randomized clinical trial study.

BACKGROUND: The United States has persistently high rates of preterm birth and low birthweight and is characterized by significant racial disparities in these rates. Innovative group prenatal care models, such as CenteringPregnancy, have been proposed as a potential approach to improve the rates of preterm birth and low birthweight and to reduce disparities in these pregnancy outcomes. OBJECTIVE: This study aimed to test whether participation in group prenatal care would reduce the rates of preterm birth and low birthweight compared with individual prenatal care and whether group prenatal care would reduce the racial disparity in these rates between Black and White patients. STUDY DESIGN: This was a randomized controlled trial among medically low-risk pregnant patients at a single study site. Eligible patients were stratified by self-identified race and ethnicity and randomly allocated 1:1 between group and individual prenatal care. The primary outcomes were preterm birth at <37 weeks of gestation and low birthweight of <2500 g. The primary analysis was performed according to the intent-to-treat principle. The secondary analyses were performed according to the as-treated principle using modified intent-to-treat and per-compliance approaches. The analysis of effect modification by race and ethnicity was planned. RESULTS: A total of 2350 participants were enrolled, with 1176 assigned to group prenatal care and 1174 assigned to individual prenatal care. The study population included 952 Black (40.5%), 502 Hispanic (21.4%), 863 White (36.8%), and 31 "other races or ethnicity" (1.3%) participants. Group prenatal care did not reduce the rate of preterm birth (10.4% vs 8.7%; odds ratio, 1.22; 95% confidence interval, 0.92-1.63; P=.17) or low birthweight (9.6% vs 8.9%; odds ratio, 1.08; 95% confidence interval, 0.80-1.45; P=.62) compared with individual prenatal care. In subgroup analysis, greater attendance in prenatal care was associated with lower rates of preterm birth and low birthweight. This effect was most noticeable for the rates of low birthweight for Black participants in group care: intent to treat (51/409 [12.5%]), modified intent to treat (36/313 [11.5%]), and per compliance (20/240 [8.3%]). Although the rates of low birthweight were significantly higher for Black participants than White participants seen in individual care (adjusted odds ratio, 2.00; 95% confidence interval, 1.14-3.50), the difference was not significant for Black participants in group care compared with their White counterparts (adjusted odds ratio, 1.58; 95% confidence interval, 0.74-3.34). CONCLUSION: There was no difference in the overall rates of preterm birth or low birthweight between group and individual prenatal care. With increased participation in group prenatal care, lower rates of preterm birth and low birthweight for Black participants were observed. The role of group care models in reducing racial disparities in these birth outcomes requires further study.

HIV And HCV adherence and treatment outcomes among people who inject drugs receiving opioid agonist therapy.

Among people who inject drugs (PWID), 60% have HCV and 50-90% of HIV-infected PWID are co-infected with HCV. Data comparing adherence to direct-acting antiviral (DAA) therapy among HCV mono-infected and HIV/HCV co-infected PWID is limited. The impact of HCV treatment initiation on HIV antiretroviral therapy (ART) adherence is also poorly understood. We assessed DAA adherence in HCV mono-infected and HIV/HCV co-infected PWID and examined changes in ART adherence and HIV outcomes following HCV treatment. Study was conducted in three Medication for Opioid use Disorder (MOUD) programs in Bronx, New York. HCV treatment adherence was measured using electronic blister packs. 2-week DAA adherence rates were compared and controlled for study arm, psychiatric illness and alcohol intoxication within the past 30 days. ART adherence was measured using participant self-report and dichotomized to "excellent" or "other". ART adherence, CD4 count, and HIV viral load were identified six months prior to, during, and six months after HCV treatment. Statistical significance was assessed with mixed-effects regression linear or logistic models. Overall DAA adherence rates among HCV mono-infected and HIV/HCV co-infected PWID were 74% (95% CI=71-78%) and 76% (95%CI=70-83%), respectively (p=.55). There were no significant changes in ART adherence, CD4 counts, or HIV viral loads prior to, during, or after HCV treatment. This is the first study assessing the impact of DAA therapy on ART adherence and HIV treatment outcomes among PWID. It is one of the first to compare DAA adherence among HCV and HIV/HCV co-infected PWID. Our data demonstrate no significant difference in DAA adherence and no significant impact of HCV treatment on ART adherence or HIV outcomes.

Adaptive thermogenesis after moderate weight loss: magnitude and methodological issues.

PURPOSE: The aim of this study was (1) to assess AT through 13 different mathematical approaches and to compare their results; and (2) to understand if AT occurs after moderate WL. METHODS: Ninety-four participants [mean (SD); BMI, 31.1 (4.3) kg/m2; age, 43.0 (9.4) years; 34% females] underwent a 1-year lifestyle intervention (clinicaltrials.gov ID: NCT03031951) and were randomized to intervention (IG, n = 49) or control groups (CG, n = 45), and all measurements were made at baseline and after 4 months. Fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and REE by indirect calorimetry. AT was assessed through 13 different approaches, varying in how REE was predicted and/or how AT was assessed. RESULTS: IG underwent a mean negative energy balance (EB) of 270 (289) kcal/day, p < 0.001), resulting in a WL of - 4.8 (4.9)% and an FM loss of - 11.3 (10.8)%. Regardless of approach, AT occurred in the IG, ranging from ~ - 65 to ~ - 230 kcal/day and three approaches showed significant AT in the CG. CONCLUSIONS: Regardless of approach, AT occurred after moderate WL in the IG. AT assessment should be standardized and comparisons among studies with different methodologies to assess AT must be avoided.

Differences in Motivating Factors for SARS-CoV-2 Vaccination and Perceptions of Infection Risk among Healthcare and EMS Personnel in South Carolina.

OBJECTIVES: Although medical workers were prioritized to receive the coronavirus disease 2019 (COVID-19) vaccination, many have declined. Even though studies have investigated differences in COVID-19-related attitudes and vaccination for workers in hospitals and long-term care facilities, none have included emergency medical services (EMS) personnel. We investigated the association between type of medical worker (EMS vs healthcare worker [HCW]) and COVID-19 vaccination, vaccine beliefs, vaccine motivators, personal protection behaviors, and risk perceptions. METHODS: The data for self-identified HCWs came from surveys distributed to randomly selected residents of South Carolina and EMS personnel recruited at a targeted surveillance testing event during the South Carolina EMS Symposium. Pearson χ2 and Fisher exact tests analyzed differences in the distribution of demographic characteristics and self-reported COVID-19 vaccination attitudes by medical workers. Multivariable logistic regression assessed the association between COVID-19 vaccination and type of medical worker, adjusting for age, sex, race, and frontline status, and assessed the associations among vaccine beliefs, vaccine motivators, personal protection behaviors, and risk perceptions by type of medical worker, adjusting for age, sex, race, frontline status, and vaccination status. RESULTS: Of the 126 respondents 57.9% were EMS, 42.1% were HCWs, and 73.6% of the cohort were self-reported frontline medical workers. Approximately two-thirds of respondents received a vaccine for COVID-19, with no significant differences between EMS and HCWs; however, EMS workers were significantly less likely to receive the vaccination out of concern about exposures at work/school (adjusted odds ratio [aOR] 0.22, 95% confidence interval [CI] 0.08-0.57), concern about exposures within the community (aOR 0.18, 95% CI 0.07-0.48), or to do their part to control the pandemic (aOR 0.20, 95% CI 0.06-0.69). EMS workers also were significantly less likely to wear a mask all/most of the time when outside the home (aOR 0.04, 95% CI 0.0-0.21) and less concerned about the spread of COVID-19 in their community as compared with HCWs (aOR 0.19, 95% CI 0.06-0.56). CONCLUSIONS: EMS personnel were significantly less concerned about the spread of COVID-19 in their community and significantly less likely to wear a mask all/most of the time while outside the home as compared with HCWs. Differences in the COVID-19-related attitudes and personal protection behaviors of EMS personnel should be used to develop targeted interventions to increase vaccine motivation and adherence to personal protection protocols.

Hepatitis C Virus Direct-Acting Antiviral Treatment Adherence Patterns and Sustained Viral Response Among People Who Inject Drugs Treated in Opioid Agonist Therapy Programs.

BACKGROUND: Adequate medication adherence is critical for achieving sustained viral response (SVR) of hepatitis C virus (HCV) among people who inject drugs (PWID). However, it is less known which patterns of direct-acting antiviral (DAA) treatment adherence are associated with SVR in this population or what factors are associated with each pattern. METHODS: The randomized 3-arm PREVAIL study used electronic blister packs to obtain daily time frame adherence data in opiate agonist therapy program settings. Exact logistic regressions were applied to test the associations between SVR and 6 types of treatment adherence patterns. RESULTS: Of the 113 participants treated with combination DAAs, 109 (96.5%) achieved SVR. SVR was significantly associated with all pattern parameters except for number of switches between adherent and missed days: total adherent daily doses (exact adjusted odds ratio [AOR] = 1.12; 95% confidence interval [CI] = 1.04-1.22), percent total doses (1.09; 1.03-1.16), days on treatment (1.16; 1.05-1.32), maximum consecutive adherent days (1.34; 1.06-2.04), and maximum consecutive nonadherent days (0.85; .74-.95 = 0.003). SVR was significantly associated with total adherent doses in the first 2 months of treatment, it was not in the last month. While alcohol intoxication was significantly associated with frequent switches, drug use was not associated with any adherence pattern. CONCLUSIONS: Consistent maintenance of adequate total dose adherence over the entire course of HCV treatment is important in achieving SVR among PWID. Additional integrative addiction and medical care may be warranted for treating PWID who experience alcohol intoxication.

Errors in the implementation, analysis, and reporting of randomization within obesity and nutrition research: a guide to their avoidance.

Randomization is an important tool used to establish causal inferences in studies designed to further our understanding of questions related to obesity and nutrition. To take advantage of the inferences afforded by randomization, scientific standards must be upheld during the planning, execution, analysis, and reporting of such studies. We discuss ten errors in randomized experiments from real-world examples from the literature and outline best practices for their avoidance. These ten errors include: representing nonrandom allocation as random, failing to adequately conceal allocation, not accounting for changing allocation ratios, replacing subjects in nonrandom ways, failing to account for non-independence, drawing inferences by comparing statistical significance from within-group comparisons instead of between-groups, pooling data and breaking the randomized design, failing to account for missing data, failing to report sufficient information to understand study methods, and failing to frame the causal question as testing the randomized assignment per se. We hope that these examples will aid researchers, reviewers, journal editors, and other readers to endeavor to a high standard of scientific rigor in randomized experiments within obesity and nutrition research.

Rates of perfect self-reported adherence to direct-acting antiviral therapy and its correlates among people who inject drugs on medications for opioid use disorder: The PREVAIL study.

Adequate adherence to direct-acting antivirals (DAAs) for hepatitis C virus (HCV) is critical to attaining sustained virologic response (SVR). In this PREVAIL study's secondary analyses, we explored the association between self-reported and objective DAAs adherence among a sample of people who inject drugs (PWID) receiving medications for opioid use disorder (MOUD) (N = 147). Self-reported adherence was recoded 3 times during treatment (weeks 4, 8 and 12) using a visual analog scale (VAS), whereas objective adherence was collected continuously during treatment using electronic blister packs. Participants who reported being perfectly adherent had significantly higher blister pack adherence in each period (weeks 4, 8 and 12; ps < .05) and over the 12-week study (p < .001) compared to those who reported being non-perfectly adherent. Whites were more likely to report perfect adherence (91.7%) than Blacks (48.7%), Latinos (52.2%) and other (75.0%) race groups. Participants who reported recent use of cocaine (63.9%) or polysubstance use (60.0%) and those who had a positive result for cocaine (62.8%) were more likely to be non-perfectly adherent, although none of these factors were associated with blister pack adherence. This study showed that the VAS could serve as a reliable option for assessing DAAs adherence among PWID on MOUD. The implementation of VAS may be an ideal option for monitoring adherence among PWID on MOUD, especially in clinical settings with limited resources. PWID on MOUD who are Black or other races than White, as well as those who report recent cocaine or polysubstance use may require additional support to maintain optimal DAA adherence.

Accounting for confounding by time, early intervention adoption, and time-varying effect modification in the design and analysis of stepped-wedge designs: application to a proposed study design to reduce opioid-related mortality.

BACKGROUND: Beginning in 2019, stepped-wedge designs (SWDs) were being used in the investigation of interventions to reduce opioid-related deaths in communities across the United States. However, these interventions are competing with external factors such as newly initiated public policies limiting opioid prescriptions, media awareness campaigns, and the COVID-19 pandemic. Furthermore, control communities may prematurely adopt components of the intervention as they become available. The presence of time-varying external factors that impact study outcomes is a well-known limitation of SWDs; common approaches to adjusting for them make use of a mixed effects modeling framework. However, these models have several shortcomings when external factors differentially impact intervention and control clusters. METHODS: We discuss limitations of commonly used mixed effects models in the context of proposed SWDs to investigate interventions intended to reduce opioid-related mortality, and propose extensions of these models to address these limitations. We conduct an extensive simulation study of anticipated data from SWD trials targeting the current opioid epidemic in order to examine the performance of these models in the presence of external factors. We consider confounding by time, premature adoption of intervention components, and time-varying effect modification- in which external factors differentially impact intervention and control clusters. RESULTS: In the presence of confounding by time, commonly used mixed effects models yield unbiased intervention effect estimates, but can have inflated Type 1 error and result in under coverage of confidence intervals. These models yield biased intervention effect estimates when premature intervention adoption or effect modification are present. In such scenarios, models incorporating fixed intervention-by-time interactions with an unstructured covariance for intervention-by-cluster-by-time random effects result in unbiased intervention effect estimates, reach nominal confidence interval coverage, and preserve Type 1 error. CONCLUSIONS: Mixed effects models can adjust for different combinations of external factors through correct specification of fixed and random time effects. Since model choice has considerable impact on validity of results and study power, careful consideration must be given to how these external factors impact study endpoints and what estimands are most appropriate in the presence of such factors.

Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy.

BACKGROUND: Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. METHODS: PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. RESULTS: Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). CONCLUSIONS: HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

Opioid Taper Is Associated with Subsequent Termination of Care: a Retrospective Cohort Study.

BACKGROUND: Opioid tapering is increasingly utilized by providers to decrease risks of chronic opioid therapy, but it is unknown whether tapering is associated with termination of care. OBJECTIVE: To determine whether patients taking chronic opioid therapy who experienced opioid tapers were at greater risk of subsequently terminating their care compared with those who were continued on their doses. DESIGN: Retrospective cohort study of patients in a large, urban health system between 2008 and 2012 with 2 years of follow-up. PARTICIPANTS: Adult patients prescribed a stable baseline dose of chronic opioid therapy of at least 25 morphine milligram equivalents per day during a baseline year. MAIN MEASURES: An opioid taper during an exposure year, defined as a reduction in the average daily dose of at least 30% from the baseline dose in both of the two 6-month periods in the year following the baseline year. Opioid dose continuation was defined as any increase in dose, no change in dose, or any decrease up to 30% compared with baseline dose in the exposure year. The primary outcome was termination of care, defined as no outpatient encounters in the health system, in the year following the exposure year. KEY RESULTS: Of 1624 patients on chronic opioid therapy, 207 (15.5%) experienced an opioid taper and 78 (4.8%) experienced termination of care. Compared with opioid dose continuation, opioid taper was significantly associated with termination of care (AOR 4.3 [95% CI 2.2-8.5]). CONCLUSIONS: Opioid taper is associated with subsequent termination of care. These findings invite caution and demonstrate the need to fully understand the risks and benefits of opioid tapers.

Factors and HCV treatment outcomes associated with smoking among people who inject drugs on opioid agonist treatment: secondary analysis of the PREVAIL randomized clinical trial.

BACKGROUND: Cigarette smoking has emerged as a leading cause of mortality among people with hepatitis C virus (HCV). People who inject drugs (PWID) represent the largest group of adults infected with HCV in the US. However, cigarette smoking remains virtually unexplored among this population. This study aimed at (1) determining prevalence and correlates of cigarette smoking among HCV-infected PWID enrolled in opiate agonist treatment programs; (2) exploring the association of smoking with HCV treatment outcomes including adherence, treatment completion and sustained virologic response (SVR); and 3) exploring whether cigarette smoking decreased after HCV treatment. METHODS: Participants were 150 HCV-infected PWID enrolled in a randomized clinical trial primarily designed to test three intensive models of HCV care. Assessments included sociodemographics, presence of chronic health and psychiatric comorbidities, prior and current drug use, quality of life, and HCV treatment outcomes. RESULTS: The majority of the patients (84%) were current cigarette smokers at baseline. There was a high prevalence of psychiatric and medical comorbidities in the overall sample of PWID. Alcohol and cocaine use were identified as correlates of cigarette smoking. Smoking status did not influence HCV treatment outcomes including adherence, treatment completion and SVR. HCV treatment was not associated with decreased cigarette smoking. CONCLUSIONS: The present study showed high prevalence of cigarette smoking among this population as well as identified correlates of smoking, namely alcohol and cocaine use. Cigarette smoking was not associated with HCV treatment outcomes. Given the detrimental effects that cigarette smoking and other co-occurring, substance use behaviors have on HCV-infected individuals' health, it is imperative that clinicians treating HCV also target smoking, especially among PWID. The high prevalence of cigarette smoking among PWID will contribute to growing morbidity and mortality among this population even if cured of HCV. Tailored smoking cessation interventions for PWID along with HCV treatment may need to be put into clinical practice. TRIAL REGISTRATION: NCT01857245 . Registered May 20, 2013.

Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial.

Background: Many people who inject drugs (PWID) are denied treatment for hepatitis C virus (HCV) infection, even if they are receiving opioid agonist therapy (OAT). Research suggests that HCV in PWID may be treated effectively, but optimal models of care for promoting adherence and sustained virologic response (SVR) have not been evaluated in the direct-acting antiviral (DAA) era. Objective: To determine whether directly observed therapy (DOT) and group treatment (GT) are more effective than self-administered individual treatment (SIT) in promoting adherence and achieving SVR among PWID receiving OAT. Design: Three-group, randomized controlled trial conducted from October 2013 to April 2017. (ClinicalTrials.gov: NCT01857245). Setting: Three OAT programs in Bronx, New York. Participants: Persons aged 18 years and older with genotype 1 HCV infection who were willing to receive HCV therapy on site in the OAT program. Of 190 persons screened, 158 were randomly assigned to a study group and 150 initiated treatment: DOT (n = 51), GT (n = 48), and SIT (n = 51). Intervention: 2 intensive interventions (DOT and GT) and 1 control condition (SIT). Measurements: Primary: adherence, measured by using electronic blister packs. Secondary: HCV treatment completion and SVR 12 weeks after treatment completion. Results: Mean age was 51 years; 65% of participants had positive results on urine drug testing during the 6 months before treatment, and 75% reported ever injecting drugs. Overall adherence, estimated from mixed-effects models using the daily timeframe, was 78% (95% CI, 75% to 81%) and was greater among participants randomly assigned to DOT (86% [CI, 80% to 92%]) than those assigned to SIT (75% [CI, 70% to 81%]; difference, 11% [CI, 5% to 18%]; Bonferroni-corrected P = 0.001). No significant difference in adherence was observed between participants randomly assigned to GT (80% [CI, 74% to 86%]) and those assigned to SIT (difference, 4.7% [CI, -2% to 11%]; Bonferroni-corrected P = 0.29). The HCV treatment completion rate was 97%, with no differences among groups (P = 0.53). Overall SVR was 94% (CI, 89% to 97%); the SVR rate was 98% in the DOT group, 94% in the GT group, and 90% in the SIT group (P = 0.152). Limitation: These findings may not be generalizable to PWID not enrolled in OAT programs. Conclusion: All models of onsite HCV care delivered to PWID in OAT programs resulted in high SVR, despite ongoing drug use. Directly observed therapy was associated with greater adherence than SIT. Primary Funding Source: National Institute on Drug Abuse and Gilead Sciences.