Conceptualizing Care Continua: Lessons from Hiv, Hepatitis C virus, Tuberculosis and implications for the Development of Improved Care and Prevention Continua

Background: To examine the application of continuum models to tuberculosis, HIV, and other conditions; to theorize the concept of continua; and to learn lessons that could inform the development of improved care and prevention continua as public health metrics. Methods: An analytic review of literature drawn from several fields of health care. Results: The continuum construct is now part of public health evaluation systems for HIV, and is increasingly used in public health and the medical literature. Issues with the comparability and optimal design of care continuum models have been raised, and their methodologic and theoretic underpinnings and scope of focus have been underaddressed. Review of relevant publications suggests that a key limitation of current models is their lack of measures reflecting incidence and mortality. Issues relating to continua data being longitudinal or cross-sectional, definition of numerators and denominators for each step, data sources, measures of timeliness of step completion, theoretic models to facilitate inferences of causes of care continuum gaps, how measures of prevention efforts, reinfection/relapses, and interactions of continua for co-occurring comorbidities should be reflected, and how analyses of differences in retention over time, across geographic regions, and in response to interventions should be conducted are critical to the development of sound care and prevention continuum models. Conclusion: Lessons learned from the application of continuum models to HIV and other conditions suggest that the application of well-formulated constructs of care and prevention continua, that depict, in well defined, standardized steps, incidence and mortality, along with degrees of and time to screening, engagement in care and prevention, treatment and treatment outcomes, including relapse or reinfection, may be vital tools in evaluating intervention and program outcomes, and in improving population health and population health metrics for a wide range conditions

Past-year prevalence of prescription opioid misuse among those 11 to 30

AbstractBackgroundThere are high levels of prescription and consumption of prescription opioids in the US. Misuse of prescription opioids has been shown to be highly correlated with prescription opioid-related morbidity and mortality including fatal and non-fatal overdose. We characterized the past-year prevalence of prescription opioid misuse among those 11–30years of age in the US.MethodsA systematic review and meta-analysis were carried out following a published protocol and PRISMA guidelines. We searched electronic databases; reports were eligible if they were published between 1/1/1990–5/30/2014, and included data on individuals 11–30years of age from the US. Study quality was assessed using the Newcastle-Ottawa Scale.ResultsA total of 3211 abstracts were reviewed for inclusion; after discarding duplicates and identifying non-eligible reports, a total of 19 unique reports, providing 34 estimates, were included in the final systematic review and meta-analysis. The range of past-year prescription opioid misuse prevalence the reports was 0.7%–16.3%. An increase in prevalence of 0.4% was observed over the years of data collection.ConclusionsThis systematic review and meta-analysis found a high prevalence of past-year prescription opioid misuse among individuals 11–30years of age. Importantly, we identified an increase in past-year prevalence 1990–2014. Misuse of prescription opioids has played an important role in national increases of fatal and non-fatal drug overdose, heroin use and injection, and HIV and HCV infection among young people. The observed high and increasing prevalence of prescription opioid misuse is an urgent public health issue

The Impact of eHealth on the Quality and Safety of Health Care: A Systematic Overview

Aziz Sheikh and colleagues report the findings of their systematic overview that assessed the impact of eHealth solutions on the quality and safety of health care

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Novel Hepatitis C Virus (HCV) Community Viral Load Measures, HCV Incidence and Prevalence, and HCV Prevention by Methadone Maintenance

Abstract Introduction The incidence of Hepatitis C virus (HCV) infection has increased in the current opioid epidemic in the United States; current estimates are that 2-3 million Americans have HCV infection. The ongoing and increasing HCV epidemic among people who use drugs (PWUD) is occurring in the context of known HCV prevention and highly efficacious and well-tolerated curative HCV treatment. The development of direct acting antivirals (DAAs) with cure rates approaching 100% dramatically changed the treatment landscape. This provides both the potential for improved individual- and population-level treatment effectiveness, and also the potential for population-level HCV ‘cure as prevention\u27 (CasP) (a key component of combined prevention) and consideration of the goal of HCV elimination. Medication assisted treatment (MAT) for opioid use disorder (OUDs) is another important component of combined HCV prevention. However, the impact of specific MAT program factors on HCV incidence remain underexplored. Assessments of the HCV care continuum have identified large gaps in the sequential steps of HCV prevention and care. Community viral load (CVL) is a measure that has been developed to aide HIV surveillance and control but has not been developed for HCV surveillance despite many commonalities between HIV and HCV with respect to transmission, prevention and treatment. Hence, novel measures of HCV CVL merit study as predictors to identify vulnerable areas and populations, and as predictors of incidence, to help focus implementation of prevention and treatment and resources. This dissertation examines outcomes of the HCV care continuum, and factors associated with linkage to HCV treatment, among PWUD in MAT, proposes novel HCV CVL measures, and examines HCV incidence, and individual-level factors associated with incidence, and the association of HCV CVL with area-level HCV incidence in an open cohort of patients receiving MAT. Methods Paper 1: A systematic review was conducted to identify conceptual and empirical applications of CVL constructs to HCV epidemiology. Using the published literature on HCV epidemiology and the HIV CVL literature, this Paper conceptualized and defined a set of HCV CVL measures constructed to address specific questions for defined populations. Papers 2 and 3: This is an observational retrospective study of an open cohort of people receiving MAT in the form of methadone for OUDs at the Mount Sinai Health System (MSHS) opioid treatment program (OTP) in New York City (NYC), the largest not-for-profit OTP in the US. The study period is 2013-2016. Paper 2: Data from patients were used to: 1) identify HCV care continuum outcomes (antibody and viral load (VL) testing; linkage-to-care; treatment receipt; and cure), 2) operationalize, calculate and examine geographic variation in engaged-in-care HCV CVLs, 3) calculate both documented and estimated unmet testing and treatment need, and 4) examine factors associated with linkage-to-HCV-care in the current era of DAAs and after implementation of qualitative reflex VL testing. Paper 3: HCV incidence was calculated among those HCV antibody tested \u3e2 times. HCV CVL was calculated among those with documented, active infection overall and by geographic area of residence. Incidence rates, incidence rate ratios, and associated factors overall and among specific subgroups were examined. Kaplan-Meier and Cox proportional hazard models were used to assess time-to-HCV-seroconversion. Results Paper 1: The systematic review found that there were no published studies either conceptualizing or applying CVL measures to HCV identifying this as an important gap in the literature. Five novel HCV CVL measures were conceptualized, using the literature on HCV epidemiology and the literature applying CVL to HIV epidemiology. This paper makes a novel and substantive contribution to the literature by developing CVL measures applicable to HCV epidemiology. This set of HCV CVL measures could be utilized to address diverse questions relevant to HCV control. One HCV CVL measure (‘engaged-in-care’) was identified to be calculated and examined further in Papers 2 and 3. Paper 2: The study included 11,267 patients. Proportions of those HCV antibody tested (52.5% -vs. 73.3%), linked to HCV care (15.7% vs 51.8%), and receiving HCV treatment (12.0% vs 44.7%) all increased significantly in 2015-16 compared with 2013-14 after implementation of on-site qualitative reflex VL testing. Hispanic ethnicity was associated with lower linkage to HCV care and Manhattan residence was associated with better linkage to care. The engaged-in-care HCV CVL measure was 6.06 log10 copies/milliliter (standard deviation: 0.926) and varied significantly by demographic subgroups and geography. Documented unmet treatment need among those engaged in care decreased significantly (88.0% vs. 55.0%) but remained high; estimated unmet treatment need among the entire study population was higher still (99.1% vs 86.0%). Paper 3: Among 8,352 patients tested, HCV prevalence was 48.7%. Among 2,535 patients seronegative at first antibody test, HCV incidence was 2.25/100 person-years of observation (PYO). Incidence was 6.70/100 PYO among those reporting main drug use by injection. Female gender, drug injection, and lower MAT retention were significantly associated with higher incidence. Female gender, drug injection and methadone doses log10 increase in HCV CVL, the HCV incidence rate was expected to be multiplied by about 2.7; although this association was not statistically significant, these results suggest the importance of further research on this association. Discussion This dissertation demonstrates that HCV CVL measures can be constructed and that there are significant area-level disparities in HCV CVL. My data suggest that measures of HCV CVL may be valuable in geographically focusing prevention and treatment efforts and that HCV CVL measures merit further study as potential predictors of HCV incidence. Analyses identified significant gaps in the HCV care continuum steps of testing, linkage-to-care, and treatment. Further improvements in rates of complete testing are needed and broader implementation of HCV reflex testing may be valuable. More effective linkage to care interventions are needed generally and particularly for those of Hispanic ethnicity. While during the study period the proportion HCV treated increased significantly, there were still very high rates of unmet treatment need suggesting that HCV control will require significant expansion of HCV treatment. The incidence rates observed support recommendations for annual HCV testing of all those in MAT, not only those who report injecting drugs. Data highlight the need for efforts to improve MAT retention and ensure adequate dosing. Further studies of and efforts to address identified sex disparities are needed. Area-level HCV CVL measures may be valuable to geographically focus prevention and treatment efforts and merit further study as predictors of incidence. PWUD engaged in MAT continue to be at risk for HCV infection. The large reservoir of PWUD chronically infected with HCV, and persistently high HCV incidence rates, reinforce the need for vigorous efforts to improve HCV care continuum outcomes and ensure access to high-quality MAT. Efforts to expand HCV treatment access and engagement are essential to promote HCV CasP and achieve HCV control among PWUD

Patterns and Gaps Identified in a Systematic Review of the Hepatitis C Virus Care Continuum in Studies among People Who Use Drugs

IntroductionSystematic reviews are useful for synthesizing data on various health conditions and for identifying gaps in available data. In the US, the main risk group for hepatitis C virus (HCV) infection is people who use drugs (PWUD); as a group, PWUD have the highest prevalence of chronic HCV. While the care continuum construct has been increasingly applied to studies of HCV care among PWUD, what constitutes the steps in an HCV care continuum is not standardized. We sought to examine the range of HCV care continuum outcomes that studies reported on, to identify gaps in the literature, and to develop strategies that allowed for valuable syntheses of care continuum data.MethodsWe conducted searches of electronic databases for published literature. Reports were eligible if they provided original data from 1990 to 2016 from the US, presented data on one or more HCV care continuum outcomes, and provided outcome data on PWUD as a distinct group.ResultsA total of 313 full-text reports were assessed for eligibility. Of 212 potentially eligible reports, 32 (15.1%) did not present outcomes for PWUD separately from those who were non-PWUD. Among 101 eligible reports, a total of 166 care continuum outcomes were extracted; outcomes could be grouped into three categories that represent the HCV care continuum: testing (39.8%, n = 66/166); linkage to care (16.9%, n = 28/166); and treatment (43.4%, n = 72/166). Seventy-four reports (73.3%, n = 74/101) presented data on only one step. Linkage to care occurred variably after only antibody, or after antibody and viral load (VL) testing. Six (5.9%, n = 6/101) reports presented data on all three steps.ConclusionReports examined a variety of HCV care continuum outcomes that could be grouped into the three steps of testing, linkage to care, and treatment. The application of this care continuum model would facilitate subsequent data synthesis for program comparison and public health evaluation. Given the two-step nature of HCV testing, analyses also need to account for variation in whether linkage to care occurred after antibody testing or after sequential antibody and VL testing. Additional data are needed on the progression of PWUD through the entire care continuum

Understanding Vaccine Perceptions and Willingness to Receive COVID-19 Vaccination: Opportunities to Strengthen Public Health Responses and COVID-19 Services for People Who Use Drugs

Background: People who use drugs (PWUD) are at high risk for COVID-19 infection, morbidity, and mortality. COVID-19 vaccines are safe and effective at reducing serious illness and death from COVID-19. There are sparse data on the perceptions and willingness of PWUD to receive COVID-19 vaccination. Materials and Methods: In order to assess the perceptions of, and willingness to receive, COVID-19 vaccination among PWUD, we conducted a rapid survey-based assessment of 100 PWUD in NYC (Spring 2021) who reported not having received COVID-19 vaccination and who reported past 30-day illicit drug use. Results: More than 80% of respondents agreed that personally receiving a COVID-19 vaccine was important for the health of others in the community, and endorsing this belief was significantly associated with COVID-19 vaccine willingness reflecting a high prevalence of altruistic beliefs (p-value: 0.01). Other reported perceptions that were significantly associated with COVID-19 vaccine willingness were believing that COVID-19 vaccines are safe for PWUD and trusting COVID-19 information from their healthcare providers (p-values < 0.05). That said, 62% reported being unwilling to receive a COVID-19 vaccine, and 70–83% had concerns about general vaccine safety/efficacy. Examining pairs of questions to explore potential ambivalence between vaccine endorsement and vaccine concerns identified that 56–65% simultaneously reported vaccine safety/efficacy concerns and beliefs that vaccination was an important intervention. Of the 75 respondents who reported past 30-day use of harm reduction and/or substance use disorder (SUD) programs, nearly 90% reported these programs as trusted sources of COVID-19 information. Conclusion: Most participants reported altruistic beliefs about the role of vaccines for community health, including COVID-19 vaccines, and this altruism was associated with willingness to be vaccinated against COVID-19. These findings suggest a complex relationship between beliefs about the role of vaccination in community health and the safety/efficacy of vaccines; this ambivalence suggests that COVID-19 vaccine willingness may not be firmly fixed, indicating potential opportunities to address questions and build vaccine confidence. Harm reduction and SUD programs could be leveraged to further engage PWUD in receipt of COVID-19 information and/or vaccination. Recognizing vaccine ambivalence, emphasizing collective and individual benefits of vaccination, and messaging from trusted sources may be promising approaches to increase vaccination in this population

Hepatitis C virus infection among HIV-positive men who have sex with men: protocol for a systematic review and meta-analysis

Background: Outbreaks of hepatitis C virus (HCV) infection have been reported in HIV-positive men who have sex with men (MSM) in North America, Europe and Asia. Transmission is believed to be the result of exposure to blood during sexual contact. In those infected with HIV, acute HCV infection is more likely to become chronic, treatment for both HIV and HCV is more complicated and HCV disease progression may be accelerated. There is a need for systematic reviews and meta-analyses to synthesize the epidemiology, prevention and methods to control HCV infection in this population. Methods/design: Eligible studies will include quantitative empirical data related to sexual transmission of HCV in HIV-positive MSM, including data describing incidence or prevalence, and associations between risk factors or interventions and the occurrence or progression of HCV disease. Care will be taken to ensure that HCV transmission related to injection drug use is excluded from the incidence estimates. Scientific databases will be searched using a comprehensive search strategy. Proceedings of scientific conferences, reference lists and personal files will also be searched. Quality ratings will be assigned to each eligible report using the Newcastle–Ottawa scale. Pooled estimates of incidence rates and measures of association will be calculated using random effects models. Heterogeneity will be assessed at each stage of data synthesis. Discussion: HIV-positive MSM are a key HCV-affected population in the US and other high-income countries. This review seeks to identify modifiable risk factors and settings that will be the target of interventions, and will consider how to constitute a portfolio of interventions to deliver the greatest health benefit. This question must be considered in relation to the magnitude of HCV infection and its consequences in other key affected populations, namely, young prescription opioid users who have transitioned to illicit opiate injection, and older injection drug users among whom HCV prevalence and incidence are extremely high. This review is part of a series of systematic reviews and meta-analyses that will synthesize the evidence across all these population groups and develop recommendations and decision tools to guide public health resource allocation. Trial registration: PROSPERO registration number: CRD4201300646