Scaling Up Hepatitis C Prevention and Treatment Interventions for Achieving Elimination in the United States: A Rural and Urban Comparison.
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SUBMITTER: Fraser H
PROVIDER: S-EPMC7415256 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Scaling Up Hepatitis C Prevention and Treatment Interventions for Achieving Elimination in the United States: A Rural and Urban Comparison.
Fraser Hannah H Vellozzi Claudia C Hoerger Thomas J TJ Evans Jennifer L JL Kral Alex H AH Havens Jennifer J Young April M AM Stone Jack J Handanagic Senad S Hariri Susan S Barbosa Carolina C Hickman Matthew M Leib Alyssa A Martin Natasha K NK Nerlander Lina L Raymond Henry F HF Page Kimberly K Zibbell Jon J Ward John W JW Vickerman Peter P
American journal of epidemiology 20190801 8
In the United States, hepatitis C virus (HCV) transmission is rising among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modeling, we investigated the impact of scaling up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky, and San Francisco, California, where HCV seroprevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service program ...[more]
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Project description:Background:The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods:We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results:With no further treatment (currently ?150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions:Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan's HCV burden will increase markedly.
| S-EPMC5913612 | biostudies-literature
Project description:BACKGROUND AND AIMS:Effective strategies are needed to address dramatic increases in hepatitis C virus (HCV) infection among people who inject drugs (PWID) in rural settings of the United States. We determined the required scale-up of HCV treatment with or without scale-up of HCV prevention interventions to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025 and 2030 in a rural US setting. DESIGN:An ordinary differential equation model of HCV transmission calibrated to HCV epidemiological data obtained primarily from an HIV outbreak investigation in Indiana. SETTING:Scott County, Indiana (population 24?181), USA, a rural setting with negligible baseline interventions, increasing HCV epidemic since 2010, and 55.3% chronic HCV prevalence among PWID in 2015. PARTICIPANTS:PWID. MEASUREMENTS:Required annual HCV treatments per 1000 PWID (and initial annual percentage of infections treated) to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025/30, either with or without scaling-up syringe service programmes (SSPs) and medication-assisted treatment (MAT) to 50% coverage. Sensitivity analyses considered whether this impact could be achieved without re-treatment of re-infections, and whether greater intervention scale-up was required due to the increasing epidemic in this setting. FINDINGS:To achieve a 90% reduction in incidence and prevalence by 2030, without MAT and SSP scale-up, 159 per 1000 PWID (initially 24.9% of infected PWID) need to be HCV-treated annually. However, with MAT and SSP scaled-up, treatment rates are halved (89 per 1000 annually or 14.5%). To reach the same target by 2025 with MAT and SSP scaled-up, 121 per 1000 PWID (19.9%) need treatment annually. These treatment requirements are threefold higher than if the epidemic was stable, and the impact targets are unattainable without retreatment. CONCLUSIONS:Combined scale-up of hepatitis C virus treatment and prevention interventions is needed to decrease the increasing burden of hepatitis C virus incidence and prevalence in rural Indiana, USA, by 90% by 2025/30.
| S-EPMC6211174 | biostudies-literature
Project description:BackgroundThe revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.MethodsWe developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions.FindingsBy 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0-15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000-670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8-16·1) new infections and 1·5 million (1·4-1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78-82) reduction in incidence and a 61% (60-62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan.InterpretationFurther improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic.FundingWellcome Trust.
| S-EPMC6484702 | biostudies-literature
Project description:Chronic diseases are increasingly becoming a health burden in lower- and middle-income countries, putting pressure on public health efforts to scale up interventions. This article reviews current efforts in interventions on a population and individual level. Population-level interventions include ongoing efforts to reduce smoking rates, reduce intake of salt and trans-fatty acids, and increase physical activity in increasingly sedentary populations. Individual-level interventions include control and treatment of risk factors for chronic diseases and secondary prevention. This review also discusses the barriers in interventions, particularly those specific to low- and middle-income countries. Continued discussion of proven cost-effective interventions for chronic diseases in the developing world will be useful for improving public health policy.
| S-EPMC3686269 | biostudies-other
Project description:BackgroundDiarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated.Methods and findingsWe use the Lives Saved Tool (LiST) to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding) were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions) and universal (assumes near 100% coverage of all interventions) scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions.ConclusionUsing currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations' Millennium Development Goal 4 (MDG4) by 2015.
| S-EPMC3062532 | biostudies-literature
Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.
2015-10-26 | GSE53522 | GEO
Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/µl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.
2015-10-26 | E-GEOD-53522 | biostudies-arrayexpress
Project description:Online education is rapidly expanding in response to rising demand for higher and continuing education, but many online students struggle to achieve their educational goals. Several behavioral science interventions have shown promise in raising student persistence and completion rates in a handful of courses, but evidence of their effectiveness across diverse educational contexts is limited. In this study, we test a set of established interventions over 2.5 y, with one-quarter million students, from nearly every country, across 247 online courses offered by Harvard, the Massachusetts Institute of Technology, and Stanford. We hypothesized that the interventions would produce medium-to-large effects as in prior studies, but this is not supported by our results. Instead, using an iterative scientific process of cyclically preregistering new hypotheses in between waves of data collection, we identified individual, contextual, and temporal conditions under which the interventions benefit students. Self-regulation interventions raised student engagement in the first few weeks but not final completion rates. Value-relevance interventions raised completion rates in developing countries to close the global achievement gap, but only in courses with a global gap. We found minimal evidence that state-of-the-art machine learning methods can forecast the occurrence of a global gap or learn effective individualized intervention policies. Scaling behavioral science interventions across various online learning contexts can reduce their average effectiveness by an order-of-magnitude. However, iterative scientific investigations can uncover what works where for whom.
| S-EPMC7334459 | biostudies-literature
Project description:Opioid misuse is a public health crisis in the United States. The origin of this crisis is associated with a sharp increase in opioid analgesic prescribing. We used the urban scaling framework to analyze opioid prescribing patterns in US commuting zones (CZs), i.e., groups of counties based on commuting patterns. The urban scaling framework postulates that a set of scaling relations can be used to predict health outcomes and behaviors in cities. We used data from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System (ARCOS) to calculate counts of oxycodone/hydrocodone pills distributed to 607 CZs in the continental US from 2006 to 2014. We estimated the scaling coefficient of opioid pill counts by regressing log(pills) on log(population) using a piecewise linear spline with a single knot at 82,363. Our results show that CZs with populations below the knot scaled superlinearly (β = 1.36), i.e., larger CZs had disproportionally larger pill counts compared to smaller CZs. On the other hand, CZs with populations above the knot scaled sublinearly (β = 0.92), i.e., larger CZs had disproportionally smaller pill counts compared to smaller CZs. This dual scaling pattern was consistent across US census regions. For CZs with population below the knot, the superlinear scaling of pills is consistent with the explanation that an increased number of successful matches between prescribers and users will lead to higher prescribing rates. The non-linear scaling behavior observed could be the result of a combination of factors, including stronger health care systems and prescribing regulation in largely populated commuting zones, as well as high availability of other opioids such as heroin in these commuting zones. Future research should explore potential mechanisms for the non-linearity of prescription opioid pills.
| S-EPMC8509933 | biostudies-literature
Project description:AimsTo examine the cost-effectiveness of hepatitis C virus (HCV) treatment of people who inject drugs (PWID), combined with medication-assisted treatment (MAT) and syringe-service programs (SSP), to tackle the increasing HCV epidemic in the United States.DesignHCV transmission and disease progression models with cost-effectiveness analysis using a health-care perspective.SettingRural Perry County, KY (PC) and urban San Francisco, CA (SF), USA. Compared with PC, SF has a greater proportion of PWID with access to MAT or SSP. HCV treatment of PWID is negligible in both settings.ParticipantsPWID data were collected between 1998 and 2015 from Social Networks Among Appalachian People, U Find Out, Urban Health Study and National HIV Behavioral Surveillance System studies.Interventions and comparatorThree intervention scenarios modeled: baseline-existing SSP and MAT coverage with HCV screening and treatment with direct-acting antiviral for ex-injectors only as per standard of care; intervention 1-scale-up of SSP and MAT without changes to treatment; and intervention 2-scale-up as intervention 1 combined with HCV screening and treatment for current PWID.MeasurementsIncremental cost-effectiveness ratios (ICERs) and uncertainty using cost-effectiveness acceptability curves. Benefits were measured in quality-adjusted life-years (QALYs).FindingsFor both settings, intervention 2 is preferred to intervention 1 and the appropriate comparator for intervention 2 is the baseline scenario. Relative to baseline, for PC intervention 2 averts 1852 more HCV infections, increases QALYS by 3095, costs $21.6 million more and has an ICER of $6975/QALY. For SF, intervention 2 averts 36 473 more HCV infections, increases QALYs by 7893, costs $872 million more and has an ICER of $11 044/QALY. The cost-effectiveness of intervention 2 was robust to several sensitivity analysis.ConclusionsHepatitis C screening and treatment for people who inject drugs, combined with medication-assisted treatment and syringe-service programs, is a cost-effective strategy for reducing hepatitis C burden in the United States.
| S-EPMC7751348 | biostudies-literature