Impact of integrated treatment of hepatitis C on happiness among people who inject drugs: results from the INTRO-HCV.

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Clara Lucas, Jørn Henrik Vold, Christer Frode Aas, Fatemeh Chalabianloo, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4000705/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract PWID are at high risk of being unhappy. However, to which degree happiness in patients with SUD is linked to infection with HCV and its treatment is unknown. The present study investigated the effect of integrated compared to standard HCV treatment on happiness in this population. This multi-center, randomized controlled trial evaluated happiness as a secondary outcome of integrated HCV treatment. From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient OAT clinics and two community care centers while standard treatment was delivered in outpatient clinics at referral hospitals, with 21% absolute difference in SVR. The level of happiness was assessed with an eleven-point Likert scale and presented as percentage (from 0% “completely unhappy” to 100% “completely happy”) . We applied a LMM to evaluate the impact of integrated HCV treatment on changes in happiness scores. At baseline, the mean happiness score for participants receiving integrated treatment was 49% (SD 26) and 52% (SD 25) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean happiness score for participants receiving integrated treatment was 51% (SD 20) and 52% (SD 23) for those receiving standard treatment. Compared to the standard HCV treatment, the happiness score tends to increase from baseline to end of treatment in the integrated HCV treatment groups, but not significantly. Further research is needed to improve the subjective experience in happiness in this population. Trial registration ClinicalTrials.gov.no NCT03155906, 16/05/2017. Substance-Related Disorders Happiness Hepatitis C Chronic Figures Figure 1 Figure 2 Introduction There is a strong relationship between health and happiness. Good health is linked to higher levels of happiness, and causality seems to run in both directions. 1,2 Happiness is defined as the subjective enjoyment of one’s life as a whole. 3 The average of happiness in the general population for 2022, based on 134 countries, was 55 out of 100, where 0 indicates extremely unhappy. 4 A decrease in happiness could be caused by the determinants of physical and mental health such as depression, poor perception of health and addiction in general population. 5,6 The level of happiness is lower in patients with chronic diseases, such as patients with psoriasis who report 53 out of 100 7 or multiple sclerosis, 46 out of 100. 8 Patients with substance use disorders (SUD) are also at high risk of being unhappy. In recent studies among patients with SUD receiving opioid agonist therapy (OAT), happiness has a been reported as 38 out of 100. 9 This might be even lower in patients with SUD and hepatitis C virus (HCV) infection, reflecting a two-hit vulnerability for unhappiness Globally, an estimated 71 million people are living with chronic HCV (HCV RNA positive) 10 HCV is the cause of severe comorbidities and impairments such as liver cirrhosis, resulting in an increased risk of liver failure, hepatocellular carcinoma and premature death. 11 Among people with HCV, about a third develop severe hepatic complications within three decades. 12 Besides, HCV and hepatitis B are among the leading causes of liver disease and transplantation worldwide. 13 Norway is a low-prevalence country in this respect regarding general population, but the burden of HCV infection is disproportionately high among people who inject drugs (PWID). Anti-HCV antibody prevalence in PWID is estimated to be greater than 60%. 14 Patients with chronic HCV have a significantly higher risk of end-stage liver diseases compared with those without a SUD. 15 Several studies demonstrate increased cirrhosis and liver-related mortality 25–30 years after HCV transmission in PWID. 16,17 Since 2014, the availability of potent direct-acting antiviral therapies (DAAs) has provided an opportunity to reverse the rising burden of HCV-related complications with high rates (> 80%) of sustained virological response (SVR). 18 Today, patients can be treated using direct-acting antivirals (DAAs) that can cure most patients with only 8–12 weeks of therapy with adverse event. 19 However, the access to patients with SUD and HCV is complex, and they have until recently been undertreated. 15 Adherence to OAT varies considerably, and may affect their chances of initiating HCV treatment. In a previous study from the INTRO-HCV trial, integrated HCV and addiction treatments involving decentralized outpatient clinics with multidisciplinary teams and close follow-up improved the sustained virological response (SVR) for PWIDs to 93% compared to standard HCV treatment with 73% SVR rates. 20 Furthermore, the INTRO-HCV trial showed that the treatment initiation rate was 98% among participants who received integrated HCV treatment, compared to 77% among those who received standard HCV treatment. Assessing and improving happiness during HCV care may ultimately lead to improved adherence to treatment and general health and reduce treatment dropouts and liver-related costs. This randomized controlled trial investigated the impact of integrated HCV infection treatment on happiness scale (HS) among PWIDs receiving oral direct-acting antivirals (DAAs) in western Norway to evaluate the effect of treatment on happiness. Even though the trial has not randomized to HCV treatment or not which would have been ethical, the 20% absolute difference in SVR will provide an opportunity to assess whether HCV treatment itself is linked to change in happiness (with a “compressed” scale). Methods Design and setting The INTRO-HCV trial is a multi-center, randomized controlled trial (ClinicalTrials.gov.no, Reference NCT03155906). 20 This study evaluated happiness as a secondary outcome of the INTRO-HCV trial. We recruited PWIDs with chronic HCV infection who were eligible for HCV treatment with DAAs in accordance with Norwegian HCV treatment guidelines (Additional file 1). Participants were recruited from eight outpatient clinics providing opioid agonist therapy (OAT) in Bergen and Stavanger, Norway, as well as two community care centers (CCCs) in Bergen providing primary healthcare to PWIDs. Enrolment was conducted from May 2017 to June 2019. For a more comprehensive description, a published protocol and the primary outcome measures of the study are available. 20,21 Ethics approval and consent to participate The present study was reviewed and approved by the Regional Ethical Committee for Health Research (REC) West, Norway (reference number: 2017/51/REK Vest). All recruited participants were informed about the study, and provided written informed consent was provided before their inclusion and randomization. Measurement We measured the level of happiness during the study period using the happiness scale (HS). The HS is a self-reported scale composed of a question on " How happy are you with your life these days? ”. The response options were denoted with numbers from 0 to 10. We present HS scores converted to a percentage scale from min-to-max (0% indicating “completely unhappy” and 100% indicating “completely happy”) Interventions In total, 289 participants were included in the study – 145 in the integrated treatment group and 144 in the standard treatment group. (For detailed information on the intervention, inclusion and exclusion criteria, sociodemographic and clinical characteristics of participants, see Table 1 and Additional File 2). The trial profile for the study is shown in Figure 1. (Figure 1 should appear in this part of the manuscript) Participants in the standard HCV treatment group were referred to the centralized outpatient infectious disease clinic at the collaborating referral hospital for HCV treatment. They were responsible for retrieving and adhering to their prescriptions, and attending assessment appointments. In addition, participants met at OAT clinics or CCCs to assess their levels of happiness. All assessments and medications for participants in the integrated treatment groups were provided onsite at the OAT clinics or CCCs, including DAAs, blood samples, and HS assessments. Compared with participants in the standard treatment group, participants in the integrated treatment group had no follow-ups in the referral hospital, and they received all assessments and medications at the local OAT clinics or CCC. Contrary to standard HCV treatment, all HCV treatment was given in parallel with the observed intake of OAT medications and other care, in line with the study protocol. (For detailed information on the standard and integrated treatment, see Additional File 2). Data collection Participants were evaluated prior to HCV treatment and at 12 weeks after the end of treatment (EOT12) to record their health status, including the level of happiness according to the HS score, sociodemographic data, current drug use, blood samples, transient elastography, and clinical examination. The health assessments were conducted by specialized research nurses in close collaboration with the clinics’ consultants in addiction medicine and infectious diseases. A medical team followed up with those who did not meet the criteria for inclusion in the study. Data from the health assessments prior to and after HCV treatment were defined as the study’s baseline and EOT12 (endpoint), respectively. (For detailed information on randomization and masking, measurements and statistical analyses, see Additional File 2.) Results Characteristics at baseline The characteristics of the participants were similar between both arms, Table 1. HCV genotype 3 was most prevalent, observed among 64% of participants in the integrated HCV treatment group and 60% in the standard HCV treatment group. (Table 1 should appear in this part of the manuscript) HS scores at baseline and EOT12 At baseline, the mean HS score for participants in the integrated HCV treatment arm was 49% (standard deviation (SD) 26) and 52% (SD 25) in the standard HCV treatment arm. At EOT12, the mean HS score for participants receiving integrated HCV treatment was 51% (SD 20) and 52% (SD 23) for those receiving standard HCV treatment. (For detailed information on the HS scores at baseline and EOT12, see Table 2, Additional file 3). The impact of integrated HCV treatment on change in the HS Integrated HCV treatment was, compared to standard HCV treatment, not significantly associated with HS, but a non-significant trend was seen with slightly more increase in happiness from baseline to EOT12 in integrated compared to standard HCV treatment (ΔHS score 3 (95% CI: -2; 8) (Additional file 4, 5, 6, 7 and 8) (intention-to-treat and per protocol analyses). Compared to the standard HCV treatment, the happiness score tends to increase from baseline to EOT12 in the integrated HCV treatment groups, but not significantly (Figure 2). (Figure 2 should appear in this part of the manuscript). Moreover, we observed substantial interindividual variabilities in HS values from baseline to EOT12 in both positive and negative directions in both groups (Additional file 5). Likewise, per protocol and sensitivity analyses without computed data showed similar results (Additional files 9 and 10). Achieving SVR was not associated with changes in the HS score from baseline to EOT12, adjusted for sociodemographic factors, injecting drug use, and types of drugs used (Additional files 11 and 12). Discussion This trial showed a no significant changes in happiness among those receiving integrated compared to standard HCV treatment. However, it should be noted that the differences in SVR rates between these two arms were 20% (absolute differences), and thus the differences related to successful HCV treatment compared to no treatment might be five times as high, and could potentially have been significantly different. However, randomising to integrated versus no treatment would not be ethical. If the trend was scaled to treatment versus no treatment (i.e., five times our observed differences), the estimated improvement in happiness might have been in the range of 10%. To our knowledge, this is the first trial conducted in outpatient OAT clinics and CCCs to investigate the impact of integrated HCV treatment on happiness among PWIDs. There is little literature regarding happiness in patients with SUD and HCV. A qualitative study examining an integrated infectious diseases/SUD treatment program showed that even if HCV was cured, this did not seem to affect the wellbeing of patients. 30 One possible explanation might be that HCV infection can be asymptomatic for many years and some patients will even progress through life without ever developing symptoms. 12,18 For those patients without severe symptoms, not perceiving substantial changes in health might not affect their level of happiness. Furthermore, there is a lack of information concerning the risks and consequences of having HCV among PWID. 14 As a consequence, having HCV and, correspondingly, achieving SVR might not influence their level of happiness. Yet, even if their physical health improves, SUD patients still have to deal with other complex situations such as underlying mental disorders and extensive polysubstance use. 6 More than half of the participants who received the integrated treatment injected drugs during the past 12 months. Despite achieving SVR, other comorbidities such as substance use and extensive injected use may affect their level of happiness. 3 In 2022, data from the Norwegian general population indicated a three-year-average happiness score of 73 out of 100, 4 while patients with SUD and HCV in our cohort reported considerably lower mean scores; 49 for those receiving integrated treatment and 52 for those receiving standard treatment. SUD entails lifelong struggles with substance use and HCV treatment might not be a priority for these patients. This is consistent with other studies in PWID, and that achieving HCV treatment is often linked with improvement in physical health, but not similarly to mental health symptoms. 31 The integrated and standard treatment groups demonstrated substantial intraindividual variation in levels of happiness over time. Considering happiness as an emotional state linked to one´s physiological reactions to life events, 5 it can be assumed that the intra-individual variations in the present study might be attributable to comorbidities and complexities among substance users. 7,10,14 Nevertheless, future research should examine possible causes of the changes in happiness scores not only in SUD patients with HCV, but in other populations as well. Recovery from dependence is a long-term process during which several life domains, and correspondingly, the perception of happiness, might change over time. 32 Assessing the levels of happiness over longer time periods, rather than a 24-week follow-up, could allow a more accurate knowledge of the long-term benefits or, alternatively, adverse effects of different treatments regimens in patients with SUD and HCV. Happiness might be an important marker of the combined outcomes that really matter for the individual patients and might serve to evaluate the long-term effectiveness of treatments. Still, less is known about the subjective experience in happiness in this population and further research is needed to develop tools for the elimination of hepatitis C infection among PWIDs. Another strength of this study is its trial design of individual randomization with balanced groups, which minimizes potential confounding and bias. Furthermore, we included PWIDs who is generally hard-to-reach. A limitation is that 32% of participants had missing data on HS at EOT12. Conclusions The present study demonstrated that integrated HCV treatment did not significantly improve happiness among PWIDs, but there were non-significant positive trends. Nevertheless, integrated treatment of HCV has other documented advantages and as no negative change was seen for happiness, there are still good arguments to integrate treatment of HCV among people who inject drugs. Abbreviations SUD: Substance use disorders OAT: Opioid agonist therapy HCV: Hepatitis C virus PWID: People who inject drugs DAA: Direct-acting antiviral therapies SVR: Sustained virological response HS: Happiness scale CCC: Community care centers REC: Regional ethical committee EOT12­: at 12 weeks after the end of treatment (EOT12) SD: Standard deviation ΔHS: Changes in happiness scores Declarations Ethics approval and consent to participate The present study was reviewed and approved by the Regional Ethical Committee for Health Research (REC) West, Norway (reference number: 2017/51/REK Vest). All recruited participants were informed about the study, and provided written informed consent was provided before their inclusion and randomization. Consent for publication Participants have consented for publication. Availability of data and materials No additional data are available due to data protection requirements. Competing interests The authors declare that they have no competing interests. Funding This study is part of the main INTRO-HCV study, which was funded by The Norwegian Research Council (no. 269855) and the Western Norway Regional Health Authority (“Åpen prosjektstøtte) with Department of Addiction Medicine, Haukeland University Hospital as responsible institution. The funders had no role in the study design, data collection and analyzes, decision to publish, nor preparation of any content in the manuscript. Authors' contributions CLG and JHV have led the study design, analysis, and article preparation. FC, CFA, EML, KAJ, and LTF have contributed in the article preparation. All authors have read and approved the final article. Acknowledgements We thank the INTRO-HCV Study Group for important contribution relating to data collection: INTRO-HCV Study Group participating investigators: Bergen: Christer Frode Aas, Vibeke Bråthen Buljovcic, Fatemeh Chalabianloo, Jan Tore Daltveit, Silvia Eiken Alpers, Lars T. Fadnes (principal investigator), Trude Fondenes Eriksen, Per Gundersen, Velinda Hille, Kristin Holmelid Håberg, Kjell Arne Johansson, Rafael Alexander Leiva, Siv-Elin Leirvåg Carlsen, Martine Lepsøy Bonnier, Lennart Lorås, Else-Marie Løberg, Mette Hegland Nordbotn, Cathrine Nygård, Maria Olsvold, Christian Ohldieck, Lillian Sivertsen, Hugo Torjussen, Jørn Henrik Vold, Jan-Magnus Økland Stavanger: Tone Lise Eielsen, Nancy Laura Ortega Maldonado, Ewa Joanna Wilk proLAR: Ronny Bjørnestad, Ole Jørgen Lygren, Marianne Cook Pierron Oslo: Olav Dalgard, Håvard Midgard, Svetlana Skurtveit Bristol: Aaron G. Lim, Peter Vickerman Author´s information 1 Facultad de Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, Madrid, Spain, 2 Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway, 3 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway, 4 Departamento de Enfermería, Facultad de Salud, Universidad Camilo José Cela, Villafranca del Castillo, Madrid, Spain. References Graham C (2008) Happiness and health: lessons–and questions–for public policy. Health Aff (Millwood) 27(1):72–87. doi: 10.1377/hlthaff.27.1.72. Diener E, Chan MY(2011) Happy people live longer: subjective well-being contributes to health and longevity. Appl Psychol Health Well Being 3(1):1–43. doi: 10.1111/j.1758-0854.2010.01045.x Veenhoven R (2017) Metrics of Subjective Well-Being: Limits and Improvements. Rotterdam: Springer Cham. 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Integrated treatment* (n = 145) Standard treatment* (n = 144) Age (years) 18-29 14 (10) 17 (12) 30-39 45 (31) 46 (32) 40-49 44 (30) 47 (33) ≥50 42 (29) 34 (23) Median (25-75%) 44 (36-52) 43 (34-49) Sex Male 103 (73) 109 (81) Educational attainment Not completed primary school 7 (5) 12 (9) Completed primary school (9 years) 69 (48) 69 (49) Completed high school (12 years) 54 (38) 46 (33) Completed college or university 13 (9) 14 (10) Opioid agonist therapy 124 (86) 126 (88) Unstable housing past 30 days 1) 21 (14) 18 (13) Injected drug use past 12 months 84 (58) 85 (62) Frequent drug use past 12 months 2) Alcohol 35 (24) 34 (25) Benzodiazepines 55 (38) 55 (40) Cannabis 77 (54) 75 (55) Opioids 17 (13) 18 (13) Stimulants (amphetamines and cocaine) 50 (35) 41 (30) Infectious diseases Hepatitis C virus genotypes 1 2 3 4 6 Hepatitis B virus infection 50 (35) <10 (1) 92 (64) <5 (0) <5 (0) 0 (0) 48 (34) <10 (4) 85 (60) <5 (1) <5 (1) 0 (0) Human immunodeficiency virus 0 (0) <5 (0) Liver stiffness Transient elastography (≥ 12.5 kPa) 26 (18) 19 (13) 1) Unstable housing was defined as living in a homeless shelter, with family or friends, or on the street during the 30 days leading up to the first health assessment (baseline); 2) Frequent drug use was defined as using substance at least weekly during the 12 months leading up to the first health assessment. 3) None basic characteristics were significantly different, comparing the integrated treatment group to the standard treatment group, with a significance level of 0.05. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4000705","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":276327475,"identity":"4b09047f-9db9-4e9c-b118-3527fd907942","order_by":0,"name":"Clara Lucas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYDACdhBRwMDAT7wWZhBhwMAg2UCyFoMDxOrgb2Z+9uGHwWF54xvJTzcwVNQR1iJxmM14Zo/BYcNtN9LMbjCcOUxYiwEzgzEDj8HhBLMbOWw3GNuIcJ4BM/tnxj9ALcYzQFr+EeEwA2YeY2aQLQYSIC0NzIS1SBzmKWaWMUg3nHHmmdmNhGNE+IW/vX0z45sKa3n+9uRnNz7UEOEwVJBAqoZRMApGwSgYBdgBAARVM0GuKYk5AAAAAElFTkSuQmCC","orcid":"","institution":"University of Bergen","correspondingAuthor":true,"prefix":"","firstName":"Clara","middleName":"","lastName":"Lucas","suffix":""},{"id":276327477,"identity":"3d9d00ba-ed87-4f7a-bf33-507a560a5b97","order_by":1,"name":"Jørn Henrik Vold","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Jørn","middleName":"Henrik","lastName":"Vold","suffix":""},{"id":276327479,"identity":"62c6d1a3-48e3-4861-af7c-040591365257","order_by":2,"name":"Christer Frode Aas","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Christer","middleName":"Frode","lastName":"Aas","suffix":""},{"id":276327480,"identity":"51b8034c-72c8-4ea6-8c97-8a0ba4dfa34b","order_by":3,"name":"Fatemeh Chalabianloo","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Chalabianloo","suffix":""},{"id":276327481,"identity":"eebcbd52-5e47-4b30-bb59-07b008f1e3e6","order_by":4,"name":"Else-Marie Løberg","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Else-Marie","middleName":"","lastName":"Løberg","suffix":""},{"id":276327482,"identity":"310a99c7-f82a-4c70-8cc4-47c0c689801a","order_by":5,"name":"Kjell Arne Johansson","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Kjell","middleName":"Arne","lastName":"Johansson","suffix":""},{"id":276327483,"identity":"35c5eb42-95da-4c5c-aa8b-c1da5f90cfc0","order_by":6,"name":"Lars Thore Fadnes","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Lars","middleName":"Thore","lastName":"Fadnes","suffix":""}],"badges":[],"createdAt":"2024-02-29 17:39:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4000705/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4000705/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52183771,"identity":"f4f6aee4-23f7-4479-ac35-e4d8c4f88091","added_by":"auto","created_at":"2024-03-07 18:15:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":194923,"visible":true,"origin":"","legend":"\u003cp\u003eTrial profile for the study.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1)\u003c/sup\u003e\u0026nbsp;Estimated numbers. HCV: hepatitis C virus; OAT: opioid agonist therapy\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4000705/v1/8cbfaa173e75c519f2a8fdbf.png"},{"id":52183772,"identity":"e4b358fb-ba52-4e12-9006-86e71cd16065","added_by":"auto","created_at":"2024-03-07 18:15:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":147060,"visible":true,"origin":"","legend":"\u003cp\u003eA linear prediction of changes in happiness sum scores from baseline to EOT12.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4000705/v1/ace41ada29e00e450fd2d8da.png"},{"id":52198029,"identity":"1b237a01-8716-401c-95f7-29ac78c918bc","added_by":"auto","created_at":"2024-03-07 20:21:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":538406,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4000705/v1/99b22c5c-f463-48f1-b796-798ae514c76a.pdf"},{"id":52183773,"identity":"a22ba3c2-8138-4e65-94b0-076d6d9b09b6","added_by":"auto","created_at":"2024-03-07 18:15:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":335725,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfiles.docx","url":"https://assets-eu.researchsquare.com/files/rs-4000705/v1/0dca2a906775d13b43821215.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of integrated treatment of hepatitis C on happiness among people who inject drugs: results from the INTRO-HCV.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThere is a strong relationship between health and happiness. Good health is linked to higher levels of happiness, and causality seems to run in both directions.\u003csup\u003e1,2\u003c/sup\u003e Happiness is defined as the subjective enjoyment of one’s life as a whole.\u003csup\u003e3\u003c/sup\u003e The average of happiness in the general population for 2022, based on 134 countries, was 55 out of 100, where 0 indicates extremely unhappy.\u003csup\u003e4\u003c/sup\u003e A decrease in happiness could be caused by the determinants of physical and mental health such as depression, poor perception of health and addiction in general population.\u003csup\u003e5,6\u003c/sup\u003e The level of happiness is lower in patients with chronic diseases, such as patients with psoriasis who report 53 out of 100 \u003csup\u003e7\u003c/sup\u003e or multiple sclerosis, 46 out of 100.\u003csup\u003e8\u003c/sup\u003e Patients with substance use disorders (SUD) are also at high risk of being unhappy. In recent studies among patients with SUD receiving opioid agonist therapy (OAT), happiness has a been reported as 38 out of 100.\u003csup\u003e9\u003c/sup\u003e This might be even lower in patients with SUD and hepatitis C virus (HCV) infection, reflecting a two-hit vulnerability for unhappiness\u003c/p\u003e \u003cp\u003eGlobally, an estimated 71\u0026nbsp;million people are living with chronic HCV (HCV RNA positive)\u003csup\u003e10\u003c/sup\u003e HCV is the cause of severe comorbidities and impairments such as liver cirrhosis, resulting in an increased risk of liver failure, hepatocellular carcinoma and premature death.\u003csup\u003e11\u003c/sup\u003e Among people with HCV, about a third develop severe hepatic complications within three decades.\u003csup\u003e12\u003c/sup\u003e Besides, HCV and hepatitis B are among the leading causes of liver disease and transplantation worldwide.\u003csup\u003e13\u003c/sup\u003e Norway is a low-prevalence country in this respect regarding general population, but the burden of HCV infection is disproportionately high among people who inject drugs (PWID). Anti-HCV antibody prevalence in PWID is estimated to be greater than 60%.\u003csup\u003e14\u003c/sup\u003e Patients with chronic HCV have a significantly higher risk of end-stage liver diseases compared with those without a SUD.\u003csup\u003e15\u003c/sup\u003e Several studies demonstrate increased cirrhosis and liver-related mortality 25–30 years after HCV transmission in PWID.\u003csup\u003e16,17\u003c/sup\u003e Since 2014, the availability of potent direct-acting antiviral therapies (DAAs) has provided an opportunity to reverse the rising burden of HCV-related complications with high rates (\u0026gt; 80%) of sustained virological response (SVR).\u003csup\u003e18\u003c/sup\u003e Today, patients can be treated using direct-acting antivirals (DAAs) that can cure most patients with only 8–12 weeks of therapy with adverse event.\u003csup\u003e19\u003c/sup\u003e However, the access to patients with SUD and HCV is complex, and they have until recently been undertreated.\u003csup\u003e15\u003c/sup\u003e Adherence to OAT varies considerably, and may affect their chances of initiating HCV treatment.\u003c/p\u003e \u003cp\u003eIn a previous study from the INTRO-HCV trial, integrated HCV and addiction treatments involving decentralized outpatient clinics with multidisciplinary teams and close follow-up improved the sustained virological response (SVR) for PWIDs to 93% compared to standard HCV treatment with 73% SVR rates.\u003csup\u003e20\u003c/sup\u003e Furthermore, the INTRO-HCV trial showed that the treatment initiation rate was 98% among participants who received integrated HCV treatment, compared to 77% among those who received standard HCV treatment. Assessing and improving happiness during HCV care may ultimately lead to improved adherence to treatment and general health and reduce treatment dropouts and liver-related costs.\u003c/p\u003e \u003cp\u003eThis randomized controlled trial investigated the impact of integrated HCV infection treatment on happiness scale (HS) among PWIDs receiving oral direct-acting antivirals (DAAs) in western Norway to evaluate the effect of treatment on happiness. Even though the trial has not randomized to HCV treatment or not which would have been ethical, the 20% absolute difference in SVR will provide an opportunity to assess whether HCV treatment itself is linked to change in happiness (with a “compressed” scale).\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eDesign and setting\u003c/p\u003e\u003cp\u003eThe INTRO-HCV trial is a multi-center, randomized controlled trial (ClinicalTrials.gov.no, Reference NCT03155906).\u003csup\u003e20\u003c/sup\u003e This study evaluated happiness as a secondary outcome of the INTRO-HCV trial. We recruited PWIDs with chronic HCV infection who were eligible for HCV treatment with DAAs in accordance with Norwegian HCV treatment guidelines (Additional file 1). Participants were recruited from eight outpatient clinics providing opioid agonist therapy (OAT) in Bergen and Stavanger, Norway, as well as two community care centers (CCCs) in Bergen providing primary healthcare to PWIDs. Enrolment was conducted from May 2017 to June 2019. For a more comprehensive description, a published protocol and the primary outcome measures of the study are available.\u003csup\u003e20,21\u003c/sup\u003e\u003c/p\u003e\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eThe present study was reviewed and approved by the Regional Ethical Committee for Health Research (REC) West, Norway (reference number: 2017/51/REK Vest). All recruited participants were informed about the study, and provided written informed consent was provided before their inclusion and randomization.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eMeasurement\u003c/h3\u003e\n\u003cp\u003eWe measured the level of happiness during the study period using the happiness scale (HS). The HS is a self-reported scale composed of a question on \u0026quot;\u003cem\u003eHow happy are you with your life these days?\u003c/em\u003e\u0026rdquo;. The response options were denoted with numbers from 0 to 10. We present HS scores converted to a percentage scale from min-to-max\u0026nbsp;(0% indicating \u0026ldquo;completely unhappy\u0026rdquo; and 100% indicating \u0026ldquo;completely happy\u0026rdquo;)\u003c/p\u003e\n\u003ch3\u003eInterventions\u003c/h3\u003e\n\u003cp\u003eIn total, 289 participants were included in the study \u0026ndash; 145 in the integrated treatment group and 144 in the standard treatment group. (For detailed information on the intervention, inclusion and exclusion criteria, sociodemographic and clinical characteristics of participants, see Table 1 and Additional File 2). The trial profile for the study is shown in Figure 1.\u003c/p\u003e\n\u003cp\u003e(Figure 1 should appear in this part of the manuscript)\u003c/p\u003e\n\u003cp\u003eParticipants in the standard HCV treatment group were referred to the centralized outpatient infectious disease clinic at the collaborating referral hospital for HCV treatment. They were responsible for retrieving and adhering to their prescriptions, and attending assessment appointments. In addition, participants met at OAT clinics or CCCs to assess their levels of happiness. All assessments and medications for participants in the integrated treatment groups were provided onsite at the OAT clinics or CCCs, including DAAs, blood samples, and HS assessments. Compared with participants in the standard treatment group, participants in the integrated treatment group had no follow-ups in the referral hospital, and they received all assessments and medications at the local OAT clinics or CCC. Contrary to standard HCV treatment, all HCV treatment was given in parallel with the observed intake of OAT medications and other care, in line with the study protocol. (For detailed information on the standard and integrated treatment, see Additional File 2).\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eParticipants were evaluated prior to HCV treatment and at 12 weeks after the end of treatment (EOT12) to record their health status, including the level of happiness according to the HS score, sociodemographic data, current drug use, blood samples, transient elastography, and clinical examination. The health assessments were conducted by specialized research nurses in close collaboration with the clinics\u0026rsquo; consultants in addiction medicine and infectious diseases. A medical team followed up with those who did not meet the criteria for inclusion in the study. Data from the health assessments prior to and after HCV treatment were defined as the study\u0026rsquo;s baseline and EOT12 (endpoint), respectively. (For detailed information on randomization and masking, measurements and statistical analyses, see Additional File 2.)\u003c/p\u003e"},{"header":"Results","content":"\u003ch3\u003eCharacteristics at baseline\u003c/h3\u003e\n\u003cp\u003eThe characteristics of the participants were similar between both arms, Table 1. HCV genotype 3 was most prevalent, observed among 64% of participants in the integrated HCV treatment group and 60% in the standard HCV treatment group.\u003c/p\u003e\n\u003cp\u003e(Table 1 should appear in this part of the manuscript)\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eHS scores at baseline and EOT12\u003c/h3\u003e\n\u003cp\u003eAt baseline, the mean HS score for participants in the integrated HCV treatment arm was 49% (standard deviation (SD) 26) and 52% (SD 25) in the standard HCV treatment arm. At EOT12, the mean HS score for participants receiving integrated HCV treatment was 51% (SD 20) and 52% (SD 23) for those receiving standard HCV treatment. (For detailed information on the HS scores at baseline and EOT12, see\u0026nbsp;Table 2, Additional file\u0026nbsp;3).\u003c/p\u003e\n\u003ch3\u003eThe impact of integrated HCV treatment on change in the HS\u003c/h3\u003e\n\u003cp\u003eIntegrated HCV treatment was, compared to standard HCV treatment, not significantly associated with HS, but a non-significant trend was seen with slightly more increase in happiness from baseline to EOT12 in integrated compared to standard HCV treatment (\u0026Delta;HS score 3 (95% CI: -2; 8) (Additional file 4, 5, 6, 7 and 8) (intention-to-treat and per protocol analyses). Compared to the standard HCV treatment, the happiness score tends to increase from baseline to EOT12 in the integrated HCV treatment groups, but not significantly (Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(Figure 2 should appear in this part of the manuscript).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMoreover, we observed substantial interindividual variabilities in HS values from baseline to EOT12 in both positive and negative directions in both groups (Additional file 5). Likewise, per protocol and sensitivity analyses without computed data showed similar results (Additional files 9 and 10). Achieving SVR was not associated with changes in the HS score from baseline to EOT12, adjusted for sociodemographic factors, injecting drug use, and types of drugs used (Additional files 11 and 12).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis trial showed a no significant changes in happiness among those receiving integrated compared to standard HCV treatment. However, it should be noted that the differences in SVR rates between these two arms were 20% (absolute differences), and thus the differences related to successful HCV treatment compared to no treatment might be five times as high, and could potentially have been significantly different. However, randomising to integrated versus no treatment would not be ethical. If the trend was scaled to treatment versus no treatment (i.e., five times our observed differences), the estimated improvement in happiness might have been in the range of 10%.\u0026nbsp;To our knowledge, this is the first trial conducted in outpatient OAT clinics and CCCs to investigate the impact of integrated HCV treatment on happiness among PWIDs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere is little literature regarding happiness in patients with SUD and HCV. A qualitative study examining an integrated infectious diseases/SUD treatment program showed that even if HCV was cured, this did not seem to affect the wellbeing of patients.\u003csup\u003e30\u003c/sup\u003e One possible explanation might be that HCV infection can be asymptomatic for many years and some patients will even progress through life without ever developing symptoms.\u003csup\u003e12,18\u003c/sup\u003e For those patients without severe symptoms, not perceiving substantial changes in health might not affect their level of happiness. Furthermore, there is a lack of information concerning the risks and consequences of having HCV among PWID.\u003csup\u003e14\u003c/sup\u003e As a consequence, having HCV and, correspondingly, achieving SVR might not influence their level of happiness.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eYet, even if their physical health improves, SUD patients still have to deal with other complex situations such as\u0026nbsp;underlying mental disorders and extensive polysubstance use.\u003csup\u003e6\u003c/sup\u003e More than half of the participants who received the integrated treatment injected drugs during the past 12 months. Despite achieving SVR, other comorbidities such as substance use and extensive injected use may affect their level of happiness.\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn 2022, data from the Norwegian general population indicated a three-year-average happiness score of 73 out of 100,\u003csup\u003e4\u003c/sup\u003e while patients with SUD and HCV in our cohort reported considerably lower mean scores; 49 for those receiving integrated treatment and 52 for those receiving standard treatment. SUD entails lifelong struggles with substance use and HCV treatment might not be a priority for these patients. This is consistent with other studies in PWID, and that\u0026nbsp;achieving HCV treatment is often linked with improvement in physical health, but not similarly to mental health symptoms.\u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThe integrated and standard treatment groups demonstrated substantial intraindividual variation in levels of happiness over time. Considering happiness as an emotional state linked to one\u0026acute;s physiological reactions to life events,\u003csup\u003e5\u003c/sup\u003e it can be assumed that the intra-individual variations in the present study might be attributable to comorbidities and complexities among substance users.\u003csup\u003e7,10,14\u003c/sup\u003e Nevertheless, future\u0026nbsp;research should examine possible causes of the changes in happiness scores not only in SUD patients with HCV, but in other populations as well.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRecovery from dependence is a long-term process during which several life domains, and correspondingly, the perception of happiness, might change over time.\u003csup\u003e32\u003c/sup\u003e Assessing the levels of happiness over longer time periods, rather than a 24-week follow-up, could allow a more accurate knowledge of the long-term benefits or, alternatively, adverse effects of different treatments regimens in patients with SUD and HCV. Happiness might be an important marker of the combined outcomes that really matter for the individual patients and might serve to evaluate the long-term effectiveness of treatments. Still, less is known about the subjective experience in happiness in this population and further research is needed to develop tools for the elimination of hepatitis C infection among PWIDs. \u0026nbsp;Another strength of this study is its trial design of individual randomization with balanced groups, which minimizes potential confounding and bias. Furthermore, we included PWIDs who is generally hard-to-reach. A limitation is that 32% of participants had missing data on HS at EOT12.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe present study demonstrated that integrated HCV treatment did not significantly improve happiness among PWIDs, but there were non-significant positive trends. Nevertheless, integrated treatment of HCV has other documented advantages and as no negative change was seen for happiness, there are still good arguments to integrate treatment of HCV among people who inject drugs.\u0026nbsp;\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eSUD: Substance use disorders\u003c/p\u003e\n\u003cp\u003eOAT: Opioid agonist therapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCV: Hepatitis C virus\u003c/p\u003e\n\u003cp\u003ePWID: People who inject drugs\u003c/p\u003e\n\u003cp\u003eDAA:\u0026nbsp;Direct-acting antiviral therapies\u003c/p\u003e\n\u003cp\u003eSVR: Sustained virological response\u003c/p\u003e\n\u003cp\u003eHS: Happiness scale\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCCC:\u0026nbsp;Community care centers\u003c/p\u003e\n\u003cp\u003eREC:\u0026nbsp;Regional ethical committee\u003c/p\u003e\n\u003cp\u003eEOT12\u0026shy;:\u0026nbsp;at 12 weeks after the end of treatment (EOT12)\u003c/p\u003e\n\u003cp\u003eSD: Standard deviation\u003c/p\u003e\n\u003cp\u003e\u0026Delta;HS: Changes in happiness scores\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eThe present study was reviewed and approved by the Regional Ethical Committee for Health Research (REC) West, Norway (reference number: 2017/51/REK Vest). All recruited participants were informed about the study, and provided written informed consent was provided before their inclusion and randomization.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003ch3\u003eParticipants have consented for publication.\u003c/h3\u003e\n\u003ch3\u003eAvailability of data and materials\u003c/h3\u003e\n\u003cp\u003eNo additional data are available due to data protection requirements.\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis study is part of the main INTRO-HCV study, which was funded by The Norwegian Research Council (no. 269855) and the Western Norway Regional Health Authority (\u0026ldquo;\u0026Aring;pen prosjektst\u0026oslash;tte) with Department of Addiction Medicine, Haukeland University Hospital as responsible institution. The funders had no role in the study design, data collection and analyzes, decision to publish, nor preparation of any content in the manuscript.\u003c/p\u003e\n\u003ch3\u003eAuthors\u0026apos; contributions\u003c/h3\u003e\n\u003cp\u003eCLG and JHV have led the study design, analysis, and article preparation. FC, CFA,\u003c/p\u003e\n\u003cp\u003eEML, KAJ, and LTF have contributed in the article preparation. All authors\u003c/p\u003e\n\u003cp\u003ehave read and approved the final article.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eWe thank the INTRO-HCV Study Group for important contribution relating to data collection:\u003c/p\u003e\n\u003cp\u003eINTRO-HCV Study Group participating investigators:\u003c/p\u003e\n\u003cp\u003eBergen: Christer Frode Aas, Vibeke Br\u0026aring;then Buljovcic, Fatemeh Chalabianloo, Jan Tore Daltveit, Silvia Eiken Alpers, Lars T. Fadnes (principal investigator), Trude Fondenes Eriksen, Per Gundersen, Velinda Hille, Kristin Holmelid H\u0026aring;berg, Kjell Arne Johansson, Rafael Alexander Leiva, Siv-Elin Leirv\u0026aring;g Carlsen, Martine Leps\u0026oslash;y Bonnier, Lennart Lor\u0026aring;s, Else-Marie L\u0026oslash;berg, Mette Hegland Nordbotn, Cathrine Nyg\u0026aring;rd, Maria Olsvold, Christian Ohldieck, Lillian Sivertsen, Hugo Torjussen, J\u0026oslash;rn Henrik Vold, Jan-Magnus \u0026Oslash;kland\u003c/p\u003e\n\u003cp\u003eStavanger: Tone Lise Eielsen, Nancy Laura Ortega Maldonado, Ewa Joanna Wilk\u003c/p\u003e\n\u003cp\u003eproLAR: Ronny Bj\u0026oslash;rnestad, Ole J\u0026oslash;rgen Lygren, Marianne Cook Pierron\u003c/p\u003e\n\u003cp\u003eOslo: Olav Dalgard, H\u0026aring;vard Midgard, Svetlana Skurtveit\u003c/p\u003e\n\u003cp\u003eBristol: Aaron G. Lim, Peter Vickerman\u003c/p\u003e\n\u003ch3\u003eAuthor\u0026acute;s information\u003c/h3\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e Facultad de Enfermer\u0026iacute;a, Fisioterapia y Podolog\u0026iacute;a, Universidad Complutense de Madrid, Madrid, Spain, \u003csup\u003e2\u003c/sup\u003e Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway, \u003csup\u003e3\u003c/sup\u003e Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway, \u003csup\u003e4\u003c/sup\u003e Departamento de Enfermer\u0026iacute;a, Facultad de Salud, Universidad Camilo Jos\u0026eacute; Cela, Villafranca del Castillo, Madrid, Spain.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGraham C (2008) Happiness and health: lessons\u0026ndash;and questions\u0026ndash;for public policy. Health Aff (Millwood) 27(1):72\u0026ndash;87. doi: 10.1377/hlthaff.27.1.72.\u003c/li\u003e\n\u003cli\u003eDiener E, Chan MY(2011) Happy people live longer: subjective well-being contributes to health and longevity. Appl Psychol Health Well Being 3(1):1\u0026ndash;43. doi: 10.1111/j.1758-0854.2010.01045.x\u003c/li\u003e\n\u003cli\u003eVeenhoven R (2017) Metrics of Subjective Well-Being: Limits and Improvements. Rotterdam: Springer Cham. Chapter 2, Measures of happiness: Which to Choose?; p 84-65. doi:10.1007/978-3-319-61810-4_4\u003c/li\u003e\n\u003cli\u003eHelliwell JF, Layard R, Sachs JD et al (2023) World Happiness Report. Available from: https://happinessreport.s3.amazonaws.com/2023/WHR+23.pdf\u003c/li\u003e\n\u003cli\u003eSingh S, Kshtriya S, Valk R (2023). Health, Hope, and Harmony: A Systematic Review of the Determinants of Happiness across Cultures and Countries. Int J Environ Res Public Health 20(4):3306. https://doi.org/10.3390/ijerph20043306\u003c/li\u003e\n\u003cli\u003eSpinhoven P, Elzinga BM, Penninx BWJH et al (2021) Temporal relationships between happiness and psychiatric disorders and their symptom severity in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). BMC Psychiatry 21(1). doi:10.1186/s12888-021-03346-4\u003c/li\u003e\n\u003cli\u003eSchuster B, Peifer C, Ziehfreund S, et al (2022) Happiness and depression in psoriasis: a cross-sectional study in Germany. Qual Life Res 31(6):1761-1773. doi:10.1007/s11136-021-02991-2\u003c/li\u003e\n\u003cli\u003eMohaghegh F, Moghaddasi M, Eslami M (2021) Disability and its association with psychological factors in multiple sclerosis patients. Mult Scler Relat Disord 49:102733. doi:10.1016/j.msard.2020.102733\u003c/li\u003e\n\u003cli\u003eBergsma A, ten Have M, Veenhoven R (2011) Most people with mental disorders are happy: A 3-year follow-up in the Dutch general population. J Posit Psychol 6(4):253-259. doi:10.1080/17439760.2011.5770869. \u003c/li\u003e\n\u003cli\u003eMeijerink H, White RA, L\u0026oslash;vlie A et al (2017) Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973\u0026ndash;2030. BMC Infect 17 (541). https://doi.org/10.1186/s12879-017-2631-2\u003c/li\u003e\n\u003cli\u003eSeeff LB (2009) The history of the \u0026quot;natural history\u0026quot; of hepatitis C (1968-2009). Liver Int 29 Suppl 1(0 1):89-99. Doi:10.1111/j.1478-3231.2008.01927.x\u003c/li\u003e\n\u003cli\u003eKielland KB, Delaveris GJ, Rogde S (2014) Liver fibrosis progression at autopsy in injecting drug users infected by hepatitis C: a longitudinal long-term cohort study. J Hepatol 60(2):260\u0026ndash;266. Doi: 10.1016/j.jhep.2013.09.022.\u003c/li\u003e\n\u003cli\u003eGlobal Burden Disease (2015) Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet 385(9963):117\u0026ndash;171. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61682-2/fulltext\u003c/li\u003e\n\u003cli\u003eNelson PK, Mathers BM, Cowie B et al (2011) Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 378(9791):571-583. doi:10.1016/S0140-6736(11)61097\u003c/li\u003e\n\u003cli\u003eJiang X, Vouri SM, Diaby V (2021) Health care utilization and costs associated with direct-acting antivirals for patients with substance use disorders and chronic hepatitis C. 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J Hepatol 74(5):1053-1063. doi:10.1016/j.jhep.2020.11.021\u003c/li\u003e\n\u003cli\u003eHannula R, S\u0026ouml;derholm J, Svendsen T et al (2021) Hepatitis C outreach project and cross-sectional epidemiology in high-risk populations in Trondheim, Norway. Ther Adv Infect Dis 28 (8):20499361211053929. doi: 10.1177/20499361211053929\u003c/li\u003e\n\u003cli\u003eFadnes LT, Aas CF, Vold JH et al (2021) Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV). PLoS Med 18(6): e1003653. https://doi.org/10.1371/journal.pmed.1003653\u003c/li\u003e\n\u003cli\u003eFadnes LT, Aas CF, Vold JH et al (2019) Integrated treatment of hepatitis C virus infection among people who inject drugs: study protocol for a randomised controlled trial (INTRO-HCV). BMC Infect Dis 19(1):943. https://doi.org/10.1186/s12879-019-4598-7\u003c/li\u003e\n\u003cli\u003eDal-R\u0026eacute; R, Janiaud P, Ioannidis JPA (2018) Real-world evidence: How pragmatic are randomized controlled trials labeled as pragmatic? BMC Med 16(1):49.\u003c/li\u003e\n\u003cli\u003eVeenhoven R (2004) World Database of Happiness. Continuous Register of Research on Subjective Appreciation of Life. In: Glatzer W, VonBelow S, Stoffregen M, editors. Challenges forquality of life in the contemporary world: Advances in quality-of-life studies, theoryand research\u0026rsquo;[Internet]. Dordrecht: KLUWER ACADEMIC PUBLISHERS [about 19p.]. 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New York, 2nd edn: CRC Press, Taylor \u0026amp; Francis Group.\u003c/li\u003e\n\u003cli\u003eDempster AP, Laird NM, Rubin DB (1977) Maximum likelihood from incomplete data via the EM Algorithm. J Roy Stat Soc Ser B (Methodol) 39(1):1\u0026ndash;38.\u003c/li\u003e\n\u003cli\u003eHox JJ, M M, Van de Schoot R (2018) Multilevel analysis. Techniques and applications. New York, Routledge: Taylor \u0026amp; Francis Group.\u003c/li\u003e\n\u003cli\u003eHervera B, Seo G, Bartholomew TS et al (2023) Implementation of an integrated infectious disease and substance use disorder team for injection drug use-associated infections: a qualitative study. Addict Sci Clin Pract 18(1):1\u0026ndash;15. Available from: https://doi.org/10.1186/s13722-023-00363-4\u003c/li\u003e\n\u003cli\u003eBuchanan-Hughes A.M, Buti M, Hanman K (2019) Health state utility values measured using the EuroQol 5-dimensions questionnaire in adults with chronic hepatitis C: a systematic literature review and meta-analysis. Qual Life Res 28: 319-297. Available from: https://doi.org/10.1007/s11136-018-1992-3\u003c/li\u003e\n\u003cli\u003eMartinelli TF, Nagelhout GE, Bellaert L (2020) Comparing three stages of addiction recovery: long-term recovery and its relation to housing problems, crime, occupation situation, and substance use. Drugs Educ Prev Policy 27(5):387\u0026ndash;96. Available from: https://doi.org/10.1080/09687637.2020.1779182\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eSociodemographic and clinical characteristics of participants.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"463\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntegrated treatment*\u003c/strong\u003e \u003cstrong\u003e\u0026nbsp; (n = 145)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStandard treatment* \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 144)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eAge (years)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.344827586206897%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.80172413793103%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.482758620689655%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.086206896551724%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.28448275862069%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.344827586206897%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.80172413793103%\" valign=\"bottom\"\u003e\n \u003cp\u003e18-29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e14 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e17 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.344827586206897%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.80172413793103%\" valign=\"bottom\"\u003e\n \u003cp\u003e30-39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e45 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e46 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.344827586206897%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.80172413793103%\" valign=\"bottom\"\u003e\n \u003cp\u003e40-49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e44 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e47 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.344827586206897%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.80172413793103%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026ge;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e42 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e34 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.344827586206897%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.80172413793103%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (25-75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e44 (36-52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e43 (34-49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eSex\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e103 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e109 (81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eEducational attainment\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eNot completed primary school \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e12 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eCompleted primary school (9 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e69 (48)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e69 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eCompleted high school (12 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e54 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e46 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eCompleted college or university\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e13 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e14 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eOpioid agonist therapy\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e124 (86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e126 (88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eUnstable housing past 30 days\u003c/em\u003e\u003csup\u003e1)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e21 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e18 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eInjected drug use past 12 months\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e84 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e85 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eFrequent drug use past 12 months\u003c/em\u003e\u003csup\u003e2)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eAlcohol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e35 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e34 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eBenzodiazepines\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e55 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e55 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eCannabis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e77 (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e75 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eOpioids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e17 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e18 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eStimulants (amphetamines and cocaine)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e50 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e41 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eInfectious diseases\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eHepatitis C virus genotypes\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHepatitis B virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e50 (35)\u003c/p\u003e\n \u003cp\u003e\u0026lt;10 (1)\u003c/p\u003e\n \u003cp\u003e92 (64)\u003c/p\u003e\n \u003cp\u003e\u0026lt;5 (0)\u003c/p\u003e\n \u003cp\u003e\u0026lt;5 (0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48 (34)\u003c/p\u003e\n \u003cp\u003e\u0026lt;10 (4)\u003c/p\u003e\n \u003cp\u003e85 (60)\u003c/p\u003e\n \u003cp\u003e\u0026lt;5 (1)\u003c/p\u003e\n \u003cp\u003e\u0026lt;5 (1)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eHuman immunodeficiency virus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;5 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003eLiver stiffness\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.14655172413793%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTransient elastography (\u0026ge; 12.5 kPa)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.094827586206897%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e26 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.379310344827587%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e19 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1)\u003c/sup\u003e Unstable housing was defined as living in a homeless shelter, with family or friends, or on the street during the 30 days leading up to the first health assessment (baseline);\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2)\u003c/sup\u003e Frequent drug use was defined as using substance at least weekly during the 12 months leading up to the first health assessment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3)\u003c/sup\u003e None basic characteristics were significantly different, comparing the integrated treatment group to the standard treatment group, with a significance level of 0.05.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Substance-Related Disorders, Happiness, Hepatitis C, Chronic","lastPublishedDoi":"10.21203/rs.3.rs-4000705/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4000705/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePWID are at high risk of being unhappy. However, to which degree happiness in patients with SUD is linked to infection with HCV and its treatment is unknown. The present study investigated the effect of integrated compared to standard HCV treatment on happiness in this population. This multi-center, randomized controlled trial evaluated happiness as a secondary outcome of integrated HCV treatment. From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient OAT clinics and two community care centers while standard treatment was delivered in outpatient clinics at referral hospitals, with 21% absolute difference in SVR. The level of happiness was assessed with an eleven-point Likert scale and presented as percentage (from 0% “completely unhappy” to 100% “completely happy”)\u003cstrong\u003e. \u003c/strong\u003eWe applied a LMM to evaluate the impact of integrated HCV treatment on changes in happiness scores. At baseline, the mean happiness score for participants receiving integrated treatment was 49% (SD 26) and 52% (SD 25) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean happiness score for participants receiving integrated treatment was 51% (SD 20) and 52% (SD 23) for those receiving standard treatment. Compared to the standard HCV treatment, the happiness score tends to increase from baseline to end of treatment in the integrated HCV treatment groups, but not significantly. Further research is needed to improve the subjective experience in happiness in this population.\u003c/p\u003e\n\u003cp\u003e\u003cb\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eClinicalTrials.gov.no NCT03155906, 16/05/2017.\u003c/p\u003e","manuscriptTitle":"Impact of integrated treatment of hepatitis C on happiness among people who inject drugs: results from the INTRO-HCV.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-07 18:15:00","doi":"10.21203/rs.3.rs-4000705/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b1ceb47e-6c8d-4f25-aa90-ea3152e6b54d","owner":[],"postedDate":"March 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-07T20:21:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-07 18:15:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4000705","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4000705","identity":"rs-4000705","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}