Assessment and treatment of hepatitis C virus infection among people who inject drugs in the opioid substitution setting: ETHOS study.

BACKGROUND: Access to hepatitis C virus (HCV) treatment remains extremely limited among people who inject drugs (PWID). HCV assessment and treatment was evaluated through an innovative model for the provision of HCV care among PWID with chronic HCV infection. METHODS: Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) was a prospective observational cohort. Recruitment was through 5 opioid substitution treatment (OST) clinics, 2 community health centers, and 1 Aboriginal community controlled health organization in New South Wales, Australia. RESULTS: Among 387 enrolled participants, mean age was 41 years, 71% were male, and 15% were of Aboriginal ethnicity. Specialist assessment was undertaken in 191 (49%) participants, and 84 (22%) commenced interferon-based treatment. In adjusted analysis, HCV specialist assessment was associated with non-Aboriginal ethnicity (adjusted odds ratio [AOR], 4.02; 95% confidence interval [CI], 2.05-7.90), no recent benzodiazepine use (AOR, 2.06; 95% CI, 1.31-3.24), and non-1 HCV genotype (AOR, 2.13; 95% CI, 1.32-3.43). In adjusted analysis, HCV treatment was associated with non-Aboriginal ethnicity (AOR, 4.59; 95% CI, 1.49-14.12), living with the support of family and/or friends (AOR, 2.15; 95% CI, 1.25-3.71), never receiving OST (AOR, 4.40; 95% CI, 2.27-8.54), no recent methamphetamine use (AOR, 2.26; 95% CI, 1.12-4.57), and non-1 HCV genotype (AOR, 3.07; 95% CI, 1.67-5.64). CONCLUSIONS: HCV treatment uptake was relatively high among this highly marginalized population of PWID. Potentially modifiable factors associated with treatment include drug use and social support.

Plasma n-3 Polyunsaturated Fatty Acids are negatively associated with obesity.

The objective of the present study was to investigate the relationship between plasma n-3 PUFA composition and weight status. A total of 124 adults, stratified by weight status: healthy weight (n 21), overweight (n 40) and obese (n 63) were recruited. Fasting blood samples, anthropometric measures and body composition were collected. Plasma fatty acid composition was determined by GC. BMI, waist circumference and hip circumference were inversely correlated with n-3 PUFA, EPA and DHA (P < 0.05 for all) in the obese group. Obese individuals had significantly lower plasma concentrations of total n-3 PUFA, compared with healthy-weight individuals (4.53 (SD 1.11) v. 5.25 (SD 1.43) %). When subjects were pooled and stratified into quartiles of total n-3 PUFA, a significant inverse trend was found for BMI (P = 0.002), waist circumference and hip circumference (P = 0.01 and P < 0.001 respectively). Higher plasma levels of total n-3 PUFA are associated with a healthier BMI, waist circumference and hip circumference. Our findings suggest that n-3 PUFA may play an important role in weight status and abdominal adiposity.

The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women.

Fish oils rich in (n-3) long-chain PUFA (LCPUFA) can reduce circulating triglycerides and raise HDL-cholesterol. Phytosterols have been shown to reduce total cholesterol and LDL-cholesterol in normocholesterolemic and hyperlipidemic populations. We investigated the combined effects of phytosterols and (n-3) LCPUFA on plasma lipid profile in hyperlipidemic individuals. This study was a 3-wk randomized, double-blind, placebo-controlled, 2 x 2 factorial trial in 4 parallel groups of 60 hyperlipidemic individuals. Subjects were randomized to receive either sunola oil or 1.4 g/d (n-3) LCPUFA capsules with or without 2 g phytosterols per day while maintaining their habitual diet. The combination of phytosterols and (n-3) LCPUFA reduced plasma total cholesterol by 13.3% (P = 0.001), which differed from (n-3) LCPUFA alone (P < 0.001). LDL-cholesterol concentrations followed the same pattern as that of plasma cholesterol with a 12.5% decrease (P = 0.002) in the combination group. The HDL-cholesterol concentration was increased by (n-3) LCPUFA (7.1%; P = 0.01) alone and in combination with phytosterols (8.6%; P = 0.04), whereas phytosterol treatment alone had no effect. Plasma triglyceride concentration was lowered by (n-3) LCPUFA (22.3%; P = 0.004) alone and in combination with phytosterols (25.9%; P = 0.005), whereas phytosterol treatment alone had no effect. In conclusion, the combined supplementation with phytosterols and (n-3) LCPUFA has both synergistic and complementary lipid-lowering effects in hyperlipidemic men and women.

Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans.

BACKGROUND: Red wine contains a naturally rich source of antioxidants, which may protect the body from oxidative stress, a determinant of age-related disease. The current study set out to determine the in vivo effects of moderate red wine consumption on antioxidant status and oxidative stress in the circulation. METHODS: 20 young (18-30 yrs) and 20 older (>or= 50 yrs) volunteers were recruited. Each age group was randomly divided into treatment subjects who consumed 400 mL/day of red wine for two weeks, or control subjects who abstained from alcohol for two weeks, after which they crossed over into the other group. Blood samples were collected before and after red wine consumption and were used for analysis of whole blood glutathione (GSH), plasma malondialdehyde (MDA) and serum total antioxidant status. RESULTS: Results from this study show consumption of red wine induced significant increases in plasma total antioxidant status (P < 0.03), and significant decreases in plasma MDA (P < 0.001) and GSH (P < 0.004) in young and old subjects. The results show that the consumption of 400 mL/day of red wine for two weeks, significantly increases antioxidant status and decreases oxidative stress in the circulation CONCLUSION: It may be implied from this data that red wine provides general oxidative protection and to lipid systems in circulation via the increase in antioxidant status.

Depression, Anxiety, and Stress Among People With Chronic Hepatitis C Virus Infection and a History of Injecting Drug Use in New South Wales, Australia.

OBJECTIVE: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. METHODS: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia). Symptoms were assessed using the Depression Anxiety Stress Scales (DASS-21). Analyses were performed using logistic regression. RESULTS: Among 415 participants (mean age 41 years, 71% male), 47%, 52%, and 36% demonstrated moderate to extremely severe symptoms of depression, anxiety, and stress, respectively. In adjusted analyses, depression symptoms were associated with recent injecting drug use [adjusted odds ratio (aOR) 1.63, 95% confidence interval (CI) 1.07-2.49), whereas stress symptoms were associated with unemployment (aOR 2.99, 95% CI 1.09-8.15) and not living with a spouse or other relatives/friends (aOR 1.55, 95% CI 1.01-2.39). Symptoms of depression, anxiety, or stress or having a history of treated mental illness were not independently associated with HCV treatment intent, specialist assessment, or treatment uptake. CONCLUSIONS: Findings suggest a need for improved interventions and care regarding mental health among people living with chronic HCV with a history of injecting drug use, but suggest that symptoms of depression, anxiety, and stress should not be immediate contraindications to HCV assessment and treatment.

Treatment for hepatitis C virus infection among people who inject drugs attending opioid substitution treatment and community health clinics: the ETHOS Study.

AIMS: To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response. DESIGN: Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1). SETTING: Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia. PARTICIPANTS: Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female). MEASUREMENTS: Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post-treatment). FINDINGS: Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age < 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR. CONCLUSIONS: People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy.

Assessment and delivery of treatment for hepatitis C virus infection in an opioid substitution treatment clinic with integrated peer-based support in Newcastle, Australia.

BACKGROUND: Among people who inject drugs (PWID), the prevalence of hepatitis C virus (HCV) infection is high; however HCV treatment uptake remains low. New models of care are needed to address the growing burden of HCV-related disease in PWID and to understand the barriers to assessment and treatment of HCV. This study evaluated assessment and treatment for HCV infection among PWID attending an opioid substitution treatment (OST) clinic with an integrated peer support worker model. METHODS: Clients with a history of IDU and chronic HCV infection, attending the Newcastle Pharmacotherapy Service, Newcastle Australia, were recruited as part of a multisite prospective observational study (the ETHOS Cohort). Additional chart review was conducted for clients not enrolled in the ETHOS Cohort. A peer support worker was introduced to complement and extend services offered by the clinical team. Client contacts and assessments with a nurse and/or peer worker were evaluated, including those who commenced HCV treatment. RESULTS: A total of 1447 clients attended the OST service during February 2009 and June 2014. Of these, 378 (26%) were assessed by a nurse and 242 (17%) by a clinician. HCV treatment was commenced by 20 (5%) participants and 15 (75%) achieved a sustained virological response (SVR). During May 2009 and July 2011, 332 nurse contacts and 726 peer worker contacts were evaluated. The nurse-led contacts were related to HCV treatment (50%) and review of pathology tests (34%), whereas peer worker contacts included discussion about HCV treatment (75%), education, counselling and/or support (53%) and general discussion about HCV infection (59%). CONCLUSION: These data demonstrate that peer support workers facilitate broader discussion about HCV treatment, education and/or support, allowing nurses to focus on HCV-related assessment and treatment. HCV treatment uptake was very low in this cohort, but SVR was high. The integration of peer support workers in treatment programs within OST clinics may address barriers to HCV care, but further studies are needed to assess their impact on assessment and treatment outcomes.

Evaluation of two community-controlled peer support services for assessment and treatment of hepatitis C virus infection in opioid substitution treatment clinics: The ETHOS study, Australia.

AIM: Peer support services have been shown to be beneficial in increasing uptake and adherence to treatment in other areas but few examples of these services exist in hepatitis C (HCV) care. This study examined the performance of two community-controlled peer support services operating within a larger study aimed at increasing access to HCV care and treatment for opiate substitution treatment (OST) clients, ETHOS. METHODS: Semi-structured interviews were conducted in two clinics with three groups of participants: clients (n=31), staff (n=8) and peer workers (n=3) and examined the operation of the service in relation to process, outputs and impacts. RESULTS: There was a very strong positive response to the peer worker services reported by staff and clients who had and had not interacted with a peer worker. A number of changes were reported that were not explicit goals of the service including providing access to additional services for clients and staff, peer workers acting as mediators between clients and staff and a less tangible notion of a changing "feel" of the clinic to a more positive and client-friendly social and physical space. Explicit goals of the service were also reported in peer workers supporting clients to consider and prepare for treatment (via blood tests and other assessments) as well as provide information and support about treatment. CONCLUSIONS: The peer support service was acceptable to clients and clinic staff. All groups of participants noted that the service met its goals of engaging clients, building trusting relationships and providing instrumental support for clients to access HCV treatment. Peer workers may also contribute to more effective deployment of health resources by preparing clients for clinical engagement with HCV health workers.

The effect of social functioning and living arrangement on treatment intent, specialist assessment and treatment uptake for hepatitis C virus infection among people with a history of injecting drug use: The ETHOS study.

BACKGROUND: The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use. METHODS: ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression. RESULTS: Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment. CONCLUSIONS: This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment uptake.

Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals.

BACKGROUND: Risk factors of cardiovascular disease such as lipid aberrations, hypertension, abdominal adiposity and elevations in systemic inflammation, are prominent aetiologies in hyperlipidemia. Supplementation with n-3 PUFA is associated with a reduction in cardiovascular events through its hypotriglyceridemic, anti-aggregatory and anti-inflammatory properties. Plant sterols have potent hypocholesterolemic properties, although their effect on the inflammatory cascade is uncertain. This study investigated the effect of combined supplementation with n-3 PUFA and plant sterols on cardiovascular risk factors, blood pressure, body composition, markers of systemic inflammation and overall risk, in hyperlipidemic individuals. METHODS: The study was a 3-week randomised, double-blind, placebo-controlled, 2 x 2 factorial design, in four parallel groups. Sixty hyperlipidemic participants were randomised to receive either sunola oil or 1.4 g/d n-3 PUFA capsules with or without 2g plant sterols per day. RESULTS: The combination of n-3 PUFA and plant sterols reduced several inflammatory markers. High sensitivity C-reactive protein (hs-CRP) was reduced by 39% (P=0.009), tumor necrosis factor-alpha (TNF-alpha) by 10% (P=0.02), interleukin-6 (IL-6) by 10.7% (P=0.009), leukotriene B(4) (LTB(4)) by 29.5% (P=0.01) and adiponectin was increased by 29.5% (P=0.05). Overall cardiovascular risk was reduced by 22.6% (P=0.006) in the combination group. CONCLUSION: We have demonstrated, for the first time that dietary intervention with n-3 PUFA and plant sterols reduces systemic inflammation in hyperlipidemic individuals. Furthermore, our results suggest that reducing inflammation provides a potential mechanism by which the combination of n-3 PUFA and plant sterols are cardioprotective.

Beyond blood lipids: phytosterols, statins and omega-3 polyunsaturated fatty acid therapy for hyperlipidemia.

Phytosterols and omega-3 fatty acids are natural compounds with potential cardiovascular benefits. Phytosterols inhibit cholesterol absorption, thereby reducing total- and LDL cholesterol. A number of clinical trials have established that the consumption of 1.5-2.0 g/day of phytosterols can result in a 10-15% reduction in LDL cholesterol in as short as a 3-week period in hyperlipidemic populations. Added benefits of phytosterol consumption have been demonstrated in people who are already on lipid-lowering medications (statin drugs). On the other hand, omega-3 fatty acid supplementation has been associated with significant hypotriglyceridemic effects with concurrent modifications of other risk factors associated with cardiovascular disease, including platelet function and pro-inflammatory mediators. Recent studies have provided evidence that the combination of phytosterols and omega-3 fatty acids may reduce cardiovascular risk in a complementary and synergistic way. This article reviews the health benefits of phytosterols and omega-3 fatty acids, alone or in combination with statins, for the treatment/management of hyperlipidemia, with particular emphasis on the mechanisms involved.