Negotiating access to medical treatment and the making of patient citizenship: the case of hepatitis C treatment.

Drawing on qualitative interview accounts with people who have injected drugs, we deploy ideas of biological and therapeutic citizenship to explore how the negotiation of access to hepatitis C treatment enacts patient citizenship potential. We find that the patient citizenship made through hepatitis C treatment divides those who are deserving from those who are not, largely in relation to their presentations of self-control, responsibility and recovery regarding drug use. Accessing treatment requires that patients negotiate their entitlement by reflexively producing the patient citizen role expected of them. In this context of rationed treatment expectation, access to treatment is constructed in relation to gratitude rather than entitlement. Rationed treatment expectation also interplays with a utilitarian approach to hepatitis C expertise. Accounts of the bio-effects of hepatitis C and its treatment as uncertain further weaken the potential for shared illness identity and biosocial membership as well as contributing to treatment delay. We conclude that the construction of hepatitis C treatment as a negotiation of 'recovery towards normality' positions people who continue to use or inject drugs as beyond patient citizenship. Our findings underscore the situated limits of therapeutic and biological citizenship, emphasising that these processes are unavoidably forces of governance.

Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial.

BACKGROUND: Some heroin addicts persistently fail to benefit from conventional treatments. We aimed to compare the effectiveness of supervised injectable treatment with medicinal heroin (diamorphine or diacetylmorphine) or supervised injectable methadone versus optimised oral methadone for chronic heroin addiction. METHODS: In this multisite, open-label, randomised controlled trial, we enrolled chronic heroin addicts who were receiving conventional oral treatment (>or=6 months), but continued to inject street heroin regularly (>or=50% of days in preceding 3 months). Randomisation by minimisation was used to assign patients to receive supervised injectable methadone, supervised injectable heroin, or optimised oral methadone. Treatment was provided for 26 weeks in three supervised injecting clinics in England. Primary outcome was 50% or more of negative specimens for street heroin on weekly urinalysis during weeks 14-26. Primary analysis was by intention to treat; data were adjusted for centre, regular crack use at baseline, and treatment with optimised oral methadone at baseline. Percentages were calculated with Rubin's rules and were then used to estimate numbers of patients in the multiple imputed samples. This study is registered, ISRCTN01338071. FINDINGS: Of 301 patients screened, 127 were enrolled and randomly allocated to receive injectable methadone (n=42 patients), injectable heroin (n=43), or oral methadone (n=42); all patients were included in the primary analysis. At 26 weeks, 80% (n=101) patients remained in assigned treatment: 81% (n=34) on injectable methadone, 88% (n=38) on injectable heroin, and 69% (n=29) on oral methadone. Patients on injectable heroin were significantly more likely to have achieved the primary outcome (72% [n=31]) than were those on oral methadone (27% [n=11], OR 7.42, 95% CI 2.69-20.46, p<0.0001; adjusted: 66% [n=28] vs 19% [n=8], 8.17, 2.88-23.16, p<0.0001), with number needed to treat of 2.17 (95% CI 1.60-3.97). For injectable methadone (39% [n=16]; adjusted: 30% [n=14]) versus oral methadone, the difference was not significant (OR 1.74, 95% CI 0.66-4.60, p=0.264; adjusted: 1.79, 0.67-4.82, p=0.249). For injectable heroin versus injectable methadone, a significant difference was recorded (4.26, 1.63-11.14, p=0.003; adjusted: 4.57, 1.71-12.19, p=0.002), but the study was not powered for this comparison. Differences were evident within the first 6 weeks of treatment. INTERPRETATION: Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimised oral methadone. UK Government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts. FUNDING: Community Fund (Big Lottery) Research section, through Action on Addiction.

p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1.

The p53 and NF-kappaB transcription factor families are important, multifunctional regulators of the cellular response to stress. Here we have investigated the regulatory mechanisms controlling p53-dependent cell cycle arrest and cross talk with NF-kappaB. Upon induction of p53 in H1299 or U-2 OS cells, we observed specific repression of cyclin D1 promoter activity, correlating with a decrease in cyclin D1 protein and mRNA levels. This repression was dependent on the proximal NF-kappaB binding site of the cyclin D1 promoter, which has been shown to bind the p52 NF-kappaB subunit. p53 inhibited the expression of Bcl-3 protein, a member of the IkappaB family that functions as a transcriptional coactivator for p52 NF-kappaB and also reduced p52/Bcl-3 complex levels. Concomitant with this, p53 induced a significant increase in the association of p52 and histone deacetylase 1 (HDAC1). Importantly, p53-mediated suppression of the cyclin D1 promoter was reversed by coexpression of Bcl-3 and inhibition of p52 or deacetylase activity. p53 therefore induces a transcriptional switch in which p52/Bcl-3 activator complexes are replaced by p52/HDAC1 repressor complexes, resulting in active repression of cyclin D1 transcription. These results reveal a unique mechanism by which p53 regulates NF-kappaB function and cell cycle progression.

Risk, shame and the public injector: a qualitative study of drug injecting in South Wales.

Drug injecting in public places is associated with elevated health harm among injecting drug users (IDUs). Yet there is little research exploring the lived experience of injecting in public places, and specifically, a need to explore the interplay of public injecting environments, risk practices and social marginalisation. We undertook 49 qualitative interviews with IDUs in South Wales, UK, in six locations. Analyses focused on injectors' narratives of injecting in public places and risk identity. Findings show how the lived experience of public injecting feeds a pervasive sense of risk and 'otherness' among street injectors, in which public injecting environments act as contextual amplifiers of social marginalisation. Injecting in public places was characterised by urgency associated with a fear of interruption, a need to maintain privacy to prevent public exposure, and an awareness or sense of shame. We argue that daily interactions involving public exposure of injecting status, combined with the negative social meanings ascribed to public places used for injection, are experienced as potentially degrading to one's sense of self. We conclude that the public injecting environment is experienced in the context of other forms of public shaming in the lives of street injectors, and is thus productive of symbolic violence. This highlights tensions between strategies seeking to create safer communities and environmental interventions seeking to reduce drug-related health harm, including recent innovations such as the 'drug consumption room' (DCR).

Drug use, health and social outcomes of hard-to-treat heroin addicts receiving supervised injectable opiate treatment: secondary outcomes from the Randomized Injectable Opioid Treatment Trial (RIOTT).

AIMS: The Randomized Injectable Opioid Treatment Trial (RIOTT) compared supervised injectable heroin (SIH) and supervised injectable methadone (SIM) with optimized oral methadone (OOM) (ISRCTN0133807). Heroin addicts (previously unresponsive to treatment) made significant reductions in street heroin use at 6 months when treated with SIH. We now examine secondary outcomes. DESIGN: Multi-site randomized controlled trial (RCT) comparing SIH versus OOM and SIM versus OOM. SETTING: Three supervised injectable opiate clinics in England. PARTICIPANTS: Chronic refractory heroin addicts continuing to inject street heroin virtually daily despite oral substitution treatment (n = 127), randomized to either SIH(n = 43), SIM(n = 42) or OOM(n = 42). All received high levels of medical and psychosocial support. SECONDARY OUTCOMES: wider drug use, crime, health and social functioning at 6 months. FINDINGS: At 6 months, no significant differences were found between treatment groups in wider drug use (crack/cocaine, benzodiazepines, alcohol), physical and mental health (SF-36) or social functioning. Within each treatment group, significant reductions were observed in crime [SIH = odds ratio (OR) 0.05; P < 0.001; SIM = OR 0.11; P = 0.002; OOM = OR 0.11; P = 0.003] and money spent per week on illicit drugs (SIH = mean change £-289.43; P < 0.001; SIM = mean change £-183.41; P < 0.001; OOM = mean change £-162.80; P < 0.001), with SIH significantly more likely to have reduced money spent on illicit drugs versus OOM (mean difference £-92.04; P < 0.001). Significant improvements were seen in physical health for SIH and SIM (SIH = mean change 3.97; P = 0.008; SIM = mean change 4.73; P = 0.002) and mental health for OOM (mean change 6.04; P = 0.013). CONCLUSIONS: Supervised injectable heroin treatment and supervised injectable methadone treatment showed no clearly identified benefit over optimized oral methadone in terms of wider drug use, crime, physical and mental health within a 6-month period, despite reducing street heroin use to a greater extent. However, all interventions were associated with improvements in these outcomes.

Preventing hepatitis C: 'common sense', 'the bug' and other perspectives from the risk narratives of people who inject drugs.

There is little published research about how people who inject drugs are responding to the hepatitis C epidemic. This study seeks to address the prevention of hepatitis C using qualitative interviews with people who inject drugs in London. We explored narratives about risk reduction and hepatitis C in the social and historical context of other risks such as HIV, vein damage and overdose. Themes of the narratives included: the importance of autonomy in the acquisition of safer injecting skills; that safer injection was regarded as 'common sense', normalised and predicated on the risk of HIV; that hepatitis C risk was relativised with HIV risk and thereby seen as less important; and that hepatitis C infection was also seen as unavoidable. These narrative forms represent significant challenges for the management of the hepatitis C epidemic, both in terms of the existing risk reduction efforts designed for HIV and in terms of the articulation of risk reduction for injectors with general public health policy.

Taming systems to create enabling environments for HCV treatment: negotiating trust in the drug and alcohol setting.

HCV (hepatitis C) treatment uptake among the population most affected - people who inject drugs - is suboptimal. Hospital based treatment provision is one evidenced barrier to HCV treatment uptake. In response, HCV treatment is increasingly located in treatment settings seen as more amenable to people who inject drugs, such as drug and alcohol services. We explored the accessibility of HCV treatment provision at two such partnerships. Data collection comprised qualitative interviews collected in 2011 and 2012 with 35 service users and 14 service providers of HCV treatment in London, United Kingdom. We draw here primarily on thematic analyses of service provider accounts, yet narratives relating to trust and environment emerged unsolicited in both user and provider accounts of negotiated HCV treatment access. A key theme in service provider accounts were strategies they deployed to 'tame' the treatment system so as to create an 'enabling environment' of care, in which trust was a critical feature. This 'taming' of the system was enacted through practices of 'negotiated flexibility', including in relation to appointments, eligibility, and phlebotomy. Service user accounts accentuated familiar environments and known health providers as those most trusted, and the potentially stigmatising effects of negotiating treatment in unfamiliar territory, especially hospital settings. Whilst noting the effects of provider strategies to negotiate flexibility on behalf of would-be patients seeking treatment, we conclude by noting the limits of trust relations in settings of constrained choice.

Treatment expectations and satisfaction of treatment-refractory opioid-dependent patients in RIOTT, the Randomised Injectable Opiate Treatment Trial, the UK's first supervised injectable maintenance clinics.

INTRODUCTION AND AIMS: The study investigates patients' pre-treatment expectations of, and post-treatment satisfaction with, supervised injectable opiate treatment delivered within UK's first such clinics within the Randomised Injectable Opiate Treatment Trial (RIOTT) (ISRCTN0133807). DESIGN AND METHODS: Data were collected from 127 chronic heroin addicts recruited to RIOTT and randomised to receive supervised injectable (heroin or methadone) treatment or optimised oral maintenance treatment at supervised injectable maintenance clinics in London, Darlington and Brighton. RESULTS: Of 127 RIOTT patients, 113 (89%) provided responses to structured enquiry about treatment expectations, and 94 (74%) subsequent responses about treatment satisfaction (at six months). Patients were hoping that injectable heroin treatment would: reduce substance misuse (81%); help achieve normality, routine and structure (16%); and increase education and work prospects (15%). At six months, an area of treatment satisfaction most commonly reported by all three trial groups was reduced substance misuse (supervised injectable heroin 59%, supervised injectable methadone 56%, optimised oral methadone 54%). Most found supervision acceptable, but some desired modifications were also identified. DISCUSSION AND CONCLUSIONS: Patients previously considered non-responsive to treatment appear to have similar treatment expectations and aspirations as other drug users in treatment. Supervised injectable opioid treatment patients consistently reported treatment satisfaction but also that more could be done to optimise aspects of current arrangement. This raised the challenging issue of the extent to which opinions of patients need to be taken into consideration in shaping future treatment provision. Future research may need to examine the extent of expectations 'fit' and the relationship between treatment sought and received.