Absence of interferon-lambda 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection

Objectives Absence of a functional interferon-lambda 4 (IFN-lambda 4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-lambda 4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and Delta G(rs1368234815) respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-lambda 4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-lambda 4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-lambda 4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-lambda 4, reduced ITPase activity improved outcome

Studies of acamprosate for the treatment of alcohol dependence

Alcohol dependence is a widespread psychiatric disorder with a prevalence of 4-6% in the adult population in western countries. Acamprosate (Calcium acetyl homotaurinate) is approved in many countries as a medication for the treatment of alcohol dependence. It is assumed that acamprosate modulates glutamate neurotransmission within the central nervous system (CNS). However, there are still uncertainties concerning some aspects of acamprosate treatment. The aim of this thesis was therefore to investigate the effect of acamprosate on certain correlates of alcohol dependence. In one experiment, 56 patients were treated for 21 days with acamprosate vs. placebo. A test battery was then administered by which subjective and physiological responses were measured following presentation of alcohol related stimuli (cue-induced craving) and/or following consumption of a small amount of alcohol (priming-induced craving) in alcohol dependent patients. The results showed that acamprosate attenuated priming-induced craving. Furthermore, acamprosate reduced the priming-induced elevation in plasma cortisol levels. There was also a negative correlation between acamprosate plasma levels and alcohol craving following a priming drink. No effect of acamprosate on cueinduced craving was observed. General craving responses and the correlation to alcohol consumption were also examined, together with neuroendocrine responses. The results showed that acamprosate attenuated general craving responses, and a strong correlation was found between craving and alcohol consumption. No treatment effects on neuroendocrine responses were found. A newly developed liquid chromatography mass spectrometry (LC MS) method was used to evaluate the pharmacokinetics of acamprosate in humans. The aim was to verify earlier pharmacokinetic data in addition to investigate the presence of acamprosate in the CNS. In a 21 days open label study, 13 healthy subjects provided plasma samples regularly and on the last day of treatment also a sample of cerebrospinal fluid (CSF). The results showed that steady state plasma levels of acamprosate was achieved within 5 days following start of treatment and remained above level of quantification for 3 days following termination of treatment. Acamprosate levels in the CSF were between 9 33 ng/mL, which is suggested to represent a pharmacologically relevant concentration. The efficacy of combining acamprosate with psychosocial intervention was investigated in alcohol dependent patients, using an extended psychosocial intervention (EPI) compared to a minimal psychosocial intervention (MPI) for 24 weeks in addition to acamprosate treatment. The results showed no differences between MPI and EPI on any drinking related measure. In conclusion, a potential mechanism by which acamprosate mediates its therapeutic effect may be by attenuating the urge to drink following an alcohol slip, and this effect may be dose-dependent. In addition, it was found that acamprosate modulates the hypothalamic pituitary adrenocortical (HPA) axis response and crosses the blood-brain barrier in humans. Finally, the results suggest that the addition of an intensive psychosocial treatment to concomitant acamprosate treatment does not add to treatment efficacy

A qualitative interview study of patient experiences of receiving motivational enhancement therapy in a Swedish addiction specialist treatment setting

Abstract Background Motivational enhancement therapy (MET) has shown to be efficacious as treatment of alcohol use disorder (AUD), in reducing alcohol consumption and related consequences. However, qualitative research on how patients perceive this treatment is lacking. The aim of this study was to explore how patients experience MET as a treatment for AUD. Methods Fifteen patients (8/7 female/male) participated in semi-structured interviews after receiving MET at a specialized addiction outpatient clinic in Sweden. Data were analyzed by thematic analysis. Results Five themes were identified: the therapist conveyed the MI-spirit, the therapist did not guide on how to reach the goal, participants were committed to change before starting treatment, participants were uncertain if treatment was enough to maintain change, and significant others were not wanted in sessions. Participants appreciated the supportive relationship with their therapist, but some experienced therapy as overly positive, with no room to talk about failure. Further, they experienced a low level of guidance in goal-setting. For some, this was empowering, while others requested more direction and advice. Participants perceived their motivational process to have started before treatment. MET was considered to be too brief. None of the participants brought a significant other to a session. Conclusions Therapist behaviors in line with MI spirit were emphasized as key to the development of a positive therapeutic relationship. More specific advice on goal-setting may be effective for supporting change in some patients. Longer treatment is requested among patients to support the patient’s self-efficacy for change. Significant others can support change without necessarily being present in sessions. Trial registration: The current trial was retrospectively registered at isrtcn.com (14539251)

An online self-directed program combining Community Reinforcement Approach and Family Training and parenting training for concerned significant others sharing a child with a person with problematic alcohol consumption: a randomized controlled trial.

BACKGROUND: There is an urgent need for interventions helping children affected by parental problematic alcohol consumption (PAC). Such interventions could target partners to individuals with PAC, partners who often themselves show impaired quality of life and mental health. The aim of this study was to investigate the efficacy of an online self-directed intervention combining components from Community Reinforcement Approach and Family Training (CRAFT) with a parenting training program for concerned significant others (CSOs) sharing a child with a co-parent with PAC. METHODS: A randomized controlled parallel-group superiority trial compared the efficacy of the online intervention for CSOs sharing a child (3-11 y/o) with a co-parent with PAC (N = 37), to an active control group (N = 39) receiving written psychoeducational material. Assessment of outcomes was conducted at baseline, 3 weeks, 8 weeks and 12 weeks. Primary outcome was children's mental health, while secondary outcomes included parental self-efficacy, CSO mental health and co-parent alcohol consumption and level of dependence. Linear mixed effect models with a factorial time variable were used to model time by group interaction effects. RESULTS: Recruitment rate was slow and a vast majority of interested CSOs were excluded at baseline assessment, mainly due experience of co-parent violence. The target sample size was not met. The intention to treat analysis did not show any significant time by group effects on either the primary or secondary outcomes during the follow-up period: the CSOs reported a significant reduction in co-parent alcohol consumption and severity of alcohol dependence and showed significant improvements in parental self-efficacy for how to handle effects of co-parent alcohol consumption, but no differences were found between the two conditions. CONCLUSIONS: The current study found no evidence supporting efficacy of a novel, online self-directed intervention on children's mental health, CSO mental health and co-parent alcohol related outcomes. Engaging in a support program or receiving information appears to initiate behavior change in the CSOs which affects the alcohol consumption and severity of dependence for co-parents with PAC. It is suggested that future studies may preferably focus on CSOs in more severely affected contexts. Trial registration The trial was pre-registered at isrctn.com reference number ISRCTN38702517, November 28, 2017

Treatment of alcohol dependence in Swedish primary care : perceptions among general practitioners

OBJECTIVE: To describe general practitioners' (GPs) attitudes to the management of patients with alcohol dependence in primary care and current treatment routines and their view on a new treatment approach; internet-based Cognitive Behavioral Therapy (iCBT). DESIGN: A qualitative interview study with ten GPs participating in a randomized controlled trial. The interviews were analyzed using qualitative content analysis. SETTING: The participating GPs were recruited via purposeful sampling from primary care clinics in Stockholm. SUBJECTS: The GPs were participants in an RCT investigating if iCBT when added to treatment as usual (TAU) was more effective than TAU only when treating alcohol dependence in primary care. RESULTS: The GPs found alcohol important to discuss in many consultations and perceived most patients open to discuss their alcohol habits. Lack of training and treatment options were expressed as limiting factors when working with alcohol dependence. According to the respondents, routines for treating alcohol dependence were rare. CONCLUSION: GPs believed that iCBT might facilitate raising questions about alcohol use and thought iCBT may serve as an attractive treatment option to some patients. The iCBT program did not require GPs to acquire skills in behavioral treatment, which could make implementation more feasible.KEY POINTSAlcohol dependence is highly prevalent, has a large treatment gap and is relevant to discuss with patients in many consultations in primary care.This study is based on interviews with 10 GPs participating in a randomized controlled trial comparing internet-based Cognitive Behavioral Therapy (iCBT) for alcohol-dependent patients to treatment as usual.GPs viewed alcohol habits as important to discuss and they perceived most patients are open to discuss this.The access to iCBT seemed to increase GPs' willingness to ask questions about alcohol and was viewed as an attractive treatment for some patients.The iCBT program did not require GPs to acquire skills in behavioral treatment, which might be timesaving and make implementation more feasible

Treating alcohol use disorders in primary care - a qualitative evaluation of a new innovation : the 15-method

OBJECTIVE: This study aims to explore how the characteristics of an innovation, the 15-method, a stepped care model for treatment of alcohol use disorders in primary care was perceived. METHODS/DESIGN/SETTING/SUBJECT: General practitioners and heads of primary care units (n = 10) that delivered the 15-method in a randomized controlled trial participated in individual interviews at two occasions in Stockholm, Sweden. Data were analyzed with theoretical thematic analysis, using Diffusion of Innovation Theory. RESULTS: The participants described that offering the 15-method met a need among their patients. Participants were positive towards the training and the manual for the method. They mentioned a previous lack of routines to work with alcohol use disorders. The 15-method was described as easy to use. It would however be more feasible to implement in a team of different professions, rather than among general practitioners only. Priorities made by regional health care managers were described as important for the implementation, as well as financial incentives. A barrier to implementation was that alcohol screening was perceived as difficult. While the 15-method was perceived as effective in reducing the patients' alcohol use and cost effective, participants expressed uncertainty about the long-term effects. CONCLUSIONS: The 15-method provides structure for treatment of alcohol use disorders and is described by general practitioners and heads as a promising approach. Being able to offer treatment for alcohol dependence may increase the uptake of alcohol interventions in primary care. KEY POINTS Little attention has been given to develop treatment models for alcohol use disorders that are adapted to primary care settings. This study describes how an innovation, the 15-method, a stepped care model for treatment of alcohol use disorders in primary care was perceived. The 15-method provides structure for treatment of alcohol use disorders in primary care and is described by general practitioners and heads as a promising approach. Being able to offer treatment for alcohol dependence may increase the uptake of alcohol interventions in primary care