A Feasibility Study of an Intervention for Structured Preparation before Detoxification in Alcohol Dependence: the SPADe trial protocol

Background: Alcohol-related harm is currently estimated to cost the National Health Service (NHS) in England £3.5bn a year. Of the estimated 1.6 million people with some degree of alcohol dependence, some 600,000 are believed to be moderately or severely dependent and may benefit from intensive treatment. Outcomes from medically assisted withdrawal, also referred to as detoxification, are often poor, with poor engagement in relapse prevention interventions and subsequent high relapse rates. Detoxification is costly both financially and to the individual. It has been found that people who experience multiple detoxifications show more emotional and cognitive impairments. These changes may confer upon them the inability to resolve conflict and increased sensitivity to stress thus contributing to increased vulnerability risk of relapse. The study aims to test the feasibility of using a group intervention aiming to prepare participants for long term abstinence before, rather than after, they have medically assisted detoxification. The current study will establish key parameters that influence trial design such as recruitment, compliance with the intervention, retention, and sensitivity of alternative outcome measures, in preparation for a future Randomised Controlled Trial (RCT). This paper presents the protocol of the feasibility study. Methods: The study corresponds to Phase 2 of the Medical Research Council (MRC) complex interventions guidelines which cover the development and feasibility testing of an intervention. The work is in three stages. The development, adaptation, and implementation of the Structured Preparation before Alcohol Detoxification (SPADe) intervention (stage 1), a randomised feasibility study with economic evaluation (stage 2) and a qualitative study (stage 3). Fifty participants will be recruited from two community alcohol treatment services in England. Participants will be randomised in two arms: the treatment as usual arm (TAU), which includes planned medically assisted detoxification and aftercare and the intervention arm in which participants will receive structured group preparation before detoxification in addition to TAU. The main outcomes are duration of continuous abstinence with no incidents of lapse or relapse, percentage of days abstinent and time to relapse. Discussion: The socioeconomic harms associated with alcohol have been well documented yet existing treatment options have not been able to reduce high relapse rates. This study will build on existing naturalistic studies underpinned by psychological interventions offered early and before detoxification from alcohol, which aim to reverse automatised habitual behaviours and thus may help us to understand how better to support people to remain abstinent and improve post detoxification outcomes. Trial registration: Name of registry: ISRCTN; Trial Registration Number: 14621127; Date of Registration: 22/02/2017; URL of trial registry record: http://www.isrctn.com/ISRCTN1462112

An exploration of identity change in post-detoxification alcohol dependent individuals

Purpose: Dependent alcohol use is a severe addictive disorder with significant enduring consequences for health and social functioning. We aimed to inductively explore the process of identity change for alcohol dependent people progressing through a ‘pre-habilitation’ intervention, alcohol detoxification and post-detoxification recovery support. Design: Qualitative study as a part of a process evaluation situated within a UK feasibility trial of a group-based intervention in preparation for structured alcohol detoxification. Semi-structured qualitative interviews (face-to-face or telephone) collected self-reported data on experiences of treatment provision as part of the feasibility trial. Thematic analysis of transcripts and iterative categorisation of identity related themes and concepts was conducted with verification of analysis undertaken by a second coder. Findings: Identity change was revealed in participant narratives around the meta themes of external (social-identity) and internal (self-identity) concepts. External influences impacting social identity were key, having influenced initiation into alcohol use, influencing acceptance of the stigmatised ‘alcoholic’ label, and then being central to the treatment journey. Internal influences on self-identity also impacted on the process of identity change. In recovery, there was hope in discovering a new ‘normal’ identity or rediscovering normality. Originality: Analysis demonstrates that moving from regular alcohol use to problematic use is a journey of identity change that is influenced at the macro (cultural), meso (group) and micro (relational) social levels. Throughout the treatment journey, social influences in gaining a new non-drinker identity are key. Findings suggest a need for long term support through treatment and community-based groups specifically to foster positive identity change that may not have been addressed previously

A feasibility trial of an intervention in alcohol dependence for structured preparation before detoxification versus usual care: the SPADe trial results

Background Individuals who are ‘moderately’ or ‘severely’ dependent consume alcohol at levels that are likely to have a severe impact on their own health and mortality, the health and behaviours of others (family members) and to have economic and social implications. Treatment guidelines suggest that treatment needs to be planned with medically assisted withdrawal (also referred to as detoxification), and aftercare support but outcomes are poor with low proportions engaging in after care and high relapse rates. An approach of structured preparation before alcohol detoxification (SPADe) puts an emphasis on introducing lifestyle changes, development of coping strategies for cravings, stress and emotions as well as introducing changes to the immediate family and social environment in advance of alcohol cessation. Such a pre-habilitation paradigm compliments the established treatment approach. The key research question was: can we design a large scale, randomised controlled trial (RCT) that will answer whether such an approach is more effective than usual care in helping individuals to maintain longer periods of alcohol abstinence? Methods This is a pragmatic, parallel, two-arm, feasibility RCT comparing SPADe and usual care against usual care only in maintaining alcohol abstinence in adults with alcohol dependence receiving care in two community addiction services in London. Feasibility outcomes, exploration of primary and secondary clinical outcomes and health economic outcomes are analysed. The trial follows the guidelines of phase 2 of the Medical Research Council (MRC) for complex interventions. Results We were able to recruit 48/50 participants during a period of 9 months. Retention in the trial for the whole period of the 12 months was 75%. Treatment compliance was overall 44%. Data completion for the primary outcome was 65%, 50% and 63% at 3, 6 and 12 months, respectively. The intervention group had more days abstinent in the previous 90 days at the 12 months (n = 54.5) versus control (n = 41.5). Conclusions The results of this feasibility trial indicate that with the appropriate modifications, a full multicentred trial would be possible to test the effectiveness and cost-effectiveness of a pre-habilitation approach such as the SPADe group intervention in addition to usual care against usual care only. Trial registration Name of registry: ISRCTN; Trial Registration Number: 14621127; Date of Registration: 22/02/2017

Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia

Background: Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia.Methods: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies.Results: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample.Conclusion: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family

Serum creatine kinase elevation associated with olanzapine treatment

On 2 May 2008, a 25-year-old male patient on olanzapine 15 mg developed mild central chest pain, and blood tests revealed a high creatine kinase (CK) value at 1016 iu/l. Troponin, CK-MB, CK:MB ratio, full blood count (FBC), urea and electrolytes (U&E), C reactive protein (CRP) and glucose were all normal. Liver enzymes were marginally raised: alanine aminotransferase (ALT) 91 iu/l, γ-glutamyl transferase (GGT) 46 iu/l, alkaline phosphatase (ALP) 137 iu/l. The ECG was normal and the chest pain later resolved and was thought likely to be due to costochondritis. A repeat blood test on 7 May revealed further elevation of CK at 1391 iu/l and olanzapine was stopped. CK continued to rise: 19 May 2857 iu/l, 20 May 3285 iu/l, and 22 May 3646 iu/l. On 30 May CK dropped to 708 iu/l, on 20 June it was 593 iu/l, and on 30 June CK was 343 iu/l. The patient was started on amisulpiride on 15 July and CK began to rise again: on 18 July it was 445 iu/l and on 31 July CK was 480 iu/l, at which time the medication was stopped. The patient did not have any signs or symptoms of physical disorder on this occasion

The Epsin 4 Gene on Chromosome 5q, Which Encodes the Clathrin-Associated Protein Enthoprotin, Is Involved in the Genetic Susceptibility to Schizophrenia

Chromosome 5q33 is a region that has previously shown good evidence of linkage to schizophrenia, with four LOD scores >3.00 in independent linkage studies. We studied 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5′ end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included two microsatellite markers, D5S1403 (P=.01) and AAAT11 (P=.009), and two single-nucleotide–polymorphism markers within the Epsin 4 gene, rs10046055 (P=.007) and rs254664 (P=.01). A series of different two- and three-marker haplotypes were also significantly associated with schizophrenia, as confirmed with a permutation test (HapA, P=.004; HapB, P=.0005; HapC, P=.007; and HapD, P=.01). The Epsin 4 gene encodes the clathrin-associated protein enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons. A genetically determined abnormality in the structure, function, or expression of enthoprotin is likely to be responsible for genetic susceptibility to a subtype of schizophrenia on chromosome 5q33.3

A Haploview generated diagram of the location of SNPs in the DNTBP1 gene that were genotyped in this study

<p><b>Copyright information:</b></p><p>Taken from "Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia"</p><p>http://www.behavioralandbrainfunctions.com/content/3/1/50</p><p>Behavioral and brain functions : BBF 2007;3():50-50.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2093937.</p><p></p> SNPs marked with an asterisk have been found to be associated with schizophrenia in previous studies. Marker to marker D' statistics are shown below with LD blocks defined as solid spine of LD with a D' > 0.8