Group music therapy with songwriting for adult patients with long-term depression (SYNCHRONY study): a feasibility and acceptability study of the intervention and parallel randomised controlled trial design with wait-list control and nested process evaluation.

BACKGROUND: Despite effective treatments, one fifth of patients develop chronic depression. Music therapy may offer a different approach. This study aimed to assess feasibility and acceptability of a music therapy intervention and trial methodology. METHODS: A parallel two-arm randomised controlled trial with wait-list control, mixed feasibility/acceptability measures and nested process evaluation. Adults with long-term depression (symptom duration > 1 year) were recruited from community mental health services and computer randomised to 42 sessions of group music therapy with songwriting three times per week or wait-list control. Depression, social functioning, distress, quality of life, satisfaction and service use were assessed by blinded researchers at enrolment, 1 week and 3 and 6 months post-therapy. Outcomes were analysed descriptively, controlling for baseline covariates. Recruitment (number eligible, participation and retention rates) and intervention (fidelity, adherence) feasibility were assessed using pre-defined stop-go criteria. Attendance, adverse events, mood, relationship satisfaction and semi-structured interviews were analysed in a nested process evaluation. RESULTS: Recruitment processes were feasible with 421 eligible, 12.7% participation and 60% (18/30) retention. Thirty participants were randomised to intervention (N = 20) and control (N = 10). Session attendance was low (mean 10.5) with four withdrawals. Music therapist adherence was good but changes to session frequency were suggested. Outcomes were available for 10/20 treatment and 9/10 wait-list participants. Depression increased in both arms post-therapy. Treatment depression scores fell below baseline 3 and 6 months post-therapy indicating improvement. Wait-list depression scores increased from baseline 3 and 6 months post-therapy. At 3 months, the treatment arm improved from baseline on all measures except satisfaction and functioning. At 6 months, quality of life, distress and functioning improved with reduction in health service contacts. High-attending participants improved more than low-attending. Seven adverse events (one serious) were reported. LIMITATIONS: As this was a feasibility study, clinical outcomes should be interpreted cautiously. CONCLUSION: A randomised controlled trial of group music therapy using songwriting is feasible with inclusion criteria and session frequency modifications, but further intervention development is required. TRIAL REGISTRATION: ISRCTN18164037 on 26.09.2016.

I know what I like, and I like what I know: Patient preferences and expectations when choosing an arts therapies group.

Patient preferences deserve consideration as they play a role in engagement with psychosocial interventions. This study sought to understand more about preferences and expectations of the arts therapies, in order to support informed decision-making. Semi-structured interviews were conducted with 17 participants in a trial of group music therapy, art therapy and dance-movement therapy. Audio recordings were transcribed. Data relating to the process of choosing their preferred arts therapies groups, expectations and experiences of the groups were analysed using framework analysis. Three overarching themes were found relating to the experience of choosing an arts therapies group and subsequently attending it: past experiences of the art forms, social interactions in the groups and expectations of helpfulness. Familiarity and perceived capability were important factors for the therapy experiences. Although each participant had a unique decision-making process, the themes offer understanding of common considerations when making a choice about engagement with the arts therapies. Clinicians should guide discussions around past experiences of the art forms, group dynamics and therapy aims during shared decision making for the arts therapies.

Preferences for group arts therapies: a cross-sectional survey of mental health patients and the general population.

OBJECTIVES: The arts therapies include music therapy, dance movement therapy, art therapy and dramatherapy. Preferences for art forms may play an important role in engagement with treatment. This survey was an initial exploration of who is interested in group arts therapies, what they would choose and why. DESIGN: An online cross-sectional survey of demographics, interest in and preferences for the arts therapies was designed in collaboration with patients. The survey took 10 min to complete, including informed consent and 14 main questions. Summary statistics, multinomial logistic regression and thematic analysis were used to analyse the data. SETTING: Thirteen National Health Service mental health trusts in the UK asked mental health patients and members of the general population to participate. PARTICIPANTS: A total of 1541 participants completed the survey; 685 mental health patients and 856 members of the general population. All participants were over 18 years old, had capacity to give informed consent and sufficient understanding of English. Mental health patients had to be using secondary mental health services. RESULTS: Approximately 60% of participants would be interested in taking part in group arts therapies. Music therapy was the most frequent choice among mental health patients (41%) and art therapy was the most frequent choice in the general population (43%). Past experience of arts therapies was the most important predictor of preference for that same modality. Expectations of enjoyment, helpfulness, feeling capable, impact on mood and social interaction were most often reported as reasons for preferring one form of arts therapy. CONCLUSIONS: Large proportions of the participants expressed an interest in group arts therapies. This may justify the wide provision of arts therapies and the offer of more than one modality to interested patients. It also highlights key considerations for assessment of preferences in the arts therapies as part of shared decision-making.

A risk stratifying tool to facilitate safe late-stage percutaneous endoscopic gastrostomy in ALS.

BACKGROUND: The safety of percutaneous endoscopic gastrostomy (PEG) insertion in amyotrophic lateral sclerosis (ALS) patients with significant respiratory compromise has been questioned. OBJECTIVES: To review the characteristics of an ALS clinic patient cohort undergoing PEG, and the introduction of a risk stratification tool with procedural adaptations for higher-risk individuals. METHODS: Patients undergoing PEG insertion were analysed (n = 107). Cases stratified as higher-risk underwent insertion in a semi-recumbent position, minimising sedation, with the option of nasal non-invasive ventilation. RESULTS: All underwent successful PEG. One-third had pre-procedure FVC ≤50% (mean, 64 ± 22%). Of those who underwent PEG insertion after introduction of risk stratification (n = 58), 39 (67%) met criteria for being higher risk, 16 (41%) of whom had FVC ≤50% (p = 0.005). High-risk patients received lower sedative doses vs. the low-risk group (midazolam 2.1 ± 1.1 vs.2.8 ± 0.95mg, p = 0.021; fentanyl 42 ± 16 vs. 60 ± 21µg, p = 0.015). Four deaths occurred within one month of insertion (attributable to the natural disease course). CONCLUSIONS: Risk stratification identified a greater number of patients with evidence of respiratory compromise than using the sole criterion of FVC ≤50%. A modified PEG procedure enabled safe insertion despite respiratory compromise, in those who might not have tolerated attempted insertion by alternative means such as radiologically-inserted gastrostomy.

Nutritional pathway for people with motor neurone disease.

This paper provides an overview of the nutritional management and care of people living with motor neurone disease (MND) in a specialist nutrition clinic. A specialist pathway of care has been developed to enable people living with MND to undergo a percutaneous endoscopic gastrostomy (PEG) procedure in a safe way; the pathway incorporates attendance at a dedicated nutrition clinic, a stratification tool to identify patients with a high periprocedural risk and a PEG insertion team with significant experience in the MND population. Since this pathway has been in place, gastrostomies have been successfully placed in patients with a forced vital capacity (FVC) of less than 50%; previously, this would not have been possible.

Inhibition of neuronal nicotinic acetylcholine receptor subtypes by alpha-Conotoxin GID and analogues.

alpha-Conotoxins are small disulfide-rich peptides from the venom of the Conus species that target the nicotinic acetylcholine receptor (nAChR). They are valuable pharmacological tools and also have potential therapeutic applications particularly for the treatment of chronic pain. alpha-Conotoxin GID is isolated from the venom of Conus geographus and has an unusual N-terminal tail sequence that has been shown to be important for binding to the alpha4beta2 subtype of the nAChR. To date, only four conotoxins that inhibit the alpha4beta2 subtype have been characterized, but they are of considerable interest as it is the most abundant nAChR subtype in the mammalian brain and has been implicated in a range of diseases. In this study, analysis of alanine-scan and truncation mutants of GID reveals that a conserved proline in alpha-conotoxins is important for activity at the alpha7, alpha3beta2, and alpha4beta2 subtypes. Although the proline residue was the most critical residue for activity at the alpha3beta2 subtype, Asp(3), Arg(12), and Asn(14) are also critical at the alpha7 subtype. Interestingly, very few of the mutations tested retained activity at the alpha4beta2 subtype indicating a tightly defined binding site. This lack of tolerance to sequence variation may explain the lack of selective ligands discovered for the alpha4beta2 subtype to date. Overall, our findings contribute to the understanding of the structure-activity relationships of alpha-conotoxins and may be beneficial for the ongoing attempts to exploit modulators of the neuronal nAChRs as therapeutic agents.

Structure-activity relationships of alpha-conotoxins targeting neuronal nicotinic acetylcholine receptors.

alpha-Conotoxins that target the neuronal nicotinic acetylcholine receptor have a range of potential therapeutic applications and are valuable probes for examining receptor subtype selectivity. The three-dimensional structures of about half of the known neuronal specific alpha-conotoxins have now been determined and have a consensus fold containing a helical region braced by two conserved disulfide bonds. These disulfide bonds define the two-loop framework characteristic for alpha-conotoxins, CCX(m)CX(n)C, where loop 1 comprises four residues (m = 4) and loop 2 between three and seven residues (n = 3, 6 or 7). Structural studies, particularly using NMR spectroscopy have provided an insight into the role and spatial location of residues implicated in receptor binding and biological activity.

Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence.

Using assay-directed fractionation of Conus geographus crude venom, we isolated alpha-conotoxin GID, which acts selectively at neuronal nicotinic acetylcholine receptors (nAChRs). Unlike other neuronally selective alpha-conotoxins, alpha-GID has a four amino acid N-terminal tail, gamma-carboxyglutamate (Gla), and hydroxyproline (O) residues, and lacks an amidated C terminus. GID inhibits alpha 7 and alpha 3 beta 2 nAChRs with IC(50) values of 5 and 3 nm, respectively and is at least 1000-fold less potent at the alpha 1 beta 1 gamma delta, alpha 3 beta 4, and alpha 4 beta 4 combinations. GID also potently inhibits the alpha 4 beta 2 subtype (IC(50) of 150 nm). Deletion of the N-terminal sequence (GID Delta 1-4) significantly decreased activity at the alpha 4 beta 2 nAChR but hardly affected potency at alpha 3 beta 2 and alpha 7 nAChRs, despite enhancing the off-rates at these receptors. In contrast, Arg(12) contributed to alpha 4 beta 2 and alpha 7 activity but not to alpha 3 beta 2 activity. The three-dimensional structure of GID is well defined over residues 4-19 with a similar motif to other alpha-conotoxins. However, despite its influence on activity, the tail appears to be disordered in solution. Comparison of GID with other alpha 4/7-conotoxins which possess an NN(P/O) motif in loop II, revealed a correlation between increasing length of the aliphatic side-chain in position 10 (equivalent to 13 in GID) and greater alpha 7 versus alpha 3 beta 2 selectivity.