Virtual adjunctive gut-directed hypnotherapy for people with Crohn's disease: A randomized controlled pilot and feasibility trial.

BACKGROUND: Gut-directed hypnotherapy appears to be a promising adjunctive treatment for people with Crohn's disease. The primary objective of this pilot trial was to evaluate feasibility and acceptability of virtually delivered hypnotherapy to determine the parameters for a future definitive trial. METHODS: This prospective, single-site, randomized controlled pilot and feasibility trial compared a 7-week course of virtually delivered adjunctive gut-directed hypnotherapy to standard medical treatment only for adults with Crohn's disease. Primary outcomes were study feasibility and intervention acceptability. Secondary outcomes were objective disease activity and patient-reported outcomes. Assessments took place at five time-points: baseline, post-intervention, and follow-up three-, six-, and 12-months post-intervention. KEY RESULTS: Recruitment took place between July 2020 and August 2021 at a tertiary hospital. Recruitment was initially slow and subsequently expanded to community settings. Thirty-seven participants were enrolled in the trial: 95% were retained at post-intervention and 76% at 12-months. Completion of online assessments was high (97-100% across all time-points) whilst objective data collection was low (34-44%). Most intervention participants completed all hypnotherapy sessions (88%) and reported being extremely satisfied (73%), despite 60% experiencing technical issues. CONCLUSION & INFERENCES: Virtually delivered hypnotherapy was acceptable to participants. Certain aspects of the trial including online assessment were feasible, while recruitment and objective data collection were challenges. Undertaking a future definitive trial will require broader recruitment scope and significant funding for widespread objective data collection. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTR#1260000348954.

Effects of acceptance and commitment therapy on fatigue for patients with cancer and other chronic health conditions: A systematic review and meta-analysis.

OBJECTIVE: Fatigue is significantly more prevalent in the chronically ill compared to healthy individuals. Fatigue is one of the most reported and debilitating symptoms in individuals with chronic health conditions. Despite this, there is limited evidence examining the efficacy of psychological interventions to reduce fatigue, with the majority having focused on Cognitive Behaviour Therapy. As Acceptance and Commitment Therapy (ACT) has shown to be efficacious in improving other outcomes for people with chronic health conditions, this systematic review and meta-analysis aimed to determine the efficacy of ACT in reducing fatigue for this population. METHODS: A systematic search in MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, US National Library of Medicine Clinical Trial Register and reference lists of relevant papers was conducted to obtain relevant studies. Inclusion criteria specified the study needed to be a randomised controlled trial which implemented an ACT predominant intervention and measured fatigue in adults with a chronic health condition. Data was pooled using the inverse-variance random effects model, with restricted maximum likelihood estimation, providing the standardized mean difference between control and experimental groups post intervention. RESULTS: The current systematic review and meta-analysis included eight RCTs. Participants with a chronic condition (including cancer and fibromyalgia) who received ACT interventions, displayed reduced levels of fatigue, indicative of a small effect (SMD = -0.16, 95% CI [-0.30, -0.01], p = 0.03). CONCLUSION: While the evidence is limited to cancer and fibromyalgia, ACT shows promise in reducing fatigue. Future research should examine ACT for fatigue in other chronic health condition populations to broaden the scope of these findings.

Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies.

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended.

Patients with inflammatory bowel disease at risk of sub-optimal outcomes report poorer biopsychosocial functioning than controls: data from two cross-sectional surveys.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Standard treatment focuses on reducing the inflammatory burden, however, not all patients respond adequately to conventional medical therapy. These patients, referred to as Patients at Risk of Suboptimal Outcomes (PARSO), have not been studied collectively. The present study aimed to understand the biopsychosocial characteristics of patients with IBD at risk of sub-optimal outcomes for targeted multi-disciplinary treatment to encourage optimal outcomes. Two cross-sectional online surveys, including 760 PARSO and 208 control (non-PARSO) participants, were conducted and their data combined. Biopsychosocial factors included quality of life, pain, disease activity, wellbeing, fatigue, stress, social support, and sleep difficulties. Results suggest that active disease, quality of life, stress, social support, sleep difficulties, fatigue, wellbeing, smoking status, IBD subtype, and pain are significantly associated with membership in a subgroup of PARSO. We also used logistic regression to explore variables associated with the total likelihood of PARSO status. Overall, the model predicted the at-risk status to a substantial degree (R2-2ll = .41, x2 = 401.53, p < .001). Younger age in years, female sex, Crohn's disease, and greater measured and subjective disease activity significantly increased the likelihood of participants being identified as PARSO; OR CI95% = 0.96 (0.95, 0.97); OR CI95% = 4.46 (2.95, 6.71); OR CI95% = 1.58 (1.05, 2.37); OR CI95% = 3.52 (2.18, 5.69); OR CI95% = 45.99 (14.11, 149.89). A biopsychosocial and personalised approach to IBD care might be necessary to support those at risk of suboptimal outcomes in achieving better long-term wellbeing.

The LIFEwithIBD Intervention: Study Protocol for a Randomized Controlled Trial of a Face-to-Face Acceptance and Commitment Therapy and Compassion-Based Intervention Tailored to People With Inflammatory Bowel Disease.

Background: There is ample evidence of the high mental health burden caused by Inflammatory Bowel Disease (IBD). Several constructs such as experiential avoidance, cognitive fusion, shame, and self-criticism have recently emerged as potential intervention targets to improve mental health in IBD. Psychotherapeutic models such as Acceptance and Commitment Therapy and compassion-based interventions are known to target these constructs. In this protocol, we aim to describe a two-arm Randomized Controlled Trial (RCT) testing the efficacy of an ACT and compassion-focused intervention named Living with Intention, Fullness, and Engagement with Inflammatory Bowel Disease (LIFEwithIBD) intervention + Treatment As Usual (TAU) vs. TAU in improving psychological distress, quality of life, work and social functioning, IBD symptom perception, illness-related shame, psychological flexibility, self-compassion, disease activity, inflammation biomarkers, and gut microbiota diversity. Methods: This trial is registered at ClinicalTrials.gov (Identifier: NCT03840707, date assigned 13/02/2019). The LIFEwithIBD intervention is an adaptation to the IBD population of the Mind programme for people with cancer, an acceptance, mindfulness, and compassion-based intervention designed to be delivered in a group format. The LIFEwithIBD intervention's structure and topics are presented in this protocol. Participants were recruited at the Gastroenterology Service of the Coimbra University Hospital between June and September 2019. Of the 355 patients screened, 61 participants were selected, randomly assigned to one of two conditions [experimental group (LIFEwithIBD + TAU) or control group (TAU)] and completed the baseline assessment. Outcome measurement took place at baseline, post-intervention, 3- and 12-month follow-ups. Discussion: Results from this RCT will support future studies testing the LIFEwithIBD intervention or other acceptance and/or compassion-based interventions for IBD.

Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis of Mood Effects.

This meta-analysis examines mood changes after bilateral subthalamic deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). Deep brain stimulation improves motor outcomes in Parkinson's disease but there appears to be conflicting reports as to subsequent mood outcomes. Pubmed, PsychINFO and SCOPUS were searched for studies assessing mood outcomes in PD patients who had undergone STN-DBS published between January 2003 and the end of January 2019. Random effects meta-analyses were conducted for all outcome groups with at least two studies homogenous in design and measure. Forty-eight studies, providing data on negative moods (such as depression, anxiety, apathy, and anger) and positive moods (pleasure and euphoria) were assessed. Results of the meta-analysis suggest that post-DBS, depression and anxiety symptoms improve and there is a reduction in negative affect, an increase in apathy, and in energy level. Although there have been reported cases of mania post-DBS surgery, the meta-analysis suggested no significant changes in symptoms of mania in the broader DBS population. Considerable heterogeneity was found and partially addressed through meta-regression and qualitative assessment of the included STN-DBS controlled studies. The major strengths of this meta-analysis, include attention to outcome validity, heterogeneity, independence of samples, and clinical utility, with the potential to improve post-operative safety through comprehensive consideration of mood and psychological adjustment. It appears that STN-DBS is a relatively safe and, in the case of mood symptomatology, an advantageous treatment of Parkinson's disease.

Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways.

The effect of N-acetylcysteine (NAC) on human cognition - A systematic review.

Oxidative stress, neuroinflammation and neurogenesis are commonly implicated as cognitive modulators across a range of disorders. N-acetylcysteine (NAC) is a glutathione precursor with potent antioxidant, pro-neurogenesis and anti-inflammatory properties and a favourable safety profile. A systematic review of the literature specifically examining the effect of NAC administration on human cognition revealed twelve suitable articles for inclusion: four examining Alzheimer's disease; three examining healthy participants; two examining physical trauma; one examining bipolar disorder, one examining schizophrenia, and one examining ketamine-induced psychosis. Heterogeneity of studies, insufficiently powered studies, infrequency of cognition as a primary outcome, heterogeneous methodologies, formulations, co-administered treatments, administration regimes, and assessment confounded the drawing of firm conclusions. The available data suggested statistically significant cognitive improvements following NAC treatment, though the paucity of NAC-specific research makes it difficult to determine if this effect is meaningful. While NAC may have a positive cognitive effect in a variety of contexts; larger, targeted studies are warranted, specifically evaluating its role in other clinical disorders with cognitive sequelae resulting from oxidative stress and neuroinflammation.

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial.

BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting. METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress. DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial. TRIAL REGISTRATION: The PANACEA trial has been registered with the Therapeutic Goods Administration, and the Australian New Zealand Clinical Trials Registry: ACTRN12614000411640 ; registered on 15 April 2014.