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Abstract Background About 30% of cancer survivors suffer from chemotherapy-induced peripheral neuropathy (CIPN) ≥6 months after completion of chemotherapy. This condition, for which treatment options are scarce, comes with limitations in daily life functioning and decreased quality of life. The current study examines the effectiveness of an online self-help intervention based on Acceptance and Commitment Therapy (ACT) in comparison to a waiting list condition (WLC) to deal with CIPN. In addition, it examines which factors moderate effects and to what extent the effects differ between guided and unguided ACT intervention. Methods A two-parallel, non-blinded randomized controlled trial (RCT) will be carried out. Adult cancer survivors who experience painful CIPN for at least 3 months and completed chemotherapy at least 6 months ago will be recruited (n=146). In the intervention condition, participants will follow an 8-week self-management course containing 6 modules regarding psychoeducation and ACT processes, including therapeutic email guidance. By means of text and experiential exercises, supplemented with illustrations, metaphors, and audio files, people will learn to carry out value-oriented activities in their daily life with pain. Participants will learn new ways of coping with pain, including reducing pain avoidance and increasing pain acceptance. Participants in the WLC will be invited to follow the intervention without therapeutic guidance 5 months after start. Pain interference is the primary outcome, while psychological distress, quality of life, CIPN symptom severity, pain intensity, psychological flexibility, mindfulness skills, values-based living, and pain catastrophizing will serve as secondary outcomes. All outcome measures will be evaluated at inclusion and baseline, early-intervention, mid-intervention, post-treatment, and 3- and 6-month post-treatment. Qualitative interviews will be conducted post-treatment regarding experiences, usage, usability, content fit, and satisfaction with the intervention. Discussion This study will provide valuable information on the effectiveness of an online self-help intervention based on ACT versus WLC for chronic painful CIPN patients. Trial registration ClinicalTrials.gov NCT05371158 . Registered on May 12, 2022. Protocol version: version 1, 24-05-2022

Background and Aims: The brain age gap (BAG), calculated as the difference between a machine learning model‐based predicted brain age and chronological age, has been increasingly investigated in psychiatric disorders. Tobacco and alcohol use are associated with increased BAG; however, no studies have compared global and regional BAG across substances other than alcohol and tobacco. This study aimed to compare global and regional estimates of brain age in individuals with substance use disorders and healthy controls. Design: This was a cross‐sectional study. Setting: This is an Enhancing Neuro Imaging through Meta‐Analysis Consortium (ENIGMA) Addiction Working Group study including data from 38 global sites. Participants: This study included 2606 participants, of whom 1725 were cases with a substance use disorder and 881 healthy controls. Measurements: This study used the Kaufmann brain age prediction algorithms to generate global and regional brain age estimates using T1 weighted magnetic resonance imaging (MRI) scans. We used linear mixed effects models to compare global and regional (FreeSurfer lobestrict output) BAG (i.e. predicted minus chronological age) between individuals with one of five primary substance use disorders as well as healthy controls. Findings Alcohol use disorder (β = −5.49, t = −5.51, p < 0.001) was associated with higher global BAG, whereas amphetamine‐type stimulant use disorder (β = 3.44, t = 2.42, p = 0.02) was associated with lower global BAG in the separate substance‐specific models. Conclusions: People with alcohol use disorder appear to have a higher brain‐age gap than people without alcohol use disorder, which is consistent with other evidence of the negative impact of alcohol on the brain. [ABSTRACT FROM AUTHOR]

Abstract Background Bipolar disorder (BD) is characterized by recurrent (hypo)manic and depressive episodes, alternating with euthymic states in which patients are relatively symptom free. Besides clinical recovery, it is important to also strive for improvement of mental well-being and personal recovery. One prominent field focussing on the improvement of well-being is positive psychology. However, studies assessing the effects of positive psychology or personal recovery interventions for people with BD are scarce and have used weak methodological designs. The study described in this protocol article aims to assess the effectiveness of a multicomponent positive psychology intervention (“Living well with bipolar disorder”) adjusted for people with BD in the euthymic phase to improve well-being and personal recovery. Method The study concerns a pragmatic randomized multicenter trial. The principle objective of the study is to assess whether the positive psychology intervention offered to BD patients in remission in addition to usual care (CAU) is more effective than CAU. The study will include 112 participants randomized to either the experimental condition receiving the intervention in addition to CAU or the control condition receiving CAU. The study population are patients with BD I or II in the euthymic phase. The inclusion criteria are 1) diagnosis of BD I or BD II, 2) between the ages of 18–65, 3) four or more supportive sessions in the last year, and 4) only residual depressive or manic symptoms. Patients are excluded if they are in a depressive or manic episode, have current addiction problems or have optimal levels of well-being. Measurements take place at baseline, post-intervention and follow-up 6 and 12 months from baseline. Outcomes of measures include positive well-being, personal recovery, psychopathology, self-compassion, positive relationships, dampening of positive affect and relapse. Discussion The outlined study will be the first RCT examining the effects of a multicomponent positive psychology intervention for patients with bipolar disorder. Several limitations, including generalizability of the results and possible attrition issues, are discussed in advance. Trial registration This study has been registered in the Netherlands Trial Register (NTR6729) on 12 October 2017.

Introduction. Acceptance and Commitment Therapy (ACT) explicitly postulates experiential avoidance (EA) and values-based living (VBL) as essential treatment processes. As outcomes from between-subject studies cannot readily be generalized to within-subject processes in individuals, we explored the unfolding of, and relationship between, EA and VBL and levels of pain interference in daily life and emotional well-being within individuals experiencing chronic pain. Methods. Using n-of-1 designs, three participants following a multidisciplinary treatment program filled out a 12-item daily questionnaire (87–110 days). After multiple imputation of missing data, McKnight Time-series analysis procedures were performed for each participant separately. The interrelationships of EA, VBL and pain intensity, and the relationship of EA and VBL beyond pain intensity with both chronic pain outcomes were assessed both concurrently (same day) and prospectively (consecutive days). Results. Both EA and VBL were associated with at least one of five outcome variables (four domains of pain interference and emotional well-being) beyond pain intensity in two participants, but not in the third participant. These associations primarily existed for concurrent, but not consecutive, days. In contrast to VBL, EA was not associated with emotional well-being for any of the three participants. Conclusions. Although the finding that ACT-processes were associated with pain outcomes on concurrent days is consistent with ACT theory, the absence of such associations on consecutive days means that alternative explanations cannot be rule out. One possibility is that pain interference fluctuates within days at a higher variability rate than was currently assessed. Future research should consider using a higher measurement frequency to be able to grasp time-lagged effects.

Chronic pain outcomes are traditionally defined in terms of disability and illness. A definition of adaptive functioning in the context of chronic pain beyond the mere absence of negative outcomes, is the ability to flourish (i.e., experience emotional, psychological and social well-being; Keyes, 2002). We explored in two chronic pain samples the prevalence and sociodemographic, physical and psychological correlates of flourishing, and complemented this exploration with a similar examination of (being at risk for) psychopathology to help contextualize findings. Sample 1 (n = 1498) was a nationally representative sample. Subgroups included people with regular joint pain (1), regular joint pain and rheumatoid arthritis (2) and without chronic pain (3). Using chi-square tests we calculated the prevalence of both mental health outcomes and examined if people with or without chronic pain were more/less likely to flourish/at risk for psychopathology. Sample 2 (n = 238) concerned baseline data of a Randomized Controlled Trial on the effectiveness of Acceptance and Commitment Therapy for chronic pain (Trompetter et al., 2015b). We performed logistic regression analysis to identify flourishers/those at risk for depression. The Mental Health Continuum-Short Form was used to measure flourishing. The prevalence of flourishing was 34% (recurrent joint pain) and 38% (recurrent joint pain and arthritis) in sample 1, and 23% in sample 2. Compared to those without chronic pain, people with chronic pain were as likely to flourish, but more likely to be at risk for psychopathology. In sample 2, both flourishing and being at risk for depression were related foremost to psychological correlates. While engaged living was the most important correlate of flourishing, pain catastrophizing and psychological inflexibility were most important correlates of being at risk for depression. In conclusion, people with chronic pain are able to flourish. Findings suggest that positive and negative chronic pain outcomes function on two different continua, with potentially unique protective and risk factors. The Psychological Flexibility model provides pathways to explain both poor and optimal functioning in the presence of chronic pain. A better understanding of people with chronic pain who are able to flourish can be a fruitful endeavor to improve chronic pain models and interventions.

Abstract Background Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Methods Patients of 8 years and older undergoing appendectomy for acute complex appendicitis – defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess – are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed. Discussion This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly. Trial registration Dutch Trial Register, NTR6128. Registered on 20 December 2016.