All-or-Nothing Behavior and Catastrophic Thinking Predict Fatigue in Inflammatory Bowel Disease: A Prospective Cohort Study.

Patients with inflammatory bowel disease (IBD) often report fatigue. However, the reasons for this are poorly understood. In this study of people with IBD, we demonstrate that all-or-nothing behavior (being very active then needing to resting a while) and catastrophic thinking (making very negative assumptions about outcomes) both predict worsening in fatigue over time.

Cognitive behavioural responses to envy: development of a new measure.

BACKGROUND: Envy is depicted as motivating destructive desires and actions intended to spoil or destroy that which is envied. AIM: To develop a new valid and reliable measure of malicious envy (C-BRES), which included items representing the cognitive, emotional and behavioural responses empirically associated with this emotion. METHOD: A total of 203 adults completed the new 22-item cognitive and behavioural responses to envy scale (C-BRES). Exploratory factor analysis was carried out to test for reliability and internal consistency of the C-BRES. Evidence towards the concurrent construct validity (convergent and discriminant) of the C-BRES was assessed through correlations with the Dispositional envy scale and other measures of psychosocial outcomes empirically linked to envy. RESULTS: Factor analysis for categorical data identified five dimensions of envy, namely: injustice, hostility, malicious action tendencies, malicious feelings and behavioural responses. The reliability indices of the five factors and the total scale were satisfactory (>0.85). Evidence towards the concurrent construct validity (convergent and discriminant) of the C-BRES is reported. In particular, envy was associated with higher levels of depression, psychoticism, neuroticism, anger and lower levels of self-esteem and quality of life. CONCLUSION: All findings support the psychometric adequacy of the C-BRES.

Cognitive behaviour therapy for distress in people with inflammatory bowel disease: A benchmarking study.

OBJECTIVE: Anxiety and depression are common in inflammatory bowel disease (IBD) and have been linked to clinical recurrence. Previous randomized controlled trials (RCT's) have found no evidence that psychological interventions enhance outcomes for people with IBD but have recruited patients without distress. This study investigates the clinical benefits of a nonrandomized uncontrolled study of clinic based cognitive behaviour therapy (CBT) for people with IBD who had moderate-severe levels of anxiety or low mood and compares the results with a previous RCT of CBT in this population. METHOD: Assessments were completed at baseline and end of treatment and included measures of low mood, generalized anxiety, quality of life (QOL), and symptomatic disease activity. The patient health questionnaire and generalized anxiety disorder 7 measures were the primary outcomes. Results in the form of a standardized effect size of treatment were compared with a previous RCT to consider if CBT had greater benefits for those with distress. RESULTS: Thirty patients were deemed appropriate for CBT, and 28 accepted treatment. The results from this clinic based CBT intervention suggest statistically significant reductions in symptoms of anxiety (<0.001), low mood (<0.001), and disease activity (p < 0.01) and increases in QOL (p < 0.001). The uncontrolled effect sizes were large and superior to those found in published RCTs. CONCLUSION: This nonrandomized uncontrolled trial of a clinic-based CBT intervention suggests that CBT may have benefits for those with moderate-severe disturbances to mood and that effect sizes can be improved by targeting those with distress. RCTs are required to establish efficacy.

A qualitative study exploring the experience of people with IBD and elevated symptoms of anxiety and low mood and the type of psychological help they would like.

BACKGROUND: People with inflammatory bowel disease (IBD) are at increased risk of developing anxiety and low mood. We sought to explore the experience of people with IBD and moderate-severe symptoms of anxiety/low mood to identify psychological processes which could be targeted in psychological interventions, as well as the kind of psychological support preferred. METHODS: Twenty-five participants with IBD and moderate-severe symptoms of anxiety/low mood were recruited for interview. Template analysis was utilised to analyse interview data. We explored the situations, cognitions and behaviour linked to symptoms of anxiety and low mood by people with IBD, as well as the kind of psychological help preferred. RESULTS: Two themes were identified within participants accounts of symptoms of anxiety; 'under performance' and 'preventing an accident'. Two further themes were identified for symptoms of low mood; 'lack of understanding' and 'stigma'. Expertise and understanding was the main theme identified for the type of psychological help desired. CONCLUSION: The analysis highlights situations, cognitions and behaviour linked to anxiety and low mood by people with IBD and the type of psychological support desired. Our findings link to the knowledge and competencies set for psychological therapist working with long-term conditions.

A systematic review of the psychological correlates of adjustment outcomes in adults with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic long term condition which poses significant psychosocial adjustment challenges. The purpose of this review was to systematically identify psychological factors related to adjustment in adults with IBD with the aim of suggesting evidence based targets that may be modifiable though psychological intervention. Twenty five studies met inclusion criteria and were included in the systematic review and a narrative synthesis was conducted. A wide range of psychological variables were addressed covering six broad categories; personality traits, interpersonal traits, stress and coping, emotions and emotional control, IBD related cognitions and non IBD related cognitions. The most consistent relationship was found between certain emotion focused coping strategies and worse adjustment outcomes in IBD. Some evidence also hi-lighted a relationship between personality traits (such as neuroticism,) perceived stress, emotions and emotional control (such as alexithymia) and IBD related cognitions (such as illness perceptions) and negative adjustment outcomes. The results of this review suggest that interventions to improve adjustment in IBD may benefit from a focus on coping strategies, perceived stress and IBD related cognitions.

Crystallographic insights into the structure-activity relationships of diazaborine enoyl-ACP reductase inhibitors.

Enoyl-ACP reductase, the last enzyme of the fatty-acid biosynthetic pathway, is the molecular target for several successful antibiotics such as the tuberculosis therapeutic isoniazid. It is currently under investigation as a narrow-spectrum antibiotic target for the treatment of several types of bacterial infections. The diazaborine family is a group of boron heterocycle-based synthetic antibacterial inhibitors known to target enoyl-ACP reductase. Development of this class of molecules has thus far focused solely on the sulfonyl-containing versions. Here, the requirement for the sulfonyl group in the diazaborine scaffold was investigated by examining several recently characterized enoyl-ACP reductase inhibitors that lack the sulfonyl group and exhibit additional variability in substitutions, size and flexibility. Biochemical studies are reported showing the inhibition of Escherichia coli enoyl-ACP reductase by four diazaborines, and the crystal structures of two of the inhibitors bound to E. coli enoyl-ACP reductase solved to 2.07 and 2.11 Šresolution are reported. The results show that the sulfonyl group can be replaced with an amide or thioamide without disruption of the mode of inhibition of the molecule.

Psychoeducation for siblings of people with severe mental illness.

BACKGROUND: Many people with severe mental illness (SMI) have siblings. Siblings are often both natural agents to promote service users' recovery and vulnerable to mental ill health due to the negative impact of psychosis within the family. Despite a wealth of research evidence supporting the effectiveness of psychoeducation for service users with SMI and their family members, in reducing relapse and promoting compliance with treatment, siblings remain relatively invisible in clinical service settings as well as in research studies. If psychoeducational interventions target siblings and improve siblings' knowledge, coping with caring and overall wellbeing, they could potentially provide a cost-effective option for supporting siblings with resulting benefits for service users' outcomes. OBJECTIVES: To assess the effectiveness of psychoeducation compared with usual care or any other intervention in promoting wellbeing and reducing distress of siblings of people affected by SMI.The secondary objective was, if possible, to determine which type of psychoeducation is most effective. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register and screened the reference lists of relevant reports and reviews (12th November 2013). We contacted trial authors for unpublished and specific data on siblings' outcomes. SELECTION CRITERIA: All relevant randomised controlled trials focusing on psychoeducational interventions targeting siblings of all ages (on their own or amongst other family members including service users) of individuals with SMI, using any means and formats of delivery, i.e. individual (family), groups, computer-based. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the abstracts and extracted data and two other authors independently checked the screening and extraction process. We contacted authors of trials to ascertain siblings' participation in the trials and seek sibling-specific data in those studies where siblings' data were grouped together with other participants' (most commonly other family members'/carers') outcomes. We calculated the risk difference (RD), its 95% confidence interval (CI) on an intention-to-treat basis. We presented continuous data using the mean difference statistic (MD) and 95% CIs. We assessed risk of bias for the included study and rated quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). MAIN RESULTS: We found 14 studies that included siblings amongst other family members in receipt of psychoeducational interventions. However, we were only able to include one small trial with relevant and available data (n = 9 siblings out of n = 84 family member/carer-participants) comparing psychoeducational intervention with standard care in a community care setting, over a duration of 21 months. There was insufficient evidence to determine the effects of psychoeducational interventions compared with standard care on 'siblings' quality of life' (n = 9, MD score 3.80 95% CI -0.26 to 7.86, low quality of evidence), coping with (family) burden (n = 9, MD -8.80 95% CI -15.22 to -2.34, low quality of evidence). No sibling left the study early by one year (n = 9, RD 0.00 CI -0.34 to 0.34, low quality of evidence). Low quality and insufficient evidence meant we were unable to determine the effects of psychoeducational interventions compared with standard care on service users' global mental state (n = 9, MD -0.60 CI -3.54 to 2.38, low quality of evidence), their frequency of re-hospitalisation (n = 9, MD -0.70 CI -2.46 to 1.06, low quality of evidence) or duration of inpatient stay (n = 9, MD -2.60 CI -6.34 to 1.14, low quality of evidence), whether their siblings received psychoeducation or not. No study data were available to address the other primary outcomes: 'siblings' psychosocial wellbeing', 'siblings' distress' and adverse effects. AUTHORS' CONCLUSIONS: Most studies evaluating psychoeducational interventions recruited siblings along with other family members. However, the proportion of siblings in these studies was low and outcomes for siblings were not reported independently from those of other types of family members. Indeed, only data from one study with nine siblings were available for the review. The limited study data we obtained provides no clear good quality evidence to indicate psychoeducation is beneficial for siblings' wellbeing or for clinical outcomes of people affected by SMI. More randomised studies are justified and needed to understand the role of psychoeducation in addressing siblings' needs for information and support.

Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer.

PURPOSE: To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells. PATIENTS AND METHODS: This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated--a 50-mg and a 200--mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. RESULTS: One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest. CONCLUSION: CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability.