Adjustment disorder in cancer patients after treatment: prevalence and acceptance of psychological treatment.

PURPOSE: To investigate the prevalence of adjustment disorder (AD) among cancer patients and the acceptance of psychological treatment, in relation to sociodemographic, clinical, and psychological factors. METHODS: Breast, prostate, and head and neck cancer patients of all stages and treatment modalities (N = 200) participated in this observational study. Patients completed the Hospital Anxiety and Depression Scale, Checklist Individual Strength, Distress Thermometer and problem list. Patients with increased risk on AD based on these questionnaires were scheduled for a diagnostic interview. Patients diagnosed with AD were invited to participate in a randomized controlled trial on the cost-effectiveness of psychological treatment. Participation in this trial was used as a proxy of acceptance of psychological treatment. Logistic regression analyses were used to investigate associated factors. RESULTS: The overall prevalence of AD was estimated at 13.1%. Sensitivity analyses showed prevalence rates of AD of 11.5%, 15.0%, and 23.5%. Acceptance of psychological treatment was estimated at 65%. AD was associated both with being employed (OR = 3.3, CI = 1.3-8.4) and having a shorter time since diagnosis (OR = 0.3, CI = 0.1-0.8). CONCLUSION: Taking sensitivity analysis into account, the prevalence of AD among cancer patients is estimated at 13 to 15%, and is related to being employed and having a shorter time since diagnosis. The majority of cancer patients with AD accept psychological treatment.

Informal caregiver well-being during and after patients' treatment with adjuvant chemotherapy for colon cancer: a prospective, exploratory study.

INTRODUCTION: Caring for a significant other during cancer treatment can be demanding. Little is known about the well-being of informal caregivers of patients with colon cancer. This study aims to examine informal caregiver well-being during adjuvant chemotherapy for colon cancer. MATERIAL AND METHODS: This exploratory longitudinal, prospective study measured the course of informal caregiver burden (Self-Perceived Pressure of Informal Care), distress (Hospital Anxiety and Depression Scale), health-related quality of life (RAND-36), marital satisfaction (Maudsley Marital Questionnaire), social support (Social Support List - Discrepancies), fatigue (Abbreviated Fatigue Questionnaire), and self-esteem (Caregiver Reaction Assessment) before (T0), during (T1), and after (T2) patients' treatment. RESULTS: Baseline data of 60 out of 76 eligible dyads (79%) were analyzed. Mean levels of informal caregiver burden and distress improved significantly over time, as did their health-related quality of life and perceived social support. At baseline, 30% and 26.7% of informal caregivers reported moderate-to-high levels of burden and clinically relevant levels of distress, respectively, which changed to 20% and 18.8% at T2. Informal caregiver burden and distress at baseline were the strongest predictors of informal caregiver burden and distress during and following patients' treatment, respectively. CONCLUSION: When informal caregivers and patients experience problems before start of adjuvant chemotherapy, problems seem to improve over time. Approximately 20% of informal caregivers remain burdened and distressed after patients' end of treatment. Paying attention to baseline distress and burden seems indicated, as these were strong predictors of informal caregivers' well-being during and after treatment.

SAFE: an eHealth intervention for women experiencing intimate partner violence - study protocol for a randomized controlled trial, process evaluation and open feasibility study.

BACKGROUND: Intimate partner violence (IPV) affects almost one in three women worldwide. However, disclosing violence or seeking help is difficult for affected women. eHealth may represent an effective alternative to the standard support offers, which often require face-to-face interaction, because of easy accessibility and possibility of anonymous usage. In the Netherlands we are developing SAFE, an eHealth intervention for female victims of IPV, which will be evaluated in a randomized controlled trial and a process evaluation, followed by an open feasibility study to assess real-world user data. METHODS/DESIGN: The randomized controlled trial is a two-arm parallel design comparing an intervention arm and a control group. The groups both have access to eHealth but differ in the offer of interactive features compared to static information. Both groups complete questionnaires at three or four time points (baseline, three months, six months, 12 months) with self-efficacy at 6 months as the primary outcome, measured with the General Self-Efficacy (GSE) scale. The process evaluation consists of quantitative data (from the website and from web evaluation questionnaires) and qualitative data (from interviews) on how the website was used and the users' experiences. DISCUSSION: eHealth has the potential to reach a large number of women who experience IPV. The internet-based design can lower access barriers and encourage help-seeking behavior ultimately reducing the lag time between subjective awareness and protective action. TRIAL REGISTRATION: Trial registered on 15 August 2017 at the Netherlands Trial Register NL7108 (NTR7313).

Caregivers of patients receiving long-term treatment with a tyrosine kinase inhibitor (TKI) for gastrointestinal stromal tumour (GIST): a cross-sectional assessment of their distress and burden.

BACKGROUND: TKIs are a long-term treatment for GIST, and may have an impact on caregivers. MATERIAL AND METHODS: For this cross-sectional study, patients and caregivers were both included when patients had been treated with TKIs for at least six months. Caregivers completed questionnaires including demographics, distress (Hospital Anxiety and Depression scale), burden (Self-Perceived Pressure from Informal Care) general health (RAND-36), comorbidity (Self-administered Comorbidity Questionnaire), social support (Social Support List - Discrepancies) and marital satisfaction (Maudsley Marital Questionnaire). Patients completed similar questionnaires, without 'burden'. We conducted analyses to explore differences between caregivers with low/moderate versus high levels of burden and low versus high levels of distress. RESULTS: Sixty-one out of seventy-one eligible couples (84%) were included in the analysis. The median age of the caregivers was 60 years; 66% were female and 78% were the patients' spouse. The median age of the patients was 66 years; 43% were female. Caregivers experienced high levels of burden and distress in 10% and 23%, respectively. Caregivers with high levels of burden perceived significantly lower mental health, less vitality, lower general health and high levels of distress. Significantly higher levels of burden were found in non-spouses, caregivers of patients with more treatment-related side-effects, caregivers who spent more hours caring, and those caring for more than one person. For distress, caregivers with high levels of distress perceived significantly more burden, lower social functioning, more role physical and emotional problems, lower mental health, less vitality and lower general health. Furthermore, high levels of distress were found in caregivers of more dependent patients and those caring for more than one person. CONCLUSIONS: Caregivers of the patients with GIST treated with TKI are managing well. There is a small, vulnerable group of caregivers with high levels of burden and/or distress, show more health-related problems, both physical and mental, and require adequate support.

Study protocol of the CORRECT multicenter trial: the efficacy of blended cognitive behavioral therapy for reducing psychological distress in colorectal cancer survivors.

BACKGROUND: Approximately one third of the colorectal cancer survivors (CRCS) experience high levels of psychological distress. Common concerns experienced by CRCS include distress related to physical problems, anxiety, fear of cancer recurrence (FCR) and depressive symptoms. However, psychological interventions for distressed CRCS are scarce. Therefore, a blended therapy was developed, combining face-to-face cognitive behavioral therapy (CBT) with online self-management activities and telephone consultations. The aim of the study is to evaluate the efficacy and cost-effectiveness of this blended therapy in reducing psychological distress in CRCS. METHODS/DESIGN: The CORRECT study is a two-arm multicenter randomized controlled trial (RCT). A sample of 160 highly distressed CRCS (a score on the Distress Thermometer of 5 or higher) will be recruited from several hospitals in the Netherlands. CRCS will be randomized to either the intervention condition (blended CBT) or the control condition (care as usual). The blended therapy covers approximately 14 weeks and combines five face-to-face sessions and three telephone consultations with a psychologist, with access to an interactive self-management website. It includes three modules which are individually-tailored to patient concerns and aimed at decreasing: 1) distress caused by physical consequences of CRC, 2) anxiety and FCR, 3) depressive symptoms. Patients can choose between the optional modules. The primary outcome is general distress (Brief Symptom Inventory-18). Secondary outcomes are quality of life and general psychological wellbeing. Assessments will take place at baseline prior to randomization, after 4 and 7 months. DISCUSSION: Blended CBT is an innovative and promising approach for providing tailored supportive care to reduce high distress in CRCS. If the intervention proves to be effective, an evidence-based intervention will become available for implementation in clinical practice. TRIAL REGISTRATION: This trial is registered in the Netherlands Trial Register ( NTR6025 ) on August 3, 2016.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

An online self-test added to colorectal cancer screening can increase the effectiveness of familial cancer risk assessment without increasing distress.

AIM: Most people who are at increased familial colorectal cancer (FCRC) risk are not identified, despite the need for enhanced surveillance colonoscopy for effective CRC prevention. An online self-test may enhance this identification. We assessed whether taking an online self-test to identify increased FCRC risk increases anxiety, distress or CRC risk perception in population-based CRC screening. METHOD: After the precolonoscopy consultation, patients who had a positive immunohistochemical occult faecal blood test (iFOBT+) in population-based CRC screening were invited by email to take an online self-test at home which returned details of family history. Anxiety (STAI-DY), distress (HADS) and CRC risk perception were assessed immediately before and after taking the online self-test and 2 weeks later. RESULTS: Of 250 participants invited, 177 (71%) completed the online self-test and psychological questionnaires and 153 (61%) completed questionnaires 2 weeks later. The median age was 65 years (range 61-75). The FCRC risk was increased in 17 participants (9.6%). Of these, 12 (6.8%) had a highly increased FCRC risk and may benefit from germline genetic testing for Lynch syndrome. In 7 of 17 participants (40%) the self-test obtained novel information on family history. Anxiety and distress levels were, and remained, below a clinically relevant level. Perception of CRC risk remained unchanged. Most participants (83%) would recommend the online self-test to others. CONCLUSION: Of those with a iFOBT+, 9.6% had a previously unidentified increasedFCRC risk and require an enhanced surveillance colonoscopy instead of iFOBT. As screening for this risk did not increase anxiety or distress, and was highly acceptable, we recommend adding the online self-test to population-based CRC screening.

Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

OBJECTIVE: Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. METHODS: We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. RESULTS: A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. CONCLUSION: Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own.

Lifestyle Risk Factors for Breast Cancer in BRCA1/2-Mutation Carriers Around Childbearing Age.

BRCA1/2-mutation carriers are at high risk of breast cancer (BC) and ovarian cancer. Physical inactivity, overweight (body mass index ≥25, BMI), smoking, and alcohol consumption are jointly responsible for about 1 in 4 postmenopausal BC cases in the general population. Limited evidence suggests physical activity also increases BC risk in BRCA1/2-mutation carriers. Women who have children often reduce physical activity and have weight gain, which increases BC risk. We assessed aforementioned lifestyle factors in a cohort of 268 BRCA1/2-mutation carriers around childbearing age (born between 1968 and 1983, median age 33 years, range 21-44). Furthermore, we evaluated the effect of having children on physical inactivity and overweight. Carriers were asked about lifestyle 4-6 weeks after genetic diagnosis at the Familial Cancer Clinic Nijmegen. Physical inactivity was defined as sports activity fewer than once a week. Carriers were categorized according to the age of their youngest child (no children, age 0-3 years and ≥4 years). In total, 48% of carriers were physically inactive, 41% were overweight, 27% smoked, and 70% consumed alcohol (3% ≥8 beverages/week). Physical inactivity was 4-5 times more likely in carriers with children. Overweight was not associated with having children. Carriers with children are a subgroup that may specifically benefit from lifestyle support to reduce BC risk.

Patient experiences with gene panels based on exome sequencing in clinical diagnostics: high acceptance and low distress.

The Radboud University Medical Center was among the first to implement two-step exome sequencing in clinical genetic diagnostics. This study is the first to evaluate patient experiences with gene panels based on exome sequencing, using quantified psychological variables: acceptance, psychological distress, expectations of heredity and unsolicited findings. Between August 2011 and July 2012, 177 patients diagnosed with early-onset colorectal/kidney cancer, deafness, blindness or movement disorder consented to diagnostic exome sequencing offered by clinical geneticists. Baseline questionnaires were sent to 141 adults, returned by 111 with median age of 49 [22-79] years and positive family history in 81%. Follow-up included 91 responders at median 4 [2-22] weeks after results from known gene panels per diagnosis group; exome-wide analysis is ongoing. Confirmed or possibly pathogenic mutations were found in 31% with one unsolicited finding (oncogenetic panel). Most patients (92%) were satisfied. There were no significant changes in heredity-specific distress (18% at baseline, 17% at follow-up) and expectations of heredity. Fewer patients expected unsolicited findings at follow-up (29% vs 18%, p = 0.01). Satisfaction and distress were equal in those with vs without mutations. In conclusion, most adults accepted and were satisfied with gene panels based on diagnostic exome sequencing, few reporting distress.

Selective attention and fear of cancer recurrence in breast cancer survivors.

BACKGROUND: Anxious people show an attentional bias towards threatening information. PURPOSE: It was investigated whether an attentional bias exists for cancer-related stimuli in breast cancer survivors and if different levels of fear of cancer recurrence would lead to different patterns of selective attention. METHODS: Breast cancer survivors with high (n = 35) and low (n = 32) fear of cancer recurrence were compared to 40 healthy female hospital employees. Specificity of attentional biases was investigated using a modified Emotional Stroop Task. Self-report measures were used to assess depression and anxiety, feelings of fatigue, and experienced traumas. RESULTS: Compared to control participants, breast cancer survivors with both high and low levels of fear of cancer recurrence showed increased interference for cancer-related words, but not for other word types. CONCLUSIONS: The findings suggest a specific attentional bias for cancer-related words in breast cancer survivors that is independent of level of fear of cancer recurrence.

Cognitive shifting and externalising problem behaviour in intellectual disability and autism spectrum disorder.

BACKGROUND: Behavioural problems are frequently reported in residential care for people with an intellectual disability (ID) in particular when they are additionally diagnosed with autism spectrum disorder (ASD). There are indications that impairment in cognitive shifting may be associated with problem behaviour. The objectives of this study were (1) to examine the relationship of cognitive shifting and severity of ASD symptoms with externalising problem behaviour in individuals with ID, with and without ASD, and (2) to examine whether a diagnosis based on shifting impairment is more predictive of externalising problem behaviour than an ASD diagnosis. METHOD: Participants consisted of adolescents and young adults with mild ID, with and without ASD (n = 41). Pearson intercorrelations were computed to explore the relationship between shifting impairment and severity of ASD symptoms on the one hand and ratings of externalising problem behaviour on the other hand. t-Tests were performed to analyse differences in externalising problem behaviour. RESULTS: Unlike ASD symptom severity, shifting scores were found to be associated with externalising problem behaviour, but only if shifting was measured using rating scales and not when using neuropsychological tasks. Externalising problem behaviour scores significantly differed when groups were classified according to shifting impairment (impaired vs. non-impaired) but not when they were classified according to ID and ASD diagnoses. CONCLUSIONS: It is proposed to use a cognition-based approach when analysing problem behaviour, thus concentrating not so much on ID and ASD diagnosis and their corresponding symptoms, but rather placing the focus on cognitive symptoms.

Executive functioning in individuals with intellectual disabilities and autism spectrum disorders.

BACKGROUND: Executive functioning (EF) is important for adequate behavioural functioning and crucial for explaining symptoms of autism spectrum disorders (ASD) in individuals with normal intelligence, but is scarcely studied in individuals with ASD and intellectual disabilities (ID). We therefore study EF in an ID population by comparing performances on three frequently studied executive functions (shifting, inhibition and updating) between individuals with ASD and individuals without ASD. When studying ID populations, one should be aware of Spearman's Law of Diminishing Returns (SLODR), as it questions the possibility of measuring separate cognitive functions in ID populations. METHODS: Six EF tasks were administered to 50 individuals with mild to borderline ID, of which half was diagnosed with ASD. In order to investigate the distinctness of the three executive functions in this ID sample, the results on the six EF tasks were subjected to principal components analysis (PCA). Subsequently, a multivariate analysis of variance (MANOVA) was performed to assess differences between the ASD and non-ASD group on shifting, inhibition and updating. RESULTS: The PCA revealed the hypothesised EF trichotomy. MANOVA analysis showed no significant group differences on EF-performance. CONCLUSIONS: Three separate executive functions were measured in this ID population, but despite much evidence that individuals with ASD display more behavioural problems and the proven relevance of EF in behavioural functioning, no significant group difference was found on shifting, inhibition or updating. After this first effort to achieve more insight into EF of individuals with ASD and ID the relation between behavioural problems and EF will require further study.

Polygenic control of autoimmune diabetes in nonobese diabetic mice.

Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susceptibility genes with fully recessive effects and have obtained evidence of linkage of ten distinct loci to diabetes or the prediabetic lesion, insulitis, indicative of a polygenic mode of inheritance. The relative importance of these loci and their interactions have been assessed using a new application of multiple polychotomous regression methods. A candidate disease gene, interleukin-2 (Il-2), which is closely linked to insulitis and diabetes, is shown to have a different sequence in NOD, including an insertion and a deletion of tandem repeat sequences which encode amino acid repeats in the mature protein.

Insulin gene region-encoded susceptibility to type 1 diabetes is not restricted to HLA-DR4-positive individuals.

Type 1 or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease of the insulin-producing pancreatic beta-cells which is determined by both genetic and environmental factors. The major histocompatibility complex and the insulin gene region (INS) on human chromosomes 6p and 11p, respectively, contain susceptibility genes. Using a mostly French data set, evidence for linkage of INS to IDDM was recently obtained but only in male meioses (suggesting involvement of maternal imprinting) and only in HLA-DR4-positive diabetics. In contrast, we find evidence for linkage in both male and female meioses and that the effect of the susceptibility gene(s) in the INS region is not dependent on the presence of HLA-DR4.

A multicentre study on spontaneous in-cage activity and micro-environmental conditions of IVC housed C57BL/6J mice during consecutive cycles of bi-weekly cage-change.

Mice respond to a cage change (CC) with altered activity, disrupted sleep and increased anxiety. A bi-weekly cage change is, therefore, preferred over a shorter CC interval and is currently the prevailing routine for Individually ventilated cages (IVCs). However, the build-up of ammonia (NH3) during this period is a potential threat to the animal health and the literature holds conflicting reports leaving this issue unresolved. We have therefor examined longitudinally in-cage activity, animal health and the build-up of ammonia across the cage floor with female and male C57BL/6 mice housed four per IVC changed every other week. We used a multicentre design with a standardised husbandry enabling us to tease-out features that replicated across sites from those that were site-specific. CC induce a marked increase in activity, especially during daytime (~50%) when the animals rest. A reduction in density from four to two mice did not alter this response. This burst was followed by a gradual decrease till the next cage change. Female but not male mice preferred to have the latrine in the front of the cage. Male mice allocate more of the activity to the latrine free part of the cage floor already the day after a CC. A behaviour that progressed through the CC cycle but was not impacted by the type of bedding used. Reducing housing density to two mice abolished this behaviour. Female mice used the entire cage floor the first week while during the second week activity in the latrine area decreased. Measurement of NH3 ppm across the cage floor revealed x3 higher values for the latrine area compared with the opposite area. NH3 ppm increases from 0-1 ppm to reach ≤25 ppm in the latrine free area and 50-100 ppm in the latrine area at the end of a cycle. As expected in-cage bacterial load covaried with in-cage NH3 ppm. Histopathological analysis revealed no changes to the upper airways covarying with recorded NH3 ppm or bacterial load. We conclude that housing of four (or equivalent biomass) C57BL/6J mice for 10 weeks under the described conditions does not cause any overt discomfort to the animals.

The role of individually targeted information to reduce anxiety before colposcopy: a randomised controlled trial.

OBJECTIVE: We investigated whether providing targeted information on an individual level by mail and by phone reduces anxiety in women referred to the colposcopy clinic. DESIGN: Randomised controlled trial. POPULATION: Women referred to the colposcopy clinic. METHODS: Between December 2007 and April 2010, 169 patients with abnormal smear results were randomised into two study arms. Group A received individually targeted information about the diagnosis and procedure by mail and phone. Group B received the standard folder about colposcopies alone. Patients were requested to fill out a questionnaire prior to their first colposcopy appointment. MAIN OUTCOME MEASURES: The questionnaire included the hospital anxiety and depression scale (HADS), and the Spielberger state-trait anxiety inventory (STAI), as well as a short self-administered questionnaire. RESULTS: Twenty women were excluded from further analyses after randomisation, leaving 149 women for evaluation. The median STAI state anxiety score was high (50.0), but there was no significant difference in median STAI state anxiety and HADS anxiety scores between both groups. However, knowledge about human papillomavirus and the colposcopy procedure did significantly increase in group A (P = 0.004). CONCLUSIONS: Anxiety levels before primary colposcopy are surprisingly high, and are not reduced following individually targeted information given before colposcopy.

Incretin-based therapies--review of the physiology, pharmacology and emerging clinical experience.

Diabetes therapies based on manipulation of the incretin system are now widely available, with millions of people receiving treatment. The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4-resistant peptides that bind to and activate the glucagon-like peptide-1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.

Resistance alleles at two non-major histocompatibility complex-linked insulin-dependent diabetes loci on chromosome 3, Idd3 and Idd10, protect nonobese diabetic mice from diabetes.

Development of diabetes in NOD mice is polygenic and dependent on both major histocompatibility complex (MHC)-linked and non-MHC-linked insulin-dependent diabetes (Idd) genes. In (F1 x NOD) backcross analyses using the B10.H-2g7 or B6.PL-Thy1a strains as the outcross partner, we previously identified several non-MHC Idd loci, including two located on chromosome 3 (Idd3 and Idd10). In the current study, we report that protection from diabetes is observed in NOD congenic strains having B6.PL-Thy1a- or B10-derived alleles at Idd3 or Idd10. It is important to note that only partial protection is provided by two doses of the resistance allele at either Idd3 or Idd10. However, nearly complete protection from diabetes is achieved when resistance alleles are expressed at both loci. Development of these congenic strains has allowed Idd3 to be localized between Glut2 and D3Mit6, close to the Il2 locus.

How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity.

BACKGROUND: Cognitive behaviour therapy (CBT) is known to reduce fatigue severity in chronic fatigue syndrome (CFS). How this change in symptomatology is accomplished is not yet understood. The purpose of the present study was to determine whether the effect of CBT on fatigue is mediated by an increase in physical activity. METHOD: Three randomized controlled trials were reanalysed, previously conducted to evaluate the efficacy of CBT for CFS. In all samples, actigraphy was used to assess the level of physical activity prior and subsequent to treatment or a control group period. The mediation hypothesis was analysed according to guidelines of Baron & Kenny [Journal of Personality and Social Psychology (1986)51, 1173-1182]. A non-parametric bootstrap approach was used to test statistical significance of the mediation effect. RESULTS: Although CBT effectively reduced fatigue, it did not change the level of physical activity. Furthermore, changes in physical activity were not related to changes in fatigue. Across the samples, the mean mediation effect of physical activity averaged about 1% of the total treatment effect. This effect did not yield significance in any of the samples. CONCLUSIONS: The effect of CBT on fatigue in CFS is not mediated by a persistent increase in physical activity.