The course of health-related quality of life in the first 2 years after a diagnosis of head and neck cancer: the role of personal, clinical, psychological, physical, social, lifestyle, disease-related, and biological factors.

PURPOSE: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors. METHODS: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment. RESULTS: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months. CONCLUSION: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment.

Effectiveness of Self-guided Tailored Implementation Strategies in Integrating and Embedding Internet-Based Cognitive Behavioral Therapy in Routine Mental Health Care: Results of a Multicenter Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: Internet-based cognitive behavioral therapy (iCBT) services for common mental health disorders have been found to be effective. There is a need for strategies that improve implementation in routine practice. One-size-fits-all strategies are likely to be ineffective. Tailored implementation is considered as a promising approach. The self-guided integrated theory-based Framework for intervention tailoring strategies toolkit (ItFits-toolkit) supports local implementers in developing tailored implementation strategies. Tailoring involves identifying local barriers; matching selected barriers to implementation strategies; developing an actionable work plan; and applying, monitoring, and adapting where necessary. OBJECTIVE: This study aimed to compare the effectiveness of the ItFits-toolkit with implementation-as-usual (IAU) in implementing iCBT services in 12 routine mental health care organizations in 9 countries in Europe and Australia. METHODS: A stepped-wedge cluster randomized trial design with repeated measures was applied. The trial period lasted 30 months. The primary outcome was the normalization of iCBT delivery by service providers (therapists, referrers, IT developers, and administrators), which was measured with the Normalization Measure Development as a proxy for implementation success. A 3-level linear mixed-effects modeling was applied to estimate the effects. iCBT service uptake (referral and treatment completion rates) and implementation effort (hours) were used as secondary outcomes. The perceived satisfaction (Client Satisfaction Questionnaire), usability (System Usability Scale), and impact of the ItFits-toolkit by implementers were used to assess the acceptability of the ItFits-toolkit. RESULTS: In total, 456 mental health service providers were included in this study. Compared with IAU, the ItFits-toolkit had a small positive statistically significant effect on normalization levels in service providers (mean 0.09, SD 0.04; P=.02; Cohen d=0.12). The uptake of iCBT by patients was similar to that of IAU. Implementers did not spend more time on implementation work when using the ItFits-toolkit and generally regarded the ItFits-toolkit as usable and were satisfied with it. CONCLUSIONS: The ItFits-toolkit performed better than the usual implementation activities in implementing iCBT services in routine practice. There is practical utility in the ItFits-toolkit for supporting implementers in developing and applying effective tailored implementation strategies. However, the effect on normalization levels among mental health service providers was small. These findings warrant modesty regarding the effectiveness of self-guided tailored implementation of iCBT services in routine practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03652883; https://clinicaltrials.gov/ct2/show/NCT03652883. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-020-04686-4.

Study retention and attrition in a longitudinal cohort study including patient-reported outcomes, fieldwork and biobank samples: results of the Netherlands quality of life and Biomedical cohort study (NET-QUBIC) among 739 head and neck cancer patients and 262 informal caregivers.

BACKGROUND: Longitudinal observational cohort studies in cancer patients are important to move research and clinical practice forward. Continued study participation (study retention) is of importance to maintain the statistical power of research and facilitate representativeness of study findings. This study aimed to investigate study retention and attrition (drop-out) and its associated sociodemographic and clinical factors among head and neck cancer (HNC) patients and informal caregivers included in the Netherlands Quality of Life and Biomedical Cohort Study (NET-QUBIC). METHODS: NET-QUBIC is a longitudinal cohort study among 739 HNC patients and 262 informal caregivers with collection of patient-reported outcome measures (PROMs), fieldwork data (interview, objective tests and medical examination) and biobank materials. Study retention and attrition was described from baseline (before treatment) up to 2-years follow-up (after treatment). Sociodemographic and clinical characteristics associated with retention in NET-QUBIC components at baseline (PROMs, fieldwork and biobank samples) and retention in general (participation in at least one component) were investigated using Chi-square, Fisher exact or independent t-tests (p< 0.05). RESULTS: Study retention at 2-years follow-up was 80% among patients alive (66% among all patients) and 70% among caregivers of patients who were alive and participating (52% among all caregivers). Attrition was most often caused by mortality, and logistic, physical, or psychological-related reasons. Tumor stage I/II, better physical performance and better (lower) comorbidity score were associated with participation in the PROMs component among patients. No factors associated with participation in the fieldwork component (patients), overall sample collection (patients and caregivers) or PROMs component (caregivers) were identified. A better performance and comorbidity score (among patients) and higher age (among caregivers) were associated with study retention at 2-years follow-up. CONCLUSIONS: Retention rates were high at two years follow-up (i.e. 80% among HNC patients alive and 70% among informal caregivers with an active patient). Nevertheless, some selection was shown in terms of tumor stage, physical performance, comorbidity and age, which might limit representativeness of NET-QUBIC data and samples. To facilitate representativeness of study findings future cohort studies might benefit from oversampling specific subgroups, such as patients with poor clinical outcomes or higher comorbidity and younger caregivers.

Exploratory Factor Analysis of Unusual Sexual Interests.

BACKGROUND: Unusual sexual interests are largely intercorrelated, yet not much is known about underlying patterns of clusters between various sexual interests. AIM: To identify underlying clusters of unusual sexual interests using exploratory factor analysis. METHODS: We conducted exploratory factor analysis with self-reported interest in a wide variety of unusual sexual acts for an online, international sample (N = 669; 61% female), and for women and men separately. Factor regression weights were correlated to self-reported sex life satisfaction, sexual outlet, and psychiatric symptoms. OUTCOMES: Participants rated the attractiveness of 50 unusual sexual activities, and reported on their sex life satisfaction (Arizona Sexual Experiences Scale), sexual outlet, and symptoms regarding ADHD (Adult ADHD Self-Report Screening Scale for DSM-5), depression, anxiety, and stress (Depression, Anxiety, and Stress Scale). RESULTS: We identified 5 factors of unusual sexual interests that were largely comparable for women and men: submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia (attraction to dirtiness or soiled things), and fetishism. For women, unusual sexual interests related to more psychiatric symptoms and higher sexual outlet, whereas this relation was less explicit for men. CLINICAL IMPLICATIONS: Different factors of unusual sexual interests may serve different underlying functions or motivations, for instance related to sexual, and emotional regulation. A better understanding of the nature of unusual sexual interests is important to be able to influence sexual interests that are unwanted or cause damage to others. STRENGTHS & LIMITATIONS: Strength of this study include its anonymity, the avoidance of sexual orientation effects, and the possibility to indicate only a slight endorsement toward sexual items. Limitations include the sample's generalizability and the truthfulness of online responding. CONCLUSION: Unusual sexual interests could be clustered into 5 factors that were largely comparable for women and men: submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia, and fetishism. Schippers EE, Smid WJ, Huckelba AL, et al. Exploratory Factor Analysis of Unusual Sexual Interests. J Sex Med 2021;18:1615-1631.

Predicting unplanned hospital visits in older home care recipients: a cross-country external validation study.

BACKGROUND: Accurate identification of older persons at risk of unplanned hospital visits can facilitate preventive interventions. Several risk scores have been developed to identify older adults at risk of unplanned hospital visits. It is unclear whether risk scores developed in one country, perform as well in another. This study validates seven risk scores to predict unplanned hospital admissions and emergency department (ED) visits in older home care recipients from six countries. METHODS: We used the IBenC sample (n = 2446), a cohort of older home care recipients from six countries (Belgium, Finland, Germany, Iceland, Italy and The Netherlands) to validate four specific risk scores (DIVERT, CARS, EARLI and previous acute admissions) and three frailty indicators (CHESS, Fried Frailty Criteria and Frailty Index). Outcome measures were unplanned hospital admissions, ED visits or any unplanned hospital visits after 6 months. Missing data were handled by multiple imputation. Performance was determined by assessing calibration and discrimination (area under receiver operating characteristic curve (AUC)). RESULTS: Risk score performance varied across countries. In Iceland, for any unplanned hospital visits DIVERT and CARS reached a fair predictive value (AUC 0.74 [0.68-0.80] and AUC 0.74 [0.67-0.80]), respectively). In Finland, DIVERT had fair performance predicting ED visits (AUC 0.72 [0.67-0.77]) and any unplanned hospital visits (AUC 0.73 [0.67-0.77]). In other countries, AUCs did not exceed 0.70. CONCLUSIONS: Geographical validation of risk scores predicting unplanned hospital visits in home care recipients showed substantial variations of poor to fair performance across countries. Unplanned hospital visits seem considerably dependent on healthcare context. Therefore, risk scores should be validated regionally before applied to practice. Future studies should focus on identification of more discriminative predictors in order to develop more accurate risk scores.

Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report).

BACKGROUND: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression. METHODS: Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS). RESULTS: Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15-1.32, R2 = 1.47%). CONCLUSIONS: By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression.

Physical activity in patients with cancer: self-report versus accelerometer assessments.

PURPOSE: The level of daily physical activity in patients with cancer is frequently assessed by questionnaires, such as the Physical Activity Scale for the Elderly (PASE). Objective assessments, with for example accelerometers, may be a good alternative. The aim of this study was to investigate the agreement between the PASE questionnaire and accelerometer-assessed physical activity in a large group of patients with different types of cancer. METHODS: Baseline accelerometer and PASE questionnaire data of 403 participants from the REACT (Resistance and Endurance Exercise After Chemotherapy, n = 227), the EXIST (Exercise Intervention After Stem-Cell Transplantation, n = 74), and NET-QUBIC (NEtherlands QUality of Life And Biomedical Cohort Studies In Cancer, n = 102) studies were available for the current analyses. Physical activity was assessed by the PASE questionnaire (total score) and accelerometers (total minutes per day > 100 counts). Linear mixed models regression analysis was used to assess the agreement between the PASE questionnaire and accelerometer-assessed physical activity. RESULTS: The mean (SD) PASE score was 95.9 (75.1) points and mean (SD) time in physical activity measured with the accelerometer was 256.6 (78.8) min per day. The agreement between the PASE score and the accelerometer data was significant, but poor (standardized regression coefficient (B) = 0.36, 95%CI = 0.27; 0.44, p < 0.01). CONCLUSION: Agreement between the PASE questionnaire and accelerometer-assessed physical activity was poor. The poor agreement indicates that they measure different physical activity constructs and cannot be used interchangeably to assess the level of daily physical activity in patients with cancer.

Dimensionality of the system usability scale among professionals using internet-based interventions for depression: a confirmatory factor analysis.

BACKGROUND: The System Usability Scale (SUS) is used to measure usability of internet-based Cognitive Behavioural Therapy (iCBT). However, whether the SUS is a valid instrument to measure usability in this context is unclear. The aim of this study is to assess the factor structure of the SUS, measuring usability of iCBT for depression in a sample of professionals. In addition, the psychometric properties (reliability, convergent validity) of the SUS were tested. METHODS: A sample of 242 professionals using iCBT for depression from 6 European countries completed the SUS. Confirmatory Factor Analysis (CFA) was conducted to test whether a one-factor, two-factor, tone-model or bi-direct model would fit the data best. Reliability was assessed using complementary statistical indices (e.g. omega). To assess convergent validity, the SUS total score was correlated with an adapted Client Satisfaction Questionnaire (CSQ-3). RESULTS: CFA supported the one-factor, two-factor and tone-model, but the bi-factor model fitted the data best (Comparative Fit Index = 0.992, Tucker Lewis Index = 0.985, Root Mean Square Error of Approximation = 0.055, Standardized Root Mean Square Residual = 0.042 (respectively χ2diff (9) = 69.82, p < 0.001; χ2diff (8) = 33.04, p < 0.001). Reliability of the SUS was good (ω = 0.91). The total SUS score correlated moderately with the CSQ-3 (CSQ1 rs = .49, p < 0.001; CSQ2 rs = .46, p < 0.001; CSQ3 rs = .38, p < 0.001), indicating convergent validity. CONCLUSIONS: Although the SUS seems to have a multidimensional structure, the best model showed that the total sumscore of the SUS appears to be a valid and interpretable measure to assess the usability of internet-based interventions when used by professionals in mental healthcare.

Assessment of Biopsychosocial Complexity and Health Care Needs: Measurement Properties of the INTERMED Self-Assessment Version.

OBJECTIVE: The INTERMED Self-Assessment questionnaire (IMSA) was developed as an alternative to the observer-rated INTERMED (IM) to assess biopsychosocial complexity and health care needs. We studied feasibility, reliability, and validity of the IMSA within a large and heterogeneous international sample of adult hospital inpatients and outpatients as well as its predictive value for health care use (HCU) and quality of life (QoL). METHODS: A total of 850 participants aged 17 to 90 years from five countries completed the IMSA and were evaluated with the IM. The following measurement properties were determined: feasibility by percentages of missing values; reliability by Cronbach α; interrater agreement by intraclass correlation coefficients; convergent validity of IMSA scores with mental health (Short Form 36 emotional well-being subscale and Hospital Anxiety and Depression Scale), medical health (Cumulative Illness Rating Scale) and QoL (Euroqol-5D) by Spearman rank correlations; and predictive validity of IMSA scores with HCU and QoL by (generalized) linear mixed models. RESULTS: Feasibility, face validity, and reliability (Cronbach α = 0.80) were satisfactory. Intraclass correlation coefficient between IMSA and IM total scores was .78 (95% CI = .75-.81). Correlations of the IMSA with the Short Form 36, Hospital Anxiety and Depression Scale, Cumulative Illness Rating Scale, and Euroqol-5D (convergent validity) were -.65, .15, .28, and -.59, respectively. The IMSA significantly predicted QoL and also HCU (emergency department visits, hospitalization, outpatient visits, and diagnostic examinations) after 3- and 6-month follow-up. Results were comparable between hospital sites, inpatients and outpatients, as well as age groups. CONCLUSIONS: The IMSA is a generic and time-efficient method to assess biopsychosocial complexity and to provide guidance for multidisciplinary care trajectories in adult patients, with good reliability and validity across different cultures.

Six-year trajectory of objective physical function in persons with depressive and anxiety disorders.

BACKGROUND: Depression and anxiety have been related to poorer self-reported physical functioning over time; however, objective measures of physical function are less frequently examined. This study assessed the 6-year trajectory of hand-grip strength and lung function in persons with depressive and/or anxiety disorders. METHODS: At four waves (baseline, 2, 4, and 6 years) hand-grip strength and lung function were assessed in 2,480 participants, aged 18-65 years, of the Netherlands Study of Depression and Anxiety. Linear mixed models were used to examine the association between baseline psychiatric status (current and remitted depression and anxiety, healthy controls) and physical function during 6-year follow-up, adjusted for sociodemographics, lifestyle, and health indicators. RESULTS: Although there were no differences in the rate of decline over time, women with current, but not remitted, depression and anxiety had poorer hand-grip strength (B = -1.34, P < .001) and poorer lung function (B = -11.91, P =.002) compared to healthy women during the entire 6-year follow-up. Associations with depression and anxiety severity measures confirmed dose-response relationships with objective physical function. In men, stronger 6-year decline of lung function was found in those with current disorders (current diagnosis-by-time: B = -11.72, P = .002) and even in those with remitted disorders (remitted diagnosis by time: B = -10.11, P = .04) compared to healthy men. CONCLUSIONS: Depression and anxiety are associated with consistently poorer hand-grip strength in women and poorer lung function in women and men over 6 years of time, implicating their long-lasting impact on physical functioning.

The clinical course of trauma-related disorders and personality disorders: study protocol of two-year follow-up based on structured interviews.

BACKGROUND: Trauma-related disorders and personality disorders are prevalent in survivors of chronic childhood trauma and neglect. Both conditions have serious consequences for patients, their families, society and public health and a high risk of development of chronicity. However, information on the long term course trajectories is lacking and predictors of course outcome in survivors of chronic childhood traumatization are unknown. The first aim of the current study is to identify two-year course trajectories of pathology in patients with trauma-related disorders and personality disorders. The second aim is to examine predictors of the course, including demographics, clinical characteristics and comorbidities. METHODS/DESIGN: The study is a naturalistic two-year follow-up of 150 patients consecutively admitted to the trauma treatment program and the personality disorder treatment program respectively at GGZ Friesland, a regular Dutch mental health care center. The only exclusion criterion is insufficient mastery of the Dutch language. Participants will be assessed after 2 years of treatment through measures that have been completed at baseline, including structured clinical interviews to measure childhood histories of trauma and neglect, (symptoms of) trauma-related disorders and personality disorders, and psychological questionnaire measures (e.g., general psychopathology, depressive symptoms and personality features). In addition, participants will complete an evaluation questionnaire to assess medication prescribed and treatment (s) received outside GGZ Friesland between baseline and follow-up. Information about (psychological and pharmacological) treatment received at GGZ Friesland during the follow-up period will be collected from patient files. DISCUSSION: This study provides insight in the two-year course of (comorbid) trauma-related disorders and personality disorders. Identifying predictors of the course of trauma-related and personality disorders will allow to differentiate clinical profiles and will offer indicators for treatment.

Differential gene expression patterns between smokers and non-smokers: cause or consequence?

The molecular mechanisms causing smoking-induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome-wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex-smokers were available from two population-based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hundred thirty-two genes were differentially expressed between current smokers and never smokers (P < 1.2 × 10-6 , Bonferroni correction). The most significant genes were G protein-coupled receptor 15 (P < 1 × 10-150 ) and leucine-rich repeat neuronal 3 (P < 1 × 10-44 ). The smoking-related genes were enriched for immune system, blood coagulation, natural killer cell and cancer pathways. By taking the data of ex-smokers into account, expression of these 132 genes was classified into reversible (94 genes), slowly reversible (31 genes), irreversible (6 genes) or inconclusive (1 gene). Expression of 6 of the 132 genes (three reversible and three slowly reversible) was confirmed to be reactive to smoking as they were differentially expressed in monozygotic pairs discordant for smoking. Cis-expression quantitative trait loci for GPR56 and RARRES3 (downregulated in smokers) were associated with increased number of cigarettes smoked per day in a large genome-wide association meta-analysis, suggesting a causative effect of GPR56 and RARRES3 expression on smoking behavior. In conclusion, differential gene expression patterns in smokers are extensive and cluster in several underlying disease pathways. Gene expression differences seem mainly direct consequences of smoking, and largely reversible after smoking cessation. However, we also identified DNA variants that may influence smoking behavior via the mediating gene expression.

Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder.

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10-8) and gene-based (p = 1.48 × 10-7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

Change in Psychosocial Health Status Over 5 Years in Relation to Adults' Hearing Ability in Noise.

OBJECTIVES: The aim of this study was to establish the longitudinal relationship between hearing ability in noise and psychosocial health outcomes (i.e., loneliness, anxiety, depression, distress, and somatization) in adults aged 18 to 70 years. An additional objective was to determine whether a change in hearing ability in noise over a period of 5 years was associated with a change in psychosocial functioning. Subgroup effects for a range of factors were investigated. DESIGN: Longitudinal data of the web-based Netherlands Longitudinal Study on Hearing (NL-SH) (N = 508) were analyzed. The ability to recognize speech in noise (i.e., the speech-reception-threshold [SRTn]) was measured with an online digit triplet test at baseline and at 5-year follow-up. Psychosocial health status was assessed by online questionnaires. Multiple linear regression analyses and longitudinal statistical analyses (i.e., generalized estimating equations) were performed. RESULTS: Poorer SRTn was associated longitudinally with more feelings of emotional and social loneliness. For participants with a high educational level, the longitudinal association between SRTn and social loneliness was significant. Changes in hearing ability and loneliness appeared significantly associated only for specific subgroups: those with stable pattern of hearing aid nonuse (increased emotional and social loneliness), who entered matrimony (increased social loneliness), and low educational level (less emotional loneliness). No significant longitudinal associations were found between hearing ability and anxiety, depression, distress, or somatization. CONCLUSIONS: Hearing ability in noise was longitudinally associated with loneliness. Decline in hearing ability in noise was related to increase in loneliness for specific subgroups of participants. One of these subgroups included participants whose hearing deteriorated over 5 years, but who continued to report nonuse of hearing aids. This is an important and alarming finding that needs further investigation.

The therapist's role in the implementation of internet-based cognitive behavioural therapy for patients with depression: study protocol.

BACKGROUND: Internet-based Cognitive Behavioural Therapy (iCBT) for the treatment of depressive disorders is innovative and promising. Various studies have demonstrated large effect sizes up to 2.27, but implementation in routine practice lags behind. Mental health therapists play a significant role in the uptake of internet-based interventions. Therefore, it is interesting to study factors that influence the therapists in whether they apply internet-based therapy or not. This study, as part of the European implementation project MasterMind, aims to identity the factors that promote or hinder therapists in the use of iCBT in depression care. METHODS/DESIGN: The uptake of iCBT by therapists in routine mental health care practice for the treatment of depression will be evaluated by a mixed method approach, to provide an understanding of the implementation factors (quantitative), and to ascertain the facilitating and hindering factors in the involvement of therapists in the implementation of iCBT (qualitative). The involvement of therapists in the implementation of iCBT is analysed following the RE-AIM framework on the five dimensions Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance. This enables us to evaluate the reach of therapists, the impact of iCBT on depression care, the extent to which therapists adopt iCBT, the extent to which iCBT is delivered as intended, and how iCBT can be maintained over time. DISCUSSION: The results will provide valuable insight into the role of therapists in the implementation of iCBT for depression in secondary mental health care settings. They will result in concrete recommendations for how therapists can be facilitated in implementing and up-scaling iCBT for depression.

A double-blind randomized controlled trial to assess the effect of bright light therapy on depression in patients with Parkinson's disease.

BACKGROUND: A disturbed circadian rhythm seems to be a causal factor in the occurrence of depressive disorders in patients with Parkinson's disease (PD). The circadian rhythm can be restored with light. Therefore, Bright Light Therapy (BLT) might be a new treatment option for depression in PD patients. METHODS/DESIGN: In this double-blind controlled trial, 84 subjects with idiopathic PD are randomized to either BLT or a control light condition. The BLT condition emits white light with an intensity of 10,000 Lux, while the control device emits dim white light of 200 Lux, which is presumed to be too low to influence the circadian rhythm. Subjects receive 30 min of home treatment twice daily for three months. Timing of treatment is based on the individual chronotype. After finishing treatment, subjects enter a follow-up period of six months. The primary outcome of the study is the severity of depressive symptoms, as measured with the Hamilton Depression Rating Scale. Secondary outcomes are alternative depression measures, objective and subjective sleep measures, and salivary melatonin and cortisol concentrations. For exploratory purposes, we also assess the effects on motor symptoms, global cognitive function, comorbid psychiatric disorders, quality of life and caregiver burden. Data will be analyzed using a linear mixed models analysis. DISCUSSION: Performing a placebo-controlled trial on the effects of BLT in PD patients is challenging, as the appearance of the light may provide clues on the treatment condition. Moreover, fixed treatment times lead to an improved sleep-wake rhythm, which also influences the circadian system. With our study design, we do not compare BLT to placebo treatment, i.e. an ineffective control treatment. Rather, we compare structuring of the sleep-wake cycle in both conditions with additional BLT in the experimental condition, and additional dim light in the control condition. Participants are not informed about the exact details of the two light devices and the expected therapeutic effect, and expectancies are rated prior to the start of treatment. Ideally, the design of a future study on BLT should include two extra treatment arms where BLT and control light are administered at random times. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on May 17th 2012 (ClinicalTrials.gov Identifier: NCT01604876 ).

Vitamin D supplementation to prevent depression and poor physical function in older adults: Study protocol of the D-Vitaal study, a randomized placebo-controlled clinical trial.

BACKGROUND: Depressive symptoms and decreased physical functioning are interrelated conditions and common in older persons, causing significant individual and societal burden. Evidence suggests that vitamin D supplementation may be beneficial for both mental and physical functioning. However, previous randomized controlled trials have yielded inconsistent results and often had suboptimal designs. This study examines the effect of vitamin D supplementation on both depressive symptoms and physical functioning in a high-risk population of older persons with low vitamin D status. METHODS/DESIGN: The D-Vitaal study is a randomized, double-blind, placebo-controlled trial investigating the effects of a daily dose of 1200 IU vitamin D3 versus placebo for one year on depressive symptoms and physical functioning (primary outcomes) in older adults. Participants (N = 155, age 60-80 years) were recruited from the general population. Eligibility criteria included the presence of depressive symptoms, ≥1 functional limitation and serum 25-hydroxyvitamin D levels between 15 and 50/70 nmol/L (depending on season). Secondary outcomes include incidence of major depressive disorder, anxiety symptoms, health-related quality of life, cognitive function and cost-effectiveness of the intervention. DISCUSSION: With this study, we aim to elucidate the effects of vitamin D supplementation on depressive symptoms and physical functioning in older persons who are at high risk of developing more substantial mental and physical problems. If effective, vitamin D supplementation can be a preventive intervention strategy that is easy to implement in the primary care setting. TRIAL REGISTRATION: Netherlands Trial Register NTR3845. Registered 6 February 2013.

Inconsistent retrospective self-reports of childhood sexual abuse and their correlates in the general population.

PURPOSE: Epidemiological research on childhood sexual abuse (CSA) and its consequences in adult life mainly relies on retrospective reports. This study explores their consistency and the correlates of inconsistent CSA self-reports in a random population sample. METHOD: A stratified subsample of 2,462 subjects (selected from a large-scale (N = 34,267) representative sample of Dutch adults aged 40 and beyond) participated in a two-phase online questionnaire survey on extra-familial CSA which was conducted on a four- to six-week interval. Subjects reporting CSA were overrepresented. Participants with consistent and inconsistent responses were compared with regard to demographics, family background, abuse severity, and clinical characteristics. Potential correlates of inconsistency were identified using logistic regression analysis. An additional questionnaire (Phase III) administered to inconsistent respondents explored possible reasons for their inconsistency. RESULTS: Of the 1,992 respondents who had reported extra-familial CSA during Phase I, 707 (35.5%) denied this in Phase II. Of the 2,462 respondents in Phase II, 727 (29.5%; 9.2% when considering sample stratification) gave a discrepant answer to the extra-familial sexual abuse item compared to their answers given in Phase I. Reports of less severe abuse, intra-familial CSA, and early parental separation predicted inconsistency. Reasons provided for inconsistency varied from misunderstanding (e.g., reporting intra-familial CSA rather than extra-familial CSA) to emotional motives (e.g., embarrassment, being overwhelmed) or practical considerations (e.g., lack of privacy while filling out the questionnaire). CONCLUSIONS: Inconsistent self-reports of extra-familial sexual abuse occur on a substantial scale and are associated with less severe forms of abuse (lack of salience) or classification difficulties (perpetrator being a family member or not). Consistency tests and probing for clarifications or corrections should be routinely conducted in order to increase the quality of CSA epidemiological research.

Depressive symptoms in Parkinson's disease are related to reduced [123I]FP-CIT binding in the caudate nucleus.

BACKGROUND: Depression is a common neuropsychiatric symptom in Parkinson's disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD. METHODS: In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by [(123)I]FP-CIT SPECT tracer binding to the dopamine transporter (DaT). RESULTS: Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients. CONCLUSIONS: These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.

A comprehensive assessment protocol including patient reported outcomes, physical tests, and biological sampling in newly diagnosed patients with head and neck cancer: is it feasible?

PURPOSE: Large cohort studies are needed taking into account cancer-related, personal, biological, psychobehavioral, and lifestyle-related factors, to guide future research to improve treatment and supportive care. We aimed to evaluate the feasibility of a comprehensive baseline assessment of a cohort study evaluating the course of quality of life (QoL). METHODS: Newly diagnosed head and neck cancer (HNC) patients were asked to participate. Assessments consisted of questionnaires (635 items), a home visit (including a psychiatric interview, physical tests, and blood and saliva collection), and tissue collection. Representativeness of the study sample was evaluated by comparing demographics, clinical factors, depression, anxiety, and QoL between responders and non-responders. Feasibility was evaluated covering the number of questions, time investment, intimacy, and physical burden. RESULTS: During the inclusion period (4 months), 15 out of 26 (60 %) patients agreed to participate. Less women participated, 13 % in responders group versus 63 % in non-responders group (p = 0.008). No other differences were found between responders and non-responders. Responders completed more than 95 % of the questionnaires' items and rated the number of questions, time investment and intimacy as feasible, and the physical and psychological burden as low. It took on average 3 h to complete the questionnaires and 1.5 h for the home visit. CONCLUSIONS: This study reveals that a comprehensive assessment including various questionnaires, physical measurements, and biological assessments is feasible according to patients with newly diagnosed HNC. A large prospective cohort study has started aiming to include 739 HNC patients and their informal caregivers in the Netherlands.