PRegnancy Outcomes after a Maternity Intervention for Stressful EmotionS (PROMISES): study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is ample evidence from observational prospective studies that maternal depression or anxiety during pregnancy is a risk factor for adverse psychosocial outcomes in the offspring. However, to date no previous study has demonstrated that treatment of depressive or anxious symptoms in pregnancy actually could prevent psychosocial problems in children. Preventing psychosocial problems in children will eventually bring down the huge public health burden of mental disease. The main objective of this study is to assess the effects of cognitive behavioural therapy in pregnant women with symptoms of anxiety or depression on the child's development as well as behavioural and emotional problems. In addition, we aim to study its effects on the child's development, maternal mental health, and neonatal outcomes, as well as the cost-effectiveness of cognitive behavioural therapy relative to usual care.</p> <p>Methods/design</p> <p>We will include 300 women with at least moderate levels of anxiety or depression at the end of the first trimester of pregnancy. By including 300 women we will be able to demonstrate effect sizes of 0.35 or over on the total problems scale of the child behavioural checklist 1.5-5 with alpha 5% and power (1-beta) 80%.</p> <p>Women in the intervention arm are offered 10-14 individual cognitive behavioural therapy sessions, 6-10 sessions during pregnancy and 4-8 sessions after delivery (once a week). Women in the control group receive care as usual.</p> <p>Primary outcome is behavioural/emotional problems at 1.5 years of age as assessed by the total problems scale of the child behaviour checklist 1.5 - 5 years.</p> <p>Secondary outcomes will be mental, psychomotor and behavioural development of the child at age 18 months according to the Bayley scales, maternal anxiety and depression during pregnancy and postpartum, and neonatal outcomes such as birth weight, gestational age and Apgar score, health care consumption and general health status (economic evaluation).</p> <p>Trial Registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2242">NTR2242</a></p

Clinical and cost-effectiveness of computerised cognitive behavioural therapy for depression in primary care: Design of a randomised trial

<p>Abstract</p> <p>Background</p> <p>Major depression is a common mental health problem in the general population, associated with a substantial impact on quality of life and societal costs. However, many depressed patients in primary care do not receive the care they need. Reason for this is that pharmacotherapy is only effective in severely depressed patients and psychological treatments in primary care are scarce and costly. A more feasible treatment in primary care might be computerised cognitive behavioural therapy. This can be a self-help computer program based on the principles of cognitive behavioural therapy. Although previous studies suggest that computerised cognitive behavioural therapy is effective, more research is necessary. Therefore, the objective of the current study is to evaluate the (cost-) effectiveness of online computerised cognitive behavioural therapy for depression in primary care.</p> <p>Methods/Design</p> <p>In a randomised trial we will compare (a) computerised cognitive behavioural therapy with (b) treatment as usual by a GP, and (c) computerised cognitive behavioural therapy in combination with usual GP care. Three hundred mild to moderately depressed patients (aged 18–65) will be recruited in the general population by means of a large-scale Internet-based screening (<it>N </it>= 200,000). Patients will be randomly allocated to one of the three treatment groups. Primary outcome measure of the clinical evaluation is the severity of depression. Other outcomes include psychological distress, social functioning, and dysfunctional beliefs. The economic evaluation will be performed from a societal perspective, in which all costs will be related to clinical effectiveness and health-related quality of life. All outcome assessments will take place on the Internet at baseline, two, three, six, nine, and twelve months. Costs are measured on a monthly basis. A time horizon of one year will be used without long-term extrapolation of either costs or quality of life.</p> <p>Discussion</p> <p>Although computerised cognitive behavioural therapy is a promising treatment for depression in primary care, more research is needed. The effectiveness of online computerised cognitive behavioural therapy without support remains to be evaluated as well as the effects of computerised cognitive behavioural therapy in combination with usual GP care. Economic evaluation is also needed. Methodological strengths and weaknesses are discussed.</p> <p>Trial registration</p> <p>The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236).</p

Verifying 4D gated radiotherapy using time-integrated electronic portal imaging: a phantom and clinical study

<p>Abstract</p> <p>Background</p> <p>Respiration-gated radiotherapy (RGRT) can decrease treatment toxicity by allowing for smaller treatment volumes for mobile tumors. RGRT is commonly performed using external surrogates of tumor motion. We describe the use of time-integrated electronic portal imaging (TI-EPI) to verify the position of internal structures during RGRT delivery</p> <p>Methods</p> <p>TI-EPI portals were generated by continuously collecting exit dose data (aSi500 EPID, Portal vision, Varian Medical Systems) when a respiratory motion phantom was irradiated during expiration, inspiration and free breathing phases. RGRT was delivered using the Varian RPM system, and grey value profile plots over a fixed trajectory were used to study object positions. Time-related positional information was derived by subtracting grey values from TI-EPI portals sharing the pixel matrix. TI-EPI portals were also collected in 2 patients undergoing RPM-triggered RGRT for a lung and hepatic tumor (with fiducial markers), and corresponding planning 4-dimensional CT (4DCT) scans were analyzed for motion amplitude.</p> <p>Results</p> <p>Integral grey values of phantom TI-EPI portals correlated well with mean object position in all respiratory phases. Cranio-caudal motion of internal structures ranged from 17.5–20.0 mm on planning 4DCT scans. TI-EPI of bronchial images reproduced with a mean value of 5.3 mm (1 SD 3.0 mm) located cranial to planned position. Mean hepatic fiducial markers reproduced with 3.2 mm (SD 2.2 mm) caudal to planned position. After bony alignment to exclude set-up errors, mean displacement in the two structures was 2.8 mm and 1.4 mm, respectively, and corresponding reproducibility in anatomy improved to 1.6 mm (1 SD).</p> <p>Conclusion</p> <p>TI-EPI appears to be a promising method for verifying delivery of RGRT. The RPM system was a good indirect surrogate of internal anatomy, but use of TI-EPI allowed for a direct link between anatomy and breathing patterns.</p

Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: report from the Quality Assurance Working Party of the randomised phase III ROSEL study

<p>Abstract</p> <p>Background</p> <p>A phase III multi-centre randomised trial (ROSEL) has been initiated to establish the role of stereotactic radiotherapy in patients with operable stage IA lung cancer. Due to rapid changes in radiotherapy technology and evolving techniques for image-guided delivery, guidelines had to be developed in order to ensure uniformity in implementation of stereotactic radiotherapy in this multi-centre study.</p> <p>Methods/Design</p> <p>A Quality Assurance Working Party was formed by radiation oncologists and clinical physicists from both academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung cancer. A literature survey was conducted and consensus meetings were held in which both the knowledge from the literature and clinical experience were pooled. In addition, a planning study was performed in 26 stage I patients, of which 22 were stage 1A, in order to develop and evaluate the planning guidelines. Plans were optimised according to parameters adopted from RTOG trials using both an algorithm with a simple homogeneity correction (Type A) and a more advanced algorithm (Type B). Dose conformity requirements were then formulated based on these results.</p> <p>Conclusion</p> <p>Based on current literature and expert experience, guidelines were formulated for this phase III study of stereotactic radiotherapy versus surgery. These guidelines can serve to facilitate the design of future multi-centre clinical trials of stereotactic radiotherapy in other patient groups and aid a more uniform implementation of this technique outside clinical trials.</p

Response time variability and response inhibition predict affective problems in adolescent girls, not in boys: the TRAILS study

The present study examines the relationship between neurocognitive functioning and affective problems through adolescence, in a cross-sectional and longitudinal perspective. Baseline response speed, response speed variability, response inhibition, attentional flexibility and working memory were assessed in a cohort of 2,179 adolescents (age 10–12 years) from the TRacking Adolescents’ Individual Lives Survey (TRAILS). Affective problems were measured with the DSM-oriented Affective Problems scale of the Youth Self Report at wave 1 (baseline assessment), wave 2 (after 2.5 years) and wave 3 (after 5 years). Cross-sectionally, baseline response speed, response time variability, response inhibition and working memory were associated with baseline affective problems in girls, but not in boys. Longitudinally, enhanced response time variability predicted affective problems after 2.5 and 5 years in girls, but not in boys. Decreased response inhibition predicted affective problems after 5 years follow-up in girls, and again not in boys. The results are discussed in light of recent insights in gender differences in adolescence and state–trait issues in depression

On the practice of the clinical implementation of enhanced dynamic wedges

Practical aspects of the clinical implementation of enhanced dynamic wedges (EDW) replacing manual wedges are presented and discussed extensively. A comparison between measured and calculated data is also presented. Relative dose distributions and wedge factors were calculated with a commercially available treatment planning system and measured in a water-phantom and with an ionization chamber. Wedge factor calculations and measurements were also compared with an independent method of wedge factor calculations available from the literature. Aspects of the clinical implementation, such as safety and quality assurance, were evaluated. Measurements and calculations agreed very well and were slightly better than results of previous studies. Profiles and percentage depth doses (PDDs) agreed within 1% to 1.5% and within 0.5%, respectively. Measured and calculated wedge factors ratios agreed within 0.5% to 1%. Calculated and measured EDW dose distributions showed excellent agreement, both relative and absolute. However, for safe and practical use, specific aspects need to be taken into consideration. Once the treatment planning system is commissioned properly, the clinical implementation of EDW is rather straightforward

Benefit of respiration-gated stereotactic radiotherapy for stage I lung cancer: An analysis of 4DCT datasets

Purpose: High local control rates have been reported with stereotactic radiotherapy (SRT) for Stage I non-small-cell lung cancer. Because high-dose fractions are used, reduction in treatment portals will reduce the risk of toxicity to adjacent structures. Respiratory gating can allow reduced field sizes and planning four-dimensional computed tomography scans were retrospectively analyzed to study the benefits for gated SRT and identify patients who derive significant benefit from this approach. Methods and Materials: A total of 31 consecutive patients underwent a four-dimensional computed tomography scan, in which three-dimensional computed tomography datasets for 10 phase bins of the respiratory cycle were acquired during free breathing. For a total of 34 tumors, the three planning target volumes (PTVs) were analyzed, namely (1) PTV10bins, derived from an internal target volume (ITV) that incorporated all observed mobility (ITV10bins), with the addition of a 3-mm isotropic setup margin; (2) PTVgating, derived from an ITV generated from mobility observed in three consecutive phases ("bins") during tidal-expiration, plus addition of a 3-mm isotropic margin; and (3) PTV10 mm, derived from the addition of a 10-mm isotropic margin to the most central gross tumor volumes in the three bins selected for gating. Results: The PTV10bins and PTVgating were, on average, 48.2% and 33.3% of the PTV10 mm, and respective mean volumes of normal tissue (outside the PTV) receiving the prescribed doses were 57.1% and 39.1%, respectively, of that of PTV10 mm. A significant correlation was seen between the extent of tumor mobility (i.e., a three-dimensional mobility vector of at least 1 cm) and reduction in normal tissue irradiation achieved with gating. The ratio of the intersecting and the encompassing volumes of GTVs at extreme phases of tidal respiration predicted for the benefits of gated respiration. Conclusion: The use of "standard population-based" margins for SRT leads to unnecessary normal tissue irradiation. The risk of toxicity is further reduced if respiration-gated radiotherapy is used to treat mobile tumors. These findings suggest that gated SRT will be of clinical relevance in selected patients with mobile tumors

Is Adaptive Treatment Planning Required for Stereotactic Radiotherapy of Stage I Non-Small-Cell Lung Cancer?

Purpose: Changes in position or size of target volumes have been observed during radiotherapy for lung cancer. The need for adaptive treatment planning during stereotactic radiotherapy of Stage I tumors was retrospectively analyzed using repeat four-dimensional computed tomography (4DCT) scans. Methods and Materials: A planning study was performed for 60 tumors in 59 patients using 4DCT scans repeated after two or more treatment fractions. Planning target volumes (PTV) encompassed all tumor mobility, and dose distributions from the initial plan were projected onto PTVs derived from the repeat 4DCT. A dosimetric and volumetric analysis was performed. Results: The repeat 4DCT scans were performed at a mean of 6.6 days (range, 2-12 days) after the first fraction of stereotactic radiotherapy. In 25% of cases the repeat PTV was larger, but the difference exceeded 1 mL in 5 patients only. The mean 3D displacement between the center of mass of both PTVs was 2.0 mm. The initial 80% prescription isodose ensured a mean coverage of 98% of repeat PTVs, and this isodose fully encompassed the repeat internal target volumes in all but 1 tumor. "Inadequate" coverage in the latter was caused by a new area of atelectasis adjacent to the tumor on the repeat 4DCT. Conclusions: Limited "time trends" were observed in PTVs generated by repeated uncoached 4DCT scans, and the dosimetric consequences proved to be minimal. Treatment based only on the initial PTV would not have resulted in major tumor underdosage, indicating that adaptive treatment planning is of limited value for fractionated stereotactic radiotherapy

Analysis of components of variance determining probability of setup errors in CBCT-guided stereotactic radiotherapy of lung tumors

PURPOSE: Online tumor matching for SABR lung setup requires margins for inaccuracies due to intra-fraction variability of breathing-averaged tumor position (BATP) and CBCT image guidance. We studied intra-fraction variability during SABR delivery using VMAT, corrected these for measurement inaccuracies, and quantified the CBCT image-guidance uncertainties. MATERIALS AND METHODS: For 193 fractions in 38 patients positioned without immobilization devices, CBCT scans were acquired before and after 2 arcs of a RapidArc treatment. A hidden marker test was performed to determine the accuracy of the CBCT system and an inter-observer test was performed to measure registration accuracy. Intra-fraction variability was calculated after correction for these components of variance, and the prediction interval for setup inaccuracies was determined. RESULTS: Correction for measurement inaccuracies reduced the intra-fraction variability of the BATP from 1.9 to 1.6 mm in AP, from 1.7 to 1.4 mm in SI and from 1.5 to 1.1 mm in LR direction (1 SD). Intra-fraction variability in bony anatomy after correction was ≤ 1 mm (1 SD). The 95% prediction interval to account for CBCT image-guidance uncertainties and intra-fraction variability was determined, and was found to be within our institutional PTV margins of 5 mm. CONCLUSIONS: Our findings show that it is essential to account for measurement and system inaccuracies when obtaining data for validating PTV margins from online CBCT image guidance