Search

Background: A pragmatic, stepped wedge trial design can be an appealing design to evaluate complex interventions in real-life settings. However, there are certain pitfalls that need to be considered. This paper reports on the experiences and lessons learned from the conduct of a cluster randomized, stepped wedge trial evaluating the effect of the Hospital Elder Life Program (HELP) in a Dutch hospital setting to prevent older patients from developing delirium.Methods: We evaluated our trial which was conducted in eight departments in two hospitals in hospitalized patients aged 70 years or older who were at risk for delirium by reflecting on the assumptions that we had and on what we intended to accomplish when we started, as compared to what we actually realized in the different phases of our study. Lessons learned on the design, the timeline, the enrollment of eligible patients and the use of routinely collected data are provided accompanied by recommendations to address challenges.Results: The start of the trial was delayed which caused subsequent time schedule problems. The requirement for individual informed consent for a quality improvement project made the inclusion more prone to selection bias. Most units experienced major difficulties in including patients, leading to excluding two of the eight units from participation. This resulted in failing to include a similar number of patients in the control condition versus the intervention condition. Data on outcomes routinely collected in the electronic patient records were not accessible during the study, and appeared to be often missing during analyses.Conclusions: The stepped wedge, cluster randomized trial poses specific risks in the design and execution of research in real-life settings of which researchers should be aware to prevent negative consequences impacting the validity of their results. Valid conclusions on the effectiveness of the HELP in the Dutch hospital setting are hampered by the limited quantity and quality of routine clinical data in our pragmatic trial. Executing a stepped wedge design in a daily practice setting using routinely collected data requires specific attention to ethical review, flexibility, a spacious time schedule, the availability of substantial capacity in the research team and early checks on the data availability and quality.Trial Registration: Netherlands Trial Register, identifier: NTR3842 . Registered on 24 January 2013. [ABSTRACT FROM AUTHOR]

Introduction: Hip and knee osteoarthritis are associated with functional limitations, pain and restrictions in quality of life and the ability to work. Furthermore, with growing prevalence, osteoarthritis is increasingly causing (in)direct costs. Guidelines recommend exercise therapy and education as primary treatment strategies. Available options for treatment based on physical activity promotion and lifestyle change are often insufficiently provided and used. In addition, the quality of current exercise programmes often does not meet the changing care needs of older people with comorbidities and exercise adherence is a challenge beyond personal physiotherapy. The main objective of this study is to investigate the short- and long-term (cost-)effectiveness of the SmArt-E programme in people with hip and/or knee osteoarthritis in terms of pain and physical functioning compared to usual care. Methods: This study is designed as a multicentre randomized controlled trial with a target sample size of 330 patients. The intervention is based on the e-Exercise intervention from the Netherlands, consists of a training and education programme and is conducted as a blended care intervention over 12 months. We use an app to support independent training and the development of self-management skills. The primary and secondary hypotheses are that participants in the SmArt-E intervention will have less pain (numerical rating scale) and better physical functioning (Hip Disability and Osteoarthritis Outcome Score, Knee Injury and Osteoarthritis Outcome Score) compared to participants in the usual care group after 12 and 3 months. Other secondary outcomes are based on domains of the Osteoarthritis Research Society International (OARSI). The study will be accompanied by a process evaluation. Discussion: After a positive evaluation, SmArt-E can be offered in usual care, flexibly addressing different care situations. The desired sustainability and the support of the participants' behavioural change are initiated via the app through audio-visual contact with their physiotherapists. Furthermore, the app supports the repetition and consolidation of learned training and educational content. For people with osteoarthritis, the new form of care with proven effectiveness can lead to a reduction in underuse and misuse of care as well as contribute to a reduction in (in)direct costs. Trial registration: German Clinical Trials Register, DRKS00028477. Registered on August 10, 2022. [ABSTRACT FROM AUTHOR]

A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination. Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4–8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells. 25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension. Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the feasibility of a short-term, multimodal trauma-focused treatment approach adapted specifically for unaccompanied refugee minors (URMs) in the Netherlands. This approach aims to overcome barriers to mental health care and to reduce symptoms of posttraumatic stress disorder (PTSD) and depression. Methods: An uncontrolled study was conducted, evaluating the main request for help, treatment integrity and feasibility, and the course of symptoms of PTSD (Children's Revised Impact of Event Scale-13) and depression (Patient Health Questionnaire modified for Adolescents). Results: In total, 41 minors were included in the study. Most participants were male (n = 27), predominately from Eritrea (75.6%) with a mean age of 16.5 (SD = 1.5). Minors mostly reported psychological problems, such as problems sleeping, and psychosocial problems, including worries about family reunification. Deviations from the approach were made to meet the current needs of the minors. Factors limiting the feasibility of the approach were often related to continuous stressors, such as news concerning asylum status. Conclusions: The results provide a first indication that this approach partly overcomes barriers to mental health care and emphasize the added value of collaborating with intercultural mediators and offering outreach care. Trial registration: The study was registered in the Netherlands Trial Register (NL8585), 10 April 2020, Retrospectively registered, https://www.trialregister.nl/trial/8585. [ABSTRACT FROM AUTHOR]

Antipsychotics are often prescribed to children and adolescents, mostly off-label. We aimed to assess adherence to recommendations of guidelines for antipsychotic prescription. We reviewed 436 medical records from 155 clinicians from 26 clinics within three Dutch child and adolescent psychiatry organizations (n = 398 outpatient, n = 38 inpatient care). We assessed target symptoms, diagnostic process, prior and concomitant treatment, and consideration of contra-indications. Multiple logistic regression assessed the role of age, sex, and psychiatric diagnosis on adherence to three main recommendations: to (1) prescribe antipsychotics only after other treatments proved insufficient, (2) always combine antipsychotics with psychosocial interventions, and (3) not prescribe multiple antipsychotics simultaneously. Most patients received off-label antipsychotics. Main target symptoms were inattention/hyperactivity (25%), aggression (24%), and other disruptive behaviors (41%). Most patients underwent diagnostic evaluation before the first prescription; however, screening of contra-indications was low (0.2–19%). About 84% had previously received psychosocial treatment and 48% other psychoactive medication, but 9% had not received any treatment. Notably, only 37% continuously received concomitant psychosocial treatment. Simultaneous use of multiple antipsychotics occurred in 3.2%. Younger children were at higher risk of non-adherence to guideline recommendations regarding prior and concomitant treatment, children with autism spectrum disorder or attention-deficit/hyperactivity disorder more likely not to receive concomitant psychosocial treatment. Sex did not significantly affect adherence. Our findings implicate insufficient adherence to important recommendations regarding antipsychotic use in children and adolescents. Especially younger children are at higher risk of receiving suboptimal care. There is an urgency to consistently offer psychosocial interventions during antipsychotic treatment. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we investigated factors associated with program adherence and patient satisfaction with a home-based physical activity program (Onco-Move, N = 77) and a supervised exercise program with a home-based component (OnTrack, N = 76).Methods: We assessed adherence via self-report (home-based program) and attendance records (supervised program). We used logistic regression analysis to identify sociodemographic, clinical and behavioural variables associated with program adherence. Patient satisfaction was assessed with self-report and is reported descriptively.Results: Fifty-one percent of Onco-Move and 62% of OnTrack participants were adherent to the home-based program, while 59% of OnTrack participants were adherent to the supervised sessions. Higher baseline physical fitness was associated with higher adherence to home-based components. Higher disease stage and having a partner were associated with adherence to OnTrack supervised sessions. Overall satisfaction with the exercise programs was high, but ratings of coaching provided by professionals for the home-based components were low. Patients offered suggestions for improving delivery of the programs.Conclusions: These findings point to factors relevant to program adherence and suggest ways in which such programs can be improved. Providing additional time and training for health care professionals could improve the quality and hopefully the effectiveness of the interventions. The use of online diaries and smartphone apps may provide additional encouragement to participants. Finally, allowing greater flexibility in the planning and availability of supervised exercise training in order to accommodate the variability in cancer treatment schedules and the (acute) side effects of the treatments could also enhance program adherence.Trial Registration: Netherlands Trial Register, NTR2159. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2159. [ABSTRACT FROM AUTHOR]

Background: There is a high need for evidence-based psychosocial treatments for adult attention-deficit hyperactivity disorder (ADHD) to offer alongside treatment as usual (TAU). Mindfulness-based cognitive therapy (MBCT) is a promising psychosocial treatment. This trial investigated the efficacy of MBCT + TAU v. TAU in reducing core symptoms in adults with ADHD. Methods: A multicentre, single-blind, randomised controlled trial (ClinicalTrials.gov: NCT02463396). Participants were randomly assigned to MBCT + TAU (n = 60), an 8-weekly group therapy including meditation exercises, psychoeducation and group discussions, or TAU only (n = 60), which reflected usual treatment in the Netherlands and included pharmacotherapy and/or psychoeducation. Primary outcome was ADHD symptoms rated by blinded clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. Outcomes were assessed at baseline, post-treatment, 3- and 6-month follow-up. Post-treatment effects at group and individual level, and follow-up effects were examined. Results: In MBCT + TAU patients, a significant reduction of clinician-rated ADHD symptoms was found at post-treatment [ M difference = −3.44 (−5.75, −1.11), p = 0.004, d = 0.41]. This effect was maintained until 6-month follow-up. More MBCT + TAU (27%) than TAU participants (4%) showed a ⩽30% reduction of ADHD symptoms (p = 0.001). MBCT + TAU patients compared with TAU patients also reported significant improvements in ADHD symptoms, mindfulness skills, self-compassion and positive mental health at post-treatment, which were maintained until 6-month follow-up. Although patients in MBCT + TAU compared with TAU reported no improvement in executive functioning at post-treatment, they did report improvement at 6-month follow-up. Conclusions: MBCT might be a valuable treatment option alongside TAU for adult ADHD aimed at alleviating symptoms. [ABSTRACT FROM AUTHOR]

Purpose A blended web-based intervention, 'eHealth module embedded in collaborative occupational health care' (ECO), aimed at return to work, was developed and found effective in sick-listed employees with common mental disorders. In order to establish the feasibility of ECO, a process evaluation was conducted. Methods Seven process components were investigated: recruitment, reach, dose delivered, dose received, fidelity, satisfaction and context. Quantitative and qualitative methods were used to collect data: an online questionnaire for the employees, website data, telephonic interviews with occupational physicians (OPs) and observations of the researchers. Results Recruitment was uncomplicated for the employees, but required several steps for the OPs. Reach was 100 % at the OP level and 76.3 % at the employee level. Dose delivered and received for OPs: 91.6 % received minimally one email message. Dose delivered and received for the employees: finishing of the different modules of ECO varied between 13 and 90 %. Fidelity: the support of the OP to the employee in ECO was lower than anticipated. Satisfaction: both employees and OPs were satisfied with the intervention. However, employees reported a need for more support in ECO. The context showed that OPs had limited time to support the employees and it was impossible for the employee to contact the OP outside their regular contacts. Conclusion Feasibility of ECO and satisfaction of employees and OPs with ECO were good. Fidelity of OPs was limited. For further implementation in the occupational health setting, especially contextual barriers regarding time limitation and accessibility of OPs for employees should be addressed. [ABSTRACT FROM AUTHOR]

Background: Ethnic differences in colon cancer (CC) care were shown in the United States, but results are not directly applicable to European countries due to fundamental healthcare system differences. This is the first study addressing ethnic differences in treatment and survival for CC in the Netherlands.Methods: Data of 101,882 patients diagnosed with CC in 1996-2011 were selected from the Netherlands Cancer Registry and linked to databases from Statistics Netherlands. Ethnic differences in lymph node (LN) evaluation, anastomotic leakage and adjuvant chemotherapy were analysed using stepwise logistic regression models. Stepwise Cox regression was used to examine the influence of ethnic differences in adjuvant chemotherapy on 5-year all-cause and colorectal cancer-specific survival.Results: Adequate LN evaluation was significantly more likely for patients from 'other Western' countries than for the Dutch (OR 1.09; 95% CI 1.01-1.16). 'Other Western' patients had a significantly higher risk of anastomotic leakage after resection (OR 1.24; 95% CI 1.05-1.47). Patients of Moroccan origin were significantly less likely to receive adjuvant chemotherapy (OR 0.27; 95% CI 0.13-0.59). Ethnic differences were not fully explained by differences in socioeconomic and hospital-related characteristics. The higher 5-year all-cause mortality of Moroccan patients (HR 1.64; 95% CI 1.03-2.61) was statistically explained by differences in adjuvant chemotherapy receipt.Conclusion: These results suggest the presence of ethnic inequalities in CC care in the Netherlands. We recommend further analysis of the role of comorbidity, communication in patient-provider interaction and patients' health literacy when looking at ethnic differences in treatment for CC. [ABSTRACT FROM AUTHOR]

The benefits of combining a cochlear implant (CI) and a hearing aid (HA) in opposite ears on speech perception were examined in 15 adult unilateral CI recipients who regularly use a contralateral HA. A within-subjects design was carried out to assess speech intelligibility testing, listening effort ratings, and a sound quality questionnaire for the conditions CI alone, CIHA together, and HA alone when applicable. The primary outcome of bimodal benefit, defined as the difference between CIHA and CI, was statistically significant for speech intelligibility in quiet as well as for intelligibility in noise across tested spatial conditions. A reduction in effort on top of intelligibility at the highest tested signal-to-noise ratio was found. Moreover, the bimodal listening situation was rated to sound more voluminous, less tinny, and less unpleasant than CI alone. Listening effort and sound quality emerged as feasible and relevant measures to demonstrate bimodal benefit across a clinically representative range of bimodal users. These extended dimensions of speech perception can shed more light on the array of benefits provided by complementing a CI with a contralateral HA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate, from a societal perspective, the cost utility and cost effectiveness of a nonpharmacologic face-to-face treatment program compared with a telephone-based treatment program for patients with generalized osteoarthritis (GOA).Methods: An economic evaluation was carried out alongside a randomized clinical trial involving 147 patients with GOA. Program costs were estimated from time registrations. One-year medical and nonmedical costs were estimated using cost questionnaires. Quality-adjusted life years (QALYs) were estimated using the EuroQol (EQ) classification system, EQ rating scale, and the Short Form 6D (SF-6D). Daily function was measured using the Health Assessment Questionnaire (HAQ) disability index (DI). Cost and QALY/effect differences were analyzed using multilevel regression analysis and cost-effectiveness acceptability curves.Results: Medical costs of the face-to-face treatment and telephone-based treatment were estimated at €387 and €252, respectively. The difference in total societal costs was nonsignificantly in favor of the face-to-face program (difference €708; 95% confidence interval [95% CI] -€5,058, €3,642). QALYs were similar for both groups according to the EQ, but were significantly in favor of the face-to-face group, according to the SF-6D (difference 0.022 [95% CI 0.000, 0.045]). Daily function was similar according to the HAQ DI. Since both societal costs and QALYs/effects were in favor of the face-to-face program, the economic assessment favored this program, regardless of society's willingness to pay. There was a 65-90% chance that the face-to-face program had better cost utility and a 60-70% chance of being cost effective.Conclusion: This economic evaluation from a societal perspective showed that a nonpharmacologic, face-to-face treatment program for patients with GOA was likely to be cost effective, relative to a telephone-based program. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improved over the last two decades. Approximately 15 % of all patients have resectable disease at diagnosis, and of those, only a subgroup has a resectable tumour at surgical exploration. Data from cohort studies have suggested that outcome can be improved by preoperative radiochemotherapy, but data from well-designed randomized studies are lacking. Our PREOPANC phase III trial aims to test the hypothesis that median overall survival of patients with resectable or borderline resectable pancreatic cancer can be improved with preoperative radiochemotherapy.Methods/design: The PREOPANC trial is a randomized, controlled, multicentric superiority trial, initiated by the Dutch Pancreatic Cancer Group. Patients with (borderline) resectable pancreatic cancer are randomized to A: direct explorative laparotomy or B: after negative diagnostic laparoscopy, preoperative radiochemotherapy, followed by explorative laparotomy. A hypofractionated radiation scheme of 15 fractions of 2.4 gray (Gy) is combined with a course of gemcitabine, 1,000 mg/m(2)/dose on days 1, 8 and 15, preceded and followed by a modified course of gemcitabine. The target volumes of radiation are delineated on a 4D CT scan, where at least 95 % of the prescribed dose of 36 Gy in 15 fractions should cover 98 % of the planning target volume. Standard adjuvant chemotherapy is administered in both treatment arms after resection (six cycles in arm A and four in arm B). In total, 244 patients will be randomized in 17 hospitals in the Netherlands. The primary endpoint is overall survival by intention to treat. Secondary endpoints are (R0) resection rate, disease-free survival, time to locoregional recurrence or distant metastases and perioperative complications. Secondary endpoints for the experimental arm are toxicity and radiologic and pathologic response.Discussion: The PREOPANC trial is designed to investigate whether preoperative radiochemotherapy improves overall survival by means of increased (R0) resection rates in patients with resectable or borderline resectable pancreatic cancer.Trial Registration: Trial open for accrual: 3 April 2013 The Netherlands National Trial Register - NTR3709 (8 November 2012) EU Clinical Trials Register - 2012-003181-40 (11 December 2012). [ABSTRACT FROM AUTHOR]

Background.In recent years, evidence supporting multimodality treatment for oesophageal, oesophagogastric junction (OGJ), and gastric cancer has accumulated. This population-based cohort-study investigates trends and predictors of utilisation of multimodality treatment for oesophagogastric cancer in the Netherlands. Patients and methods.Data were obtained from the Netherlands Cancer Registry regarding patients with oesophageal (n = 5450), OGJ (n = 2168) and gastric cancer (n = 6683) without distant metastases who had undergone R0 or R1 surgery diagnosed between 2000 and 2012. Follow-up was completed until February 2014. Preoperative/postoperative chemotherapy and/or radiotherapy combined with surgery were considered multimodality treatment. Logistic regression analysis was performed to analyse the association of age, gender, socioeconomic status, clinical T and N classification, hospital type, comprehensive cancer centre network region, and year of diagnosis, with multimodality treatment receipt. Additional analyses were performed to explore differences in trends of utilisation of multimodality treatment between academic and non-academic hospitals. Results.Multimodality treatment utilisation for oesophageal, OGJ and gastric cancer increased significantly to 90%, 85% and 56% in 2012, respectively. In oesophageal and OGJ cancer patients, preoperative chemoradiotherapy was most frequently administered (85% and 47% in 2012, respectively), and in gastric cancer patients preoperative chemotherapy (47% in 2012). Lower age, higher clinical T and N classification, and diagnosis in more recent years were significantly associated with more frequent multimodality treatment receipt. The adoption of most types of multimodality treatment in academic hospitals preceded non-academic hospitals by a year. Conclusion.In the Netherlands, the utilisation of multimodality treatment for oesophagogastric cancer has significantly increased during the past decade, especially in oesophageal and OGJ cancer. Multimodality treatment utilisation was especially dependent on patient and tumour characteristics and year of diagnosis, but multimodality treatment trends seem to be related to the publication of landmark studies, participation in nationally running clinical trials, and hospital type, preceding national guidelines. [ABSTRACT FROM PUBLISHER]

The article focuses on a study that was conducted to find side effects and benefits of adjuvant systemic therapy for early stage breast cancer and changes in treatment preferences of oncologists over the time. Topics discussed include adjuvant therapy for lobular tumors that are larger than half centimeter, treatment benefits of endocrine therapy, consideration of treatment efficacy as an important factor by patients and survival benefit of chemotherapy and endocrine therapy.

Since the generalisability of trial-based economic evaluations may be limited, there is an increasing focus on real-world cost-effectiveness. Real-world studies involve evaluating the effects and costs of treatments in daily clinical practice. This study reports on the real-world resource use and costs of adjuvant treatments of stage III colon cancer in a population-based observational study. Analyses were based on a detailed retrospective medical chart review which was conducted for 206 patients with colon cancer treated in 2005 and 2006 in the Netherlands. Mean total costs per patient were €9681 for 5- FU/ LV, €9736 for capecitabine, €32 793 for FOLFOX and €18 361 for CAPOX. Drug costs and the costs related to hospitalisations for chemotherapy administration were the main cost drivers. We identified a potential for substantial cost-savings when the 48 h administration of 5 FU/ LV in the FOLFOX regimen were to take place in an outpatient setting or be replaced by oral capecitabine as in the CAPOX regimen. This analysis based on detailed real-life data clearly indicates that clinical choices made in oncology based on efficacy of therapy have economic consequences. Considering today's reality of finite healthcare resources, these economic consequences deserve a formal role in clinical decision making, for instance in guideline development. [ABSTRACT FROM AUTHOR]

Purpose: To explore the associations between (improvement in) fatigue and (improvement in) clinical and cognitive factors in patients with chronic widespread pain (CWP), participating in multidisciplinary rehabilitation treatment. Methods: Data were used from baseline, 6 and 18 months of follow-up during a prospective cohort study of 120 CWP patients who completed multidisciplinary rehabilitation treatment. Cross-sectional and longitudinal relationships were analyzed between fatigue, clinical (i.e. pain, interference of pain and depression) and pain related cognitive factors (i.e. negative emotional cognitions, active cognitive coping, and control and chronicity beliefs). Results: Higher levels of pain, interference of pain, depression, negative emotional cognitions, and negative control and chronicity beliefs were associated with a higher level of fatigue. Improvement in depression was related to improvement in fatigue. Conclusions: In CWP patients, worse clinical status, and dysfunctional pain-related cognitions are associated with a higher level of fatigue. Our results suggest that improvement in depression might be a mechanism of improvement in fatigue. Furthermore, improvement in fatigue seems to be independent of improvement in pain related cognitions. Targeting fatigue in multidisciplinary pain treatment may need specific strategies. [ABSTRACT FROM AUTHOR]

Background. Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Material and methods. Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed. Study endpoints were change in breast density over time, and correlations between breast density and locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast cancer (CBC). Results. Mammograms of 378 patients (181 tamoxifen, 197 exemestane) were included in the current per protocol analyses. Baseline breast density was low (breast density score < 50% in 75% of patients) and not different between patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error 0.17). Breast density did not change during treatment in exemestane (p = 0.25) or tamoxifen users (p = 0.59). No relation was observed between breast density and the occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45-1.68, p = 0.67], a DR (HR 1.02, 95% CI 0.77-1.35, p = 0.90), or CBC (HR 1.31, 95% CI 0.63-2.72, p = 0.48). Conclusion. The in general low breast density score in early postmenopausal breast cancer patients did not substantially change over time, and this pattern was not different between tamoxifen and exemestane users. Breast density was not a predictive marker for efficacy of adjuvant endocrine therapy. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Systematic review of the literature. • OBJECTIVES: To review and assess the peer-reviewed literature on the effectiveness of physical therapy interventions in treating lumbopelvic pain during pregnancy. • BACKGROUND: Current guidelines on interventions for lumbopelvic pain during pregnancy differ in their recommendations for assessment and intervention. Recent publications may allow revising current recommendations for the treatment of this complex problem. • METHODS: An electronic search strategy was conducted in PubMed, PEDro, Scopus, and CINAHL of literature published from January 1992 to November 2013. Two authors independently assessed all abstracts for eligibility. Articles were independently rated for quality by 2 authors, using the Cochrane Back Review Group criteria for methodological quality. Where possible, effect sizes were calculated for the different interventions. • RESULTS: A total of 22 articles (all randomized controlled trials) reporting on 22 independent studies were included. Overall, the methodological quality of the studies was moderate. Data for 4 types of interventions were considered: a combination of interventions (7 studies, n = 1202), exercise therapy (9 studies, n = 2149), manual therapy (5 studies, n = 360), and material support (1 study, n = 115). • CONCLUSION: All included studies on exercise therapy, and most of the studies on interventions combined with patient education, reported a positive effect on pain, disability, and/or sick leave. Evidence-based recommendations can be made for the use of exercise therapy for the treatment of lumbopelvic pain during pregnancy. [ABSTRACT FROM AUTHOR]

To evaluate a nonanthracycline-containing regimen consisting of 24 weekly administrations of paclitaxel, carboplatin, and trastuzumab as neo-adjuvant therapy for human epidermal growth factor receptor 2 ( HER2)-positive breast cancer. Patients with stage II or III breast cancer, including inflammatory disease, with HER2 overexpression (immunohistochemistry and/or fluorescent in situ hybridization) were treated with 24 weekly administrations of paclitaxel 70 mg/m2, carboplatin AUC = 3 mg/mL/minute, and trastuzumab 2 mg/kg (loading dose 4 mg/kg). In cycles 7, 8, 15, 16, 23, and 24, only trastuzumab was given. The primary end point was pathologic complete response ( pCR) in both breast and axilla. Of 61 evaluable patients, 61% had stage II disease and 75% were node-positive. The median NRI (Neoadjuvant Response Index, a measure of the degree of downstaging by chemotherapy) of all patients was 0.86. Twenty-seven (44%) had a NRI of 1.0, which corresponds to pCR in breast and lymph nodes. The most commonly reported grade 3/4 toxicities were neutropenia (72%) and thrombocytopenia (36%). Dose reduction was necessary in 51% of the patients. A weekly carboplatin-paclitaxel-trastuzumab neo-adjuvant regimen is highly active in HER2-positive breast cancer with an acceptable toxicity profile. A multicenter phase 2 trial has recently reached its accrual target and will serve as a basis for a subsequent randomized phase 3 study comparing this regimen to a similar regimen preceded by anthracyclines. [ABSTRACT FROM AUTHOR]

Background. Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. Methods. All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. Results. A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92-0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00-1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97-0.99; p < 0.001). Conclusions. The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups. [ABSTRACT FROM AUTHOR]

Background. Little is known about how well guidelines about adjuvant chemotherapy in colon cancer are followed in daily practice. We evaluated the current guideline, which is based on the MOSAIC trial, by examining implementation, treatment patterns and disease-free survival. Material and methods. We analysed a population-based cohort of 391 patients treated with adjuvant chemotherapy for stage III colon cancer in 2005-2006. Data were gathered from the Dutch Cancer Registry and medical records of 19 hospitals. Patients were classified according to whether or not they fulfilled MOSAIC trial eligibility criteria. Results. The administered regimens were: fluorouracil-leucovorin (17 patients), capecitabine (93), fluorouracil-leucovorin plus oxaliplatin (145), and capecitabine plus oxaliplatin (136). After its inclusion in national guidelines, oxaliplatin was prescribed in 16 hospitals within six months. Patients receiving oxaliplatin were younger and had less comorbidity than other patients. Dose schedules corresponded well with guidelines. Two-year disease-free survival probability of oxaliplatin patients meeting MOSAIC eligibility criteria was 78.4% (95% CI 72.5-84.3), which was comparable to MOSAIC trial results. Conclusion. Guidelines for adjuvant chemotherapy in stage III colon cancer are generally well followed in daily practice. However, uncertainty remains regarding the optimal treatment of elderly patients and patients with comorbidities, which underscores the need for practical clinical trials including these patients. [ABSTRACT FROM AUTHOR]

We tested the effects on problem-solving, anxiety and depression of 12-week group-based self-management cancer rehabilitation, combining comprehensive physical training (PT) and cognitive-behavioural problem-solving training (CBT), compared with PT. We expected that PT + CBT would outperform PT in improvements in problem-solving (Social Problem-Solving Inventory-Revised (SPSI-R)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), and that more anxious and/or depressed participants would benefit most from adding CBT to PT. Cancer survivors (aged 48.8 ± 10.9 years, all cancer types, medical treatment completed) were randomly assigned to PT + CBT (n = 76) or PT (n = 71). Measurement occasions were: before and post-rehabilitation (12 weeks), 3- and 9-month follow-up. A non-randomised usual care comparison group (UCC) (n = 62) was measured at baseline and after 12 weeks. Longitudinal intention-to-treat analyses showed no differential pattern in change between PT + CBT and PT. Post-rehabilitation, participants in PT and PT + CBT reported within-group improvements in problem-solving (negative problem orientation; p < 0.01), anxiety (p < 0.001) and depression (p < 0.001), which were maintained at 3- and 9-month follow-up (p < 0.05). Compared with UCC post-rehabilitation, PT and PT + CBT only improved in anxiety (p < 0.05). CBT did not add to the effects of PT and had no extra benefits for higher distressed participants. PT was feasible and sufficient for durably reducing cancer survivors' anxiety. [ABSTRACT FROM AUTHOR]

Several methods have been proposed to treat combat veterans with Posttraumatic Stress Disorder (PTSD). Still, a recent review reports on high drop-out and non response rates. This has motivated work in the design of a software application to support and increase the appeal of traditional face-to-face trauma-focused psychotherapy. The research followed a situated cognitive engineering approach, which included a domain analysis, scenarios and claims analysis based on experts reviews (N=10), user evaluations, and a case study. This resulted in the identification of nine core application functions: (1) provide a flexible way of storytelling, (2) provide a structured way of storytelling, (3) prevent losing track of changed and added events, (4) ensure patient trust, (5) ensure usage for therapists with different backgrounds, (6) ensuring awareness of treatment, (7) provide a personal approach, (8) prevent unexpected exposure to emotional material, (9) and ensure an appealing and motivating approach throughout the therapy. These functions formed the basis for the design of a military multi-modal memory restructuring (Military - 3MR) system, which focuses on restructuring and relearning of past events. The system allows the patient and therapist to visualize past events using personal photos, narrative text, online geographical maps, webcam snapshots, and patient created 3-D virtual worlds. Results of the usability evaluation (N=18) suggest key design features, such as the time line, content management, and the 3- D world editor, meet an acceptable perceived usability level. Results of a storytelling experiment (N=18) between telling an autobiographical story with or without the Military-3MR system found that with the system, time referencing and event description were more precise, and a smaller time period in the story was covered. In the case study, the veteran suffering from combat-related PTSD was pleased with the system and felt encouraged talking about past events. [ABSTRACT FROM AUTHOR]

Background. Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. Objective. This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with cognitive behavioral therapy with physical training alone and with no intervention. Design. In this multicenter randomized controlled trial, 147 survivors of cancer were randomly assigned to a group that received physical training combined with cognitive-behavioral therapy (PT+CBT group, n = 76) or to a group that received physical training alone (PT group, n=71). In addition, a nonintervention control group (WLC group) consisting of 62 survivors of cancer who were on the waiting lists of rehabilitation centers elsewhere was included. Setting. The study was conducted at 4 rehabilitation centers in the Netherlands. Patients. All patients were survivors of cancer. Intervention. Physical training consisting of 2 hours of individual training and group sports took place twice weekly, and cognitive-behavioral therapy took place once weekly for 2 hours. Measurements. Fatigue was assessed with the Multidimensional Fatigue Inventory before and immediately after intervention (12 weeks after enrollment). The WLC group completed questionnaires at the same time points. Results. Baseline fatigue did not differ significantly among the 3 groups. Over time, levels of fatigue significantly decreased in all domains in all groups, except in mental fatigue in the WLC group. Analyses of variance of postintervention fatigue showed statistically significant group effects on general fatigue, on physical and mental fatigue, and on reduced activation but not on reduced motivation. Compared with the WLC group, the PT group reported significantly greater decline in 4 domains of fatigue, whereas the PT+CBT group reported significantly greater decline in physical fatigue only. No significant differences in decline in fatigue were found between the PT+CBT and PT groups. Conclusions. Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training. INSET: The Bottom Line. [ABSTRACT FROM AUTHOR]

Previous studies showed substantial improvement of survival rates in patients with cancer in the last two decades. However, lower survival rates have been reported for older patients compared to younger patients. In this population-based study, we analyzed treatment patterns and the survival of patients with breast cancer (BC) and colorectal cancer (CRC). Patients with stages I–III BC and CRC and diagnosed between 2003 and 2012 were selected from the Netherlands Cancer Registry (NCR). Trends in treatment modalities were evaluated with the Cochran-Armitage trend test. Trends in five-year overall survival were calculated with the Cox hazard regression model. The Ederer II method was used to calculate the five-year relative survival. The relative excess risk of death (RER) was estimated using a multivariate generalized linear model. During the study period, 98% of BC patients aged <75 years underwent surgery, whereas for patients ≥75 years, rates were 79.3% in 2003 and 66.7% in 2012 (p < 0.001). Most CRC patients underwent surgery irrespective of age or time period, although patients with rectal cancer aged ≥75 years received less surgery or radiotherapy over the entire study period than younger patients. The administration of adjuvant chemotherapy increased over time for CRC and BC patients, except for BC patients aged ≥75 years. The five-year relative survival improved only in younger BC patients (adjusted RER 0.95–0.96 per year), and was lower for older BC patients (adjusted RER 1.00, 95% Confidence Interval (CI) 0.98–1.02, and RER 1.00; 95% CI 0.98–1.01 per year for 65–74 years and ≥75 years, respectively). For CRC patients, the five-year relative survival improved over time for all ages (adjusted RER on average was 0.95 per year). In conclusion, the observed survival trends in BC and CRC patients suggest advances in cancer treatment, but with striking differences in survival between older and younger patients, particularly for BC patients. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to assess the impact of a multimodal intervention on emergency department (ED) crowding and patient flow in a Dutch level 1 trauma center. Methods: In this cross-sectional study, we compare ED crowding and patient flow between a 9-month pre-intervention period and a 9-month intervention period, during peak hours and overall (24/7). The multimodal intervention included (1) adding an emergency nurse practitioner (ENP) and (2) five medical specialists during peak hours to the 24/7 available emergency physicians (EPs), (3) a Lean programme to improve radiology turnaround times, and (4) extending the admission offices' openings hours. Crowding is measured with the modified National ED OverCrowding Score (mNEDOCS). Furthermore, radiology turnaround times, patients' length of stay (LOS), proportion of patients leaving without being seen (LWBS) by a medical provider, and unscheduled representations are assessed. Results: The number of ED visits were grossly similar in the two periods during peak hours (15,558 ED visits in the pre-intervention period and 15,550 in the intervention period) and overall (31,891 ED visits in the pre-intervention period vs. 32,121 in the intervention period). During peak hours, ED crowding fell from 18.6% (pre-intervention period) to 3.5% (intervention period), radiology turnaround times decreased from an average of 91 min (interquartile range 45–256 min) to 50 min (IQR 30–106 min., p < 0.001) and LOS reduced with 13 min per patient from 167 to 154 min (p < 0.001). For surgery, neurology and cardiology patients, LOS reduced significantly (with 17 min, 25 min, and 8 min. respectively), while not changing for internal medicine patients. Overall, crowding, radiology turnaround times and LOS also decreased. Less patients LWBS in the intervention period (270 patients vs. 348 patients, p < 0.001) and less patients represented unscheduled within 1 week after the initial ED visit: 864 (2.7%) in the pre-intervention period vs. 645 (2.0%) patients in the intervention period, p < 0.001. Conclusions: In this hospital, a multimodal intervention successfully reduces crowding, radiology turnaround times, patients' LOS, number of patients LWBS and the number of unscheduled return visits, suggesting improved ED processes. Further research is required on total costs of care and long-term effects. [ABSTRACT FROM AUTHOR]