Aims To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to... Show moreAims To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT).Methods and results Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (A interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM.Conclusion Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.[GRAPHICS]. Show less
Eshuis, L.V.; Gelderen, M.J. van; Zuiden, M. van; Nijdam, M.J.; Vermetten, E.; Olff, M.; Bakker, A. 2021
Background: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD... Show moreBackground: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD) treatment by increasing a patient's sense of presence during exposure therapy. This study aimed to systematically review current evidence regarding the efficacy of VRET and ARET as PTSD treatment. Methods: A systematic electronic database search, a systematic quality assessment and two meta-analyses were conducted in accordance with PRISMA guidelines. Results: Eleven studies on the efficacy of VRET for PTSD (n = 438) were found, but no studies on the efficacy of ARET. The majority of VRET studies were of a low quality and had heterogeneous results. Meta-analyses showed VRET outperformed waitlist control (standardized mean difference -0.64 (95% CI -1.05 to -0.22)) while no significant difference was found between VRET and active treatment conditions (standardized mean difference -0.25 (95% CI -0.77 to 0.27)). Conclusion: VRET was superior to waitlist control groups and as effective as other psychotherapies. However, the results showed considerable heterogeneity due to the low number of studies and variety of VRET methods. VRET may be an effective alternative to current treatments and shows promise for the treatment of PTSD patients that have not responded to previous treatment. Future research should focus on high quality RCTs, including information on side effects and adverse events, with sufficient numbers of participants. This study recognizes a research gap regarding the efficacy of ARET, while it may have potential for PTSD treatment. Show less
Even after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The... Show moreEven after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The first part of this thesis investigated the challenges of the treatment decision-making process in patients with (severe) TBI by focussing on three factors considered to be important in this process: patient outcome, in-hospital healthcare consumption, and in-hospital costs. The second part investigated the procedural difficulties in TBI research efficiency by focussing on the process of institutional review board approval and the use of informed consent procedures in patients with TBI with an inability to provide informed consent. Finally, we elaborate on the role of patient outcome and in-hospital costs in the acute treatment decision-making process in patients with severe TBI and make suggestions to optimize future research initiatives. Show less
Versluis, J.M.; Hendriks, A.M.; Weppler, A.M.; Brown, L.J.; Joode, K. de; Suijkerbuijk, K.P.M.; ... ; Jalving, M. 2021
Introduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with... Show moreIntroduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma.Patients and methods: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation.Results: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences.Conclusion: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes. & ordf;2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Lelie-van der Zande, R.; Koster, E.S.; Teichert, M.; Bouvy, M.L. 2021
Background The Dutch general practitioners (GP) guideline for urinary tract infections (UTI) recommends patient-initiated treatment for women with recurring UTI. In countries other than the... Show moreBackground The Dutch general practitioners (GP) guideline for urinary tract infections (UTI) recommends patient-initiated treatment for women with recurring UTI. In countries other than the Netherlands, community pharmacists play a role in dispensing antibiotics for recurring UTI without preceding GP consultation. Objective To study GP and pharmacist opinions regarding the desirability of patient-initiated treatment, including potential pharmacist support for, and consequences of, facilitated access to antibiotics. Setting Dutch community pharmacies that cooperate with at least two GPs in their regional primary care network. Method Pharmacists in a postgraduate education program invited their residency pharmacist and 2-3 GPs to anonymously complete an online questionnaire. Questions related to diagnosis, treatment and potential role of the pharmacist. Answers were formulated as multiple-choice or ratings on a 5-point Likert scale. Data were analysed per professional group using descriptive statistics. Answers of pharmacists and GP to corresponding questions were analysed using a Chi-square test (p < 0.05). Main outcome measure Desirability of patient-initiated treatment and supporting role of the pharmacist. Results A total of 170 GPs and 76 pharmacists completed the questionnaires. Of the GPs, 35.1% supported patient-initiated treatment. Of the pharmacists, 69.7% were willing to dispense an antibiotic to a patient without preceding GP consultation after performing a probability check. In total, 65.7% of GPs and 44.7% of pharmacists thought that facilitated access to antibiotics would increase use of antibiotics (p < 0.05). Conclusion Support of GPs for facilitated access to antibiotic treatment by patient-initiated UTI treatment was limited, even with pharmacist support. The majority of pharmacists were willing to dispense an antibiotic after a probability check of an episode of recurring UTI, but both pharmacists and GPs were concerned about overuse of antibiotics. Show less
Background The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific... Show moreBackground The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of breast cancer. Methods Women included in the Netherlands Cancer Registry and diagnosed during four periods in weeks 2-17 of 2020 were compared with reference data from 2018/2019 (averaged). Weekly incidence was calculated by age group and tumor stage. The number of women receiving initial treatment within 3 months of diagnosis was calculated by period, initial treatment, age, and stage. Initial treatment, stratified by tumor behavior (ductal carcinoma in situ [DCIS] or invasive), was analyzed by logistic regression and adjusted for age, socioeconomic status, stage, subtype, and region. Factors influencing time to treatment were analyzed by Cox regression. Results Incidence declined across all age groups and tumor stages (except stage IV) from 2018/2019 to 2020, particularly for DCIS and stage I disease (p < 0.05). DCIS was less likely to be treated within 3 months (odds ratio [OR](wks2-8): 2.04, ORwks9-11: 2.18). Invasive tumors were less likely to be treated initially by mastectomy with immediate reconstruction (ORwks12-13: 0.52) or by breast conserving surgery (ORwks14-17: 0.75). Chemotherapy was less likely for tumors diagnosed in the beginning of the study period (ORwks9-11: 0.59, ORwks12-13: 0.66), but more likely for those diagnosed at the end (ORwks14-17: 1.31). Primary hormonal treatment was more common (ORwks2-8: 1.23, ORwks9-11: 1.92, ORwks12-13: 3.01). Only women diagnosed in weeks 2-8 of 2020 experienced treatment delays. Conclusion The incidence of breast cancer fell in early 2020, and treatment approaches adapted rapidly. Clarification is needed on how this has affected stage migration and outcomes. Show less
Boer, F.L.; Eikelder, M.L.G. ten; Geloven, N. van; Kapiteijn, E.H.; Gaarenstroom, K.N.; Hughes, G.; ... ; Poelgeest, M.I.E. van 2021
Objective. To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). Materials & methods. This... Show moreObjective. To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). Materials & methods. This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. Results. The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-riskclinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40?56%) and 31% (95% CI 23?39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. Conclusion. Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.Objective. To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM).Materials & methods. This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis.Results. The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-riskclinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno-or targeted therapy.Conclusion. Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Hoeboer, C.; Roos, C. de; Son, G.E. van; Spinhoven, P.; Elzinga, B. 2021
Background: Maltreatment by a primary caregiver is an important risk factor for the development of PTSD symptoms. Whereas meta-analyses indicate that parental emotional abuse is one of the most... Show moreBackground: Maltreatment by a primary caregiver is an important risk factor for the development of PTSD symptoms. Whereas meta-analyses indicate that parental emotional abuse is one of the most common forms of maltreatment, the impact of emotional abuse on PTSD symptoms and treatment effectiveness is still unclear, especially in children.Objective: We aimed to investigate the impact of parental emotional abuse on PTSD symptom severity and effectiveness of trauma treatment in children and adolescents.Method: In an outpatient sample (N = 287, mean age = 15.5 years), emotional abuse, index traumatic event, and PTSD symptoms were assessed at baseline. Thereafter, patients received evidence-based treatment for trauma-related symptoms embedded in a broader (systemic) treatment package. In a subsample (n = 130, mean age = 15.3 years) PTSD symptoms were assessed again 6 and 12 months after baseline.Results: Emotional abuse (rather than any other type of maltreatment) was associated with more severe PTSD symptoms in all symptom clusters. This was independent of whether emotional abuse was reported as index traumatic event or not. Moreover, PTSD symptoms were significantly reduced 6 months after the start of trauma-focused treatment, and emotional abuse was associated with more severe PTSD symptoms over the course of treatment.Conclusions: These findings underline the detrimental nature of emotional maltreatment in the context of PTSD symptomatology and treatment effectiveness. This calls for routine assessment of parental emotional abuse in the diagnostic phase, even when this is not the reason of referral. Show less
