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Coronary flow velocity reserve (CFVR) is defined as the ratio between coronary flow velocity during maximal hyperemia and coronary flow at rest. Gold-standard techniques to measure CFVR are either invasive or require radiation and are therefore inappropriate for large-scale adoption. More than 30 years ago, echocardiography was demonstrated to be a reliable tool to assess CFVR, and its field of application rapidly expanded. Although initially validated to assess the hemodynamic relevance of a coronary stenosis, CFVR by echocardiography was later used to investigate coronary microcirculation. Microvascular dysfunction was detected in many different conditions, ranging from organ transplantation to inflammatory disorders and from metabolic diseases to cardiomyopathies. Moreover, it has been proven that CFVR by echocardiography not only detects coronary microvascular involvement but is also an effective prognostic factor that allows a precise risk stratification of the patients. In this review, we will summarize the many applications of CFVR by echocardiography, focusing on the coronary involvement of systemic diseases.

BackgroundSafety planning-type interventions (SPTIs) for patients at risk of suicide are often used in clinical practice, but it is unclear whether these interventions are effective.AimsThis article reports on a meta-analysis of studies that have evaluated the effectiveness of SPTIs in reducing suicidal behaviour and ideation.MethodWe searched Medline, EMBASE, PsycINFO, Web of Science and Scopus from their inception to 9 December 2019, for studies that compared an SPTI with a control condition and had suicidal behaviour or ideation as outcomes. Two researchers independently extracted the data. To assess suicidal behaviour, we used a random-effects model of relative risk based on a pooled measure of suicidal behaviour. For suicidal ideation, we calculated effect sizes with Hedges’ g. The study was registered at PROSPERO (registration number CRD42020129185).ResultsOf 1816 unique abstracts screened, 6 studies with 3536 participants were eligible for analysis. The relative risk of suicidal behaviour among patients who received an SPTI compared with control was 0.570 (95% CI 0.408–0.795, P = 0.001; number needed to treat, 16). No significant effect was found for suicidal ideation.ConclusionsTo our knowledge, this is the first study to report a meta-analysis on SPTIs for suicide prevention. Results support the use of SPTIs to help preventing suicidal behaviour and the inclusion of SPTIs in clinical guidelines for suicide prevention. We found no evidence for an effect of SPTIs on suicidal ideation, and other interventions may be needed for this purpose.

Abstract. Background: Increasing rail transportation requires appropriate railway suicide preventive measures. Aims: The investigation of trends in railway suicide during 2008–2018, a period in which preventive measures were taken by Dutch railway infrastructure manager ProRail. Methods: Generalized linear regression models for railway suicide were developed for the period 1970–2007 with general suicide rate, railway traffic intensity, and a combination of these variables as regressors. Subsequently, the best-fitting model was used to investigate trends in railway suicide after 2007 by comparing in retrospect observed values with the expected outcomes of the regression model. Results: An adequate regression model for railway suicide was obtained using both general suicide rate and railway traffic intensity as regressors. Based on this model, while national suicide mortality and railway traffic increased, a distinct relative decline in railway suicides was found from 2012 onward. Conclusions: This decline of railway suicides in the Netherlands may indicate that preventive measures taken by ProRail were effective and prevented around 85 railway suicides annually, a reduction of 30%.

© 2020 The Authors. Suicide and Life-Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of SuicidologyBackground: Suicidal behavior is the result of complex interactions between many different factors that change over time. A network perspective may improve our understanding of these complex dynamics. Within the network perspective, psychopathology is considered to be a consequence of symptoms that directly interact with one another in a network structure. To view suicidal behavior as the result of such a complex system is a good starting point to facilitate moving away from traditional linear thinking. Objective: To review the existing paradigms and theories and their application to suicidal behavior. Methods: In the first part of this paper, we introduce the relevant concepts within network analysis such as network density and centrality. Where possible, we refer to studies that have applied these concepts within the field of suicide prevention. In the second part, we move one step further, by understanding the network perspective as an initial step toward complex system theory. The latter is a branch of science that models interacting variables in order to understand the dynamics of complex systems, such as tipping points and hysteresis. Results: Few studies have applied network analysis to study suicidal behavior. The studies that do highlight the complexity of suicidality. Complexity science offers potential useful concepts such as alternative stable states and resilience to study psychopathology and suicidal behavior, as demonstrated within the field of depression. To date, one innovative study has applied concepts from complexity science to better understand suicidal behavior. Complexity science and its application to human behavior are in its infancy, and it requires more collaboration between complexity scientists and behavioral scientists. Conclusions: Clinicians and scientists are increasingly conceptualizing suicidal behavior as the result of the complex interaction between many different biological, social, and psychological risk and protective factors. Novel statistical techniques such as network analysis can help the field to better understand this complexity. The application of concepts from complexity science to the field of psychopathology and suicide research offers exciting and promising possibilities for our understanding and prevention of suicide.

Background The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer. Methods Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary. Results All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers. Conclusions Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning. Trial registration The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

The Multi-Objective Real-Valued Gene-pool Optimal Mixing Evolutionary Algorithm (MO-RV-GOMEA) has been proven effective and efficient in solving real-world problems. A prime example is optimizing treatment plans for prostate cancer brachytherapy, an internal form of radiation treatment, for which equally important clinical aims from a base protocol are grouped into two objectives and bi-objectively optimized. This use of MO-RV-GOMEA was recently successfully introduced into clinical practice. Brachytherapy can also play an important role in treating cervical cancer. However, using the same approach to optimize treatment plans often does not immediately lead to clinically desirable results. Concordantly, medical experts indicate that they use additional aims beyond the cervix base protocol. Moreover, these aims have different priorities and can be patient-specifically adjusted. For this reason, we propose a novel adaptive objective configuration method to use with MO-RV-GOMEA so that we can accommodate additional aims of this nature. Based on results using only the base protocol, in consultation with medical experts, we configured key additional aims. We show how, for 10 patient cases, the new approach achieves the intended result, properly taking into account the additional aims. Consequently, plans resulting from the new approach are preferred by medical specialists in 8/10 cases.

Simple Summary Chemoradiation with photon radiotherapy is very effective as a locally advanced cervical cancer (LACC) treatment. However, the majority of women with LACC experience treatment-related toxicity involving the gastrointestinal and urogenital tracts and the immune system. Compared to that of photon therapy, proton therapy substantially reduces undesired dose to the organs around the tumor, leading to a decrease in radiotherapy-related side-effects. At present, few studies on proton therapy in patients with LACC will be conducted. The PROTECT trial aims to evaluate the differences in side effects between photon therapy and proton therapy, both combined with chemotherapy, for LACC. Fifteen patients will be enrolled per treatment group. Information will be collected on the differences in dose to the organs around the tumor, treatment-related side effects, and the impact on the immune system. This information will be used to assess the potential of proton therapy as an innovative treatment for LACC. Abstract External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient’s quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.

BACKGROUND: Recent studies in patients and general population have reported the role of left ventricular (LV) longitudinal strain (LS) as an independent predictor of outcome. However, there are few data on changes in LS over time. We therefore investigated in a general population clinical correlates of temporal changes in LS. We also explored the potential correlation between temporal changes in LV volumes and LS. METHODS AND RESULTS: We measured LV end-systolic (ESV) and end-diastolic (EDV) volumes by conventional echocardiography and LS by 2D speckle tracking in 627 participants (mean age 50.6 years, 51.4% women; 41.3% hypertensives) at baseline and after 4.7 years. For statistical analysis, we used the absolute values of LS. In stepwise regression, the magnitude of the decrease in all LV LS indexes over time was greater in men than in women (P

Background: Suicidality could be associated with specific combinations of biological, social and psychologicalfactors. Therefore, depressive episodes with suicidal ideation could be different from depressive episodeswithout suicidal ideation in terms of latent variable structures.Methods: In this study we compared latent variable structures between suicidal and non-suicidal depressedpatients using confirmatory factor analysis (CFA), following a measurement invariance test procedure. Patients(N = 919) suffering from major depressive disorder were selected from the Netherlands Study of Depression andAnxiety (NESDA) and split into a group that showed no symptoms of suicidal ideation (non-SI; N = 691) and asuicidal ideation (SI) group that had one or more symptoms of suicidal ideation (N = 228). Depression andanxiety symptoms were measured using the short form of the Mood and Anxiety Symptoms Questionnaire(MASQ-D30).Results: CFA implied a difference in latent variable structures between the non-SI sample (CFI 0.957; RMSEA0.041) and the SI sample (CFI 0.900; RMSEA 0.056). Subsequent multiple-group CFA showed violations ofmeasurement invariance. The General distress and Anhedonic depression subscales were best indicated byhopelessness and lack of optimism in the SI sample and by dissatisfaction and not feeling lively in the non-SIsample. Overall, the SI sample had higher scores and lower inter-item correlations on the Anhedonic depressionitems.Limitations: We have included very mild cases of suicidal ideation in our SI sample.Conclusions: On a latent variable level, depression with suicidal ideation differs from depression without suicidalideation. Results encourage further research into the symptom structure of depression among suicidal patients

Background The evidence for the effectiveness of e-mental health interventions among ethnic minorities is still preliminary. This mixed methods study investigates the feasibility of a culturally adapted, guided online intervention with the intention to understand how it works and for whom to inform refinement. It also examines its likely effectiveness in reducing suicidal ideation when compared with the treatment as usual. Methods Turkish migrants with mild to moderate suicidal thoughts were recruited from the general population using social media and newspaper advertisements. The intervention group obtained direct access to a 6-week guided online intervention while participants in the waiting list condition had to wait for 6 weeks. The intervention is based on an existing online intervention and was culturally adapted. Participants in both conditions completed baseline, post-test, and follow-up questionnaires on suicidal ideation (primary outcome), depression, worrying, hopelessness, suicide attempt and self-harm, acculturation, quality of life, and usability. In addition, participants were interviewed to examine the feasibility and mechanisms of action in more depth. The responses were analysed by inductive thematic analysis. Results Eighty-five people signed up via the study website, and we included 18 (10 intervention, 8 waitlist control). While the therapeutic benefits were emphasised (e.g. feeling connected with the intervention), the feasibility was judged to be low. The main reasons given were not having severe suicidal thoughts and not being represented by the culturally adapted intervention. No suicide attempts were recorded during the study. The suicidal ideation, depression, and hopelessness scores were improved in both groups. Conclusion Although intended to be a definitive trial, the current study became a feasibility study with process evaluation to understand the components and how they operate. The online intervention was not superior to the control condition. Future studies need to attend the implementation issues raised including measures of stigma, acculturation, and careful cultural adaptations alongside more attention to coaching and relational support. They should also consider how to improve engagement alongside selection of those who are motivated to use online interventions and offer alternatives for those who are not. Trial registration Netherlands Trial Register, NTR5028. Registered on 1 March 2015

An amendment to this paper has been published and can be accessed via the original article.

PURPOSE: The individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an ultrashort echo time (UTE) MRI sequence could be used to visualize the individual channels to enable MR-only treatment planning for rectal cancer.METHODS AND MATERIALS: We used a radial three-dimensional (3D) UTE pulse sequence and acquired images of phantoms and two patients with rectal cancer. We rigidly registered a UTE image and CT scan of an applicator phantom, based on the outline of the applicator. One observer compared channel positions on the UTE image and CT scan in five slices spaced 25 mm apart. To quantify geometric distortions, we scanned a commercial 3D geometric quality assurance phantom and calculated the difference between detected marker positions on the UTE image and corresponding marker positions on two 3D T-1-weighted images with opposing readout directions.RESULTS: On the UTE images, there is sufficient contrast to discern the individual channels. The difference in channel positions on the UTE image compared with the CT was on average -0.1 +/- 0.1 mm (left-right) and 0.1 +/- 0.3 mm (anteroposterior). After rigid registration to the 3D T-1-weighted sequences, the residual 95th percentile of the geometric distortion inside a 550-mm-diameter sphere was 1.0 mm (left-right), 0.9 mm (anteroposterior), and 0.9 mm (craniocaudal).CONCLUSIONS: With a UTE sequence, the endorectal applicator and individual channels can be adequately visualized in both phantom and patients. The geometrical fidelity is within an acceptable range. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of American Brachytherapy Society.

Background There is a strong stigma attached to mental disorders preventing those affected from getting psychological help. The consequences of stigma are worse for racial and/or ethnic minorities compared to racial and/or ethnic majorities since the former often experience other social adversities such as poverty and discrimination within policies and institutions. This is the first systematic review and meta-analysis summarizing the evidence on the impact of differences in mental illness stigma between racial minorities and majorities. Methods This systematic review and meta-analysis included cross-sectional studies comparing mental illness stigma between racial minorities and majorities. Systematic searches were conducted in the bibliographic databases of PubMed, PsycINFO and EMBASE until 20th December 2018. Outcomes were extracted from published reports, and meta-analyses, and meta-regression analyses were conducted in CMA software. Results After screening 2787 abstracts, 29 studies with 193,418 participants (N = 35,836 in racial minorities) were eligible for analyses. Racial minorities showed more stigma than racial majorities (g = 0.20 (95% CI: 0.12 ~ 0.27) for common mental disorders. Sensitivity analyses showed robustness of these results. Multivariate meta-regression analyses pointed to the possible moderating role of the number of studies with high risk of bias on the effect size. Racial minorities have more stigma for common mental disorders when compared with majorities. Limitations included moderate to high risk of bias, high heterogeneity, few studies in most comparisons, and the use of non-standardized outcome measures. Conclusions Mental illness stigma is higher among ethnic minorities than majorities. An important clinical implication of these findings would be to tailor anti-stigma strategies related with mental illnesses according to specific racial and/or ethnic backgrounds with the intention to improve mental health outreach.

Background Many persons with autism spectrum disorder (ASD) are treated in long-term specialised care. In this population, suicidal behaviour troubles patients, families, and specialists in the field because it is difficult to treat. At present, there is no documented effective therapy for suicidal behaviour in ASD (Autism Research 7:507-521, 2014; Crisis 35:301-309, 2014). Dialectical Behaviour Therapy (DBT) is an efficacious treatment programme for chronically suicidal and/or self-harm behaviour in patients with Borderline Personality Disorder (J Psychiatry 166:1365-1374, 2014; Linehan MM. Cognitive behavioural therapy of borderline personality disorder. 1993). This study will evaluate the efficacy of DBT in persons with ASD and suicidal/ self- destructive behaviour in a multicentre randomised controlled clinical trial. Method One hundred twenty-eight persons with autism and suicidal and/or self-harming behaviour will be recruited from specialised mental healthcare services and randomised into two conditions: 1) the DBT condition in which the participants have weekly individual cognitive behavioural therapy sessions and a 2.5 h skills training group session twice per week during 6 months, and 2) the treatment as usual condition which consists of weekly individual therapy sessions of 30–45 min with a psychotherapist or social worker. Assessments will take place at baseline, at post-treatment (6 months), and after a follow-up period of 12 months. The mediators will also be assessed at 3 months. The primary outcome is the level of suicidal ideation and behaviour. The secondary outcomes are anxiety and social performance, depression, core symptoms of ASD, quality of life, and cost-utility. Emotion regulation and therapeutic alliance are hypothesised to mediate the effects on the primary outcome. Discussion The results from this study will provide an evaluation of the efficacy of DBT treatment in persons with ASD on suicidal and self-harming behaviour. The study is conducted in routine mental health services which enhances the generalisability of the study results to clinical practice. Trial registration ISRCTN96632579. Registered 1 May 2019. Retrospectively registered.

Background: The evidence for the effectiveness of e-mental health interventions among ethnic minorities is still preliminary. This mixed methods study investigates the feasibility of a culturally adapted, guided online intervention with the intention to understand how it works and for whom to inform refinement. It also examines indications for its effectiveness in reducing suicidal ideation when compared with the treatment as usual. Methods: Turkish migrants (first and second generation) with mild to moderate suicidal thoughts were recruited from the general population using social media and newspaper advertisements. The intervention group obtained direct access to a 6 weeks guided online intervention while participants in the waiting list condition had to wait for 6 weeks. The intervention is based on an existing online intervention and was culturally adapted. Participants in both conditions completed baseline, post-test, and follow up questionnaires on suicidal ideation (primary outcome), depression, worrying, hopelessness, suicide attempt and self-harm, acculturation, quality of life, and usability. In addition, participants were interviewed to examine the feasibility and mechanisms of action in more depth. The responses were analysed by inductive thematic analysis. Results: A total of 85 people signed up via the study website and 18 (10 intervention, 8 waitlist control) were included. While the therapeutic benefits were emphasised (e.g. feeling connected with the intervention), the feasibility was judged to be low. The main reasons given were: not having severe suicidal thoughts and not being represented by the culturally adapted intervention. No suicide attempts were recorded during the study. The suicidal ideation, depression and hopelessness scores were improved in both groups. Conclusion: The online intervention, as might be expected in a small feasibility study, was not superior to the control condition. Future studies need to attend the implementation issues raised including measures of stigma, acculturation, careful cultural adaptations alongside more attention to coaching and relational support. They should also consider how to improve engagement alongside selection of those who are motivated to use online interventions and offer alternatives for those who are not. Trial registration: NTR5028. Registered 1 March 2015, https://www.trialregister.nl/trial/4926

In cardiovascular studies, two related parameters that determine the same physical variable are often recorded. Interpretation of the calculated indicators presented in the form of ratios and differences is difficult, since they can be associated with several combinations of primary data giving the same value.Aim.To find a way to overcome this limitation and take a more comprehensive approach.Material and methods.We analyzed the data on left ventricular volume and blood pressure (BP) in 275 patients (women — 207), obtained using echocardiography and BP monitor. To calculate a lost companion (c) value based on a difference or dimensionless ratio, we applied the Pythagorean theorem. The lost companion isdefined as the hypotenuse in each study area. To calculate the pulse pressure companion (PP), the following formula was used: PP(c)=Ö(SBP2+SBP2). Similar methods were applied to ejection fraction (EF), augmentation pressure (AG) and AG/PP ratio, resulting in the ratio called augmentation index (AIx).Results.1. Mean blood pressure (MBP) acts as a surrogate for the PP companion (PPc) values (R=0,970, N=257). 2. We have identified correlations between PPc and pulse wave velocity (R=0,397, N=193), and AGc with AIx (75) (R=0,662, N=198). 3. EF has an inverse relationship with the end diastolic volume (EDV) (R=-0,559, N=187), and the ventricular-arterial coupling (VAC) correlates with ESV (r=-0,627, N=180). 4. Comparison of EDV and VACc revealed R of 0,949.Conclusion.Companions calculated from the available data can have significant additional diagnostic value without the need for additional measurements. It is important to note that the combination of traditional ratio-based and suggested companions allows for more accurate data on individual patients.

BACKGROUND: Quantification of ventricular performance requires a comprehensive metric which is manageable for patient care and clinical trials. Ejection fraction (EF) has been embraced as an attractive candidate. However, being a dimensionless ratio, EF has serious limitations. METHODS: We aim to identify what information is not recognized when limiting the volume-related analysis by exclusively relying on EF. This investigation applies the volume domain concept, relating end-systolic volume (ESV) to end-diastolic volume (EDV). This approach allows graphical identification of the information not covered by EF. Implications for atria, left ventricle (LV) and right ventricle (RV) are investigated in healthy individuals, and cardiac patient groups using various imaging modalities. RESULTS: The Pythagorean theorem indicates that the hypotenuse which relates any {EDV, ESV} combination to EF corresponds with the information not covered by the single metric EF. The impact of the recovered EF companion (EFC) is illustrated in healthy adults (N = 410, LV 2D echocardiography), heart transplant patients (N = 101, LV CT), individuals with heart failure (N = 197, biplane angiocardiography), for the RV with corrected Fallot (N = 124, MRI), diameters for left atrium (N = 49, MRI) and area for right atrium (N = 51, MRI). For any limited EF range we find a spectrum of EFC values, showing that the two metrics contain (partly) independent information, and emphasizing that the sole use of EF only partially conveys the full information available. CONCLUSIONS: The EFC is a neglected companion, containing information which is additive to EF. Analysis based on ESV and EDV is preferred over the use of EF. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:270 pages:237-243 ispartof: location:Netherlands status: published

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago. ispartof: ADVANCES IN PHYSIOLOGY EDUCATION vol:42 issue:1 pages:130-139 ispartof: location:United States status: published

ObjectiveIt is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients' outcomes compared with primary surgery.DesignPatients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication.Results602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome.ConclusionsOur data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients.

Suicide prevention is a major health care responsibility in need of new perspectives. This study reviews Zero Suicide, an emerging approach to suicide prevention that embraces the aspirational goal of zero suicides among patients treated in health care systems or organizations. Zero Suicide is gaining international momentum while at the same time evoking objections and concerns. Fundamental to Zero Suicide is a multilevel system view on suicide prevention, with three core elements: a direct approach to suicidal behaviors; continual improvement of the quality and safety of care processes; and an organizational commitment to the aspirational goal of zero suicides. The rationale and evidence for these components are clarified and discussed against the backdrop of concerns and objections that focus on possible undesired consequences of the pursuit of zero suicide, in particular for clinicians and for those who are bereaved by suicide. It is concluded that it is rational to pursue zero suicides as an aspirational goal, provided the journey toward zero suicides is undertaken in a systemic and sustained manner, in a way that professionals feel supported, empowered, and protected against blame and inappropriate guilt.

Purpose To evaluate the feasibility of fiducial markers as a surrogate for gross tumor volume (GTV) position in image-guided radiation therapy of rectal cancer. Methods and Materials We analyzed 35 fiducials in 19 patients with rectal cancer who received short-course radiation therapy or long-course chemoradiation therapy. Magnetic resonance imaging examinations were performed before and after the first week of radiation therapy, and daily pre- and postirradiation cone beam computed tomography scans were acquired in the first week of radiation therapy. Between the 2 magnetic resonance imaging examinations, the fiducial displacement relative to the center of gravity of the GTV (COGGTV) and the COGGTV displacement relative to bony anatomy were determined. Using the cone beam computed tomography scans, inter- and intrafraction fiducial displacement relative to bony anatomy were determined. Results The systematic error of the fiducial displacement relative to the COGGTV was 2.8, 2.4, and 4.2 mm in the left-right, anterior-posterior (AP), and craniocaudal (CC) directions, respectively. Large interfraction systematic errors of up to 8.0 mm and random errors up to 4.7 mm were found for COGGTV and fiducial displacements relative to bony anatomy, mostly in the AP and CC directions. For tumors located in the mid and upper rectum, these errors were up to 9.4 mm (systematic) and 5.6 mm (random) compared with 4.9 mm and 2.9 mm for tumors in the lower rectum. Systematic and random errors of the intrafraction fiducial displacement relative to bony anatomy were ≤2.1 mm in all directions. Conclusions Large interfraction errors of the COGGTV and the fiducials relative to bony anatomy were found. Therefore, despite the observed fiducial displacement relative to the COGGTV, the use of fiducials as a surrogate for GTV position reduces the required margins in the AP and CC directions for a GTV boost using image-guided radiation therapy of rectal cancer. This reduction in margin may be larger in patients with tumors located in the mid and upper rectum compared with the lower rectum.

Background and study aims To facilitate image guidance during radiotherapy of rectal cancer, we investigated the feasibility of fiducial marker placement. This study aimed to evaluate technical success rate and safety of two endoscopic ultrasound (EUS)-guided placement strategies and four fiducial types for rectal cancer patients. Patients and methods This prospective multicenter study included 20 participants who were scheduled to undergo rectal cancer treatment with neoadjuvant short-course radiotherapy or chemoradiation. EUS-guided endoscopy was used for fiducial placement at the tumor site (n = 10) or in the mesorectal fat and in the tumor (n = 10). Four fiducial types were used (Visicoil 0.75 mm, Visicoil 0.50 mm, Cook, Gold Anchor). The endpoints were technical success rate and retention of fiducials, the latter of which was evaluated on cone-beam computed tomography scans during the first five radiotherapy fractions. Results A total of 64 fiducials were placed in 20 patients. For each fiducial type, at least three fiducials were successfully placed in all patients. Technical failure consisted of fiducial blockage within the needle (n = 2) and ejection of two preloaded fiducials at once (n = 4). No serious adverse events were reported. In three patients, one of the fiducials was misplaced without clinical consequences; two in the prostate and one in the intraperitoneal cavity. After a median time of 17 days after placement (range 7 – 47 days), a total of 42/64 (66 %) fiducials were still present (24/44 intratumoral vs. 18/20 mesorectal fiducials, P = 0.009). Conclusions Placement of fiducials in rectal cancer patients is feasible, however, retention rates for intratumoral fiducials were lower (55 %) than for mesorectal fiducials (90 %).

Highlights • Mesorectal-only RT for early rectal cancer requires dedicated planning guidelines. • A multi-centre study was conducted to identify planning objectives. • Robust optimisation objectives for organs at risk are presented., Background and purpose Organ preservation strategies are increasingly being explored for early rectal cancer. This requires revision of target volumes according to disease stage, as well as new guidelines for treatment planning. We conducted an international, multicentre dose planning study to develop robust planning objectives for modern radiotherapy of a novel mesorectal-only target volume, as implemented in the STAR-TReC trial (NCT02945566). Materials and methods The published literature was used to establish relevant dose levels for organ at risk (OAR) plan optimisation. Ten representative patients with early rectal cancer were identified. Treatment scans had mesorectal target volumes as well as bowel cavity, bladder and femoral heads outlined, and were circulated amongst the three participating institutions. Each institution produced plans for short course (SCRT, 5 × 5 Gy) and long course (LCRT, 25 × 2 Gy) treatment, using volumetric modulated arc therapy on different dose planning systems. Optimisation objectives for OARs were established by determining dose metric objectives achievable for ≥90% of plans. Results Sixty plans, all fulfilling target coverage criteria, were produced. The planning results and literature review suggested optimisation objectives for SCRT: V10Gy

Purpose The HERBERT study was a dose-finding feasibility study of a high-dose rate endorectal brachytherapy (HDREBT) boost after external beam radiotherapy (EBRT) in elderly patients with rectal cancer who were unfit for surgery. This analysis evaluates the association of patient, tumor and dosimetric parameters with tumor response and toxicity after HDREBT in definitive radiotherapy for rectal cancer. Patients and methods The HERBERT study included 38 inoperable patients with T2-3N0-1 rectal cancer. Thirteen fractions of 3 Gy EBRT were followed by three weekly HDREBT applications of 5–8 Gy per fraction. Clinical and dosimetric parameters were tested for correlation with clinical complete response (cCR), sustained partial/complete response (SR), patient reported bowel symptoms, physician reported acute and late proctitis (CTCAE v3) and endoscopically scored toxicity. Results Thirty-five patients completed treatment and were included in the current analyses. Twenty of 33 evaluable patients achieved a cCR, the median duration of a sustained response was 32 months. Tumor volume at diagnosis showed a strong association with clinical complete response (OR 1.15; p = 0.005). No dose–response correlation was observed in this cohort. Prescribed dose to the brachytherapy CTV (D90) correlated with acute and late physician reported proctitis while CTV volume, CTV width and high dose regions in the CTV (D1cc/D2cc) were associated with endoscopic toxicity at the tumor site. Conclusion Tumor volume is the most important predictive factor for tumor response and a higher dose to the brachytherapy CTV increases the risk of severe clinically and endoscopically observed proctitis after definitive radiotherapy in elderly patients with rectal cancer.

Background and purpose A GTV boost is suggested to result in higher complete response rates in rectal cancer patients, which is attractive for organ preservation. Fiducials may offer GTV position verification on (CB)CT, if the fiducial-GTV spatial relationship can be accurately defined on MRI. The study aim was to evaluate the MRI visibility of fiducials inserted in the rectum. Materials and methods We tested four fiducial types (two Visicoil types, Cook and Gold Anchor), inserted in five patients each. Four observers identified fiducial locations on two MRI exams per patient in two scenarios: without (scenario A) and with (scenario B) (CB)CT available. A fiducial was defined to be consistently identified if 3 out of 4 observers labeled that fiducial at the same position on MRI. Fiducial visibility was scored on an axial and sagittal T2-TSE sequence and a T1 3D GRE sequence. Results Fiducial identification was poor in scenario A for all fiducial types. The Visicoil 0.75 and Gold Anchor were the most consistently identified fiducials in scenario B with 7 out of 9 and 8 out of 11 consistently identified fiducials in the first MRI exam and 2 out of 7 and 5 out of 10 in the second MRI exam, respectively. The consistently identified Visicoil 0.75 and Gold Anchor fiducials were best visible on the T1 3D GRE sequence. Conclusion The Visicoil 0.75 and Gold Anchor fiducials were the most visible fiducials on MRI as they were most consistently identified. The use of a registered (CB)CT and a T1 3D GRE MRI sequence is recommended.

Suicide is a major public health problem, and it remains unclear which processes link suicidal ideation and plans to the act of suicide. Growing evidence shows that the majority of suicidal patients diagnosed with major depression or bipolar disorder report repetitive suicide-related images and thoughts (suicidal intrusions). Various studies showed that vividness of negative as well as positive intrusive images may be reduced by dual task (e.g. eye movements) interventions taxing the working memory. We propose that a dual task intervention may also reduce frequency and intensity of suicidal imagery and may be crucial in preventing the transition from suicidal ideation and planning to actual suicidal behaviour. This study aims a) to evaluate the effectiveness of an Eye Movement Dual Task (EMDT) add-on intervention targeting suicidal imagery in depressed patients, b) to explore the role of potential moderators and mediators in explaining the effect of EMDT, and c) to evaluate the cost-effectiveness of EMDT. We will conduct a multi-center randomized clinical trial (RCT) evaluating the effects of EMDT in combination with usual care (n = 45) compared to usual care alone (n = 45). Participants will fill in multiple online batteries of self-report questionnaires as well as complete a semi-structured interview (Intrusion Interview), and online computer tasks. The primary outcome is the frequency and intrusiveness of suicidal imagery. Furthermore, the vividness, emotionality, and content of the suicidal intrusions are evaluated; secondary outcomes include: suicidal behaviour and suicidal ideation, severity of depression, psychological symptoms, rumination, and hopelessness. Finally, potential moderators and mediators are assessed. If proven effective, EMDT can be added to regular treatment to reduce the frequency and vividness of suicidal imagery. The study has been registered on October 17th, 2018 at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR7563 ).

Recognizing the importance of digital communication, major suicide prevention helplines have started offering crisis intervention by chat. To date there is little evidence supporting the effectiveness of crisis chat services. To evaluate the reach and outcomes of the 113Online volunteer-operated crisis chat service, 526 crisis chat logs were studied, replicating the use of measures that were developed to study telephone crisis calls. Reaching a relatively young population of predominantly females with severe suicidality and (mental) health problems, chat outcomes for this group were found to be comparable to those found for crisis calls to U.S. Lifeline Centers in 2003-2004, with similar but not identical associations with specific helpers' styles and attitudes. Our findings support a positive effect of the 113Online chat service, to be enhanced by practice standards addressing an apparent lack of focus on the central issue of suicidality during chats, as well as by the development of best practices specific for online crisis intervention.

Currently, little is known about the views that Turkish migrants holdtowards suicide, which may differ from the narratives held by nativeinhabitants of their host countries. Central to improving the provision ofmental health services, furthering our knowledge of these views isimportant. The aim of this research was to explore Turkish culturalunderstandings on suicide and help-seeking for suicide. A qualitativestudy included data from 6 focus groups and 7 individual interviewswith 38 Turkish-speaking lay people and 4 key informants living in theNetherlands or the UK during the year 2014/2015. Through the analysisof participants’ stories and narratives, the following key themes emergedin relation to suicide: suicide as an escape from failure and as a failure initself; acculturation orientation; parenting style; and shame and stigma.There were more similarities than differences between the themesamong laypersons and key informants from two countries. Canınakıymak (crushing life energy) was a strong metaphor for personaldistress. Suicide was perceived as a failing of responsibilities towards thefamily and community. Future research should aim to give voice to allethnocultural groups to further the present understanding of suicideand help-seeking processes in these communities

In this editorial, we discuss how mobile phone technology has the potential to move the field forward in terms of understanding suicide risk as well as laying foundations for the development of effective treatments/interventions. We have focused on mobile health technology given the rapid growth of mobile health approaches in suicide prevention (De Jaegere & Portzky, 2014; Mishara & Kerkhof, 2013) and psychological research more generally (Myin-Germeys et al., 2009; Nock, Prinstein, & Sterba, 2009; Palmier-Claus et al., 2011) and because mobile phone use is ubiquitous, with 75% of the world having access to a mobile phone (Kay, 2011). (aut. ref.)

More suicidal ideation and higher rates of attempted suicide are found in Turkish people when compared with the general population in Europe. Acculturation processes and related distress may explain an elevated risk of suicide. The current study investigates the association between acculturation and suicidal ideation among Turkish migrants in the Netherlands. The mediating effect of hopelessness and moderating effect of secure attachment are also examined. A total of 185 Turkish migrants living in the Netherlands were recruited through social media and through liaison with community groups. They completed an online survey including validated measures of suicidal ideation, hopelessness, acculturation and attachment style. Mediation and moderation analyses were tested using bootstrapping. Higher participation was associated with less hopelessness and less suicidal ideation. Greater maintenance of one's ethnic culture was associated with higher hopelessness and higher suicidal ideation. Greater participation was associated with less suicidal ideation particularly amongst those with less secure attachment styles. Turkish migrants who participate in the host culture may have a lower risk of developing suicidal thinking. Participation may protect against suicidal thinking, particularly among those with less secure attachment styles.

Specific and systematic data on health care providers' behaviour is needed to futher improve the care provided to suicidal patiënts in mental health care facilities.br/METHOD: Explorative observational study of all suicidal incidents (n=50) that occurred in a Dutch mental health care facility over a one year period. Incidents were evaluated using KEHR SUICIDE, a questionnaire that assesses to what extent health care providers' conduct was compliant to the suicide practice guideline in the context of patients' suicidal behaviour. Associations between health care providers' and patients' features and guideline compliant behaviours of health care providers were calculated by logistic regression models.br/RESULTS: Health care providers showed less guideline compliant behaviour when the patient had a psychotic, substance abuse or development disorder or had no axis 1 disorder. A positive association was found between guideline compliant behaviour and the extent to which the incident had been expected. CONCLUSION Guideline compliant behaviour of mental health care providers appears to be related to the axis 1 disorder of patients in a Dutch mental health care facility. Still, the application of guideline compliant behaviour concerning suïcide incidents shows room for improvement. KEHR SUICIDE is shown to be a helpful tool for multidisciplinary evaluation of suicidal incidents as it provides specific, ready-made information by which mental health care facilities can guide, examine and adjust suicide prevention policy. The outcomes provide hypotheses that may be examined in future research.

Background It remains difficult to predict and prevent suicidal behaviour, despite growing understanding of the aetiology of suicidality. Clinical guidelines recommend that health care professionals develop a safety plan in collaboration with their high-risk patients, to lower the imminent risk of suicidal behaviour. Mobile health applications provide new opportunities for safety planning, and enable daily self-monitoring of suicide-related symptoms that may enhance safety planning. This paper presents the rationale and protocol of the Continuous Assessment for Suicide Prevention And Research (CASPAR) study. The aim of the study is two-fold: to evaluate the feasibility of mobile safety planning and daily mobile self-monitoring in routine care treatment for suicidal patients, and to conduct fundamental research on suicidal processes. Methods The study is an adaptive single cohort design among 80 adult outpatients or day-care patients, with the main diagnosis of major depressive disorder or dysthymia, who have an increased risk for suicidal behaviours. There are three measurement points, at baseline, at 1 and 3 months after baseline. Patients are instructed to use their mobile safety plan when necessary and monitor their suicidal symptoms daily. Both these apps will be used in treatment with their clinician. Conclusion The results from this study will provide insight into the feasibility of mobile safety planning and self-monitoring in treatment of suicidal patients. Furthermore, knowledge of the suicidal process will be enhanced, especially regarding the transition from suicidal ideation to behaviour. The study protocol is currently under revision for medical ethics approval by the medical ethics board of the Vrije Universiteit Medical centre Amsterdam (METc number 2017.512/NL62795.029.17)., Highlights • Mobile applications provide opportunities to enhance suicide prevention methods. • Patients can augment personalised safety plans by monitoring their own mental state. • Real-time monitoring data of psychological processes can be analysed to improve our understanding of suicidality and develop new technology for suicide prevention.

In The Netherlands, on average 40% of all suicides concern patients treated by mental healthcare institutions (MHIs). Recent evidence indicates that implemented guideline recommendations significantly reduce the odds for patients to die by suicide. Implementation of the multidisciplinary guideline for diagnosis and treatment of suicidal behaviors is a main objective of the Dutch National Suicide Prevention Strategy. To this end, 24 MHIs that collectively reported 73% of patient suicides in 2015 received an educational outreach intervention offered by the national center of expertise. Aim: To investigate changes in levels of implementation of guideline recommendations; and to assess the degree of variation on suicide prevention policies and practices between MHIs. Methods: Implementation study with a prospective cohort design studying change over time on all domains of a Suicide Prevention Monitor, a guideline-based instrument assessing suicide prevention policies and practices within MHIs. Data were collected in six-month intervals between 2015 and 2017. Results: MHIs improved significantly on four out of ten domains: the development of an organizational suicide prevention policy; monitoring and trend-analysis of suicides numbers; evaluations after suicide; and clinician training. No improvement was measured on the domains pertaining to multi-annual training policies; collaborative care with external partners; recording and evaluation of suicide attempts; routine assessment of suicidality in all patients; safety planning and involving next of kin and carers. Furthermore, marked practice variation between MHIs was found which did not decrease over time. Conclusion: This study shows significant improvement in the implementation of four out of ten guideline-based suicide prevention policies in 24 specialist mental healthcare institutions in The Netherlands. The implementation level of suicide prevention policies and practices still appears to vary significantly between MHIs in The Netherlands.

Introduction: The HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity. Material and methods: A brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 x 3 Gy) followed by three weekly HDREBT applications (5-8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon's signed rank test, paired t-test and Spearman's correlation were used. Results: Patient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and >= 3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12-18 months after treatment. Conclusion: For elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated. (C) 2018 Elsevier B.V. All rights reserved.

Background: Ejection fraction (EF) is commonly applied as a clinically relevant metric to assess ventricular function. The numerical value of EF depends on the interplay between end-systolic volume (ESV) and end-diastolic volume (EDV). Remarkably, the relative impact of the two constitutive components on EF received little attention. Methods: Three patient groups not using beta-blockers were analyzed for a robust investigation into the relative contribution of ESV and EDV when assessing EF: cardiac patients (N = 155) with left ventricular (LV) data obtained by biplane ventriculography, near-normals (N = 276) by gated SPECT investigation, and an MRI-based post Fallot repair study including right ventricular (RV) data (N = 124), besides LV. We compared various routes to evaluate EF via linear and several types of nonlinear regression with ESV as independent variable. Advanced statistics was applied to evaluate sex-specific differences. Results: In all cases ESV emerges as the dominant component of EF, with less (P < 0.0001) impact of EDV. The relationship for EF versus ESV is nonlinear (P < 0.0001), and similar for both sexes. A linear approach may be inadequate and generate erroneous statistical outcomes when comparing subgroups of patients. Conclusions: Values for EF primarily depend on ESV, both for LV and RV. This relationship is essentially nonlinear, and similar for both sexes. A logarithmic approximation is convenient and often acceptable. However, application of linear regression for EF vs ESV may lead to incorrect conclusions, particularly when comparing males and females.

In this planning study, we investigated the dosimetric benefit of repeat CT-based treatment planning at each fraction vs. the use of a single CT-based treatment plan for all fractions for high-dose-rate endorectal brachytherapy (HDREBT) for rectal cancer.We included 11 patients that received a CT scan with applicator in situ for all three fractions. The treatment plan of the first fraction was projected on the repeat CT scans to simulate the use of a single treatment plan. In addition, replanning was performed on the repeat CT scans, and these were compared to the corresponding projected treatment plans.Repeat CT-based treatment planning resulted on average in a 21% higher (p = 0.01) conformity index compared to single CT-based treatment planning. Projecting the initial treatment plan to the repeat CT scans of fraction two and three, 12/22 fractions reached a CTV D98 of 85% of the prescribed dose of 7 Gy, which increased to 14/22 using replanning. For the remaining fractions, median CTV D98 was 4.2 Gy, and an intervention would be necessary to correct applicator balloon setup or to remove remaining air and/or feces between the CTV and the applicator.Using a single CT-based treatment plan for all fractions may result in a suboptimal treatment at later fractions. Therefore, repeat CT imaging should be the minimal standard practice in HDREBT for rectal cancer to determine whether an intervention would be necessary. Replanning based on repeat CT imaging resulted in more conformal treatment plans and is therefore recommended.

According to the Canadian law legalizing physicians to provide medical assistance in dying (MAID) under certain circumstances, the patients alone determine if their suffering cannot be relieved under conditions "that they consider acceptable." This contrasts with the laws on MAID in the Netherlands, which require that physicians only grant access to MAID if they concur with the patient that there are no other potential means of alleviating the suffering. In the Netherlands, when a doctor believes that other means to reduce the suffering exist, they must be tried before having access to MAID. This criterion is often applied and is considered an essential precaution to ensure that lives are not ended prematurely when other viable interventions exist. The Canadian emphasis on the patient's right to decide whether to try potential alternatives a physician may suggest, such as palliative care, instead of dying by MAID, gives patients the liberty to make informed decisions, even when they may not seem to be in their best interest. This contrasts with the belief in the Netherlands that the state has an obligation to protect citizens from making decisions that are not in their best interest, such as choosing to die when the "intolerable suffering" can be diminished sufficiently for the person to abandon the desire to end the suffering by dying. The Canadian parliament, when they consider expanding access to MAID, should incorporate the Dutch due care safeguards to ensure that death is not the solution when other ways of reducing suffering exist.