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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.

Abstract. Background: Online forums that enable peer-to-peer interaction are widespread and readily available. Aim: This study aimed to identify the reach, benefits, and potential harmful effects for visitors to an online forum embedded in a suicide prevention platform in The Netherlands. Method: The study collected web-based questionnaires from online forum users and moderated posts. Descriptive quantitative and qualitative analyses were performed. Results: The online forum had 330 members in 2017, of whom 130 were active users (posting at least one message). Respondents ( n = 106) experienced from a high severity of suicidal ideation (78%). A minority (12%) visited the forum to find suicide methods and 3% to find a suicide partner. Among respondents who had visited the forum more than once ( n = 49), 53% reported no changes in feelings directly after forum use, 35% felt better and 12% felt worse. Peer support and anonymity were the most mentioned benefits, whereas no personal contacts and few reactions to postings were perceived as limitations. Suicide threats and the search for methods were the main reasons for moderating posts. Limitations: Usage habits and user experiences were available from a relatively small group that visited the forum more than once. Conclusion: In its current form, the forum has a low reach with few benefits and a potential for harm for its users. With a questionable benefit-to-risk ratio, the added value of the online forum appears to be small.

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).

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.

Objective: The majority of individuals with suicidal ideation do not receive help, and every year close to 800,000 people die by suicide. This study aimed to investigate the effectiveness of a guided internet-based self-help program compared to a waiting list control group in reducing suicidal ideation. Methods: In a randomized controlled trial, 402 individuals with suicidal ideation were assigned to a guided internet-based self-help program or a waiting list control group from September 13, 2016, to September 2, 2018. The primary outcome was suicidal ideation measured with the Beck Scale for Suicide Ideation at postintervention (6 weeks after baseline). Results: Participants assigned to the internet-based self-help program experienced at postintervention a significant reduction on the primary outcome of suicidal ideation (mean difference: 2.91; 95% CI, 1.28 to 4.54; P = .0005, Cohen's d = 0.25) compared to the waiting list control group and on the secondary outcomes of hopelessness (mean difference: 1.98; 95% CI, 0.97 to 3.99) and worrying (mean difference: 5.19; 95% CI, 2.36 to 8.10). Six months later (follow-up), the difference between the groups remained significant for suicidal ideation, hopelessness, and worrying. A total of 28 (16.8%) of the participants in the intervention group reported negative effects from the internet-based self-help program. Conclusions: Internet-based self-help therapy was associated with a reduction in suicidal ideation at postintervention and 6-month follow-up. Some participants found it challenging to work with the therapeutic exercises, and we recommend that internet-based self-help therapy be implemented in mental health clinics or crisis lines, where support or online counseling is available. Trial Registration: ClinicalTrials.gov identifier: NCT02872610.

Suicide is a major public health issue, and treatment of suicidal thoughts may contribute to its prevention. Provision of online treatment of suicidal ideation may reduce barriers that suicidal individuals experience in face-to-face treatment. We therefore aimed at evaluating the effectiveness of a web-based intervention targeting a reduction of suicidal ideation. We carried out a two-arm, parallel-design, randomised controlled trial in the general population in Flanders (Belgium) (registered as NCT03209544). Participants who were 18 years or older and experienced suicidal ideation were included. The intervention group (n = 365) received access to the unguided web-based intervention, and the control group (n = 359) was placed on a waitlist. Assessments were carried out at baseline and at 6 and 12 weeks. Participants reported high levels of suicidal ideation, depression, hopelessness, worrying, and anxiety at baseline. Compared to the control group, participants in the intervention group experienced a significant decline in suicidal ideation, depression, hopelessness, worrying, and anxiety both at post-test and at follow-up. An important limitation of the study was a high dropout rate, in particular in the intervention group. Our findings suggest that the online self-help intervention was more effective in reducing suicidal ideation and suicide-related symptoms than a waitlist control in a severely affected population. It can help in filling the gap between crisis help and face-to-face treatment.

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.