End-ot-lite decisions in Dutch medical practice

In the end, death comes to us all. This reality has not changed during centuries of attempting to unravel the mysteries of life and death. Even today, death is the most unescapable event in each human life. Life and time before death, however, have altered considerably. At least two changes are responsible for this. The first is that, over the past hundred and fifty years, man has succeeded in changing his condition in such a way that, in the well developed countries, average life expectancy has doubled. The strongly reduced perinatal and infant mortality have caused death to disappear almost completely from daily life in the Netherlands. A second Important development is of much more recent date, basically dating only from after World War Ii: the development of modern medicine. Medical practice today is increasingly able to assist in curing the sick, in making life bearable for the sick and extending life for a shorter or longer period of time. In other words: death still comes to everyone, but the time at which this happens isoften partly determined by decisions whether to stop or to continue treatment. Obviously, this does not hold for all deaths. People still die from accidents or from acute fatal diseases such as acute myocardial infarction. In all non-sudden deaths, however, patient and physician are involved in a shorter or longer disease process. A considerable difference compared with the situation existing over one hundred years ago, when In some municipalities more than half of all deceased had no physician's assistance during their preceding disease. Now that medicine can offer so much in terms of prolonging life and relieving suffering, the physician's task at the end of life is expanding. In the past, this task primarily Involved the provision of terminal care. Increasingly, decision-making by the physician is among the medical responsibilities at the end of life

Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration

Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms

Evaluation of an adaptive implementation program for cognitive adaptation training for people with severe mental ilness:A cluster-randomized controlled trial

Introduction Cognitive Adaptation Training (CAT) is a psychosocial intervention focusing on reducing the impact of cognitive disorders on daily functioning in people with severe mental illness (SMI). Similar to many evidence based practices (EBP), implementation of CAT in routine care lags behind, despite the established effectiveness of the intervention. This so called ‘science-to-service gap’ is a widespread problem in mental health care. We developed an innovative implementation program to facilitate implementation of CAT and similar interventions in routine care. Objectives The aim of this study is to evaluate the effectiveness of the implementation program and to determine factors that impede or facilitate the implementation process. Methods We conducted a multicenter cluster randomized controlled trial comparing the implementation program to a single training program in four mental health institutions (a total of 21 rehabilitation teams) in The Netherlands. Focus groups, semistructured interviews and questionnaires were used at multiple levels of service delivery (service user, professional, team, organization). Assessments took place before, during and after implementation and at follow-up, adding up to a total duration of 14 months. Data were analyzed using multilevel modeling. Results Data collection is complete and analyses on the effectiveness of the implementation program are ongoing. Preliminary analyses show that team climate (p<.008) and organizational climate (p<.043) significantly predict the attitudes of mental health providers toward EBP. Conclusions This implementation research may provide important information about the implementation of psychosocial interventions in practice and may result in a program that is useful for Cognitive Adaptation Training, and possibly for psychosocial interventions in general

Cognitive-behavior therapy for children and adolescents with anxiety disorders:A meta-analysis of secondary outcomes

Anxiety-focused cognitive-behavioral therapy (CBT) effectively reduces anxiety in children and adolescents. An important remaining question is to what extent anxiety-focused CBT also affects broader outcome domains. Additionally, it remains unclear whether parental involvement in treatment may have impact on domains other than anxiety. A meta-analysis (nstudies = 42, nparticipants = 3239) of the effects of CBT and the moderating role of parental involvement was conducted on the following major secondary outcomes: depressive symptoms, externalizing behaviors, general functioning, and social competence. Randomized controlled trials were included when having a waitlist or active control condition, a youth sample (aged<19) with a primary anxiety disorder diagnosis receiving anxiety-focused CBT and reported secondary outcomes. Controlled effect sizes (Cohen's d) were calculated employing random effect models. CBT had a large effect on general functioning (-1.25[-1.59;0.90], nstudies = 17), a small to moderate effect on depressive symptoms (-0.31[-0.41;-0.22], nstudies = 31) and a small effect on externalizing behaviors (-0.23[-0.38;-0.09], nstudies = 12) from pre-to post-treatment. Effects remained or even further improved at follow-up. Social competence only improved at follow-up (nstudies = 6). Concluding, anxiety-focused CBT has a positive effect on broader outcome domains than just anxiety. Higher parental involvement seemed to have beneficial effects at follow-up, with improvements in general functioning and comorbid symptoms

Evaluation of an adaptive implementation program for Cognitive Adaptation Training for people with severe mental illness:Protocol for a randomized controlled trial

Background: Cognitive Adaptation Training is a psychosocial intervention that focuses on reducing the negative effects of cognitive disorders, especially executive functions such as planning and targeted action. International research has shown that Cognitive Adaptation Training enhances multiple aspects of daily functioning in people with severe mental illnesses. Despite this evidence, implementation of the intervention into routine care remains a challenge. Objective: In this implementation research, a newly developed implementation program based on previous experience and scientific literature, is tested. The primary aim of this research is to assess the effectiveness of the implementation program. The secondary aim of this study is to evaluate the factors that impede or facilitate the implementation of Cognitive Adaptation Training. Methods: To test the effectiveness of the implementation program, a multicenter cluster randomized controlled trial was conducted comparing the implementation program to a single training program in four mental health institutions in The Netherlands. Focus groups, semistructured interviews, and questionnaires were used at multiple levels of service delivery (service user, professional, team, organization) to identify factors that may hamper or facilitate implementation. The RE-AIM framework was applied to measure the implementation effectiveness. Following this framework, the primary outcomes were Reach, Intervention Effectiveness, Adoption, Implementation, and Maintenance. These are assessed before, during, and after implementation. The research had a total duration of 14 months, with a follow-up measurement at 14 months. Data will be analyzed using multilevel modeling. Results: The study was funded in April 2018. Data collection occurred between November 2018 and January 2020. In total, 21 teams of 4 mental health institutions agreed to participate. Data analysis is ongoing and results are expected to be published in December 2020. Conclusions: This implementation research may provide important information about the implementation of psychosocial interventions in practice and may result in a program that is useful for Cognitive Adaptation Training, and possibly for psychosocial interventions in general. Trial registration: The Netherlands Trial Register (NL7989); https://www.trialregister.nl/trial/7989. International Registered Report Identifier (IRRID): DERR1-10.2196/17412

Histories of Social Functioning and Mental Healthcare in Severely Dysfunctional Dual-Diagnosis Psychiatric Patients

Abstract Disengagement from mental health services is a major obstacle to the treatment of homeless dual-diagnosis patients (i.e., those with severe mental illness and substance-use disorder). A subgroup of these patients is considered to be treatment resistant and we aim to explore whether patients’ reasons for disengagement may stem from negative experiences in their lives and treatment histories. This retrospective, explorative study examined the medical files of 183 severely dysfunctional dual-diagnosis patients who had been admitted involuntarily to a new specialized clinic for long-term treatment. Most patients shared common negative experiences with respect to childhood adversities, low school achievement, high levels of unemployment, discontinuity of care, and problems with the judicial system. The lifetime histories of treatment-resistant, severely dysfunctional dual-diagnosis patients showed a common pattern of difficulties that may have contributed to treatment resistance and disengagement from services. If these adversities are targeted, disengagement may be prevented and outcome improved

REFLEX, a social-cognitive group treatment to improve insight in schizophrenia:Study protocol of a multi-center RCT

BACKGROUND: Insight is impaired in a majority of people with schizophrenia. Impaired insight is associated with poorer outcomes of the disorder. Based on existing literature, we developed a model that explains which processes may possibly play a role in impaired insight. This model was the starting point of the development of REFLEX: a brief psychosocial intervention to improve insight in schizophrenia. REFLEX is a 12-sessions group training, consisting of three modules of four sessions each. Modules in this intervention are: "coping with stigma", "you and your personal narrative", and "you in the present". METHODS/DESIGN: REFLEX is currently evaluated in a multicenter randomized controlled trial. Eight mental health institutions in the Netherlands participate in this evaluation. Patients are randomly assigned to either REFLEX or an active control condition, existing of cognitive remediation exercises in a group. In a subgroup of patients, fMRI scans are made before and after training in order to assess potential haemodynamic changes associated with the effects of the training. DISCUSSION: REFLEX is one of the few interventions aiming specifically to improving insight in schizophrenia and has potential value for improving insight. Targeting insight in schizophrenia is a complex task, that comes with several methodological issues. These issues are addressed in the discussion of this paper. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN5024753

Determinants of Quality of Life and Treatment Satisfaction During Long-Term Involuntary In-patient Treatment of Dual-Diagnosis Patients

INTRODUCTION: Treatment resistance and disengagement from mental health services are major obstacles in the treatment of dual diagnosis patients with Severe Mental Illness. The patients in this study were admitted to a long-term involuntary treatment facility. AIM OF THE STUDY: To study which patient experiences and perceptions are related to the outcome measures Subjective Quality of Life (SQOL) and Treatment Satisfaction (TS) during the long-term involuntary treatment. METHODS: Patients were invited for an interview by an independent researcher, which included self-report questionnaires. The structured interviews included self-assessing Helping Alliance, Insight, Attitude toward involuntary admission, Perceived coercion and Perceived benefit were studied as determinants of SQOL and TS. The relationship between the determinants and the outcomes were analyzed by linear regression analysis. RESULTS: Patient reported outcomes from dual diagnosis patients in a long-term treatment facility, showed that most of the patients, in spite of the involuntary character of the treatment, were satisfied with the treatment. With respect to the determinants of SQOL and TS the perceptions that “My opinion is taken into account” and “Perceived benefits of the treatment” are strong predictors of both the outcomes. CONCLUSIONS: The current study shows that the most important aspects for treatment satisfaction and quality of life of dual-diagnosis patients admitted involuntary to long-term treatment, are being listened to (being taken seriously) and experiencing improvements during treatment. These qualities reflect the goals of Shared Decision Making and Perceived Procedural Justice in treatment. The study also corroborates earlier findings that even when treated involuntarily, patients might not hold particular negative views regarding their treatment

Measuring empathy in schizophrenia:The Empathic Accuracy Task and its correlation with other empathy measures

Introduction: Empathy is an interpersonal process impaired in schizophrenia. Past studies have mainly used questionnaires or performance-based tasks with static cues to measure cognitive and affective empathy. We used the Empathic Accuracy Task (EAT) designed to capture dynamic aspects of empathy by using videoclips in which perceivers continuously judge emotionally charged stories. We compared individuals with schizophrenia with a healthy comparison group and assessed correlations among EAT and three other commonly used empathy measures. Method: Patients (n = 92) and a healthy comparison group (n = 42) matched for age, gender and education completed the EAT, the Interpersonal Reactivity Index, Questionnaire of Cognitive and Affective Empathy and Faux Pas. Differences between groups were analyzed and correlations were calculated between empathy measurement instruments. Results: The groups differed in EAT performance, with the comparison group outperforming patients. A moderating effect was found for emotional expressivity of the target: while both patients and the comparison group scored low when judging targets with low expressivity, the comparison group performed better than patients with more expressive targets. Though there were also group differences on the empathy questionnaires, EAT performance did not correlate with questionnaire scores. Conclusions: Individuals with schizophrenia benefit less from the emotional expressivity of other people than the comparison group, which contributes to their impaired empathic accuracy. The lack of correlation between the EAT and the questionnaires suggests a distinction between self-report empathy and actual empathy performance. To explore empathic difficulties in real life, it is important to use instruments that take the interpersonal perspective into account. (C) 2019 Published by Elsevier B.V