People Diagnosed with Myasthenia Gravis have Lower health-related quality of life and Need More Medical and Caregiver Help in Comparison to the General Population:Analysis of Two Observational Studies

Introduction: Myasthenia gravis (MG) is a neuromuscular disease causing extreme muscular fatigue, triggering problems with vision, swallowing, speech, mobility, dexterity, and breathing. This analysis intended to estimate the health-related quality-of-life impact, the medical burden, and the need for caregiver help of people diagnosed with MG. Methods: MyRealWorld-MG (MRW) is an observational study among adults diagnosed with MG in 9 countries. The General Population Norms (POPUP) observational study enrolled representative members of the general population in 8 countries. In both digital studies, respondents entered personal characteristics and provided data on medical conditions, EQ-5D-5L, HUI3, MG-Activities of Daily Living (MG-ADL), sick leave, caregiver help, and medical care utilization. Results: In MRW (n = 1859), 58.4% of respondents had moderate-to-severe MG. Average utility values were lower in MRW versus POPUP (0.739 vs. 0.843 for EQ-5D-5L; 0.493 vs. 0.746 for HUI3), and declined with more severe disease (0.872, 0.707, 0.511 EQ-5D-5L utilities and 0.695, 0.443, 0.168 HUI3 utilities for mild, moderate, and severe MG, respectively). Taking sick leave in the past month was 2.6 times more frequent among people diagnosed with MG compared to the general population (34.4% vs. 13.2%) and four times more people diagnosed with MG reported needing help from a caregiver (34.8% vs. 8.3%). Use of medical care was twice as likely in MRW in comparison with POPUP (51.9% vs. 24.6%). Conclusion: This direct comparison of people diagnosed with MG and the general population using two large international studies revealed significant negative impact of MG. Results were consistent across all outcomes, in all countries.</p

The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population

Introduction: Myasthenia gravis (MG) is a rare neuromuscular disorder marked by a variable combination of weakness of eye, bulbar, respiratory, axial, and limb muscles. This study compared the experience of people with MG regarding breathing, fatigue, sleep, pain/discomfort, mental health, and usual activities with the general population. Methods: The MyRealWorld-MG digital, multinational study enrolled patients with MG and collected demographics, PROMIS-Dyspnea, PROMIS-Sleep Disturbance, FACIT-Fatigue, EQ-5D-5L, Health Utilities Index (HUI-3), Hospital Anxiety and Depression Scale (HADS), MG-Activities of Daily Living (MG-ADL), and MG-Quality-of-Life (MG-QoL-15r). Comparisons with the general population were based on PROMIS population norms, published literature, or on data from a digital, multinational, observational study which enrolled a representative sample of the general population (POPUP). Results: In MyRealWorld-MG (N = 2074), patients experienced higher intensity, frequency, and duration of PROMIS shortness of breath than a US population (p &lt; 0.0001). Patients with MG had higher PROMIS-Sleep Disturbance scores than POPUP (53.7 vs 50.0, p &lt; 0.0001), and 54.9% of patients had clinically severe FACIT-Fatigue scores vs 6.8% in POPUP (p &lt; 0.0001). Among patients with MG, 69.6% and 18.5% had moderate-to-severe HADS-Anxiety and HADS-Depression compared to 20.3% and 6.9% in POPUP (p &lt; 0.001). Statistically significant and strong associations were found between fatigue, sleep, dyspnea, usual activities, and emotions. All outcomes worsened with more severe disease. Conclusion: A considerable burden was observed in this comparison of breathing, sleep, fatigue, mental health, and usual activities between patients with MG and the general population, using data from two international studies and published population norms. Even mildly affected patients had significantly worse outcomes than the general population.</p

The Dutch Recidivism Monitor

The Dutch Recidivism Monitor is a long-term research project that conducts standardised measurements of recidivism amongst diverse groups of offenders. This project will enable the Ministry of Security and Justice to obtain a clearer overview as to the disposals of penal interventions and the course of criminal careers amongst both juvenile and adult offenders. Measurements as part of the Recidivism Monitor are carried out using the same fixed method. Consequently, the results of the research are mutually comparable. In the case of important groups of offenders, measurements are repeated at specific intervals, so that it is possible to depict the development of recidivism and to examine the subsequent criminal career courses of offenders in these groups

Augmenting PTSD treatment with physical activity: study protocol of the APPART study (Augmentation for PTSD with Physical Activity in a Randomized Trial)

Background New intensive trauma-focused treatment (TFT) programmes that incorporate physical activity have been developed for people with post-traumatic stress disorder (PTSD). However, the unique contribution of physical activity within these intensive TFT programmes has never been investigated in a controlled manner. Objectives This randomized controlled trial will investigate the effectiveness of physical activity added to an intensive TFT programme. In addition, the study aims to investigate the underlying mechanisms of the effects of physical activity on the change in PTSD symptoms. Methods Individuals with PTSD (N = 120) will be randomly allocated to two conditions: a physical activity or a non-physical active control condition. All participants will receive the same intensive TFT lasting eight days within two consecutive weeks, in which daily prolonged exposure and EMDR therapy sessions, and psycho-education are combined. The amount of physical activity will differ per condition. While the physical activity condition induces daily physical activities with moderate intensity, in the non-physical active control condition no physical activity is prescribed; but instead, a controlled mixture of guided (creative) tasks is performed. The two primary outcome measures are change in PTSD symptoms from pre- to post-treatment and at six months follow-up, measured with the Clinician-Administered PTSD Scale (CAPS-5), and the PTSD Checklist for DSM-5 (PCL-5). Additionally, self-reported sleep problems, depressive symptoms, emotion regulation, dissociation symptoms and anxiety sensitivity will be measured as potential underlying mechanisms. Conclusions This study will contribute to the research field of augmentation strategies for PTSD treatment by investigating the effectiveness of physical activity added to intensive TFT. Trial registration This trial is registered in the Netherlands Trial Register (Trial NL9120)

Recidivism report 1997-2007. Trends in the reconviction rate of Dutch offenders

In the field of Dutch criminal law there is a comprehensive policy programme called ‘Working on Reduction of Recidivism’. Various measures are being implemented to help reduce the risk of prosecuted offenders relapsing into criminal behaviour. Some years ago, definite targets were formulated with respect to two offender groups. Between 2002 and 2010, the medium-term recidivism for both juvenile offenders sanctioned by court or PPS, and adult exprisoners will have to be reduced by 10 percentage points (VbbV, 2007). With regard to the latter group, the target was recently enhanced: by 2020, the reconviction rate of ex-prisoners must be reduced by 25 percent (MvJ, 2009). The Recidivism Monitor study constitutes a means of checking whether the realisation of the target figures holds a steady course. Each year, the WODC calculates the reconviction rate of Dutch offenders. Nearly all persons in the Netherlands who came into contact with the Dutch judicial system as a suspect are included in the study. The measurements relate to five populations: adult offenders sanctioned by court or Public Prosecutor’s Service (PPS), juvenile offenders sanctioned by court or PPS, ex-prisoners, former inmates of juvenile detention centres and former offenders placed under an entrustment order. Recently, the relapse among former offenders placed under an entrustment order was reported separately (Bregman & Wartna, 2010). This fact sheet outlines recidivism in the other four offender populations. Specifically, the study relates to juveniles and adults who were sanctioned by court or PPS or released from a penitentiary institution in the 1997-2007 period

Antibodies against p53 are associated with poor prognosis of colorectal cancer.

Mutation of the p53 gene is a common event in colorectal cancer. This alteration can result in cellular accumulation of p53 and may also induce p53 antibodies. Accumulation of p53 in tumour cells has been associated with poor prognosis of colorectal cancer. We tested preoperative sera from 255 patients with colorectal cancer by enzyme-linked immunosorbent assay (ELISA). A total of 70.2% had reactivity that was higher than the 'low' control serum. Employing a cut-off level of 10% of the 'high' control sample, 25.5% of the patients were positive for p53 antibodies. The presence of p53 antibodies correlated with the following prognostic factors: histological differentiation grade, shape of the tumour, and tumour invasion into blood vessels. Patients with p53 antibodies were shown to have decreased survival and decreased disease-free survival. Specifically for patients with cancer stage A and B1 the presence of p53 antibodies selected a subgroup with poor prognosis

Sticky criticism? Affective and neural responses to parental criticism and praise in adolescents with depression

Background Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied. Methods Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views. Results In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more. Conclusions Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.</p

Sticky criticism? Affective and neural responses to parental criticism and praise in adolescents with depression

Background Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied. Methods Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views. Results In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more. Conclusions Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.</p

Recidivism report 2002-2008. Trends in the reconviction rate of Dutch offenders

Policy programmes in the field of Dutch criminal law often aim at the reduction of recidivism; measures are taken to lower the risk of prosecuted offenders relapsing into criminal behaviour. Some years ago, specific targets were formulated with respect to two major offender groups. For convicted juvenile offenders, and for adult ex-prisoners, the medium-term recidivism will have to be reduced by 10 percentage points between 2002 and 2010 (VbbV, 2007). The current government also endorses the need to suppress recidivism (DSP, 2011). A substantial part of crime in the Netherlands is committed by persons who have been prosecuted before. Therefore, crime prevention is also the prevention of recidivism. The Recidivism Monitor is an ongoing research project carried out by the WODC. With this instrument the realisation of the recidivism targets can be monitored. Each year, the WODC reports on the reconviction rate of Dutch offenders. Nearly all persons who were suspect in a penal case are included in the study. The standard measurements of the Recidivism Monitor relate to five offender populations: adult offenders sanctioned by court or Public Prosecutor’s Service (PPS), juvenile offenders sanctioned by court or PPS, ex-prisoners, former inmates of juvenile detention centres and former offenders placed under an entrustment order (tbs).1 The reconviction rates in the tbs-sector are reported on separately (see int. al. Bregman & Wartna, 2011). This fact sheet outlines known recidivism in the other four offender populations. Specifically, the study relates to juveniles and adults who were sanctioned by court or PPS or released from a penitentiary institution in the years between 2002, the first year of the target period, and 2008, the latest year for which statistics are currently available

Combined assessment of the tumor-stroma ratio and tumor immune cell infiltrate for immune checkpoint inhibitor therapy response prediction in colon cancer

The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor-stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of response to neoadjuvant therapy in multiple cancer types. In the current work, we predicted the likelihood of ICI therapy responsivity of 335 therapy-naive colon adenocarcinoma tumors from The Cancer Genome Atlas, using bioinformatics approaches. The TSR was scored on diagnostic tissue slides, and tumor-infiltrating immune cells (TIICs) were inferred from transcriptomic data. Tumors with high stromal content demonstrated increased T regulatory cell infiltration (p = 0.014) but failed to predict ICI therapy response. Consequently, we devised a hybrid tumor microenvironment classification of four stromal categories, based on histological stromal content and transcriptomic-deconvoluted immune cell infiltration, which was associated with previously established transcriptomic and genomic biomarkers for ICI therapy response. By integrating these biomarkers, stroma-low/immune-high tumors were predicted to be most responsive to ICI therapy. The framework described here provides evidence for expansion of current histological TIIC quantification to include the TSR as a novel, easy-to-use biomarker for the prediction of ICI therapy response.Experimentele farmacotherapi