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    The Mental Health Quality of Life Questionnaire (MHQoL)

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    Purpose: The purpose of this study was to develop and psychometrically evaluate a new quality of life measure for use in people with mental health problems—the Mental Health Quality of Life questionnaire (MHQoL). Methods: The MHQoL dimensions were based on prior research by Connell and colleagues, highlighting the seven most important quality of life dimensions in the context of mental health. Items were generated following a systematic review we performed and through inviting expert opinion. A focus group and an online qualitative study (N = 120) were carried out to assess the face and content validity of the MHQoL. The MHQoL was further tested for its internal consistency, convergent validity, known-group validity and test–retest reliability among mental healthcare service users (N = 479) and members of the general population (N = 110). Results: The MHQoL consists of a descriptive system (MHQoL-7D), including s items covering seven dimensions (self-image, independence, mood, relationships, daily activities, physical health, future) and a visual analogue scale of general psychological well-being (MHQoL-VAS). Internal consistency was high (Cronbach's ∝ = 0.85) and correlations between MHQoL-7D scores and related measures (EQ-5D-5L, MANSA, ICECAP-A, and BSI) supported convergent validity. The intraclass correlation coefficient of the MHQoL-7D sum score for test–retest reliability was 0.85. Known-group validity was supported by the ability to detect significant differences in MHQoL-7D levels between service users and the general population, and between groups with different levels of psychological distress. Conclusion: The MHQoL demonstrated favourable psychometric properties and showed promise as a simple and effective measure to assess quality of life in people with mental health problems.</p

    Effects of raising the bar on medical student study progress

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    Context: Medical schools seek for measures to improve their students’ study progress and are responsible for a diverse student population. Objectives: The effect of a stricter academic dismissal (AD) policy in medical school on short-term and long-term study progress was investigated in a longitudinal cohort study. In addition, differential effects for subgroups were assessed by intersecting gender, ethnicity and prior education (intersectional framework). Methods: Participants were first-year Bachelor students enrolled in 2011 to 2016 in a Dutch medical school. For cohorts 2011-2013, the AD policy consisted of a minimum of 67% of Year-1 credits required to remain enrolled (67%-policy, n = 1189), and for cohorts 2014-2016, this bar was raised to 100% of Year-1 credits (100%-policy, n = 1233). Outcome measures on study progress were Year-1 completion and dropout (short term) and Bachelor completion in three and four years (long term). Results: Overall, Year-1 completion rates increased under the 100%-policy compared to the 67%-policy (OR = 2.50, 95%-CI:2.06-3.03, P &lt;.001). Yet, this increase was not present for students with non-standard prior education – except for males with a migration background (OR = 7.19, 95%-CI:2.33-25.73, P &lt;.01). The dropout rate doubled under the 100%-policy (OR = 2.41, 95%-CI:1.68-3.53, P &lt;.001). Mainly students with standard prior education dropped out more often (OR = 3.68, 95%-CI:2.37-5.89, P &lt;.001), except for males with a migration background. Bachelor completion rates after three and four years were not positively affected by the 100%-policy. Notably, females without a migration background and with non-standard prior education suffered from the 100%-policy regarding Bachelor completion after three years (OR = 0.29, 95%-CI:0.11-0.76, P &lt;.05). Conclusions: Despite increased dropout rates, the stricter AD policy improved Year-1 completion rates – especially for under-represented subgroups, thereby improving study progress without harming student diversity on the short term. However, these positive effects did not hold regarding Bachelor completion rates indicating that long-term effects require higher performance standards throughout the Bachelor, which in turn may harm other subgroups and thereby student diversity.</p

    Do perceived social neighborhood factors explain the association between neighborhood age composition and mental health among Dutch older adults?

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    Background: In the light of urbanization and aging, a crucially relevant policy question is how to shape neighborhoods to foster healthy aging. An important debate is whether older adults should group in neighborhoods, or whether a more mixed neighborhood age composition is more beneficial to health and well-being. We therefore assessed the association between neighborhood age structure and mental health and the mediating role of individual perceptions of neighborhood social factors. Methods: We conducted multivariable linear regression models and causal mediation analyses in 1255 older adults of the Dutch Globe study. The neighborhood age structure was measured in 2011 as the homogeneity of the age composition (using the Herfindahl-Hirschman index, range from 0 to 100, a higher score indicating more homogeneity) and the percentage of specific age groups in a neighborhood. Mental health was measured in 2014 by the Mental Health Inventory-5 score (range 0 to 100, a higher score indicating better mental health). Potential mediators were assessed in 2011 and included perceptions of neighborhood social cohesion, feeling at home in a neighborhood, and social participation. Results: A more homogeneous age composition (not specified for age) and a higher percentage of children living in a neighborhood were associated with better mental health, the other age categories were not. Social cohesion, feeling at home and social participation did not mediate the associations. Conclusions: The neighborhood age composition may be an interesting but currently insufficiently understood entry point for policies to improve older adult’s mental health status.</p

    Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring

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    There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case–control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89–0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85–1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85–0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69–0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.</p

    Marker placement sensitivity of the Oxford and Rizzoli foot models in adults and children

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    Understanding the effect of individual marker misplacements is important to improve the repeatability and aid to the interpretation of multi-segment foot models like the Oxford and Rizzoli Foot Models (OFM, RFM). Therefore, this study aimed to quantify the effect of controlled anatomical marker misplacement on multi-segment foot kinematics (i.e. marker placement sensitivity) as calculated by OFM and RFM in a range of foot sizes. Ten healthy adults and nine children were included. A combined OFM and RFM marker set was placed on their right foot and a static standing trial was collected. Each marker was replaced ± 10 mm in steps of 1 mm over the three axes of a foot coordinate system. For each replacement the change in segment orientation (tibia, hindfoot, midfoot, forefoot) was calculated with respect to the reference pose in which no markers were replaced. A linear fit was made to calculate the sensitivity of segment orientation to marker misplacement in °/mm. Additionally, the effect of foot size on the sensitivity was determined using linear regressions. For every foot segment of both models, at least one marker had a sensitivity ≥ 1.0°/mm. Highest values were found for the markers at the posterior aspect of the calcaneus in OFM (1.5°/mm) and the basis of the second metatarsal in RFM (1.4°/mm). Foot size had a small effect on 40% of the sensitivity values. This study identified markers of which consistent placement is critical to prevent clinically relevant errors (&gt;5°). For more repeatable multi-segment models, the role of these markers within the models’ definitions needs to be reconsidered.</p

    Contemporary issues with stuttering

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    Purpose: During the 2019 Fourth Croatia Clinical Symposium, speech-language pathologists (SLPs), scholars, and researchers from 29 countries discussed speech-language pathology and psychological practices for the management of early and persistent stuttering. This paper documents what those at the Symposium considered to be the key contemporary clinical issues for early and persistent stuttering. Methods: The authors prepared a written record of the discussion of Symposium topics, taking care to ensure that the content of the Symposium was faithfully reproduced in written form. Results: Seven contemporary issues for our field emerged from the Symposium. Conclusion: Effective early intervention is fundamental to proper health care for the disorder. However, as yet, there is no consensus about the timing of early intervention and how it should be managed. Currently, clinical translation is a barrier to evidence-based practice with early stuttering, and proactive strategies were suggested for junior SLPs. Apprehension emerged among some discussants that treatment of early stuttering may cause anxiety. For persistent stuttering, assessment procedures were recommended, as were strategies for dealing with childhood bullying. There was agreement that SLPs are the ideal professionals to provide basic cognitive-behavior therapy for clients with persistent stuttering. Questions were raised about our discipline standards for basic professional preparation programs for stuttering management.</p

    Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA)

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    Background: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. Methods: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. Discussion: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. Trial registration: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL</p

    Validity of the Rotterdam Elderly Pain Observation Scale for institutionalised cognitively impaired Dutch adults

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    Background: The Rotterdam Elderly Pain Observation Scale (REPOS) has not yet been validated for institutionalised cognitively impaired adults. To fill this gap of knowledge, we tested psychometric properties of the REPOS when used for pain assessment in this population. Methods: In this multicentre observational study, residents were filmed during a possibly painful moment and at rest. Healthcare professionals were asked to rate residents' pain by means of a Numeric Rating Scale (NRS)-proxy. Two researchers assessed pain with the REPOS and the Chronic Pain Scale for Non Verbal Adults with Intellectual Disabilities (CPS-NAID) from video-recordings. Results: In total, 168 observations from 84 residents were assessed. Inter-observer reliability between the two researchers was good, with Cohen's kappa 0.72 [95% confidence interval (CI) 0.64 to 0.79]. Correlation between the REPOS and CPS-NAID for a possibly painful moment was 0.73 (95% CI 0.65 to 0.79). Sensitivity (85%) and specificity (61%) for the detection of pain were calculated with REPOS ≥ 3 and NRS ≥ 4 as a reference value. Item response theory analysis shows that the item grimace displayed perfect discrimination between residents with and without pain. Conclusion: The REPOS is a reliable and valid instrument to assess pain in cognitively impaired individuals.</p

    Dolichoarteriopathies of the extracranial internal carotid artery

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    Background and purpose: Dolichoarteriopathies of the extracranial part of the internal carotid artery (ICA) are associated with cerebrovascular events, yet information on their prevalence and risk factors remains limited. The aim of the present study therefore was to study the prevalence and risk factors of dolichoarteriopathies in a sample of patients with cerebrovascular symptoms from the Plaque At RISK (PARISK) study. Methods: In a random sample of 100 patients from the PARISK study, multidetector computed tomography angiography (MDCTA) was performed as part of clinical workup. On MDCTA, we evaluated the extracranial trajectory of the ICA by measuring the length (in millimeters), the tortuosity index (TI; defined as the ICA length divided by the shortest possible distance from bifurcation to skull base), and dolichoarteriopathy type (tortuosity, coiling or kinking). Next, we investigated the association between cardiovascular risk factors and these measurements using linear and logistic regression analyses. Results: The mean (standard deviation) length of the ICA was 93 (± 14) mm, with a median (interquartile range) TI of 1.2 (1.1–1.3). The overall prevalence of dolichoarteriopathies was 69%, with tortuosity being the most common (72%), followed by coiling (20%), and kinking (8%). We found that age and obesity were associated with a higher TI: difference per 10-year increase in age: 0.05 (95% confidence interval [CI] 0.02–0.08) and 0.16 (95% CI 0.07–0.25) for obesity. Obesity and hypercholesterolemia were associated with a more severe type of dolichoarteriopathy (odds ratio [OR] 2.07 [95% CI 1.04–4.12] and OR 2.17 [95% CI 1.02–4.63], respectively). Conclusion: Dolichoarteriopathies in the extracranial ICA are common in patients with cerebrovascular symptoms, and age, obesity and hypercholesterolemia may play an important role in the pathophysiology of these abnormalities.</p

    Neutralization of MERS coronavirus through a scalable nanoparticle vaccine

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    MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans.</p

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