Objectives
Individuals with post‐traumatic stress disorder (PTSD) have neurocognitive deficits in verbal memory and executive functioning. In this study, we examined whether memory and executive ...functioning changed over the course of treatment and which clinical variables were associated with change.
Design
Neuropsychological assessments were administered at baseline and endpoint of a randomized controlled trial as secondary outcome.
Methods
Trauma survivors (n = 88) diagnosed with PTSD received trauma‐focused psychotherapy within a 17‐week randomized controlled trial. Neuropsychological tests were the California Verbal Learning Test, Rivermead Behavioural Memory Test, Stroop Color Word Test, and Trail Making Test.
Results
Significant, small‐ to medium‐sized improvements in verbal memory, information processing speed, and executive functioning were found after trauma‐focused psychotherapy (Cohen's d 0.16–0.68). Greater PTSD symptom decrease was significantly related to better post‐treatment neurocognitive performance (all p < .005). Patients with comorbid depression improved more than patients with PTSD alone on interference tasks (p < .01). No differences emerged between treatment conditions and between patients on serotonergic antidepressants and those who were not.
Conclusions
This study suggests that neurocognitive deficits in PTSD can improve over the course of trauma‐focused psychotherapy and are therefore at least partly reversible. Improvements over treatment are in line with previous neuropsychological and neuroimaging studies and effect sizes exceed those of practice effects. Future research should determine whether these changes translate into improved functioning in the daily lives of the patients.
Practitioner points
Patients with PTSD have difficulties performing verbal memory tasks (e.g., remembering a grocery list, recall of a story) and executive functioning tasks (e.g., shifting attention between two tasks, ignoring irrelevant information to complete a task).
Verbal memory, information processing speed, and executive functioning significantly improved in patients with post‐traumatic stress disorder over the course of trauma‐focused psychotherapy.
Improvements were equal in size for two different trauma‐focused psychotherapies (Eye movement desensitization and reprocessing therapy and brief eclectic psychotherapy for PTSD).
Medium‐sized effects were found for recall of a story, whereas effects in other aspects of verbal memory, information processing speed, and executive functioning were small‐sized.
No causal attributions can be made because we could not include a control group without treatment for ethical reasons.
Findings may be more reflective of patients who completed treatment than patients who prematurely dropped out as completers were overrepresented in our sample.
Prevalence of posttraumatic stress disorder (PTSD) in refugees is reportedly higher in comparison to the general population. Refugee children specifically are often coping with trauma and loss and ...are at risk for mental health difficulties. With staggering numbers of people seeking refuge around the world and 50% being 18 years or younger, research examining the effects of trauma-focused therapies for refugee children with PTSD is highly needed. Both Eye Movement Desensitization and Reprocessing (EMDR) therapy and the child version of Narrative Exposure Therapy (KIDNET) have been used for refugees, although these treatment methods have not been systematically compared. The aim of the current study is to investigate the effectiveness of EMDR and KIDNET, compared to a waitlist control group and with each other, offered to refugee children.
A randomized controlled three-arm trial has been designed. The primary outcome is PTSD diagnosis and symptom severity assessed with the Clinician-Administered PTSD Scale for Children DSM5 (CAPS-CA-5) at baseline (T1), 1 month post-treatment, or after 8 weeks of waiting (T2) and 3 months follow-up (T3). Additionally, instruments to assess posttraumatic stress symptoms, behavioral and emotional problems, and quality of life perception in children aged 8-18 are conducted at T1, T2, and T3.
This is the first RCT that examines the effectiveness of EMDR and KIDNET in refugee children aged 8-18 years specifically, compared to a waitlist control group intended to reduce PTSD diagnosis and severity of posttraumatic stress symptoms and comorbid complaints in a growing and challenging population.
Dutch Trial Register NL40769 . Retrospectively registered on June 16, 2021.
A bioanalytical assay for the new poly(ADP-ribose) polymerase-1 inhibitor olaparib in combination with melphalan was developed and validated. For the quantitative assay, human plasma samples were ...pre-treated on ice using protein precipitation with 2% (v/v) acetic acid in acetonitrile containing erlotinib and melphalan-d
8 as internal standards. The extract was diluted with water and injected into the chromatographic system. This system consisted of a sub-2
μm particle, trifunctional bonded octadecyl silica column with an isocratic elution using 0.01% (v/v) of formic acid in a mixture of water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10–5000
ng/ml calibration range for both drugs. The lowest level of this range corresponded to the lower limit of quantification. Within day precisions were 3.0–9.3%, between day precisions 6.0–9.8% and accuracies were between 101 and 110% for the whole calibration range. After validation the assay was used to assess the pharmacokinetics of olaparib in a patient with metastatic breast carcinoma. In addition, systemic exposure of melphalan was monitored in patients subjected to isolated hepatic perfusion with this drug. Both applications show that the new assay can be applied for human pharmacokinetic studies for both drugs.
Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, ...such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.
To improve the quality of care, guidance methodologies can be very helpful for supervisors, practitioners and other stakeholders. A counseling methodology provides an employee with a shared view and ...concrete tools to act more systematically. This enhances acting skills and helps to better respond to specific needs and wishes of clients. This makes working according to methods one of the ways for professionalization. But what exactly is a counseling methodology? Which ones exist in the Netherlands? And for which target groups have they been developed? On the basis of ten criteria, 28 counseling methods were found and summarized. De Grote Methodiekengids, the result of two years of research by Alliade's Department of Applied Scientific Research (PWO), helps to make a choice for each target group on the basis of practical applicability and scientific foundation, among other things. This independent guide is indispensable for supervisors, policy makers, administrators, managers, researchers, remedial educationalists and psychologists in intellectual disability care. De Grote Methodiekengids compiles the available information from public sources and prevents each care facility from having to do comparative methodology research all over again.
Transmission of SARS-CoV-2 is driven by contact, fomite, and airborne transmission. The relative contribution of different transmission routes remains subject to debate. Here, we show Syrian hamsters ...are susceptible to SARS-CoV-2 infection through intranasal, aerosol and fomite exposure. Different routes of exposure present with distinct disease manifestations. Intranasal and aerosol inoculation causes severe respiratory pathology, higher virus loads and increased weight loss. In contrast, fomite exposure leads to milder disease manifestation characterized by an anti-inflammatory immune state and delayed shedding pattern. Whereas the overall magnitude of respiratory virus shedding is not linked to disease severity, the onset of shedding is. Early shedding is linked to an increase in disease severity. Airborne transmission is more efficient than fomite transmission and dependent on the direction of the airflow. Carefully characterized SARS-CoV-2 transmission models will be crucial to assess potential changes in transmission and pathogenic potential in the light of the ongoing SARS-CoV-2 evolution.
Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast‐growing scientific field. In the last decade urinary ...extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV‐based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.
Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum (ER). Selective removal of certain ER domains via autophagy (termed as ER-phagy) has ...emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control in the ER.
Detection of leptomeningeal metastasis is hampered by limited sensitivities of currently used techniques: MRI and cytology of cerebrospinal fluid (CSF). Detection of cell-free tumor DNA in CSF has ...been proposed as a tumor-specific candidate to detect leptomeningeal metastasis at an earlier stage. The aim of this study was to investigate mutation and aneuploidy status in CSF-derived cell-free DNA (cfDNA) of patients with breast cancer with a clinical suspicion of leptomeningeal metastasis.
cfDNA was isolated from stored remnant CSF and analyzed by targeted next-generation sequencing (NGS;
= 30) and the modified fast aneuploidy screening test-sequencing system (mFAST-SeqS;
= 121). The latter method employs selective amplification of long interspaced nuclear elements sequences that are present throughout the genome and allow for fast and cheap detection of aneuploidy. We compared these results with the gold standard to diagnose leptomeningeal metastasis: cytology.
Leptomeningeal metastasis was cytology proven in 13 of 121 patients. Low DNA yields resulted in insufficient molecular coverage of NGS for the majority of samples (success rate, 8/30). The mFAST-SeqS method, successful in 112 of 121 (93%) samples, detected genome-wide aneuploidy in 24 patients. Ten of these patients had cytology-proven leptomeningeal metastasis; 8 additional patients were either concurrently diagnosed with central nervous system metastases by radiological means or developed these soon after the lumbar puncture. The remaining six cases were suspected of leptomeningeal metastasis, but could not be confirmed by cytology or imaging. Aneuploidy was associated with development of leptomeningeal metastasis and significantly worse overall survival.
Aneuploidy in CSF-derived cfDNA may provide a promising biomarker to improve timely detection of leptomeningeal metastasis.
Currently available injectable drugs that target proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce serum LDL cholesterol and improve cardiovascular outcomes. This phase 2 study assessed ...NNC0385-0434, an oral PCSK9 inhibitor, in individuals receiving oral lipid-lowering therapy.
In this randomised, double-blind, placebo-controlled and active-controlled trial, 42 research sites across seven countries (Belgium, Germany, Greece, Japan, the Netherlands, Poland, and the USA) recruited individuals with established atherosclerotic cardiovascular disease (aged ≥40 years) or at high risk of atherosclerotic cardiovascular disease (aged >50 years), who had LDL cholesterol concentration of at least 1·8 mmol/L and were receiving maximum tolerated statins and stable lipid-lowering therapy. The study randomly allocated participants (3:1) with an interactive web response system to receive either NNC0385-0434 (15 mg, 40 mg, or 100 mg) once a day co-formulated with the oral absorption enhancer sodium N-8-(2-hydroxybenzoyl)amino caprylate (500 mg); placebo; or open-label evolocumab (140 mg) every 2 weeks administered subcutaneously. Blinding was performed within each dose level. The primary endpoint was percentage change from baseline in LDL cholesterol measured by β quantification at week 12. All randomly assigned participants received at least one dose of treatment and were included in both safety and efficacy analyses. The trial was registered on ClinicalTrials.gov, NCT04992065, and is completed.
Between Aug 16, 2021, and Jan 28, 2022, we randomly assigned 267 patients to one of the three NNC0385-0434 dose cohorts (n=53 per cohort), matching placebo (n=54), or open-label evolocumab (n=54). The study population comprised 82 (31%) women and 185 (69%) men; mean age was 64·3 years (SD 9·0). Baseline mean LDL cholesterol concentration was 2·7 mmol/L (SD 0·8). Treatment with NNC0385-0434 resulted in reductions in LDL cholesterol from baseline to week 12, of 32·0 percentage points (95% CI 20·9 to 43·0) in the 15 mg cohort, 44·9 percentage points (33·8 to 56·0) in the 40 mg cohort, and 61·8 percentage points (50·7 to 72·9) in the 100 mg cohort, compared with the placebo group (p<0·0001 for each). Patients treated with evolocumab had similar LDL cholesterol reductions (59·6% SE 4·1 decrease from baseline) to patients receiving NNC0385-0434 100 mg (56·2% 4·0). The estimated treatment difference between NNC0385-0434 100 mg and evolocumab 140 mg was 3·4 percentage points 95% CI -7·8 to 14·7. The most frequently reported adverse event was COVID-19, which affected 31 (12%) of 267 patients, with similar numbers across treatment groups. Investigative sites reported gastrointestinal disorders as the most frequent treatment-related adverse event (26 patients and 35 events total in the three NNC0385 cohorts and one patient and one event each in the placebo and evolocumab cohorts). No deaths or treatment-related serious adverse events occurred.
This study showed excellent 12-week LDL cholesterol lowering efficacy and good patient tolerance of an oral PCSK9 inhibitor, NNC0835-0434, similar to an injectable drug. However, the sponsor chose to discontinue further development of NNC0835-0434 due to portfolio considerations.
Novo Nordisk.
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