E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.

Purpose: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism. Methods: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47. Results: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission. Conclusion: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia.

Pain monitoring app leads to less pain in children with cancer at home: Results of a randomized controlled trial.

BACKGROUND: The authors developed a pain monitoring app offering educational information, and real-time health care professional feedback on clinically significant pain (>4 numeric rating scale [NRS]-11) for children with cancer to reduce pain at home. METHODS: This monocenter, nonblinded randomized controlled trial enrolled Dutch children (0-18 years old) receiving cancer treatment (≥3 months after diagnosis, ≥2 months treatment remaining). Children were randomly assigned to use the app or receive usual care (two parallel groups). We assessed whether use of the app yielded less clinically significant pain (aim 1) and whether it affected pain severity, duration, interference, pain management strategies, and parental emotional well-being (aim 2). The app was also evaluated by families (aim 3). RESULTS: A total of 94 children were randomized to use the app (15 drop-outs), and 90 were to receive care as usual (11 drop-outs). The app group (n = 79, mean age: 7.5 [5.1] years, 48% girls, 63% hemato-oncology diagnosis) reported significantly less clinically significant pain compared to usual care (n = 79, mean age: 7.5 [5.4] years, 52% girls, 65% hemato-oncology diagnosis) (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.198-0.734]) (aim 1), as well as significantly lower pain severity (ß = -0.27; 95% CI, -0.407 to -0.142). No differences were found for duration, interference, or management strategies. Parents in the app group reported significantly less distress compared to usual care (ß = -0.84; 95% CI, -1.61 to -0.03]) (aim 2). Families generally evaluated the app positively (aim 3). CONCLUSIONS: Use of the app resulted in less clinically significant pain at home. The exact working mechanisms of the app should be further elucidated.

Prevalence and clinical correlations of SF3B1 variants in lactotroph tumours.

OBJECTIVE: A somatic mutational hotspot in the SF3B1 gene was reported in lactotroph tumours. The aim of our study was to examine the prevalence of driver SF3B1 variants in a multicentre independent cohort of patients with lactotroph tumours and correlate with clinical data. DESIGN AND METHODS: This was a retrospective, multicentre study involving 282 patients with lactotroph tumours (including 6 metastatic lactotroph tumours) from 8 European centres. We screened SF3B1 exon 14 hotspot for somatic variants using Sanger sequencing and correlated with clinicopathological data. RESULTS: We detected SF3B1 variants in seven patients with lactotroph tumours: c.1874G > A (p.Arg625His) (n = 4, 3 of which metastatic) and a previously undescribed in pituitary tumours variant c.1873C > T (p.Arg625Cys) (n = 3 aggressive pituitary tumours). In two metastatic lactotroph tumours with tissue available, the variant was detected in both primary tumour and metastasis. The overall prevalence of likely pathogenic SF3B1 variants in lactotroph tumours was 2.5%, but when we considered only metastatic cases, it reached the 50%. SF3B1 variants correlated with significantly larger tumour size; higher Ki67 proliferation index; multiple treatments, including radiotherapy and chemotherapy; increased disease-specific death; and shorter postoperative survival. CONCLUSIONS: SF3B1 variants are uncommon in lactotroph tumours but may be frequent in metastatic lactotroph tumours. When present, they associate with aggressive tumour behaviour and worse clinical outcome.

Development of a Duplex Serological Multiplex Assay for the Simultaneous Detection of Epstein-Barr Virus IgA and IgG Antibodies in Nasopharyngeal Carcinoma Patients.

Epstein-Barr virus (EBV) IgA and IgG antibodies in serum from nasopharyngeal carcinoma (NPC) patients are well-established markers for EBV-positive NPC. Luminex-based multiplex serology can analyze antibodies to multiple antigens simultaneously; however, the detection of both IgA and IgG antibodies requires separate measurements. Here we describe the development and validation of a novel duplex multiplex serology assay, which can analyze IgA and IgG antibodies against several antigens simultaneously. Secondary antibody/dye combinations, as well as serum dilution factors, were optimized, and 98 NPC cases matched to 142 controls from the Head and Neck 5000 study (HN5000) were assessed and compared to data previously generated in separate IgA and IgG multiplex assays. EBER in situ hybridization (EBER-ISH) data available for 41 tumors was used to calibrate antigen-specific cut-offs using receiver operating characteristic (ROC) analysis with a prespecified specificity of ≥90%. A directly R-Phycoerythrin-labeled IgG antibody in combination with a biotinylated IgA antibody and streptavidin-BV421 reporter conjugate was able to quantify both IgA and IgG antibodies in a duplex reaction in a 1:1000 serum dilution. The combined assessment of IgA and IgG antibodies in NPC cases and controls from the HN5000 study yielded similar sensitivities as the separate IgA and IgG multiplex assays (all > 90%), and the duplex serological multiplex assay was able to unequivocally define the EBV-positive NPC cases (AUC = 1). In conclusion, the simultaneous detection of IgA and IgG antibodies provides an alternative for the separate IgA/IgG antibody quantification and may present a promising approach for larger NPC screening studies in NPC endemic areas.

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome.

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing's disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

Behavioral Studies Using Large-Scale Brain Networks - Methods and Validations.

Mapping human behaviors to brain activity has become a key focus in modern cognitive neuroscience. As methods such as functional MRI (fMRI) advance cognitive scientists show an increasing interest in investigating neural activity in terms of functional connectivity and brain networks, rather than activation in a single brain region. Due to the noisy nature of neural activity, determining how behaviors are associated with specific neural signals is not well-established. Previous research has suggested graph theory techniques as a solution. Graph theory provides an opportunity to interpret human behaviors in terms of the topological organization of brain network architecture. Graph theory-based approaches, however, only scratch the surface of what neural connections relate to human behavior. Recently, the development of data-driven methods, e.g., machine learning and deep learning approaches, provide a new perspective to study the relationship between brain networks and human behaviors across the whole brain, expanding upon past literatures. In this review, we sought to revisit these data-driven approaches to facilitate our understanding of neural mechanisms and build models of human behaviors. We start with the popular graph theory approach and then discuss other data-driven approaches such as connectome-based predictive modeling, multivariate pattern analysis, network dynamic modeling, and deep learning techniques that quantify meaningful networks and connectivity related to cognition and behaviors. Importantly, for each topic, we discuss the pros and cons of the methods in addition to providing examples using our own data for each technique to describe how these methods can be applied to real-world neuroimaging data.

A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms.

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires neuroanatomical expertise. We previously released an open-source dataset of stroke T1w MRIs and manually-segmented lesion masks (ATLAS v1.2, N = 304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the field. Here we present ATLAS v2.0 (N = 1271), a larger dataset of T1w MRIs and manually segmented lesion masks that includes training (n = 655), test (hidden masks, n = 300), and generalizability (hidden MRIs and masks, n = 316) datasets. Algorithm development using this larger sample should lead to more robust solutions; the hidden datasets allow for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke research.

Improved pasireotide response in USP8 mutant corticotroph tumours in vitro.

Cushing's disease is a rare but devastating and difficult to manage condition. The somatostatin analogue pasireotide is the only pituitary-targeting pharmaceutical approved for the treatment of Cushing's disease but is accompanied by varying efficacy and potentially severe side effects. Finding means to predict which patients are more likely to benefit from this treatment may improve their management. More than half of corticotroph tumours harbour mutations in the USP8 gene, and there is evidence of higher somatostatin receptor 5 (SSTR5) expression in the USP8-mutant tumours. Pasireotide has a high affinity for SSTR5, indicating that these tumours may be more sensitive to treatment. To test this hypothesis, we examined the inhibitory action of pasireotide on adrenocorticotrophic hormone synthesis in primary cultures of human corticotroph tumour with assessed USP8 mutational status and in immortalized murine corticotroph tumour cells overexpressing human USP8 mutants frequent in Cushing's disease. Our in vitro results demonstrate that pasireotide exerts a higher antisecretory response in USP8-mutant corticotroph tumours. Overexpressing USP8 mutants in a murine corticotroph tumour cell model increased endogenous somatostatin receptor 5 (Sstr5) transcription. The murine Sstr5 promoter has two binding sites for the activating protein 1 (AP-1) and USP8 mutants possibly to mediate their action by stimulating AP-1 transcriptional activity. Our data corroborate the USP8 mutational status as a potential marker of pasireotide response and describe a potential mechanism through which USP8 mutants may regulate SSTR5 gene expression.

Genetics of Cushing's disease.

Corticotroph tumours are primarily sporadic monoclonal neoplasms and only rarely found in genetic syndromes. Recurrent mutations in the ubiquitin specific protease 8 (USP8) gene are found in around half of cases. Mutations in other genes such as USP48 and NR3C1 are less frequent, found in less than ~20% of cases. TP53 and ATXR mutations are reported in up to one out of four cases, when focusing in USP8 wild type or aggressive corticotroph tumours and carcinomas. At present, USP8 mutations are the primary driver alterations in sporadic corticotroph tumours, TP53 and ATXR mutations may indicate transition to more aggressive tumour phenotype. Next generation sequencing efforts have identified additional genomic alterations, whose role and importance in corticotroph tumorigenesis remains to be elucidated.

Nasopharyngeal carcinoma patients from Norway show elevated Epstein-Barr virus IgA and IgG antibodies prior to diagnosis.

BACKGROUND: IgA antibodies against few Epstein-Barr virus (EBV) proteins are established serological markers for nasopharyngeal carcinoma (NPC). We recently validated a novel, comprehensive EBV marker panel and showed that IgA, but also IgG antibodies against multiple EBV proteins are highly sensitive and specific for EBV-positive NPC at diagnosis. However, data about these novel biomarkers as prospective markers for NPC are sparse. METHODS: This study included 30 incident NPC cases and 60 matched controls from the Norwegian Janus Serum Bank. For 21 NPCs, molecular EBV and human papillomavirus (HPV) status were assessed by EBER-ISH and HPV DNA/RNA testing by PCR, respectively. IgA and IgG serum antibodies against 17 EBV antigens were analyzed in prediagnostic sera of cases (median lead time 14 years) and controls using multiplex serology. Sensitivities were calculated using receiver operating characteristic analysis pre-specified to yield 90% specificity in the control group. From 10 cases, serial samples were available. RESULTS: Quantitative EBV antibody levels were significantly elevated among all cases (p < 0.05) for three IgA and six IgG antibodies. The highest sensitivities for defining 12 EBER-ISH-positive NPCs were observed for BGLF2 IgA (67%) and BGLF2 IgG (83%). Increased IgA and IgG antibody levels between the first and last draw before diagnosis were observed for EBER-ISH positive, but not for EBER-ISH negative NPCs. Among 21 molecularly analyzed NPCs, 4 EBER-ISH negative NPCs showed concomitant positivity to HPV type-specific DNA and RNA; 3 NPCs were HPV16 and 1 NPC was HPV18 positive. CONCLUSION: Both, EBV IgA and IgG antibody levels are significantly elevated many years before diagnosis of EBV-positive NPCs in Norway, an NPC low-incidence region. This study provides insights into one of the largest available prospective sample collections of NPCs in a non-endemic country.

A comparison of food and alcohol disturbance (FAD) in sorority and non-sorority women.

Objective: College students who are members of groups in which appearance and alcohol norms are highly salient may be at particular risk for engaging in food and alcohol disturbance (FAD) behaviors. This study compared demographically-matched sorority- and non-sorority members on FAD and associated behaviors. Participants: College women who self-identified as being in a sorority (n = 95) were matched with non-sorority peers (n = 95) on age, body mass index (BMI), ethnicity, and race. Methods: Participants completed an online survey assessing alcohol use, eating disorder symptoms, appearance-related peer pressure, FAD behaviors, and demographic information. Mann-Whitney U tests and generalized linear models tested hypotheses. Results: Sorority members reported more alcohol use and FAD behaviors; however, after controlling for year in school, alcohol use, and eating disorder symptoms, Greek status no longer predicted FAD behaviors. Conclusions: Differences in FAD behaviors across sorority- and non-sorority women were due to differences in alcohol consumption.

Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study.

BACKGROUND: Long COVID is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To better understand the long-term course and etiology of symptoms we analyzed a cohort of patients with COVID-19 prospectively. METHODS: Patients were included at 5 months after acute COVID-19 in this prospective, noninterventional, follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n = 96; 32.3% hospitalized, 55.2% females) were included in this analysis of symptoms, quality of life (based on an SF-12 survey), laboratory parameters including antinuclear antibodies (ANAs), and SARS-CoV-2 antibody levels. RESULTS: At month 12, only 22.9% of patients were completely free of symptoms and the most frequent symptoms were reduced exercise capacity (56.3%), fatigue (53.1%), dyspnea (37.5%), and problems with concentration (39.6%), finding words (32.3%), and sleeping (26.0%). Females showed significantly more neurocognitive symptoms than males. ANA titers were ≥1:160 in 43.6% of patients at 12 months post-COVID-19 symptom onset, and neurocognitive symptom frequency was significantly higher in the group with an ANA titer ≥1:160 versus <1:160. Compared with patients without symptoms, patients with ≥1 long-COVID symptom at 12 months did not differ significantly with respect to their SARS-CoV-2 antibody levels but had a significantly reduced physical and mental life quality compared with patients without symptoms. CONCLUSIONS: Neurocognitive long-COVID symptoms can persist ≥1 year after COVID-19 symptom onset and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titer elevations. This may indicate autoimmunity as a cofactor in etiology of long COVID.

Hippocampal asymmetry of regional development and structural covariance in preterm neonates.

Premature birth is associated with a high prevalence of neurodevelopmental impairments in surviving infants. The hippocampus is known to be critical for learning and memory, yet the putative effects of hippocampal dysfunction remain poorly understood in preterm neonates. In particular, while asymmetry of the hippocampus has been well noted both structurally and functionally, how preterm birth impairs hippocampal development and to what extent the hippocampus is asymmetrically impaired by preterm birth have not been well delineated. In this study, we compared volumetric growth and shape development in the hippocampal hemispheres and structural covariance (SC) between hippocampal vertices and cortical thickness in cerebral cortex regions between two groups. We found that premature infants had smaller volumes of the right hippocampi only. Lower thickness was observed in the hippocampal head in both hemispheres for preterm neonates compared with full-term peers, though preterm neonates exhibited an accelerated age-related change of hippocampal thickness in the left hippocampi. The SC between the left hippocampi and the limbic lobe of the premature infants was severely impaired compared with the term-born neonates. These findings suggested that the development of the hippocampus during the third trimester may be altered following early extrauterine exposure with a high degree of asymmetry.

Neuromarkers from Whole-Brain Functional Connectivity Reveal the Cognitive Recovery Scheme for Overt Hepatic Encephalopathy after Liver Transplantation.

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with overt hepatic encephalopathy (OHE). Liver transplantation (LT) can restore liver function, but how it reverses the impaired brain function is still unclear. MRI of resting-state functional connectivity can help reveal the underlying mechanisms that lead to these cognitive deficits and cognitive recovery. In this study, 64 patients with cirrhosis (28 with OHE; 36 without OHE) and 32 healthy control subjects were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated presurgical and postsurgical neurocognitive performance in cirrhosis patients using psychomotor tests. Network-based statistics found significant disrupted connectivity in both groups of cirrhotic patients, with OHE and without OHE, compared with control subjects. However, the presurgical connectivity disruption in patients with OHE affected a greater number of connections than those without OHE. The decrease in functional connectivity for both OHE and non-OHE patient groups was reversed after LT to the level of control subjects. An additional hyperconnected network (i.e., higher connected than control subjects) was observed in OHE patients after LT. Regarding the neural-behavior relationship, the functional network that predicted cognitive performance in healthy individuals showed no correlation in presurgical cirrhotic patients. The impaired neural-behavior relationship was re-established after LT for non-OHE patients, but not for OHE patients. OHE patients displayed abnormal hyperconnectivity and a persistently impaired neural-behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery compared with those without, which needs further clarification in future studies.

Reducing pain in children with cancer at home: a feasibility study of the KLIK pain monitor app.

PURPOSE: This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home. METHODS: Children (8-18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0-7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP's) from the hospital's Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4-6) or 30 min (scores 7-10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews. RESULTS: Twenty-seven children (M age = 7.3 years, 51.8% male) and six HCP's participated. Sixty-three percent (N = 17) of families used the app on a daily basis during three weeks, and 18.5% (N = 5) reported pain scores twice daily during that time (family adherence). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP's followed-up with families within the set timeframe (HCP adherence). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP's), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts. CONCLUSION: Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home.

Robust Cortical Thickness Morphometry of Neonatal Brain and Systematic Evaluation Using Multi-Site MRI Datasets.

The human brain grows the most dramatically during the perinatal and early post-natal periods, during which pre-term birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal magnetic resonance imaging (MRI) pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the cerebrospinal fluid (CSF)/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 pre-term and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532 ± 0.035 mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with post-menstrual age (PMA) at scan (p < 0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3 mm at 28 weeks of PMA to 1.8 mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.

Pain at home during childhood cancer treatment: Severity, prevalence, analgesic use, and interference with daily life.

BACKGROUND: Pain is a common symptom in childhood cancer. Since children spend more time at home, families are increasingly responsible for pain management. This study aimed at assessing pain at home. PROCEDURE: In this longitudinal observational study (April 2016-January 2017), pain severity and prevalence, analgesic use, and pain interference with daily life (Brief Pain Inventory Short Form) were assessed for 4 consecutive days around the time of multiple chemotherapy appointments. Descriptive statistics (frequencies and percentages) were used to report pain severity (with clinically significant pain defined as: score ≥ 4 on "worst pain" or "average pain in the last 24 h"), pain prevalence, and analgesic use. Mixed models were estimated to assess whether patient characteristics were associated with pain severity, and whether pain severity was associated with interference with daily life. RESULTS: Seventy-three children (50.7% male) participated (1-18 years). A majority (N = 57, 78%) experienced clinically significant pain at least once, and 30% reported clinically significant pain at least half the time. In 33.6% of scores ≥ 4, no medication was used. We found an association between pain severity and interference with daily life: the higher the pain, the bigger the interference (estimated regression coefficient = 1.01 [95% CI 0.98-1.13]). CONCLUSIONS: The majority of children experienced clinically significant pain at home, and families frequently indicated no medication use. A stronger focus on education and coaching of families seems essential, as well as routine screening for pain in the home setting.

Electrophysiological correlates of the spatial temporal order judgment task.

The study investigated auditory temporal processing on a tens of milliseconds scale that is the interval when two consecutive stimuli are processed either together or as distinct events. Distinctiveness is defined by one's ability to make correct order judgments of the presented sounds and is measured via the spatial temporal order judgement task (TOJ). The study aimed to identify electrophysiological indices of the TOJ performance. Tone pairs were presented with inter-stimulus intervals (ISI) varying between 25 and 75 ms while EEG was recorded. A pronounced amplitude change in the P2 interval was found between the event-related potential (ERP) of tone pairs having ISI = 55 and 65 ms, but it was a characteristic only of the group having poor behavioral thresholds. With the two groups combined, the amplitude change between these ERPs in the P2 interval showed a medium-size correlation with the behavioral threshold.