Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks.

BACKGROUND: Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. OBJECTIVE: This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. METHODS: We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. RESULTS: Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. CONCLUSION: We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00007966, 04/05/2015).

Gender Differences in Task Specific Dystonia: What Can we Learn from Musician's Dystonia?

BACKGROUND: Musician's Dystonia (MD) is a task specific, focal dystonia which usually occurs only at the instrument. The pathophysiology is not fully understood, but several risk factors like over-practice and genetic predisposition are known. Interestingly, 80% of those affected are men, which stands in contrast to the gender distribution in other focal dystonias, such as cervical dystonia. OBJECTIVES: Our aim was to evaluate the difference in women and men with regard to risk factors leading to MD. METHODS: We investigated known risk factors for MD in a large cohort of 364 MD patients by retrospectively collecting data on practice behavior and family history. RESULTS: In line with previous studies, we found a ratio of ~4:1 men to women. Age at onset of MD was significantly lower in women; however, subsequent analysis revealed that it was a positive family history (FH+) and not gender that was associated with a lower age at onset. Furthermore, we found that those with negative family history had accumulated more practice time until onset of MD. CONCLUSIONS: These results imply that the earlier age at onset in women did not depend on gender but was due to the higher proportion of a positive family history. In contrast, men were less likely to have a positive family history, suggesting that genetic factors may not be the primary reason for the higher prevalence of MD in men. Instead, differences in practice behaviors between men and women may contribute to this gender disparity.

The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis.

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management. OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

Protocol for an international multicenter randomized controlled trial assessing treatment success and safety of peroral endoscopic myotomy vs endoscopic balloon dilation for the treatment of achalasia in children.

INTRODUCTION: Achalasia is a rare neurodegenerative esophageal motility disorder characterized by incomplete lower esophageal sphincter (LES) relaxation, increased LES tone and absence of esophageal peristalsis. Achalasia requires invasive treatment in all patients. Conventional treatment options include endoscopic balloon dilation (EBD) and laparoscopic Heller's myotomy (LHM). Recently, a less invasive endoscopic therapy has been developed; Peroral Endoscopic Myotomy (POEM). POEM integrates the theoretical advantages of both EBD and LHM (no skin incisions, less pain, short hospital stay, less blood loss and a durable myotomy). Our aim is to compare efficacy and safety of POEM vs. EBD as primary treatment for achalasia in children. METHODS AND ANALYSIS: This multi-center, and center-stratified block-randomized controlled trial will assess safety and efficacy of POEM vs EBD. Primary outcome measure is the need for retreatment due to treatment failure (i.e. persisting symptoms (Eckardt score > 3) with evidence of recurrence on barium swallow and/or HRM within 12 months follow-up) as assed by a blinded end-point committee (PROBE design). DISCUSSION: This RCT will be the first one to evaluate which endoscopic therapy is most effective and safe for treatment of naïve pediatric patients with achalasia.

Practice behaviors as trigger factor for the onset of Musicians' Dystonia.

Musician's Dystonia (MD) is a task-specific movement disorder that results in an involuntary cramping of muscles involved in playing an instrument such as the upper limbs or the embouchure. It is usually painless and occurs in general only at the instrument. The pathophysiology of MD is not completely understood. The present study aimed at assessing differences in practice behaviors between pianists affected by MD and Healthy Controls (HC) in the years preceding the onset of the disease. Thus, we investigated to what extent practice quantity can be considered a trigger of Musicians' Dystonia. The results showed that despite comparable practice behaviors in childhood, MD pianists incremented the amount of daily practice to a greater extent than their healthy colleagues, especially in the second and in the third decade of life. Thus, subsequent logistic regression analysis showed that high amounts of daily practice might significantly increase the risk of developing MD. Furthermore, gender-related differences in practice behaviors across groups were identified, indicating that male pianists from the MD group might not have practiced significantly more than HC male pianists before the onset of the disease. To the authors' knowledge, these are the first empirical evidence of the role of dysfunctional practice behaviors in triggering MD, which has clinical and educational implications.

Embouchure Dystonia as a Network Disease.

While the pathophysiology of embouchure dystonia, a sub-entity of musician's dystonia, is still not fully understood, recent research has shown that it involves alterations of several brain functions and networks. Maladaptive plasticity in sensorimotor integration, sensory perception, and deficient inhibitory mechanisms at cortical, subcortical, and spinal level seem to contribute to its pathophysiology. Furthermore, functional systems of the basal ganglia and the cerebellum are involved, clearly pointing toward a network disorder. We therefore propose a novel network model, based on electrophysiological and recent neuroimaging studies highlighting embouchure dystonia.

Age-Dependent Electroencephalogram Features in Infants Under Spinal Anesthesia Appear to Mirror Physiologic Sleep in the Developing Brain: A Prospective Observational Study.

BACKGROUND: Infants under spinal anesthesia appear to be sedated despite the absence of systemic sedative medications. In this prospective observational study, we investigated the electroencephalogram (EEG) of infants under spinal anesthesia and hypothesized that we would observe EEG features similar to those seen during sleep. METHODS: We computed the EEG power spectra and spectrograms of 34 infants undergoing infraumbilical surgeries under spinal anesthesia (median age 11.5 weeks postmenstrual age, range 38-65 weeks postmenstrual age). Spectrograms were visually scored for episodes of EEG discontinuity or spindle activity. We characterized the relationship between EEG discontinuity or spindles and gestational age, postmenstrual age, or chronological age using logistic regression analyses. RESULTS: The predominant EEG patterns observed in infants under spinal anesthesia were slow oscillations, spindles, and EEG discontinuities. The presence of spindles, observed starting at about 49 weeks postmenstrual age, was best described by postmenstrual age ( P =.002) and was more likely with increasing postmenstrual age. The presence of EEG discontinuities, best described by gestational age ( P = .015), was more likely with decreasing gestational age. These age-related changes in the presence of spindles and EEG discontinuities in infants under spinal anesthesia generally corresponded to developmental changes in the sleep EEG. CONCLUSIONS: This work illustrates 2 separate key age-dependent transitions in EEG dynamics during infant spinal anesthesia that may reflect the maturation of underlying brain circuits: (1) diminishing discontinuities with increasing gestational age and (2) the appearance of spindles with increasing postmenstrual age. The similarity of these age-dependent transitions under spinal anesthesia with transitions in the developing brain during physiological sleep supports a sleep-related mechanism for the apparent sedation observed during infant spinal anesthesia.

The potential of rectal swabs to differentiate simple and complex appendicitis in children with a microbiota-based test.

Currently, accurate biomarkers differentiating simple (phlegmonous) from complex (gangrenous and/or perforated) appendicitis in children are lacking. However, both types may potentially require different treatment strategies, and the search for diagnostic modalities remains warranted. Previously, we demonstrated a distinct microbiota (both an increased bacterial diversity and abundance) in the appendix of children with complex compared to simple appendicitis. From the same cohort of patients we have collected 35 rectal swabs under general anesthesia prior to appendectomy and microbiota analysis was performed by IS-pro, a 16S-23S rDNA-based clinical microbiota profiling technique. Using the obtained IS-profiles, we performed cluster analyses (UPGMA), comparison of diversity (Shannon Diversity Index) and intensity (abundance in relative fluorescence units) on phylum level, and comparison on species level of bacteria between simple and complex appendicitis. Regarding these analyses, we observed no clear differences between simple and complex appendicitis. However, increased similarity of the microbial composition of the appendix and rectal swab was found within children with complex compared to simple appendicitis. Furthermore, PLS-DA regression analysis provided clear visual differentiation between simple and complex appendicitis, but the diagnostic power was low (highest AUC 0.65).   Conclusion: Microbiota analysis of rectal swabs may be viable to differentiate between simple and complex appendicitis prior to surgery as a supervised classification model allowed for discrimination of both types. However, the current diagnostic power was low and further validation studies are needed to assess the value of this method. What is Known: • Simple and complex appendicitis in children may require different treatment strategies, but accurate preoperative biomarkers are lacking. • Clear differentiation can be made between both types in children based upon the microbial composition in the appendix. What is New: • Increased similarity was found between the microbial composition of the appendix and rectal swab within children with complex compared to simple appendicitis. • Using a supervised classification model rectal swabs may be viable to discriminate between simple and complex appendicitis, but the diagnostic power was low.

Follow-up of infants with colic into childhood: Do they develop behavioural problems?

AIM: To assess whether infants with colic (IC) demonstrate persisting developmental dysregulation into childhood, manifested as behavioural problems, and to determine if these behavioural problems are associated with parenting factors. METHODS: Preschool children with a history of IC at the age of 0-3 months, as defined by the Wessel criteria, were invited to participate in an observational follow-up study, in which their caregivers completed the Child Behaviour Checklist (CBCL). Raw scores and clinical-range scores on the internalising, externalising and total behavioural problems scales were compared with a Dutch normative sample using independent t-tests and Chi-square tests. For the clinical-range scores, multivariable logistic regressions (odds ratios [99% confidence interval, CI]) were used to adjust for confounders and to identify variables associated with behavioural problems. RESULTS: Two hundred and fifty-eight children with a history of IC (median age 5.1 (interquartile range, IQR 4.6-5.5) years, 51.9% boys) were included. The cases had a significantly higher adjusted risk (adjusted odds ratios (aORs) [99% CI]) of scoring in the clinical range of the emotionally reactive, internalising and total problems scale (2.96 [1.24-7.06]; 2.50 [1.35-4.62]; 2.98 [1.46-6.07], respectively). Internalising (P < 0.001), externalising (P < 0.001) and total (P < 0.001) behavioural problems in children with a history of IC were associated with higher parenting stress scores. CONCLUSIONS: Children with a history of IC demonstrated significantly more internalising behavioural problems at preschool age compared to the norm sample. Specific advice and support need to be available for parents to understand and regulate the behaviour of their child, from infancy to childhood.

Implementing Nonoperative Treatment Strategy for Simple Pediatric Appendicitis: A Qualitative Study.

INTRODUCTION: A nonoperative treatment strategy (NOT) with antibiotics for children with simple appendicitis could reduce anesthesia and surgery-related complications. As the implementation of a new treatment in routine clinical practice may take years, this study aims to identify barriers and facilitators for implementation of NOT for children with simple appendicitis. MATERIALS AND METHODS: To identify barriers and facilitators for its implementation, we conducted 14 semistructured interviews and a focus group with health insurance/hospital policymakers, surgical clinicians, and young people-together with their parents-who have been treated surgically or with antibiotics. Transcripts were open coded and categorized as per the framework for healthcare innovations by Fleuren et al. RESULTS: We identified four main themes: (1) Appendicitis is a well-known disease. Children, parents, and clinicians regard appendectomy as routine and safe, making them reluctant toward other treatment options. (2) Clinicians regard uptake of NOT in the national appendicitis guideline necessary for its implementation. (3) For identification of patients best suited for NOT more experience and scientific evidence is needed. (4) Appendectomy and NOT have different risk and benefits making the treatment choice depended on individual patient preferences. CONCLUSIONS: By addressing how NOT and operative treatment are regarded by patients and surgeons could have a substantial impact on the implementation of NOT for children with simple appendicitis. Furthermore, the individual preferences of patients need to be taken into account when choosing between operative and NOT. In other words, offering NOT in a shared decision-making model seems the first appropriate step in its implementation.

Prevalence of suspected child abuse in children with constipation: a case-control study.

BACKGROUND: A possible association between child abuse and neglect (CAN) and functional constipation (FC) has been described in adults, however, limited data are available in children. Our objective was to determine the prevalence of suspected CAN in children with FC as compared with their healthy peers. METHODS: A case-control study was carried out in children aged 3-10 years. Children with FC were recruited at a tertiary outpatient clinic, and healthy controls were recruited at schools. Parents were asked to fill out questionnaires about the history and behaviour of their child, children were inquired using a semistructured interview about experienced traumatic events and sexual knowledge. The interview was scored by two independent observers. The prevalence of suspected CAN was determined according to the questionnaires and interview. RESULTS: In total, 228 children with FC and 153 healthy controls were included. Both groups were age and gender comparable (50% females, median age 6 years (not significant)). No significant difference in the prevalence of suspected CAN was found between children with FC and healthy controls (23.3% vs 30.1%, 95% CI 0.44 to 1.12, p=0.14), including a suspicion of sexual, emotional and physical abuse. CONCLUSION: Suspected CAN was detected in both children with FC as in healthy controls. The possible association between CAN and FC in children could not be confirmed.

Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic.

PURPOSE: Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. METHODS: Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality. RESULTS: Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05). CONCLUSION: BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent.

Identification of the optimal treatment strategy for complex appendicitis in the paediatric population: a protocol for a multicentre prospective cohort study (CAPP study).

INTRODUCTION: In daily practice large heterogeneity in the treatment of children with complex appendicitis exists. Complex appendicitis can be divided into two subtypes; complex appendicitis with and without appendiceal mass and/or abscess. As complex appendicitis is associated with high morbidity and costs, identification of the optimal treatment strategy is essential. In this article, we present the study protocol for the CAPP (Complex Appendicitis in the Pediatric Population) study. METHODS AND ANALYSIS: This nation-wide, multi-centre, comparative, non-randomised prospective cohort study includes all children <18 years old with a preoperative suspicion of complex appendicitis, which is based on imaging confirmed acute appendicitis and predefined criteria regarding the severity of appendicitis. Eligible patients are recruited in more than 30 hospitals. Open appendectomy will be compared with laparoscopic appendectomy for children without appendiceal mass and/or abscess and initial non-operative treatment (ie, intravenous antibiotics with or without percutaneous drainage) to direct appendectomy for children with appendiceal mass and/or abscess. Based on historical data supplied by the participating hospitals and an inclusion period of 2 years and 9 months, a sample size of 1308 patients is aimed. Primary outcome is the proportion of patients experiencing any complication at 3 months follow-up. Reported complications will be assessed by an independent adjudication committee. Secondary outcomes include, but are not limited to, quality of life, and (in)direct costs. To adjust for baseline differences and selection bias, outcomes will be compared after propensity score analysis (inverse probability weighting and stratification). ETHICS AND DISSEMINATION: The Medical Ethics Review Committee of the Amsterdam UMC, location AMC, declared that the Medical Research involving Human Subjects Act (WMO) did not apply to this study. Therefore, no official approval was required by national law. Study results will be presented in peer-reviewed scientific journals and at (inter)national conferences. TRIAL REGISTRATION NUMBERS: NCT04755179; NL9371.

International Core Outcome Set for Acute Simple Appendicitis in Children: Results of a Systematic Review, Delphi Study, and Focus Croups With Young People.

OBJECTIVE: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children. SUMMARY OF BACKGROUND DATA: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS. METHODS: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS. RESULTS: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications. CONCLUSION: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

The child's perception on monitoring inflammatory bowel disease activity.

To determine the perception of children with inflammatory bowel disease (IBD) regarding monitoring tests, we first compared the reported discomfort and patient perspective during gastro-intestinal (GI)-endoscopy, magnetic resonance entrography (MRE), and ultrasound (US) and, in a second comparison, patient preference on non-invasive tests (venipuncture, sampling stool and US). A cross-sectional study in children 8-18 years undergoing an US, MRE, and GI-endoscopy for diagnosis or follow-up of IBD. After each procedure, the children filled out the Discomfort during research procedures questionnaire (DISCO-RC). Items of the DISCO-RC are as follows: nervousness, annoyance, pain, fright, boredom, and tiredness. Answers range from "not" (= 0 points) to "extremely" (= 4 points) (range total score: 0-24). Differences between the procedures were assessed with Friedman test, with subsequent Wilcoxon signed-rank test. The children were also asked which non-invasive test they preferred not to undergo regularly (venipuncture, stool-sampling, or US). Answers were analyzed with χ2-test. Forty-nine patients (27 (55%) female, median age 15 (range 9-17)) were included. The children reported to be most nervous, frightened, and tired after GI-endoscopy (median: 1, 1, 2 points, respectively), equally annoyed by MRE and GI-endoscopy (median 1 point), and equally bored by MRE and US. GI-endoscopy was ranked as most discomfortable, followed by MRE and US (total DISCO-RC scores: 7 vs. 5 vs. 2, p < 0.001). Most of the children preferred not to sample stool or perform venipuncture regularly (n = 20 (41%, both) (p < 0.001)).Conclusion: Our results suggest that the children with IBD report low discomfort after US, MRE, and GI-endoscopy. US is preferred as a monitoring tool, also among non-invasive monitoring tests. GI-endoscopy was most discomfortable. What is Known: • Children with inflammatory bowel disease need to be monitored frequently for disease activity. • Adult studies - including a systematic review - on acceptability of monitoring tools among IBD patients showed mixed results. What is New: • Children in our study ranked gastro-intestinal endoscopy as most discomfortable, followed by MRE and US. • With regard to non-invasive monitoring, most children preferred not to sample stool or perform venipuncture regularly, and preferred US.

Reactions of non-abused children aged 3-9 years to the Sexual Knowledge Picture Instrument: an interview-based study.

Background: The Sexual Knowledge Picture Instrument (SKPI) is a child-friendly picture book that was developed as a diagnostic tool for sexual abuse in young children and is currently being validated. The aim of the current study was to explore the verbal and non-verbal reactions of non-abused Dutch children, aged 3-9 years, to the SKPI and to assess differences in reactions between genders and age groups. Methods and analysis: Subject recruitment took place at preschools and primary schools. All children underwent a recorded video semi-structured interview with the SKPI. Interview recordings were scored by an independent rater who used scoring lists for verbal and non-verbal reactions. Non-parametric tests were used in statistical analyses. Results: Of the 90 children (median age 5 years) participating in the study, most correctly named the genitals and their non-sexual functions. Only 34 showed an understanding of the picture depicting adult sexuality, with just one child describing a sexual function. Girls (n=45) gave more correct answers (median 87%) than boys (n=45, median 78%; p=0.006). Giggling was the most frequently observed non-verbal reaction, with a total of 186 instances in 54 children. Conclusion: Non-abused children up to 9 years of age showed only limited knowledge of the sexual function of the genitals and hardly any insight into adult sexuality.

Diagnostic accuracy of fibrosis tests in children with non-alcoholic fatty liver disease: A systematic review.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD. METHODS: We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard. RESULTS: Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. CONCLUSION: Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.