New Users of Antipsychotics Among Children and Adolescents in 2008–2017: A Nationwide Register Study

IntroductionRecently, prescribing antipsychotics for children and adolescents has been increasing in many countries. These drugs are often prescribed off-label, although antipsychotics have been associated with adverse effects. We determined the recent incidence of antipsychotic use among children and adolescents in Finland.MethodsFinnish National Prescription Register including all Finnish inhabitants receiving reimbursement for pharmaceuticals was searched for subjects of 1 to 17 years of age who had started an antipsychotic drug between January 1, 2008, and December 31, 2017 (n = 26,353). Between 2008 and 2017, the range of number of Finnish children and adolescents aged 1 to 17 years was 1.01 to 1.03 million/year. The incidence was calculated by dividing the number of new users by all age- and sex-matched Finnish inhabitants in the year.ResultsBetween 2008 and 2017, the incidence of antipsychotic use among children and adolescents increased from 2.1 to 3.8 per 1000 individuals, respectively. In children aged 7 to 12 years, the incidence of antipsychotic use 1.4-folded (from 1.9 (95% CI: 1.8–2.0) to 2.7 (95% CI: 2.5–2.9) per 1000) with a cumulative increase of 0.2% per year (χ2 = 51.0, p <0.0001). In adolescents aged 13 to 17 years, the incidence 2.2-folded (from 4.3 (95% CI: 4.1–4.5) to 9.4 (95% CI: 9.1–9.8) per 1000) with a cumulative increase of 0.6% per year (χ2 = 590.3, p <0.0001). The increase in the incidence of use was steeper in girls (2.3-fold) than in boys (1.4-fold) (χ2 = 85.6, p <0.0001), especially between 2015 and 2017 (1.6-fold and 1.2-fold, respectively) (χ2 = 151.7, p <0.0001). The year 2011 was the turning point when the incidence in girls exceeded the incidence in boys, and the incidence of quetiapine use exceeded that of risperidone use.ConclusionsThe incidence of antipsychotic use increased between 2008 and 2017, especially in adolescent girls. The use of quetiapine increased, although it has few official indications in children and adolescents. Future studies should investigate the reasons for increasing use of antipsychotics, especially quetiapine, in children and adolescents.Peer reviewe

Impairments of executive functionin young children referred to child psychiatric outpatient clinic

Few studies have reported on the quantity and quality of executive function (EF) deficits in young children referred to child psychiatric outpatient clinic with multiple psychiatric symptoms. We evaluated the EF deficits with the Attention and Executive Function Rating Inventory-Preschool (ATTEX-P) filled out by day care teachers for 4- to 7-year-old clinical group (n = 171) and reference group (n = 709). Family background information was collected from all families by parent questionnaire. Diagnoses of the referred children were collected from medical records. Clinical group exhibited higher mean ranks across the ATTEX-P Total score and all nine subscales than reference group (p <.001). Most of the children in the clinical group (58.5%) showed a significant amount of EF deficits (ATTEX-P Total score over clinical cut-off) including distractibility (55.6%) and impulsivity (53.8%) regardless of their diagnoses. In a multiple logistic regression model (controlling for age, gender and parental education), children in the clinical group had increased risk (odds ratio (OR)) = 10.6, 95% confidence interval (CI) = [6.88, 16.2], p <.001) for scoring over the clinical cut-off point on the ATTEX-P Total score. Assessment of EFs should be a routine part of the treatment plan in young children referred to child psychiatric outpatient clinic as it may guide the treatment choices.Peer reviewe

Finnish children who experienced narcolepsy after receiving the Pandemrix vaccine during the 2009-2010 H1N1 pandemic demonstrated high level of psychosocial problems

https://doi.org/10.1111/apa.16233ABSTRACT Aim We assessed psychosocial burdens in children who developed narcolepsy after receiving the Pandemrix H1N1 vaccine during the 2009-2010 pandemic. Parental quality of life was also assessed. Methods This multicentre study covered four of the five Finnish University Hospital Districts, which dealt with about 90% of the paediatric narcolepsy cases after the Pandemrix vaccination. The medical records of children diagnosed from 2010-2014 were reviewed. The questionnaires included the Youth Self Report (YSR), Children?s Depression Inventory (CDI), the Child Behaviour Checklist (CBCL) and questions on parental resources, stress and quality of life. Results We obtained the medical records of 94 children who were aged 5-17 years at the time of their narcolepsy diagnosis and questionnaire data for 73 of those children. Most children had strong narcolepsy symptoms 25% had CDI scores that suggested depression. In addition, 41% had total CBCL problem scores above the clinically significant limit and 48% were anxious, withdrawn and had somatic complaints. Sleep latency was weakly associated with the CBCL total problem score. Half of the children needed psychiatric interventions and parental stress was common. Conclusion Depression and behavioural problems were common in children with narcolepsy after the Pandemrix vaccination and their parents frequently reported feeling stressed.Peer reviewe

Statistical Evaluation of Different Mathematical Models for Diffusion Weighted Imaging of Prostate Cancer Xenografts in Mice

Purpose To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer.Methods Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm(2), respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential).Results Significant changes were observed in DWI data during the tumor growth, indicated by ADC(m), ADC(s), and ADC(k). Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1-4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model.Conclusion Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.</p

Prospective comparison of F-18-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Peer reviewe

Docetaxel chemotherapy response in PC3 prostate cancer mouse model detected by rotating frame relaxations and water diffusion

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times TRAFF2 and TRAFF4 than with the continuous wave T1ρ, adiabatic T1ρ, adiabatic T2ρ, T1, T2 or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n = 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames, T1 and T2, continuous wave T1ρ, adiabatic T1ρ and adiabatic T2ρ relaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored using T2-weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn, T1ρ,T2ρ and conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short- and long-term responses were obtained with T1, while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFn compared with all others. The tumor volume decreased after a two-week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published

Discrepancies between Radiology Specialists and Residents in Fracture Detection from Musculoskeletal Radiographs

(1) Background: The aim of this study was to compare the competence in appendicular trauma radiograph image interpretation between radiology specialists and residents. (2) Methods: In this multicenter retrospective cohort study, we collected radiology reports from radiology specialists (N = 506) and residents (N = 500) during 2018–2021. As a reference standard, we used the consensus of two subspecialty-level musculoskeletal (MSK) radiologists, who reviewed all original reports. (3) Results: A total of 1006 radiograph reports were reviewed by the two subspecialty-level MSK radiologists. Out of the 1006 radiographs, 41% were abnormal. In total, 67 radiographic findings were missed (6.7%) and 31 findings were overcalled (3.1%) in the original reports. Sensitivity, specificity, positive predictive value, and negative predictive value were 0.86, 0.92, 0.91 and 0.88 respectively. There were no statistically significant differences between radiology specialists’ and residents’ competence in interpretation (p = 0.44). However, radiology specialists reported more subtle cases than residents did (p = 0.04). There were no statistically significant differences between errors made in the morning, evening, or night shifts (p = 0.57). (4) Conclusions: This study found a lack of major discrepancies between radiology specialists and residents in radiograph interpretation, although there were differences between MSK regions and in subtle or obvious radiographic findings. In addition, missed findings found in this study often affected patient treatment. Finally, there are MSK regions where the sensitivity or specificity is below 90%, and these should raise concerns and highlight the need for double reading and should be taken into consideration in radiology education.Peer reviewe

Radiomics and machine learning of multisequence multiparametric prostate MRI: Towards improved non-invasive prostate cancer characterization

Purpose To develop and validate a classifier system for prediction of prostate cancer (PCa) Gleason score (GS) using radiomics and texture features of T2-weighted imaging (T2w), diffusion weighted imaging (DWI) acquired using high b values, and T2-mapping (T2). Methods T2w, DWI (12 b values, 0–2000 s/mm2), and T2 data sets of 62 patients with histologically confirmed PCa were acquired at 3T using surface array coils. The DWI data sets were post-processed using monoexponential and kurtosis models, while T2w was standardized to a common scale. Local statistics and 8 different radiomics/texture descriptors were utilized at different configurations to extract a total of 7105 unique per-tumor features. Regularized logistic regression with implicit feature selection and leave pair out cross validation was used to discriminate tumors with 3+3 vs >3+3 GS. Results In total, 100 PCa lesions were analysed, of those 20 and 80 had GS of 3+3 and >3+3, respectively. The best model performance was obtained by selecting the top 1% features of T2w, ADCm and K with ROC AUC of 0.88 (95% CI of 0.82–0.95). Features from T2 mapping provided little added value. The most useful texture features were based on the gray-level co-occurrence matrix, Gabor transform, and Zernike moments. Conclusion Texture feature analysis of DWI, post-processed using monoexponential and kurtosis models, and T2w demonstrated good classification performance for GS of PCa. In multisequence setting, the optimal radiomics based texture extraction methods and parameters differed between different image types. </div