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Intro: The COVID-19 pandemic has triggered global collaborative efforts on response and research to detect SARS-CoV-2 particles not just in the human population but also in wastewater. While the examination of clinical samples from COVID-19 patients links SARS-CoV-2 to specific individuals, the analysis of an amalgam of human feces through environmental surveillance (ES) links SARSCoV-2 to populations and communities served by the wastewater system. Studies on SARS-CoV-2 in the environment were already done in high-resource countries. However, its epidemiology in wastewater bodies in the Philippines is limited. In this study, we used the National ES for Polio and Other Pathogens Network to investigate the molecular epidemiology and transmission dynamics of SARS-CoV-2 at the outset of the pandemic. Methods: This is a retrospective study of 250 wastewater samples collected from May 2020 to July 2021. Samples were processed using the two-phase concentration technique. Pepper mild mottle virus RNAs were quantified as the internal control. Real-time PCR was used to detect the N-gene of the SARS-CoV-2. Whole genomes were sequenced using the COVID-19 ARTIC v4.0. Phylogenetic and mutation analysis were done and lineage assignments were established using the PANGOLIN software. Findings: Forty-two percent (107/250) of the environmental samples detected SARS-CoV-2 particles. Fifty-nine samples with Ct values ≤38 were sequenced and the whole genome analysis revealed B.1.1 and B.6. lineages of SARS-CoV-2. When viral load were plotted with the weekly cases in the respective site, we observed that SARS-CoV2 can be detected in wastewater weeks before the spike of cases in the community. Conclusion: This is the first report on the detection of B.1.1 and B.6 SARS-CoV-2 particles in waste/surface waters in the Philippines. With the declining incidence of COVID-19 cases, this study provided data regarding the feasibility of establishing environmental surveillance for SARS-CoV-2 as a supplemental tool for human or case monitoring especially in resource-limited settings.

Background. Early patient referral correlates with improved patient survival on dialysis. We examine whether early referral and a planned first dialysis affect quality of life (QoL). Methods. All patients commencing dialysis in nine centres in seven European countries between 1 July 1998 and 31 October 1999 were recruited. Definitions: early referral=followed by a nephrologist >1 month before first dialysis (<1 month=late referral); planned=early referral and previous serum creatinine >300 µmol/l and non-urgent first dialysis (early referral and no creatinine >300 µmol/l or urgent first dialysis=unplanned). QoL was measured at 8 weeks using a visual analogue scale (VAS) and Short Form 36 (SF-36). Results. VAS was significantly higher in early referral patients [mean (SD) 58.4 (20) vs 50.4 (19), P=0.005], particularly if the first dialysis was planned [60.7 (20) vs 54.2 (20), P=0.03]. Planned patients also had higher SF-36 mental summary scores [45.4 (12) vs 39.7 (11), P=0.003], role emotional scores [58.0 (43) vs 30.9 (38), P=0.003], and mental health scores [63.7 (24) vs 54.6 (22), P=0.01] than unplanned patients. Adjusting for centre and other confounding variables showed that having a planned first dialysis had an independent effect on QoL (VAS, and the SF-36's mental summary score, physical functioning, role physical, general health, role emotional and mental health). Early referral had no independent effect on QoL. Socio-economic status had an important positive effect on physical QoL. Conclusions. While the effect of early referral to a nephrologist on QoL appeared centre dependent, a smooth transition onto dialysis was associated with significantly better early QoL, independent of other variables. [ABSTRACT FROM AUTHOR]

Non-specific effects of methylphenidate treatment, including expectancy and regression to the mean effects, contribute to the overall effect of methylphenidate on attention-deficit/hyperactivity disorder (ADHD) symptoms. Knowledge on the extent to which non-specific effects contribute to the overall effect and whether regression to the mean explains part of the non-specific effects, is currently lacking. A double-blind, randomized, placebo-controlled, cross-over trial was used to compare parent and teacher ratings of child ADHD symptoms at baseline and during treatment with placebo and 5, 10, 15 and 20 mg of methylphenidate, twice daily. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). The extent to which non-specific effects contributed to the effects of methylphenidate was determined by ADHD symptom reductions observed with placebo versus reductions observed with active doses of methylphenidate. The influence of regression to the mean was examined by estimating the contribution of baseline ADHD symptom severity to the effects observed with placebo treatment. Data were analyzed using multilevel analyses. We observed significant non-specific effects of methylphenidate for parent-rated ADHD symptoms, but not for teacher-rated symptoms. For parent reported hyperactive/impulsive symptoms, higher baseline symptoms predicted larger effects with placebo, indicating regression to the mean effects. For parent-reports, a significant part of the overall effect of methylphenidate treatment is explained by non-specific effects. Our findings stress the importance of taking non-specific effects into account when evaluating methylphenidate treatment, by including teacher-reports and using a double baseline assessment during titration. Comparing active medication with a placebo in the titration trial has the potential to identify non-specific effects., (© 2024. The Author(s).)

Background and Objectives: Concerns exist regarding the rising use of methylphenidate. A double-blind, placebo-controlled methylphenidate titration (PCT) for children with attention-deficit/hyperactivity disorder (ADHD) has shown potential to improve titration (i.e., detection of placebo responders and larger ADHD symptom improvement) in experimental settings. This study aims to determine if these advantages can be transferred to clinical settings., Method: Children (aged 5-13 years) with an ADHD diagnosis and an indication to start methylphenidate (MPH) treatment were recruited. Participants were randomized to PCT or care as usual (CAU) in a 1:1 ratio followed by a 7-week randomized controlled trial (T1) and 6-month, naturalistic, open-label follow-up (T2). Parents, teachers, and physicians rated ADHD symptoms, ADHD medication use, MPH dosing, and treatment satisfaction using questionnaires., Results: A total of 100 children were enrolled and randomized to PCT (n = 49) or CAU (n = 51). In the PCT group, we found 8.2% placebo responders, 16.3% non-responders, and 65.3% responders to MPH. With PCT compared with CAU, a significantly larger number of children discontinued MPH (T1: 24.5 vs 5.9%, p = 0.009; T2: 41.7 vs 10.4%, p < 0.001) and refrained from using other pharmacological treatment (T1: 20.4 vs 3.9%, p = 0.013; T2: 20.83 vs 6.25%, p = 0.002). At both timepoints, there were no significant differences between the groups in the average dose of MPH, ADHD symptoms, or treatment satisfaction., Conclusions: PCT can be used to improve detection of children who do not benefit from MPH, and may therefore potentially reduce overtreatment of ADHD with MPH., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The access to and uptake of evidence-based behavioral parent training for children with behavioral difficulties (i.e., oppositional, defiant, aggressive, hyperactive, impulsive, and inattentive behavior) are currently limited because of a scarcity of certified therapists and long waiting lists. These problems are in part due to the long and sometimes perceived as rigid nature of most evidence-based programs and result in few families starting behavioral parent training and high dropout rates. Brief and individually tailored parenting interventions may reduce these problems and make behavioral parent training more accessible. This protocol paper describes a two-arm, multi-center, randomized controlled trial on the short- and longer-term effectiveness and cost-effectiveness of a brief, individually tailored behavioral parent training program for children with behavioral difficulties., Methods: Parents of children aged 2-12 years referred to a child mental healthcare center are randomized to (i) three sessions of behavioral parent training with optional booster sessions or (ii) care as usual. To evaluate effectiveness, our primary outcome is the mean severity of five daily ratings by parents of four selected behavioral difficulties. Secondary outcomes include measures of parent and child behavior, well-being, and parent-child interaction. We explore whether child and parent characteristics moderate intervention effects. To evaluate cost-effectiveness, the use and costs of mental healthcare and utilities are measured. Finally, parents' and therapists' satisfaction with the brief program are explored. Measurements take place at baseline (T0), one week after the brief parent training, or eight weeks after baseline (in case of care as usual) (T1), and six months (T2) and twelve months (T3) after T1., Discussion: The results of this trial could have meaningful societal implications for children with behavioral difficulties and their parents. If we find the brief behavioral parent training to be more (cost-)effective than care as usual, it could be used in clinical practice to make parent training more accessible., Trial Registration: The trial is prospectively registered at ClinicalTrials.gov (NCT05591820) on October 24th, 2022 and updated throughout the trial., (© 2024. The Author(s).)

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121)., (© 2023. The Author(s).)

Background: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases., Summary: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care., Key Messages: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Parenting programs are effective for children with externalizing problems, but not always easily accessible for parents. In order to facilitate accessibility, we developed a self-help parenting program, consisting of a manual and online part. The efficacy of the program in reducing children's externalizing problems was compared to waitlist in a randomized controlled trial. In addition, two versions of the program were exploratively compared, one with and one without biweekly telephonic support. Candidate moderators (child and parent factors) and parental satisfaction were also examined. We randomly assigned 110 families to one of the following three conditions: the support condition, the no support condition, or the waitlist condition. Intervention duration was 15 weeks. Outcomes were collected at baseline (T0), 8 weeks (T1), 15 weeks (T2), and 28 weeks (T3) and included daily telephonic measurements of parent-rated externalizing behavior and the Intensity scale of the parent-rated Eyberg Child Behavior Inventory (ECBI). Main analyses compared outcomes at T2, using longitudinal regressions with T0 as fixed factor. Results showed that children improved significantly more on both outcomes in the intervention condition compared to waitlist, with small to medium effect sizes. Parental satisfaction was high. Neither differences in efficacy nor in parental satisfaction were found between the support and no support condition. No moderators were detected. The newly developed self-help parenting program is effective in reducing children's externalizing behavior problems and may help improve access to evidence-based care., (© 2022. The Author(s).)

Background: Behavioural parent training is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but little is known about the extent to which initial benefits are maintained., Aims: This meta-analytic review investigated longer-term (i.e., more than 2 months post-intervention) child and parental outcomes of behavioural parent training for children with ADHD., Materials & Methods: We searched for randomized controlled trials and examined ADHD symptoms, behavioural problems, positive parenting, negative parenting, parenting sense of competence, parent-child relationship quality, and parental mental health as outcomes. We included 27 studies (31 interventions; 217 effect sizes), used multilevel random-effects meta-analyses for between- and within-group comparisons (pre-intervention to follow-up and post-intervention to follow-up), and explored twelve predictors of change., Results: Between pre-intervention and follow-up ( M  = 5.3 months), we found significant small-to-moderate between-group effects of the intervention on ADHD symptoms, behavioural problems, positive parenting, parenting sense of competence and parent-child relationship quality. Within-group findings show sustained improvements in the intervention conditions for all outcome domains. There were few significant changes from post-intervention to follow-up. Additionally, the large majority of the individual effect sizes indicated sustained outcomes from post-intervention to follow-up. There were seven significant predictors of change in child outcomes, including stronger reductions in ADHD symptoms of girls and behaviour problems of younger children. In contrast with some meta-analyses on short-term effects, we found no differences between masked and unmasked outcomes on ADHD symptoms at follow-up., Discussion & Conclusion: We conclude that behavioural parent training has longer-term benefits for children's ADHD symptoms and behavioural problems, and for positive parenting behaviours, parenting sense of competence and quality of the parent-child relationship., Competing Interests: Prof. Dr. van der Oord has co‐developed a planning‐focused and solution‐focused treatment and other behavioural treatments, but has no financial interest in any of these. She has received research grants from ZonMw and the Research Foundation Flanders (FWO). She was an advisor of the Dutch ADHD guideline groups and is a member of a working group on ADHD of the Superior Health Council of Belgium. Dr. Luman has co‐developed a self‐help teacher training program, without financial interests. She has received research grants from ZonMw and was an advisor of the Dutch ADHD guideline groups. Prof. Dr. van den Hoofdakker has received royalties as one of the editors of “Sociaal Onhandig” (published by Van Gorcum), a Dutch book for parents that can be used in parent training. She has been involved in the development and evaluation of several parent and teacher training programs, without financial interests. She has been a member of Dutch ADHD guideline and practice standard groups. Dr. Dekkers, Dr. Hornstra, Dr. Leijten, Prof. Dr. Hoekstra, Dr. Groenman and Ms. Doffer have reported no biomedical financial interests or potential conflicts of interest., (© 2023 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Behavioral parent training (BPT) is an evidence-based treatment for children with attention-deficit/hyperactivity disorder (ADHD). Stimulus control techniques (antecedent-based techniques, e.g., clear rules, instructions) and contingency management techniques (consequent-based techniques, e.g., praise, ignore) are the most common ones that are being taught to parents in BPT. However, research into the additive effects of these techniques is scarce. In this replicated single-case experimental ABC phase design, including six children on stable medication for ADHD (8-11 years) and their parents, the added efficacy of consequent-based techniques on top of antecedent-based techniques was evaluated. After a baseline period (phase A), we randomized the commencement time of two sessions parent training in antecedent-based techniques and two sessions parent training in consequent-based techniques for each child. Children's behaviors were assessed by daily parent ratings of selected problem behaviors and an overall behavior rating. Although visual inspection showed that behavior improved for most children in both phases, randomization tests did not demonstrate the added efficacy of the consequent-based techniques on top of the antecedent-based techniques. Limitations of the study and recommendations for future single-case experiments in this population are discussed.

Patients with chronic kidney disease (CKD) are at higher cardiovascular risk than the general population. Cardiovascular diseases, vascular calcification among them, are the leading cause of death in these patients. Factors influencing vascular calcification are oxidative stress, inflammation, and accumulation of uremic toxins during CKD. Uric acid is a cardiorenal toxin that accumulates in the case of kidney malfunction. The primary therapy for replacing kidney function and removing toxins from end-stage renal disease patients is hemodialysis. Effective removal of toxins can be estimated by blood or dialysate lab analysis or optical monitoring. In this study, the authors tested a miniaturized optical sensor for monitoring uric acid levels and removal for the first time in a more extensive clinical study, including Hemodialysis (HD) and Post-dilutional online hemodiafiltration (HDF) procedures with different settings in Tallinn, Estonia. The results (Mean±SD, Lab vs. Sensor) of the uric acid concentration 57.20±34.05 vs. 57.22±33.09 µmol/L, reduction ratio 68.72±10.91 vs. 67.89±12.48 %, and total removed amount 7.00±2.10 vs. 7.33±2.29 mmol did not differ significantly from the values obtained from the clinical laboratory (p<0.05).Clinical Relevance-During this study, a miniaturized optical sensor was tested for the first time in the clinic in different dialysis settings. The results confirm that the sensor is reliable for regularly monitoring cardiorenal toxin uric acid removal during hemodialysis.

Objective: More knowledge on the impact of classroom setting on behavior of children with ADHD may help us to better adjust classroom settings to the needs of this group., Method: We observed ADHD behaviors of 55 children with ADHD and 34 typically developing peers (6-12 years) during classroom transitions, group lessons, and individual seatwork., Results: Multivariate analyses revealed that levels of motor and verbal hyperactivity increased during classroom transitions compared to group lessons and individual seatwork. Children in the ADHD group were more off-task, across settings. There were no interactions between group and setting., Conclusions: Children with ADHD were similarly affected by classroom setting compared to typically developing peers, despite being more off-task across settings. Further research into whether the observed increase in hyperactivity during classroom transitions may be problematic or possibly even beneficial for children with ADHD is recommended.

Background: This metaregression analysis examined which behavioral techniques that are commonly used in behavioral parent and teacher training programs for children with attention-deficit/hyperactivity disorder (ADHD) were related to program effectiveness on children's behavioral outcomes., Methods: We included 32 randomized controlled trials (N = 2594 children) investigating behavioral parent training, teacher training, or a combination, in children with ADHD under 18 years. Outcomes were symptom counts of total ADHD, inattention, and hyperactivity-impulsivity and behavioral problems. The dosage of techniques was extracted from the intervention manuals. Metaregression was used to assess which techniques and intervention characteristics (setting, delivery method, duration, and home-school collaboration) were associated with intervention effectiveness., Results: Higher dosage of psycho-education for parents was associated with smaller effects on behavioral problems and, only in case of parent training, also with smaller effects on ADHD symptoms. Higher dosage of teaching parents/teachers to use negative consequences was associated with larger effects on behavioral problems. Individual training compared with group training was associated with larger effects on ADHD and hyperactivity-impulsivity symptoms., Conclusions: This study provides first insights into the specific techniques that are essential in behavioral parent and teacher training programs for children with ADHD. This knowledge can eventually be used to improve and tailor interventions., (© 2022 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

An important question in mental healthcare for children is whether treatments are effective and safe in the long run. Here, we comment on a recent editorial perspective by Roest et al. (2022), who argue, based on an overview of systematic reviews, 'that there is no convincing evidence that interventions for the most common childhood disorders are beneficial in the long term'. We believe that the available evidence does not justify this conclusion and express our concern regarding the harmful effects of their message. We show that there is evidence to suggest beneficial longer term treatment effects for each of the disorders and explain why evidence-based treatment should be offered to children with mental disorders., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Kt/V urea is the most used marker to estimate dialysis adequacy; however, it does not reflect the removal of many other uraemic toxins, and a new approach is needed. We have assessed the feasibility of estimating intradialytic serum time-averaged concentration (TAC) of various uraemic toxins from their spent dialysate concentrations that can be estimated non-invasively online with optical methods., Methods: Serum and spent dialysate levels and total removed solute (TRS) of urea, uric acid (UA), indoxyl sulphate (IS) and β2-microglobulin (β2M) were evaluated with laboratory methods during 312 haemodialysis sessions in 78 patients with four different dialysis treatment settings. TAC was calculated from serum concentrations and evaluated from TRS and logarithmic mean concentrations of spent dialysate (M ln D)., Results: Mean (± standard deviation) intradialytic serum TAC values of urea, UA, β2M and IS were 10.4 ± 3.8 mmol/L, 191.6 ± 48.1 µmol/L, 13.3 ± 4.3 mg/L and 82.9 ± 43.3 µmol/L, respectively. These serum TAC values were similar and highly correlated with those estimated from TRS [10.5 ± 3.6 mmol/L ( R 2  = 0.92), 191.5 ± 42.8 µmol/L ( R 2  = 0.85)] and from M R 2  = 0.59) and 82.7 ± 40.0 µmol/L ( R 2  = 0.85)] and from M ln D [10.7 ± 3.7 mmol/L ( R 2  = 0.92), 191.6 ± 43.8 µmol/L ( R 2  = 0.80), 12.9 ± 3.2 mg/L ( R 2  = 0.63) and 82.2 ± 38.6 µmol/L ( R 2  = 0.84)], respectively., Conclusions: Intradialytic serum TAC of different uraemic toxins can be estimated non-invasively from their concentration in spent dialysate. This sets the stage for TAC estimation from online optical monitoring of spent dialysate concentrations of diverse solutes and for further optimization of estimation models for each uraemic toxin., Competing Interests: A.F. has received consultancy or speaker fees from Otsuka, AstraZeneca, Vifor Pharma and Alnylam. A.O. is the former CKJ Editor-in-Chief and has received grants from Sanofi and consultancy or speaker fees or travel support from Advicciene, Astellas, AstraZeneca, Amicus, Amgen, Fresenius Medical Care, GlaxoSmithKline, Bayer, Sanofi-Genzyme, Menarini, Kyowa Kirin, Alexion, Idorsia, Chiesi, Otsuka, Novo Nordisk and Vifor Fresenius Medical Care Renal Pharma and is director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra AstraZeneca-UAM of chronic kidney disease and electrolytes. V.M.P.-G. has received grants from Catedra Mundipharma-UAM and Catedra AstraZeneca-UAM and consultancy or speaker fees or travel support from Kyowa Kirin, Alexion and Otsuka AstraZeneca and Sanofi-Genzyme. M.S. has received grants from Hansa Biopharma and consulting fees from Hansa Biopharma, Chemocentryx, AstraZeneca and Vifor Pharma. All other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: One of the COVID-19 pandemic consequences that has affected families the most is school lockdowns. Some studies have shown that distance learning has been especially challenging for families with a child with neurodevelopmental disorders such as ADHD or ASD. However, previous studies have not taken the heterogeneity of these disorders into account. The aim of the present study was therefore to investigate differences between families with a child with ADHD, ASD, or both conditions, and to examine the role of underlying deficits in executive functioning (EF) in both children and parents in relation to negative and positive effects of distance learning., Methods: Survey data assessing both negative and positive experiences of distance learning were collected from parents with a child aged 5-19 years in seven Western European countries: the UK, Germany, Spain, Sweden, the Netherlands, Italy, and Belgium. Altogether, the study included 1010 families with a child with ADHD and/or ASD and an equally large comparison group of families with a child without mental health problems. We included measures of three different types of negative effects (i.e., effects on the child, effects on the parent, and lack of support from school) and positive effects on the family., Results: Results confirmed that families with a child with ADHD, ASD or a combination of ADHD and ASD showed higher levels of both negative and positive effects of distance learning than the comparison group. However, few differences were found between the clinical groups. Group differences were more pronounced for older compared to younger children. Regarding the role of both ADHD/ASD diagnosis and EF deficits, primarily children's EF deficits contributed to high levels of negative effects. Parent EF deficits did not contribute significantly beyond the influence of child EF deficits. Families of children with ADHD/ASD without EF deficits experienced the highest levels of positive effects., Conclusions: School closings during COVID-19 have a major impact on children with EF problems, including children with neurodevelopmental disorders. The present study emphasizes that schools should not focus primarily on whether a student has a neurodevelopmental disorder, but rather provide support based on the student's individual profile of underlying neuropsychological deficits., (© 2022. The Author(s).)

Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior association. We hypothesized that polygenic (risk) scores for antisocial and aggressive behaviors (ASB-PRS) would be related to amygdala morphology. Using the Broad Antisocial Behavior Consortium genome-wide association study (GWAS; mostly population based cohorts), we calculated ASB-PRS in the NeuroIMAGE I ADHD case-control sample with varying levels of DBD symptomatology (n=679 from 379 families, aged 7 - 29). We first investigated associations of several ASB-PRS p value thresholds with the presence of DBD symptoms and self-reported antisocial behavior (ASB) to determine the threshold for further analyses. This PRS was then related to amygdala volume and shape using regression and vertex-wise analyses. Our results showed associations of ASB-PRS with the presence of DBD symptoms, self-reported ASB, and left basolateral amygdala shape, independent of ADHD symptom severity and ADHD-PRS, with a relative outward displacement of the vertices. No associations of ASB-PRS, DBD symptoms or self-reported ASB with amygdala volume were found. Our results indicate that genetic risk for antisocial and aggressive behaviors is related to amygdala shape alterations, and point to genetic sharing across different DBD and ASB and aggression-related phenotypes as a spectrum of genetically related quantitative traits. Additionally, our findings support the utility of vertex-based shape analyses in genetic studies of ASB, aggression, and DBDs., Competing Interests: Declaration of Competing Interest Jan K. Buitelaar has been a consultant to/advisory board member of/and/or a speaker for Janssen Cilag BV, Eli Lilly, Shire, Lundbeck, Roche, and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, or royalties. Stephen V Faraone received income, potential income, travel expenses continuing education support and/or research support from Takeda, OnDosis, Tris, Otsuka, Arbor, Ironshore, Rhodes, Akili Interactive Labs, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. Barbara Franke has received educational speaking fees from Medice. All other authors declare that they have no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Optical online methods are used to monitor the haemodialysis treatment efficiency of end stage kidney disease (ESKD) patients. The aim of this study was to analyse the effect of the administration of UV-absorbing drugs, such as paracetamol (Par), on the accuracy of optical monitoring the removal of uremic toxins uric acid (UA) and indoxyl sulfate (IS) during standard haemodialysis (HD) and haemodiafiltration (HDF) treatments. Nine patients received Par in daily dosages 1−4 g for 30 sessions. For 137 sessions, in 36 patients the total daily dosage of UV-absorbing drugs was less than 500 mg, and for 6 sessions 3 patients received additional UV-absorbing drugs. Par administration slightly affected the accuracy of optically assessed removal of UA expressed as bias between optically and laboratory-assessed reduction ratios (RR) during HD but not HDF employing UV absorbance of spent dialysate (p < 0.05) at 295 nm wavelength with the strongest correlation between the concentration of UA and absorbance. Corresponding removal of IS based on fluorescence at Ex280/Em400 nm during HD and HDF was not affected. Administration of UV-absorbing drugs may in some settings influence the accuracy of optical assessments in spent dialysate of the removal of uremic solutes during haemodialysis treatment of ESKD patients.

Behavioral teacher training is an effective intervention for children with attention-deficit/hyperactivity disorder (ADHD). Intervention effectiveness may be enhanced by including intervention components that carry the strongest evidence for their effectiveness. A previous article of this group showed that both antecedent- (i.e., stimulus-control) and consequent-based (i.e., contingency management) techniques were highly effective in reducing daily teacher-rated, individually selected problem behaviors in a specific situation of the child. Effects were observed up to three months post intervention. Here, we tested whether effects were also present in teacher-rated and masked DSM-based assessments that comprise the full range of ADHD and oppositional defiant disorder (ODD) symptoms, as well as on teacher-rated impairment. Teachers of 90 children with (subthreshold) ADHD (6-12 years) were randomly assigned to one of three conditions: a short (two sessions), individualized intervention consisting of either a) antecedent-based techniques or b) consequent-based techniques; or c) waitlist. Multilevel analyses showed that both sets of techniques were effective in reducing teacher-rated ADHD symptoms and impairment immediately after the intervention and up to three months later, as compared to waitlist. Masked observations of ADHD behavior were in line with teacher ratings, with effects being most pronounced for inattention. No effects on teacher-rated or masked ODD behavior were found. This study showed that antecedent- and consequent-based techniques were effective in improving classroom ADHD symptoms and impairment. Long-term changes in teacher-rated ADHD are promising. These results extend previous findings and show the potential of short individually tailored interventions in classroom settings as treatment of ADHD symptoms., (© 2022. The Author(s).)

Children with attention-deficit/hyperactivity disorder (ADHD) symptoms often experience social and emotional problems. Impaired facial emotion recognition has been suggested as a possible underlying mechanism, although impairments may depend on the type and intensity of emotions. We investigated facial emotion recognition in children with (subthreshold) ADHD and controls using a novel task with children's faces of emotional expressions varying in type and intensity. We further investigated associations between emotion recognition accuracy and social and emotional problems in the ADHD group. 83 children displaying ADHD symptoms and 30 controls (6-12 years) completed the Morphed Facial Emotion Recognition Task (MFERT). The MFERT assesses emotion recognition accuracy on four emotions using five expression intensity levels. Teachers and parents rated social and emotional problems on the Strengths and Difficulties Questionnaire. Repeated measures analysis of variance revealed that the ADHD group showed poorer emotion recognition accuracy compared to controls across emotions (small effect). The significant group by expression intensity interaction (small effect) showed that the increase in accuracy with increasing expression intensity was smaller in the ADHD group compared to controls. Multiple regression analyses within the ADHD group showed that emotion recognition accuracy was inversely related to social and emotional problems, but not prosocial behavior. Not only children with an ADHD diagnosis, but also children with subthreshold ADHD experience impairments in facial emotion recognition. This impairment is predictive for social and emotional problems, which may suggest that emotion recognition may contribute to the development of social and emotional problems in these children., (© 2021. The Author(s).)

Objective: Neurocognitive deficits are at the heart of explanatory models of attention-deficit/hyperactivity disorder (ADHD), and lead to significant impairments in daily life. Determining the dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigating possible impairing effects of high doses is therefore important., Method: Placebo-controlled trials were included that investigated MPH dosing effects on neurocognitive functions in children and adolescents (aged 5-18 years) diagnosed with ADHD. Effect sizes (standardized mean differences [SMDs]) were calculated for different neurocognitive functions (baseline speed, variability in responding, nonexecutive memory and executive memory, inhibitory control, and cognitive flexibility) and, if available, for ADHD symptoms. Meta-regression analysis were used to investigate linear effects of dose (mg/kg/dose), and separate meta-analyses compared SMDs for 3 MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose), and high (0.61-1.00 mg/kg/dose)., Results: A total of 31 studies fulfilled inclusion criteria, comprising 804 children with ADHD. Methylphenidate had beneficial effects on all neurocognitive functions (d = 0.20-0.73). Significant linear dosing effects were found for ADHD symptoms and lower-order neurocognitive functions (baseline speed, variability in responding, nonexecutive memory), with greater enhancement of functioning with increasing dose. No dosing effects were found for higher-order neurocognitive functions (executive memory, inhibitory control, and cognitive flexibility). No detrimental effects of MPH were found on any of the investigated functions., Conclusion: Methylphenidate was superior to placebo in improving ADHD symptoms and a broad range of neurocognitive functions; however, effects sizes regarding the effects of dose vary substantially between functions. Our data highlight the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Behavioral parent training is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but it is unknown which of its components are most effective. This meta-regression analysis investigated which specific behavioral techniques that parents learn in parent training are associated with effects on parental outcomes., Method: A search was performed for randomized controlled trials on parent training for children with ADHD, with positive parenting, negative parenting, parenting sense of competence, parent-child relationship quality, and parental mental health as outcome measures. After screening 23,026 publications, 29 studies contributing 138 effect sizes were included (N = 2,345). For each study, the dosage of 39 behavioral techniques was derived from intervention manuals, and meta-regression determined which techniques were related to outcomes., Results: Parent training had robust small- to medium-sized positive effects on all parental outcomes relative to control conditions, both for unblinded and probably blinded measures. A higher dosage of techniques focusing on the manipulation of antecedents of behavior was associated with better outcomes on parenting sense of competence and parental mental health, and a higher dosage of techniques focusing on reinforcement of desired behaviors was related to larger decreases in negative parenting. Higher dosages of psychoeducation were negatively related to parental outcomes., Conclusion: Although techniques were not investigated in isolation, the results suggested that manipulation of antecedents of behavior and reinforcement techniques are key components of parent training for children with ADHD in relation to parental outcomes. These exploratory findings may help to strengthen and tailor parent training interventions for children with ADHD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of the present study was to examine parental experiences of homeschooling during the COVID-19 pandemic in families with or without a child with a mental health condition across Europe. The study included 6720 parents recruited through schools, patient organizations and social media platforms (2002 parents with a child with a mental health condition and 4718 without) from seven European countries: the UK (n = 508), Sweden (n = 1436), Spain (n = 1491), Belgium (n = 508), the Netherlands (n = 324), Germany (n = 1662) and Italy (n = 794). Many parents reported negative effects of homeschooling for themselves and their child, and many found homeschooling to be of poor quality, with insufficient support from schools. In most countries, contact with teachers was limited, leaving parents with primary responsibility for managing homeschooling. Parents also reported increased levels of stress, worry, social isolation, and domestic conflict. A small number of parents reported increased parental alcohol/drug use. Some differences were found between countries and some negative experiences were more common in families with a child with a mental health condition. However, differences between countries and between families with and without a mental health condition were generally small, indicating that many parents across countries reported negative experiences. Some parents also reported positive experiences of homeschooling. The adverse effects of homeschooling will likely have a long-term impact and contribute to increased inequalities. Given that school closures may be less effective than other interventions, policymakers need to carefully consider the negative consequences of homeschooling during additional waves of the COVID-19 pandemic and future pandemics., (© 2021. The Author(s).)

Objective: Behavioral interventions are well established treatments for children with attention-deficit/hyperactivity disorder (ADHD). However, insight into moderators of treatment outcome is limited., Method: We conducted an individual participant data meta-analysis (IPDMA), including data of randomized controlled behavioral intervention trials for individuals with ADHD <18 years of age. Outcomes were symptoms of ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) and impairment. Moderators investigated were symptoms and impairment severity, medication use, age, IQ, sex, socioeconomic status, and single parenthood., Results: For raters most proximal to treatment, small- to medium-sized effects of behavioral interventions were found for symptoms of ADHD, inattention, hyperactivity/impulsivity (HI), ODD and CD, and impairment. Blinded outcomes were available only for small preschool subsamples and limited measures. CD symptoms and/or diagnosis moderated outcome on ADHD, HI, ODD, and CD symptoms. Single parenthood moderated ODD outcome, and ADHD severity moderated impairment outcome. Higher baseline CD or ADHD symptoms, a CD diagnosis, and single parenthood were related to worsening of symptoms in the untreated but not in the treated group, indicating a protective rather than an ameliorative effect of behavioral interventions for these children., Conclusion: Behavioral treatments are effective for reducing ADHD symptoms, behavioral problems, and impairment as reported by raters most proximal to treatment. Those who have severe CD or ADHD symptoms, a CD diagnosis, or are single parents should be prioritized for treatment, as they may evidence worsening of symptoms in the absence of intervention., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In some lockdowns during the COVID-19 pandemic in 2020 and 2021, schools were closed and children attended distance learning., Aim: To investigate parental experiences of the effects of distance learning on the wellbeing of child and parent(s), and whether this differed between children with and without mental health problems and their parents., Method: Parents of children with (n = 192) and without (n = 271) mental health problems reported their experiences with distance learning. We investigated whether experiences differed between groups of parents, and whether experiences were influenced by characteristics of parents., Results: Parents of children with mental health problems reported the quality of distance learning and the ability of their child to participate as lower relative to other parents. These differences increased when parents themselves were in higher need of support. General experiences and the levels of stress reported by parents did not differ between groups. Parents reported an increase in their child&rsquo;s digital media use, particularly for children with mental health problems., Conclusion: Children with mental health problems seem more negatively affected by distance learning, especially when parents have problems themselves. These findings are in line with multiple recent studies and argue for minimizing distance learning.

Objective: Behavioral parent training (BPT) is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but little is known about the effects of separate techniques parents learn in BPT., Method: In a three-armed randomized controlled microtrial including parents of 92 children (4-12 years) with ADHD, we examined the efficacy of two sessions parent training involving either stimulus control techniques (antecedent-based condition (AC)) or contingency management techniques (consequent-based condition (CC)), compared to a waitlist. Primary outcome was daily parent-rated problem behaviors, secondary outcomes were parent-rated symptoms of ADHD and oppositional defiant disorder (ODD), and mental health-care consumption. Measures were completed at baseline (T0), immediately after the training (T1), at two weeks (T2) and three months (T3) follow-up. We also explored whether child and parent characteristics moderated treatment effects., Results: Compared to the waitlist, in the AC, daily rated problem behaviors improved at T1 ( d = .56) and T2 ( d = .65); in the CC, these behaviors only improved at T2 ( d = .53). Daily rated problem behaviors within both conditions remained stable between T2 and T3. In the AC compared to the other conditions, inattention symptoms decreased at T1 and T2. For both active conditions compared to waitlist, hyperactivity-impulsivity symptoms decreased only at T2 and ODD symptoms did not decrease. No moderators were identified. Mental health-care consumption after training was low and did not differ between the active conditions., Conclusions: Brief training of parents in antecedent- or consequent-based techniques improves problem behaviors of children with ADHD. Antecedent-based techniques appear to be especially important to target inattention.

Objective : Behavioral teacher training is the most effective classroom-based intervention for children with attention-deficit/hyperactivity disorder (ADHD). However, it is currently unknown which components of this intervention add to its effectiveness and for whom these are effective. Method : In this microtrial, teachers of 90 children with impairing levels of ADHD symptoms (6-12 years) were randomly assigned to one of three conditions: a short (2 sessions), individualized intervention consisting of either (A) antecedent-based techniques (stimulus control), (B) consequent-based techniques (contingency management) or (C) waitlist. Primary outcome was the average of five daily assessments of four individualized problem behaviors, assessed pre and post intervention and three months later. Moderation analyses were conducted to generate hypotheses on child, teacher and classroom factors that may contribute to technique effectiveness. Results : Multilevel analyses showed that both antecedent- and consequent-based techniques were equally and highly effective in reducing problem behaviors compared to the control condition (Cohen's d =.9); effects remained stable up to three months later. Child's age and class size were moderators of technique effectiveness. For younger children, consequent-based techniques were more effective than antecedent-based techniques, whereas for older children the effect was in the opposite direction. Further, beneficial effects of antecedent-based techniques increased when the number of students per class decreased, whilst effectiveness of consequent-based techniques did not depend on class size. Conclusions : This study shows that both antecedent- and consequent-based techniques are highly effective in reducing problem behavior of children with ADHD. Interventions may be adapted to the child's age and class size.

Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is associated with several neurocognitive impairments. Whether these impairments influence the effectiveness of techniques that are commonly used in behavioral teacher training for ADHD has not been investigated so far., Method: In this microtrial, teachers of 90 children with ADHD symptoms (6-12 years) were randomly assigned to a short intervention consisting of either antecedent-based (stimulus-control) techniques or consequent-based (contingency management) techniques, or to a waitlist control condition. Primary outcome was the daily assessment of individually selected problem behavior, assessed pre- and post-intervention. Potential neurocognitive moderators of treatment effect included teacher ratings of cognitive control, reward, and punishment sensitivity, and measures derived from computerized neurocognitive tasks, including attentional lapses, interference control, visuospatial working memory, and emotional functioning. Intervention condition by moderator interactions were assessed in separate multilevel mixed models., Results: Lapses of attention, working memory, and emotional functioning interacted with intervention effectiveness. Antecedent-based techniques were effective independent of these neurocognitive functions; consequent-based techniques were (more) effective when these functions were more impaired. The effectiveness of techniques was neither related to interference control nor to teacher-rated neurocognitive functioning., Conclusions: This study showed that child neurocognitive functioning influences the effectiveness of behavioral teacher techniques for children with ADHD symptoms. Findings suggest that antecedent-based techniques may be effective for all children, while consequent-based techniques have added value particularly for children who suffer from low visuospatial working memory, low emotional functioning, and/or large numbers of attentional lapses., Competing Interests: The authors report no conflict of interest., (© 2021 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objective: To assess attention-deficit/hyperactivity disorder (ADHD) symptoms in the classroom, most often teacher rating scales are used. However, clinical interviews and observations are recommended as gold standard assessment. This systematic review and meta-analysis evaluates the validity of teacher rating scales. Method: Twenty-two studies ( N = 3,947 children) assessing ADHD symptoms using teacher rating scale and either semi-structured clinical interview or structured classroom observation were meta-analyzed. Results: Results showed convergent validity for rating scale scores, with the strongest correlations ( r = .55-.64) for validation against interviews, and for hyperactive-impulsive behavior. Divergent validity was confirmed for teacher ratings validated against interviews, whereas validated against observations this was confirmed for inattention only. Conclusion: Teacher rating scales appear a valid and time-efficient measure to assess classroom ADHD; although validated against semi-structured clinical interviews, there were only a few studies available. Low correlations between ratings and structured observations of inattention suggest that observations could add information above rating scales.

Serotonin (5-HT) is an important factor for prenatal neurodevelopment whereby its neurotrophic actions can be regulated through maternal-fetal interactions. We explored if maternal 5-HTTLPR genotype is associated with clinical and cognitive measures of attention-deficit/hyperactivity disorder (ADHD) and comorbid autism spectrum disorder (ASD) in typically-developing and ADHD-diagnosed offspring, beyond classical inheritance and environmental- and comorbidity-mediators/confounders. Family-based variance decomposition analyses were performed incorporating 6-31 year-old offsprings' as well as parental genotypes of 462 ADHD and control families from the NeuroIMAGE cohort. Dependent measures were offsprings' ADHD symptom- and ASD trait-scores and cognitive measures including executive functioning (including response inhibition and cognitive flexibility), sustained attention, reward processing, motor control, and emotion recognition. Offsprings' stereotyped behavior was predicted by an interaction between maternal 5-HTTLPR genotype and offsprings' sex. Furthermore, offspring of mothers with low-expressing genotypes demonstrated larger reward-related reductions in reaction time. While specifically adult male offspring of these mothers reported a faster reversal learning with less errors, specifically young female offspring of these mothers were more accurate in identifying happy faces. Adult offspring from the mothers with low-expressing 5-HTTLPR genotypes were also slower in identifying happy faces. However, this association seemed to be mediated by offsprings' high anxiety levels. In sum, we found some support for a role of the maternal 5-HT system in modulating fetal brain development and behavior. Offsprings' cognitive measures might be more sensitive to small alterations within the maternal 5-HT system than their ADHD and ASD clinical phenotypes. Further studies are needed to specify the association between maternal genotype and risk for neurodevelopmental disorders., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The current study examined instrumental learning in ADHD. Method: A total of 58 children with ADHD and 58 typically developing (TD) children performed a probabilistic learning task using three reward probability conditions (100%, 85%, 70% reward). After a learning phase, application of what was learned was assessed in a test phase. Results: Results showed that children with ADHD performed less accurate compared with TD children during the learning phase, particularly in the 100% and 85% reward probability conditions. These findings were accompanied by a blunted learning rate in the first few task trials. Furthermore, children with ADHD showed poorer application of what was learned. Conclusion: To conclude, children with ADHD show initial learning problems, but increased performance in a similar manner as TD children independent of the probability of reward, although they fail to apply their knowledge. Findings are of clinical relevance as the application of knowledge is important to successfully adapt to daily challenges in life.

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of β2-microglobulin (β2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of β2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated β2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of β2M were not statistically different ( p > 0.35). Dialytic elimination of MM uremic toxin β2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.

Background: There is an increased interest in 'late-onset' attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood., Methods: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning., Results: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks., Conclusions: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD., (© 2020 Association for Child and Adolescent Mental Health.)

Introduction: Behavioural parent training (BPT) is a well-established treatment for children with attention-deficit/hyperactivity disorder (ADHD). BPT is based on the hypothesis that improvements in parenting are mediators of improvements in children's behaviours. However, meta-analyses show considerate heterogeneity in effects of BPT on child outcomes, and meta-analyses on parenting outcomes are scarce. Also, few studies have investigated parenting factors as mediators of child outcomes. This study aims to examine the effects and moderators of BPT on parenting outcomes and whether improvements in parenting mediate amelioration of behaviour and impairment in children with ADHD., Methods and Analyses: We will conduct an individual participant data meta-analysis (IPDMA), making use of individual data of existing trials, and giving the opportunity for highly powered moderator analyses. This IPDMA will be performed by the Psychosocial ADHD INTervention (PAINT) collaboration. We will include randomised controlled trials of BPT, for individuals with ADHD below 18 years old. Systematic searches have been performed to locate relevant papers. Authors are currently contacted to share their data with the PAINT-IPDMA project. We will examine effects of BPT on parenting outcomes (eg, positive and negative parenting, management of affect, perceived parenting competence, parenting stress), moderators of these effects (eg, parental depression, parenting stress, severity of the child's ADHD symptoms) and subsequently perform mediation analyses where parenting outcomes are modelled as mediators of child outcomes (eg, symptoms and severity of ADHD, comorbid psychopathology and impairment)., Ethics and Dissemination: We will include data from randomised control trials for which ethical approval has been received and consent forms have been signed. Deidentified data will be provided by the original investigators. We aim to disseminate our findings through peer-reviewed scientific journals, presentations at (inter)national scientific meetings, newsletters, the website of our project and the Dutch academic workspace ADHD., Prospero Registration Number: CRD42017069877., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: This study investigated whether improvements in working memory, reaction time, lapses of attention, interference control, academic motivation, and perceived competence mediated effects of methylphenidate on math performance. Method: Sixty-three children (ADHD diagnosis; methylphenidate treatment; age 8-13; IQ > 70) were randomly allocated to a 7-day methylphenidate or placebo treatment in this double-blind placebo-controlled crossover study and compared with 67 controls. Data were collected at schools and analyzed using mixed-model analysis. Methylphenidate was hypothesized to improve all measures; all measures were evaluated as potential mediators of methylphenidate-related math improvements. Results: Controls mostly outperformed the ADHD group. Methylphenidate did not affect measures of cognitive functioning ( p = .082-.641) or academic motivation ( p = .199-.865). Methylphenidate improved parent ratings of their child's self-perceived competence ( p < .01), which mediated methylphenidate efficacy on math productivity. Conclusion: These results question the necessity of improvements in specific cognitive and motivational deficits associated with ADHD for medication-related academic improvement. They also stimulate further study of perceived competence as a mediator.

Objective: Oppositional Defiant Disorder (ODD) is highly prevalent in Attention-Deficit/Hyperactivity Disorder (ADHD) and may account for inconsistencies in findings on neurocognitive functioning in ADHD. Our aim was to assess cool and hot executive functioning (EF) and temporal processing in ADHD with and without comorbid ODD to elucidate the effects of comorbid ODD. Method: ADHD-only ( n = 82), ADHD + ODD ( n = 82), and controls ( n = 82), with mean age 16 years ( SD = 3.1), matched for age, gender, IQ, and ADHD type (clinical groups) were assessed on cool EF (inhibition, working memory), hot EF (reinforcement processing, emotion recognition), and temporal processing (time production and reproduction). Results: Individuals with ADHD + ODD showed abnormalities in inhibition, working memory, facial emotion recognition, and temporal processing, whereas individuals with ADHD-only were solely impaired in working memory and time production. Conclusion: Findings suggest that ODD carries a substantial part of the EF deficits observed in ADHD and contrast with current theories of neurocognitive impairments in ADHD.

In this study, simultaneous removal assessment of marker molecules from three uremic toxin groups was performed during different hemodialysis treatment modalities using optical characteristics of spent dialysate. Results from optical measurements were compared with the results from chemical laboratory. Ten chronic dialysis patients, mean age 59 ± 15 years, were included in the study during 40 hemodialysis sessions. Low-flux hemodialysis (HD), high-flux hemodialysis (HF), and postdilutional online hemodiafiltration (HDF) with different settings were used. The reduction ratio (RR) and total removed solute (TRS) of three uremic solutes were determined: small molecular weight urea, middle molecular β2-microglobulin (B2M), and protein-bound indoxyl sulfate (IS). Concentrations of these solutes in the spent dialysate were measured by laboratory (lab) and optical (opt) methods, in the serum by laboratory methods, and calculated RR values in percentage were compared accordingly. Total removed solute was obtained from the total dialysate collection (TDC) using lab and opt methods. The highest RR values were found for urea and B2M, and the lowest for IS. The difference between RR of lab and opt results estimated as mean accuracy (BIAS) was ≤8.1% for all three solutes. Good correspondence between TRS lab vs. opt was achieved, resulting in strong linear correlation values R from 0.727 for urea to 0.971 for IS. Accuracy for TRS values as BIAS ± standard error (SE), comparing lab vs. opt, showed no statistical difference for any of the observed uremic solutes (P > 0.05). The accuracy of the optical method was not influenced by the dialysis modality (HD, HF, and HDF).

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session ( p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis ( p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.

Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence (ND). It remains unclear whether and how stimulant treatment may affect this risk. We aimed to investigate how stimulant use profiles influence the risk of SUDs and ND, using a novel data-driven community detection analysis to construct different stimulant use profiles. Comprehensive lifetime stimulant prescription data and data on SUDs and ND were available for 303 subjects with ADHD and 219 controls, with a mean age 16.3 years. Community detection was used to define subgroups based on multiple indicators of treatment history, start age, treatment duration, total dose, maximum dose, variability, stop age. In stimulant-treated participants, three subgroups with distinct medication trajectories were distinguished (late-and-moderately dosed, n = 91; early-and-moderately dosed, n = 51; early-and-intensely dosed, n = 103). Compared to stimulant-naïve participants (n = 58), the early-and-intense treatment group had a significantly lower risk of SUDs and ND (HR = 0.28, and HR = 0.29, respectively), while the early-and-moderate group had a significantly lower risk of ND only (HR = 0.30). The late-and-moderate group was at a significantly higher risk of ND compared to the other two treatment groups (HR = 2.66 for early-and-moderate, HR = 2.78 for early-and-intense). Our findings show that in stimulant-treated adolescents with ADHD, long-term outcomes are associated with treatment characteristics, something that is often ignored when treated individuals are compared to untreated individuals.