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Background: Sleep problems are common in adults with ADHD and may be bidirectionally associated with ADHD severity and other psychiatric symptoms. We investigated the prevalence of positive screenings for various sleep disorders, and their association with psychiatric comorbidities in a large sample of adults with ADHD from a specialized outpatient clinic. Methods: We included data of 3,691 adult patients diagnosed with ADHD, who had filled out a screener for sleep disorders (Holland Sleep Disorders Questionnaire (HSDQ)) as part of routine diagnostic assessment. The HSDQ screens for the sleep disorders insomnia, parasomnia, hypersomnia, circadian rhythm sleep disorders (CRSD), restless legs syndrome (RLS)/periodic limb movement disorder (PLMD), and sleep-related breathing disorders (SBD). As delayed sleep phase syndrome (DSPS) is very frequent in ADHD, we additionally screened for DSPS. Psychiatric comorbidities were diagnosed through clinical assessment and the Mini International Neuropsychiatric Interview (M.I.N.I.) Plus, which assesses 26 psychiatric disorders following the classification of the DSM-5. All data were retrieved from the electronic patient files. Results: Mean age was 35.4 and 49.4% of the patients were female. About 60% of the adults with ADHD screened positive for any sleep disorder. Highest prevalences were found for symptoms of DSPS (36%), insomnia (30%), and RLS/ PLMD (29%). Sleep problems in adults with ADHD were associated with comorbid depression, anxiety, substance use disorder, personality disorder, and post-traumatic stress disorder. Conclusion: Adults with ADHD often report sleep problems, which are associated with specific psychiatric comorbidities. Systematic screening for sleep disorders in adult patients with ADHD can contribute to a better understanding of their complaints and may aid improved and integrated treatment for the sleep and psychiatric problems.

Background: ADHD is highly comorbid with Delayed Sleep Phase Syndrome (DSPS). Both are associated with obesity and diabetes, which can be caused by long-term dysregulations of appetite and glucose metabolism. This study explores hormones involved in these processes and the effects of chronotherapeutic interventions in a small sample of adults with ADHD and DSPS. Methods: Exploratory, secondary analysis of data from the PhASE study, a three-armed randomized clinical trial, are presented, including 37 adults (18-53 years) with ADHD and DSPS receiving three weeks of 0.5 mg/day (1) placebo, (2) melatonin, or (3) melatonin plus 30 minutes of bright light therapy (BLT). Leptin (appetite-suppressing), ghrelin (appetite-stimulating), insulin, insulin-like growth factor-1 (IGF-1), and glucose were measured from blood collected at 08:00 hours. Salivary cortisol was collected during the first 30 minutes after awakening and self-reported appetite was assessed. Results: Baseline leptin and IGF-1 levels were higher than reference ranges, and ghrelin and cortisol levels were lower, while insulin and glucose were normal. Melatonin treatment decreased leptin and insulin. Other outcomes remained unchanged and melatonin + BLT had no effects. Conclusion: Due to the small sample size and exploratory nature of the study, results should be interpreted with caution. Overall, these results show no strong indications for dysregulation of appetite and glucose metabolism to suggest high risk of obesity and diabetes in this small sample of adults with ADHD and DSPS. However, baseline appetite was suppressed, likely because measurements took place in the early morning which could be considered the biological night for this study population. Melatonin treatment seemed to cause subtle changes in appetite-regulating hormones suggesting increased appetite. Chronotherapeutic treatment may affect appetite-regulating hormones by advancing the biological rhythm and/or altering eating behaviors, but this remains to be investigated in larger samples using detailed food diaries.

In the past 40 years, accumulating evidence suggested that autistic individuals are at an increased risk of suicidal thoughts and behaviors. This study examined the occurrence of various potential risk factors for lifetime suicidal behavior and suicidal thoughts in the past month in a Dutch cohort (Netherlands Autism Register) of autistic individuals using the Suicidal Behaviors Questionnaire (SBQ-R) and the Suicidal Ideation Attributes Scale (SIDAS). Our results show that the majority (80%) of the initial sample (N = 1164) had thought about or attempted suicide in their lifetime, of which 15% had attempted suicide. In the final sample (n = 421), backward linear regression analyses identified the following predictors for suicidal behavior: psychiatric comorbidity, loneliness, and higher number of autistic traits, F(3, 240) = 21.22, p < 0.001, with R[superscript 2] of 0.21. For suicidal thoughts in the past month, psychiatric comorbidity and a higher number of autistic traits were significant predictors, F(2, 241) = 20.34, p < 0.001, with R[superscript 2] of 0.14. In sum, additional risk markers for suicidal thoughts and behaviors in autistic individuals (e.g. number of autistic traits) should be considered when assessing the suicide risk in autistic individuals. Future research should focus on adapting suicide prevention interventions for autistic individuals, such as addressing loneliness as one of the intervention strategies.

Autistic adults experience high rates of unemployment, yet research investigating what predicts employment success produces inconsistent results. By utilising longitudinal person-oriented analyses, this study aimed to identify employment trajectories of autistic adults to better understand what may predict stable autistic employment. Participants were 2449 autistic adults (1077 men, 1352 women, 20 non-binary, M = 42.25 years, SD = 14.24), recruited via the Netherlands Autism Register. Latent class analysis utilising employment status across eight annual waves was used to identify longitudinal employment profiles. Fit indices and the interpretability of results indicated a four-class model best fit the data, with profiles reflecting stable unemployment (n = 1189), stable employment (n = 801), early unemployment increasing in probability of employment (n = 183) and high probability of employment reducing across time to low employment (n = 134). Multinominal analyses suggested that compared to the 'stable unemployment' group, membership in the 'stable employment' profile was predicted by fewer autistic traits, lower age, male gender, higher education and diagnosis age, and fewer co-occurring conditions. Higher education predicted both other profiles, with lower age and fewer co-occurring conditions predicting membership in the increasing employment class. Taken together, findings highlight the utility of person-oriented approaches in understanding the longitudinal challenges autistic adults experience maintaining employment and identifies key areas of support.

Gastrointestinal symptoms and their relation to physical and mental aspects in adults with an autism spectrum disorder (ASD) are poorly understood, despite their high prevalence. Therefore, the aim of this study is to examine psychological, behavioural and biological factors associated with gastrointestinal symptoms in adults with ASD (traits). We included 31,185 adults from the Lifelines Study. Using multivariable logistic regression, we analysed the association between gastrointestinal symptoms and psychological, behavioural (questionnaire-assessed) and physically measured biological factors in adults with ASD (n = 309), without ASD (n = 30,876), and in the quartiles with highest (n = 7783) and lowest (n = 7783) Autism Spectrum Quotient-10 sum scores. In the ASD-group, gastrointestinal symptoms were associated with psychiatric comorbidity (odds ratio: 2.71, 95% confidence interval: 1.51-4.85), more stress (odds ratio: 1.15, 95% confidence interval: 1.06-1.26), and worse perceived health (odds ratio: 2.32, 95% confidence interval: 1.62-3.34). In the quartile with the highest Autism Spectrum Quotient-10 sum scores, gastrointestinal symptoms were also associated with these psychological factors, and with less physical activity (odds ratio: 0.95, 95% confidence interval: 0.92-0.98). Our study demonstrates that not only adults with ASD but also adults with autistic traits are at increased risk for gastrointestinal symptoms, which is associated with psychological and behavioural factors. This suggests that an integrated psychosomatic approach of gastrointestinal symptoms in adults with ASD (traits) is needed.

Autism is a heterogeneous diagnosis with symptoms that present in different ways. There is a large variety of interventions for autistic individuals. However, little is known about who chooses which specific interventions. We aimed to explore intervention prevalence and predict intervention use, based on demographic and autism-specific characteristics. This study used data on autistic children (N = 1464, aged 1-17 years) from the Netherlands Autism Register. Most children (88%) had received therapies, and about half had received medication. Intervention use was mostly related to additional factors (lower IQ, special education and co-occurring diagnoses). Children with a lower IQ received less therapies, children attending special education or with a co-occurring diagnosis received more therapies. Children in special education or with a co-occurring diagnosis were more likely to receive several types of therapy and medication. Older age, higher IQ and being female were related to more guideline (autism-specific) or mainstream (targeting co-occurring problems) therapy use. Lower parental education was related to more mainstream medication use. More severe sensory issues increased the chance of other medication use. Other autism-specific characteristics (autism severity, social skills, repetitive and restrictive behaviours) were not related to intervention use. More transdiagnostic interventions should be available for children with autism who have additional difficulties.

Widespread use of the Internet in 21st century society is not risk-free. This paper studies the comorbidity of some problematic uses of Internet with depression in order to assess their correlation. With that aim, a meta-analysis of 19 samples obtained from 13 different studies (n=33,458) was carried out. The subjects of these studies are adolescents between the ages of 12 and 18 years ([mu]=15.68) from different cultures and continents (Europe, Euro-Asia, America and Asia). The effect size obtained from the use of a random-effects model (r=0.3, p<0.000) is significant, moderate and positive, thus confirming the relation between pathologic uses of the Internet and depression. Moreover, meta-regression test results showed that 9% of the variance (R2=0.09) is associated with the male gender, while age and culture are not significant variables. The variability rate of the studies is high (I2=87.085%), as a consequence of heterogeneity rather than publication bias, as Egger's regression test shows (1-tailed p-value=0.25; 2-tailed p-value=0.50, and [sigma]=1.57). Therefore, the need for specific interventions in secondary education dealing with this issue is evident to ensure that it does not extend into adult life.

Introduction: Diagnosing dementia in people with severe/profound intellectual (and multiple) disabilities (SPI(M)D) is complex. Whereas existing dementia screening instruments as a whole are unsuitable for this population, a number of individual items may apply. Therefore, this study aimed to identify applicable items in existing dementia screening instruments. Methods: Informant interviews about 40 people with SPI(M)D were conducted to identify applicable items in the Dementia Scale for Down Syndrome, Behavioral and Psychological Symptoms of Dementia in Down Syndrome II scale, Dementia Questionnaire for persons with Mental Retardation and Social competence Rating scale for people with Intellectual Disabilities. Results: Among 193 items, 101 items were found applicable, categorized in 5 domains: behavioral and psychological functioning (60 items), cognitive functioning (25), motor functioning (6), activities of daily living (5) and medical comorbidities (5). Conclusion: Identifying applicable items for people with SPI(M)D is an essential step in developing a dedicated dementia screening instrument for this population.

A retrospective chart study of patients on open-label aripiprazole treatment was conducted in the Netherlands to add to the knowledge of aripiprazole in children and young adults with mild and borderline intellectual disabilities (IDs). Fifty-three youths, mean age 14.7 ± 3.4 years and mean IQ 64.5 ±13.8, were included. Treatment responders were defined as "much improved" or "very much improved" based on the Clinical Global Impression-Improvement scale. For 83% of the patients, disruptive behavior was the main target symptom. The overall response rate was 30% after 1-4 weeks and 69% after 5-8 weeks. The 5-8 weeks responders showed a response rate of 64% at 22-26 weeks. Mild adverse events were observed in 53% of the patients of which fatigue and weight gain were the most common. Seven patients (13.2%) discontinued because of adverse events. In 53 children and young adults with mild and borderline IDs, aripiprazole was effective in both the short and the long term. No serious adverse events were observed.

Adolescents, particularly those with autism spectrum disorders, increasingly use psychiatric emergency services. Such risk is further greater in girls. Available knowledge on young people with autism during crises lacks understanding of gender differences and of differences between typically developing adolescents and adolescents with autism. After psychiatric emergency consultations, we therefore compared the symptomatology and comorbidity of girls and boys with autism, and also to their typically developing male and female counterparts. We used registry data (2009-2017) on 1378 adolescents aged 12-18 years referred for urgent consultation to mobile psychiatric emergency services. This showed an increase in diagnoses of autism spectrum disorder from 7.9% in 2009 to 18.1% in 2016; autistic girls showed a steeper increase than autistic boys. A higher percentage of girls than boys with autism presented with comorbid anxiety disorders and a higher risk of suicide or self-harm, while the persistence of their complaints over time was rated lower. Adolescents with autism experienced more severe impairment in overall functioning, while being diagnosed less often with comorbid disorders as compared to typically developing adolescents. Outpatient care for autistic youth should include easy access to specialized professionals to help young people with autism cope with the challenges of adolescence.

Autistic individuals may be at risk of premature mortality, and physical health comorbidity increases this risk; however, most studies fail to include older autistic adults or consider lifestyle-related factors that affect health. We developed an anonymous, online physical health survey. The final sample included n = 2368 individuals (mean age = 41.42), and of these, n = 1156 were autistic individuals (mean age = 40.98). We utilized three sex-stratified statistical models to determine the prevalence of cancer, cardiovascular conditions, respiratory conditions, and diabetes. All three models indicate that autistic females are more likely to have cardiovascular conditions, respiratory conditions, asthma, low blood pressure, arrhythmias, and prediabetes than non-autistic females, and autistic males are more likely to have arrhythmias than non-autistic males; these results suggest that autistic individuals carry increased risks for these conditions when compared to the general population, even after controlling for age, ethnicity, education level, body mass index, smoking, and alcohol use. Further, these risks may differ depending on biological sex for autistic individuals. Autistic adults, and particularly autistic females, have greater and wider-ranging risks than previously thought, even after controlling for demographic and lifestyle-related factors. Although this is a large sample of autistic adults across the lifespan, future research should employ larger, population-based samples to confirm these findings.

Although the link between self-esteem and psychopathology has been well established, studies on self-esteem in individuals with autism spectrum disorder are lacking. In this study, we aimed to (1) compare explicit and implicit self-esteem of youth with autism spectrum disorder to typically developing peers and to (2) explore relationships of implicit-, explicit-, and discrepant self-esteem measures with co-occurring internalizing and externalizing problems in youth with autism spectrum disorder. For this purpose, 25 individuals with autism spectrum disorder and 24 individuals as age and intelligence quotient--matched controls aged 8-16 years participated in this study. Results showed lower explicit self-esteem in autism spectrum disorder compared to typically developing youth and no differences in implicit self-esteem between groups. In youth with autism spectrum disorder, low explicit self-esteem was related to co-occurring depression symptoms, whereas lower implicit self-esteem was related to externalizing symptoms. These results show that youth with autism spectrum disorder are at risk for developing low explicit self-esteem, which appears to be related to often co-occurring internalizing symptoms. This emphasizes the need to focus more on self-esteem in assessment and treatment of youth with autism spectrum disorder.

Background: There is a need to systematically compare and contrast mortality predictors and disparities in people with intellectual disabilities (ID) for global prevention strategy development. Method: Bibliographic databases and grey literature were searched using systematic review methodology and the machine learning tool "Abstrackr." Results: Fifty-four relevant articles and reports published from 2010 to 2019 were identified. Nearly all (n = 53) were from high-income countries. Mortality disparities were apparent and consistent across countries and publication years, with no evidence of a decrease over time. People with ID can still expect to live 12-23 years less than the general population and are particularly vulnerable to deaths from respiratory infections and epilepsy. Conclusions: Both population and individual-level approaches to prevention are indicated to tackle the continuing mortality disparities in people with ID, including consideration of reasonable adjustments in general population efforts to reduce health inequalities.

Introduction: Families have a significant role in the lives of people with intellectual disabilities and challenging behaviors. However, it is not clear how actively families are involved when people with intellectual disabilities and challenging behaviors are living in out-of-home care. This scoping review explored the frequency and type of family involvement in the application of a person-centered approach in the care for people with intellectual disabilities and challenging behaviors. Methods: Authors conducted electronic searches through six databases: Embase, Medline, Web of Science, PsycINFO, Cochrane Central, and Google Scholar (2005 to 2019) and evaluated relevant publications. Results: Based on the 15 articles identified, only five articles report on family involvement. In addition, frequency of contact, and how family is involved appears to differ between different person-centered approaches. Conclusion: More active family involvement in person-centered approaches for people with intellectual disabilities and challenging behaviors is recommended.

Autism spectrum disorder and anxiety are highly comorbid conditions. Understanding the underlying traits of anxiety in autism spectrum disorder is crucial to prevent and treat it efficiently. Hence, this study determined whether social communication difficulties or restricted repetitive behaviors are stronger risk factors for anxiety symptoms in autistic adults in a large cohort. Data on 742 autistic adults from the Netherlands Autism Register were included in the study. Hierarchical regression was implemented to evaluate whether social communication difficulties (Autism-Spectrum Quotient social behavior factor) and restricted repetitive behaviors (Adult Routines Inventory) were predictive of anxiety (Hospital Anxiety and Depression Scale) controlling for age and sex. When considered together, restricted repetitive behaviors stood out as significant positive predictors of anxiety symptoms (lower-order restricted repetitive behaviors, [Beta] = 0.32, p < 0.001; higher-order restricted repetitive behaviors, [Beta] = 0.15, p = 0.001), whereas social communication difficulties did not ([Beta] = 0.06, p = 0.11). Sex did not moderate these associations (p > 0.05). Non-social autistic traits are stronger predictors of anxiety symptoms than social traits in autistic adults. Increased attention to restricted repetitive behaviors should be given to improve current support programs for autistic adults with anxiety and to identify autistic individuals at risk.

Autism and depression often co-occur. Through network analysis, we seek to gain a better understanding of this co-occurrence by investigating whether (1) autism and depression share overlapping groups of symptoms and/or (2) are connected through a bridge of mastery or worry symptoms. This is addressed in two complimentary studies: (1) Study 1 focusing on depressed (N = 258) and non-depressed adults (N = 117), aged 60-90 years; (2) Study 2 focusing on autistic (N = 173) and non-autistic adults (N = 70), aged 31-89 years. Self-report questionnaire data were collected on autistic traits (AQ-28), depression symptoms (Study 1: Inventory of Depressive Symptomatology Self Report; Study 2: Symptom Checklist 90--Revised depression subscale), worry (Worry Scale-R) and mastery (the Pearlin Mastery Scale). For both studies, data were analysed by creating glasso networks and subsequent centrality analyses to identify the most influential variables in the respective networks. Both depressed and autistic adults are highly similar in the perceived amount of worries and lack of control. While caution is needed when interpreting the pattern of findings given the bootstrapping results, findings from both studies indicate that overlapping symptoms do not fully explain the co-occurrence of autism and depression and the perception of having control over your life, that is, mastery seems a relevant factor in connecting autism and depression.

Phenotypic elements of autism spectrum disorder can be masked by attention-deficit/hyperactivity disorder symptoms, potentially leading to a misdiagnosis or delaying an autism spectrum disorder diagnosis. This study explored differences in the age of autism spectrum disorder diagnosis between participants with previously diagnosed attention-deficit/hyperactivity disorder versus autism spectrum disorder-only respondents. Children and adolescents, but not adults, initially diagnosed with attention-deficit/hyperactivity disorder received an autism spectrum disorder diagnosis an average of 1.8 years later than autism spectrum disorder--only children, although the findings regarding the adult sample should be interpreted with caution. Gender differences were also explored, revealing that the delay in receiving an autism diagnosis was 1.5 years in boys and 2.6 years in girls with pre-existing attention-deficit/hyperactivity disorder, compared with boys and girls without prior attention-deficit/hyperactivity disorder. No significant gender differences were observed in the adult sample. We argue that overlapping symptoms between autism spectrum disorder and attention-deficit/hyperactivity disorder might delay a formal diagnosis of autism either by leading to a misdiagnosis of attention-deficit/hyperactivity disorder or by making it difficult to identify the presence of co-occurring autism spectrum disorder conditions once an initial diagnosis of attention-deficit/hyperactivity disorder has been obtained. Current findings highlight the need to recruit multidimensional and multidisciplinary screening procedures to assess for potential emerging autism spectrum disorder hallmarks in children and adolescents diagnosed or presenting with attention-deficit/hyperactivity disorder symptoms.

The high rates of comorbidity with substance use disorders in general psychiatry patients demand enhanced competences from psychiatry residents in addiction medicine. The aim of this article is to improve knowledge, skills and attitudes in psychiatric residents in treating patients with comorbid substance-related disorders (SUD). Four seminars with all residents on relevant and actual knowledge on substance-related disorders and a small group experience of five sessions on improving skills and attitudes in dealing with patients are described and evaluated quantitatively and qualitatively. Both quantitative evaluations show that seminars and small group experiences are highly appreciated. Concerning the seminar, residents appreciated, in particular, to study and present selected up-to-date literature and the positive learning environment. The small group experience resulted in sharing feelings and thoughts about patients with SUD and mutual support. The results show that the goals of these two methods of education have been met. This means that these two methods can be integrated in the training of residents in psychiatry to increase knowledge, skills and attitudes concerning addiction.

Two explanations for resolving dyslexia were investigated, one assuming resolving underlying deficits and another assuming compensatory mechanisms based on cognitive strengths. Thirty-six Dutch gifted secondary-school students with either persistent (n = 18) or resolving (n = 18) dyslexia participated. Groups, matched on IQ, were assessed on dyslexia- and intelligence-related cognitive risk and protective factors. Findings for the risk factors showed support for both the resolving-deficit and compensatory-mechanism theories: Resolving and persistent groups were comparable on phoneme deletion and nonalphanumeric rapid automatized naming, but resolvers outperformed students with persistent dyslexia on spoonerisms and alphanumeric rapid automatized naming. For the protective factors, resolvers consistently showed more pronounced cognitive strengths in verbal areas relevant for literacy development, which is in line with the compensatory-mechanism theory. We conclude that, besides underlying deficits resolving to some extent, compensation is a plausible explanation for resolving literacy difficulties in gifted students.

Children and adolescents with Autism Spectrum Disorder (ASD) often show comorbid emotional and behavior problems. The aim of this longitudinal study is to examine the relation between emotion control (i.e., negative emotionality, emotion awareness, and worry/rumination) and the development of internalizing and externalizing problems. Boys with and without ASD (N = 157; age 9-15) were followed over a period of 1.5 years (3 waves). We found that baseline levels of worry/rumination was a specific predictor of later externalizing problems for boys with ASD. Furthermore, the developmental trajectory of worry/rumination predicted the development of internalizing and externalizing problems in both groups. Our findings suggest that worry/rumination may constitute a transdiagnostic factor underlying both internalizing and externalizing problems in boys with and without ASD.

Studies have shown an increase of symptoms of autism spectrum disorder (ASD) in gender dysphoria (GD). Various hypotheses try to explain this possible co-occurrence (e.g., a role of resistance to change, stereotyped behaviors or prenatal testosterone exposure). This study examined ASD symptoms with the Children's Social Behavior Questionnaire (CSBQ) in 490 children with GD compared to 2507 typically developing (TD) and 196 children with ASD. CSBQ total scores of the GD sample were in between scores from the TD and ASD sample. The GD sample showed elevated levels of autistic symptomatology on all subdomains, not only on stereotyped and resistance to change. Further, no gender differences and interaction effects were found on the total CSBQ, making a sole role for prenatal testosterone unlikely.

The aim of this study was to examine developmental links between disobedience and teacher-child closeness in a sample of boys with psychiatric disorders (i.e., emotional and behavioral disorders (EBD) and autism spectrum disorders (ASD)) and special educational needs who are placed in special education. More specifically, this study examined whether developmental links were different between boys with EBD (n = 150) versus boys with ASD (n = 122). Developmental links between disobedience and teacher-child closeness were investigated by incorporating a multi-informant perspective using teacher, child, and peer ratings and analyzed using autoregressive cross-lagged models across three waves within one school year. Results showed that in general, developmental links between teacher-child closeness and disobedience were stronger for boys with EBD than for boys with ASD. Specifically, boys with EBD experiencing less teacher-child closeness showed more disobedience, which in turn negatively affected their relationship development according to teacher ratings. Surprisingly, for boys with ASD, higher levels of disobedience predicted higher levels of teacher-rated teacher-child closeness during the school year. Our results offer more insight into the differential impact of teacher-child closeness on the behavioral problems for children with EBD and ASD.

The study aimed to explore predictors of treatment effectiveness in a sample of 79 children with ASD who received cognitive behavioral therapy (CBT) for their anxiety disorders. Severity of anxiety disorders and anxiety symptoms were used to measure treatment effectiveness and was assessed pre-treatment, post-treatment, 3 months-, 1 and 2 years after CBT. Child characteristics and maternal anxiety did not predict treatment effect. Children with anxious fathers and children in "un-involved" families had less anxiety symptoms at pre-treatment and displayed a less steep decline. Children from "authoritarian" families showed higher pre-treatment anxiety levels but responded quite well to treatment. Findings stress the importance of parent (father) and family factors in the treatment of anxiety disorders in youth with ASD.

Employing a large sample of children from Dutch regular elementary schools, this study assessed the contributing and discriminating values of reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD) to two types of phonological processing skills, phonemic awareness (PA) and rapid automatized naming (RAN). A second objective was to investigate whether comorbidity of RD and ADHD should be considered as an additive phenomenon as to RAN and PA. A total of 1,262 children, aged 8 to 13 years, were classified as RD (n = 121), ADHD (n = 17), comorbid (RD+ADHD; n = 16), or control (n = 1,108). Phonological processing was assessed by standardized tests of PA and RAN. Disability groups were compared to each other and contrasted to the control group. Although results indicate substantial effects for all three disability groups on both types of phonological processing, and the RAN/PA compound measure in particular, effect sizes were considerably larger for the RD groups, as compared to the ADHD-only group. Theoretical and practical implications are discussed.

Accurate population rates of depression can inform allocation of health resources and service planning, to counter the impact of depression on quality of life and morbidity. A systematic review of the rates of depression in children and adults with autism spectrum disorders (ASD) and without intellectual disability (high-functioning [HF] ASD) was conducted. Nineteen studies met inclusion criteria. Reported rates of depression varied; the reasons for this are discussed including availability of psychometrically valid and reliable measures of depression for people with HF ASD, and heterogeneity of study design. Further examination of the phenomenology of depression in HF ASD linked to the development of psychometrically valid assessment measures would facilitate epidemiological studies, improve clinical case recognition, and inform treatments and interventions.

The Strengths and Weaknesses Heuristic (S&W Heuristic) was constructed in order to reduce biased assessments of students with (suspicion of) Intellectual Giftedness in co-occurrence with Autism Spectrum Disorder (IG + ASD) and to establish a well-founded interconnection between assessment data and intervention indications. The current study is the second in the validation process of the S&W Heuristic. An in-depth analysis of three assessment dossiers of Dutch IG-students with possible characteristics of ASD is focused upon. The core question is whether the S&W Heuristic is of added value to diminish bias in any direction and increase systematicity. The results indicate that bias, mainly directed at Strengths, as well as unsystematicity were present in different stages of two assessment dossiers. The conclusion is that the S&W Heuristic seems to pave the way for systematicity and less bias in assessment processes of students with (suspicion of) IG + ASD.

This study investigated how gifted children with dyslexia might be able to mask literacy problems and the role of possible compensatory mechanisms. The sample consisted of 121 Dutch primary school children that were divided over four groups (typically developing [TD] children, children with dyslexia, gifted children, gifted children with dyslexia). The test battery included measures of literacy (reading/spelling) and cognitive abilities related to literacy and language (phonological awareness [PA], rapid automatized naming [RAN], verbal short-term memory [VSTM], working memory [WM], grammar, and vocabulary). It was hypothesized that gifted children with dyslexia would outperform children with dyslexia on literacy tests. In addition, a core-deficit model including dyslexia-related weaknesses and a compensational model involving giftedness-related strengths were tested using Bayesian statistics to explain their reading/spelling performance. Gifted children with dyslexia performed on all literacy tests in between children with dyslexia and TD children. Their cognitive profile showed signs of weaknesses in PA and RAN and strengths in VSTM, WM, and language skills. Findings indicate that phonology is a risk factor for gifted children with dyslexia, but this is moderated by other skills such as WM, grammar, and vocabulary, providing opportunities for compensation of a cognitive deficit and masking of literacy difficulties.

"Falling out" of education is a rampant problem among gifted children and adults in the Netherlands. An educated guess is that one-third of the gifted adults are unhappy with where they are in their lives and careers. This article discusses ways in which parents or teachers can make a difference by seeing the whole gifted child, creating materials to match educational needs, and advocating for appropriate programs and services. The article discusses two resources that are used in the Netherlands to prevent gifted kids from dropping out of school or help them once they have dropped out of school: (1) "fitting education" and (2) Feniks Talent, a dropout center. "Fitting education" is the Dutch variety of No Child Left Behind, which at its most basic level, is a regional budget allocated to schools in order to keep as many children as possible in regular education. Feniks Talent focuses solely on gifted dropouts, many of whom are twice-exceptional. At Feniks Talent, staff gather gifted youth in groups of 60, exposing them to the peer group that many never encountered in their school career. In these group sessions, students learn how to develop and reintegrate into society, either through school or through learning on the job.

This study investigated risk and protective factors associated with dyslexia and literacy development, both at the group and individual level, to gain more insight in underlying cognitive profiles and possibilities for compensation in high-IQ children. A sample of 73 Dutch primary school children included a dyslexic group, a gifted-dyslexic group, and a borderline-dyslexic group (i.e., gifted children with relative literacy problems). Children were assessed on literacy, phonology, language, and working memory. Competing hypotheses were formulated, comparing the core-deficit view to the twice-exceptionality view on compensation with giftedness-related strengths. The results showed no indication of compensation of dyslexia-related deficits by giftedness-related strengths in gifted children with dyslexia. The higher literacy levels of borderline children compared to gifted children with dyslexia seemed the result of both fewer combinations of risk factors and less severe phonological deficits in this group. There was no evidence for compensation by specific strengths more relevant to literacy development in the borderline group. Accordingly, the findings largely supported the core-deficit view, whereas no evidence for the twice-exceptionality view was found. Besides practical implications, the findings also add to knowledge about the different manifestations of dyslexia and associated underlying cognitive factors at the higher end of the intelligence spectrum.

This longitudinal study explores differences between native Dutch and immigrant Moroccan adolescents in the relationship between internalizing and externalizing problems across time. By using generalized estimating equations (GEE), the strength and stability of associations between internalizing and externalizing problems in 159 Moroccan and 159 Dutch adolescents was studied over a period of 4 years. No differences in strength of co-occurring problems were found between Moroccan and Dutch adolescents. However, for Moroccan adolescents, associations between problems increased over time, whereas in Dutch adolescents, associations remained stable. The increase of co-occurring problems may be a result of undertreatment and increasing complexity of problems in Moroccans during adolescence. The results of this study imply that investigating processes leading to co-occurring problems in subgroups of adolescents, such as immigrant youths, is needed to optimize prevention and intervention efforts.

Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that all the endophenotypic impairments that were reviewed in attention deficit/hyperactivity disorder were also present in autism spectrum disorder, suggesting a continuity model with attention deficit/hyperactivity disorder as "a light form of autism spectrum disorder." Using existing data, 75 adults with autism spectrum disorder and 53 with attention deficit/hyperactivity disorder were directly compared on autistic symptoms with the autism spectrum quotient, and on the endophenotypic measure of temperament and character, using the Abbreviated (Dutch: Verkorte) Temperament and Character Inventory. Based on the hypothesis that attention deficit/hyperactivity disorder and autism spectrum disorder are disorders on a continuous spectrum, autism spectrum quotient scores and abbreviated Temperament and Character Inventory scores were expected to be different from normal controls in both disorders in a similar direction. In addition, the autism spectrum quotient and abbreviated Temperament and Character Inventory scores were expected to be closely correlated. These conditions applied to only two of the seven Abbreviated Temperament and Character Inventory scales (harm avoidance and self-directedness), suggesting that temperament and character as an endophenotype of autism spectrum disorder and attention deficit/hyperactivity disorder provides only partial support for the continuity hypothesis of autism spectrum disorder and attention deficit/hyperactivity disorder.

Limited quality of social relations, milder symptom severity and higher intelligence were shown to account for higher anxiety levels in autism spectrum disorders. The current study replicated and extended earlier findings by combining these three determinants of anxiety in autism spectrum disorders in one study. The sample consisted of 134 school-aged children with autism spectrum disorders, of whom 58 (43%) had a co-morbid anxiety disorder according to the Diagnostic Interview Schedule for Children--Parent version. In this sample, we tested associations between these determinants and anxiety univariately and multivariately to clarify the unique contribution of all determinants. Since we hypothesized that the association between limited quality of social relations and anxiety would be amplified by low symptom severity and/or high intelligence, we additionally tested for moderating effects. We found that higher anxiety levels were associated with a lower quality of social relations and lower symptom severity. In this mainly high-functioning sample, intelligence was not related to anxiety levels. No moderation effects were found. Since lower quality of social relations and lower symptom severity are associated with higher anxiety levels in children with autism spectrum disorders, therapeutic interventions aimed at reducing anxiety in autism spectrum disorders should pay attention to improving social relations, and presumably children with a lower symptom severity could benefit most from such interventions.

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to diagnoses and co-occurring behavioral and emotional problems. Six classes with distinct profiles were discerned. Three classes showed profiles not completely in line with the proposed DSM-5 conceptualization of autism. These classes included relatively many cognitively able individuals with PDD-not otherwise specified. However, profiles seemed to suit other diagnostic categories, such as social communication disorder. These alternative diagnoses could retain eligibility for services, and might adequately fit more specifically targeted interventions.

Background: In the Netherlands, no self-report screening questionnaire for anxiety in people with intellectual disabilities (ID) was available yet. Therefore, we have translated the Glasgow Anxiety Scale for people with an Intellectual Disability (GAS-ID) into Dutch and studied its reliability and validity in adults with borderline, mild or moderate ID. Method: Test-retest reliability was studied in 66 participants, convergent validity against the Anxiety sub-scale of the Hospital, Anxiety and Depression Scale (HADS-A) in 96, and criterion validity against psychiatric diagnosis in 195 participants. Results Internal consistency was "alpha" = 0.86 and test-retest reliability ICC = 0.89 (95% CI: 0.82-0.93). Correlation with the HADS-A was "r" = 0.61 (95% CI: 0.47-0.72); sensitivity was 83.9% (95% CI: 72.2-91.2) and specificity was 51.8% (95% CI: 43.6-59.9) using a cut-off score of 17. Missed diagnoses (false-negatives) were mostly specific phobias. Of the false-positives, 38 of 66 participants (58%) had another psychiatric diagnosis. Conclusions The Dutch version of the GAS-ID is a reliable screening instrument with satisfactory sensitivity, but moderate specificity for anxiety disorders. Although specificity for anxiety disorders is only moderate, high scores appear to be indicative of other psychiatric problems too, justifying referral for psychiatric assessment of false-positives. (Contains 2 tables.)

Objective: The authors explored associations between ADHD symptoms, seasonal depressive symptoms, lifestyle, and health. Method: Adult ADHD patients ("n" = 202) and controls ("n" = 189) completed the ASESA questionnaire involving lifestyle, eating pattern, and physical and psychological health, and validated measures on ADHD and sleep. ASESA is the Dutch acronym for Inattention, Sleep, Eating pattern, Mood, and General health questionnaire. Results: Indication for delayed sleep phase syndrome (DSPS) was 26% in patients and 2% in controls (p less than 0.001). Patients reported shorter sleep, longer sleep-onset latency, and later midsleep. Shorter ("R"[superscript 2] = 0.21) and later ("R"[superscript 2] = 0.27) sleep were associated with hyperactivity, male gender, younger age, and seasonal depressive symptoms. Seasonal depressive symptoms were related to hyperactivity, female gender, unemployment, and late sleep (pseudo "R"[superscript 2] = 0.28). Higher body mass index (BMI) was associated with shorter sleep in patients (rho = -0.16; "p" = 0.04) and controls (rho = -0.17; "p" = 0.02). Longer sleep showed lower odds for indication of metabolic syndrome (OR = -0.17; "p" = 0.053). Conclusion: DSPS is more prevalent in ADHD and needs further investigation to establish treatment to prevent chronic health issues. (Contains 5 tables.)

Simple Summary: This study investigated the impact of the general health status on the survival of patients with high-grade chondrosarcoma, a rare type of bone cancer. This systemic health status is often summarized using the American Society of Anesthesiologists (ASA) score. By analyzing data from 249 patients, the study found that a higher ASA score, older age, and more aggressive tumors were linked to poorer survival rates. This study highlights that a patient's general health, especially for those with severe systemic diseases, should be considered when determining treatment plans, alongside traditional factors like tumor grade and age. These findings can improve decision-making for complex surgeries in patients with high-grade chondrosarcoma. Background: Due to the relatively advanced age and high mortality rate of patients with high-grade chondrosarcoma (CS), it is important to holistically assess patient- and tumor characteristics in multidisciplinary team and shared decision-making with regard to treatment options. While current prognostic models include multiple tumor and treatment characteristics, the only patient characteristics that are commonly included are age and gender. Based on clinical experience, we believe that factors related to patient preoperative systemic health status such as the American Society of Anesthesiologists (ASA) score may be equally important prognostic factors for overall survival (OS). Methods: A retrospective nationwide cohort study was identified from four specialized bone sarcoma centers in The Netherlands. Patients with a primary CS grade II, III, and dedifferentiated CS were eligible. Prognostic factors including age at presentation, gender, ASA score, CVD, tobacco use, BMI, histological tumor grade, tumor size, pathological fracture, presentation after unplanned excision, type of surgery and surgical margin were evaluated. The outcome measure was OS at the time of surgery. The Kaplan–Meier methodology was employed to estimate OS; a log-rank test was used to assess the difference in survival. To study the impact of prognostic factors on OS, a multivariate Cox proportional hazard regression model was estimated. Results: In total, 249 patients were eligible for this study, and 89 were deceased at the end of follow-up. In multivariate analysis, histological grade (HR 2.247, 95% CI 1.334–3.783), ASA score III (HR 2.615, 95% CI 1.145–5.976, vs. ASA I), and age per year (HR: 1.025, 95% CI 1.004–1.045) were negatively associated with OS. No association was found between tobacco use, BMI, gender or cardiovascular disease and OS in this cohort. Pathological fracture and tumor size were only associated with OS in univariate analysis. Conclusions: This multicenter study is the first on sarcomas to include ASA in a prognostic model. Results show that ASA score as a proxy for patients' systemic health status should be included when providing a prognosis for patients with a high-grade primary CS, besides the conventional risk factors such as tumor grade and age. Specifically, severe systemic disease (ASA score III) is a strong negative predictor. Conversely, we found no difference in OS between ASA scores I and II. These findings aid multidisciplinary team and shared decision-making with regard to these complex sarcoma patients that often require life-changing surgeries. Level of Evidence: Prognostic level III. See the instructions for authors for the complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Cardiac rehabilitation (CR) can reduce mortality and improve physical functioning in older patients, but current programs do not support the needs of older patients with comorbidities or frailty, for example due to transport problems and physical limitations. Home-exercise-based cardiac rehabilitation (HEBCR) programs may better meet these needs, but physiotherapy guidelines for personalising HEBCR for older, frail patients with cardiovascular disease are lacking. Purpose: To provide expert recommendations for physiotherapists on how to administer HEBCR to older adults with comorbidities or frailty. Methods: This Delphi study involved a panel of Dutch experts in physiotherapy, exercise physiology, and cardiology. Three Delphi rounds were conducted between December 2020 and February 2022. In the first round panellists provided expertise on applicability and adaptability of existing CR-guidelines. In the second round panellists ranked the importance of statements about HEBCR for older adults. In the third round panellists re-ranked statements when individual scores were outside the semi-interquartile range. Consensus was defined as a semi-interquartile range of ≤ 1.0. Results: Of 20 invited panellists, 11 (55%) participated. Panellists were clinical experts with a median (interquartile range) work experience of 20 (10.5) years. The panel reached a consensus on 89% of statements, identifying key topics such as implementing the patient perspective, assessing comorbidity and frailty barriers to exercise, and focusing on personal goals and preferences. Conclusion: This Delphi study provides recommendations for personalised HEBCR for older, frail patients with cardiovascular disease, which can improve the effectiveness of CR-programs and address the needs of this patient population. Prioritising interventions aimed at enhancing balance, lower extremity strength, and daily activities over interventions targeting exercise capacity may contribute to a more holistic and effective approach, particularly for older adults. [ABSTRACT FROM AUTHOR]

Background Mood and anxiety disorders are heterogeneous conditions with variable course. Knowledge on latent classes and transitions between these classes over time based on longitudinal disorder status information provides insight into clustering of meaningful groups with different disease prognosis. Methods Data of all four waves of the Netherlands Mental Health Survey and Incidence Study-2 were used, a representative population-based study of adults (mean duration between two successive waves = 3 years; N at T0 = 6646; T1 = 5303; T2 = 4618; T3 = 4007; this results in a total number of data points: 20 574). Presence of eight mood and anxiety DSM-IV disorders was assessed with the Composite International Diagnostic Interview. Latent class analysis and latent Markov modelling were used. Results The best fitting model identified four classes: a healthy class (prevalence: 94.1%), depressed-worried class (3.6%; moderate-to-high proportions of mood disorders and generalized anxiety disorder (GAD)), fear class (1.8%; moderate-to-high proportions of panic and phobia disorders) and high comorbidity class (0.6%). In longitudinal analyses over a three-year period, the minority of those in the depressed-worried and high comorbidity class persisted in their class over time (36.5% and 38.4%, respectively), whereas the majority in the fear class did (67.3%). Suggestive of recovery is switching to the healthy class, this was 39.7% in the depressed-worried class, 12.5% in the fear class and 7.0% in the high comorbidity class. Conclusions People with panic or phobia disorders have a considerably more persistent and chronic disease course than those with depressive disorders including GAD. Consequently, they could especially benefit from longer-term monitoring and disease management. [ABSTRACT FROM AUTHOR]

People with intellectual disabilities (ID) experience complex medical care needs and high levels of multimorbidity. In mainstream healthcare, these needs might remain undetected leading to unmanaged health problems and avoidable deaths. In the Netherlands, general practitioners (GPs) can refer to specialized ID physicians when ID‐specific expertise is required. Little is known about the characteristics of specialized medical care for people with ID. This study explores the characteristics of specialized medical care for people with ID, including the interplay between medical‐, psychological‐, and context‐related problems. A retrospective cohort study using medical records of patients with ID who had visited the outpatient ID practice in Nijmegen, the Netherlands. Medical records (n = 128) were analyzed using descriptive statistics, focusing on (1) reasons for initial consultation, (2) health‐related problems identified during initial consultation, and (3) disciplines involved following initial consultation. Analyses were performed separately for patients who were referred by a medical professional and patients who visited the practice for proactive health checks related to the etiological diagnosis. Patients often initially visit the outpatient ID practice for one type of complaint, most often psychological. Diverse, multiple, and interconnected problems were identified during specialized medical ID consultation. A range of specialist professionals (n = 25) were involved by the ID physician. The health‐related problems of people with ID seen at the outpatient ID practice are diverse and interconnected, and originate from an interplay between medical‐, psychological‐, and context‐related problems. This complexity is not mirrored in the reasons for referring to the outpatient ID practice. It is essential to go beyond medical views and assess health complaints in an integrated way, including the way ID can influence all levels (physical, mental, contextual) of the experienced health issue within the context of everyday life. [ABSTRACT FROM AUTHOR]

Background Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults. Methods Participants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU (n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling. Results Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85–9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month (B = −4.00, p = 0.009, 95% CI −6.97 to −1.02, d = 0.27) and 6-month follow-up (B = −3.20, p = 0.032, 95% CI −6.13 to −0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month (B = −0.57, p = 0.732, 95% CI −3.83 to 2.69) nor after 6-month follow-up (B = −0.44, p = 0.793, 95% CI −3.69 to 2.82). Conclusions The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use. Trial registration: Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219). [ABSTRACT FROM AUTHOR]

Background: Comorbidity is increasingly important in the medical literature, with ever-increasing implications for diagnosis, treatment, prognosis, management and health care. The objective of this study is to measure casual versus causal comorbidity in primary care in three family practice populations. Methods: This is a longitudinal observational study using the Transition Project datasets. Transition Project family doctors in the Netherlands, Malta and Serbia recorded details of all patient contacts in an episode of care structure using electronic medical records and the International Classification of Primary Care, collecting data on all elements of the doctor-patient encounter, including diagnoses (1,178,178 in the Netherlands, 93,606 in Malta, 405,150 in Serbia), observing 158,370 patient years in the Netherlands, 43,577 in Malta, 72,673 in Serbia. Comorbidity was measured using the odds ratio of both conditions being incident or rest-prevalent in the same patient in one-year dataframes, as against not, corrected for the prior probability of such co-occurrence, between the 41 joint most prevalent (joint top 20) episode titles in the three populations. Specific associations were explored in different age groups to observe the changes in odds ratios with increasing age as a surrogate for a temporal or biological gradient. Results: The high frequency of observed comorbidity with low consistency in both clinically and statistically significant odds ratios across populations indicates more casual than causal associations. A causal relationship would be expected to be manifest more consistently across populations. Even in the minority of cases where odds ratios were consistent between countries and numerically larger, those associations were observed to weaken with increasing patient age. Conclusion: After applying accepted criteria for testing the causality of associations, most observed primary care comorbidity is due to chance, likely as a result of increasing illness diversity. Trial registration: This study was performed on electronic patient record datasets made publicly available by the University of Amsterdam Department of General Practice, and did not involve any patient intervention. Key points: Comorbidity is very commonly observed in primary care patients. Most of the comorbidity observed in primary care is due to chance, and causal relationships between co-occurring diseases are uncommon. Most observed comorbidity may be an artefact of increasing illness diversity. Comorbidity studies require appropriate classifications and episode of care models. [ABSTRACT FROM AUTHOR]

Simple Summary: This nationwide cohort study evaluated the incidence and severity of immune-related adverse events (irAEs) in melanoma patients receiving adjuvant versus advanced anti-PD-1 therapy. A total of 1465 advanced melanoma patients and 908 adjuvant-treated patients were included. Patients in the adjuvant group were younger, had superior ECOG performance status, and had fewer comorbidities compared to those in the advanced group. No significant difference was observed in the incidence of grade III-IV irAEs between the two groups. However, higher ECOG status (>1) and the presence of any comorbidities were independently associated with an increased risk of irAE development across both treatment settings. Although adjuvant therapy was not linked to a heightened risk of severe irAEs compared to advanced therapy, it was more frequently discontinued due to toxicity in the adjuvant group. These findings provide critical insights for informing patient consultations regarding adjuvant anti-PD-1 treatment. Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment. [ABSTRACT FROM AUTHOR]

Introduction: The aim of our study was to validate the original Charlson Comorbidity Index (1987) (CCI) and adjusted CCI (2011) as a prediction model for 30-day and 1-year mortality after hip fracture surgery. The secondary aim of this study was to verify each variable of the CCI as a factor associated with 30-day and 1-year mortality. Methods: A prospective database of two-level II trauma teaching hospitals in the Netherlands was used. The original CCI from 1987 and the adjusted CCI were calculated based on medical history. To validate the original CCI and the adjusted CCI, the CCI was plotted against the observed 30-day and 1-year mortality, and the area under the curve (AUC) was calculated. Results: A total of 3523 patients were included in this cohort study. The mean of the original CCI in this cohort was 5.1 (SD ± 2.0) and 4.6 (SD ± 1.9) for the adjusted CCI. The AUCs of the prediction models were 0.674 and 0.696 for 30-day mortality for the original and adjusted CCIs, respectively. The AUCs for 1-year mortality were 0.705 and 0.717 for the original and adjusted CCIs, respectively. Conclusions: A higher original and adjusted CCI is associated with a higher mortality rate. The AUC was relatively low for 30-day and 1-year mortality for both the original and adjusted CCIs compared to other prediction models for hip fracture patients in our cohort. The CCI is not recommended for the prediction of 30-day and 1-year mortality in hip fracture patients. [ABSTRACT FROM AUTHOR]

To determine the course of adherence to physical activity (PA) recommendation in hip/knee osteoarthritis patients before and after hip/knee arthroplasty (THA/TKA). Moreover, we explored predictors for non-adherence 12 months postoperatively. Primary THA/TKA were included in a multicenter observational study. Preoperatively and 6/12 months postoperatively, patients reported engagement in moderate-intensity PA in days/week in the past 6 months (PA-recommendation (≥30 min of moderate-intensity ≥5 days/week)). We included predictors stratified by preoperative adherence: sex, age, BMI, comorbidities, smoking, living/working status, season, mental health, HOOS/KOOS subscales before and 6 months postoperatively, and 6-month adherence. (1005 THA/972 TKA) Preoperatively, 50% of the population adhered. Adherence increased to 59% at 6 and 12 months. After 12 months, most patients remained at their preoperative PA level, 11% of the preoperative adherers decreased, while 20% of the preoperative non-adherers increased their PA level. In all different groups, adherence to the PA recommendation at 6 months was identified as a predictor (OR-range: 0.16–0.29). In addition, BMI was identified as predictor in the THA adherent (OR = 1.07; 95%CI [1.02–1.15]) and TKA non-adherent groups (OR = 1.08; 95%CI [1.03–1.12]). THA non-adherent group not having paid work (OR = 0.53; 95%CI [0.33–0.85]), and in the TKA adherent group, lower KOOS subscale symptoms (OR = 1.03; 95%CI [1.01–1.05]) were associated with non-adherence. Majority of patients remained at their preoperative PA level. Non-adherence at 6 months was highly predictive for 12-month non-adherence. Physical activity (PA) is crucial to decrease mortality risk, especially among patients suffering from osteoarthritis, as these patients have the potential to become more physically active after arthroplasty surgery. We found that physical function and pain improved, but 69% of the patients remained at their preoperative PA level, while 11% decreased and 20% increased their PA levels. Using this information shortly after surgery, orthopedic surgeons and other health care professionals can address patients at risk for decreased PA levels and provide PA advice. [ABSTRACT FROM AUTHOR]

Background: General practitioners (GPs) specialized in cardiovascular disease (GPSI-CVD) may suspect heart failure (HF) more easily than GPs not specialized in CVD. We assessed whether GPSI-CVD consider investigations aimed at detecting HF more often than other GPs in two clinical scenarios of an older male person with respiratory and suggestive HF symptoms. Methods: In this vignette study, Dutch GPs evaluated two vignettes. The first involved a 72-year-old man with hypertension and a 30 pack-year smoking history who presented himself with symptoms of a common cold, but also shortness of breath, reduced exercise tolerance, and signs of fluid overload. The second vignette was similar but now the 72-year-old man was known with chronic obstructive pulmonary disease (COPD). GPs could select diagnostic tests from a multiple-choice list with answer options targeted at HF, COPD or exacerbation of COPD, or lower respiratory tract infection. With Pearson Chi-square or Fisher's exact test differences between the two GP groups were assessed regarding the chosen diagnostic tests. Results: Of the 148 participating GPs, 25 were GPSI-CVD and 123 were other GPs. In the first vignette, GPSI-CVD more often considered performing electrocardiography (ECG) than other GPs (64.0% vs. 32.5%, p = 0.003). In the second vignette, GPSI-CVD were more inclined to perform both ECG (36.0% vs. 12.2%, p = 0.003) and natriuretic peptide testing (56.0% vs. 32.5%, p = 0.006). Conclusions: Most GPs seemed to consider multiple diagnoses, including HF, with GPSI-CVD more likely performing ECG and natriuretic peptide testing in an older male person with both respiratory and suggestive HF symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive Behavioural Analysis System of Psychotherapy (CBASP) is the first therapy specifically developed for persistent depressive disorder (PDD). This study aimed to identify predictors of favourable treatment outcome after group CBASP and assess change in depression severity over 24 weeks. Design: A prospective cohort study was conducted in patients with PDD treated with group- CBASP. Methods: Outcomes were depression severity measured by the Inventory of Depression Severity--self- report (IDS- SR) after 6 and 12 months. Potential predictors investigated were baseline depression severity, prior antidepressant use, age, family status, income source, age of onset and childhood trauma. Multivariate logistic regression was performed to assess their effects with a ≥25% IDS- SR score decrease as the dependent variable. Results: The IDS- SR score (range 0--84) significantly decreased from 37.78 at start to 33.45 at 6 months, an improvement which was maintained at 12 months. Having paid work and no axis I comorbidity significantly predicted favourable response. In the groups without a favourable outcome predictor a substantial percentage still showed at least partial response (16.7% and 19.2%). Conclusions: Source of income and axis I comorbidity were predictors of response to group- CBASP. Within the group without favourable outcome predictors, a subgroup showed at least partial response. These results suggest that group- CBASP has promise for patients who do not respond to standard treatments. Future studies should include outcome measures that take into account comorbidity and other clinically relevant changes, such as social functioning. [ABSTRACT FROM AUTHOR]

Background: Almost all patients with Neurofibromatosis type 1 (NF1) develop cutaneous neurofibroma (cNF), benign dermal tumours that have a large impact on the patient's Quality of Life (QoL). The French cNF-Skindex is the first questionnaire to specifically assess cNF-related QoL in patients with NF1. We aimed to adapt and validate a Dutch version of the cNF-Skindex. Methods: The questionnaire was translated using forward and backwards translation, and subsequently administered to a sample of 59 patients on two separate occasions. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating internal consistency and test-retest reliability, by calculating Cronbach's alpha and Spearman's rank correlation coefficients. The EQ-5D-5L and SF-36 were used to evaluate convergent validity, using Spearman's rank correlation coefficients. An exploratory factor analysis was performed to study the data's internal structure. Multivariable linear regression was used to model the relationship between patient characteristics and the cNF-Skindex. Results: The Dutch cNF-Skindex demonstrated excellent feasibility and reliability (Cronbach's alpha 0.96, test-retest correlation coefficient 0.88). Convergent validity was confirmed for the EQ-5D-5L and relevant SF-36 scales. All items and subdomains from the original questionnaire were confirmed following exploratory factor analysis. The patient characteristics included in the multivariable linear regression were not significantly associated with the cNF-Skindex score. Conclusions: The Dutch cNF-Skindex displayed excellent psychometric properties, enabling use in the Netherlands. [ABSTRACT FROM AUTHOR]

Background: Persons with multimorbidity may gain from person-centred care compared with the current protocolised chronic-disease management in Dutch general practice. Given time constraints and limited resources, it is essential to prioritise those most in need of an assessment of person-centred chronic-care needs. Aim: To develop and validate a prioritisation algorithm based on routine electronic medical record (EMR) data that distinguishes between patients with multimorbidity who would, and those who would not, benefit from an extended person-centred consultation to assess person-centred chronic-care needs, as judged by GPs. Design and setting: A mixed-methods study was conducted in five general practices in the north-west region of the Netherlands. Four out of the five practices were situated in rural areas. Method: Multivariable logistic regression using EMR data to predict the GPs' judgement on patients' anticipated benefit from an extended consultation, as well as a thematic analysis of a focus group exploring GPs' clinical reasoning for this judgement were conducted. Internal validation was performed using 10-fold cross-validation. Multimorbidity was defined as the presence of ≥3 chronic conditions. Results: In total, EMRs from 1032 patients were included in the analysis; of these, 352 (34.1%) were judged to have anticipated benefit. The model's cross-validated C-statistic was 0.72 (95% confidence interval = 0.70 to 0.75). Calibration was good. Presence of home visit(s) and history of myocardial infarction were associated with anticipated benefit. Thematic analysis revealed three dimensions feeding anticipated benefit: GPs' cause for concern, patients' mindset regarding their conditions, and balance between received care/expected care needed. Conclusion: This algorithm may facilitate automated prioritisation, potentially avoiding the need for GPs to personally triage the whole practice population that has multimorbidity. However, external validation of the algorithm and evaluation of actual benefit of consultation is recommended before implementation. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the prediction of quality of life by frailty and disability in a baseline sample of 479 Dutch community-dwelling people aged 75 years or older using a follow-up period of 8 years. Regarding frailty, we distinguish between physical, psychological, and social frailty. Concerning physical disability, we distinguish between limitations in performing activities in daily living (ADL) and instrumental activities in daily living (IADL). The Tilburg Frailty Indicator (TFI) and the Groningen Activity Restriction Scale (GARS) were used to assess frailty domains and types of disability, respectively. Quality of life was determined by the WHOQOL-BREF containing physical, psychological, social, and environmental domains. In our study, 53.9% of participants were woman, and the mean age was 80.3 years (range 75–93). The study showed that psychological frailty predicted four domains of quality of life and physical frailty three. Social frailty was only found to be a significant predictor of social quality of life and environmental quality of life. ADL and IADL disability proved to be the worst predictors. It is recommended that primary healthcare professionals (e.g., general practitioners, district nurses) focus their interventions primarily on factors that can prevent or delay psychological and physical frailty, thereby ensuring that people's quality of life does not deteriorate. [ABSTRACT FROM AUTHOR]

Simple Summary: Transoral Robotic Surgery (TORS) is increasingly used for various conditions, yet its success and failure remain underexplored. In this multicenter study, we assessed 220 TORS interventions across 211 patients. Success criteria differed by condition, including tumor identification for CUP, resection margins for malignancies, and symptom improvement for benign cases like OSA and chronic lingual tonsillitis. Predictors of success varied, with factors such as patient comorbidity, tumor characteristics, and demographics playing roles. Conversely, failure predictors encompassed postoperative complications and pain, linked to patient health and demographics. These insights into TORS outcomes may aid in patient selection and counseling across different conditions, informing clinical practice and enhancing patient care. Transoral Robotic Surgery (TORS) is utilized for treating various malignancies, such as early-stage oropharyngeal cancer and lymph node metastasis of an unknown primary tumor (CUP), and also benign conditions, like obstructive sleep apnea (OSA) and chronic lingual tonsillitis. However, the success and failure of TORS have not been analyzed to date. In this retrospective observational multicenter cohort study, we evaluated patients treated with TORS using the da Vinci surgical system. Success criteria were defined as identification of the primary tumor for CUP, >2 mm resection margin for malignant conditions, and improvement on respiratory polygraphy and tonsillitis complaints for benign conditions. A total of 220 interventions in 211 patients were included. We identified predictors of success, such as low comorbidity status ACE-27, positive P16 status, and lower age for CUP, and female gender and OSA severity for benign conditions. For other malignancies, no predictors for success were found. Predictors of failure based on postoperative complications included high comorbidity scores (ASA) and anticoagulant use, and for postoperative pain, younger age and female gender were identified. This study provides valuable insights into the outcomes and predictors of success and failure in TORS procedures across various conditions and may also help in patient selection and counseling. [ABSTRACT FROM AUTHOR]