Person-centred Approaches to Psychopathology in the ABCD Study: Phenotypes and Neurocognitive Correlates.

Issues with classifying psychopathology using narrow diagnostic categories have prompted calls for the use of dimensional approaches. Yet questions remain about how closely dimensional approaches reflect the way symptoms cluster in individuals, whether known risk factors (e.g. preterm birth) produce distinct symptom phenotypes, and whether profiles reflecting symptom clusters are associated with neurocognitive factors. To identify distinct profiles of psychopathology, latent class analysis was applied to the syndrome scales of the parent-reported Child Behaviour Checklist for 11,381 9- and 10- year-olds from the Adolescent Brain Cognitive Development study. Four classes were identified, reflecting different profiles, to which children were assigned probabilistically; Class 1 (88.6%) reflected optimal functioning; Class 2 (7.1%), predominantly internalising; Class 3 (2.4%), predominantly externalising; and Class 4 (1.9%), universal difficulties. To investigate the presence of a possible preterm behavioural phenotype, the proportion of participants allocated to each class was cross-tabulated with gestational age category. No profile was specific to preterm birth. Finally, to assess the neurocognitive factors associated with class membership, elastic net regressions were conducted revealing a relatively distinct set of neurocognitive factors associated with each class. Findings support the use of large datasets to identify psychopathological profiles, explore phenotypes, and identify associated neurocognitive factors.

Brief Report: Local-Global Processing and Co-occurrence of Anxiety, Autistic and Obsessive-Compulsive Traits in a Non-clinical Sample.

PURPOSE: Increased local-to-global interference has been found in those with ASD, AD and OCD, and as such, may represent a transdiagnostic marker. As a first step to investigating this, we aimed to assess the overlap in traits of these disorders in a non-clinical sample, and whether local-global processing relates to the traits of the three conditions. METHODS: Participants (n = 149) completed questionnaires including the Autism Quotient (AQ), the Obsessive-Compulsive Inventory (OCI-R) and the Zung Self-rating Anxiety Scale (SAS) and an online version of the Navon task. Behavioural metrics of interference and precedence were extracted from the task and correlated with trait scores. RESULTS: We found moderate to strong correlations between the total scores for ASD, anxiety and OCD. Most local-global processing indices did not relate to traits. CONCLUSION: The study found evidence for an overlap in autism, anxiety and obsessive-compulsive traits in a non-clinical sample. However, local-global processing, as measured by the Navon task, did not appear to underpin symptomatology in the sample and could not be considered a transdiagnostic marker. Future research should investigate the value of alternate metrics.

A comparison of simultaneous and sequential visuo-spatial memory in children born very preterm.

Research suggests that children born very preterm (≤32 weeks' gestation) are at greater risk of impairments in information processing (particularly when information is presented simultaneously rather than sequentially) and visuo-spatial short-term and working memory relative to children born at term. This study compared the performance of children born very preterm with their term-born peers to elucidate the nature of group differences in these areas. 113 children (65 very preterm; 48 term-born) aged 8-to-11 years completed four visuo-spatial recall tasks. Tasks varied by presentation type (simultaneous or sequential) and memory type (short-term or working memory). Both groups recalled more locations in simultaneous than sequential tasks, and in short-term than working memory tasks. In short-term memory tasks, children born at term recalled more locations than children born very preterm for the sequential task, but groups did not differ on the simultaneous task. The opposite pattern was observed in the working memory tasks, with no group differences on the sequential task, but better performance on the simultaneous task for children born at term. Our findings indicate that simultaneous processing may not be impaired in children born very preterm per se, with poorer performance observed only under high cognitive demand. This interaction suggests very preterm birth may affect the level of cognitive resources available during feature integration, the consequences of which become apparent when resources are already stretched. The impact of interactions with cognitive demand in this population should be an important consideration for educational support strategies, and for assessment in research and clinic.

Health-related quality of life and work productivity in UK patients with HER2-positive breast cancer: a cross-sectional study evaluating the relationships between disease and treatment stage.

BACKGROUND: The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood. METHODS: This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance. RESULTS: Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p < 0.003). Proportions of employed patients were 50.6%, 50.9% and 27.5% in Groups 1, 2 and 3, respectively. For patients in part-time employment, the number of hours worked was significantly higher in Group 2 patients versus Group 3 (p = 0.002). Group 2 also had significantly lower levels of work absenteeism and overall work impairment compared with Group 1 (p < 0.001). Patients in Group 3 reported worse health utility scores (p ≤ 0.002), moderate or worse problems in the EQ-5D-5L self-care and usual activity domains (p ≤ 0.001), and lower HRQoL as assessed by FACT summary scores (p < 0.001 for FACT-B and -G) than Groups 1 and 2. Poorer HRQoL was significantly associated with higher work impairment (p < 0.001), with the strongest relationships being observed between activity impairment and HRQoL (Pearson's r: 0.67). CONCLUSIONS: Metastatic disease and treatment of HER2-positive BC adversely impacted on work productivity and HRQoL. The results of this study support the idea that being able to delay or prevent the metastatic recurrence of BC, for example by extending the time patients are in remission or at early stage of BC, has wider benefits in terms of patient productivity and HRQoL.

Standard Gamble to Derive Utility Health States for Limbal Stem Cell Deficiency.

PURPOSE: To generate UK health-related quality-of-life (HRQoL) data for adult patients with moderate-to-severe limbal stem cell deficiency (LSCD), unilateral or bilateral, due to physical or chemical ocular burns to help inform economic evaluations of treatments. PATIENTS AND METHODS: EQ-5D-3L with vision bolt-on scores was prospectively measured for one of five clinical scenarios of LSCD described in vignettes in a demographically representative population of 520 UK adults. These were converted to health state utilities using three different UK value sets. A standard gamble (SG) was then undertaken using 12 SG scenarios to examine the component drivers of health utility for the treatment of LSCD. RESULTS: For the EQ-5D-3L scenarios, the mean disutility for LSCD with poor visual acuity, pain and disfigurement in both eyes compared to one eye was -0.084 (range=-0.156 to -0.045 across the value sets). The mean disutility of bilateral LSCD with pain, disfigurement, and poor visual acuity compared to unilateral LSCD with only poor visual acuity in one eye was -0.104 (range=-0.151 to -0.078). Similarly, where one eye was affected, pain and disfigurement in combination were associated with a greater mean disutility than improvements in visual acuity alone: -0.011 (range=-0.04 to 0.005). Mean SG utilities were within a narrow range (0.682-0.765). Where one eye was affected, the main driver was disfigurement: mean utility was 0.731 (0.709-0.753) compared to 0.682 (0.659-0.704) when disfigurement was removed compared to vision restored to normal. For bilateral LSCD, mean utilities were 0.693 (0.672-0.715) for normal vision and 0.75 (0.73-0.771) when disfigurement and pain were removed. CONCLUSION: Improvements in pain and disfigurement appeared to be the main factors driving differences in health utilities associated with symptom profiles in LSCD, with improvements in visual acuity having lesser impact.

Dementia medical screening using mobile applications: A systematic review with a new mapping model.

Early detection is the key to successfully tackling dementia, a neurocognitive condition common among the elderly. Therefore, screening using technological platforms such as mobile applications (apps) may provide an important opportunity to speed up the diagnosis process and improve accessibility. Due to the lack of research into dementia diagnosis and screening tools based on mobile apps, this systematic review aims to identify the available mobile-based dementia and mild cognitive impairment (MCI) apps using specific inclusion and exclusion criteria. More importantly, we critically analyse these tools in terms of their comprehensiveness, validity, performance, and the use of artificial intelligence (AI) techniques. The research findings suggest diagnosticians in a clinical setting use dementia screening apps such as ALZ and CognitiveExams since they cover most of the domains for the diagnosis of neurocognitive disorders. Further, apps such as Cognity and ACE-Mobile have great potential as they use machine learning (ML) and AI techniques, thus improving the accuracy of the outcome and the efficiency of the screening process. Lastly, there was overlapping among the dementia screening apps in terms of activities and questions they contain therefore mapping these apps to the designated cognitive domains is a challenging task, which has been done in this research.

Using drift diffusion modeling to understand inattentive behavior in preterm and term-born children.

OBJECTIVE: Children born very preterm are at increased risk of inattention, but it remains unclear whether the underlying processes are the same as in their term-born peers. Drift diffusion modeling (DDM) may better characterize the cognitive processes underlying inattention than standard reaction time (RT) measures. This study used DDM to compare the processes related to inattentive behavior in preterm and term-born children. METHOD: Performance on a cued continuous performance task was compared between 33 children born very preterm (VP; ≤ 32 weeks' gestation) and 32 term-born peers (≥ 37 weeks' gestation), aged 8-11 years. Both groups included children with a wide spectrum of parent-rated inattention (above average attention to severe inattention). Performance was defined using standard measures (RT, RT variability and accuracy) and modeled using a DDM. A hierarchical regression assessed the extent to which standard or DDM measures explained variance in parent-rated inattention and whether these relationships differed between VP and term-born children. RESULTS: There were no group differences in performance on standard or DDM measures of task performance. Parent-rated inattention correlated significantly with hit rate, RT variability, and drift rate (a DDM estimate of processing efficiency) in one or both groups. Regression analysis revealed that drift rate was the best predictor of parent-rated inattention. This relationship did not differ significantly between groups. CONCLUSIONS: Findings suggest that less efficient information processing is a common mechanism underlying inattention in both VP and term-born children. This study demonstrates the benefits of using DDM to better characterize atypical cognitive processing in clinical samples. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Preferences for the administration of testosterone gel: evidence from a discrete choice experiment.

Objectives: Differences in testosterone replacement therapy (TRT) gel products may affect patient satisfaction, quality-of-life, and treatment response and adherence. This study investigated preferences for TRT gel in terms of formulation and administration. Methods: 525 male adults aged 45 years and over completed a discrete choice experiment. Respondents made repeated choices between two hypothetical testosterone gel treatments described according to four attributes: form, ease of use, impact of use on showering/swimming, and location/dosage of the application. Choice data were analyzed using a latent class model. Results: Three preference classes were identified. Respondents across all classes displayed a preference for the gel being dispensed in smaller units with accurate dosing, waiting shorter times after the gel application before swimming/showering, and using 2.5 gm of gel to be applied to the inner thigh/abdomen as opposed 5 gm to shoulder/abdomen. The importance of these characteristics differed across classes, with preference class membership predicted by age and education level. For instance, younger men (aged 45-64 years) were more likely to belong to a class that prioritized reduced waiting time before being able to undertake activities. Formulation was not an important driver of choice. Conclusions: Preferences demonstrate a predilection for TRT gel dispensed in small units allowing precise dosing, shorter waiting time after application, and application to the inner thigh/abdomen. However, the strength of importance of these characteristics differs between men. This study highlights the attributes of TRT gel considered important to patient subgroups, and which may ultimately affect treatment response, medication adherence, and patient quality-of-life.

The impact of increased post-progression survival on the cost-effectiveness of interventions in oncology.

Purpose: Cost-effectiveness analyses (CEA) of new technologies typically include "background" costs (eg, all "related" health care costs other than the specific technology under evaluation) as well as drug costs. In oncology, these are often expensive. The marginal cost-effectiveness ratio (ie, the extra costs and QALYs associated with each extra period of survival) calculates the ratio of background costs to QALYs during post-progression. With high background costs, the incremental cost-effectiveness ratio (ICER) can become less favorable as survival increases and the ICER moves closer to the marginal cost-effectiveness ratio, making cost-effectiveness prohibitive. This study assessed different methods to determine whether high ICERs are caused by high drug costs, high "background costs" or a combination of both and how different approaches can alter the impact of background costs on the ICER where the marginal cost-effectiveness ratio is close to, or above, the cost-effectiveness threshold. Methods: The National Institute for Health and Care Excellence oncology technology appraisals published or updated between October 2012 and October 2017 were reviewed. A case study was selected, and the CEA was replicated. Three modeling approaches were tested on the case study model. Results: Applying one-off "transition" costs during post-progression reduced the ongoing "incremental" costs of survival, which meant that the marginal cost-effectiveness ratio was substantially reduced and problems associated with additional survival were less likely to impact the ICER. Similarly, the use of two methods of additional utility weighting for end-of-life cases meant that the marginal cost-effectiveness ratio was reduced proportionally, again lessening the impact of increased survival. Conclusion: High ICERs can be caused by factors other than the cost of the drug being assessed. The economic models should be correct and valid, reflecting the true nature of marginal survival. Further research is needed to assess how alternative approaches to the measurement and application of background costs and benefits may provide an accurate assessment of the incremental benefits of life-extending oncology drugs. If marginal survival costs are incorrectly calculated (ie, by summing total post-progressed costs and dividing by the number of baseline months in that state), then the costs of marginal survival are likely to be overstated in economic models.

Process utilities for topical treatment in atopic dermatitis.

PURPOSE: Management of atopic dermatitis (AD) typically requires application of topical treatments, often multiple times a day. The cosmetic properties and burdensome application of these treatments can be detrimental to quality of life (QoL). Patients who achieve good disease control through use of systemic therapies may reduce the frequency and amount of topical applications, improving QoL. This study aimed to quantify the utility and disutility for topical AD treatment processes. METHODS: Seven vignettes describing different skincare regimens for people with moderate-to-severe AD were developed with input from healthcare professionals. 484 respondents from the general population completed time trade-off items for each vignette. Utility values for each regimen, and disutilities associated with the impact of changes to skincare regimens, were calculated. Analysis of variance assessed differences between skincare regimens. RESULTS: As skincare regimens increased in intensity (0.7968 for the most intense; 0.9999 for the least), utility values decreased. There were no statistically significant differences between skincare regimens followed by patients with good disease control (0.9862 to 0.9999); however, when compared to those involving topical corticosteroids and emollient combinations (0.7968 to 0.8835), significant differences were observed (p < 0.001). The largest disutilities (0.1521 to 0.1705) were between skincare regimens describing the use of topical corticosteroids plus emollient and those followed by patients with good disease control. CONCLUSIONS: The application of topical treatments has a detrimental effect on QoL, which increases with the duration and frequency of applications. Further research is needed to investigate how health and process utilities interact and both can be integrated into medical decision-making.

Eye movement data reveal increased attention to combined health warnings on cigarette packs.

INTRODUCTION: In 2016 the UK introduced standardised pack design regulations, limiting branding and aiming to increase the salience of health warnings. Existing evidence suggests that the effectiveness of pack design in focusing a smoker's attention toward warnings may depend on how much they smoke. Our study aimed to directly compare attention to branding and warnings between the pre-regulation and post-regulation packs in smokers, and to determine whether this was affected by the amount smoked, to assess the effectiveness of the new policies. METHOD: 47 adult smokers were recruited, including daily and non-daily smokers to ensure a wide range in cigarettes smoked per week. Eye movement data were recorded while images of cigarette packs were displayed sequentially on screen. Each trial presented one of two types of cigarette pack; pre-regulation packs with a text health warning, or post-regulation packs compliant with governmental guidance introduced in 2016, with plain branding and a combined pictorial and text health warning. Eye movement data were compared between packs, covarying the number of cigarettes smoked per week. RESULTS: Eye movement analysis revealed that smokers attended more to health warnings and less to branding when looking at post-regulation packs compared with pre-regulation packs. These effects did not relate to number of cigarettes smoked per week. CONCLUSION: Standardised regulations for cigarette packs successfully direct smokers' attention away from branding, and towards health warnings, with no association with cigarettes smoked per week. This study adds to the growing body of evidence advocating broader uptake of similar packaging regulations.

Economic cost of congenital CMV in the UK.

OBJECTIVE: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital disability. It can disrupt neurodevelopment, causing lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed, for the first time, to estimate the annual economic burden of managing cCMV and its sequelae in the UK. DESIGN: The study collated available secondary data to develop a static cost model. SETTING: The model aimed to estimate costs of cCMV in the UK for the year 2016. PATIENTS: Individuals of all ages with cCMV. MAIN OUTCOME MEASURES: Direct (incurred by the public sector) and indirect (incurred personally or by society) costs associated with management of cCMV and its sequelae. RESULTS: The model estimated that the total cost of cCMV to the UK in 2016 was £732 million (lower and upper estimates were between £495 and £942 million). Approximately 40% of the costs were directly incurred by the public sector, with the remaining 60% being indirect costs, including lost productivity. Long-term impairments caused by the virus had a higher financial burden than the acute management of cCMV. CONCLUSIONS: The cost of cCMV is substantial, predominantly stemming from long-term impairments. Costs should be compared against investment in educational strategies and vaccine development programmes that aim to prevent virus transmission, as well as the value of introducing universal screening for cCMV to both increase detection of children who would benefit from treatment, and to build a more robust evidence base for future research.

Cognitive predictors of parent-rated inattention in very preterm children: The role of working memory and processing speed.

Inattention is one of the most common neurobehavioral problems following very preterm birth. Attention problems can persist into adulthood and are associated with negative socio-emotional and educational outcomes. This study aimed to determine whether the cognitive processes associated with inattention differ between term-born and very preterm children. Sixty-five children born very preterm (<33+0 weeks' gestation) aged 8-11 years were recruited alongside 48 term-born controls (?37 20 +0 weeks' gestation). Both groups included children with a wide spectrum of parent-rated inattention (above average attention to severe inattention) measured as a continuous dimension using the Strengths and Weaknesses of ADHD and Normal-Behavior (SWAN) scale. The children completed tests to assess basic cognitive processes and executive function. A hierarchical multiple regression analysis was implemented to assess which neurocognitive processes explained variance in parent-rated inattention and whether these differed between preterm and term-born children. In both groups, poorer verbal and visuospatial short-term memory and poorer visuospatial working memory independently explained variance in parent-rated inattention. Slower motor processing speed explained variance in inattention among very preterm children only. The cognitive mechanisms associated with parent-rated inattention were predominantly overlapping between groups, but relationships between motor processing speed and inattention were unique to very preterm children. These associations may reflect risk factors for inattention in term and very preterm children. Future research should assess the efficacy of these cognitive processes as potential targets for intervention.

Item banking and computer-adaptive testing in clinical trials: Standing in sight of the PROMISed land.

The use of patient-reported outcome instruments (PRO) in clinical trials in order to capture the impacts of treatment on patients is widespread. However, regulatory agencies have over the past decade highlighted the need for PROs that are fit for purpose and target relevant aspects of the patient's condition. Many legacy PROs were developed with little patient input, are lengthy, and may lack relevance having not been modified or adapted as medical treatments have advanced. Computer-adaptive test (CAT) systems provide the possibility of targeted approaches to capturing patient-centric data, while minimising patient burden. Coupled with greater patient input in the development of PROs, CAT offers the opportunity of overcoming the shortcomings of the previous generation of PROs. This paper describes the some of the issues facing legacy PROs, current regulatory guidance, and initiatives, such as the Patient-Reported Outcome Measurement Information System (PROMIS), as well as the early signs of use of CAT to capture PRO data in clinical trials.

Utility elicitation in adults and children for allergic rhinoconjunctivitis and associated health states.

PURPOSE: Allergic rhinitis and asthma symptoms are detrimental to health-related quality of life (HRQoL). Health technology appraisal agencies often require cost-utility analysis when assessing new interventions. Appropriate utility estimates, which quantify the value of different conditions in cost-utility analyses, are scarce for allergic rhinitis and asthma health states. This study aimed to generate utilities for allergic rhinitis and asthma health states from a European general population sample of adults and children. METHODS: Health state descriptions incorporating symptoms, impact of symptoms on daily life and symptom treatment were developed using clinical guidelines. Descriptions were amended with clinician and patient input, and incorporated into a survey in which each health state was followed by a standard gamble (adults) or visual analogue scale (children) item. The survey was distributed to samples of adults and children aged 8 to 11 from four European countries that were stratified to represent the general population within that country. RESULTS: 1454 adults and 1082 children completed the survey. Mean health utilities ranged from 0.635 to 0.880 and those elicited in children were lower (0.635 to 0.705) than those elicited in adults (0.812 to 0.880). Disutilities assessing the impact of increased allergic rhinitis severity and comorbidities were also greater in children than in adults. CONCLUSIONS: Symptoms of allergic rhinitis and asthma were valued as having a clinically meaningful impact on HRQoL. Children valued health states as poorer than adults, and further research should investigate whether this reflects true preferential differences or results from methodological and/or comprehension differences between the two groups.

Prolonging the response movement inhibits the feed-forward motor program in the sustained attention to response task.

Despite widespread use in clinical and experimental contexts, debate continues over whether or not the Sustained Attention to Response Task (SART) successfully measures sustained attention. Altering physical aspects of the response movement required to SART stimuli may help identify whether performance is a better measure of perceptual decoupling, or response strategies and motor inhibition. Participants completed a SART where they had to manually move a mouse cursor to respond to stimuli, and another SART where this extra movement was not required, as in a typical SART. Additionally, stimuli were located at either a close or a far distance away. Commission errors were inversely related to distance in the manual movement condition, as the farther distance led to longer response times which gave participants more time to inhibit prepotent responses and thus prevent commission errors. Self-reported measures of mental demand and fatigue suggested there were no differences in mental demands between the manual and automatic condition; instead the differences were primarily in physical demands. No differences were found for task-unrelated thoughts between the manual and automatic condition. The movement effect combined with participants' subjective reports are evidence for time dependent action stopping, not greater cognitive engagement. These findings support a response strategy perspective as opposed to a perceptual decoupling perspective, and have implications for authors considering using the SART. Applied implications of this research are also discussed.