To confirm your appointment, please press one: Examining demographic and health system interface factors that predict missed appointments in a pediatric outpatient neuropsychology clinic.

Objective: Missed patient appointments have a substantial negative impact on patient care, child health and well-being, and clinic functioning. This study aims to identify health system interface and child/family demographic characteristics as potential predictors of appointment attendance in a pediatric outpatient neuropsychology clinic. Method: Pediatric patients (N = 6,976 across 13,362 scheduled appointments) who attended versus missed scheduled appointments at a large, urban assessment clinic were compared on a broad array of factors extracted from the medical record, and the cumulative impact of significant risk factors was examined. Results: In the final multivariate logistic regression model, health system interface factors that significantly predicted more missed appointments included a higher percentage of previous missed appointments within the broader medical center, missing pre-visit intake paperwork, assessment/testing appointment type, and visit timing relative to the COVID-19 pandemic (i.e. more missed appointments prior to the pandemic). Demographic characteristics that significantly predicted more missed appointments in the final model included Medicaid (medical assistance) insurance and greater neighborhood disadvantage per the Area Deprivation Index (ADI). Waitlist length, referral source, season, format (telehealth vs. in-person), need for interpreter, language, and age were not predictive of appointment attendance. Taken together, 7.75% of patients with zero risk factors missed their appointment, while 22.30% of patients with five risk factors missed their appointment. Conclusions: Pediatric neuropsychology clinics have a unique array of factors that impact successful attendance, and identification of these factors can help inform policies, clinic procedures, and strategies to decrease barriers, and thus increase appointment attendance, in similar settings.

"It starts with a knock on the door": Caregiver and provider perspectives on healthcare communication for youth with intellectual and developmental disabilities.

OBJECTIVES: Effective healthcare communication (HCC) is critical for youth with intellectual and developmental disabilities (IDD) who may have complex healthcare needs. The goal of this study was to gain family caregiver and provider perspectives on facilitators and challenges to effective HCC for youth with IDD. METHODS: Caregivers of, and providers for youth with IDD were recruited from the community to participate in virtual focus group (FG) sessions. FGs were 60-90 min long and were facilitated by a research team consisting of caregivers and providers. The FGs were recorded, transcribed, and coded inductively for HCC themes. RESULTS: Nineteen stakeholders participated in the FGs (caregivers: n = 14; providers: n = 5). Twenty-three themes were coded from the transcripts and were categorized by whether they focused on providers, caregivers, or healthcare systems. CONCLUSIONS: Provider behaviors such as active listening and demonstrating humility were found to be critical for effective HCC. Fewer caregiver factors, such as advocacy, and systems factors such as visit format, emerged from the FG data. FG themes represent challenges that future interventions must address. PRACTICE IMPLICATIONS: Efforts to improve HCC, and thus healthcare outcomes for youth with IDD, should address challenges identified by caregivers and providers.

Association of Time in Bed, Social Jetlag, and Sleep Disturbances With Cognitive Performance in Children With ADHD.

OBJECTIVES: Children with ADHD commonly exhibit sleep disturbances, but there is limited knowledge about how sleep and sleep timing are associated with cognitive dysfunction in children with ADHD. METHODS: Participants were 350 children aged 5 to 12 years diagnosed with ADHD. Three sleep-related constructs-time in bed, social jetlag (i.e., discrepancy in sleep timing pattern between school nights and weekend nights), and sleep disturbances were measured using a caregiver-report questionnaire. Linear regression models assessed the associations between sleep-related constructs and cognitive performance. RESULTS: After adjustment for sociodemographic variables, there were few associations between time in bed or sleep disturbances and cognitive performance, however, greater social jetlag was negatively associated with processing speed (ß = -.20, 95% CI [-0.35, -0.06]), visually-based reasoning (ß = -.13, 95% CI [-0.27, 0.00]), and language-based reasoning (ß = -.22, 95% CI [-0.36, -0.08]); all p < .05). CONCLUSION: Social jetlag, but not time in bed or disturbances, was associated with lower cognitive performance among children with ADHD.

Association Between Neighborhood Deprivation and Child Cognition in Clinically Referred Youth.

OBJECTIVE: When socioeconomic status is measured at the individual and/or family level, it has long been associated with cognition in children. However, the association between neighborhood deprivation, an index of community-level socioeconomic status, and child cognition is not fully understood. The goal of this study was to investigate (1) the relationship between neighborhood deprivation and child cognitive functioning and (2) whether child age moderates the relationship between cognitive functioning and neighborhood deprivation. METHODS: This study included 9878 children, ages 3 through 17 years (M = 10.4 yrs, SD = 3.4 yrs). Data were gathered from children referred for and evaluated at an urban, outpatient neuropsychology assessment clinic between 2006 and 2022, located in the Mid-Atlantic region of the United States. Neighborhood socioeconomic status was measured at the census block level using the Area Deprivation Index composite. RESULTS: There was a 20-point median difference in overall intelligence between the neighborhoods with the lowest and highest levels of deprivation. Overall intelligence and verbal comprehension, compared with working memory, fluid reasoning, and processing speed, demonstrated the strongest negative association with neighborhood deprivation (all p < 0.05). Older children had lower overall intelligence scores compared with younger children in neighborhoods with high levels of deprivation ( p < 0.01), suggesting a cumulative influence of poverty exposure. CONCLUSION: This study demonstrates the stark disparities in child cognitive functioning across levels of neighborhood deprivation. Findings support the importance of access to early interventions and services that promote intellectual growth and verbal capacity among children who live in neighborhoods with great deprivation.

Bootstrap Exploratory Graph Analysis of the WISC-V with a Clinical Sample.

One important aspect of construct validity is structural validity. Structural validity refers to the degree to which scores of a psychological test are a reflection of the dimensionality of the construct being measured. A factor analysis, which assumes that unobserved latent variables are responsible for the covariation among observed test scores, has traditionally been employed to provide structural validity evidence. Factor analytic studies have variously suggested either four or five dimensions for the WISC-V and it is unlikely that any new factor analytic study will resolve this dimensional dilemma. Unlike a factor analysis, an exploratory graph analysis (EGA) does not assume a common latent cause of covariances between test scores. Rather, an EGA identifies dimensions by locating strongly connected sets of scores that form coherent sub-networks within the overall network. Accordingly, the present study employed a bootstrap EGA technique to investigate the structure of the 10 WISC-V primary subtests using a large clinical sample (N = 7149) with a mean age of 10.7 years and a standard deviation of 2.8 years. The resulting structure was composed of four sub-networks that paralleled the first-order factor structure reported in many studies where the fluid reasoning and visual-spatial dimensions merged into a single dimension. These results suggest that discrepant construct and scoring structures exist for the WISC-V that potentially raise serious concerns about the test interpretations of psychologists who employ the test structure preferred by the publisher.

Improved parent self-efficacy following pediatric evaluation: Evidence for value of a telemedicine approach in psychological and neuropsychological assessment.

Objective: While considerable inquiry is currently underway into the comparability of psychological test results obtained in onsite/in-person settings versus telemedicine settings, there has been less attention given to the comparability of the impact/outcome of the assessment process across settings. The current quality improvement study conceptualized impact/outcome according to the model of Austin et al. and sought to determine whether the prior finding of increased parent self-efficacy following onsite neuropsychological assessment was also observed when psychological and neuropsychological assessment was conducted via a telemedicine modality. Method: In the course of standard care delivery, ratings from Austin et al.'s four parent self-efficacy items were obtained at time 1 prior to patients' assessment visits and then again at time 2 either (1) following their last assessment/feedback visit (the Complete Assessment group; n = 157) or (2) in the middle of the assessment process prior to the last planned visit (the Incomplete Assessment group; n = 117). Results: Analyses revealed significant findings for time and time × group. Parent self-efficacy ratings improved over time in both groups, with significantly higher ratings in the Complete Assessment group at time 2. When compared to reference means from the in-person/onsite Austin et al. study, ratings from the current study found comparable improvement in parent self-efficacy achieved via telemedicine assessment in the Complete Assessment group. Conclusions: These data support the use of telemedicine based psychological and neuropsychological evaluation and provide preliminary evidence that the impact/outcome is comparable with in-person/onsite assessment.

Characterizing and comparing adaptive and academic functioning in children with low average and below average intellectual abilities.

Objective The recent American Academy of Clinical Neuropsychology (AACN) consensus statement on uniform labeling of performance test scores places children who were previously characterized as having "borderline intellectual functioning" within the low average (LA; full scale intellectual quotient (FSIQ) between 80-89) or below average (BA; FSIQ between 70-79) categories. Given limited research examining functional differences across FSIQ groups using AACN's uniform labeling, this study examined adaptive and academic functioning by FSIQ group in youth referred for (neuro)psychological evaluation. Primary comparisons of interest were between LA and BA groups. MethodParticipants were 2,516 children between 6 to 13 years with standardized measures of intellectual, adaptive, and academic functioning. Participants were included if their FSIQ ranged from average to exceptionally low. Group differences in adaptive functioning and academic achievement were examined. ResultsThe LA group did not differ from the BA group in overall adaptive functioning and several domains of adaptive functioning (i.e. social, practical), but demonstrated slightly stronger adaptive skills in the conceptual domain. While the LA group evidenced slightly better word reading and math computation scores than the BA group, these statistically significant differences were not clinically -meaningful. ConclusionsIn this clinically referred sample, children with LA and BA intellectual abilities demonstrated similar adaptive skills, but slightly different academic achievement. Both groups demonstrated lower adaptive and academic functioning than children with average range FSIQs. These results suggest that adaptive functioning should be assessed during (neuro)psychological evaluations even when children do not have extremely low FSIQs.

Can We Expand the Pool of Youth Who Receive Telehealth Assessments for ADHD? Covariates of Service Utilization.

BACKGROUND: During the COVID-19 pandemic, telehealth became widely utilized for healthcare, including psychological evaluations. However, whether telehealth has reduced or exacerbated healthcare disparities for children with Attention-Deficit/Hyperactivity Disorder (ADHD) remains unclear. METHODS: Data (race, ethnicity, age, insurance type, ADHD presentation, comorbidities, and distance to clinic) for youth with ADHD (Mage = 10.97, SDage = 3.42; 63.71% male; 51.62% White) were extracted from the medical record at an urban academic medical center. Three naturally occurring groups were compared: those evaluated in person prior to COVID-19 (n =780), in person during COVID-19 (n = 839), and via telehealth during COVID-19 (n = 638). RESULTS: Children seen via telehealth were significantly more likely to be older, White, have fewer comorbid conditions, and live farther from the clinic than those seen in person. CONCLUSIONS: The current study suggests that telehealth has not eliminated barriers to care for disadvantaged populations. Providers and institutions must take action to encourage telehealth use among these groups.

Does Assessment Format Matter? A Comparison of In-Person Versus Teletesting Scores for Youth with ADHD.

OBJECTIVE: This study examined test score equivalency between traditional in-person assessment and teletesting among youth diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). METHOD: In all, 896 youth with ADHD, ages 5-21 years, were administered cognitive, academic achievement, and verbal fluency measures via either teletesting (n = 448) or traditional in-person assessment (n = 448). The teletesting and in-person groups were matched on age, sex, and insurance type (as a proxy for income). RESULTS: Results indicated no significant differences in test scores obtained via in-person and teletesting evaluations across all examined measures. CONCLUSION: Clinically referred youth with ADHD perform similarly on measures of cognitive functioning, academic achievement, and verbal fluency, regardless of whether these measures are administered in-person or via teletesting. While additional evidence for equivalent psychometric properties of neuropsychological instruments administered remotely is needed, this study offers support for the validity of remote administration among youth with ADHD.

An abbreviated WISC-5 model for identifying youth at risk for intellectual disability in a mixed clinical sample.

OBJECTIVE: The correct "dosing" of neuropsychological assessment is of interest for the purposes of cost management and the personalization of medicine/assessment. In this context, embedded IQ screening, rather than routine comprehensive IQ testing, may be useful in identifying youth at risk for Intellectual Disability (ID) for whom further assessment is needed. This retrospective, cross-sectional study examined subtests from the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-5) needed to identify youth with Full Scale IQ (FSIQ) ≤75. METHOD: Data were obtained from a large pediatric clinically referred sample (N = 4,299; Mean Age = 10.7 years; Range = 6-16y; 66% male; 54% White; 29% receiving Public Insurance), divided into training (n = 2149) and test (n = 2150) samples. RESULTS: In the training sample, sequential and additive regression-based models for predicting FSIQ comprised of one (Block Design [BD]), two (BD + Similarities [SI]), three (BD + SI + Matrix Reasoning [MR]), and four (BD + SI + MR + Digit Span [DS]) subtests of the WISC-5 explained 61.3%, 82.7%, 88.5%, and 93.0% of FSIQ variance, respectively. Using a predicted FSIQ ≤ 80 as a cut score to identify persons with observed FSIQ ≤75, the two subtest (BD + SI) model showed strong sensitivity (83.4), specificity (90.5), and negative predictive value (96.2) in the test sample; however, positive predictive value was low (65.3%). Three and four subtest models provided incremental, but modest gains in classification metrics. CONCLUSIONS: Findings suggest the first several subtests of the WISC-5 can be used to identify clinically referred youth at risk for ID who subsequently require full administration of the WISC-5 for consideration of an ID diagnosis.

Long-term stability of Wechsler Intelligence Scale for Children-fifth edition scores in a clinical sample.

This study investigated the stability of Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V) scores for 225 children and adolescents from an outpatient neuropsychological clinic across, on average, a 2.6 year test-retest interval. WISC-V mean scores were relatively constant but subtest stability score coefficients were all below 0.80 (M = 0.66) and only the Verbal Comprehension Index (VCI), Visual Spatial Index (VSI), and omnibus Full Scale IQ (FSIQ) stability coefficients exceeded 0.80. Neither intraindividual subtest difference scores nor intraindividual composite difference scores were stable across time (M = 0.26 and 0.36, respectively). Rare and unusual subtest and composite score differences as well as subtest and index scatter at initial testing were unlikely to be repeated at retest (kappa = 0.03 to 0.49). It was concluded that VCI, VSI, and FSIQ scores might be sufficiently stable to support normative comparisons but that none of the intraindividual (i.e. idiographic, ipsative, or person-relative) measures were stable enough for confident clinical decision making.

How much testing can a kid take? Feasibility of collecting pediatric patient experience ratings of neuropsychological and psychological assessment.

Parent-reported satisfaction is an important outcome measure in pediatric neuropsychology; however, self-report of patient experience following lengthy pediatric assessments has been under-investigated. Written at a first grade reading level and utilizing touch screen and read-aloud functionality, a set of 15 operationally-focused items were administered to evaluate pediatric patient experience of neuropsychological and psychological assessment. One-hundred ninety-seven clinically-referred patients (M age = 11.74, SD = 3.17, range = 5.86-19.02 years, 56% male) answered the post-assessment survey. The majority of patients (n = 167; 84.77%) accurately completed the initial two validity items, even though many had parent-reported ratings of reading difficulty. More than a third of patients indicated that the assessment made them tired (39%), but fewer patients reported feeling bored (13%) or worried (7%) during testing. Moreover, most patients reported having fun (66%) and many indicated that testing was preferable to other activities typically performed at that same time (i.e., school, homework). Responses to items assessing the child's interactions with the clinician and the child's effort provided little variation and were answered in a socially desirable manner. Items that focused upon the child's personal response to the assessment appointment (e.g., boredom, worry), however, elicited greater variance in patient responding. In general, patient responses did not suggest that assessment was an aversive experience. Overall, these proof of concept findings suggest that most referred pediatric patients, even those with learning issues, may be capable of independently navigating and completing self-report questionnaires while providing differential responses to items assessing clinical experience. Self-report questionnaires appear to be a feasible method for acquiring pediatric patient-reported experiences of assessment.

What's race got to do with it? Informant rating discrepancies in neuropsychological evaluations for children with ADHD.

OBJECTIVE: To evaluate race-based discrepancies in informant ratings and in rates of Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosis among a clinically referred sample of Black and White children. METHOD: Demographic information and ratings of inattention, hyperactivity/impulsivity, and conduct were collected from caregivers and teachers as part of neuropsychological evaluations at an outpatient clinic. The final sample included 3,943 children (6-18 years), of which 70% were White and 30% were Black. RESULTS: Teachers, but not caregivers, endorsed more inattentive symptoms and conduct problems for Black than for White children, irrespective of ADHD diagnostic status and socioeconomic status (SES), and after controlling for child sex, child age, and learning difficulties. Teachers endorsed more hyperactive/impulsive symptoms for Black children with ADHD of lower SES than for White children with these characteristics. Caregivers of Black children of higher SES reported fewer hyperactive/impulsive symptoms than caregivers of White children of higher SES. Despite differences in teachers' ratings by race, diagnostic rates of ADHD in the context of neuropsychological evaluations were comparable for Black and White children. CONCLUSIONS: Consistent with previous literature, teachers endorsed more ADHD and conduct problems in Black children. Within our clinically referred sample, this may reflect teacher bias rather than actual prevalence differences by rafce, given that Black caregivers endorsed fewer or similar numbers of symptoms relative to White caregivers. This lack of racial disparities in rates of ADHD diagnosis is inconsistent with findings in community- and population-based samples, and reflectspossible benefit of the use of neuropsychological evaluations in diagnostic decision-making for ADHD.

Pediatric neuropsychological evaluation via telehealth: Novel models of care.

Objective: As the coronavirus pandemic extends across the globe, the impacts have been felt across domains of industry. Neuropsychology services are no exception. Methods for neuropsychological assessments, which typically require an in-person visit, must be modified in order to adhere to social distancing and isolation standards enacted in an effort to slow the pandemic. How can providers continue to meet the needs of patients referred for neuropsychology evaluations, while respecting federal and state guidelines for safety and ethical mandates? We offer a novel, tiered model of care, successfully implemented in response to mandated social distancing, in a large, pediatric neuropsychology program.Method: We describe the considerations and challenges to be addressed in transitioning a large neuropsychology department to a new model of care, including triaging referrals, developing -or rediscovering - types of services to meet the needs of a virtual patient population, and helping patients, parents, and providers to adjust to these new models.Conclusions: Lessons learned as a function of rapid changes in care models have implications for the field of neuropsychology as a whole as well as for future flexibility in meeting the needs of pediatric patients and their families.

Transitioning to telehealth neuropsychology service: Considerations across adult and pediatric care settings.

Objectives: In response to the 2020 COVID-19 pandemic, traditional, in-person neuropsychological assessment services paused in most settings. Neuropsychologists have sought to establish new guidelines and care models using telehealth neuropsychology (teleNP) services. The need to adapt to remote technology became the most difficult challenge to date for existing practice models. Results: Primary considerations for transitioning to teleNP include scope and limitations of the telehealth modality, informed consent for telehealth services, patient privacy and confidentiality, test security, and validity of telehealth assessments. Given timelines for fully re-opening clinical settings, access to traditional models of neuropsychological care remains unclear. These considerations will remain relevant even upon return to an in-office practice, as many assessment models will likely continue with teleNP to some extent. Specialists will need to consider the unique needs of their populations in ensuring quality care, as diagnostic differences and patient age will impact participation in teleNP. Conclusions: As the COVID-19 pandemic lingers, teleNP presents an opportunity as well as a challenge for neuropsychologists looking to provide patient care in the context of social distancing and stay-at-home restrictions. In this transformative time, the field of neuropsychology has opportunities to advance beyond traditional settings and focus on alternative delivery of patient care.

Construct Validity of the WISC-V in Clinical Cases: Exploratory and Confirmatory Factor Analyses of the 10 Primary Subtests.

Independent exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) research with the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V) standardization sample has failed to provide support for the five group factors proposed by the publisher, but there have been no independent examinations of the WISC-V structure among clinical samples. The present study examined the latent structure of the 10 WISC-V primary subtests with a large (N = 2,512), bifurcated clinical sample (EFA, n = 1,256; CFA, n = 1,256). EFA did not support five factors as there were no salient subtest factor pattern coefficients on the fifth extracted factor. EFA indicated a four-factor model resembling the WISC-IV with a dominant general factor. A bifactor model with four group factors was supported by CFA as suggested by EFA. Variance estimates from both EFA and CFA found that the general intelligence factor dominated subtest variance and omega-hierarchical coefficients supported interpretation of the general intelligence factor. In both EFA and CFA, group factors explained small portions of common variance and produced low omega-hierarchical subscale coefficients, indicating that the group factors were of poor interpretive value.

Initial Examination of the BRIEF2 in Clinically Referred Children With and Without ADHD Symptoms.

Objective: Clinical utility of the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) was examined in 1,381 clinically referred youth (62.5% male, 5 to 18 years) with and without ADHD symptoms. Method: Participants included children with restricted inattentive symptoms (IA only), restricted hyperactivity/impulsivity symptoms (HI only), symptoms in both domains (Combined), and non-ADHD clinical comparison. Results: Greater hyperactivity (Combined, HI only) was associated with higher Behavior Regulation (BRI) and Emotion Regulation (ERI) scores, whereas greater inattentiveness (IA only, Combined) was associated with higher Cognitive Regulation scores. Effect sizes were largest for Inhibit, Working Memory, and Organization of Materials scales; these scales discriminated children with and without ADHD symptoms and restricted inattentive and hyperactive presentations. Conclusion: The BRIEF2 distinguishes associated features of ADHD and the day-to-day executive impact. Sensitivity was consistently poorer than specificity. The referred nature of the sample and examination of restricted presentations suggest additional work is needed to examine whether ERI and BRI are dissociable.

Proliferation Tumour Marker Network (PTM-NET) for the identification of tumour region in Ki67 stained breast cancer whole slide images.

Uncontrolled proliferation is a hallmark of cancer and can be assessed by labelling breast tissue using immunohistochemistry for Ki67, a protein associated with cell proliferation. Accurate measurement of Ki67-positive tumour nuclei is of critical importance, but requires annotation of the tumour regions by a pathologist. This manual annotation process is highly subjective, time-consuming and subject to inter- and intra-annotator experience. To address this challenge, we have developed Proliferation Tumour Marker Network (PTM-NET), a deep learning model that objectively annotates the tumour regions in Ki67-labelled breast cancer digital pathology images using a convolution neural network. Our custom designed deep learning model was trained on 45 immunohistochemical Ki67-labelled whole slide images to classify tumour and non-tumour regions and was validated on 45 whole slide images from two different sources that were stained using different protocols. Our results show a Dice coefficient of 0.74, positive predictive value of 70% and negative predictive value of 88.3% against the manual ground truth annotation for the combined dataset. There were minimal differences between the images from different sources and the model was further tested in oestrogen receptor and progesterone receptor-labelled images. Finally, using an extension of the model, we could identify possible hotspot regions of high proliferation within the tumour. In the future, this approach could be useful in identifying tumour regions in biopsy samples and tissue microarray images.

The use of 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) as a non-invasive pharmacodynamic biomarker to determine the minimally pharmacologically active dose of AZD8835, a novel PI3Kα inhibitor.

BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development. It has been used widely with PI3K inhibitors both clinically and pre-clinically because of the role of the PI3K pathway in glucose metabolism. In this study we investigated the potential of 18F-FDG PET as a non-invasive pharmacodynamic biomarker for AZD8835. We sought to understand if 18F-FDG PET could determine the minimally effective dose of AZD8835 and correlate with other pharmacodynamic biomarkers for validation of its use in clinical development. 18F-FDG PET scans were performed in nude mice in the BT474C breast xenograft model. Mice were fasted prior to imaging and static 18F-FDG PET was performed. Treatment groups received AZD8835 by oral gavage at a dose volume of 10ml/kg. Treatment groups received either 3, 6, 12.5, 25 or 50mg/kg AZD8835. Tumour growth was monitored throughout the study, and at the end of the imaging procedure, tumours were taken and a full pharmacodynamic analysis was performed. RESULTS: Results showed that AZD8835 reduced 18F-FDG uptake at a dose of 12.5, 25 and 50mg/kg with no significant reduction at doses of 3 and 6mg/kg. These results were consistent with other pharmacodynamics biomarkers measured and show 18F-FDG PET as a sensitive biomarker with the ability to determine the minimal effective dose of AZD8835. CONCLUSIONS: Our pre-clinical studies support the use of 18F-FDG PET imaging as a sensitive and non- invasive pharmacodynamic biomarker (understanding the role of PI3K signalling in glucose uptake) for AZD8835 with a decrease in 18F-FDG uptake observed at only two hours post treatment. The decrease in 18F-FDG uptake was dose dependent and data showed excellent PK/PD correlation. This data supports and parallels observations obtained with this class of compounds in patients.

Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a secondary analysis of data from a randomised controlled trial.

Asthma mortality surveys report delays in seeking medical review and overuse of beta-agonist therapy as factors contributing to a fatal outcome. However, the strength of these associations is limited because many asthma deaths are unwitnessed. We undertook a secondary analysis of data from a 24-week randomised controlled trial of 303 patients with high-risk asthma, randomised to combination budesonide/formoterol inhaler according to a single maintenance and reliever therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever (Standard) regimen. Medication use was measured by electronic monitors. The thresholds for high, marked and extreme beta-agonist use days were defined in the single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of budesonide/formoterol in excess of four maintenance doses, respectively; and in the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively. Whether a medical review was obtained within 48 h of an overuse episode was determined by review of data collected during the study by participant report. The mean (standard deviation) proportion of days in which high, marked and extreme beta-agonist overuse occurred without medical review within 48 h was 0·94(0·20), 0·94(0·15) and 0·94(0·17), and 0·92(0·19), 0·90(0·26) and 0·94(0·15) for single maintenance and reliever therapy and Standard regimens, respectively. In at least 90% of days, in which beta-agonist overuse occurred, patients did not obtain medical review within 48 h of beta-agonist overuse, regardless of the magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist regimen. RELIEVER INHALER OVERUSE AND DELAY IN MEDICAL REVIEW IN ASTHMA: In asthma, overuse of beta-agonist reliever medication and delay in seeking medical review in an exacerbation are linked to asthma deaths. Janine Pilcher at the Medical Research Institute of New Zealand, and co-workers, conducted a review of data from a study of 303 adult patients with severe asthma, followed over 24 weeks. The patients were allocated to either a budesonide/formoterol, or a salbutamol inhaler to take for symptom relief, in addition to their maintenance treatment. Inhalers were fitted with electronic monitors, to accurately document every use. In both groups, on 90% of days when an exacerbation requiring excess use of an inhaler occurred, patients did not follow-up with medical professionals within 48 h as advised. Further, in both groups, 'extreme' reliever inhaler use was recorded at least once in around one in four patients.