Anxiety in Turner syndrome: Engaging community to address barriers and facilitators to diagnosis and care.

Turner syndrome (TS), caused by complete or partial loss of the second sex chromosome, is associated with complex medical manifestations. The TS community identifies anxiety as a major contributor to reduced quality of life. The study aimed to improve understanding of anxiety symptomatology, diagnosis, and care in individuals with TS. A mixed methods design integrated community engagement, including community leaders as co-investigators and a community advisory board, an online survey (N = 135), and in-depth interviews (N = 10). The majority of respondents reported that anxiety symptoms occur two or more days per week, with self-advocates reporting more frequent symptoms than caregivers (p = 0.03). Self-advocates reported feeling anxious more often at school/work; both rater groups reported anxiety-related behaviors were most likely to be expressed at home. Insomnia was the most common symptom of anxiety endorsed across age and rater groups (>70%). Anxiety symptoms and triggers changed with age and often were undiagnosed or untreated during childhood. Therapy and medication were reported as helpful by most respondents who had tried these strategies. Qualitative themes included: 'Triggers for anxiety are related to TS', 'Anxiety impacts the whole family', and 'Opportunities for early identification and intervention'.

From Evidence-Based Guidelines to Clinical Practice: Pediatric Neuropsychology Care in Multidisciplinary Clinics.

OBJECTIVE: High demand for pediatric neuropsychological care has highlighted the time- and resource-intensive nature of traditional comprehensive evaluations. Emerging care models address these constraints by facilitating tiered neuropsychological services provided in various contexts, including multidisciplinary clinics (MDCs). We aim to demonstrate feasibility and acceptability of tiered neuropsychological care in MDCs through examples from a single institution. METHODS: A review of all current MDC practices at a tertiary pediatric care center was conducted to describe clinic workflow, services provided, and triage strategies. Pediatric neuropsychologists (n = 5) and other health care providers (n = 31) completed a survey focused on experience with neuropsychology consultation in MDCs. RESULTS: Neuropsychologists provided care in 11 MDCs, including universal monitoring with consultative interviews and questionnaires, as well as targeted screening. Neuropsychologists (89%) and other health professionals (100%) reported that tiered neuropsychological services improved patient care within MDCs. Other health professionals reported utilizing results from neuropsychology MDC care to inform their clinical approach (48-90%), referrals (58%), and treatment or surveillance decisions (55-71%). CONCLUSION: Tiered neuropsychological care in pediatric MDCs is feasible, and provider experience ratings indicate high acceptability. Practical steps for development of MDCs are provided, including identifying teams, clinic goals and outcomes, operational logistics, and billing.

Cognitive dysfunction in pediatric systemic lupus erythematosus: current knowledge and future directions.

Cognitive dysfunction (CD) is a neurologic complication of pediatric systemic lupus erythematosus (SLE) that remains poorly understood and understudied, despite the potential negative effects of CD on long-term socioeconomic status and quality of life. Data regarding the prevalence and risk factors for CD in pediatric SLE as well as the optimal screening, treatment, and long-term outcomes for CD are lacking. In this review, we present current knowledge on CD in pediatric SLE with a focus on the application to clinical practice. We discuss the challenges in diagnosis, clinical screening methods, potential impacts, and interventions for this complication. Finally, we discuss the remaining gaps in our knowledge of CD in pediatric SLE, and avenues for future research efforts.

Lifetime risk of herpes zoster in the population of Beijing, China.

Objectives: We aimed to estimate the current and future lifetime risks (LTR) of herpes zoster (HZ) and postherpetic neuralgia (PHN), as well as their respective number of annual incident cases in Beijing, China, if individuals were not vaccinated against HZ. Study design: Mathematical model built in Microsoft Excel, de novo. Methods: A hypothetical cohort of 1,000 people was simulated from age 0-100 or until death to generate LTRs of HZ/PHN in Beijing, China. LTR was defined as the risk of developing HZ/PHN at least once in the person's lifetime. The current number of annual incident HZ/PHN cases were also calculated by multiplying up-to-date population data and the annual age-specific incidence of HZ/PHN. For both LTR and annual incident cases, current estimates were projected into the year 2035 to investigate the impact of an aging population. Scenario and deterministic sensitivity analyses (DSA) were conducted to validate the model outcomes. Results: In Beijing, the current and future LTRs of HZ (PHN) were 32.4% (2.8%) and 34.8% (3.3%), respectively. The current and future annual incident cases of HZ (PHN) of individuals aged ≥50 years were 68,394 (7,801) cases among 7.04 million individuals and 88,676 (9,649) cases among 9.08 million individuals, respectively. The scenario analyses demonstrated that modelled results were likely to underestimate the LTR of HZ. Results were robust under the DSA. Conclusions: Given an aging population, HZ poses a significant, growing burden on individuals, the society, and healthcare system of China, highlighting the need for preventative measures such as vaccination.

Neuropsychological and mental health concerns in a multicenter clinical sample of youth with turner syndrome.

Clinical practice guidelines for individuals with Turner syndrome (TS) recommend screening for neuropsychological concerns (NC) and mental health concerns (MHC). However, current provider screening and referral patterns for NC and MHC are not well characterized. Additionally, prevalence of and risk factors for NC and MHC vary across studies. This multicenter chart review study examined the prevalence, risk factors for, and management of NC and MHC in a cohort of 631 patients with TS from three pediatric academic medical centers. NC and/or MHC were documented for 48.2% of patients. Neuropsychological evaluation recommendations were documented for 33.9% of patients; 65.4% of the sample subsequently completed these evaluations. Mental health care recommendations were documented in 35.0% of records; subsequent documentation indicated that 69.7% of these patients received such services. Most notably, rates of documented MHC, NC, and related referrals differed significantly by site, suggesting the need for standardized screening and referral practices. TS diagnosis in early childhood was associated with an increased risk of NC. Spontaneous menarche was associated with increased risk of MHC. Younger age at growth hormone initiation was associated with both increased risk of isolated NC and co-occurring NC and MHC. Mosaic karyotype was associated with decreased risk of NC and MHC.

Cost-Effectiveness Analysis Update of the Adjuvanted Recombinant Zoster Vaccine in Japanese Older Adults.

INTRODUCTION: This study aimed to update cost-effectiveness and public health impact estimates of the two-dose recombinant zoster vaccine (RZV) compared with no vaccination against herpes zoster (HZ) in the Japanese population aged 65 years. List price of the vaccine and latest RZV efficacy and waning estimates were incorporated. METHODS: A multicohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of one million people aged 65 years over their remaining lifetime (base case). Age-stratified vaccine efficacy and waning rates were updated on the basis of the latest clinical trial data (interim ZOE-LTFU; NCT02723773). First-dose coverage was assumed at 40%, and second-dose compliance was assumed at 95%. Costs and outcomes were discounted at 2% annually, and the incremental cost-effectiveness ratio (ICER) was calculated from payer and societal perspectives. The societal perspective considered productivity loss due to suffering HZ, or due to suffering HZ and time required for vaccination. Sensitivity analyses explored the overall uncertainties in the model. Scenario analyses for Japanese adults aged 50, 60, 70, 80, ≥ 50, and ≥ 65 years (main scenario) were conducted. An ICER below ¥5-6 million/quality-adjusted life-year (QALY) was considered cost-effective. RESULTS: RZV was estimated to prevent 71,423 HZ cases and 15,858 post-herpetic neuralgia (PHN) cases per million people aged 65 years compared with no vaccine in Japan. The ICER was ¥4,205,515 from a payer perspective and was most sensitive to assumptions regarding vaccine efficacy waning, proportion of patients with HZ developing PHN, and HZ incidence. From societal perspectives, ICERs were ¥3,854,192 (productivity loss from suffering HZ only) and ¥4,622,212 (productivity loss from suffering HZ and time required for vaccination). Overall, the results were considered robust under extensive sensitivity and scenario analyses. CONCLUSION: Vaccination against HZ with RZV is cost-effective compared with no vaccination in Japanese adults aged 65 years.

Fertility Counseling Practices for Patients with Turner Syndrome in Pediatric Endocrine Clinics: Results of a Pediatric Endocrine Society Survey.

INTRODUCTION: Turner syndrome (TS) is associated with a high risk of primary ovarian insufficiency. Current guidelines recommend early fertility counseling for affected youth and their families. This study assessed clinical providers' (MD, NP, or PA) fertility counseling practices for girls with TS. METHODS: TS providers were invited to complete a survey via the Pediatric Endocrine Society listserv. Descriptive statistics summarized variables of interest. Correlations were used to identify associations between barriers/practice characteristics and fertility preservation (FP) referral. Thematic analysis was used to examine qualitative responses. RESULTS: 119 providers completed the survey. Seventy percent reported discussing fertility implications of TS routinely in pediatric care. Fifty-six percent reported often or always referring patients with spontaneous menarche to FP specialists, whereas only 19% reported often or always referring their patients without spontaneous menarche (p < 0.001). Barriers associated with FP referral frequency included unfamiliarity with FP options, belief that FP is not a possible goal for their patients, and absence of a local reproductive endocrinologist. Qualitatively, four referral barrier themes were identified: (1) questionable utility of referral, (2) lack of perceived interest among patients/families, (3) provider barriers (e.g., lack of knowledge), (4) logistical/structural barriers to accessing fertility-related care. DISCUSSION/CONCLUSION: Pediatric endocrinology providers report inconsistently discussing fertility implications of TS. The frequency of referral to an FP specialist and factors/barriers affecting the decision to refer remain variable. Future research should focus on expanding provider education, addressing barriers to high-quality fertility counseling and referral for patients with TS, and investigating FP outcomes in TS.

Neuropsychological Screening in Pediatric Multidisciplinary Clinics: Group Characteristics and Predictive Utility.

OBJECTIVE: To evaluate the feasibility of administering caregiver-report neuropsychological screening measures in pediatric multidisciplinary clinics (MDCs) and investigate predictive utility for cognitive and academic difficulties on follow-up testing. METHOD: The Pediatric Perceived Cognitive Functioning (Peds PCF) and Colorado Learning Difficulties Questionnaire (CLDQ) were administered to caregivers of youth with history of brain tumor (BT), non-central nervous system (CNS) cancer, or Fontan circulation as part of routine neuropsychological consultation in MDCs from 2017 to 2019. We examined cross-sectional differences on screening measures, and relationships between screening and intellectual and academic test performance in a subset who presented for follow-up neuropsychological evaluation. Receiver operating characteristic (ROC) curve analysis was used to identify suggested cut scores on screening measures for predicting who would most benefit from further evaluation. RESULTS: Screening was completed with 192 families. Children with history of non-CNS cancer (n = 29) had fewer parent-reported cognitive and academic concerns compared with either BT (n = 88) or Fontan (n = 75) groups. Peds PCF and CLDQ scores were related to intellectual and academic test performance in the group presenting for neuropsychological evaluation (n = 68). ROC curve analysis identified cut scores across screening measures with maximal sensitivity and specificity for detecting neuropsychological difficulties. CONCLUSIONS: It is feasible to utilize parent rating measures during neuropsychological consultation in pediatric MDCs. The Peds PCF and CLDQ demonstrated sensitivity to intellectual and academic difficulties in children with significant medical histories. Screening may be a helpful tool for pediatric neuropsychologists and other professionals during MDC consultation to inform clinical management.

Potential public health impact of the adjuvanted recombinant zoster vaccine among people aged 50 years and older in Beijing.

Herpes zoster (HZ) is a painful, unilateral rash which occurs upon reactivation of latent varicella zoster virus due to age-related immunity decline or immuno-suppression. In 2019, the recombinant zoster vaccine (RZV) was the first vaccine to be approved in China for HZ prevention. This study aimed to estimate the potential public health impact of RZV vaccination, compared with the status quo of no vaccination, in individuals ≥50 years of age (YOA) in Beijing, by adapting the published ZOster ecoNomic Analysis (ZONA) model. We considered 5% and 50% vaccination coverage for the private market (near-term post-launch) and mass vaccination (long-term) settings respectively. In the base-case analysis of both market settings, second-dose compliance was set to 80%. Coverage and second-dose compliance rates were varied under scenario and sensitivity analyses. In the base case, mass vaccination with RZV was estimated to prevent 435,681 HZ cases, 51,558 postherpetic neuralgia (PHN) cases, and 15,703 cases of other HZ-related complications in the overall ≥50 YOA cohort over their remaining lifetime, compared with no vaccination. Under the same base-case scenario, 14,247 hospitalizations and 1,031,387 outpatient visits could be avoided. The 50-59 YOA cohort had the highest contributions to the overall reduction in HZ cases, its complications and related healthcare resource utilization. Results were robust under numerous scenario and sensitivity analyses. This analysis demonstrates the potential of RZV vaccination to substantially reduce the public health burden of HZ among individuals ≥50 YOA, and may inform appropriate vaccination strategies for HZ prevention, particularly in urban settings within China.

A review of rotavirus vaccine use in Asia and the Pacific regions: challenges and future prospects.

INTRODUCTION: Rotavirus infection causes a significant proportion of diarrhea disease burden in children <5 years of age in Asia and the Pacific regions. The World Health Organization recommends that rotavirus vaccination should be included in national immunization programs to prevent rotavirus gastroenteritis (RVGE). AREAS COVERED: A literature review was performed to identify and summarize published evidence on RVGE epidemiology and status of rotavirus vaccine use, including the impact and cost-effectiveness of rotavirus vaccination programs in Asia and the Pacific regions (49 countries) during the period 2000-2018. EXPERT OPINION: Rotavirus vaccination programs have successfully reduced the burden of RVGE in many countries. However, such programs still do not exist in most Asia-Pacific countries, and therefore the burden of RVGE remains high in children <5 years of age. Challenges to vaccine implementation include a lack of surveillance data; safety concerns around intussusception; a general lack of awareness about RVGE disease epidemiology and vaccines among physicians, policy-makers, and parents; insufficient cost-effectiveness analyses; and potential issues with vaccine affordability including vaccination costs and lack of political will. Recommendations to overcome these challenges include developing cost-effectiveness analyses for more diverse national and regional settings, providing non-governmental support for low-income countries, and improving advocacy efforts.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus (RV) infection causes acute gastroenteritis (GE) in children under 5 years of age.Rotavirus vaccination (RVV) implementation has been slow in Asia and the Pacific (AP) regions, which could be responsible for the region falling behind in their fight against RVGE.What is new?RVV via national immunization programs (NIPs) is available in 8/49 countries and through the private market or non-governmental support in other countries. Coverage rates vary between countries, possibly driven by the mechanism through which RVV is available.A substantial positive impact of RVV on RVGE disease burden with a very low risk of intestinal intussusception for up to 7 days after RVV has been documented in the AP regions.Economic evaluation studies, mainly cost-effectiveness analyses, predict a significant reduction in treatment costs related to RVGE and its complications showing that RVV is good value for money.What is the impact?The prospect of continued safe and effective use of RVV in the AP regions is promising.Challenges to RVV implementation include establishing evidence of burden of disease, poor awareness of rotavirus vaccines, limited evidence from cost-effectiveness analyses from several countries, issues of affordability of the vaccine and a lack of political will.Recommendations for RVV implementation into the NIPs include conducting clinical and cost-effectiveness studies in countries where these are not available, establishing reliable surveillance mechanisms, providing non-governmental support for low-income countries and improving advocacy efforts.Maintenance of high vaccination coverage is needed in countries that have implemented national RVV programs.Graphical abstract[Formula: see text].

Neurodevelopmental and Mental Health Screening for Patients with Turner Syndrome in Pediatric Endocrine Clinics: Results of a Pediatric Endocrine Society Survey.

INTRODUCTION: International Turner syndrome (TS) Clinical Practice Guidelines recommend screening for neurodevelopmental (ND) and mental health (MH) concerns in girls with TS; however, it remains unclear whether this is implemented in current practice. The objective of this mixed methods study was to assess screening practices for ND and MH in girls with TS from the perspective of pediatric endocrinologists. METHODS: Pediatric Endocrine Society members who provide care for girls with TS were invited to complete an electronic survey on screening practices. Descriptive statistics were used to summarize quantitative results concurrently with thematic analysis of free-text survey responses. RESULTS: A total of 124 surveys were completed (86% attending pediatric endocrinologists, 81% at academic institutions). Overall, 25% of providers reported their patients with TS received both ND and MH screenings. Only 9 (9%) respondents endorsed screening for ND concerns themselves, while more providers (26%) reported they screen for MH concerns. Multiple barriers to screening for ND and MH concerns within the clinical setting were endorsed. Nearly all providers (>93%) reported they would consider using a short, validated screening tool for ND and MH concerns if such tools were available. DISCUSSION: A minority of pediatric endocrinologists currently perform ND or MH screening for patients with TS, however, many would be interested in implementing a brief screening tool into their clinical practice. Given almost all girls with a TS diagnosis receive care from pediatric endocrinologists at least annually, this may be an effective method to increase the proportion of girls with TS who receive recommended screenings.

Economic Evaluation of Human Rotavirus Vaccine in Thailand.

INTRODUCTION: Rotavirus gastroenteritis is the leading cause of severe diarrhoea among young children < 5 years old. Previous cost-effectiveness analyses on rotavirus (RV) vaccination in Thailand have generated conflicting results. The aim of this current study is to evaluate the economic impact of introducing RV vaccination in Thailand, using updated Thai epidemiological and cost data. METHODS: Both cost-utility analysis (CUA) and budget impact analysis (BIA) of human rotavirus vaccine (HRV) under a universal mass vaccination (UMV) programme were conducted. A published static, deterministic, cross-sectional population model was adapted to assess costs and health outcomes associated with RV vaccination among Thai children < 5 years old during 1 year for CUA and over a 5-year period (2019-2023) for BIA. Data identified through literature review were incorporated into the model after consultation with local experts. Base case CUA was conducted from a societal perspective with quality-adjusted life year (QALY) discounted at 3% annually. Scenario analyses as well as one-way and probabilistic sensitivity analyses were conducted to assess the robustness of the base case CUA results. Costs were updated to 2017. RESULTS: At 99% coverage, HRV vaccination would substantially reduce RV-related disease burden. With an incremental cost-effectiveness ratio (ICER) of Thai baht (THB) 49,923/QALY gained, HRV vaccination versus no vaccination was cost-effective when assessed against a local threshold of THB 160,000/QALY gained. Scenario and sensitivity analyses confirmed the cost-effectiveness with all resultant ICERs falling below the willingness-to-pay threshold. HRV use in the UMV programme was estimated to result in a net expenditure of about THB 255-281 million to the Thai government in the 5th year of the programme, depending on vaccine uptake. CONCLUSION: HRV vaccination is estimated to be cost-effective in Thailand. The budget impact following inclusion of HRV into the UMV programme is expected to be partially offset by substantial reductions in RV-related disease costs. FUNDING: GlaxoSmithKline Biologicals SA GSK STUDY IDENTIFIER: HO-17-18213.

Cost-Effectiveness Analysis of Human Papillomavirus Vaccination in Adolescent Girls in Taiwan

Objective: Three vaccines are available to Taiwanese young girls for cervical cancer (CC) prevention. Here we evaluate the cost-effectiveness of the two-dose (2D) AS04-adjuvanted HPV-16/18 vaccine (2D-AS04-HPV- 16/18v)+screening compared with a screening programme alone, with 2D human papillomavirus 6/11/16/18 vaccine (2D-4vHPVv)+screening, and with 2D/three-dose (3D) human papillomavirus 6/11/16/18/31/33/45/52/58 vaccine (9vHPVv)+screening, for Taiwan universal mass vaccination. Methods: A static Markov cohort model simulated the natural history of human papillomavirus (HPV) infection and CC screening for a 12-year-old cohort of Taiwanese girls (N=120,000). The model ran in 1-year cycles over the cohort's lifetime. Vaccine efficacy irrespective of HPV type was considered in the analysis for each vaccine. Input data were obtained from published literature, local databases, government reports and websites, and expert opinion. The analysis incorporated direct medical costs only, with an annual discount rate of 3.0%. The threshold was determined as 1 Gross Domestic Product per capita (New Taiwan dollar [NT$] 727,818; year 2016). Results: The 2D-AS04-HPV-16/18v+screening yielded 0.0365 quality-adjusted life year (QALY) gained at an additional cost of NT$ 5,770 per person compared with the screening programme alone. This resulted in an incremental cost-effectiveness ratio well below the threshold. Compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening, discounted results demonstrated additional QALYs gained at lower cost for 2D-AS04-HPV- 16/18v+screening, making it dominant over both 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening. Conclusions: Vaccinating Taiwanese girls with 2D-AS04-HPV-16/18v in addition to screening to prevent CC is cost-effective compared with using a screening programme alone and the dominant option compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening.

Clinical developmental, neuropsychological, and social-emotional features of Turner syndrome.

Individuals with Turner syndrome (TS) are at risk for a constellation of neurocognitive and psychosocial differences, although there is significant individual variability in these features. TS is associated with an increased risk for difficulties with visual-spatial reasoning, visual-spatial memory, attention, executive functioning, motor, and math skills. Additionally, increased rates of social difficulties, anxiety, and depression are observed. There can be significant interplay between all of these factors contributing to the behavioral phenotype. Neuropsychological features and previous research are reviewed. Clinical considerations and recommendations for evaluation and treatment of psychological and behavioral difficulties are provided, including consideration of medical features in TS, as well as therapies, educational supports, and medication treatment. Future research is needed to evaluate effectiveness of different treatments for neuropsychological and psychosocial features of TS, including modification and validation of existing evidence-based treatments and new approaches to care.

Understanding the economic impact of intravascular ultrasound (IVUS).

AIMS: To examine the cost-effectiveness of intravascular ultrasound (IVUS) use during percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in treating coronary artery disease (CAD). METHODS AND RESULTS: A Markov model was constructed with a lifetime horizon to compare costs and health outcomes between IVUS-guided PCI and PCI guided solely by angiography from an Italian healthcare payer perspective. The population examined included CAD patients undergoing PCI with DES. From a healthcare payer perspective, the resulting incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year was negative in the base-case scenario (i.e., IVUS benefit assumed to persist beyond the first year). When IVUS benefit was assumed to be limited to the first year, the ICER increased to €9,624. This conclusion remained consistent even when scenarios varied regarding the duration of the device's effect. Furthermore, benefits of using IVUS were greater for patients with acute coronary syndrome, renal insufficiency, and diabetes. CONCLUSIONS: Using IVUS with angiography is a dominant strategy in Italy, and results demonstrate that it is desirable to target those at a greater risk of restenosis (i.e., patients with diabetes, chronic kidney disease, and acute coronary syndrome), who tend to benefit more from accurate stent implantation. Further information is necessary regarding the long-term benefits of IVUS, however sensitivity analysis presented in this research demonstrates a strong argument supporting the cost-effectiveness of IVUS.

The relationship between the self-report BASC-2 validity indicators and performance validity test failure after pediatric mild traumatic brain injury.

In adult populations, research on methodologies to identify noncredible performance and exaggerated symptoms during neuropsychological evaluations has grown exponentially in the past two decades. Far less work has focused on methods appropriate for children. Although several recent studies have used stand-alone performance validity tests with younger populations, a near absence of pediatric work has investigated other indices to identify response bias. The present study examined the relationship between the validity scales from the self-report Behavior Assessment System for Children, Second Edition (BASC-2) and performance on the Medical Symptom Validity Test (MSVT), a stand-alone performance validity test. The sample consisted of 274 clinically referred patients with mild traumatic brain injuries aged 8 through 17 years. Fifty patients failed the MSVT based on actuarial criteria. The majority of these patients (92%) provided valid self-report BASC-2 profiles, with only three patients (6%) producing an invalid profile due to an elevated F index. Analysis of valid/invalid self-report BASC-2 profiles and MSVT pass/fail did not reveal a significant relationship (p = 0.471, two-tailed Fisher's exact test). These findings suggest that performance validity tests like the MSVT provide substantively different information about the validity of a neuropsychological profile than that provided by the self-report validity scales of the BASC-2.

Cognitive and medical features of chromosomal aneuploidy.

This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed.

Attention-deficit hyperactivity disorder symptoms in children and adolescents with sex chromosome aneuploidy: XXY, XXX, XYY, and XXYY.

OBJECTIVE: Attentional problems, hyperactivity, and impulsivity have been described as behavioral features associated with sex chromosome aneuploidy (SCA). In this study, the authors compare attention-deficit hyperactivity disorder (ADHD) symptoms in 167 participants aged 6 to 20 years with 4 types of SCA (XXY n = 56, XYY n = 33, XXX n = 25, and XXYY n = 53). They also evaluate factors associated with ADHD symptomatology (cognitive and adaptive scores, prenatal vs postnatal ascertainment) and describe the clinical response to psychopharmacologic medications in a subset of patients treated for ADHD. METHODS: Evaluation included medical and developmental history, cognitive and adaptive functioning assessment, and parent and teacher ADHD questionnaires containing DSM-IV criteria. RESULTS: In the total study group, 58% (96/167) met DSM-IV criteria for ADHD on parent-report questionnaires (36% in XXY, 52% in XXX, 76% in XYY, and 72% in XXYY). The Inattentive subtype was most common in XXY and XXX, whereas the XYY and XXYY groups were more likely to also have hyperactive/impulsive symptoms. There were no significant differences in Verbal, Performance, or Full Scale IQ between children with symptom scores in the ADHD range compared with those below the ADHD range. However, adaptive functioning scores were significantly lower in the group whose scores in the ADHD range were compared with those of the group who did not meet ADHD DSM-IV criteria. Those with a prenatal diagnosis of XXY were less likely to meet criteria for ADHD compared with the postnatally diagnosed group. Psychopharmacologic treatment with stimulants was effective in 78.6% (66/84). CONCLUSIONS: Children and adolescents with SCA are at increased risk for ADHD symptoms. Recommendations for ADHD evaluation and treatment in consideration of other aspects of the SCA medical and behavioral phenotype are provided.

Phase 2 trial of Linifanib (ABT-869) in patients with advanced non-small cell lung cancer.

INTRODUCTION: This study assessed activity and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, in patients with locally advanced or metastatic non-small cell lung cancer. METHODS: In this open-label trial (NCT00517790), patients who received one to two prior lines of systemic therapy were randomized to oral linifanib 0.10 mg/kg (low dose) or 0.25 mg/kg (high dose) once daily. Tumor responses were assessed by independent central imaging review every 8 weeks. The primary end point was progression-free rate at 16 weeks. Secondary end points included objective response rate, time to progression, progression-free survival, and overall survival. Safety was also assessed. RESULTS: Between August 2007 and October 2008, 139 patients were enrolled; 60% had two or more prior regimens, and 88% had nonsquamous cell carcinoma. The objective response rate (low dose and high dose) was 5.0% (3.1 and 6.8%), progression-free rate at 16 weeks was 33.1% (32.3 and 33.8%), median time to progression was 3.6 months (3.6 and 3.7 months), median progression-free survival was 3.6 months (3.5 and 3.6 months), and median overall survival was 9.0 months (10.0 and 8.3 months). The most common linifanib-related adverse events were fatigue (42%), decreased appetite (38%), hypertension (37%), diarrhea (32%), nausea (27%), palmar-plantar erythrodysesthesia (24%), and proteinuria (22%). These events were more common in the high-dose group. The most common linifanib-related grade 3 or 4 adverse event was hypertension (14%). CONCLUSIONS: Linifanib is active in advanced non-small cell lung cancer as second- or third-line therapy. Increased adverse event rates were observed at the high dose of linifanib.