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Background: With improved survival of adults with congenital heart disease (CHD) comes a need to understand the lifelong outcomes of this population. The aim of this paper is to describe the rationale and design of Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE), a study to determine long-term medical, neurocognitive, and psychosocial outcomes among adults with a history of intervention for CHD and to identify factors associated with those outcomes., Methods: CHD PULSE is a cross-sectional survey conducted from September 2021 to April 2023 among adults aged 18 and older with a history of at least 1 intervention for CHD at 1 of 11 participating U.S. centers in the Pediatric Cardiac Care Consortium. Participants with CHD were asked to complete a 99-question survey on a variety of topics including: demographics, surgeries, health insurance, health care, heart doctors, general health, height and weight, education and work history, reproductive health (for women only), and COVID-19. To construct a control group for the study, siblings of survey respondents were invited to complete a similar survey. Descriptive statistics for demographics, disease severity, center, and method of survey completion were computed for participants and controls. Comparisons were made between participants and non-participants to assess for response bias and between CHD participants and sibling controls to assess for baseline differences., Results: Among the 14,322 eligible participants, there were 3,133 respondents (21.9%) from 48 U.S. states with surveys returned for inclusion in the study. Sibling contact information was provided by 691 respondents, with surveys returned by 326 siblings (47.2%). The median age of participants was 32.8 years at time of survey completion, with an interquartile range of 27.2 years to 39.7 years and an overall range of 20.1 to 82.9 years. Participants were predominantly female (55.1%) and of non-Hispanic White race/ethnicity (87.1%). There were no differences between participants and non-participants regarding severity of CHD. Compared to nonparticipants, participants were more likely to be female, of older age, and be of non-Hispanic White race/ethnicity. Enrolled siblings were more likely to be female and slightly younger than participants., Conclusions: With surveys from 3,133 participants from across the U.S., CHD PULSE is poised to provide keen insights into the lifelong journey of those living with CHD, extending beyond mere survival. These insights will offer opportunities for informing strategies to enhance and improve future outcomes for this population of patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Clean intermittent catheterization (CIC) is the gold standard for the management of urinary retention. Students with special healthcare needs who require CIC can be supported by school nurses who have knowledge and expertise in the management of CIC including an understanding of available products, reinforcement of proper technique, and resources available to promote student independence. This article will discuss the variety and unique features of CIC products and tips to overcoming barriers in bladder management.

Introduction: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied., Objective: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo., Method: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted., Results: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment., Discussion: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument., (© 2023 S. Karger AG, Basel.)

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials)., Competing Interests: Declaration of Competing Interest CL-P, VF-F, RE, PR-H, BA, and SL declare no competing financial interests. BS, NB reported receiving funding by BONFOR. SM reported having been involved in clinical trials conducted by Janssen and Lundbeck outside the submitted work. LTvE reported serving on advisory boards, delivering lectures, and receiving travel grants within the last 3 years from Eli Lilly and Co, Janssen-Cilag, Novartis, Shire, UCB, GlaxoSmithKline, Servier Laboratories, Janssen, and Cyberonics. MC reported serving on the advisory boards of Eli Lilly and Co, Janssen, and Novartis; receiving speaker honoraria from Eli Lilly and Co and Novartis; and participating in phase 3 studies with Eli Lilly and Co and Novartis outside the submitted work. CJ received speakers’ fees from Shire, Novartis and Medice and was a member of the adult ADHD Advisory Board of the latter company. CJ received speakers’ honoraria from Janssen, Novartis, Shire and Medice, and has been member of the adult ADHD Advisory Board of the two latter companies. ES is scientific advisor for Takeda Germany. MAH reported being the author and editor of diagnostic instruments published by the Hogrefe publishing group. MR reported serving as a member of the advisory boards of Medice, Eli Lilly and Co, and Janssen; serving as a member of the speakers’ bureaus of Medice, Eli Lilly and Co, Shire, and Novartis; and performing clinical studies for Medice. WR reported receiving honoraria from Medice; serving as a member of the advisory board of Medice; and participating in clinical trials sponsored by the Federal Ministry of Education and Research, Novartis, and Medice. BK reported receiving honoraria from Medice, Servier Laboratories, and Eli Lilly and Co; serving as a member of the advisory boards of Medice, Servier Laboratories, and Shire; receiving personal fees and nonfinancial support from Medice, Eli Lilly and Co, and Han-Huber publishers; and being the author and editor of book chapters on ADHD psychopathology and diagnostic instruments published by the Hogrefe publishing group. AP reported serving on the advisory board for Shire/Takeda, Boehringer, Janssen-Cilag, and Medice Arzneimittel; receiving honoraria from Takeda, Medice; receiving travel support from Janssen-Cilag; and delivering lectures, participating in phase 3 studies, and receiving travel grants from Eli Lilly and Co, Janssen-Cilag, Medice, Novartis, Shire, Boehringer; and being the author of books and articles on psychotherapy published by Elsevier, Hogrefe, Schattauer, Kohlhammer, and Karger publishers. All other authors declare no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Maintenance of telomere length has long been established to play a role in the biology of cancer and several studies suggest that it may be especially important in myeloid malignancies. To overcome potential bias in confounding and reverse causation of observational studies, we use both a polygenic risk score (PRS) and inverse-variance weighted (IVW) Mendelian randomization (MR) analyses to estimate the relationship between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk in 498 cases and 2099 controls and myelodysplastic syndrome (MDS) risk in 610 cases and 1759 controls. Genetic instruments derived from four recent studies explaining 1.23-4.57% of telomere variability were considered. We used multivariable logistic regression to estimate odds ratios (OR, 95% confidence intervals [CI]) as the measure of association between individual single-nucleotide polymorphisms and myeloid malignancies. We observed a significant association between a PRS of longer predicted LTL and AML using three genetic instruments (OR = 4.03 per ~1200 base pair [bp] increase in LTL, 95% CI: 1.65, 9.85 using Codd et al. [Codd, V., Nelson, C.P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J.L., Hottenga, J.J., Fischer, K., Esko, T., Surakka, I. et al. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet., 45, 422-427 427e421-422.], OR = 3.48 per one-standard deviation increase in LTL, 95% CI: 1.74, 6.97 using Li et al. [Li, C., Stoma, S., Lotta, L.A., Warner, S., Albrecht, E., Allione, A., Arp, P.P., Broer, L., Buxton, J.L., Alves, A.D.S.C. et al. (2020) Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length. Am. J. Hum. Genet., 106, 389-404.] and OR = 2.59 per 1000 bp increase in LTL, 95% CI: 1.03, 6.52 using Taub et al. [Taub, M.A., Conomos, M.P., Keener, R., Iyer, K.R., Weinstock, J.S., Yanek, L.R., Lane, J., Miller-Fleming, T.W., Brody, J.A., Raffield, L.M. et al. (2022) Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom., 2.] genetic instruments). MR analyses further indicated an association between LTL and AML risk (PIVW ≤ 0.049) but not MDS (all PIVW ≥ 0.076). Findings suggest variation in genes relevant to telomere function and maintenance may be important in the etiology of AML but not MDS., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: We report on women's mental health care desires following a miscarriage, medical termination, or abortion., Method: 689 women completed a questionnaire on reproductive history, health care following miscarriage/medical termination/abortion, and current mental health. Descriptive statistics and logistic regression analyses examined: miscarriage/termination/abortion incidence, desires for mental health support following miscarriages/terminations/abortions, and current mental health., Results: Of 365 women with a pregnancy history, 37% reported ≥1 miscarriage, 9% ≥1 medical termination, 16% ≥1 abortion, and 3% endorsed all three. Current mental health did not differ between women with a history of miscarriage/termination/abortion and those with only live births (p = 0.82). Following miscarriage, 68% of women discussed options for the medical management of pregnancy loss with their provider, 32% discussed grief/loss, and 25% received mental health care recommendations. Engagement in mental health services was reported by 16% of women with a history of miscarriage, 38% after medical termination, and 19% following an abortion. Of women who became pregnant after their most recent miscarriage/termination/abortion and did not receive mental health care, 55% wished they had received services during the subsequent pregnancy., Conclusions: Women desire mental health care after miscarriages, medical terminations, or abortions, warranting improved access to mental health care for these individuals., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Peripheral nerve stimulation (PNS) limits the image encoding performance of both body gradient coils and the latest generation of head gradients. We analyze a variety of head gradient design aspects using a detailed PNS model to guide the design process of a new high-performance asymmetric head gradient to raise PNS thresholds and maximize the usable image-encoding performance., Methods: A novel three-layer coil design underwent PNS optimization involving PNS predictions of a series of candidate designs. The PNS-informed design process sought to maximize the usable parameter space of a coil with <10% nonlinearity in a 22 cm region of linearity, a relatively large inner diameter (44 cm), maximum gradient amplitude of 200 mT/m, and a high slew rate of 900 T/m/s. PNS modeling allowed identification and iterative adjustment of coil features with beneficial impact on PNS such as the number of winding layers, shoulder accommodation strategy, and level of asymmetry. PNS predictions for the final design were compared to measured thresholds in a constructed prototype., Results: The final head gradient achieved up to 2-fold higher PNS thresholds than the initial design without PNS optimization and compared to existing head gradients with similar design characteristics. The inclusion of a third intermediate winding layer provided the additional degrees of freedom necessary to improve PNS thresholds without significant sacrifices to the other design metrics., Conclusion: Augmenting the design phase of a new high-performance head gradient coil by PNS modeling dramatically improved the usable image-encoding performance by raising PNS thresholds., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: Post-acute sequelae after COVID-19 are still associated with knowledge gaps and uncertainties at the end of 2022, e.g., prevalence, pathogenesis, treatment, and long-term outcomes, and pose challenges for health providers in medical management. The aim of this study was to contribute to the understanding of the multi-faceted condition of long-/ post-COVID. It was designed to evaluate whether a prior SARS-CoV-2 infection during the first COVID-19 wave in Germany increases the rate of disease, as measured via a record of insurance data on diagnoses, symptoms, and treatment, in the subsequent 12 months compared with matched control groups without recorded SARS-CoV-2 infection., Method: 50 outcome variables at disease, symptom and treatment levels (14 main categories and 36 sub-categories; new diagnoses) were defined from health insurance data. Logistic regression was carried out for two groups of patients tested positive in a PCR test in March/April 2020 for SARS-CoV-2, compared to the respective risk-adjusted (age, administrative region, 1:5 propensity-score matching), contemporaneous control group without prior documented SARS-CoV-2 infection (CG): First, individuals with outpatient treatment of acute COVID-19, indicating a not severe course (COV-OUT), and second, individuals with inpatient treatment of acute COVID-19, indicating a severe course (COV-IN) were compared with their respective control group., Results: The mortality rate in COV-OUT ( n  = 32,378) and COV-IN ( n  = 5,998) groups is higher compared to their control groups with odds ratio (OR) 1.5 [95%CI (1.3, 1.6)] and 1.7 [95%CI (1.5, 1.8)] respectively. Both groups were more likely to have experienced at least one outcome compared to their CG [OR = 1.4, 95%CI (1.4, 1.4)]; OR = 2.5, 95%CI [2.4, 2.6]). 42/37 (COV-IN/COV-OUT) outcome variables showed increased ORs. COV-OUT: Loss of taste and smell [OR = 5.8, 95%CI (5.1, 6.6)], interstitial respiratory diseases [OR = 2.8, 95%CI (2.0, 4.1)] and breathing disorders [OR = 3.2, 95%CI (2.2, 4.7)] showed the highest ORs. COV-IN: Interstitial respiratory diseases [OR = 12.2, 95%CI (8.5, 17.5)], oxygen therapy [OR = 8.1, 95%CI (6.4, 10.2)] and pulmonary embolism/anticoagulation [OR = 5.9, 95%CI (4.4, 7.9)] were the most pronounced., Conclusion: Following a SARS-CoV-2 infection during the first wave of the COVID-19 pandemic in Germany, 8.4 [COV-OUT, 95%CI (7.7, 9.1)] respectively 25.5 [COV-IN, 95%CI (23.6, 27.4)] percentage points more subjects showed at least one new diagnosis/symptom/treatment compared to their matched CG (COV-OUT: 44.9%, CG: 36.5%; COV-IN: 72.0%, CG: 46.5%). Because the symptoms and diagnoses are so varied, interdisciplinary and interprofessional cooperation among those providing management is necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Müller, Stengel, Roesler, Schillinger, Dräther, Günster, Tillmanns, Erhart, Szecsenyi and Merle.)

The response to the COVID-19 pandemic has amplified stress and social isolation for many children, but those children living with a diagnosis of autism spectrum disorder (ASD) have been disproportionately affected. Prior to the pandemic, children with ASD often faced social isolation due to struggles with their social communication and social development. Planning for children with ASD to return to community experiences, including school, appointments, and even recreational activities, will require an understanding of the impact of COVID-19 on the child and their family. As the child and family are working to adjust to changes like new routines, sleep patterns, and sensory issues as a result of the pandemic, the pediatric nursing community should be knowledgeable and prepared to develop creative opportunities to meet the needs of this vulnerable population.

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response., Competing Interests: JB has been in the past 3 years a consultant to/member of advisory board of / and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. LR has received grant or research support from, served as a consultant to, and served on the speakers' bureau of Eli Lilly and Co., Janssen, Medice, Novartis and Shire. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LR have received unrestricted educational and research support from the following pharmaceutical companies: Eli Lilly and Co., Janssen, and Novartis. LR has received authorship royalties from Oxford Press and ArtMed and travel grants from Shire to take part in the 2018 APA annual meeting and from Novartis to take part of the 2016 AACAP annual meeting. Barbara Franke has received educational speaking fees from Medice and Shire. SB discloses that he has in the last 5 years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, Clarion Healthcare, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer and UTB. DB serves as an unpaid scientific advisor for an EU-funded neurofeedback trial unrelated to the present work. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. DC served in an advisory or consultancy role for Medice, Novartis, Shire/Takeda. He received conference support or speaker's fee by Medice, Servier and Shire/Takeda. He has been involved in clinical trials conducted by Shire. He received royalties from Oxford University Press. The present work is unrelated to the above grants and relationships. In the past year, SF received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili, Enzymotec, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received support from: Shire, Ironshore, Neurovance, Alcobra, Rhodes, CogCubed, KemPharm, Enzymotec, Akili, Neurolifesciences, Lundbeck/Takeda, Otsuka, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is principal investigator of www.adhdinadults.com. Guilherme V. Polanczyk has been in the past 3 years a consultant, member of advisory board, and/or speaker for Shire/Takeda and Medice. He received travel expenses for continuing education support from Shire/Takeda and royalties from Editora Manole. In the past three years, Jeffrey Newcorn is/has been an advisor and/or consultant for Adlon Therapeutics, Akili Interactive, Alcobra, Arbor, Cingulate Therapeutics, Enzymotec, KemPharm, Lundbeck/Takeda, Medice, NLS, Rhodes, Shire, and Supernus. He was a DSMB member for Pfizer and Sunovion, and received research funds from Enzymotec, Otsuka, Shire and Supernus. He also has received speaker fees from Shire for disease-state presentations, and served as a consultant for the US National Football League. BV has served as consultant to Medice and Teva Pharm. Markus Gleitz is an employee of Medice Arzneimittel Pütter GmbH & Co. KG. MS received research support from Supernus, Shire, and Akili Interactive labs and in the past year has served in a advisory or consultancy capacity to Genomind, NLS, Shire/Takeda, Supernus, and Sunovian. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KAJ declared a shared affiliation with the author DC to the handling editor at the time of review., (Copyright © 2022 Buitelaar, Bölte, Brandeis, Caye, Christmann, Cortese, Coghill, Faraone, Franke, Gleitz, Greven, Kooij, Leffa, Rommelse, Newcorn, Polanczyk, Rohde, Simonoff, Stein, Vitiello, Yazgan, Roesler, Doepfner and Banaschewski.)

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: Intracranial germ cell tumor (iGCT) survivors have multiple risk factors for growth hormone (GH) deficiency, a commonly reported late effect in childhood cancer survivors. The objective of this study is to examine the prevalence of GH deficiency among childhood iGCT survivors., Methods: Participants were previously enrolled in the Germ Cell Tumor Epidemiology Study (GaMETES), a case parent triad study conducted using the Children's Oncology Group registry protocols, including 216 cases with iGCTs. Data on late effects and outcomes are available for 129 iGCT cases who consented for a follow-up study including a self-administered questionnaire and medical record retrieval. GH deficiency was identified via self-report and validated through medical record review. Chi-squared and Fisher's exact tests were used to examine cases with GH deficiency predating iGCT detection. Logistic regression was used to identify predictors of GH deficiency as a late effect., Results: Of 129 iGCT cases who participated in the late effects study, 45% had GH deficiency; 18% had GH deficiency predating the iGCT and 27% developed GH deficiency within a median of 19 months after diagnosis. Younger age at diagnosis, suprasellar location, and higher radiation doses were associated with GH deficiency as a late effect., Conclusions: GH deficiency is highly prevalent as an early clinical sign for iGCT and frequently arises as an early late effect after treatment. Additional investigation is needed to address earlier detection and treatment for this highly prevalent late effect in iGCT survivors., Competing Interests: Financial Disclosures/Conflict of interest: Bradley S Miller is a consultant for Ascendis, BioMarin, Novo Nordisk, Pfizer, Sandoz, Tolmar and Vertice. His affiliations did not have any impact on his participation in this study as this was a retrospective clinical study. The other authors have no relevant financial or non-financial interests to disclose.

School-age children are not immune to COVID-19 or the pronounced and persistent symptoms associated with a long-COVID diagnosis. Students may present with a variety of symptoms affecting their physical, cognitive, and mental health. The school community should be educated on the school-based interventions and recommendations for creating an individualized safe and successful return to school plan. As we await approval for vaccinations in school-age children younger than 12 years and continue to reposition ourselves to the waves of this pandemic and new variants of the virus, understanding the medical and educational long-term effects on our students may be a long-term need.

Background: Young children in the household are a known risk factor for maternal CMV infection and consequently, congenital infection in infants. However, little is known about viral shedding in pre-school aged children., Objectives: To estimate the prevalence of CMV DNA shedding and CMV antibodies among healthy children and their mothers., Study Design: A study of children ages 0 through 5 years was undertaken at the 2019 Minnesota State Fair. Children and their mothers were assessed for CMV shedding by procurement of a saliva swab for CMV PCR testing. An optional finger-stick for capillary blood was used to assess CMV antibodies., Results: A total of 109 children and 85 mothers were enrolled. The prevalence of CMV saliva shedding among children (mean age 3.1 years, SE=0.16) and their mothers was 12/109 (11.0%) and 1/85 (1.2%), respectively. The prevalence of CMV DNA among children peaked at 3 years of age (26%) while the mean viral load was greatest at one year of age (236,693 IU/mL). CMV IgG antibodies among those who agreed to a finger-stick were detected in 16/35 mothers (45.7%) and 0/7 children (0%). Mothers of children aged 5 years or greater had the highest seroprevalence (61.5%)., Conclusions: The prevalence of CMV salivary shedding in this unselected sample of young children was approximately 11.0%. The overall maternal seroprevalence in our sample was <50%, suggesting these women are at risk for acquisition of a primary CMV infection in subsequent pregnancies., (Copyright © 2022. Published by Elsevier B.V.)

Background and Objectives: Muscular variations of the ventral thoracic wall are generally common and of great clinical interest., Materials and Methods: An unusual muscular variation of the ventral thoracic wall was observed and dissected in a West-European female body donor., Results: An interclavicularis anticus digastricus muscle was observed and studied. It originated from the manubrium sterni and inserted bilaterally to the clavicles. Both muscle bellies were interconnected by a tendon on the ventral surface of the manubrium sterni. The muscle was innervated by branches of the lateral pectoral nerve., Conclusions: The interclavicularis anticus digastricus muscle is a muscular variation of the ventral thoracic wall of unknown prevalence. This variation might be of clinical interest in orthopaedics and thoracic surgery. It is also a vulnerable structure during infraclavicular insertion of a subclavian vein catheter or fractures of the clavicle., (© 2021. The Author(s).)

Attention-deficit/hyperactivity disorder (ADHD) is commonly accompanied by functional impairments within personal, professional, and social context as well as further psychological distress. The role of perceived stress has been examined in this regard, although little is known about the influence of stress coping strategies. We examined the dynamics between ADHD symptomatology, stress coping strategies, and life impairments in a sample of 230 clinical and non-clinical adult individuals. ADHD was associated with low probability of choosing adaptive but high probability of implementing maladaptive stress coping strategies as well as with increased life impairments. Adaptive stress coping showed little effects beyond the associations between ADHD and life impairments, whereas some maladaptive coping strategies increased current life impairments over and above the effects of ADHD and further psychological distress. The present findings emphasize the need of professional support in adults with ADHD and the necessity to include stress coping strategies in respective treatment approaches aimed at reducing life impairments., (© 2021. The Author(s).)

Objective: Research supports the importance of emotional symptoms in adults with attention-deficit/hyperactivity disorder (ADHD), which are not reflected in the DSM-5 or ICD-10 criteria. The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) assesses these symptoms, plus inattention, hyperactivity, and impulsivity. This scale allowed us to divide adult ADHD into 2 subtypes in a 2015 publication: ADHD inattentive presentation and ADHD emotional dysregulation presentation. The present study refines this observation using a larger, more diverse sample., Methods: Eight double-blind adult ADHD clinical trials (encompassing 1,490 subjects) were selected because they included assessment with the WRAADDS; a second, alternative ADHD measure; and the Clinical Global Impressions-Severity of Illness scale (CGI-S). These data were subjected to confirmatory factor analyses, and ADHD presentations were compared, including treatment response., Results: The original factor structure fit poorly with these new data. However, an alternative 2-factor solution fit both the original and the new subjects. ADHD inattentive presentation (n = 774) was defined by the inattention factor, and ADHD emotional dysregulation presentation (n = 620) was defined by additional elevation of the emotional dysregulation factor. The proportion of ADHD emotional dysregulation presentation ranged from 25% to 73% across the 8 studies. The emotional dysregulation presentation was associated with both a greater severity as measured by the CGI-S (P < .001) and more manifestations of childhood ADHD as measured by the Wender Utah Rating Scale (P < .001)., Conclusions: Factor analytic results supported the validity of 2 adult ADHD presentations based on levels of emotional dysregulation. This system offers a more clinically relevant approach to the diagnosis of ADHD in adults than does the DSM system., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

The Specialized Health Needs Interagency Collaboration (SHNIC) program at the Kennedy Krieger Institute is a community-based program that provides on-site training and technical assistance to safely manage the integration of children with special health needs into educational and community settings. SHNIC frequently receives seizure education requests throughout the school year, specifically regarding vagus nerve stimulation. Vagus nerve stimulation involves an implanted medical device used to deliver electrical pulses to the vagus nerve for additional seizure management. The school nurse needs to understand the purpose and function of the hidden medical device, including the parameters for use of the device and magnet, safety considerations, and side effects. SHNIC has developed educational materials specific to vagus nerve stimulation to aid the school nurse in providing staff training, developing care plans, and creating a safe school experience for students with special health needs.

Background: Males with Klinefelter syndrome (KS) (47,XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. To date, there are no reports characterizing the prevalence of KS among male GCT cases., Methods: The authors used array genotyping data from a Children's Oncology Group epidemiology study to estimate the prevalence of KS in males with GCTs (433 males aged birth-19 years). Using Fisher's exact tests, the authors examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and several birth characteristics between cases of KS-GCT and GCT cases without chromosomal abnormalities. Using publicly available data, the authors estimated the 1-year risk, risk ratio, and corresponding 95% confidence interval of GCTs among KS cases., Results: Based on analysis of array genotyping data, 3% of male GCT cases (13 cases) had KS. The additional X chromosome was of maternal origin in 7 of the 13 cases. Of these 13 KS cases, 5 of 9 KS-GCT cases with parental questionnaire data (56%) reported a diagnosis of KS. No significant differences were observed with regard to patient or birth characteristics between KS-GCT and non-KS-GCT cases. KS-GCT cases were significantly more likely to be diagnosed with mediastinal tumors than non-KS-GCT cases (P<.01). The authors estimated the risk of developing a GCT among males with KS to be 0.00025, or 1 per 4000 males (risk ratio, 18.8; 95% confidence interval, 11.7-30.0)., Conclusions: Compared with males without chromosomal abnormalities, males with KS are more likely to be diagnosed with a mediastinal GCT. The presence of KS should be considered in males with a diagnosis of mediastinal GCT. In the current study, the authors report that approximately one-third of males with mediastinal germ cell tumors have Klinefelter syndrome, and therefore screening of these individuals for the syndrome may be warranted. Males with Klinefelter syndrome are 19 times as likely as males without Klinefelter syndrome to develop germ cell tumors., (© 2018 American Cancer Society.)

Background: Abnormal DNA methylation may be important in germ cell tumour (GCT) aetiology, as germ cells undergo complete epigenetic reprogramming during development. GCTs show differences in global and promoter methylation patterns by histologic subtype. We conducted an epigenome-wide study to identify methylation differences by GCT histology., Methods: Using the Illumina HumanMethylation450K array we measured methylation in 154 paediatric GCTs (21 germinomas/seminomas/dysgerminoma, 70 yolk sac tumours [YST], 9 teratomas, and 54 mixed histology tumours). We identified differentially methylated regions (DMRs) between GCT histologies by comparing methylation beta values., Results: We identified 8,481 DMRs (FWER < 0.05). Unsupervised hierarchical clustering of individual probes within DMRs resulted in four high level clusters closely corresponding to tumour histology. Clusters corresponding to age, location, sex and FFPE status were not observed within these DMRs. Germinomas displayed lower levels of methylation across the DMRs relative to the other histologic subtypes. Pathway analysis on the top 10% of genes with differential methylation in germinomas/seminomas/dysgerminoma compared to YST suggested angiogenesis and immune cell-related pathways displayed decreased methylation in germinomas/seminomas/dysgerminoma relative to YST., Conclusions: Paediatric GCT histologies have differential methylation patterns. The genes that are differentially methylated may provide insights into GCT aetiology including the timing of GCT initiation.

One of the "hidden" medical devices in the school setting is the baclofen pump, which is used for the treatment of spasticity. The goals of spasticity treatment are to decrease muscle tone, deformity, and pain in order to maximize function and ease of care for both child and caregiver. The use of an intrathecal baclofen pump, often for children with cerebral palsy, spinal cord injury, brain injury, or stroke, has been effective in spasticity treatment. It is important for school nurses to be aware of the safety implications associated with this type of device. The Specialized Health Needs Interagency Collaboration (SHNIC) program at the Kennedy Krieger Institute has complied education and materials that explain the use of baclofen pumps in children with spasticity and the role of the school nurse in providing staff training, developing emergency care plans, and creating a safe school environment for children with special health needs.

Background: Studies of family history of cancer in paediatric germ cell tumours (GCTs) are few, and none has had sufficient sample size to specifically evaluate family history of GCT., Methods: We utilised family history data from a paediatric GCT study to calculate standardised incidence ratios (SIR) for GCT and other cancers using age- and sex-specific incidence rates from the SEER Program., Results: This analysis included 7998 relatives of paediatric GCT probands. We observed a higher number of GCT cases than expected in male and female relatives of probands (SIR=2.38, 95% CI 1.25, 3.51 for males; SIR=14.3, 95% CI 0.29, 28.4 for females). Further, we observed a particularly strong SIR for relatives of probands with intracranial GCT (SIR=8.07, 95% CI 3.51, 12.6). The SIR for relatives of probands with ovarian GCT was also elevated but did not reach statistical significance (SIR 4.35, 95% CI 0-9.27). Other notable associations include elevated SIRs for melanoma in male relatives and reduced SIRs for lymphatic/haematologic malignancies in male and female relatives., Conclusions: These results support the hypothesis that familial aggregation of GCT occurs in males and females.

Germ cell tumors (GCT) are a rare form of childhood cancer that originate from the primordial germ cell. Recent genome-wide association studies (GWAS) have identified susceptibility alleles for adult testicular GCT (TGCT). We test whether these SNPs are associated with GCT in pediatric and adolescent populations. This case-parent triad study includes individuals with GCT diagnosed between ages 0 and 19. We evaluated 26 SNPs from GWAS of adult TGCT and estimated main effects for pediatric GCT within complete trios (N = 366) using the transmission disequilibrium test. We used Estimation of Maternal, Imprinting and interaction effects using Multinomial modelling to evaluate maternal effects in non-Hispanic white trios and dyads (N = 244). We accounted for multiple comparisons using a Bonferroni correction. A variant in SPRY4 (rs4624820) was associated with reduced risk of GCT (OR [95% CI]: 0.70 [0.57, 0.86]). A variant in BAK1 (rs210138) was positively associated with GCT (OR [95% CI]: 1.70 [1.32, 2.18]), with a strong estimated effect for testis tumors (OR [95% CI]: 3.31 [1.89, 5.79]). Finally, a SNP in GAB2 (rs948662) was associated with increased risk for GCT (OR [95% CI]: 1.56 [1.20, 2.03]). Nominal associations (P < 0.05) were noted for eight additional loci. A maternal effect was observed for KITLG SNP rs4474514 (OR [95% CI]: 1.66 [1.21, 2.28]) and a paternal parent-of-origin effect was observed for rs7221274 (P = 0.00007), near TEX14, RAD51C, and PPM1E. We observed associations between SNPs in SPRY4, BAK1, and GAB2 and GCTs. This analysis suggests there may be common genetic risk factors for GCT in all age groups., (© 2017 Wiley Periodicals, Inc.)

The role of school nurse today not only includes making a thorough assessment of the child but also the knowledge and skill to understand hidden medical devices. As of 2011, there were approximately 14.6 million children in the United States living with special health care needs. Many of these children could have hidden medical devices. The Specialized Health Needs Interagency Collaboration (SHNIC) program at the Kennedy Krieger Institute received requests for in-person training regarding ventriculoperitoneal (VP) shunts.

Benzene exposure is one of the few well-established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) using population-based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota driver's license/identification card list. Chemical exposures were measured by self-report. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). We included 265 MDS cases, 420 AML cases and 1388 controls. We observed significant associations between both MDS and AML and benzene (OR = 1.77, 95% CI 1.19, 2.63 and OR = 2.10, 95% CI 1.35, 3.28, respectively) and vinyl chlorides (OR = 2.05, 95% CI 1.15, 3.63 and OR = 2.81, 95% CI 1.14, 6.92). Exposure to soot, creosote, inks, dyes and tanning solutions and coal dust were associated with AML (range ORs = 2.68-4.03), while no association was seen between these exposures and MDS (range ORs = 0.57-1.68). Pesticides and agricultural chemicals were not significantly associated with AML or MDS. Similar results were observed in analyses stratified by sex. In addition to providing risk estimates for benzene from a population-based sample, we also identified a number of other occupational and residential chemicals that were significantly associated with AML; however, all exposures were reported by only a small percentage of cases (≤10%). While chemical exposures play a clear role in the etiology of myeloid malignancy, these exposures do not account for the majority of cases., (© 2016 UICC.)

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non-Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS-R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population-based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Importance: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence in adulthood. There is a recognized need to assess the efficacy of psychotherapy in adult ADHD., Objective: To evaluate the efficacy of cognitive behavioral group psychotherapy (GPT) compared with individual clinical management (CM) and that of methylphenidate hydrochloride compared with placebo., Design, Setting, and Participants: Prospective, multicenter, randomized clinical trial of 18- to 58-year-old outpatients with ADHD from 7 German study centers. Patients were recruited between January 2007 and August 2010, treatment was finalized in August 2011, and final follow-up assessments occurred in March 2013., Interventions: Sessions of GPT and CM were held weekly for the first 12 weeks and monthly thereafter (9 months). Patients received either methylphenidate or placebo for 1 year., Main Outcomes and Measures: The primary outcome was the change in the ADHD Index of the Conners Adult ADHD Rating Scale from baseline to the end of the 3-month intensive treatment (blinded observer ratings). Secondary outcomes included ADHD ratings after 1 year, blinded observer ratings using the Clinical Global Impression Scale, and self-ratings of depression., Results: Among 1480 prescreened patients, 518 were assessed for eligibility, 433 were centrally randomized, and 419 were analyzed as randomized. After 3 months, the ADHD Index all-group baseline mean of 20.6 improved to adjusted means of 17.6 for GPT and 16.5 for CM, with no significant difference between groups. Methylphenidate (adjusted mean, 16.2) was superior to placebo (adjusted mean, 17.9) (difference, -1.7; 97.5% CI, -3.0 to -0.4; P = .003). After 1 year, treatment effects remained essentially stable. Descriptive analyses showed that methylphenidate was superior to placebo in patients assigned to GPT (difference, -1.7; 95% CI, -3.2 to -0.1; P = .04) or CM (difference, -1.7; 95% CI, -3.3 to -0.2; P = .03). Regarding depression, no significant differences were found. In contrast, GPT was superior to CM for all visits in the Clinical Global Impression global assessment of effectiveness., Conclusion and Relevance: Highly structured group intervention did not outperform individual CM with regard to the primary outcome. Psychological interventions resulted in better outcomes during a 1-year period when combined with methylphenidate as compared with placebo., Trial Registration: isrctn.org Identifier: ISRCTN54096201.

Adult ADHD is a frequent psychiatric disorder affecting relevant aspects of an individual's life. The aim of our study group was to carry out the first randomized controlled multicenter study to evaluate the effects of psychotherapy compared to clinical management in combination with psychopharmacological treatment with methylphenidate (MPH) or placebo (Plac) in a factorial four-arm design. Here, we present the enrollment procedure and description of adult ADHD patients recruited for the trial. Four hundred and thirty-three adult patients with ADHD were randomized at seven study sites in Germany to four treatment conditions: manualized dialectical-behavioral-therapy-based group psychotherapy (GPT) plus MPH or Plac, or clinical management (CM) including supportive counseling plus MPH or Plac with weekly sessions in the first 12 weeks and monthly sessions thereafter. Assessment for eligibility included standardized scales and instruments. After prescreening of 1,480 patients, 518 were evaluated for trial participation and 433 were randomized. The main reasons for prescreening failure were lack of interest in participating (n = 205), difficulties in meeting the time and effort requirements for participation (n = 186), and contraindications for psychopharmacological treatment with MPH (n = 194). The full analysis set (FAS) comprised 419 adult ADHD patients (mean age 35.2 years, males/females 1:1). Fifty-seven percent of the patients suffered from the combined ADHD subtype. Prevalence of at least one current or lifetime axis-I comorbidity was 66 %. Axis-II comorbidity rates was 18 % (patients with comorbid borderline and antisocial personality disorders were excluded). Our network was able to recruit an adult ADHD sample essentially comparable to community samples. A selection bias was created by excluding patients unable or unwilling to participate, or who had somatic and psychiatric contraindications for stimulant treatment (Current Controlled Trials ISRCTN54096201, FUNDING: Federal Ministry of Education and Research 01GV0606).

Background: A hormonal aetiology is one explanation for the lower incidence of myeloid leukaemia in women compared with men., Methods: In this population-based case-control study, we evaluated associations between exogenous hormone use and reproductive history and myeloid leukaemia, overall and by disease subtype., Results: We observed a suggestive association between oral contraceptive use and acute myeloid leukaemia (odds ratio=0.55, 95% confidence interval=0.32-0.96). Hormone replacement therapy and reproductive factors were not associated with risk., Conclusion: Despite the biological plausibility for a role of oestrogen in leukaemogenesis, other aetiologic factors are likely to explain the differing incidence rates in males and females.

Background: Infant leukaemia is likely initiated in utero., Methods: We examined whether analgesic use during pregnancy was associated with risk by completing telephone interviews of the mothers of 441 infant leukaemia cases and 323 frequency-matched controls, using unconditional logistic regression., Results: With the exception of a reduced risk for infant acute myeloid leukaemias with non-aspirin non-steroidal anti-inflammatory drugs (NSAID) use early in pregnancy (odds ratios=0.60; confidence intervals: 0.37-0.97), no statistically significant associations were observed for aspirin, non-aspirin NSAIDs, or acetaminophen use in early pregnancy or after knowledge of pregnancy., Conclusion: Overall, analgesic use during pregnancy was not significantly associated with the risk of infant leukaemia.

Background: Prenatal supplementation has been inversely associated with childhood, but not with infant, leukaemia., Methods: Mothers of 443 cases of infant leukaemia diagnosed during 1996-2006 and 324 frequency-matched controls completed interviews. Associations were evaluated by unconditional logistic regression., Results: We observed no associations between prenatal vitamin (odds ratio (OR)=0.79, 95% confidence interval (CI): 0.44-1.42) or iron supplementation (OR=1.07, 95% CI: 0.75-1.52) and infant leukaemia after adjustment for race/ethnicity and income. Similar results were observed for leukaemia subtypes analysed separately., Conclusion: The observed null associations may be attributable to high supplementation rates and/or national fortification programmes.

Unlabelled: The growing interest in organic and natural foods warrants a greater need for information on the food safety of these products. In this study, samples were taken from 2 pasture flock farms (N = 178; feed, water, drag swabs, and insect traps), pasture flock retail carcasses (N = 48) and 1 pasture flock processing facility (N = 16) over a period of 8 mo. A total of 105 Campylobacter isolates were obtained from 53 (30%), 36 (75%), and 16 (100%) samples from the farms, retail carcasses, and processing facility, respectively. Of the 105 isolates collected, 65 were C. jejuni, 31 were C. coli, and 9 were other Campylobacter spp. Using PCR, the C. jejuni isolates were further analyzed for virulence genes involved in colonization and survival (flaA, flaC, cadF, dnaJ, racR, cbrR), invasion (virB11, ciaB, pldA), protection against harsh conditions (sodB, htrA, clpA), toxin production (cdtA, cdtB, cdtC), siderophore transport (ceuE), and ganglioside mimicry (wlaN). In addition, the short variable region of the flaA locus (flaA SVR) was sequenced to determine the genetic diversity of the C. jejuni isolates. The flaA SVR diversity indices increased along the farm to carcass continuum. PCR-based analysis indicated a low prevalence of 5 genes involved in colonization (dnaJ, ciaB, pldA, racR, virB11). The results of this survey indicate that the prevalence of Campylobacter on organic retail carcasses is similar to prevalence reports of Campylobacter on conventional retail carcasses. However, the genetic diversity of the flaA SVR genotypes increased along the farm to carcass continuum that contrasted with conventional poultry studies., Practical Application: Campylobacter jejuni is a leading cause of foodborne illness with poultry and poultry products being leading sources of infection. Free-range and pasture flock chickens are becoming more popular; however, there is an inherent biosecurity risk that can increase the prevalence of foodborne pathogens in these flocks. This study aimed to determine sources and characterize C. jejuni isolated from pasture flocks.

Vitamin supplements have been proposed for children with Down's syndrome (DS) with claims of improving cognitive abilities, or immune or thyroid function. Several studies have shown decreased levels of zinc in this population. Because children with DS have a 50-fold increased risk of developing acute leukaemia during the first 5 years of life, we explored the relation between child vitamin and herbal supplement use and the risk of leukaemia in a case-control study. During the period 1997-2002, we enrolled 158 children with DS aged 0-18 years that were diagnosed with acute lymphoblastic leukaemia (ALL) (n = 97) or acute myeloid leukaemia (AML) (n = 61) at participating Children's Oncology Group institutions. We enrolled 173 DS children without leukaemia (controls), selected from the cases' primary care clinic and frequency-matched on age. Data were collected via telephone interviews with mothers of the index child regarding use of multivitamins, zinc, vitamin C, iron and herbal supplements, including age at first use, frequency and duration. Among controls, 57% reported regular multivitamin use (>/=3 times/week for >/=3 months) compared with 48% of ALL cases and 61% of AML cases. We found no evidence of an association between children's regular multivitamin use and ALL or AML (adjusted odds ratios [OR] = 0.94 [95% CI 0.52, 1.70] and 1.90 [0.73, 4.91] respectively). There was a suggestion of an increased risk for AML associated with regular multivitamin use during the first year of life or for an extended duration (ORs = 2.38 [0.94, 5.76] and 2.59 [1.02, 6.59] respectively). Despite being the largest study of DS-leukaemia, our sample size was small, resulting in imprecise effect estimates. Future research should include larger sample sizes as well as a full assessment of diet including vitamin supplementation to adequately examine the relation between nutritional status and childhood leukaemia.

As random digit dialing becomes increasingly unfeasible for many types of studies, alternative methods for control selection are needed, especially for studies of childhood cancer. US birth registries are an appealing source of young control children because they are population based, provide demographic and pregnancy data for comparison of participants with the study base, and maintain data that enable matching on birth characteristics. Here the authors describe the ability of US birth registries to release information sufficient to locate potential control subjects for two ongoing case-control studies of hepatoblastoma and infant leukemia. The birth registries of 32 states, in which 75.8% of US children 0-5 years of age resided in 2004, agreed to participate in control selection. Data sufficient to track participants and to characterize nonrespondents were available from a majority of registries. These results suggest that birth registries may be used to select controls for studies of rare childhood diseases on a national scale.

Since the mid-1990s, epidemiologists have anecdotally reported difficulty in recruiting controls using random digit dialing (RDD), but few empirical data have been published. From 1982 to 2003, epidemiologists from the Children's Oncology Group conducted 17 case-control studies using RDD controls. Data for calculating RDD and field response rates were available from eight and 13 of these studies, respectively. Over the period of analysis, the contact rate declined 2.5% per year (95% confidence interval (CI): -3.4, -1.6; p = 0.001), from above 90% in the 1980s to 63-69% in the most recent studies. The response rate (the product of the contact and cooperation rates) showed a decline parallel to that of the contact rate (-2.4% per year, 95% CI: -3.2, -1.6; p < 0.001), from above 80% in the 1980s to 50-67% after the mid-1990s. Field response rates appeared to have declined modestly. The overall response rate (the product of the RDD response and field response rates) paralleled that of the RDD response rate and decreased 2.4% per year (95% CI: -2.7, -2.0; p < 0.001). The current low response rates for RDD indicate a substantial potential for selection bias and a need to seek alternative sources of controls.

Leukemias with MLL gene rearrangements predominate in infants (<1 year of age), but not in older children, and may have a distinct etiology. High birth weight, higher birth order, and prior fetal loss have, with varying consistency, been associated with infant leukemia, but no studies have reported results with respect to MLL status. Here, we report for the first time such an analysis. During 1999 to 2003, mothers of 240 incident cases (113 MLL(+), 80 MLL(-), and 47 indeterminate) and 255 random digit dialed controls completed a telephone interview. Odds ratios and 95% confidence intervals for quartile of birth weight, birth order, gestational age, maternal age at delivery, prior fetal loss, pre-pregnancy body mass index, and weight gain during pregnancy were obtained using unconditional logistic regression; P for linear trend was obtained by modeling continuous variables. There was a borderline significant linear trend of increasing birth weight with MLL(+) (P = 0.06), but not MLL(-) (P = 0.93), infant leukemia. Increasing birth order showed a significant inverse linear trend, independent of birth weight, with MLL(+) (P = 0.01), but not MLL(-) (P = 0.18), infant leukemia. Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies.

Compared with the general pediatric population, children with Down's syndrome have a much higher risk of acute leukemia. This case-control study was designed to explore potential risk factors for acute lymphoblastic leukemia and acute myeloid leukemia in children with Down's syndrome living in the United States or Canada. Mothers of 158 children with Down's syndrome and acute leukemia (97 acute lymphoblastic leukemia, 61 acute myeloid leukemia) diagnosed between January 1997 and October 2002 and mothers of 173 children with Down's syndrome but without leukemia were interviewed by telephone. Positive associations were found between acute lymphoblastic leukemia and maternal exposure to professional pest exterminations (odds ratio = 2.25, 95% confidence interval: 1.13, 4.49), to any pesticide (odds ratio = 2.18, 95% confidence interval: 1.08, 4.39), and to any chemical (odds ratio = 2.72, 95% confidence interval: 1.17, 6.35). Most of the associations with acute myeloid leukemia were nonsignificant, and odds ratios were generally near or below 1.0. This exploratory study suggests that household chemical exposure may play a role in the development of acute lymphoblastic leukemia in children with Down's syndrome.

Background: Periconceptional vitamin supplementation reduces the risk of neural tube defects, and possibly may reduce the risk of certain childhood malignancies, including acute lymphoblastic leukemia (ALL). Because children with Down syndrome (DS) experience a 20-fold higher risk of leukemia than the general population, the authors evaluated whether periconceptional vitamin supplementation reduced the risk of leukemia in children with DS., Methods: From 1997 to 2002, 158 children ages birth-18 years with DS and acute leukemia (n = 61 children with acute myeloid leukemia [AML] and n = 97 children with ALL) were enrolled through the Children's Oncology Group in North America. Children with DS alone (n = 173) were identified through the cases' pediatric clinics and frequency matched to cases on age. Mothers of cases and controls completed a telephone interview that included questions regarding vitamin supplement use in the periconceptional period and after knowledge of pregnancy., Results: A decreased risk of leukemia was observed with vitamin supplementation in the periconceptional period (odds ratio [OR] = 0.63; 95% confidence interval [95% CI], 0.39-1.00). When stratified by leukemia type, the reduced risk was observed for ALL (OR = 0.51; 95% CI, 0.30-0.89), but not for AML (OR = 0.92; 95% CI, 0.48-1.76). Compared with vitamin use in the periconceptional period, use only after knowledge of pregnancy was associated with an increased risk of leukemia (OR = 1.61; 95% CI, 1.00-2.58). This was observed for both ALL and AML., Conclusions: These data added to a growing body of evidence that suggests that periconceptional vitamin use may be protective in the development of certain childhood cancers.

Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given the potential role of infections in the aetiology of leukaemia in children without DS, we investigated whether there was an association between early-life infections and acute leukaemia in children with DS. Maternal infections during pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997 and 2002. DS controls (N=173) were selected from the cases' primary care clinics and frequency matched on age at leukaemia diagnosis. Data were collected on demographics, child's medical history, mother's medical history, and other factors by maternal interview. Analyses were conducted using unconditional logistic regression adjusted for potential confounders. A significant negative association was observed between acute leukaemia and any infection in the first 2 years of life (adjusted odds ratio (OR)=0.55, 95% confidence interval (CI) (0.33-0.92); OR=0.53, 95% CI (0.29-0.97); and OR=0.59, 95% CI (0.28-1.25) for acute leukaemia combined, ALL, and AML respectively). The association between acute leukaemia and maternal infections during pregnancy was in the same direction but not significant. This study offers support for the hypothesis that early-life infections may play a protective role in the aetiology of acute leukaemia in children with DS.

This qualitative study was conducted to determine cultural influences in end-of-life care among Jewish people. The conceptual framework for this study was drawn from Leininger's culture care theory. Informants consisted of 16 professional caregivers, family members, and rabbis who had experience with end-of-life care for Jewish patients. Interviews using open-ended and focused questions were used to gather informants' descriptions of their generic values, beliefs, and practices. Findings revealed the strong influence of religious, cultural, and historical factors in caring. Sanctity of life and life promotion are central to Judaism. Caring is a communal obligation that unites the family and community into a cohesive unit. Attitudes toward death are influenced by beliefs about afterlife and suffering. The value put on expert knowledge influences patients' and family members' expectations of professional caregivers. Similarities and differences were noted among different groups of informants.

Objective: We sought to assess the fertilization, implantation, and ongoing pregnancy rates with a minimal precycle and ongoing cycle monitoring protocol for in vitro fertilization and embryo transfer., Study Design: Retrospective review was conducted of 103 consecutive cycles of fresh in vitro fertilization and embryo transfer from 1996 to 1998. Precycle screening included semen analysis without strict morphologic analysis, and hysterosalpingography-sonohysterography within the last year. Serum prolactin, serum thyroid-stimulating hormone, reactive plasma reagin, human immunodeficiency virus, rubella titer, blood type, hepatitis B surface antigen, and hepatitis C antibody testing was performed on all patients within 3 months of cycle initiation. Women > or =37 years old underwent clomiphene challenge testing. The monitoring protocol included the following: baseline transvaginal ultrasonography after 12 to 14 days of midluteal gonadotropin-releasing hormone agonist down-regulation to assess endometrial thickness and adnexal appearance, transvaginal ultrasonography for follicle evaluation at 7 and 10 days, serum estradiol assay if > or =20 follicles, quantitative beta-human chorionic gonadotropin 12 to 14 days after pre-embryo transfer, repeat quantitative beta-human chorionic gonadotropin 3 to 5 days later, and transvaginal ultrasonography for intrauterine gestational sac confirmation 7 to 9 days after the initial positive pregnancy test result. The dose of gonadotropin used remained constant unless the sonogram obtained on day 7 indicated a suboptimal response (<3 follicles each, with an average diameter of 10 to 12 mm) or hyperresponse (> or =15 follicles with an average diameter of 10 to 12 mm)., Results: The per embryo implantation rate (fetal cardiac activity) was 13.1%, and the live birth rate per 100 pre-embryo transfers was 31.5 for patients < or =40 years old. The average number of pre-embryos transferred was 3.1. The singleton pregnancy rate was 71%, and there were no multiple gestations greater than twins. The mean number of oocytes fertilized was 66%. There was 1 case of failed fertilization with intracytoplasmic sperm injection. There were two other cases of failed fertilization. One case of severe ovarian hyperstimulation occurred in spite of cryopreservation of all embryos., Conclusions: In vitro fertilization and embryo transfer can be accomplished with minimal precycle testing and ongoing cycle monitoring without compromising fertilization, implantation, and ongoing pregnancy rates. This results in reduced overall costs for couples.

In a total of 10 patients with dementia of the Alzheimer-type (DAT) and in 10 healthy controls near-infrared spectroscopy (NIRS), a new non-invasive optical method, was used to measure the changes of concentrations of oxy- (O2HB) and deoxyhemoglobin (HHB) in left and right hemispheric prefrontal brain tissue areas during performance of the Verbal Fluency Test (VFT). On a neuropsychological level, the healthy subjects performed better in the VFT than patients with DAT. Statistical analysis of the relative concentrations of O2HB and HHB measured with NIRS during performance of the VFT revealed a significant interaction of the hemispheric effects with the diagnosis. A possible interpretation of this finding is that a good performance in the VFT relies on a predominantly left hemispheric activation observed in controls, whereas a low number of correct responses is associated with a loss of this asymmetric activation in patients with DAT. Although both, patients and controls, performed better in the category version of the VFT, the metabolic effects of this task were significantly less pronounced than in the letter version. This indicates that different energy demands, according to the type of access to the memory stores, may be interpreted as the result of a less energy-demanding access to categorically stored information and adds further evidence to the view that memory departments in humans are organized according to categorical principles.

In order to improve the pregnancy rate per oocyte retrieval while reducing the chance of multiple-gestations, a technique of cryopreservation of human embryos was used for our initial study consisting of 100 infertile patients undergoing in vitro fertilization (IVF) procedure. These patients combined a "fresh" embryo transfer with cryopreservation. The embryos were cryopreserved with 1,2-propanediol. Twenty-nine (29%) patients achieved ongoing pregnancies from the fresh embryo transfer. Thirty patients received a transfer of thawed embryos in a natural cycle. Nine of these patients achieved ongoing pregnancies. Combining these 2 transfers results in a 38% ongoing pregnancy rate. Forty-one patients have yet to receive their frozen embryos. The current success rate in this study indicates that over 50% of the patients in this group can expect to become pregnant by the time all the cryopreserved embryos have been transferred.

Clinical follow-up of 24 patients who developed left ventricular aneurysm early after myocardial infarction is presented. All patients developed left ventricular failure within two weeks of infarction. The indication for operation was resistant left ventricular failure in 21 patients and a combination of left ventricular failure and unstable angina in three. Complete occlusion or severe stenosis (greater than 70 per cent) of the left anterior descending coronary artery was the most common findings. There were 3 hospital (12.5 per cent) and 2 late (8.3 per cent) deaths. Impairment of septal mobility was associated with a poor prognosis. All patients who develop progressive left ventricular failure early following myocardial infarction should be clinically and haemodynamically evaluated for the presence of left ventricular aneurysm. Surgical resection of the aneurysm and correction of associated lesions should be aggressively pursued.

Airway obstruction in children has many causes. Although vascular rings may have early onset of symptoms there was considerable delay in establishing the correct diagnosis. Barium swallow is diagnostic. Other tests, such as angiocardiography, bronchoscopy, bronchography, and lung scan are usually unnecessary. Pulmonary sling is a less common cause of vascular obstruction. Barium swallow showing anterior indentation at the level of the pulmonary hilum is diagnostic. Cysts and tumors are other causes of severe airway obstruction. The diagnostic and operative problems in three patients are discussed as examples. It is concluded that barium swallow is the most important single investigation in the evaluation of airway obstruction.

Six patients developed severe, unexplained, chronic bronchopulmonary disease from 3 to 13 years after the onset of nonspecific inflammatory disease of the colon. All had chronic bronchitis, bronchiectasis was diagnosed in four, and an obstructive type of pulmonary dysfunction was noted in five. Four of the six, including the two with only chronic bronchitis, had no history of smoking. There was an initial correlation between the pulmonary symptoms and the intestinal disease, except in two patients who developed overt pulmonary disease following total proctocolectomy. The frequent occurence of extraintestinal lesions has suggested that ulcerative colitis and regional enteritis are systemic disorders. Chronic unexplained bronchopulmonary disease may be another infrequent complication in such patients.

Between 1968 and 1980, 51 children had an operation for various forms of vascular ring. Additional cardiac malformations were present in five patients, and six had noncardiac congenital anomalies. Although symptoms started within the first month of life in 39 infants, only 16 came to operation under three months of age, and a delay of more than six months occurred in 15. Stridor, often life-threatening, and recurrent infections were the most common symptoms, but dysphagia was also important. The reasons for delay in diagnosis are discussed. Barium swallow provided the diagnosis in 44 patients and suggested it in a further four patients. Innominate artery compression of the trachea was not diagnosed by barium swallow. Operations of various types were performed. Accuracy in diagnosis is important because not all patients could be treated through the classic left thoracotomy. Severe tracheomalacia was responsible for the only two deaths in the series; one of these had tracheostomy performed in the referring hospital, the second child also had Fallot's tetralogy. The large majority of the patients have done well, 76% being asymptomatic at follow-up. Minimal to moderate stridor persists among the remainder to the present time.

Although gonadoblastoma is known to be associated with the presence of a Y chromosome, this case report of a 15-year-old patient with gonadal dysgenesis, gonadoblastoma, and an idic(Xq-) chromosome provides evidence for the occurrence of gonadoblastoma even in the absence of a Y chromosome. A review of previous cases reported to have gonadoblastoma in the absence of a Y chromosome revealed that the presence of some breast development was the common denominator among those patients. Therefore, a patient who presents with gonadal dysgenesis with some breast development, but lacks a Y chromosome may observe as close scrutiny as the patient with gonadal dysgenesis in the presence of a Y chromosome.