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Purpose: Corticosteroids, which are a mainstay in the treatment of acute lymphoblastic leukemia (ALL), have a well-documented adverse effect on sleep. We sought to characterize the effects of dexamethasone on sleep over an entire 28-day treatment cycle using actigraphy, an objective measure of sleep., Methods: The sleep of 25 children aged 2-9 years (mean 4.5 years) with ALL treated with dexamethasone were evaluated during maintenance chemotherapy using a within-subject experimental design, actigraphy, and standardized questionnaires to assess sleep, sleep problems, and fatigue., Results: During the five days of dexamethasone treatment, sleep time increased during the night (535 vs. 498 min; p = 0.004) and daytime napping increased the following day (14 vs. 0 min; p = 0.002), and the number of wake episodes during the night was lower (14 vs. 20; p =  ≤ 0.001). However, when assessed individually, sleep-onset time, efficiency, and wake after sleep onset during the night were unchanged during dexamethasone treatment; when the cumulative effect of all of these factors was assessed, there was a statistically and clinically significant increase in nighttime sleep duration during dexamethasone treatment., Conclusions: During the five days of treatment with dexamethasone, an increase in nighttime sleep as well as daytime napping was observed in young children with ALL. The increases in sleep duration return to baseline one day after the discontinuation of dexamethasone., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Pleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases., Methods: Patients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported. Germline DICER1 mutations were sought with Sanger sequencing., Results: There were 435 cases, and a central review confirmed 350 cases to be PPB; 85 cases (20%) were another entity. Thirty-three percent of the 350 PPB cases were type I or type I regressed (type Ir), 35% were type II, and 32% were type III or type II/III. The median ages at diagnosis for type I, type II, and type III patients were 8, 35, and 41 months, respectively. The 5-year overall survival (OS) rate for type I/Ir patients was 91%; all deaths in this group were due to progression to type II or III. OS was significantly better for type II versus type III (P = .0061); the 5-year OS rates were 71% and 53%, respectively. Disease-free survival (DFS) was also significantly better for type II versus type III (P = .0002); the 5-year DFS rates were 59% and 37%, respectively. The PPB type was the strongest predictor of outcome. Metastatic disease at the diagnosis of types II and III was also an independent unfavorable prognostic factor. Sixty-six percent of the 97 patients tested had a heterozygous germline DICER1 mutation. In this subset, the DICER1 germline mutation status was not related to the outcome., Conclusions: Cystic type I/Ir PPB has a better prognosis than type II, and type II has a better outcome than type III. Surveillance of DICER1 carriers may allow the earlier detection of cystic PPB before its progression to type II or III PPB and thereby improve outcomes., (© 2014 American Cancer Society.)

This study examined the stability of risky driving behaviour from late adolescence to early adulthood among 823 young Australian drivers participating in an ongoing longitudinal study. This issue was explored by examining the stability of risky driving between the ages of 19-20 and 23-24 years (1) across the cohort and (2) among individuals. Focusing on cohort-wide trends, a modest reduction in the occurrence of speeding was observed across the sample between 19-20 and 23-24 years. However, drink-driving increased markedly over this period, and driving without a seatbelt or helmet for part of a trip also rose. Rates of other risky driving behaviours remained relatively unchanged. With regard to trends among individuals, while a decrease was evident in the risky driving propensities of many who had been classified as moderate or high risky drivers at age 19-20, 48% of the former group, and 77% of the latter group, still exhibited risky driving tendencies at 23-24 years. Together, these findings suggest a fair degree of stability in risky driving from late adolescence to early adulthood among this sample of Australian youth, highlighting the continuing need for road safety initiatives targeting young drivers beyond their first years of licensure., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT) are both associated with germline mutations in DICER1. In this brief report, a maternal history of SLCT led to identification of a deleterious DICER1 mutation in the patient and her asymptomatic infant. Radiographic screening revealed a large Type I PPB, which was completely resected. Identification of DICER1 mutation carriers and imaging of children at risk for PPB may allow detection of PPB in its earliest and most curable form, leading to increased likelihood of surgical cure and decreased risks of treatment-related late effects., (© 2014 Wiley Periodicals, Inc.)

Background: Little is known about infections among adult survivors of childhood cancer. The authors report the occurrence of infections and risk factors for infections in a large cohort of survivors of childhood cancer., Methods: The Childhood Cancer Survivor Study cohort was used to compare incidence rates of infections among 12,360 5-year survivors of childhood cancer with the rates of 4023 siblings. Infection-related mortality of survivors was compared with that of the US population. Demographic and treatment variables were analyzed using Poisson regression to determine the rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for associations with infectious complications., Results: Compared with the US population, survivors were at an increased risk of death from infectious causes (standardized mortality ratio [SMR], 4.2; 95% CI, 3.2-5.4), with the greatest risk observed among females (SMR, 3.2; 95% CI, 1.5-6.9) and among those who had been exposed to total body irradiation (SMR, 7.8; 95% CI, 1.8-33.0). Survivors also reported higher rates than siblings of overall infectious complications (RR, 1.3; 95% CI, 1.2-1.4) and higher rates of all categories of infection., Conclusions: Survivors of childhood cancer remain at elevated risk for developing infectious-related complications, and they have a higher risk of infection-related mortality years after therapy. Further investigation is needed to provide insight into the mechanisms for the observed excess risks., (© 2014 American Cancer Society.)

Germline mutations in DICER1 are associated with increased risk for a wide variety of neoplastic conditions, including pleuropulmonary blastoma (PPB), cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, botryoid embryonal rhabdomyosarcoma of the uterine cervix, ciliary body medulloepithelioma, pineoblastoma, pituitary blastoma and nodular thyroid hyperplasia or thyroid carcinoma. These tumors may be seen in isolation or in constellation with other characteristic tumor types in individuals or family members. Here we describe the medical history of a child with a heterozygous, loss of function germline DICER1 mutation and multiple tumors associated with the syndrome.. Although germline mutations in DICER1 are rare, tumors of these types will be seen by practicing pathologists and should prompt consideration of an underlying DICER1 mutation.

Background: Medical school attrition is important--securing a place in medical school is difficult and a high attrition rate can affect the academic reputation of a medical school and staff morale. More important, however, are the personal consequences of dropout for the student. The aims of our study were to examine factors associated with attrition over a ten-year period (2001-2011) and to study the personal effects of dropout on individual students., Methods: The study included quantitative analysis of completed cohorts and qualitative analysis of ten-year data. Data were collected from individual student files, examination and admission records, exit interviews and staff interviews. Statistical analysis was carried out on five successive completed cohorts. Qualitative data from student files was transcribed and independently analysed by three authors. Data was coded and categorized and key themes were identified., Results: Overall attrition rate was 5.7% (45/779) in 6 completed cohorts when students who transferred to other medical courses were excluded. Students from Kuwait and United Arab Emirates had the highest dropout rate (RR = 5.70, 95% Confidence Intervals 2.65 to 12.27;p < 0.0001) compared to Irish and EU students combined. North American students had a higher dropout rate than Irish and EU students; RR = 2.68 (1.09 to 6.58;p = 0.027) but this was not significant when transfers were excluded (RR = 1.32(0.38, 4.62);p = 0.75). Male students were more likely to dropout than females (RR 1.70, .93 to 3.11) but this was not significant (p = 0.079).Absenteeism was documented in 30% of students, academic difficulty in 55.7%, social isolation in 20%, and psychological morbidity in 40% (higher than other studies). Qualitative analysis revealed recurrent themes of isolation, failure, and despair. Student Welfare services were only accessed by one-third of dropout students., Conclusions: While dropout is often multifactorial, certain red flag signals may alert us to risk of dropout including non-EU origin, academic struggling, absenteeism, social isolation, depression and leave of absence. Psychological morbidity amongst dropout students is high and Student Welfare services should be actively promoted. Absenteeism should prompt early intervention. Behind every dropout statistic lies a personal story. All medical schools have a duty of care to support students who leave the medical programme.

This study examined the co-occurrence of risky driving with a range of externalising and internalising problems among 1055 young Australian drivers participating in an ongoing, 23-year longitudinal study. This issue was examined by: (1) investigating the co-occurrence of risky driving and other problem outcomes at 19-20 years; (2) exploring the rate of single and multiple problems among high, moderate and low young risky drivers and (3) investigating connections between risky driving in early adulthood and adolescent problem behaviours. Concurrent and longitudinal associations between risky driving and both substance use (alcohol, cigarette and marijuana use, binge drinking) and antisocial behaviour were found. However, risky driving generally appeared unrelated to internalising problems (depression, anxiety) and early sexual activity. Overall, young risky drivers varied considerably in the number and types of problem behaviours exhibited, although the great majority (70%) had displayed at least one other type of problem behaviour.

The purpose of this study was to compare the clinical root coverage achieved with two connective tissue grafts that were removed from the same donor area at different times and used in subepithelial grafts for root coverage. Sixty patients, each of whom had two connective tissue grafts removed from the same donor area at different times, were included in this study. The connective tissue grafts were used in two different subepithelial grafts for root coverage. The subepithelial grafts with both the first and second connective tissue grafts produced statistically significant changes in recession, probing depth, width of keratinized tissue, and attachment level. The changes obtained in the clinical measurements were not statistically significantly different between the first and second connective tissue grafts. The mean percentages of root coverage with the first and second connective tissue grafts were 95.4% and 98.2%, respectively, a statistically significant difference. None of the factors evaluated (sex, age, smoking history, and time between the two surgeries) could be related to statistically significant differences in the mean root coverage obtained. In this study, the second connective tissue graft produced greater mean root coverage than the first connective tissue graft.

Young drivers are significantly over-represented among those injured or killed in road traffic accidents. Young adults' greater tendency to engage in risky driving behaviours has been implicated in their high crash involvement rate. While considerable research has examined the driving patterns of young adults and situational factors associated with their involvement in crashes, less is known about the characteristics or circumstances in young drivers' earlier lives that may have contributed to their current driving behaviour. This issue was explored using data from the Australian Temperament Project (ATP), a large longitudinal community-based study, which commenced in 1983 with 2443 families and has followed children's psychosocial development from infancy to early adulthood. During the most recent survey wave when participants were aged 19-20 years, information was collected from young adults about their driving experiences and behaviour. A series of analyses indicated that it was possible to distinguish a group of young adults who engaged in high risky driving behaviour (high group) from a group who engaged in low levels of risky driving behaviour (low group) from mid childhood. Young drivers with a tendency towards risky driving differed from others on aspects of temperament style, behaviour problems, social competence, school adjustment and interpersonal relationships. The implications of these findings for initiatives to reduce risky driving behaviour are discussed.

The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations.