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Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 (

Background: Torus (buckle) fractures of the wrist are the most common fractures in children, involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up, or would equally recover by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, school absences and NHS costs. Objectives: To establish whether treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (“offer of bandage”), provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (“rigid immobilisation”). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: 23 UK Emergency Departments. Participants: 965 children (4-15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online encrypted randomisation service. Exclusion criteria included presentation >36 hours after injury, multiple injuries and inability to complete follow-up. Interventions: Offer of bandage (n= 489) of whom the bandage was applied in 458, versus rigid immobilisation (n= 476). Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: Pain at 3-days post-randomisation measured using the WongBaker FACES Pain Rating Scale. Secondary outcomes were the PROMIS Upper Extremity score for children, health related quality of life (QoL), complications, school absence, analgesia use and resource use collected up to 6 weeks post-randomisation. Results: 94% of participants provided primary outcome data. Pain was equivalent at the 3 day primary outcome for both groups. With reference to the pre-specified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was -0.10; 95% CI -0.37 to 0.17 and the per-protocol population was -0.06; 95% CI -0.34 to 0.21. There was equivalence in pain for both age subgroups (4-7 and 8–15 years). There was no difference in the rate of complications, with five (1.0%) in the offer of bandage group and three (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, QoL or school absence at any point during follow-up. Analgesia use was marginally higher at Day 1 in the offer of bandage group (83% vs 78% participants), though was no different at other times. The offer of bandage significantly reduced the cost of treatment, and had a high probability of cost-effectiveness. Limitations: Families had a strong pre-existing preference for rigid immobilisation. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of bandage in children with a distal radius torus fracture.

Background Trajectories of attention-deficit hyperactivity disorder (ADHD) traits spanning early childhood to mid-life have not been described in general populations across different geographical contexts. Population trajectories are crucial to better understanding typical developmental patterns. Methods We combined repeated assessments of ADHD traits from five population-based cohorts, spanning ages 3 to 45 years. We used two measures: (i) the Strengths and Difficulties Questionnaire (SDQ) hyperactive-inattentive subscale (175 831 observations, 29 519 individuals); and (ii) scores from DSM-referenced scales (118 144 observations, 28 685 individuals). Multilevel linear spline models allowed for non-linear change over time and differences between cohorts and raters (parent/teacher/self). Results Patterns of age-related change differed by measure, cohort and country: overall, SDQ scores decreased with age, most rapidly declining before age 8 years (-0.157, 95% CI: -0.170, -0.144 per year). The pattern was generally consistent using DSM scores, although with greater between-cohort variation. DSM scores decreased most rapidly between ages 14 and 17 years (-1.32%, 95% CI: -1.471, -1.170 per year). Average scores were consistently lower for females than males (SDQ: -0.818, 95% CI: -0.856, -0.780; DSM: -4.934%, 95% CI: -5.378, -4.489). This sex difference decreased over age for both measures, due to an overall steeper decrease for males. Conclusions ADHD trait scores declined from childhood to mid-life, with marked variation between cohorts. Our results highlight the importance of taking a developmental perspective when considering typical population traits. When interpreting changes in clinical cohorts, it is important to consider the pattern of expected change within the general population, which is influenced by cultural context and measurement.

BackgroundHigher body mass index (BMI) in childhood is associated with lower academic achievement.ObjectiveTo explore potential pathways linking childhood BMI with educational attainment.MethodsUsing data from the Avon Longitudinal Study of Parents and Children prospective cohort study (N = 6949), we assessed the association between BMI z-scores at 11.7 years and educational attainment at 16 (General Certificate of Secondary Education [GCSE] results). Depressive symptoms, externalizing behaviours, bullying and school enjoyment were considered as potential mediators. Mediators were examined individually and jointly using sequential causal mediation.ResultsHigher BMI z-scores were associated with lower GCSE scores (females β = −3.47 95% CI −5.54, −1.41 males β = −4.33 95% CI −6.73, −1.94). Together, bullying, externalizing symptoms, depressive symptoms and school enjoyment mediated 41.9% of this association in females, and 23.3% in males. In males, evidence for mediation was weak (confidence intervals for all indirect effects spanned the null). In both females and males, most of the mediation was driven by externalizing symptoms.ConclusionsThe detrimental effect of higher BMI on educational attainment appears to be partly explained by externalizing behaviours, particularly in females. Interventions to support behavioural problems may help the academic achievement of children with a higher body weight. Background: Higher body mass index (BMI) in childhood is associated with lower academic achievement. Objective: To explore potential pathways linking childhood BMI with educational attainment. Methods: Using data from the Avon Longitudinal Study of Parents and Children prospective cohort study (N = 6949), we assessed the association between BMI z-scores at 11.7 years and educational attainment at 16 (General Certificate of Secondary Education [GCSE] results). Depressive symptoms, externalizing behaviours, bullying and school enjoyment were considered as potential mediators. Mediators were examined individually and jointly using sequential causal mediation. Results: Higher BMI z-scores were associated with lower GCSE scores (females β = −3.47 95% CI −5.54, −1.41 males β = −4.33 95% CI −6.73, −1.94). Together, bullying, externalizing symptoms, depressive symptoms and school enjoyment mediated 41.9% of this association in females, and 23.3% in males. In males, evidence for mediation was weak (confidence intervals for all indirect effects spanned the null). In both females and males, most of the mediation was driven by externalizing symptoms. Conclusions: The detrimental effect of higher BMI on educational attainment appears to be partly explained by externalizing behaviours, particularly in females. Interventions to support behavioural problems may help the academic achievement of children with a higher body weight.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas. Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Background: Human papillomavirus (HPV)-based screening is rapidly replacing cytology as the cervical screening modality of choice. In addition to being more sensitive than cytology, it can be done on self-collected vaginal or urine samples. This study will compare the high-risk HPV positivity rates and sensitivity of self-collected vaginal samples using four different collection devices and a urine sample. Methods: A total of 620 women referred for colposcopy were invited to provide an initial stream urine sample collected with the Colli-Pee device and take two vaginal self-samples, using either a dry flocked swab (DF) and a wet dacron swab (WD), or a HerSwab (HS) and Qvintip (QT) device. HPV testing was performed by the BD Onclarity HPV Assay. Results: A total of 600 vaginal sample pairs were suitable for analysis, and 505 were accompanied by a urine sample. Similar positivity rates and sensitivities for CIN2+ and CIN3+ were seen for DF, WD, and urine, but lower values were seen for QT and HS. No clear user preferences were seen between devices, but women found urine easiest to collect, and were more confident they had taken the sample correctly. The lowest confidence in collection was reported for HS. Conclusions: Urine, a DF swab, and WD swab all performed well and were well received by the women, whereas the Qvintip and HerSwab devices were less satisfactory. Impact: This is the first study to compare five self-sampling methods in the same women taken at the same time. It supports wider use of urine or vaginal self-sampling for cervical screening.

Background:Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (Methods:We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: Results:Esophageal adenocarcinoma incidence has increased in patients Conclusions:Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma–free survival.Impact:Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma–specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.

To describe the clinical, endoscopic, and histologic features in patients with acute esophageal necrosis (AEN).In this retrospective cohort study, patients who were diagnosed as having AEN at Mayo Clinic sites in Minnesota, Florida, and Arizona between January 1, 1996, and January 31, 2021, were included. Data were collected on patient clinical characteristics and endoscopic and pathologic findings.The study included 79 patients with AEN with a median (range) age of 64 years (12 to 91 years); 53 (67.1%) were men. Predominant presenting symptoms were hematemesis (49 of 79 [62.0%]), abdominal pain (29 [36.7%]), and melena (20 [25.3%]). Shock was the triggering event for AEN in 49 (62.0%). The 30- and 90-day mortality were 24.0% (19 of 79) and 31.6% (25), respectively. The presence of coexisting infection or bacteremia was significantly associated with 90-day mortality (P.01). Endoscopically, involvement of the distal third only, distal two-thirds only, and entire esophagus was observed in 31.6% (24 of 76), 39.5% (30), and 29.0% (22), respectively. The length of esophageal involvement correlated with duration of hospitalization (P=.05). The endoscopic appearance of the esophageal mucosa ranged from predominantly white (21 of 44 [47.7%]) to mixed white and black (13 [29.6%]) to predominantly black (10 [22.7%]), and sloughing was present in 18 (40.9%). In the 26 patients with histopathologic findings available for review, 25 (96.1%) had necrosis and/or ulceration with abundant pigmentation. Among the 79 patients, 39 (49.4%) had a follow-up esophagogastroduodenoscopy; 26 of these 39 patients (66.7%) had resolution while 5 had persistent AEN, 4 of whom had improvement. Esophageal strictures developed in 7 of the 39 patients (18.0%).Acute esophageal necrosis is a serious condition observed in critically ill patients. Its endoscopic appearance can be highly variable. In patients with an unclear diagnosis, esophageal biopsies may be helpful given the characteristic histologic findings.

BACKGROUND: Hyperpolarized helium 3 magnetic resonance imaging ((3)He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children. OBJECTIVE: To evaluate the safety of (3)He MRI in children and adolescents with asthma. MATERIALS AND METHODS: This was a retrospective observational study. (3)He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8–18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 (3)He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO(2)) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8–12 years, 13–15 years, 16–18 years) using linear mixed-effects models. RESULTS: There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO(2) after (3)He MRI. The youngest age group (8–12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after (3)H inhalation, and an increased SpO(2) post MRI. CONCLUSION: The use of (3)He MRI is safe in children and adolescents with asthma.

Background Dysphagia is the most common symptom in advanced esophageal cancer patients. Esophageal stent placement (SP) is a common palliation method but can be associated with significant morbidity. Limited data exist regarding the ability of spray cryotherapy (SC) prolong time to SP. Methods A Mayo Clinic (Rochester, MN) patient database was reviewed for cases with a SC indication of esophageal cancer palliation from 2007–2019. Procedures were performed using a liquid nitrogen SC system to apply 2–5 separate 20 second freeze and 60 second thaw cycles based on tumor characteristics. Primary outcome was time to subsequent palliative SP. Results Of 56 patients (71.4% male, mean age 77.8 ± 10.2 years) who underwent a total of 199 SC sessions (mean 3.6 ± 2.7, range 1–12 per patient), 41 had adenocarcinoma and 15 squamous cell carcinoma (SCC). Overall, 13 patients underwent subsequent SP within a mean duration of 15.7 ± 11.0 months over a mean follow-up duration of 25.6 ± 29.4 months. Treatment did produce stenosis in 16 patients, who required dilation within a mean period of 193.1 ± 294.1 days; notably, 10 patients had a history of preceding malignant strictures requiring dilation. Two patients experienced bleeding requiring transfusion, whereas 1 experienced perforation at the start of SC. Prior chemotherapy and/or radiation was not associated with developing an SC-related complication (risk ratio (RR) 1.5; 95% CI 0.6–3.7, P > 0.4). Conclusions SC appears to be an effective and safe modality to palliate esophageal cancer in appropriate candidates. Majority of patients who undergo SC avoid the need for future SP. If patients eventually require SP, they are able to, on average, defer stenting for >1 year from SC initiation.

Introduction: Human papillomavirus–vaccinated cohorts, irrespective of age, will likely reduce their subsequent screening requirements, thus opening opportunities for global cost reduction and program sustainability. The determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated. Study design: This was an intervention study. Setting/participants: Study participants were women aged 25–45 years, attending opportunistic or population-based cervical cancer screening in Belgium, Denmark, Finland, France, Germany, Slovenia, Spain, Sweden, and the United Kingdom between April 2016 and May 2018. Intervention: Study participants completed a questionnaire on awareness and attitudes on adult female human papillomavirus vaccination and were invited to receive free human papillomavirus vaccination. Main outcome measures: Main outcome measures were acceptance, uptake, and completion of vaccination schedule. Determinants of vaccine uptake were explored using multilevel logistic models in 2019. Results: Among 3,646 participants, 2,748 (range by country=50%–96%) accepted vaccination, and 2,151 (range=30%–93%) received the full vaccination course. The factors associated with higher vaccine acceptance were previous awareness of adult female (OR=1.22, 95% CI=1.00, 1.48) and male (OR=1.59, 95% CI=1.28, 1.97) vaccination. Women in stable relationships (OR=0.56, 95% CI=0.45, 0.69) or with higher educational level (OR=0.76, 95% CI=0.63, 0.93) were more likely to refuse vaccination. Recruitment by postal invitation versus personal invitation from a healthcare professional resulted in lower vaccine acceptance (OR=0.13, 95% CI=0.02, 0.76). Vaccination coverage of >70% of adolescent girls in national public programs was of borderline significance in predicting human papillomavirus vaccine uptake (OR=3.23, 95% CI=0.95, 10.97). The main reasons for vaccine refusal were vaccine safety concerns (range=30%–59%) and the need for more information on human papillomavirus vaccines (range=1%–72%). No safety issues were experienced by vaccinated women. Conclusions: Acceptance and schedule completion were largely dependent on recruitment method, achieved coverage of national vaccination programs, and personal relationship status. Knowledge of benefits and safety reassurance may be critical to expanding vaccination target ages. Study results suggest that there are no major opinion barriers in adult women to human papillomavirus vaccination, especially when vaccination is offered face to face in healthcare settings. Trial Registration: EudraCT Number 2014-003177-42. publishedVersion

Background & Aims Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett’s esophagus (BE) in a multi-center (5-site) clinical study. Methods Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-μm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. Results 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. Conclusions The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.

DAL’s contribution to this paper is supported by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC grant agreement no 669545) and a UK National Institute of Health Senior Investigator (NF-0616-10102). TC’s contribution is supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No 733206 (LifeCycle). MLV has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707404. The opinions expressed in this document refect only the author’s view. The European Commission is not responsible for any use that may be made of the information it contains. The INfancia y Medio Ambiente (INMA)-Sabadell cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; CP18/00018; PI041436; PI081151; PI1100610 incl. FEDER funds). ISGlobal acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S). SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). JJ holds Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (Co-funded by European Social Fund “Investing in your future”). MC holds a Miquel ServetI cotract (CP16/00128) awarded by the Instituto de Salud Carlos III (co-funded by European Social Fund "Investing in your future"). The INMA-Asturias cohort is funded by grants from Instituto de Salud Carlos III (FISS PI 04/2018, FISS PI09/02311, FISS PI13/02429, FISS PI18/00909 including FEDER funds) and University of Oviedo. This study was funded by Instituto de Salud Carlos III through the projects ‘CP14/00108 & PI16/00261’ (co-funded by European Regional Development Fund ‘A way to make Europe’) (…), Alemany, S., Avella-García, C., Liew, Z., García-Esteban, R., Inoue, K., Cadman, T., López-Vicente, M., González, L., Riaño Galán, I., Andiarena, A., Casas, M., Margetaki, K., Strandberg-Larsen, K., Lawlor, D.A., El Marroun, H., Tiemeier, H., Iñiguez, C., Tardón, A., Santa-Marina, L., Júlvez, J., Porta, D., Chatzi, L., Sunyer, J.

Rationale and Objectives To determine lobar ventilation patterns in asthmatic lungs with hyperpolarized 3He magnetic resonance imaging (HP 3He MRI). Materials and Methods Eighty-two subjects (14 normal, 48 mild-to-moderate asthma, and 20 severe asthma) underwent HP 3He MRI, computed tomography (CT), and pulmonary function testing. After registering proton to 3He images, we segmented the lungs from proton MRI and further segmented the five lung lobes (right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]; left upper lobe and left lower lobe [LLL]) by referring to the lobar segmentation from CT. We classified the gas volume into four signal intensity levels as follows: ventilation defect percent (VDP), low ventilation percent, medium ventilation percent, and high ventilation percent. The local signal intensity variations in the ventilated volume were estimated using heterogeneity score (Hs). We compared each ventilation level and Hs measured in the whole lung and lobar regions across the three subject groups. Results In mild-to-moderate asthma, the RML and RUL showed significantly greater VDP than the two lower lobes (RLL and LLL) (P ≤ .047). In severe asthma, the pattern was more variable with the VDP in the RUL significantly greater than in the RLL (P = .026). In both asthma groups, the lower lobes (RLL and LLL) showed significantly higher high ventilation percent and Hs compared to the three upper lobes (all P ≤ .015). Conclusions In asthma, the RML and RUL showed greater ventilation abnormalities, and the RLL and LLL were more highly ventilated with greater local heterogeneity. These findings may facilitate guided bronchoscopic sampling and localized airway treatment in future studies.

BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. METHODS: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. RESULTS: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.). ispartof: GASTROINTESTINAL ENDOSCOPY vol:88 issue:4 pages:647-654 ispartof: location:United States status: published

This study used the Camberwell Assessment of Need for adults with Developmental and Intellectual Disabilities (CANDID) to examine the social, physical health and mental health needs of 168 young people (aged 14-24 years) with neurodevelopmental disorders and compared young person and parent ratings of need. Agreement was poor in 21 out of 25 domains. Parents consistently reported higher levels of need than young people in the majority of domains although young people with ADHD reported significantly more needs in physical health, eyesight/hearing, seizures, other mental health problems and safety of others than their parents. Both parent and young person perspectives of needs are necessary to ensure that needs that are predictive of current or future poor outcomes are not missed.

Background: Human papillomavirus (HPV) testing from clinician-collected cervical and self-collected cervico-vaginal samples is more sensitive for detecting CIN2+/CIN3+ than cytology-based screening, stimulating interest in HPV testing from urine. The objective was to determine the performance of the Trovagene HPV test for the detection of CIN2+ from urine and PreservCyt cervical samples. Methods: Women referred for colposcopy at St Mary's Hospital (London, United Kingdom), following abnormal cytology, were recruited to this diagnostic accuracy study by convenience sampling (September 2011 to April 2013). A total of 501 paired urine and cervical samples were collected. Primary outcomes were sensitivity for CIN2+/CIN3+ and specificity for Results: Trovagene HPV test sensitivity and specificity from PreservCyt were similar to well-established tests [sensitivity for CIN3+ (n = 145) 96.3% (95% confidence interval (CI), 89.6–99.2); CIN2+ (n = 81) 94.5% (95% CI, 89.4–97.6); specificity for Conclusions: Trovagene HPV test's performance on PreservCyt cervical samples was comparable with established HPV tests. Sensitivity in urine, although slightly lower, may nevertheless be adequate for self-sampling. This referral population's higher HPV positivity rate affects specificity, warranting further studies in a screening population. Impact: This may prove useful for women not attending for cervical screening. Cancer Epidemiol Biomarkers Prev; 26(7); 1053–9. ©2017 AACR.

Objective:There is emerging evidence that cognitive behavioral therapy (CBT) can be effective for treating anxiety and depression in people living with dementia (PLWD). Discriminating between thoughts and feelings is a critical element of CBT and also of relevance to emotional understanding more generally. The aim of the present study was the structured adaptation and preliminary validation of an existing measure of thought–feeling discrimination for use in PLWD.Methods/Design:The Behavior Thought Feeling Questionnaire (BTFQ) was adapted via expert and service-user consultation for use in PLWD. One hundred two PLWD and 77 people aged over 65 years who did not have measurable cognitive impairments completed the adapted measure along with two measures of emotional recognition and reasoning. The factor structure of this measure was examined and the measure reduced.Results:Factor analysis suggested a two-factor solution with thought and feeling items loading on separate factors. The behavior items were not included in scoring due to high cross-loading and ceiling effects, leaving a 14-item measure with two subscales. Thus, an adapted measure was created (named the BTFQ-D), which showed moderate convergent validity in the PLWD but not the older adult sample. Both thought and feeling subscales showed good internal consistency.Conclusions:The BTFQ-D showed preliminary validity as a measure of thought–feeling discrimination in PLWD. It may have utility in measuring readiness for CBT as part of clinical assessment. Further validation is required.

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims ...

Highlights • First comparison of HPV tests in PreservCyt and SurePath, 2 samples from each woman. • Nucleic acid HPV tests showed similar performance in PreservCyt and SurePath. • Manufacturers’ recommended pre-treatment protocols must be observed., Background Two transport media, PreservCyt and SurePath, are widely used for cervical cytology screening. There are concerns that they may perform differently for HPV testing. Objectives A comparison of the performance of six different HPV tests in SurePath and PreservCyt in a referral population using two samples from each woman. The primary goal was to compare the performance of each test in the two media. Comparisons between assays and viral load comparisons between media were secondary aims. Study design Two cervical samples were collected in random order at the same visit in women with abnormal cytology. One sample was placed in 20 ml of PreservCyt and the other in 10 ml of SurePath. Aliquots were taken for 4 DNA based tests: digene HC2 High-Risk HPV DNA Test, Abbott Realtime, BD Onclarity and Genera PapType, an RNA based test—: Hologic Aptima and a protein test: OncoHealth. Results 630 sample pairs were included in the analyses. For all tests except the protein test sensitivities were in excess of 90% for CIN2+ and 95% for CIN3+ for both media and with no significant differences except for a lower sensitivity for CIN2+ of Aptima in SurePath (93% vs 98%, P = 0.005). Specificity for

The purpose of this work was to quantify the redistribution of ventilation-weighted signal in the lungs of asthmatic subjects during a breath-hold using high temporal-spatial resolution hyperpolarized (HP) He-3 MRI. HP He-3 MRI was used to obtain time-resolved, volumetric images of lung ventilation during breath-hold in 39 human subjects classified as either healthy/nondiseased ( n = 14), mild-to-moderate asthmatic ( n = 17), or severely asthmatic ( n = 8). Signals were normalized to a standard lung volume, so that voxels within the lung from all 39 subjects could be analyzed as a group to increase statistical power and enable semiautomated classification of voxels into 1 of 5 ventilation level categories (ranging from defect to hyperintense). End-inspiratory ventilation distribution and temporal rates of mean signal change for each of the five ventilation categories were compared using ANOVA. Time rates of signal change were hypothesized to represent underlying gas redistribution processes, potentially influenced by disease. We found that mild-to-moderate asthmatic subjects showed the greatest rate of signal change, even though those with severe asthma had the greatest end-inspiration ventilation heterogeneity. The observed results support the existence of local differences in airway resistances associated with the different obstructive patterns in the lungs for severe vs. mild-to-moderate asthmatic subjects.

Adolescents and adults with autism spectrum disorder (ASD) are at elevated risk of co-occurring mental health problems. These are often undiagnosed, can cause significant impairment, and place a very high burden on family and carers. Detecting co-occurring disorders is extremely important. However, there is no validated screening tool for this purpose. The aim of this pilot study is to test the utility of the strengths and difficulties questionnaire (SDQ) to screen for co-occurring emotional disorders and hyperactivity in adolescents and adults with ASD. The SDQ was completed by 126 parents and 98 individuals with ASD (in 79 cases both parent and self-report were available from the same families). Inter-rater reliability, test-retest stability, internal consistency, and construct validity were examined. SDQ subscales were also compared to clinically utilized measures of emotional disorders and hyperactivity to establish the ability to predict risk of disorder. Inter-rater reliability (r = 0.42), test-retest stability (r = 0.64), internal consistency (α = 0.52-0.81) and construct validity (r = 0.42-0.57) for the SDQ subscales were comparable to general population samples. Parent- and self-report SDQ subscales were significantly associated with measures of anxiety, depression and hyperactivity (62-74% correctly classified). Parent-report performed significantly better than self-report; adults with ASD under-reported difficulties. The SDQ shows promise as a simple and efficient way to screen for emotional disorders and hyperactivity in adolescents and adults with ASD that could help reduce the impact of these disorders on individuals and their families. However, further more systematic attempts at validation are warranted. Autism Res 2016, 9: 1353-1363. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

INTRODUCTION: Studies have shown that dysplasia in Barrett's esophagus (BE) has a predilection for the right hemisphere. There is limited information on the longitudinal distribution. The aim was to determine both the longitudinal and circumferential distributions of dysplasia and early neoplasia from 3 prospective studies. METHODS: This is a pooled analysis from 3 prospective studies of patients with treatment-naive BE. Both circumferential and longitudinal locations (for BE segments greater than 1 cm) of dysplastic and early neoplastic lesions were recorded. RESULTS: A total of 177 dysplastic and early neoplastic lesions from 91 patients were included in the pooled analysis; of which 59.3% (n = 105) were seen on high-definition white light endoscopy, 29.4% (n = 52) on advanced imaging, and 11.2% (n = 20) with random biopsies. The average Prague score was C3M5. Of 157 lesions within BE segments greater than 1 cm, 49 (34.8%) lesions were in the proximal half, whereas 92 lesions (65.2%) were in the distal half (P < 0.001). The right hemisphere of the esophagus contained 55% (86/157) of the total lesions compared with 45% (71/157) for the left hemisphere (P = 0.02). This was because of the presence of high-grade dysplasia being concentrated in the right hemisphere compared with the left hemisphere (60% vs 40%, P = 0.002). DISCUSSION: In this pooled analysis of prospective studies, both low-grade dysplasia and high-grade dysplasia are more frequently found in the distal half of the Barrett's segment. This study confirms that the right hemisphere is a hot spot for high-grade dysplasia. Careful attention to these locations is important during surveillance endoscopy.

ObjectivesTo describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.DesignA cross-sectional, single-centre study.SettingA large, teaching hospital based in Central London with tertiary infection services.Participants236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men.MeasuresInformation on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report.ResultsThe 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off.ConclusionThere was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19.

BACKGROUND: MRI of hyperpolarized (129)Xenon (HP (129)Xe) is increasingly utilized for investigating pulmonary function. Solubility of HP (129)Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology. PURPOSE: Quantifying global average and regional repeatability of Barrier:gas, RBC:gas and RBC:Barrier ratios derived from dissolved-phase (129)Xe imaging and their dependence on inter-visit changes in lung inflation volume. STUDY TYPE: Prospective. POPULATION: 14 healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (8 female, 5 male, ages 24–69, 53.8±13.9). FIELD STRENGTH: 1.5 Tesla. ASSESSMENT: Subjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at 2 different time points, with approximately 1 month between visits. RBC:Gas, Barrier:Gas and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs). STATISTICAL TESTS: Repeatablilty was quantified using Bland Atlman plots, coefficient of repeatability, coefficient of variation (CV) and intra-class correlation coefficients (ICC). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intra-class correlations, and t-test for Spearman correlations and regression. RESULTS: Mean RBC:Gas, Barrier:Gas and RBC:Barrier had CVs of 19.2%, 20.0% and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79 and 0.92, respectively. Inter-visit differences in RBC:Barrier were significantly correlated with inter-visit differences in DLCO (r=0.93,P=0.007). Significant correlations with inter-visit lung volume differences and inter-visit differences in mean RBC:Gas (r=−0.73,P=0.005) and Barrier:Gas (r=−0.69,P=0.009) were found. DATA CONCLUSION: Three commonly used (129)Xe MRI based measures of gas-exchange show good repeatability, particularly Barrier:RBC ratio which did not depend on lung inflation volume and was strongly associated with inter-visit changes in DLCO.

ObjectivesAnxiety and depression are common and deleterious comorbidities in people living with dementia (PLWD). Cognitive behavioural therapy (CBT) is one of the few promising treatments; however, it is unclear whether PLWD have the necessary prerequisites to engage in this. Having an understanding of cognitive mediation, that a thought mediates the relationship between an antecedent event and its emotional consequence, is key for engaging with CBT and is also a critical component of emotion regulation. There are no measures of this construct validated for PLWD. This study aims to adapt and validate an existing measure for this population. A secondary aim is to assess its applicability in older adults (OA) without a recognised neurocognitive impairment.MethodsA measure of cognitive mediation was adapted via expert and service user consultation for use in PLWD. A total of 102 PLWD and 77 OA without neurocognitive impairments completed the adapted measure along with two measures of emotion recognition and reasoning. Factor structure was examined separately in both samples, and the measure reduced, with convergent validity assessed.ResultsA final measure of 10 items (named the CM‐Dem) was subject to factor analysis yielding a single factor solution. The measure showed good psychometric properties in PLWD, including good model fit, high internal consistency, inter‐rater reliability, and moderate convergent validity with related constructs. In contrast, poor validity was found in OA, especially a lack of convergent validity.ConclusionsThe CM‐Dem has clinical and research utility as a measure of cognitive mediation in PLWD, but less so in OA.

A wealth of research now exists surrounding use of the WHO surgical safety checklist. This paper reviews the literature regarding checklist use in developing countries. Results identify a lack of available literature specific to developing countries despite this potentially being where the greatest impact could be observed. Unique challenges of checklist use are discussed and opportunities for future research focusing on use of the checklist in developing countries suggested.

BACKGROUND: Esophageal food impaction is relatively common and increasing over time. Treatment ranges from medications to invasive endoscopic therapies. The endoscopic push technique has been advised against in favor of endoscopic retrieval for safety concerns. We sought to assess use patterns and safety of treatments for food impaction in a population-based retrospective review. METHODS: A database of recorded esophageal food impactions in Olmsted County, MN, USA, from 1975–2011 was reviewed for patient demographics, treatment, and complications. RESULTS: A total of 645 impactions occurred, with increasing incidence over time, peaking at 23.2 per year (2000–2004). Medications (almost exclusively glucagon) were successful in relieving impactions 34.5% of the time when trialed. Urgent endoscopy was common (74.0%), as was the need for endoscopic therapy (67.1%). Endoscopic therapy increased over time, with the endoscopic push technique becoming most common. Esophageal complications (deep mucosal injury or perforation) increased over time but remained rare (peak 11%). There was no difference in complications between push and retrieval techniques. CONCLUSIONS: The endoscopic push technique is safe in comparison to endoscopic retrieval in esophageal food impactions. While complications surrounding impaction have increased, they remain rare. Medication trials are reasonable, as long as they do not delay endoscopy, and may prevent the need for emergent endoscopy in one-third of cases.

PURPOSE: To compare the performance of three-dimensional radial ultrashort echo time (UTE) oxygen-enhanced (OE) MRI with that of hyperpolarized helium 3 ((3)He) MRI with respect to quantitative ventilation measurements in patients with cystic fibrosis (CF). MATERIALS AND METHODS: In this prospective study conducted from June 2013 to May 2015, 25 participants with CF aged 10–55 years (14 male; age range, 13–55 years; 11 female; age range, 10–37 years) successfully underwent pulmonary function tests, hyperpolarized (3)He MRI, and OE MRI. OE MRI used two sequential 3.5-minute normoxic and hyperoxic steady-state free-breathing UTE acquisitions. Seven participants underwent imaging at two separate examinations 1–2 weeks apart to assess repeatability. Regional ventilation was quantified as ventilation defect percentage (VDP) individually from OE MRI and hyperpolarized (3)He MRI by using the same automated quantification tool. Bland-Altman analysis, intraclass correlation coefficient (ICC), Spearman correlation coefficient, and Wilcoxon signed-rank test were used to evaluate repeatability. RESULTS: In all 24 participants, the global VDP measurements from either OE MRI (ρ = −0.66, P < .001) or hyperpolarized (3)He MRI (ρ = −0.75, P < .001) were significantly correlated with the percentage predicted forced expiratory volume in 1 second. VDP reported at OE MRI was 5.0% smaller than (P = .014) but highly correlated with (ρ = 0.78, P < .001) VDP reported at hyperpolarized (3)He MRI. Both OE MRI-based VDP and hyperpolarized (3)He MRI-based VDP demonstrated good repeatability (ICC = 0.91 and 0.95, respectively; P ≤ .001). CONCLUSION: In lungs with cystic fibrosis, ultrashort echo time oxygen-enhanced MRI showed similar performance compared with hyperpolarized (3)He MRI for quantitative measures of ventilation defects and their repeatability. © RSNA, 2018 Online supplemental material is available for this article.

With the emergence of eosinophilic esophagitis (EoE) as a common cause of food impaction (FI) and a presumed increase in incidence of EoE in the population, the effect on the incidence of FI has not been well described. The aim of this study is to describe the incidence of FI and endoscopic findings in these patients and the association with EoE. A population-based retrospective chart review of the Rochester Epidemiology Project database was performed to identify all patients within Olmsted County that presented with FI from 1976 to 2012. A review of all endoscopic findings, biopsy results, and demographic data was performed. 497 patients were identified with FI from 1976 to 2012. The overall incidence of FI has changed from 1976 to 2012 (Fig. 1) (P

ObjectiveSurveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett’s oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines.DesignData on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies.Results594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4–4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI −7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia).ConclusionsBE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Author(s): Cadman, Tim; Belsky, Jay; Pasco Fearon, Richard M | Abstract: BackgroundInsecure attachment in infancy is associated with a range of later socioemotional problems; therefore, it is important to identify at-risk children so that support can be provided. However, there are currently no well-validated brief measures of infant attachment. The aim of this study is to create a brief version of the Attachment Q-Sort (AQS), one of the gold-standard measures of attachment.MethodData was used from the National Institute of Child Health and Development Study of Child Care and Youth Development (N = 1,364). The factor structure of the AQS was explored, and Item Response Theory was used to select a reduced number of items. Convergent validity of the shortened measure was assessed through associations with the Strange Situation Procedure. Correlations with sensitivity, externalising, and social competence were also examined.ResultsThe Brief Attachment Scale (BAS-16) was created consisting of two scales of eight items, relating to (a) harmonious interaction with the caregiver and (b) proximity-seeking behaviours. The BAS-16 showed comparable convergent, discriminant, and concurrent validity to the full AQS.ConclusionThis brief version of the AQS shows potential as a screening measure for insecure attachment in infancy. Further development and validation is required in separate samples.

Although the endoscopic submucosal dissection (ESD) has been established to be more efficacious in the treatment of superficial gastrointestinal neoplasia than the piecemeal resection, its use is still limited due to the concern about serious adverse events particularly in the west. Newer ESD knives have been developed that have been said to be safer than the first-generation devices. We aimed to report a Western single center experience regarding the initial safety and performance of ESD for superficial esophageal neoplasia treated with the Clutch Cutter (DP2618DT; Fujifilm Corporation, Tokyo, Japan). Our main outcome was safety in terms of bleeding or perforation. Secondary outcomes included en bloc resection and the R0 resection. Fourteen patients with superficial esophageal neoplasia underwent 15 ESDs using the Clutch Cutter. The mean age was 65 ± 16.7 years and 10 (71.4%) males. Eight (57%) patients had esophageal adenocarcinoma, 3 (21.4%) had high-grade dysplasia, 1 (7%) had nodular low-grade dysplasia, and 2 (14.3%) had squamous cell carcinoma. Mild anticipated intraprocedural bleeding was present with most procedures. However, no significant postoperative bleeding or perforation was encountered. One patient had mild chest pain postprocedure. En bloc resection was achieved in all lesions 100%. Histological R0 was achieved in 5/12 lesions (41.6%). The mean length of the resected area was 24.8 ± 13 mm (IQR: 17-30 mm). All patients were safely discharged home after overnight observation. In conclusion, this is the largest series of esophageal ESD using the multimodal Clutch Cutter in the United States; we found that the device effectively achieved en bloc resection of superficial esophageal neoplasia without significant adverse events. The use of the Clutch Cutter should be considered as one option to minimize adverse events during ESD in the Western population.

Striatal cholinergic (ChAT) and parvalbumin (PV) interneurons exert powerful influences on striatal function in health and disease, yet little is known about the organization of their inputs. Here using rabies tracing, electrophysiology and genetic tools, we compare the whole-brain inputs to these two types of striatal interneurons and dissect their functional connectivity in mice. ChAT interneurons receive a substantial cortical input from associative regions of cortex, such as the orbitofrontal cortex. Amongst subcortical inputs, a previously unknown inhibitory thalamic reticular nucleus input to striatal PV interneurons is identified. Additionally, the external segment of the globus pallidus targets striatal ChAT interneurons, which is sufficient to inhibit tonic ChAT interneuron firing. Finally, we describe a novel excitatory pathway from the pedunculopontine nucleus that innervates ChAT interneurons. These results establish the brain-wide direct inputs of two major types of striatal interneurons and allude to distinct roles in regulating striatal activity and controlling behavior.

High‐risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV‐positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV‐positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P, What's new? DNA testing for high‐risk human papillomaviruses (hrHPVs) can both detect and predict the development of precancerous cervical lesions. Limitations in specificity, however, necessitate the generation of triage strategies to minimize unneeded colposcopy among hrHPV‐positive women. According to this study, triage may be readily affected using a DNA methylation classifier based on the human gene EPB41L3 and the late gene regions of HPV16, HPV18, HPV31 and HPV33. The devised classifier outperformed triage by HPV16/18 genotyping in a cohort of hrHPV‐positive patients. The strategy could fill a key role in hrHPV triage in cervical screening programs.

BackgroundADHD in childhood is associated with development of negative psychosocial and behavioural outcomes in adults. Yet, relatively little is known about which childhood and adulthood factors are predictive of these outcomes and could be targets for effective interventions. To date follow-up studies have largely used clinical samples from the United States with children ascertained at baseline using broad criteria for ADHD including all clinical subtypes or the use of DSM III criteria.AimsTo identify child and adult predictors of comorbid and psychosocial comorbid outcomes in ADHD in a UK sample of children with DSM-IV combined type ADHD.MethodOne hundred and eighteen adolescents and young adults diagnosed with DSM-IV combined type ADHD in childhood were followed for an average of 6 years. Comorbid mental health problems, drug and alcohol use and police contact were compared for those with persistent ADHD, sub-threshold ADHD and population norms taken from the Adult Psychiatric Morbidity Study 2007. Predictors included ADHD symptomology and gender.ResultsPersistent ADHD was associated with greater levels of anger, fatigue, sleep problems and anxiety compared to sub-threshold ADHD. Comorbid mental health problems were predicted by current symptoms of hyperactivity-impulsivity, but not by childhood ADHD severity. Both persistent and sub-threshold ADHD was associated with higher levels of drug use and police contact compared to population norms.ConclusionsYoung adults with a childhood diagnosis of ADHD showed increased rates of comorbid mental health problems, which were predicted by current levels of ADHD symptoms. This suggests the importance of the continuing treatment of ADHD throughout the transitional years and into adulthood. Drug use and police contact were more common in ADHD but were not predicted by ADHD severity in this sample.

BACKGROUND Persistent infection %by with high risk human papillomavirus (hrHPV) types causes cervical cancer but most women who test positive are at very low risk of neoplasia. Strategies are needed which can retain high sensitivity of hrHPV testing but reduce the number of false-positives. We showed previously that a combination DNA methylation triage assay for HPV types 16, 18 and 31 and human gene EPB41L3 was useful to identify high grade cervical lesions. OBJECTIVE Assess whether measurement of DNA methylation in HPV type 33 can improve the previous classifier. METHODS A London colposcopy referral group of 1493 women of whom 556 (37%) had histologically-confirmed CIN (cervical intraepithelial neoplasia) 2 or 3 that included 114 HPV33 positive women with methylation measured for three L2 CpGs 5557, 5560 and 5566. Discrimination performance was assessed for the new classifier S5, built by adding HPV33 to the earlier classifier. RESULTS HPV33 methylation measurement improved prediction among HPV33 positive women. Receiver operating characteristic analyses showed an area under the curve (AUC) for HPV33 methylation of 0.68 (95% CI 0.57-0.78). The earlier risk score was significantly improved by HPV33 methytlation (AUC = 0.82 vs 0.80; P < 0.001). For 90% sensitivity the specificity for CIN2/3 was 49% (95% CI 46-52%). CONCLUSIONS Measurement of HPV33 DNA methylation contributes independent diagnostic information to EPB41L3 and HPV16, HPV18 and HPV31, and is superior to genotyping. Other HPV and human methylation target regions might be useful to further improve S5.

A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research.To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage.Volunteer and patient repeatability.Eighteen human subjects (five asthma, six CF, and seven normal subjects).Respiratory-gated free-breathing 3D radial UTE (80 μs) sequence at 1.5T.Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map.The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test-retest repeatability was evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC).Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test-retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons).3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test-retest repeatability.2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1287-1297.

Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes.

To determine the 1) incidence of subglottic stenosis in infants and children following cardiac surgery with cardiopulmonary bypass and 2) risk factors associated with its development.Retrospective cohort study.Tertiary children's hospital in California.Infants and children who underwent cardiac surgery with cardiopulmonary bypass.Diagnosis of subglottic stenosis by tracheoscopy.The incidence of subglottic stenosis at our institution during the study period was 0.7%. Young age (p = 0.014), prolonged cardiopulmonary bypass (p = 0.03), and prolonged mechanical ventilation (p0.01) were associated with the development of subglottic stenosis. Gender, chromosomal anomaly, presence of a cuffed endotracheal tube, and lowest core temperature during cardiopulmonary bypass were not associated with the development of subglottic stenosis.The incidence of subglottic stenosis was less than that previously reported in this population. Although the incidence is relatively low, subglottic stenosis is a serious complication of tracheal intubation and all measures to prevent subglottic stenosis should be undertaken.

Background Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. Objectives To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. Methods 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). Results 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90–2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. Conclusion Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result.

Testing for high-risk (hr) types of human papillomavirus (HPV) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (CIN2/3) disease, the precursor of cervical cancer. However, it has a relatively low specificity. Our objective was to develop a prediction rule with a higher specificity, using combinations of human and HPV DNA methylation. Exfoliated cervical specimens from colposcopy-referral cohorts in London were analyzed for DNA methylation levels by pyrosequencing in the L1 and L2 regions of HPV16, HPV18, HPV31 and human genes EPB41L3, DPYS and MAL. Samples from 1,493 hrHPV-positive women were assessed and of these 556 were found to have CIN2/3 at biopsy; 556 tested positive for HPV16 (323 CIN2/3), 201 for HPV18 (73 CIN2/3) and 202 for HPV31 (98 CIN2/3). The prediction rule included EPB41L3 and HPV and had area under curve 0.80 (95% CI 0.78–0.82). For 90% sensitivity, specificity was 36% (33–40) and positive predictive value (PPV) was 46% (43–48). By HPV type, 90% sensitivity corresponded to the following specificities and PPV, respectively: HPV16, 38% (32–45) and 67% (63–71); HPV18, 53% (45–62) and 52% (45–59); HPV31, 39% (31–49) and 58% (51–65); HPV16, 18 or 31, 44% (40–49) and 62% (59–65) and other hrHPV 17% (14–21) and 21% (18–24). We conclude that a methylation assay in hrHPV-positive women might improve PPV with minimal sensitivity loss.

Background Dysplastic Barrett’s esophagus (BE) lesions ≤2 cm in size can be targeted for en-bloc endoscopic mucosal resection (EMR). White-light endoscopy can underestimate the size of a lesion, limiting complete resection. Volumetric laser endomicroscopy (VLE) provides high-resolution cross-sectional imaging of BE. Epithelial glands are a VLE feature associated with BE dysplasia. We study the association between VLE gland quantification and outcome of resection. Methods EMR specimens of BE lesions targeted for en-bloc resection were imaged with VLE using an established protocol. Manual and automated quantification of epithelial glands was performed blinded to resection outcome. The presence of epithelial glands at the resection margins was recorded. Histologic en-bloc (R0) resection of the targeted lesion was defined by the absence and incomplete (R1) resection by the presence of dysplasia/neoplasia at specimen margins. Results Thirty-seven EMRs with a mean (standard deviation) size of 1.04 (0.37) cm were imaged with VLE. The highest grade of dysplasia found was low-grade dysplasia (n = 12), high-grade dysplasia (n = 19), and intramucosal cancer (n = 6). The en-bloc resection rate was 37.8% (R0, n = 14; R1, n = 23). The mean (standard deviation) number of epithelial glands quantified with VLE was 13.0 (6.7) and 28.8 (23.9) for R0 and R1 specimens, respectively, with a significant mean difference of 15.8 glands (95% confidence interval, 2-29; P = .02). The presence of glands at the specimen margin was associated with incomplete resection (P Conclusion Systematic quantification of BE epithelial glands using VLE can determine the outcome of endoscopic resection. VLE may have a potential role in assessment of lesion margins.

Background: Research has revealed that passive nature viewing (viewing nature scenes without actually being in nature) has many health benefits but little is known about the best method of offering this complementary modality. Aims: The purpose of this pilot program was to evaluate the impact of a passive nature viewing program set to music on stress reduction in adults living in the community. Description and Evaluation: A pre- and postsurvey design along with weekly recordings of stress and relaxation levels were used to evaluate the effect of this passive nature viewing program on stress reduction. Participants watched one of three preselected nature scenes for 5 minutes a day over 1 month and rated their stress and relaxation levels weekly on a 100-mm Visual Analogue Scale before and after viewing the nature DVD. Quantitative analysis were not performed because of the less number of subjects ( n = 10) completing the study. Qualitative analysis found five key categories that have an impact on program use: (a) technology, (b) personal preferences, (c) time, (d) immersion, and (e) use of the program. Conclusions and Implications: Holistic nurses may consider integrating patient preferences and immersion strategies in the design of future passive nature viewing programs to reduce attrition and improve success.

Objectives To assess the association between Barrett esophagus (BE) and the metabolic syndrome in patients with and without reflux symptoms and to determine whether this association is reflux independent and metabolically driven. Patients and Methods Case patients with BE and controls were residents of Olmsted County, Minnesota (1999-2006). Two control groups (one with and one without symptoms of gastroesophageal reflux) were identified from a cohort of patients who had responded to a validated gastrointestinal symptom questionnaire. Cases and controls were individually matched by age, sex, and duration of follow-up. Controls did not have a known diagnosis of BE. The association of the metabolic syndrome and its individual components with BE was assessed using univariate and multivariate conditional logistic regression separately for each control group. Results A total of 309 patients were included (103 BE cases, 103 controls with reflux symptoms, and 103 controls without reflux symptoms). A total of 64% of cases, 47% of controls with reflux symptoms, and 50% of controls without reflux symptoms had the metabolic syndrome. The metabolic syndrome was associated with a 2-fold increased risk of BE relative to those with (odds ratio, 2.00; 95% CI, 1.10-3.65; P =.02) and without (odds ratio, 1.90; 95% CI, 1.03-3.60; P =.04) reflux symptoms. This association was independent of smoking, alcohol consumption, and body mass index and remained robust with sensitivity analysis. Conclusion The metabolic syndrome is associated with BE independent of reflux symptoms, which may reflect a reflux-independent pathway of BE pathogenesis.

Background and Aims Volumetric laser endomicroscopy (VLE) provides a circumferential scan that enables visualization of the subsurface layers of the esophageal wall at 7 μm resolution. The aims of this study were to identify VLE features of Barrett's esophagus (BE) neoplasia and to develop a VLE prediction score. Methods A database of VLE images from endoscopic resection specimens, precisely correlated with histology, from patients with BE with and without neoplasia was used. Features potentially predictive for early BE neoplasia were identified by unblinded evaluation of 25 VLE-histology images. In a learning phase, 20 VLE images with or without BE neoplasia were scored by 2 VLE experts, blinded to histology. A prediction score was created by using multivariable logistic regression analyses and validated by scoring 40 VLE images (50% neoplastic) by using area under receiver operating characteristic (ROC) curve (AUC) analysis. Results Three VLE features independently predictive for BE neoplasia were identified: (1) lack of layering; (2) higher surface than subsurface signal; (3) presence of irregular, dilated glands/ducts. A VLE neoplasia prediction score was developed with the following: (1) 6 points; (2) 6 or 8 points for equal or higher surface signal; and (3) 5 points. The ROC curve of this prediction score showed an AUC of 0.81 (95% confidence interval, 0.71-0.90). A cut-off value of ≥8 was associated with sensitivity and specificity of 83% and 71%, respectively. Conclusions When high-quality ex vivo VLE-histology correlation was used, the VLE features of layering, surface signal, and irregular glands/ducts were independently and significantly associated with BE neoplasia. A VLE prediction score for BE neoplasia was developed and validated, with promising accuracy. (Clinical trial registration number: NCT01862666.)