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OBJECTIVE The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure. METHODS The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network. RESULTS The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98–1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages. CONCLUSIONS This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

OBJECTIVE Hydrocephalus can impact all areas of health, including physical, cognitive, and social-emotional functioning. The social-emotional health of children who have had surgery for hydrocephalus is not well characterized. In this study, the authors sought to examine social-emotional functioning using the Behavior Assessment System for Children, Third Edition (BASC-3) and the Hydrocephalus Outcome Questionnaire (HOQ) in 66 children aged 5 to 17 years. METHODS Caregivers of pediatric patients with hydrocephalus completed the BASC-3 and the HOQ. BASC-3 internalizing, externalizing, and executive functioning caregiver-reported scores were compared with the BASC-3 normative sample using one-sample t-tests to evaluate overall social-emotional functioning. BASC-3 scores were correlated with the social-emotional domain of the HOQ using Pearson’s r to determine if the HOQ accurately captured the social-emotional functioning of children with hydrocephalus in a neurosurgery setting. BASC-3 and HOQ scores of children with different etiologies of hydrocephalus were compared using the Kruskal-Wallis one-way analysis of variance to determine if differences existed between the following etiologies: intraventricular hemorrhage secondary to prematurity, myelomeningocele, communicating congenital hydrocephalus, aqueductal stenosis, or other. RESULTS Children with hydrocephalus of all etiologies had more difficulties with social-emotional functioning compared with normative populations. Children with different hydrocephalus etiologies differed in executive functioning and overall HOQ scores but not in internalizing symptoms, externalizing symptoms, or social-emotional HOQ scores. The social-emotional domain of the HOQ correlated more strongly with the BASC-3 than did the physical and cognitive domains. CONCLUSIONS These results have provided evidence that children who have had surgery for hydrocephalus may be at increased risk of social-emotional and behavioral difficulties, but etiology may not be particularly helpful in predicting what kinds or degree of difficulty. The results of this study also support the convergent and divergent validity of the social-emotional domain of the HOQ.

Diet is a key modifier of risk of inflammatory bowel disease development and potentially a treatment option in patients with established disease. International organisations in gastroenterology and inflammatory bowel disease have published guidelines for the role of diet in disease onset and its management. Here, we discuss the major overarching themes arising from these guidelines and appraise recent literature on the role of diet for inflammatory bowel disease prevention, treatment of active disease and maintenance of remission, considering these themes. Except for exclusive enteral nutrition in active Crohn’s disease, we currently possess very little evidence to make any further dietary recommendations for the management of inflammatory bowel disease. There is also currently uncertainty on the extrapolation of epidemiological dietary signals on risk of disease development and preclinical experiments in animal models to management, once disease is established. Until high-quality evidence from clinical research becomes available, the only specific recommendations for inflammatory bowel disease we might safely give are those of healthy eating which apply for the general population for overall health and well-being.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Endomyocardial biopsy (EMB) is a common procedure used to aid in the diagnosis of diffuse myocardial diseases and, less commonly, in the diagnosis of cardiac tumors. As cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount, and additional imaging, like transesophageal echocardiography is often required for guidance. The use of intracardiac echocardiography (ICE) to guide biopsy has been described, but there is no consensus on a standardized approach. We report our institutional approach with three cases of ICE-directed EMB performed with the 2.4 mm Jawz bioptome directed with an 8.5-Fr Agilis NxT steerable introducer. All cases were performed under guidance with the AcuNav ICE probe. There were no procedural complications and a definitive diagnosis was obtained in all three cases. We also review the available published cases of ICE-guided EMB in the literature-noting the different procedural approaches, complication rate, and diagnostic yield. There were only two negative biopsies reported among the published cases and no reported complications. Our review of all these cases suggests that ICE-guidance for EMB is superior to other forms of imaging in its ease of use and high definition of right-sided cardiac structures. We also feel that the use of the Agilis steerable sheath allows for more precise directing of the bioptome and is a critical component in performing a successful targeted biopsy.

Aims To examine whether moderate adolescent cannabis use has neurocognitive effects that are unexplained by familial confounds, which prior family-controlled studies may not have identified. Design A quasi-experimental, sibling-comparison design was applied to a prospective, observational study of adolescents with moderate cannabis use. Participants were recruited from 2001 to 2006 (mean age = 17 years). A second wave of data was collected from 2008 to 2013 (mean age = 24 years). Setting Two US metropolitan communities. Participants A total of 1192 adolescents from 596 families participated in this study. Participants were primarily male (64%) and racially and ethnically diverse (non-Hispanic white = 45%). A sibling in each family was a clinical proband identified due to delinquent behaviors. Whereas prior family-controlled studies have used samples of primarily infrequent cannabis users (mean = 1-2 days/month), participants here endorsed levels of cannabis use comparable to findings from epidemiological cohort studies (mean = 7-9 days/month). Measurements Semi-structured clinical interviews assessed drug use, and a neuropsychological battery assessed cognitive abilities. Covariates included age at assessment, gender and alcohol use. Findings After correcting for multiple testing, a greater frequency and earlier onset of regular cannabis use were associated with poorer cognitive performance, specifically on tests of verbal memory. Further, after accounting for familial factors shared by siblings and alcohol use, poorer verbal memory performance was still associated with greater life-time frequency of cannabis use at wave 1 [b = -0.007 (-0.002, -0.012), adjusted P = 0.036]; earlier cannabis use at wave 2 [b = -0.12 (-0.05, -0.19), adjusted P = 0.006; b = -0.14 (-0.06, -0.23), adjusted P = 0.006]; and greater frequency of past 6 months use at wave 2 [b = -0.02 (-0.01, -0.03), adjusted P = 0.002; b = -0.02 (-0.01, -0.03), adjusted P = 0.008]. Conclusions Moderate adolescent cannabis use may have adverse effects on cognitive functioning, specifically verbal memory, that cannot be explained by familial factors.

Malnutrition is common in patients with Crohn's disease and negatively influences immunity and quality of life. The optimal tools for nutrition assessment in patients with Crohn's disease are not clearly defined and lead to variations in practice. With this review, we aimed to appraise the existing evidence for nutrition assessment of patients with Crohn's disease compared with healthy controls and provide a comprehensive guide with relevant measures applicable to clinical practice. A literature search using Medline, Embase, and Scopus from inception to October 1, 2018, was conducted. Forty-one articles that assessed body composition, muscle strength, micronutrient status and/or dietary intake in adults with Crohn's disease compared with an age- and sex-matched healthy individuals were included. There were heterogeneous findings on nutritional status in patients with Crohn's disease compared with healthy controls. Only one article reported a clinically significant difference for body mass index; however, significant deficits in fat mass, fat-free mass, and muscle strength were observed in patients with Crohn's disease compared with healthy controls, with more pronounced differences with increasing disease activity and length of diagnosis. Most research reported significantly lower serum micronutrients in patients with Crohn's disease compared with healthy controls. Half of studies measuring micronutrient intake reported lower intakes in patients with Crohn's disease compared with healthy controls. Fruit and vegetable intake was also lower in patients with Crohn's disease. Difficulties characterizing the type and prevalence of malnutrition exist due to the heterogeneous nature of Crohn's disease and warrants continued investigation. As a result of this review, we advocate that a nutrition assessment should include more parameters than weight and body mass index.

Introduction: Although collecting faeces and blood samples are considered non-invasive methods of monitoring Crohn’s disease (CD), these methods are less preferred by some patients. This study utilized urine as an alternative to evaluate four disease biomarkers in young adults with active CD before and after exclusive enteral nutrition (EEN) therapy. Methods: Urine samples collected at baseline (W0) and after 8 weeks (W8) of EEN therapy were assayed by ELISA for levels of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), claudin-3, and calprotectin. Levels of each biomarker were also compared with standard clinical parameters, including disease indexes, nutrient, and inflammatory markers. Results: Of the paired urine samples from 14 patients, 10 were female and 12 were newly diagnosed with CD. Urinary I-FABP:Cr (standardized to urine Cr) levels were significantly reduced, while urinary L-FABP:Cr levels increased following EEN therapy. Urinary L-FABP:Cr correlated positively with serum insulin-like growth factor 1 (IGF-1) (r = 0.60, p = 0.02). Urinary CLND3:Cr and calprotectin:Cr levels were not significantly different after treatment. Conclusion: I-FABP is a potential urinary biomarker of disease activity in adults with CD, while urinary L-FABP may be an indirect marker of nutritional status in adults with CD. CLND3 and calprotectin do not appear to have roles as urinary biomarkers in CD. These findings warrant further investigations using a larger sample size.

Introduction: Diabetes mellitus is a significant cause of morbidity and mortality. Foot-related complications affect 2–2.5% of people with diabetes. There is significant variation in outcomes for patients with diabetic foot disease within the UK. The multidisciplinary approach to diabetic foot disease is well publicised and protocols, guidance and consensus approaches exist for most components of the management of diabetic foot disease. Antimicrobial therapy to treat diabetic foot infections based on microbiological sampling and culture is well documented, but no consensus exists on how these samples should be obtained, processed and reported. Methods: A literature review was undertaken to establish the reporting of techniques used in obtaining and processing microbiological samples in diabetic foot disease to establish if consensus exists in the methodologies used with a view to develop best practice guidelines. Results: Six out of 102 papers reported all processes in obtaining and processing microbiological samples. Conclusion: No gold standard consensus exists for microbiological sampling of diabetic foot infections, preventing optimisation of this aspect of management of diabetic foot disease and ultimately potentially adversely affecting the outcomes of this growing patient cohort.

The genetic architecture of numerous smoking behaviors is highly polygenic, but these genetic effects are heterogeneous and depend on moderating factors. Here, we used common SNPs from the UK Biobank to investigate heterogeneous genetic effects for smoking heaviness using cigarettes per day (CPD) records, smoking initiation (SI), and smoking cessation (SC). We assessed heterogeneous effects across levels of sex, age of smoking initiation, major depressive disorder (MDD) DSM-V-like diagnosis, generalized anxiety disorder (GAD) DSM-V-like diagnosis, and whether an individual has seen a psychiatrist for nerves, anxiety, tension, or depression. We observed suggestive evidence of heterogeneous genetic effects for CPD and SC, moderated by MDD and GAD, respectively [ (SE = 0.15) between MDD cases and controls, and (SE = 0.28) between GAD cases and controls, p < 0.05]. We detected 5 SNPs with genome-wide significant evidence of heterogeneous effects moderated by either MDD or GAD (p-value < 5×10-8) for CPD and SC. We also observed strong evidence for heterogeneous genetic effects for SI between sexes (between-sex , SE = 0.02). While we detected no individual SNPs that were moderated by sex at genome-wide significance (all p-value > 5×10-8), we observed evidence of novel genome-wide significant SI-SNP associations using sex-stratified GWAS; six loci were discovered in either men or women separately that were not identified in a previous smoking meta-analysis that had a 6-fold larger, sex-combined sample. Furthermore, using several independent testing samples, there was suggestive evidence that the prediction ability of a polygenic risk score (PRS) for smoking initiation improved through the utilization of sex-specific SNP effects. This work suggests that a more nuanced approach to GWAS analyses is warranted, as potential heterogeneous effects can complicate variant discovery and polygenic risk score accuracy.Author SummarySmoking imposes a heavy health burden and is highly polygenic in architecture. Consistent with most complex traits, many causal loci have yet to be identified, even when using the largest available samples. One possible reason for the difficulty in inferring genetic variants associated with such complex traits is that common genetic variants possess context-dependent (or heterogeneous) effects. Utilizing the UK Biobank, we find evidence for heterogeneous SNP effects on smoking initiation, heaviness, and cessation among psychiatric disorder cases and controls and between sexes. Failure to model such heterogeneity (when accounting for sample size) resulted in lower independent sample predictive ability. This work encourages a more nuanced approach to GWAS and polygenic risk prediction. The assumption that all genetic effects are homogeneous limits our understanding of complex traits when heterogeneous effects are present.

Background Arterial ligation has been described in the literature as a safe and effective procedure with a relatively low number of patients requiring major amputations. Methods We performed a retrospective analysis of a prospectively held database of all patients who underwent arterial ligation for infected femoral pseudoaneurysms due to chronic intravenous drug abuse from January 2012 to March 2018. Information recorded for each patient included age, gender, blood investigations, microbiologic results, diagnostic modality, operative details, outcome of surgery, postoperative complications, and follow-up. Results There were 25 patients identified, with 2 of them undergoing bilateral ligations. It was more common in men (4:1), and the mean age at presentation was 39.7 years (standard deviation 8.2 y). Nine patients underwent major limb amputation for severe limb ischemia (7 transfemoral amputations and two 53 hip disarticulation). Average hospital stay was 24 days, and there was no mortality. We found a trend with a higher level of arterial ligation, leading to a higher rate of amputation. Conclusions Our study is the first to show that there is a trend toward a higher risk of amputation with a higher level of ligation in this cohort of patients, and therefore, we suggest avoidance of external iliac artery ligation even at the most distal part just under the ligament, leaving the circumflex iliac vessel in circuit. Arterial ligation also carries a higher risk of major amputation than previously reported.

Objectives Early bedside post-operative monitoring of infrainguinal bypass surgery is currently based on subjective clinical findings and handheld Doppler signals. Infrared thermal imaging is an objective and reproducible technique that has been proven to be a reliable and accurate method to measure skin temperature. The aim of this prospective study was to assess infrared thermal imaging as a predicting tool of bypass graft outcome in the immediate post-operative period and assess the angiosome concept. Methods This was a prospective cohort study of 25 patients undergoing infrainguinal bypass. Demographic and clinical data were prospectively collected and included gender, age, co-morbidities, pre- and post-operative ankle brachial pressure indices, surgery undertaken and patency of run-off vessels. Infrared thermal imaging was undertaken pre- and post-operatively to assess thermal changes to the feet following revascularisation. Results We found that an increase in temperature from pre- to post-operative was significantly associated with bypass patency. An increase in temperature was found to have a positive predictive value of 75%, a negative predictive value of 100%, a sensitivity of 100% and specificity of 89% for predicting graft patency. Conclusions Infrared thermal imaging can be used to measure temperature related changes of the microcirculation post-operatively and predict bypass outcomes in the immediate post-operative period.

AIMS: The current meta-analysis tested independent and composite associations of three commonly studied alcohol metabolism alleles with alcohol use disorder (AUD) within East Asians as well as characterized potential moderating factors in these associations. METHODS: For meta-analysis, 32 articles were selected that investigated ALDH2 (n = 17,755), ADH1B (n = 13,591) and ADH1C (n = 4,093) associations with AUD in East Asians. RESULTS AND CONCLUSIONS: All three variants were associated with AUD across allelic and genotypic models: ALDH2, ORs = 0.25, P < 0.001; ADH1B, ORs = 0.22–0.49, P < 0.001; ADH1C, ORs = 0.26–0.46, P < 0.001. Composite analyses suggested genetic associations did not differ across ALDH2*2 and ADH1B*2, correcting for multiple comparisons. Moderation analyses suggested ADH1B was more strongly associated with AUD among samples with cases recruited from treatment than the community. Also, strength of ALDH2 and/or ADH1B associations varied with mean age and proportion of men in cases and controls. Findings support medium to large and unique associations of ALDH2, ADH1B, and ADH1C with AUD in East Asians. Results also identified novel methodological and sample characteristics that may modulate strength of these associations.

On February 27 to 28, 2018, the Produce Safety Alliance convened a national water summit in Covington, KY to discuss the requirements of the United States Food and Drug Administration's (FDA) Food Safety Modernization Act Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption (Produce Safety Rule [PSR]). The goals of the meeting were to better understand the challenges growers face in implementing the requirements in Subpart E-Agricultural Water and work collaboratively to develop practical solutions to meet fruit and vegetable production needs while protecting public health. To meet these goals, the summit engaged a diverse group of stakeholders including growers, researchers, extension educators, produce industry members, and regulatory personnel. Key outcomes included defining implementation barriers due to diversity in water sources, distribution systems, commodity types, climates, farm size, and production activities. There was an articulated need for science-based solutions, such as the use of agricultural water system assessments and sharing of federal, state, and regional water quality data, to ensure qualitative and quantitative standards reduce microbial risks. These identified challenges and needs resulted in significant debate about whether reopening the PSR-Subpart E for modification or attempting to address concerns through guidance would provide the best mechanism for alleviating concerns. In addition, training, outreach, and technical assistance were identified as vital priorities once the concerns are formally addressed by FDA. The water summit highlighted the critical need for transparency of FDA's progress on reevaluating the Subpart E requirements to help guide growers' decisions regarding the use of agricultural water.

BACKGROUND: High-dose oral vitamin D (stoss) is a novel treatment in children with inflammatory bowel disease (IBD). Vitamin D supplementation may have benefits in IBD beyond bone health including reduced disease activity and improvements in inflammatory markers. The aim of this study was to retrospectively assess the efficacy, safety and impact on disease activity of single oral high-dose vitamin D3 therapy in New Zealand (NZ) children with IBD and vitamin D deficiency. METHODS: In this retrospective chart review, children with IBD and vitamin D deficiency [serum 25-OH vitamin D level (25-OHD) 75 nmol/L. One child had a serum calcium of 2.7 (normal range, 2.2 to 2.6 mmol/L) 2 weeks after treatment, which normalized on repeat testing 10 days later. PCDAI scores, mean platelet count, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) all reduced significantly from baseline to 3 months following stoss therapy. CONCLUSIONS: Single high-dose oral vitamin D therapy was used successfully and safely to manage vitamin D deficiency in these children with IBD. An improvement in inflammatory markers and disease activity scores also occurred following stoss therapy.

Noisy, intermediate-scale quantum (NISQ) computing devices have become an industrial reality in the last few years, and cloud-based interfaces to these devices are enabling exploration of near-term quantum computing on a range of problems. As NISQ devices are too noisy for many of the algorithms with a known quantum advantage, discovering impactful applications for near-term devices is the subject of intense research interest. We explore quantum-assisted machine learning (QAML) on NISQ devices through the perspective of tensor networks (TNs), which offer a robust platform for designing resource-efficient and expressive machine learning models to be dispatched on quantum devices. In particular, we lay out a framework for designing and optimizing TN-based QAML models using classical techniques, and then compiling these models to be run on quantum hardware, with demonstrations for generative matrix product state (MPS) models. We put forth a generalized canonical form for MPS models that aids in compilation to quantum devices, and demonstrate greedy heuristics for compiling with a given topology and gate set that outperforms known generic methods in terms of the number of entangling gates, e.g., CNOTs, in some cases by an order of magnitude. We present an exactly solvable benchmark problem for assessing the performance of MPS QAML models, and also present an application for the canonical MNIST handwritten digit dataset. The impacts of hardware topology and day-to-day experimental noise fluctuations on model performance are explored by analyzing both raw experimental counts and statistical divergences of inferred distributions. We also present parametric studies of depolarization and readout noise impacts on model performance using hardware simulators., 31 pages. 18+49 figures

We describe a quantum-assisted machine learning (QAML) method in which multivariate data is encoded into quantum states in a Hilbert space whose dimension is exponentially large in the length of the data vector. Learning in this space occurs through applying a low-depth quantum circuit with a tree tensor network (TTN) topology, which acts as an unsupervised feature extractor to identify the most relevant quantum states in a data-driven fashion. This unsupervised feature extractor then feeds a supervised linear classifier and encodes the output in a small-dimensional quantum register. In contrast to previous work on \emph{quantum-inspired} TTN classifiers, in which the embedding map and class decision weights did not map the data to well-defined quantum states, we present an approach that can be implemented on gate-based quantum computing devices. In particular, we identify an embedding map with accuracy similar to exponential machines (Novikov \emph{et al.}, arXiv:1605.03795), but which produces valid quantum states from classical data vectors, and utilize manifold-based gradient optimization schemes to produce isometric operations mapping quantum states to a register of qubits defining a class decision. We detail methods for efficiently obtaining one- and two-point correlation functions of the decision boundary vectors of the quantum model, which can be used for model interpretability, as well as methods for obtaining classifications from partial data vectors. Further, we show that the use of isometric tensors can significantly aid in the human interpretability of the correlation functions extracted from the decision weights, and may produce models that are less susceptible to adversarial perturbations. We demonstrate our methodologies in applications utilizing the MNIST handwritten digit dataset and a multivariate timeseries dataset of human activity recognition., Comment: 20 pages, 15 figures. Abstract slightly shortened to fit arXiv requirements

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs

Despite the many barriers to receiving care, children with asthma must have access to regular care and frequent follow-up visits. The usual barriers to the provision of asthma care have been made even more complicated by the current COVID-19 pandemic. To minimize the disruption of care due to the necessary constraints dictated by COVID-19, the televisit provides a practical solution that can assess the child’s current level of symptom control, reinforce asthma education, and determine treatment options. This article provides the tools and guidelines to facilitate the implementation of successful televisits to provide uninterrupted care for children with asthma., Highlights • Televisits are the work-around that mitigates the disruption to usual care appointments for children with asthma during COVID-19 and after. • Televisit sessions provide families with the continued reinforcement necessary for maintaining the course for good asthma control • Televisits address medical, pharmaceutical and administrative issues in real time • Televisits moved into usual care has the potential to reduce the low follow up rate common to children with asthma

Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INToverall) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, Neffective=132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the wellbeing spectrum (|rg|> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range |rg|=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. The pattern of genetic correlations suggests that childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalising symptoms over time and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Good Agricultural Practices (GAPs) training programs were developed to provide guidance to fruit and vegetable growers on how to reduce food safety risks on the farm. These programs have been enhanced over the years due, in part, to increasing buyer and regulatory requirements. However, the costs of implementing additional food safety practices has been identified as a primary barrier to long-term farm financial feasibility, particularly for smaller scale producers. A survey of past participants in New York State revealed that increasing food safety improvements facilitated by GAPs have not significantly impacted the size of farm operations or the types of crops grown. In terms of farm size, we show that both the financial costs and financial benefits of food safety improvements increase with farm size, but at decreasing rates. In so doing, relatively higher market sales gains per acre by smaller farms from additional food safety investments offset the relatively higher costs to them of their implementation. We also demonstrate that benefits of food safety improvements were significantly higher for farms that had third-party food safety audits and for those that market primarily through wholesale channels. The results should prove welcome by educators as they encourage participation by all scales of producers in GAPs trainings and for growers in understanding that food safety investments can support both reduced microbial risks and sales growth.

Background and AimsThe incidence of inflammatory bowel disease [IBD] is rising worldwide and no cure is available. Many patients require surgery and they often present with nutritional deficiencies. Although randomised controlled trials of dietary therapy are lacking, expert IBD centres have long-established interdisciplinary care, including tailored nutritional therapy, to optimise clinical outcomes and resource utilisation. This topical review aims to share expertise and offers current practice recommendations to optimise outcomes of IBD patients who undergo surgery.MethodsA consensus expert panel consisting of dietitians, surgeons, and gastroenterologists, convened by the European Crohn’s and Colitis Organisation, performed a systematic literature review. Nutritional evaluation and dietary needs, perioperative optimis ation, surgical complications, long-term needs, and special situations were critically appraised. Statements were developed using a Delphi methodology incorporating three successive rounds. Current practice positions were set when ≥80% of participants agreed on a recommendation.ResultsA total of 26 current practice positions were formulated which address the needs of IBD patients perioperatively and in the long term following surgery. Routine screening, perioperative optimisation by oral, enteral, or parenteral nutrition, dietary fibre, and supplements were reviewed. IBD-specific situations, including management of patients with a restorative proctocolectomy, an ostomy, strictures, or short-bowel syndrome, were addressed.ConclusionsPerioperative dietary therapy improves the outcomes of IBD patients who undergo a surgical procedure. This topical review shares interdisciplinary expertise and provides guidance to optimise the outcomes of patients with Crohn’s disease and ulcerative colitis. taking advantage of contemporary nutrition science.

Study ObjectivesEstimate the genetic relationship of cannabis use with sleep deficits and eveningness chronotype.MethodsWe used linkage disequilibrium score regression (LDSC) to analyze genetic correlations between sleep deficits and cannabis use behaviors. Secondly, we generated sleep deficit polygenic risk scores (PRSs) and estimated their ability to predict cannabis use behaviors using logistic regression. Summary statistics came from existing genome wide association studies (GWASs) of European ancestry that were focused on sleep duration, insomnia, chronotype, lifetime cannabis use, and cannabis use disorder (CUD). A target sample for PRS prediction consisted of high-risk participants and participants from twin/family community-based studies (n = 796, male = 66%; mean age = 26.81). Target data consisted of self-reported sleep (sleep duration, feeling tired, and taking naps) and cannabis use behaviors (lifetime use, number of lifetime uses, past 180-day use, age of first use, and lifetime CUD symptoms).ResultsSignificant genetic correlation between lifetime cannabis use and eveningness chronotype (rG = 0.24, p < 0.01), as well as between CUD and both short sleep duration (p = 0.02) and insomnia (rG = 0.20, p = 0.02). Insomnia PRS predicted earlier age of first cannabis use (β = −0.09, p = 0.02) and increased lifetime CUD symptom count use (β = 0.07, p = 0.03).ConclusionCannabis use is genetically associated with both sleep deficits and an eveningness chronotype, suggesting that there are genes that predispose individuals to both cannabis use and sleep deficits.

Study Objectives Estimate the genetic relationship of cannabis use with sleep deficits and an eveningness chronotype. Methods We used linkage disequilibrium score regression (LDSC) to analyze genetic correlations between sleep deficits and cannabis use behaviors. Secondly, we generated sleep deficit polygenic risk score (PRS) and estimated their ability to predict cannabis use behaviors using linear and logistic regression. Summary statistics came from existing genome-wide association studies of European ancestry that were focused on sleep duration, insomnia, chronotype, lifetime cannabis use, and cannabis use disorder (CUD). A target sample for PRS prediction consisted of high-risk participants and participants from twin/family community-based studies (European ancestry; n = 760, male = 64%; mean age = 26.78 years). Target data consisted of self-reported sleep (sleep duration, feeling tired, and taking naps) and cannabis use behaviors (lifetime ever use, number of lifetime uses, past 180-day use, age of first use, and lifetime CUD symptoms). Results Significant genetic correlation between lifetime cannabis use and an eveningness chronotype (rG = 0.24, p < 0.001), as well as between CUD and both short sleep duration ( Conclusion Cannabis use is genetically associated with both sleep deficits and an eveningness chronotype, suggesting that there are genes that predispose individuals to both cannabis use and sleep deficits.

In light of the evolving COVID-19 pandemic, the Association of American Medical Colleges (AAMC) and Liaison Committee on Medical Education (LCME) released a joint statement in March 2020 recommending an immediate suspension of medical student participation in direct patient contact. As graduating medical students who will soon begin residency, the authors fully support this recommendation. Though paid health care workers, like residents, nurses, and environmental services staff, are essential to the management of COVID-19 patients, medical students are not. Students’ continued involvement in direct patient care will contribute to SARS-CoV-2 exposures and transmissions and will waste already limited personal protective equipment. By decreasing nonessential personnel in health care settings, including medical students, medical schools will contribute to national and global efforts to “flatten the curve.” The authors also assert that medical schools are responsible for ensuring medical student safety. Without the protections provided to paid health care workers, students are uniquely disadvantaged within the medical hierarchy; these inequalities must be addressed before medical students are safely reintegrated into clinical roles. Although graduating medical students and institutional leadership may worry that suspending clinical rotations might prevent students from completing graduation requirements, the authors argue the ethical obligation to “flatten the curve” supersedes usual teaching responsibilities. Therefore, the authors request further guidance from the LCME and AAMC regarding curricular exemptions/alternatives and adjusted graduation timelines. The pool of graduating medical students affected by this pause in direct patient contact represents a powerful reserve, which may soon need to be used as the COVID-19 pandemic continues to challenge the U.S. health care infrastructure.

Pulmonary physiologic assessments are critical for the care and study of pediatric respiratory disease. In 2019, there were numerous contributions to this topic in Pediatric Pulmonology.

Background It is probable that psychosocial factors predict adherence to exclusive enteral nutrition (EEN). Conscientiousness is an intrapersonal factor associated with greater medication adherence and healthy eating behaviours. This sub-study aimed to determine whether adherence to EEN was associated with conscientiousness. Methods Two groups of adults aged 16-40 years, were recruited to use EEN. Adults with active Crohn's disease used either EEN for 8 weeks or 2 weeks of EEN followed by 6 weeks of partial enteral nutrition (PEN). A control group of healthy adults used EEN for 2 weeks. Participants who reported eating food during EEN, ate more than one meal per day during PEN, or could not initiate or tolerate the oral nutritional supplements were defined as non-adherent. Conscientiousness was measured using the conscientiousness subset of the Big Five Inventory. Results Thirty-eight patients with active Crohn's disease (mean age 24.8 years) and 21 healthy adults (mean age 27.3 years) completed the conscientiousness questionnaire. In the Crohn's disease group, 23 (59%) completed and adhered to the treatments compared to 17 (81%) healthy adults; their conscientiousness scores were similar. Adherence and completion by the Crohn's disease group were associated with a greater mean conscientiousness score 35.57 (95% confidence interval = 32.88-38.25) compared to 30.13 (95% confidence interval = 26.53-33.73) in the non-adherent Crohn's disease group (P = 0.014). Conclusions Conscientiousness was associated with treatment adherence. EEN can be a cognitively and emotionally demanding treatment for active adults with Crohn's disease; thus, considering personality traits may help determine suitable candidates.

Background Limb tourniquet pressures > 100 mmHg before tightening system use eases achieving arterial occlusion, minimizes tightening system problems, and probably minimizes discomfort. This study examined effects of buckle and strap features on converting pulling force to strap pressure. Study Design Twenty-two buckle and strap combinations were evaluated using a thigh-diameter, ballistic gel cylinder and 3 thighs. Weights of 14.11, 27.60, and 41.11 kg provided pulling force. The contribution of buckle movement was evaluated: all buckles on gel and 12 on thighs allowed limited vertical movement, 12 on gel and 4 on thighs held static. Results Force conversion patterns per combination were similar on gel and thighs, including greatest force conversion with some buckle movement allowed. Smooth, round redirect buckles without engagement of a strap-securing mechanism had the best conversions of pulling force to tourniquet pressure; 2 achieved arterially occlusive pressures, neither commercially available. Among hook-and-loop secured tourniquets and threaded for self-securing tourniquets, the Generation 7 Combat Application Tourniquet (C-A-T7) and the Tactical Ratcheting Medical Tourniquet (Tac RMT) had the best conversions of pull to pressure (thigh applications/each weight, mean ± SD: C-A-T7 91 ± 11, 164 ± 30, 228 ± 34 mmHg; Tac RMT 82 ± 13, 150 ± 16, 222 ± 17 mmHg). Other Ratcheting Medical Tourniquets with the same buckle but different strap fabrics performed less well. Even lower pressures occurred with the Tactical Mechanical Tourniquet, the Special Operations Forces Tactical Tourniquet, the Parabelt, and the SAM XT Extremity Tourniquet (165 ± 11, 178 ± 13, 131 ± 14, and 106 ± 14 mmHg, all at 41.11 kg, respectively). Conclusions Buckle design and strap fabric affect the conversion of pulling force to tourniquet strap pressure. Low-friction, smooth, round redirects allow the best conversion.

Background and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. Methods: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. Results: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19–60%]. Shared and unique environmental factors explained 39% (95% CI = 20–56%) and 22% (95% CI = 16–29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

BACKGROUND AND AIMS: Adolescents with conduct and substance use problems are at increased risk for premature mortality, but the extent to which these risk factors reflect family- or individual-level differences and account for shared or unique variance is unknown. This study examined common and independent contributions to mortality hazard in adolescents ascertained for conduct disorder (CD) and substance use disorder (SUD), their siblings and community controls, hypothesizing that individual differences in CD and SUD severity would explain unique variation in mortality risk beyond that due to clinical/control status and demographic factors. DESIGN: Mortality analysis in a prospective study (Genetics of Antisocial Drug Dependence Study) that began in 1993. Multi-site sample recruited in San Diego, California and Denver, Colorado, USA. PARTICIPANTS: A total of 1463 clinical probands were recruited through the juvenile correctional system, court-mandated substance abuse treatment programs and correctional schools, along with 1399 of their siblings, and 904 controls. MEASUREMENTS: Mortality and cause-of-death were assessed via National Death Index search (released October, 2017). FINDINGS: There were 104 deaths documented among 3766 (1168 female) adolescents and young adults (average age 16.79 years at assessment, 32.69 years at death/censoring). Mortality hazard for clinical probands and their siblings was 4.99 times greater than that of controls (95% confidence interval = 2.40-10.40; P

Objective The aim of this review was to identify the evidence regarding the optimal duration of compression therapy after endovenous ablation of varicose veins. Methods Electronic databases were searched for studies assessing the use of compression after endovenous ablation in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The primary outcomes for this study were pain score and complications. Secondary outcomes were time to full recovery, quality of life score, leg circumference, bruising score, and compliance rates. Results Following strict inclusion and exclusion criteria, five studies were included in our review, including a total of 734 patients. The short-duration compression therapy ranged from 4 hours to 2 days, whereas the longer duration ranged from 3 to 15 days. A single study showed a better outcome in terms of complications with a short compression therapy. A single study showed a benefit to pain and quality of life with extended compression therapy, whereas the others did not. There was no significant difference in terms of bruising, recovery time, and leg swelling. Conclusions Our review showed that there is no evidence for the extended use of compression after endovenous ablation of varicose veins.

Objective To examine if a substance use disorder (SUD), especially cannabis use disorder in adolescence, predicts future medical cannabis card status among high-risk youth. Methods Data collection occurred in Denver and San Diego. We recruited adolescents, with or at high risk for SUD and conduct problems (hereafter probands) and their siblings (n = 654). Baseline (Wave 1) assessments took place between 1999 and 2008, and follow-up (Wave 2) took place between 2010 and 2013. In initial bivariate analyses, we examined whether baseline DSM-IV cannabis abuse/dependence (along with other potential predictors) was associated with possessing a medical cannabis card in young adulthood (Wave 2). Significant predictors were then included in a multiple binomial regression. Self-reported general physical health was also evaluated at both time points. Finally, within Wave 2, we tested whether card status was associated with concurrent substance dependence. Results About 16% of the sample self-reported having a medical cannabis card at follow-up. Though bivariate analyses demonstrated that multiple predictors were significantly associated with Wave 2 card status, in our multiple binomial regression only cannabis abuse/dependence and male sex remained significant. At Wave 2, those with a medical cannabis card were significantly more likely to endorse criteria for concurrent cannabis dependence. There was no significant difference in self-reported general physical health. Conclusions Cannabis abuse/dependence and male sex positively predicted future medical cannabis card holder status among a sample of high risk adolescents. Physicians conducting evaluations for medical cannabis cards should carefully evaluate and consider past and concurrent cannabis addiction.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Background Literature indicates that Inflammatory Bowel Disease (IBD) patients (pts), who are at high risk of malnutrition, often adjust their diet following diagnosis and wish to receive specialised nutrition advice from their healthcare team. Dietitians (DTs) are health professionals (HPs) with specialist nutrition expertise. Our aim was to assess nutrition advice provided by different HPs. Methods Electronic surveys were disseminated to New Zealand IBD pts, DTs and gastroenterologists (GIs) asking about experience of, and practice providing, IBD nutrition advice. DTs and GIs were asked which nutrition interventions they recommend. DTs responded separately for Crohn’s disease (CD) and Ulcerative Colitis (UC) while GIs responded about IBD pts as a group. Results Surveys were completed by 407 pts, 79 DTs and 40 GIs. Almost all (97%) GIs report their IBD pts ask about nutrition and 95% said they provide nutrition advice. DTs and GIs commonly recommended specific diets: modified fibre, high protein/energy and low fermentable carbohydrate diets, with occasional use of some other diet regimes (Table 1). Half of the pts (52%) had seen a DT for advice and 31% had received nutrition advice from other HPs, commonly their GI, general practitioner or IBD nurse. Some patients (13%) received nutrition advice from other practitioners: nutritionist, naturopath, other medical doctors, counsellor, cannabis practitioner, integrated health professional, osteopath and herbalist. Patients frequently received general nutrition advice and specific diet advice including various strict exclusion diets and herbal, probiotic and vitamin/mineral supplements from DTs and non-DT HPs (Table 1). No DTs or GIs recommended low carb, high fat, sugar free or ketogenic diets in IBD, which were recommended to pts by other HPs. Conclusion Pts with IBD often ask for nutrition advice but only half had seen a DT. The advice given by HPs (medical and non-medical) varies and it appears that this high-risk group of pts is not always offered advice with evidence of scientific benefit in pts with IBD. Pts would benefit from greater access to DTs with IBD expertise.

Background Conscientiousness is a personality trait characterised by the ability to control impulses, delay gratification, set and reach goals, and plan in advance. Conscientious people are more likely to be non-smokers, do physical activity and practice healthy eating behaviours. They are also more likely to be adherent to medication. The aim of this study was to assess whether people with Crohn’s disease who score high on conscientiousness are more likely to be adherent to enteral nutrition (EN) therapy than low scorers. Methods Adults aged 16 to 40 years with newly diagnosed Crohn’s disease or having a flare of disease were invited by their gastroenterologist to use nutrition therapy to induce disease remission. Nutrition therapy was either eight weeks of exclusive enteral nutrition (EN) or two weeks of exclusive EN followed by six weeks of partial EN and one meal per day. A convenience control group of healthy participants with no history of gastrointestinal symptoms was also recruited to use exclusive EN for two weeks. Adherence to EN was self-reported fortnightly using a standardised questionnaire. Non-adherence was defined as patients who repeatedly ate foods while using EN or ate more than one meal per day on partial EN. Patients who could not initiate or did not tolerate the EN formula were included in the non-adherent group. Prior to starting nutrition therapy, conscientiousness was measured using the well-validated conscientiousness subset of the Big Five Inventory. Results Twenty-three (59%) of the 39 patients recruited with Crohn’s disease completed and adhered to the eight-week treatment. Reasons for non-adherence by the 14 patients who did not complete treatment included: could not initiate EN (n = 4), non-response at week 4 (n = 2), intolerance of EN (n = 7) or repeated eating of food or started eating food again prior to the end of treatment (n = 2). Seventeen (81%) of the 21 healthy controls completed and adhered to 2 weeks of exclusive EN. Reasons for non-adherence were could not initiate EN (n = 3) or intolerance of the formula (n = 1). Adherence and completion of EN therapy were associated with a greater mean conscientiousness score 35.57 (95% CI: 32.88, 38.25) compared with the non-adherence group mean 30.13 (95% CI: 26.53, 33.73), p = 0.014. Mean conscientiousness score of the healthy controls who completed exclusive EN was similar to the Crohn’s disease group (36.65 (95% CI: 33.53, 39.77), p > 0.05). Conclusion Conscientiousness was associated with adherence to EN therapy. EN therapy can be a cognitively and emotionally demanding treatment and this personality trait should ideally be considered when determining suitable candidates for EN therapy.

Background Micronutrient deficiencies are common in inflammatory bowel disease (IBD) due to the inflammatory burden and changes in dietary intake. Vitamin C, an essential water-soluble antioxidant required for tissue repair and immune function, is found primarily in fresh fruit and vegetables however, this food group is more often avoided by people with IBD compared with the general population. This research aimed to determine serum vitamin C status in subjects with active Crohn’s disease, measure urinary vitamin C excretion in healthy controls (HC) and Crohn’s disease patients before and after exclusive enteral nutrition (EEN) and assess associations between inflammatory markers and vitamin C. Methods Stored serum and random urine samples prospectively collected from adults with mild to moderately active Crohn’s disease and adult HC were analysed. Both HC and Crohn’s disease groups received EEN with a known vitamin C content for two weeks. Serum and urinary vitamin C were measured using high-performance liquid chromatography with electrochemical detection. Urinary vitamin C was standardised to urinary creatinine. Non-parametric t-tests and correlations were performed. Results EEN was initiated in 38 patients (aged 16 to 39 years old). Inadequate serum vitamin C ( Conclusion Patients with active Crohn’s disease had inadequate vitamin C status. EEN increased urinary vitamin C excretion in both Crohn’s disease and HC, suggesting low baseline dietary vitamin C intake and potentially enhanced utilisation. Further research with a larger patient cohort would provide a greater understanding of vitamin C metabolism in active Crohn’s disease.

To provide novel insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing up to 4,503 OD cases, 4,173 opioid-exposed controls, and 32,500 opioid-unexposed controls. Among the variants identified, rs9291211 was associated with OE (a comparison of exposed vs. unexposed controls; z=-5.39, p=7.2×10−8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N>360,000) found association of this variant with propensity to use dietary supplements (p=1.68×10−8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (z=4.69, p=10−6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (z=5.55, p=2.9×10−8) and a significant association with musculoskeletal disorders in the UK Biobank (p=4.88×10−7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (N=466,571) was positively associated with OD (OD cases vs. unexposed controls, p=8.1×10−5; OD cases vs. exposed controls, p=0.054) and OE (exposed controls vs. unexposed controls, p=3.6×10−5). A PRS based on a GWAS of neuroticism (N=390,278) was positively associated with OD (OD cases vs. unexposed controls, p=3.2×10−5; OD cases vs. exposed controls, p=0.002) but not with OE (p=0.671). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls (exposed vs. unexposed) in studies of addiction.

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = −5.39, p = 7.2 × 10–8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10–8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10–6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10–8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10–7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10–5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10–5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10–5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.

Background In sub-Saharan Africa, shortages of trained healthcare workers and limited resources necessitate innovative and cost-effective approaches for training, supervising, and mentoring. This qualitative case study describes participants’ and trainers’ perspectives and experiences with a text messaging component of a blended training course in HIV counseling and testing in Zimbabwe, using minimal resources in terms of staff time and equipment requirements. This component included a whole-group discussion forum as well as two-person partner discussions designed to promote reflection and analysis, teamwork, and active learning. Case presentation The Ministry of Health and Child Care (MoHCC) of Zimbabwe collaborated with the International Training and Education Center for Health (I-TECH) on adaptation of a 5-day in-service training in HIV Testing Services for Children and Adolescents. The new 7-week blended format included in-person sessions, tablet-based self-study, and discussions using the text messaging application, WhatsApp. Between August 2016 and January 2017, 11 cohorts (293 participants in total) were trained with this new curriculum, incorporating text messaging to support peer-to-peer and work-based education. Data collected included training participants’ feedback, key informant interviews with the training team, and thematic analysis of WhatsApp messages from full-cohort discussions and a sampling of one-to-one partner discussions. A total of 293 healthcare workers from 233 health facilities across all provinces in Zimbabwe completed the blended learning course. Participants strongly endorsed using WhatsApp groups as part of the training. In the whole-group discussions, the combined cohorts generated over 6300 text messages. Several categories of communication emerged in analysis of group discussions: (1) participants’ case experiences and questions; (2) feedback and recommendations for work issues raised; (3) inquiries, comments, and responses about course assignments and specific course content; (4) encouragement; and (5) technical challenges encountered using the blended learning methodology. Case discussions were complex, including patient history, symptoms, medications, and psychosocial issues—child abuse, adherence, and disclosure. Conclusions Using text messaging in a communication platform that is an ongoing part of healthcare workers’ daily lives can be an effective adjunct to in-service training, minimizing isolation and providing interactivity, supporting students’ ability to fully integrate content into new skill attainment.

Background Patients with inflammatory bowel disease (IBD) can have hidden nutrition risks that generic malnutrition screening tools, which place too much emphasis on body mass index (BMI), are not able to identify, therefore some IBD patients that would benefit from dietary interventions are missed. By identifying nutrition risk using an IBD-specific screening tool, early detection of nutrition risk may be able to prevent development of malnutrition and improve clinical outcomes. Aim This study aimed to develop and test an IBD-specific nutrition self-screening tool (IBD-NST). Methods IBD patients were recruited prospectively to independently complete IBD-NST and Malnutrition Universal Screening Tool (MUST). Subjective global assessment (SGA) and hand grip strength (HGS) were completed by a dietitian. The IBD-NST scored nutrition risk as low (0), moderate (1) or high (≥2), including questions on BMI, unintentional weight loss, and a combination of active disease and nutrition concerns. Scores were compared to sub-optimal (15% below the mean) HGS, mid-upper arm muscle circumference (MAMC), BMI, weight loss >5% and SGA. Chi2 compared dichotomous outcomes and Receiver Operator Characteristic curves were used for prediction assessment with a cut off of AUC Results 101/116 patients (87%) were recruited, 54 (53%) were female, 61 (60%) had CD, 33 (33%) had UC and 7 (7%) had IBD-U. Mean (SD) age was 40 (14) years and BMI was 24.6 kg/m2 (4.3). SGA identified 11/91 (12%) with malnutrition and IBD-NST and MUST identified a similar number of patients at nutrition risk (table 1). Twelve patients were low risk for MUST but high risk for IBD-NST due to having a flare and concerns about their nutrition. Unlike SGA and MUST, IBD-NST nutrition risk was not predicted by BMI (AUC=0.286 (SE 0.06) (95% CI 0.17, 0.40)). No significant difference in suboptimal HGS was seen across BMI categories of underweight (7/9 (78%)), healthy (28/46 (61%)), overweight (14/23 (61%)) and obese (6/12 (50%) p=0.642). Patients with >5% weight loss (13/101 (13%)) or suboptimal HGS (56/101 (55%)) were significantly more likely to be at nutrition risk using IBD-NST, MUST and SGA. Patients with suboptimal MAMC (10/66 (15%)) were not significantly more likely to be at nutrition risk using IBD-NST or MUST. Conclusion The IBD-NST identifies more patients with high nutrition risk and places less importance on BMI than SGA or MUST. Finally, we confirm that BMI is a poor indicator of HGS in IBD supporting a reduced importance in identifying nutrition risk. Further work is underway to test the repeat-reliability the IBD-NST.

BACKGROUND: Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.METHODS: This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m 2 twice daily on days 1–14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13.FINDINGS: Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37–60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6–59·1) in the capecitabine group compared with 36·4 months (29·7–44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63–1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55–0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30–44) in the observation group (adjusted HR 0·75, 95% CI 0·58–0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6–35·9) in the capecitabine group and 17·5 months (12·0–23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8–46·3) in the capecitabine group and 17·4 months (12·0–23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (INTERPRETATION: Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.FUNDING: Cancer Research UK and Roche.

OBJECTIVES: Research suggests that high adherence to Mediterranean dietary pattern significantly improve depression and anxiety symptoms. Thus, the objective was to utilize the novel and validated Mediterranean Diet Serving Score (MDSS) method to assess habitual intake of a study cohort, which evaluated SunGold(®) kiwifruit and psyllium powder interventions, against the Mediterranean diet recommendations. The link between the MDSS and mental wellbeing were then explored. METHODS: The project's data was collected during the randomized cross-over controlled trial Christchurch Irritable Bowel Syndrome cohort to investigate mechanisms for gut relief and improved transit - Psyllium and Kiwifruit translation study (COMFORT-PSYKI). Participants were randomized into two interventions: psyllium powder or SunGold(®) kiwifruit. MDSS was evaluated from dietary records with the recommended serving sizes obtained from the New Zealand Food Composition Database. Depression and anxiety score were collected through the Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: The habitual diet of the participants (n = 45, mean age 39 ± 15 years) had a low MDSS (mean 5.04 ± 2.38, out of 24 points) when compared against the Mediterranean pyramid recommendations. Their MDSS improved with daily consumption of two SunGold(®) kiwifruit significantly (mean 6.27 ± 2.81, P-value

Background Guidelines recommend that Inflammatory Bowel Disease (IBD) patients should have access to specialised dietitian support. Literature suggests that patients are often dissatisfied with their access to reliable nutrition information and dietitian services. Our aim was to assess whether New Zealand (NZ) dietetic services were meeting the expectations of patients. Methods In early 2020 an electronic survey to explore experience of dietetic services was disseminated to approximately 2000 patients (and parents) by Crohn’s and Colitis NZ and IBD health professionals. Quantitative responses were analysed via non-parametric methods and qualitative responses were analysed via inductive analysis. Results Responses were received from 407 IBD patients. Participants were asked if it ‘is useful for patients diagnosed with IBD to have access to a dietitian for nutrition advice?’ with 86% responding ‘Yes’ and 12% ‘Maybe’. Almost all (95%) patients had nutrition topics that they would like to discuss with a dietitian but only 52% had seen a dietitian and 45% had never been referred. Patients were interested in various nutrition topics (Table 1). Most (65%) would like access to a dietitian whenever a new nutrition issue arises. The most frequent nutrition advice received was to follow a specific diet, most commonly a low fermentable carbohydrate diet followed by a low residue diet, or general nutrition advice. Two-thirds (66%) of respondents found the dietitian advice at least moderately useful while 18% reported it was not at all useful. Patients who saw a dietitian in a private clinic were more likely to find the advice useful (p=0.0001), as were those who had received written advice (p Common themes in response to open-ended questions included: frustration at difficulty accessing dietetic services; desire for routine dietitian referral at diagnosis and ongoing access; the need for dietitians to have specialist knowledge of IBD; a perception that some medical staff believe nutrition is not relevant in IBD management. Conclusion Many patients have never been referred to a dietitian and a proportion of patients did not find dietitian advice useful. Dietitian advice appears to be on the topics most commonly of interest to patients. Access to dietetic services needs to improve and exploration is needed to elucidate why some aspects of services are not meeting patient expectations.

Chronic diarrhoea affects up to 14% of adults, it impacts on quality of life and its cause can be variable. Patients with chronic diarrhoea are presented with a plethora of dietary recommendations, often sought from the internet or provided by those who are untrained or inexperienced. In this review, we summarise the possible causes of chronic diarrhoea that can be managed by diet, the symptom improvement and quality of life benefits but also the potential risks of such dietary treatments. Clinicians need to consider both the benefits and risks of dietary treatments before making dietary recommendations to manage chronic diarrhoea. The pivotal role that dietitians have in ensuring optimal symptom improvement without jeopardising nutritional and overall health is discussed.

To describe why adolescent females who initiated HPV vaccination completed or did not complete the series.Semi-structured interviews were conducted with parents/guardians of 11-17 year old female adolescents and their pediatric primary care providers in one inner-city public clinic and three private practices to ascertain why girls who initiated HPV vaccination did or did not complete the series. Qualitative analysis was used to identify perceived barriers and facilitators of completion.65 parents/guardians participated: 37 whose daughters received 1 or 2 HPV vaccine doses and 28 whose daughters completed the series. 89% (n = 33) of parents who did not complete the series intended to do so, but were not reminded by the clinic or encountered logistical barriers. Four (11%) decided to stop the vaccine series. 33 providers participated: 24 physicians, 3 nurse practitioners, and 6 registered nurses. Half (n = 14, 52%) of the providers said they told parents when the next doses were due but relied on parents to schedule appointments, 11 (41%) scheduled the second dose when the first dose was given, and 2 (7%) tried to immunize patients when they returned for other appointments. None of the four practices had a reminder/recall system in place to ensure series completion. Of note, neither parents nor providers stated that the need for three doses was a barrier to series completion.Most failure to complete the HPV vaccine series occurred because providers expected parents to make appointments while parents expected to be reminded. Increased use of reminder/recall systems and team-based care with clear communication of expectations regarding appointment scheduling could increase completion rates.

The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diet has been extensively researched, but not in the management of older adults with functional gastrointestinal symptoms. This study determines the positive and negative impacts of this dietary treatment in older adults with chronic diarrhea. A non-blinded intervention study was conducted with adults over 65 years with chronic diarrhea referred for colonoscopy where no cause was found. Participants followed a dietitian-led low FODMAP diet for six weeks and completed a structured assessment of gastrointestinal symptoms, the Hospital Anxiety and Depression scale, and a four-day food diary before and after the intervention. Twenty participants, mean age 76 years, were recruited. Adherence to the low FODMAP diet was acceptable, mean daily FODMAP intake reduced from 20.82 g to 3.75 g (p &lt, 0.001) during the intervention and no clinically significant changes in macro- or micronutrient intakes were observed. There were clinically significant improvements in total gastrointestinal symptoms (pre diet 21.15/88 (standard deviation SD = 10.99), post diet 9.8/88 (SD = 9.58), p &lt, 0.001) including diarrhea (pre diet 9.85 (SD = 3.84), post diet 4.05 (SD = 3.86), p &lt, 0.001) and significant reductions in anxiety (pre diet 6.11/21 (SD = 4.31), post diet 4.26/21 (SD = 3.38), p &lt, 0.05). In older adults the low FODMAP diet is clinically effective and does not jeopardise nutritional intake when supervised by an experienced dietitian.

OBJECTIVES: Dietary fibre supplementation is recognised as important for functional gastrointestinal disorders (FGID). The exact role of the microbiome in this relationship remains unclear. We explored differences in dietary fibre intake, GI symptoms and the fecal microbiome in those with FGID. METHODS: The COMFORT cohort is an observational case control study examining FGID, particularly irritable bowel syndrome (IBS) aetiology (Ethics 16/NTA/21). Participants prospectively completed a food and GI symptoms diary over 3 days. Severity of GI symptoms and mood disorders were assessed using clinical questionnaires; SAGIS and PROMIS for GI symptoms and HADS for anxiety and depression. Fecal samples were analysed by shotgun sequencing; 95 healthy controls (HC), 22 constipation IBS (IBS-C) and 50 diarrhea IBS (IBS-D). Taxonomic classifications were assigned by aligning sequences against the NCBI non-redundant database using DIAMOND. RESULTS: Diet diaries were completed by 292 participants (176 cases, 71.2% female). Average daily fibre intake was higher in HC compared to FGID (23.99g, 95% CI = –2.06-0.55; 20.28g, 95% CI = -1.96-0.45; P |0.5|). At the genus level, Blautia were correlated with diarrhea and faecal incontinence (canonical r > 0.5). CONCLUSIONS: Higher fibre consumption was associated with decreased bloating, anxiety and depression in different FGID subgroups. IBS was also associated with altered fecal microbiome composition including some taxa linked to carbohydrate and hydrogen metabolism. FUNDING SOURCES: Funded by the Ministry of Business, Innovation and Employment through the High-Value Nutrition National Science Challenge.