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The Prevent Alcohol and Risk-related Trauma in Youth (P.A.R.T.Y.) program is an immersive hospital-based education program designed to reduce trauma in adolescents. The efficacy of the program in reducing risk-taking attitudes and preventing traumatic injuries has been proven through various methodologies. However, there is currently no study that has investigated the efficacy of the program using a validated, multi-domain questionnaire. This study outlines the design of the P.A.R.T.Y. Program Questionnaire (PPQ) and validates it through examining its construct and criterion validity as well as its internal consistency. Its capacity to risk-stratify participants was compared against the RT-18, a robust, 18-item risk-profiling instrument. The PPQ and the RT-18 were completed by New South Wales school students (N = 458) aged 15 to 18. The PPQ was designed in consultation with relevant field experts to optimise engagement and sensitivity. Examination of the construct validity of the PPQ was performed through exploratory factor analysis which demonstrated the presence of two underlying factors which aligned with the constructed two-scenario questionnaire format. The PPQ was shown to be internally consistent with a Cronbach's alpha of 0.77. Individual scenarios were shown to be internally consistent as well (α = 0.69, α = 0.66). The PPQ also identified high risk and low risk participants effectively as demonstrated by comparison against the risk stratification performed with the RT-18 (p-value0.001). This suggests the PPQ demonstrates criterion validity. Hence, the PPQ is an effective and valid tool for assessing risk-taking attitudes in adolescent populations.

Background Macrolides are recommended as an adjunctive treatment for patients with moderate to severe chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. The objective of this study was to examine temporal trends in the provision of long-term macrolide therapy, specifically before and after publication of the landmark MACRO trial in August 2011 showing efficacy of macrolides for this indication. Methods We performed an interrupted time series analysis using population-level health administrative data. The study cohort consisted of all Ontario residents who had COPD, were using at least 1 long-acting inhaler, and were aged 65 years and older between Apr. 1, 2004, and Mar. 31, 2018. We compared the baseline characteristics of eligible patients before and after publication of the MACRO trial. Our primary outcome was overall prevalence of long-term macrolide therapy; secondary outcomes were incidence of COPD-related hospitalizations, emergency department visits and outpatient exacerbations requiring high-dose steroids in each quarter. We performed an interrupted time series analysis to assess for changes in the incidence of macrolide prophylaxis by quarter-year over the study period. Results The rate of long-term macrolide use increased from 0.8 per 1000 people in 2004 to 13.8 per 1000 people in 2018 (in the severe COPD group, the rate increased from 1.3 to 32.3 per 1000 people). The interrupted time series analysis showed that, before 2011, the prevalence of macrolide prophylaxis increased at a rate of 0.44 (95% confidence interval [CI] 0.39-0.50) per 1000 people per year; after 2011, the rate of increase grew by 1.18 (95% CI 1.07-1.29) per 1000 people to 1.63 (95% CI 1.56-1.69) per 1000 people per year. The seasonal pattern of COPD-related health care visits remained stable over the study period, and there was no detectable reduction in hospitalizations or emergency department visits at the population level. Interpretation In the past decade, there has been a significant rise in the use of long-term macrolide therapy for patients with COPD. As this practice becomes increasingly common, it will be important to monitor its potential benefits on COPD exacerbations but also its potential effects on adverse events and antimicrobial resistance patterns.

BackgroundDespite a clear association seen in congenitally infected children, the effect of postnatal cytomegalovirus (CMV) infection during early childhood on cognitive development has not yet been determined.MethodsCMV-infection status was obtained based on serological measurements when children were 7 years old. Using population-based longitudinal data, we employed multivariate Poisson regression with a robust variance estimator to characterize the relationship between childhood CMV infection and adverse neurocognitive outcomes in children. Suboptimal neurocognitive outcomes were compared between CMV-positive and CMV-negative children using various cognitive assessments from 8 to 15 years of age. Children were evaluated on the cognitive domains of language, reading, memory and general intelligence, with a suboptimal score being >2 standard deviations lower than the mean score. Approximate Bayes factor (ABF) analysis was used to determine the level of evidence for the observed associations.ResultsWith adjustment for potential confounders, we observed that early-childhood CMV infection was associated with suboptimal total intelligence quotient (IQ) at 8 years of age [incidence-rate ratio (IRR) = 2.50, 95% confidence interval (CI) 1.35–4.62, ABF = 0.08], but not with suboptimal total IQ at 15 years of age (IRR = 0.97, 95% CI 0.43–2.19, ABF = 1.68). Suboptimal attentional control at 8 years (IRR = 1.74, 95% CI 1.13–2.68, ABF = 0.18) and reading comprehension at 9 years (IRR = 1.93, 95% CI 1.12–3.33, ABF = 0.24) were also associated with CMV infection. ABF analysis provided strong evidence for the association between CMV infection and total IQ at 8 years, and only anecdotal evidence for attentional control at 8 years and reading comprehension at 9 years. All other cognitive measures assessed were not associated with CMV infection.ConclusionIn this large-scale prospective cohort, we observed some evidence for adverse neurocognitive effects of postnatal CMV infection on general intelligence during early childhood, although not with lasting effect. If confirmed, these results could support the implementation of preventative measures to combat postnatal CMV infection.

Background With the challenges that aging populations pose to health care, interventions that facilitate alleviation of age-related morbidities are imperative. A prominent risk factor for developing age-related morbidities is immunosenescence, characterized by increased chronic low-grade inflammation, resulting in T-cell exhaustion and senescence. Contact with nature and associated physical activities have been shown to boost immunity in older adults and may be promoted in the form of horticultural therapy (HT). We aimed to examine the effects of HT on immunosenescence. Method We conducted a randomized controlled trial with 59 older adults assigned to either the HT intervention or waitlist control group. Older adults in the HT intervention group underwent HT intervention program over 6 months. Venous blood was drawn at baseline and at the third and sixth month from the commencement of this study. For participants who attended all 3 blood collection time points (HT: n = 22; waitlist: n = 24), flow cytometry analysis was performed on whole blood samples to evaluate the kinetics of lymphocyte subsets over the intervention period, revealing the composition of CD4+ and CD8+ subsets expressing exhaustion markers—CD57, CTLA4, and KLRG1. Enzyme-linked immunosorbent assays were employed to measure changes in plasma IL-6 levels. Results HT is associated with increased numbers of naive CD8+ T cells and fewer CTLA4-expressing terminally differentiated effector CD4+ and CD8+ memory T cells re-expressing CD45RA (TEMRA). Furthermore, IL-6 levels were reduced during HT, and the frequencies of naive and TEMRA CD8+ T cells were found to be associated with IL-6 levels. Conclusion HT is associated with a reduction in the levels of biomarkers that measure the extent of T-cell exhaustion and inflammaging in older adults. The positive effects of HT on T-cell exhaustion were associated with the reduction of IL-6 levels.

The safe release of a patient from hospital care after bariatric surgery depends upon the achievement of satisfactory health status. Here, we describe a new objective scale (the Readiness for Discharge, RFD Scale) to measure the patient’s suitability for hospital discharge after bariatric surgery. We conducted a retrospective, observational analysis of data collected in a randomized clinical trial of an enhanced recovery after surgery protocol for laparoscopic sleeve gastrectomy from 3/15/2018 to 1/12/2019. Nursing staff assessed 122 patients every 4–8 h after surgery using a checklist to document 5 components: ambulation, vital signs, pain, nausea, and oral intake of clear fluid. Satisfaction of each component was scored as “1” (satisfactory) or “0” (not satisfactory). Scores were summed and analyzed for patterns. RFD = 5 marked the patient as ready for discharge. Sufficient intake of clear liquid was the last RFD component satisfied in 87% of patients. Two overall response patterns emerged: “Steady Progressors” (n = 51) whose RFD score rose steadily from 0 to 5 without reversion to a lower score; and “Oscillators” (n = 71) who had at least one temporary decrease in RFD score on the way to attaining 5, or showed a simultaneous oscillation of components without change in RFD. The RFD checklist allows objective scoring of medical readiness for discharge after LSG and has the potential to improve clinical communication.

The United States (U.S.) is characterized by some of the poorest sexual health outcomes in the industrialized world, as indicated by the teen and unplanned pregnancy rates, rate of sexually transmi...

Within the field of occupational therapy, the issue of transitioning from an entry-level master's degree to an entry-level doctorate degree is under debate. As such, it is important to investigate the impact of the transition in order to help make educated decisions about the potential future of the profession.This study analyzed retrospective data collected from six cohorts at one Midwestern university to analyze the impact of the transition to an entry-level doctorate on diversity, admission and matriculation rates, and fieldwork reservations. No statistical difference in diversity between masters and doctorate level cohorts was found but it is of note that it approached significance (χ2 (1) = 3.32, p = 0.07). There was a slight decrease in number of total students that applied to the program (7.75%) and the number of fieldwork reservations (5.23%), however this was accounted for by a 60% increase in occupational therapy programs in the state the study took place. Results of this study provide preliminary data of how one university has succeeded in the transition to an entry-level doctorate and can be used to inform other programs as they consider this transition.

Focused clinical question With the 2018 AAP/EFP disease classification with the staging and grading systems, does risk assessment for different ethnic group result in a different focus for clinical needs? This comparative analysis aimed to assess two previously reported cohort studies in African-American (Af-A) and Asian-American (As-A) as to the risk for these two populations for clinical attachment loss (CAL) and gingival phenotype. Summary In comparison of As-A and Af-A cohorts, As-A had higher frequency of thin tissue phenotype, less width of keratinized gingiva (KGW), and more gingival recession (GR). On other hands, Af-A showed higher prevalence of thick phenotype, longer total tooth length and root length (RL). These gingival and dental anatomical patterns suggest there are differential risk for GR, patterns for CAL, and periodontal prognosis between two cohorts. Conclusion(s) Because of nature of dental and gingival anatomy between these two cohorts, As-A are more susceptible in GR and the short RL affords this population less ability to withstand the clinical presentation of periodontal disease. From a therapeutic perspective, clinicians should evaluate patients with different risk assessment based on their dental and gingival characterization. Af-A may have clinical characteristics that makes this population less at risk for mucogingival defects. Conversely, phenotype modification therapy should be considered when treating As-A because of the high prevalence of thin tissue phenotype, inadequate KGW, and GR. Clinicians should also diligently monitor periodontal CAL around the teeth with shorter RL in periodontal or orthodontic therapy for better teeth prognosis.

Left ventricular outflow tract obstruction resulting from strut impingement upon the interventricular septum is a rare complication of bioprosthetic mitral valve insertion. Obstruction is more likely to develop when a small, high profile prosthetic valve is inserted into a patient with a small outflow tract. The likelihood of this complication may be reduced by appropriate modification of surgical technique.

Background/Objectives Juvenile melanoma (before 20 years of age) is a rare condition with poorly defined risk factors. We describe features of juvenile melanoma in Western Australia over the last two decades. Method A retrospective review of juvenile melanomas was conducted from prospectively maintained databases, reviewed for patients’ characteristics, clinical information, histology, treatment, recurrence and survival data. Results Altogether 95 cases of juvenile melanoma were reported to the Western Australian Cancer Registry between 2000 and 2013. Of these, 27 patients were referred to the Western Australian Melanoma Advisory Service. Over 72% were aged between 13 and 19 years. The most common site for primary melanoma was the head and neck (31.8%). Eight patients (36.4%) had a pre-existing naevus, 13.6% reported 1–5 blistering sunburns in the past and 59.1% had a Fitzpatrick skin grade of 3 or less. Most (88%) were diagnosed with a primary invasive lesion at presentation. Superficial spreading melanomas predominated (27.3%). All but one patient had localised disease at presentation, with six patients undergoing further treatment, including chemotherapy and neck dissection for metastases. At the time of review, two patients had died, due to stroke and metastatic disease. Conclusions Juvenile melanoma remains a rarity in Western Australia despite a very high incidence of adult melanoma. Unlike in adults, no definitive risk factors have been established. A significant proportion of this cohort had a pre-existing naevus and while most melanomas occurred in sun-exposed areas in light-skinned individuals the association between sunburn and melanoma was not strong.

This report of findings describes students’ self-reported difficulty and anxiety during test taking and the effect of deliberate gasping or diaphragmatic breathing on the ability to solve math problems. During the evaluation of an experiential classroom activity, 103 university students filled out a short questionnaire about performance anxiety and blanking out when taking exams. Then, they were asked to solve math problems while either gasping or slow diaphragmatic breathing. Students reported a high frequency of blanking out (mean = 5.3), difficulty during exams (mean = 6.7), and difficulty with math (mean = 6.2) on a scale from 1 (never) to 10 (always). The students reported significantly more difficulty in solving math problems when gasping than during slow breathing (p < .01) and significantly more anxiety during gasping (p < .01) than during slow breathing (p < .01) when solving math problems. Most students were completely surprised how their breathing patterns affected their ability to perform a simple math test. Numerous students have reported that when they implemented this slow breathing approach at the moment they felt anxiety, their anxiety slightly decreased and they would perform better on exams. Included are comments to improve study habits, memory consolidation, and how to incorporate somatic feedback of breathing patterns into learning and training within other settings such as during neurotherapy.

Questions: What perceptions do physiotherapists have about their role in managing the physical health of people with severe and persistent mental illness (SPMI)? What are the barriers to treating physical health conditions in this clinical population, and what enablers may improve access to physiotherapy services? Design: Mixed-methods research design combining focus groups, interviews and an online survey. Participants: Eighty-eight Australian registered physiotherapists: 31 in the focus groups and interviews (mean age 32 years, 68% female) and 57 in the survey (mean age 38 years, 86% female). Methods: Focus groups and interviews explored participants' understanding of mental illness; their role in managing the physical health of people with SPMI; and the barriers and enablers to service delivery. Key themes were derived using an inductive approach. The survey was used to determine physiotherapists' attitudes and knowledge regarding mental illness; perceived role of physiotherapy in mental health; and need for professional development in the mental health area. Participant characteristics and survey information were analysed using descriptive statistics. Results: Qualitative and quantitative results were confirmatory. Participants indicated that physiotherapists can play a role in the management of physical health conditions in people with SPMI. Participants also stated that such treatment was part of their job, given the extensive evidence that physiotherapy interventions are effective for the comorbidities that are common among people with SPMI. Barriers included: limited education about and confidence in how to manage people with SPMI; health system structure; and stigmatisation of people with SPMI. Conclusion: Physiotherapists are ideally poised to become leaders in managing the physical health of people with SPMI. To improve the physical health in this important yet overlooked population, it is recommended that: physiotherapists take up general mental health training opportunities; undergraduate physiotherapy education increases content in this clinical area; physiotherapy-specific professional development opportunities are developed further; and health system barriers are addressed. Key words: Physiotherapy, Physical therapy, Severe mental illness, Mental health, Physical activity

Background: Young children living in urban slums are vulnerable to malnutrition and subsequently poor health outcomes, but data on the correlates of stunting, underweight, wasting, and anemia specifically among 10–18 month-old children in India remain limited. Objective: In this analysis, we sought to describe the prevalence of and examine correlates for different markers of undernutrition, including stunting, underweight, and anemia among 10–18 month-old children living in urban slums, an understudied vulnerable group. Methods: Children and their mothers (n = 323) were screened for anthropometry, demographics, and complete blood counts for hemoglobin concentration between March and November 2017 (Clinicaltrials.gov ID: NCT02233764). Correlates included child and mother's age, sex, birth order, birth weight, illness episodes, hemoglobin concentration, family income, maternal height, and maternal education level. Risk ratios (RR, 95% CI) for binary outcomes (stunting, underweight, wasting and anemia) and mean differences (β, 95% CI) for continuous outcomes (anthropometric Z-scores, hemoglobin concentration) were calculated using multivariate binomial and linear regression (SAS 9.4). Results: The prevalence of stunting was 31.2%, underweight 25.1%, wasting (9.0%), and anemia (76%) among all children. Male children had a higher prevalence of poor growth indices and lower anthropometric Z-scores than females. Male sex, low birthweight, shorter maternal height, report of ≥1 episodes of illness within the past month, older maternal age, and birth order ≥2 were also associated with poor growth and anemia in multivariate models. Correlates of undernutrition were different among females and males. Female children had a 40% (20, 60%) higher risk of anemia associated with diarrhea, and male children who were firstborn had a 20% (0, 70%) lower risk of anemia. Conclusions: These results show that poor growth and anemia among young children is prevalent in urban slums of Mumbai, and that sex of the child may play an important role in informing interventions to address undernutrition.

A chart review was performed of 38 children diagnosed with autism spectrum disorder (ASD) by 3 years of age at an inner-city developmental program who subsequently experienced resolution of ASD symptomatology and no longer met diagnostic criteria for ASD at follow-up an average of 4 years later. Demographic, developmental/cognitive data, Childhood Autism Rating Scale, and Autism Diagnostic Observation Schedule data as available were reviewed from the initial diagnostic evaluation and at the time of follow-up. Services received by the children between the time of diagnosis and follow-up, educational setting at the time of follow-up, and emotional/behavioral and learning diagnoses made by the multidisciplinary team at follow-up were reviewed. The findings indicate that residual emotional/behavioral and learning problems were present at follow-up in the vast majority of children in this group and that the majority continued to require educational support.

Left ventricular outflow tract obstruction is a serious complication of mitral valve surgery (repair and replacement) and transcatheter mitral valve replacement. An appreciation of the various mechanisms which cause outflow obstruction in these settings is critical to avoiding this complication and to initiating appropriate treatment. This article discusses the mechanisms, pathophysiology, and imaging of left ventricular outflow tract obstruction which can arise following insertion of a variety of mitral valve prosthetics.

The single-cell-based computational models treat the cells as separate independent entities with individually regulated cell processes of growth, death, quiescence, and motility. Each cell behavior is influenced by interactions with other cells and with the surrounding environment. In the hybrid single-cell-based models, the microenvironment is represented by continuous concentrations of oxygen, nutrients, matrix, and drugs. By design, such models can handle significant differences between individual cells and can trace dynamic changes arising in these cells over time. Therefore, in contrast to continuous models that relay on averaged values, the single-cell-based models are ideally suited to address the heterogeneities observable in various biological systems, and to test diverse biological mechanisms. In this article, we present the off-lattice single-cell-based hybrid model MultiCell-LF and discuss how this model can be applied to various aspects of tumor heterogeneity, both on cellular and microenvironment level. In particular, we focus on intra-, inter-, and extracellular variability in tumor tissue, and present several simulations that address these phenomena.

Background and objective To monitor therapies targeted to epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC), we investigated Peroxiredoxin 6 (PRDX6) as a biomarker of response to anti-EGFR agents. Methods We studied cells that are sensitive (H3255, HCC827) or resistant (H1975, H460) to gefitinib. PRDX6 was examined with either gefitinib or vehicle treatment using enzyme-linked immunosorbent assays. We created xenograft models from one sensitive (HCC827) and one resistant cell line (H1975) and monitored serum PRDX6 levels during treatment. Results PRDX6 levels in cell media from sensitive cell lines increased significantly after gefitinib treatment vs. vehicle, whereas there was no significant difference for resistant lines. PRDX6 accumulation over time correlated positively with gefitinib sensitivity. Serum PRDX6 levels in gefitinib-sensitive xenograft models increased markedly during the first 24 hours of treatment and then decreased dramatically during the following 48 hours. Differences in serum PRDX6 levels between vehicle and gefitinib-treated animals could not be explained by differences in tumor burden. Conclusions Our results show that changes in serum PRDX6 during the course of gefitinib treatment of xenograft models provide insight into tumor response and such an approach offers several advantages over imaging-based strategies for monitoring response to anti-EGFR agents.

Questions How do mental health professionals perceive the role of physiotherapists in the care of people with severe and persistent mental illness, and what factors do they perceive as influencing access to physiotherapy services? How do people with severe and persistent mental illness understand the potential role of physiotherapy in their healthcare, and what factors do they perceive as influencing access to physiotherapy services? Design Qualitative study. Participants Twenty-four mental health professionals and 35 people with severe and persistent mental illness. Methods Interview schedules were developed to explore participants' understanding of physiotherapy, as well as barriers and enablers to service access. Focus groups and interviews were conducted for each group of participants. Transcripts were analysed using an inductive approach to derive key themes. Results Both the mental health professionals and the people with severe and persistent mental illness expressed a limited understanding of the role and relevance of physiotherapy for physical health in mental healthcare. Common barriers to service access were cost, transport and lack of motivation. Likewise, enablers of reduced cost, provision of transport and education about physiotherapy to improve their understanding were identified. The health system structure and perceived lack of mental health knowledge by physiotherapists influenced referrals from mental health professionals. Consequently, education in mental health for physiotherapists and integration of the service within mental health were identified as potential enablers to physiotherapy access. Conclusion Limited understanding about physiotherapy and its relevance to physical health in mental healthcare among mental health professionals and people with severe and persistent mental illness was found to be a key factor influencing service access. Limited physiotherapy presence and advocacy within mental health were also highlighted. There is a need for greater understanding about physiotherapy among stakeholders, and for physiotherapists to be well equipped with skills and knowledge in mental health to facilitate greater involvement. [Lee S, Waters F, Briffa K, Fary RE (2017) Limited interface between physiotherapy primary care and people with severe mental illness: a qualitative study. Journal of Physiotherapy 63: 168–174]

Rationale:Consensus guidelines on the management of methotrexate-induced nephrotoxicity using glucarpidase (Voraxaze) may be relatively unfamiliar to the nephrology community.Presenting concerns of the patient:A 61-year-old man with intravascular large B-cell lymphoma was admitted for cycle #1 of high-dose methotrexate (HDMTX) following 2 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. On admission, he was clinically euvolemic and had a creatinine clearance of 98 mL/min. He received standard HDMTX toxicity prophylaxis with volume expansion, urinary alkalinization, and leucovorin rescue.Diagnoses:Despite prophylactic efforts, he developed a severe acute kidney injury, creatinine 63 to 226 µmol/L (2.56 mg/dL), following HDMTX, impaired methotrexate clearance, and neurotoxicity manifested by status epilepticus.Interventions:He was given glucarpidase to convert extracellular methotrexate into its inactive metabolites, glutamate and DAMPA (4-deoxy-4-amino- N10-methylpteroic acid) at 52 hours post-HDMTX. Cross-reactivity between commercial methotrexate immunoassays with DAMPA led to falsely elevated methotrexate concentrations for much longer than expected based on the current guideline (5 days instead of Outcomes:The patient remained nonoliguric and did not develop acute indications for dialysis. Serum creatinine peaked at 608 µmol/L (6.88 mg/dL) 6 days after HDMTX. He ultimately had a full renal and neurologic recovery.Lessons learned:Glucarpidase is an effective option for nonrenal elimination of methotrexate-induced nephrotoxicity. Timing of methotrexate concentration monitoring to assess for toxicity, how to access the drug, and the need for ongoing monitoring by mass spectrometry beyond the guideline recommendation are highlighted for centers where HDMTX therapy may be used.

Purpose Previous research on children with HCV has examined patient psychosocial outcomes but little is known about the impact of HCV and its prolonged treatment, which includes weekly injections and oral medications for 6–12 months, on caregivers and families. The present study aimed to address this gap. Design and Methods Using a case series design (N = 10), baseline distress levels of individuals and families as well as changes during HCV treatment were examined. A brief patient, caregiver, and family assessment packet was given before and immediately after treatment, but before the final outcome of treatment was known. During the study period, 10 families at our site began treatment for HCV. Each family was given a battery assessing patient quality of life, (the Pediatric Quality of Life Inventory; PedsQL), caregiver distress related to their child's illness (Impact of Events Scale; IES), and overall family functioning (Family Assessment Device; FAD). Results At baseline, patients displayed poorer quality of life than population norms, caregiver distress was elevated and family functioning was also in the “stressed” range. After treatment, all parameters worsened. Conclusions In conclusion, in this case series of patients in treatment for HCV, significant psychosocial distress was noted for individuals and families and this was exacerbated over the course of treatment. Practice Implications Caregivers may benefit from additional support given the implications of HCV and grueling nature of its treatment. Broadly, the impact of continuous intensive treatments on families perhaps should be monitored.

Arnon R, Annunziato R, Schiano T, Miloh T, Baisley M, Sogawa H, Contreras AG, Lee S, Kerkar N. Orthotopic liver transplantation for adults with Alagille syndrome. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01574.x. © 2011 John Wiley & Sons A/S. Abstract: Introduction: Alagille syndrome (AGS) is an inherited multisystem disorder, and liver transplantation (LT) may be required in pediatric patients with AGS (P-AGS). There are limited data regarding the outcomes of LT in adults with AGS (A-AGS). Aim: To determine and compare the outcomes of LT in A-AGS vs. P-AGS as well as A-AGS vs. adults with biliary atresia (A-BA). Methods: Adults (>18 yr), with AGS and BA, and children (≤18 yr), with AGS who underwent isolated first LT between 10/1987 and 5/2008, were identified from the UNOS database. Results: Forty-four of 79 400 adults transplanted for AGS were compared with 407 P-AGS and 56 A-BA, respectively. A-AGS patients had a significantly higher rate of encephalopathy, lower serum albumin, and higher serum creatinine in comparison with P-AGS. One- and five-yr patient and graft survival in A-AGS who underwent LT were not significantly different in comparison with either P-AGS or A-BA (A-AGS patient survival: 95.5%, 90.9%, P-AGS: 88. 7%, 86.2%, A-BA: 89.3%, 87.5%; A-AGS graft survival: 84.1%, 79. 5%, P-AGS: 80.3%, 76%. 1%, A-BA: 82.1%, 78.6%, respectively). Conclusion: The outcome of first LT in A-AGS is excellent compared with the overall reported adult patient and graft survival. Although A-AGS were sicker than P-AGS at transplant, their outcomes were comparable with that of P-AGS.

Background Laboratory turn-around-times (TATs) for identification (ID) and antimicrobial susceptibilities (AST) can delay prescription of adequate and/or optimal antimicrobial (ABX) therapy in septic patients leading to poor outcomes. The Accelerate Pheno™ system (Accelerate Diagnostics, USA) (AXDX) is a rapid ID and AST system with potential to improve TATs. Figure 1: Changes in Antibiotics Ordered for Gram-negative Bacilli Bloodstream Infections following Gram, ID, and AST Results. Figure 2: Time to Actual and Potential Antibiotic Tailoring Varying by ID and AST Method. Methods 70 prospective non-duplicate blood cultures with Gram-negative bacilli were loaded onto AXDX. AXDX TATs were compared with TATs associated with current methods [ID by MALDI-TOF Vitek® MS (bioMérieux) using short-incubation plates, AST by Vitek® 2 (bioMérieux)]; modified current methods (calling MALDI ID and Vitek® 2 AST and releasing Vitek® 2 AST prior to purity plate review); and former methods (ID and AST by Vitek® 2), the latter determined by laboratory data review of 134 blood cultures from 2011. Impact of the change in TAT on ABX use was determined by chart review. Results Gram stain, ID and AST results led to tailoring of ABX in 88.6% of patients impacting 22.9%, 31.4%, and 64.3% of patients at 2.5h, 19.0h, and 62.1h respectively post positive blood culture using current methods (Figures 1 and 2). AXDX generated the shortest ID and AST TATs with the potential to shorten the time to ABX tailoring due to ID and AST to 1.3h and 6.7h respectively. Calling ID and AST results directly to physicians or releasing AST results from Vitek® 2 prior to purity plate review would also have the potential to significantly improve time to ABX change compared with current methods. Conclusion Among the methods compared, AXDX has the greatest potential impact on time to appropriate antibiotics following reports of ID and AST results in Gram-negative bacilli bloodstream infections. Calling ID or AST results directly to physicians could also improve time to ABX tailoring. Impact of engaging antimicrobial stewardship teams requires further study. Disclosures S. M. Poutanen, Accelerate Diagnostics: Research Contractor and Scientific Advisor, Consulting fee and Research support

Background AXDX reports ID/AST in

Primitive neuroectodermal tumours are amongst the most common paediatric tumours of the central nervous system. These tumours are composed of undifferentiated cells and a variable component of more differentiated cell types. Most analysis of these tumours has focused on molecules normally found in the differentiated cells or those found in all primitive neuronal precursors. In this article we describe recent advances in understanding of the molecular processes involved in normal neurogenesis. We discuss the relevance of these data to the biology of neuronal tumours and describe strategies we and others have adopted to investigate the usefulness of molecules found in undifferentiated neuronal tissues in understanding the events which underlie oncogenesis in this tumour type.

Objective: Cervical cancer is a leading cause of cancer mortality in South Africa. However, little is known about oral human papillomavirus (HPV) infection in high human immunodeficiency virus (HIV) seroprevalence settings. Method: Thirty-four adult heterosexual couples attending an HIV testing center in Soweto, South Africa were enrolled. Each participant provided an oral rinse sample and genital swab, which were tested for 37 types of HPV DNA, and completed a risk behavior survey. Results: Median age was 31 years and 9% (3/34) of men and 29% (10/34) of women enrolled tested HIV-positive; median CD4 count was 437 cells/mm3. Oral HPV prevalence was similar in women and men (12 vs. 18%, p = 0.48), and was non-significantly higher in HIV-infected vs. HIV-uninfected (23 vs. 13%, p = 0.34) subjects. Most men (82%) and women (84%) reported ever performing oral sex. Median number of lifetime sexual partners was “2–5” while median number of lifetime oral sex partners was 1. Oncogenic HPV subtypes were detected in 4% of oral, 26% of penile, and 74% of vaginal samples, including HPV16 in 1, 12, and 21% of these samples respectively. Genital HPV prevalence was significantly higher than oral HPV prevalence (75 vs. 15%, p ≤ 0.001). Thirty-five percent of couples (12/34) had at least one type-specific concordant vaginal-penile HPV infection but only one of nine couples with oral HPV had concordant oral–oral infection. However, 67% (4/6) of men and 25% (1/4) of women with oral HPV infection had partners with concordant genital HPV infection. Implications and Impact: Oral–oral HPV concordance between couples is low, but oral-genital and genital–genital HPV concordance is higher, including concordance of male oral HPV infection with their partners’ vaginal HPV infection. This data is consistent with possible transmission of vaginal HPV infection to the oral cavity of sexual partners performing oral sex.

Cocoa is a dry, powdered, nonfat component product prepared from the seeds of the Theobroma cacao L. tree and is a common ingredient of many food products, particularly chocolate. Nutritionally, cocoa contains biologically active substances that may affect human health: flavonoids (epicatechin and oligomeric procyanidins), theobromine, and magnesium. Theobromine and epicatechin are absorbed efficiently in the small intestine, and the nature of their conjugates and metabolites are now known. Oligomeric procyanidins are poorly absorbed in the small intestine, but catabolites are very efficiently absorbed after microbial biotransformation in the colon. A significant number of studies, using in vitro and in vivo approaches, on the effects of cocoa and its constituent flavonoids have been conducted. Most human intervention studies have been performed on cocoa as an ingredient, whereas many in vitro studies have been performed on individual components. Approximately 70 human intervention studies have been carried out on cocoa and cocoa-containing products over the past 12 years, with a variety of endpoints. These studies indicate that the most robust biomarkers affected are endothelial function, blood pressure, and cholesterol level. Mechanistically, supporting evidence shows that epicatechin affects nitric oxide synthesis and breakdown (via inhibition of nicotinamide adenine di-nucleotide phosphate oxidase) and the substrate arginine (via inhibition of arginase), among other targets. Evidence further supports cocoa as a biologically active ingredient with potential benefits on biomarkers related to cardiovascular disease. However, the calorie and sugar content of chocolate and its contribution to the total diet should be taken into account in intervention studies.

This is a case report of the first patient with Alagille syndrome (AGS) to undergo a partial internal biliary diversion (PIBD) for the treatment of symptoms refractory to medical therapy. Alagille syndrome is a hereditary disease resulting in chronic cholestasis and hypercholesterolemia that can lead to severe and intractable pruritus and disfiguring and debilitating xanthomas. PIBD has proven to be an effective treatment option for other causes of cholestatic liver disease. This report reviews the immediate and 2-year follow-up of a patient after this surgical procedure. The results suggest that PIBD has potential to provide relief of intractable symptoms and improve the quality of life in patients with AGS while avoiding an external stoma. It does not, however, appear to prevent the progression of liver disease. Long-term follow-up is still needed.

Author(s): Hosking, Anna-Marie; Coakley, Brandon J; Chang, Dorothy; Talebi-Liasi, Faezeh; Lish, Samantha; Lee, Sung Won; Zong, Amanda M; Moore, Ian; Browning, James; Jacques, Steven L; Krueger, James G; Kelly, Kristen M; Linden, Kenneth G; Gareau, Daniel S | Abstract: ObjectivesEarly melanoma detection decreases morbidity and mortality. Early detection classically involves dermoscopy to identify suspicious lesions for which biopsy is indicated. Biopsy and histological examination then diagnose benign nevi, atypical nevi, or cancerous growths. With current methods, a considerable number of unnecessary biopsies are performed as only 11% of all biopsied, suspicious lesions are actually melanomas. Thus, there is a need for more advanced noninvasive diagnostics to guide the decision of whether or not to biopsy. Artificial intelligence can generate screening algorithms that transform a set of imaging biomarkers into a risk score that can be used to classify a lesion as a melanoma or a nevus by comparing the score to a classification threshold. Melanoma imaging biomarkers have been shown to be spectrally dependent in Red, Green, Blue (RGB) color channels, and hyperspectral imaging may further enhance diagnostic power. The purpose of this study was to use the same melanoma imaging biomarkers previously described, but over a wider range of wavelengths to determine if, in combination with machine learning algorithms, this could result in enhanced melanoma detection.MethodsWe used the melanoma advanced imaging dermatoscope (mAID) to image pigmented lesions assessed by dermatologists as requiring a biopsy. The mAID is a 21-wavelength imaging device in the 350-950 nm range. We then generated imaging biomarkers from these hyperspectral dermoscopy images, and, with the help of artificial intelligence algorithms, generated a melanoma Q-score for each lesion (0 = nevus, 1 = melanoma). The Q-score was then compared to the histopathologic diagnosis.ResultsThe overall sensitivity and specificity of hyperspectral dermoscopy in detecting melanoma when evaluated in a set of lesions selected by dermatologists as requiring biopsy was 100% and 36%, respectively.ConclusionWith widespread application, and if validated in larger clinical trials, this non-invasive methodology could decrease unnecessary biopsies and potentially increase life-saving early detection events. Lasers Surg. Med. 51:214-222, 2019. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.