Peroperative administration of tranexamic acid in sleeve gastrectomy to reduce hemorrhage: a double-blind randomized controlled trial.

INTRODUCTION: In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG). METHODS: In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality. RESULTS: In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien-Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported. CONCLUSION: This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications.

Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs.

Short-term memory dysfunction is a key early feature of Alzheimer's disease (AD). Psychiatric patients may be at higher risk for memory dysfunction and subsequent AD due to the negative effects of stress and depression on the brain. We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The top candidate biomarkers were then tested in an independent cohort for ability to predict state short-term memory, and trait future positive neuropsychological testing for cognitive impairment. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Additional top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto positive controls for our whole-genome gene expression discovery approach. Biological pathway analyses implicate LXR/RXR activation, neuroinflammation, atherosclerosis signaling, and amyloid processing. Co-directionality of expression data provide new mechanistic insights that are consistent with a compensatory/scarring scenario for brain pathological changes. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a molecular basis for clinical co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin). Our work contributes to the overall pathophysiological understanding of memory disorders and AD. It also opens new avenues for precision medicine- diagnostics (assement of risk) as well as early treatment (pharmacogenomically informed, personalized, and preventive).

Communicating diagnostic uncertainty in the acute and emergency medical setting: A systematic review and ethical analysis of the empirical literature.

BACKGROUND: diagnostic uncertainty is ubiquitous. Its communication to patients requires further investigation. AIMS: To determine: 1) What is known about how and why diagnostic uncertainty is communicated in acute care; 2) evidence of the effects of (not) communicating diagnostic uncertainty in the acute setting; 3) associated ethical issues. METHODS: systematic review of Medline, Web of Science and SCOPUS for (acute or emergency care) AND (diagnostic uncertainty) AND (ethics OR behaviours). Critical interpretive synthesis and ethical analysis were conducted. RESULTS AND CONCLUSION: Nine studies (primarily surveys and interviews) were identified. Doctors are not trained in communicating diagnostic uncertainty and perceive it to have negative effects on patients; however not communicating diagnostic uncertainty can disempower patients, resulting in delayed/missed diagnoses or inappropriate use of resource.

Mixed methods analysis of factors influencing change in clinical behaviours of non-physician anaesthetists in Kenya following obstetric anaesthesia training.

Maternal mortality rates in low-middle income countries remain high, with sub-Saharan Africa accounting for two-thirds of global maternal deaths. Inadequate staff training is one of the main contributors to anaesthesia-related deaths and the Association of Anaesthetists developed the Safe Anaesthesia from Education course in collaboration with the World Federation of Societies of Anaesthesiologists to address this training gap. We aimed to evaluate the impact of this course among Kenyan participants. Mixed methodologies and secondary analyses of anonymised data were used to study translation of learning into practice. In total, 103 participants from 66 facilities who attended courses between 2016 and 2017 were analysed. Ninety (87%) participants who were followed up completed knowledge tests. Baseline median (IQR [range]) knowledge test score was 41 (37-43 [21-46]). There was a significant improvement in median (IQR [range]) knowledge test score immediately post-course (43 (41-45 [33-48]); p < 0.001) which was sustained at 3-6 month follow-up (43 (41-45 [32-50]); p < 0.001 compared with baseline). Eighty-four of the 103 participants were observed in their workplace and capability, opportunity and motivation-behaviour framework was used to study the barriers and facilitators to practice change. Psychological capability and reflective motivation were the main factors enabling positive behaviour change such as team communication and pre-operative assessment, whereas physical and social opportunity accounted for the main barriers to behaviours such as performing the surgical safety checklist. Our study demonstrates that the Safe Anaesthesia from Education obstetric course is relevant in the low-resource setting and may lead to knowledge translation in clinical practice.

Microrheology and Spatial Heterogeneity of Staphylococcus aureus Biofilms Modulated by Hydrodynamic Shear and Biofilm-Degrading Enzymes.

Particle tracking microrheology was used to investigate the viscoelasticity of Staphylococcus aureus biofilms grown in microfluidic cells at various flow rates and when subjected to biofilm-degrading enzymes. Biofilm viscoelasticity was found to harden as a function of shear rate but soften with increasing height away from the attachment surface in good agreement with previous bulk results. Ripley's K-function was used to quantify the spatial distribution of the bacteria within the biofilm. For all conditions, biofilms would cluster as a function of height during growth. The effects of proteinase K and DNase-1 on the viscoelasticity of biofilms were also investigated. Proteinase K caused an order of magnitude change in the compliances, softening the biofilms. However, DNase-1 was found to have no significant effects over the first 6 h of development, indicating that DNA is less important in biofilm maintenance during the initial stages of growth. Our results demonstrate that during the preliminary stages of Staphylococcus aureus biofilm development, column-like structures with a vertical gradient of viscoelasticity are established and modulated by the hydrodynamic shear caused by fluid flow in the surrounding environment. An understanding of these mechanical properties will provide more accurate insights for removal strategies of early-stage biofilms.

Global Sensitivity Analysis of High-Dimensional Neuroscience Models: An Example of Neurovascular Coupling.

The complexity and size of state-of-the-art cell models have significantly increased in part due to the requirement that these models possess complex cellular functions which are thought-but not necessarily proven-to be important. Modern cell models often involve hundreds of parameters; the values of these parameters come, more often than not, from animal experiments whose relationship to the human physiology is weak with very little information on the errors in these measurements. The concomitant uncertainties in parameter values result in uncertainties in the model outputs or quantities of interest (QoIs). Global sensitivity analysis (GSA) aims at apportioning to individual parameters (or sets of parameters) their relative contribution to output uncertainty thereby introducing a measure of influence or importance of said parameters. New GSA approaches are required to deal with increased model size and complexity; a three-stage methodology consisting of screening (dimension reduction), surrogate modeling, and computing Sobol' indices, is presented. The methodology is used to analyze a physiologically validated numerical model of neurovascular coupling which possess 160 uncertain parameters. The sensitivity analysis investigates three quantities of interest, the average value of [Formula: see text] in the extracellular space, the average volumetric flow rate through the perfusing vessel, and the minimum value of the actin/myosin complex in the smooth muscle cell. GSA provides a measure of the influence of each parameter, for each of the three QoIs, giving insight into areas of possible physiological dysfunction and areas of further investigation.

Public health practitioners' views of the 'Making Every Contact Count' initiative and standards for its evaluation.

BACKGROUND: National Health Service England encourages staff to use everyday interactions with patients to discuss healthy lifestyle changes as part of the 'Making Every Contact Count' (MECC) approach. Although healthcare, government and public health organisations are now expected to adopt this approach, evidence is lacking about how MECC is currently implemented in practice. This study explored the views and experiences of those involved in designing, delivering and evaluating MECC. METHODS: We conducted a qualitative study using semi-structured interviews with 13 public health practitioners with a range of roles in implementing MECC across England. Interviews were conducted via telephone, transcribed verbatim and analysed using an inductive thematic approach. RESULTS: Four key themes emerged identifying factors accounting for variations in MECC implementation: (i) 'design, quality and breadth of training', (ii) 'outcomes attended to and measured', (iii) 'engagement levels of trainees and trainers' and (iv) 'system-level influences'. CONCLUSIONS: MECC is considered a valuable public health approach but because organisations interpret MECC differently, staff training varies in nature. Practitioners believe that implementation can be improved, and an evidence-base underpinning MECC developed, by sharing experiences more widely, introducing standardization to staff training and finding better methods for assessing meaningful outcomes.

How do members of a fire and rescue service perceive expanding their roles to deliver more health care services?

BACKGROUND: Increasingly, public sector workers are being required to expand their roles into public health. Fire and rescue services, as part of the Emergency Medical Response trial, are at the forefront of role expansion, with increasing capacity due to reducing numbers of fires in recent years. Firefighter roles, successfully implemented, include responding to cardiac arrests and conducting checks on health and wellbeing in people's own homes. In this study, we explored fire service members' perceptions about this role expansion, to increase understanding of how role expansion can be introduced and supported. METHODS: We interviewed 21 firefighters and team members about their perceptions of new roles. Interviews were conducted, transcribed and thematically analysed until reaching thematic saturation. RESULTS: Perspectives differed for responding to cardiac arrests and wellbeing checks. Cardiac arrests were seen as aligned with core roles and thus more acceptable. For both types of new role participants wanted more training and opportunities to provide feedback on implementation. CONCLUSIONS: How team members viewed role expansion depended on new role alignment with core role, training and being able to give feedback to management to shape future services.

The Safer Anaesthesia from Education (SAFE)® paediatric anaesthesia course: educational impact in five countries in East and Central Africa.

There is an urgent need to improve access to safe surgical and anaesthetic care for children living in many low- and middle-income countries. Providing quality training for healthcare workers is a key component of achieving this. The 3-day Safer Anaesthesia from Education (SAFE)® paediatric anaesthesia course was developed to address the specific skills and knowledge required in this field. We undertook a project to expand this course across five East and Central African countries (Ethiopia, Kenya, Malawi, Uganda and Zambia) and train local faculty. This study reports the outcomes from course evaluation data, exploring the impact on knowledge, skills and behaviour change in participants. Eleven courses were conducted in a 15-month period, with 381 participants attending. Fifty-nine new faculty members were trained. Knowledge scores (0-50 scale) increased significantly from mean (SD) 37.5 (4.7) pre-course to 43.2 (3.5) post-course (p < 0.0001). Skills scores (0-10 scale) increased significantly from 5.7 (2.0) pre-course to 8.0 (1.5) post-course (p < 0.0001). One hundred and twenty-six participants in Malawi, Uganda and Zambia were visited in their workplace 3-6 months later. Knowledge and skills were maintained at follow-up, with scores of 41.5 (5.0) and 8.3 (1.4), respectively (p < 0.0001 compared with pre-course scores). Content analysis from interviews with these participants highlighted positive behaviour changes in the areas of preparation, peri-operative care, resuscitation, management of the sick child, communication and teaching. This study indicates that the SAFE paediatric anaesthesia course is an effective way to deliver training, and could be used to help strengthen emergency and essential surgical care for children as a component of universal health coverage.

Perimenarchal air pollution exposure and menstrual disorders.

STUDY QUESTION: What is the association between perimenarchal exposure to total suspended particulate (TSP) in air, menstrual irregularity phenotypes and time to menstrual cycle regularity? SUMMARY ANSWER: Exposures to TSP during high school are associated with slightly increased odds of menstrual irregularity and longer time to regularity in high school and early adulthood. WHAT IS KNOWN ALREADY: The menstrual cycle is responsive to hormonal regulation. Particulate matter air pollution has demonstrated hormonal activity. However, it is not known if air pollution is associated with menstrual cycle regularity. STUDY DESIGN, SIZE, DURATION: Cross sectional study of 34 832 of the original 116 430 women (29.91%) enrolled in 1989 from the Nurses' Health Study II (NHSII). The follow-up rate for this analytic sample was 97.76% at the 1991 survey. PARTICIPANTS/MATERIALS, SETTING, METHODS: Annual averages of TSP were available for each year of high school attendance. We created three case definitions including high school menstrual irregularity and androgen excess. The time to menstrual cycle regularity was reported by participants as <1 year, 1-2 years, 3-4 years, 5 years or longer, or never on the baseline questionnaire. Odds ratios and 95% confidence intervals (CI) were calculated for 45 µg/m3 increases in TSP exposure, adjusted for risk factors for menstrual irregularity. MAIN RESULTS AND THE ROLE OF CHANCE: In multivariable adjusted models, we observed that for every 45 µg/m3 increase in average high school TSP there was an increased odds (95%CI) of 1.08 (1.03-1.14), 1.08 (1.02-1.15) and 1.10 (0.98-1.25) for moderate, persistent, and persistent with androgen excess irregularity phenotypes, respectively. TSP was also associated with a longer time to cycle regularity, with stronger results among women with older ages at menarche and those living in the Northeast or the West. LIMITATIONS, REASONS FOR CAUTION: The outcomes of menstrual regularity and time to cycle regularity were retrospectively assessed outcomes and may be susceptible to recall bias. There is also the potential for selection bias, as women had to live until 2011 to provide addresses. WIDER IMPLICATIONS OF THE FINDINGS: Temporal exposure to air pollution in the adolescent and early adulthood window may be especially important, given its association with phenotypes of menstrual irregularity. The data from this study agrees with existing literature regarding air pollution and reproductive tract diseases. STUDY FUNDING/COMPETING INTEREST(S): Shruthi Mahalingaiah: Reproductive Scientist Development Program HD000849, and a research grant from the Boston University Department of Obstetrics and Gynecology, Stacey Missmer: R01HD57210 from the National Institute of Child Health and Human Development and the Massachusetts Institute of Technology Center for Environmental Health Sciences Translational Pilot Project Program, R01CA50385 from the National Cancer Institute, Jaime Hart and Francine Laden: 5R01ES017017 from the National Institute for Environmental Health Sciences, Jaime Hart: P30 ES00002 from the National Institute for Environmental Health Sciences at the National Institute of Health, The Nurses' Health Study II is supported by infrastructure grant UM1CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services The authors have no conflicts of interest to declare.

What maximizes the effectiveness and implementation of technology-based interventions to support healthcare professional practice? A systematic literature review.

BACKGROUND: Technological support may be crucial in optimizing healthcare professional practice and improving patient outcomes. A focus on electronic health records has left other technological supports relatively neglected. Additionally, there has been no comparison between different types of technology-based interventions, and the importance of delivery setting on the implementation of technology-based interventions to change professional practice. Consequently, there is a need to synthesise and examine intervention characteristics using a methodology suited to identifying important features of effective interventions, and the barriers and facilitators to implementation. Three aims were addressed: to identify interventions with a technological component that are successful at changing professional practice, to determine if and how such interventions are theory-based, and to examine barriers and facilitators to successful implementation. METHODS: A literature review informed by realist review methods was conducted involving a systematic search of studies reporting either: (1) behavior change interventions that included technology to support professional practice change; or (2) barriers and facilitators to implementation of technological interventions. Extracted data was quantitative and qualitative, and included setting, target professionals, and use of Behaviour Change Techniques (BCTs). The primary outcome was a change in professional practice. A thematic analysis was conducted on studies reporting barriers and facilitators of implementation. RESULTS: Sixty-nine studies met the inclusion criteria; 48 (27 randomized controlled trials) reported behavior change interventions and 21 reported practicalities of implementation. The most successful technological intervention was decision support providing healthcare professionals with knowledge and/or person-specific information to assist with patient management. Successful technologies were more likely to operationalise BCTs, particularly "instruction on how to perform the behavior". Facilitators of implementation included aligning studies with organisational initiatives, ensuring senior peer endorsement, and integration into clinical workload. Barriers included organisational challenges, and design, content and technical issues of technology-based interventions. CONCLUSIONS: Technological interventions must focus on providing decision support for clinical practice using recognized behavior change techniques. Interventions must consider organizational context, clinical workload, and have clearly defined benefits for improving practice and patient outcomes.

Nursing Child Assessment Satellite Training Parent-Child Interaction Scales: Comparing American and Canadian Normative and High-Risk Samples.

PURPOSE: Many nurses rely on the American Nursing Child Assessment Satellite Training (NCAST) Parent-Child Interaction (PCI) Teaching and Feeding Scales to identify and target interventions for families affected by severe/chronic stressors (e.g. postpartum depression (PPD), intimate partner violence (IPV), low-income). However, the NCAST Database that provides normative data for comparisons may not apply to Canadian families. The purpose of this study was to compare NCAST PCI scores in Canadian and American samples and to assess the reliability of the NCAST PCI Scales in Canadian samples. METHODS: This secondary analysis employed independent samples t-tests (p < 0.005) to compare PCI between the American NCAST Database and Canadian high-risk (families with PPD, exposure to IPV or low-income) and community samples. Cronbach's alphas were calculated for the Canadian and American samples. RESULTS: In both American and Canadian samples, belonging to a high-risk population reduced parents' abilities to engage in sensitive and responsive caregiving (i.e. healthy serve and return relationships) as measured by the PCI Scales. NCAST Database mothers were more effective at executing caregiving responsibilities during PCI compared to the Canadian community sample, while infants belonging to the Canadian community sample provided clearer cues to caregivers during PCI compared to those of the NCAST Database. Internal consistency coefficients for the Canadian samples were generally acceptable. CONCLUSIONS: The NCAST Database can be reliably used for assessing PCI in normative and high-risk Canadian families. PRACTICAL IMPLICATIONS: Canadian nurses can be assured that the PCI Scales adequately identify risks and can help target interventions to promote optimal parent-child relationships and ultimately child development.

Adding muscle where you need it: non-uniform hypertrophy patterns in elite sprinters.

Sprint runners achieve much higher gait velocities and accelerations than average humans, due in part to large forces generated by their lower limb muscles. Various factors have been explored in the past to understand sprint biomechanics, but the distribution of muscle volumes in the lower limb has not been investigated in elite sprinters. In this study, we used non-Cartesian MRI to determine muscle sizes in vivo in a group of 15 NCAA Division I sprinters. Normalizing muscle sizes by body size, we compared sprinter muscles to non-sprinter muscles, calculated Z-scores to determine non-uniformly large muscles in sprinters, assessed bilateral symmetry, and assessed gender differences in sprinters' muscles. While limb musculature per height-mass was 22% greater in sprinters than in non-sprinters, individual muscles were not all uniformly larger. Hip- and knee-crossing muscles were significantly larger among sprinters (mean difference: 30%, range: 19-54%) but only one ankle-crossing muscle was significantly larger (tibialis posterior, 28%). Population-wide asymmetry was not significant in the sprint population but individual muscle asymmetries exceeded 15%. Gender differences in normalized muscle sizes were not significant. The results of this study suggest that non-uniform hypertrophy patterns, particularly large hip and knee flexors and extensors, are advantageous for fast sprinting.

Clinical factors associated with C-reactive protein in chronic spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine clinical factors associated with plasma C-reactive protein (CRP) in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA, USA. METHODS: Participants provided a blood sample, completed a respiratory health questionnaire and underwent dual X-ray absorptiometry (DXA) to assess total and regional body fat. Linear regression models were used to assess cross-sectional associations with plasma CRP. RESULTS: In multivariable models, factors associated with a higher CRP included a greater BMI, urinary catheter use, a respiratory illness in the past week and non-white race. Mean CRP also increased with decreasing mobility (motorized wheelchair >hand-propelled wheelchair >walk with an assistive device >walk independently). Results were similar when adjusting for percentage android, gynoid, trunk or total fat mass in place of BMI. Level and completeness of SCI was not associated with CRP in multivariable models. CONCLUSIONS: Clinical characteristics common in chronic SCI are associated with plasma CRP. These factors are more important than the level and completeness of SCI and some are potentially modifiable.

Job demands, resources and mental health in UK prison officers.

BACKGROUND: Research findings indicate that working as a prison officer can be highly stressful, but the aspects of work that predict their mental health status are largely unknown. AIMS: To examine, using elements of the demands-resources model, the extent to which work pressure and several potential resources (i.e. control, support from managers and co-workers, role clarity, effective working relationships and positive change management) predict mental health in a sample of UK prison officers. METHODS: The Health and Safety Executive Management Standards Indicator Tool was used to measure job demands and resources. Mental health was assessed by the General Health Questionnaire-28. The effects of demands and resources on mental health were examined via linear regression analysis with GHQ score as the outcome. RESULTS: The study sample comprised 1267 prison officers (86% male). Seventy-four per cent met 'caseness' criteria for mental health problems. Job demands, poor interpersonal relationships, role ambiguity and, to a lesser extent, low job control and poor management of change were key predictors of mental health status. CONCLUSIONS: The findings of this study can help occupational health practitioners and psychologists develop structured interventions to improve well-being among prison officers.

Clinical utility of multigene profiling assays in early-stage breast cancer.

BACKGROUND: This clinical practice guideline was developed to determine the level of evidence supporting the clinical utility of commercially available multigene profiling assays and to provide guidance about whether certain breast cancer patient populations in Ontario would benefit from alternative tests in addition to Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.). METHODS: A systematic electronic Ovid search of the medline and embase databases sought out systematic reviews and primary literature. A systematic review and practice guideline was written by a working group and was then reviewed and approved by Cancer Care Ontario's Molecular Oncology Advisory Committee. RESULTS: Twenty-four studies assessing the clinical utility of Oncotype dx, Prosigna (NanoString Technologies, Seattle, WA, U.S.A.), EndoPredict (Myriad Genetics, Salt Lake City, U.S.A.), and MammaPrint (Agendia, Irvine, CA, U.S.A.) were included in the evidence base. CONCLUSIONS: The clinical utility of multigene profiling assays is currently established for an appropriate subset of patients with estrogen receptor-positive, her2-negative, node-negative breast cancer for whom a decision to give chemotherapy is difficult to make. For patients with estrogen receptor-positive tumours who receive tamoxifen alone, Oncotype dx, Prosigna, and EndoPredict validly identify a low-risk population with favourable outcomes, indicating that a low-risk assay result is actionable and the decision to withhold chemotherapy is supported. Clinical evidence indicates that a high Oncotype dx recurrence score can predict for chemotherapy benefit, but a high Prosigna or EndoPredict score, although prognostic, is not, based on clinical trial evidence, directly actionable. Prosigna and EndoPredict are statistically more likely to identify a population at risk for recurrence beyond 5 years, but that information is currently not actionable because of a lack of interventional studies.

2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection.

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.

Adult air pollution exposure and risk of infertility in the Nurses' Health Study II.

STUDY QUESTION: Is there an association between air pollution exposures and incident infertility? SUMMARY ANSWER: Increased exposure to air pollution is associated with an increased incidence of infertility. WHAT IS KNOWN ALREADY: Exposures to air pollution have been associated with lower conception and fertility rates. However, the impact of pollution on infertility incidence is unknown. STUDY DESIGN, SIZE, DURATION: Prospective cohort study using data collected from 116 430 female nurses from September 1989 to December 2003 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertility was defined by report of attempted conception for ≥12 months without success. Participants were able to report if evaluation was sought and if so, offer multiple clinical indications for infertility. After exclusion, 36 294 members were included in the analysis. Proximity to major roadways and ambient exposures to particulate matter less than 10 microns (PM10), between 2.5 and 10 microns (PM2.5-10), and less than 2.5 microns (PM2.5) were determined for residential addresses for the 36 294 members between the years of 1993 and 2003. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable adjusted Cox proportional hazard models with time-varying covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Over 213 416 person-years, there were 2508 incident reports of infertility. Results for overall infertility were inconsistent across exposure types. We observed a small increased risk for those living closer to compared to farther from a major road, multivariable adjusted HR = 1.11 (CI: 1.02-1.20). This was consistent for those reporting primary or secondary infertility. For women living closer to compared to farther from a major road, for primary infertility HR = 1.05 (CI: 0.94-1.17), while for secondary infertility HR = 1.21 (CI: 1.07-1.36). In addition, the HR for every 10 µg/m(3) increase in cumulative PM2.5-10 among women with primary infertility was 1.10 (CI: 0.96-1.27), and similarly was 1.10 (CI: 0.94-1.28) for those with secondary infertility. LIMITATIONS, REASONS FOR CAUTION: Within the 2 year window of infertility diagnosis, we do not have the exact date of diagnosis or the exact timing of the start of attempting conception. As infertility status and subtypes of infertility were prospectively collected biennially, we were unable to tightly examine the timing of exposures on incidence of infertility. In terms of exposure quantification, we used ambient air pollution exposures as a proxy for personal exposures, potentially leading to exposure misclassification. However, several studies suggest that ambient measurements are an acceptable surrogate for individual level exposures in most populations. WIDER IMPLICATIONS OF THE FINDINGS: We observed an association between all size fractions of PM exposure, as well as traffic-related air pollution, and incidence of infertility. Of note, the strongest association was observed between cumulative average exposures over the course of follow-up and the risk of infertility, suggesting that chronic exposures may be of greater importance than short-term exposures. STUDY FUNDING/COMPETING INTERESTS: The work for this paper was supported by the following: S.M.: Reproductive Scientist Development Program HD000849, and the Building Interdisciplinary Research Careers in Women's Health HD043444, the Boston University CTSI 1UL1TR001430, and a research grant from the Boston University Department of Obstetrics and Gynecology, S.A.M.: R01HD57210 from the National Institute of Child Health and Human Development and the Massachusetts Institute of Technology Center for Environmental Health Sciences Translational Pilot Project Program, R01CA50385 from the National Cancer Institute, J.E.H. and F.L.: 5R01ES017017 from the National Institute for Environmental Health Sciences, 5 P42 ES007381 from the National Institute of Environmental Health at the National Institute of Health. L.V.F.: T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Nurses' Health Study II is additionally supported by infrastructure grant UM1CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services. The authors have no actual or potential competing financial interests to disclose.

Clostridium difficile infection diagnosis in a paediatric population: comparison of methodologies.

The increasing incidence of Clostridium difficile infection (CDI) in paediatric hospitalised populations, combined with the emergence of hypervirulent strains, community-acquired CDI and the need for prompt treatment and infection control, makes the rapid, accurate diagnosis of CDI crucial. We validated commonly used C. difficile diagnostic tests in a paediatric hospital population. From October 2011 to January 2012, 150 consecutive stools were collected from 75 patients at a tertiary paediatric hospital in Perth, Western Australia. Stools were tested using: C. Diff Quik Chek Complete, Illumigene C. difficile, GeneOhm Cdiff, cycloserine cefoxitin fructose agar (CCFA) culture, and cell culture cytotoxin neutralisation assay (CCNA). The reference standard was growth on CCFA or Cdiff Chromagar and PCR on isolates to detect tcdA, tcdB, cdtA, and cdtB. Isolates were PCR ribotyped. The prevalence of CDI was high (43 % of patients). Quik Chek Complete glutamate dehydrogenase (GDH) demonstrated a low negative predictive value (NPV) (93 %). Both CCNA and Quik Chek Complete toxin A/B had poor sensitivity (33 % and 29 % respectively). Molecular methods both had 89 % sensitivity. Algorithms using GDH + Illumigene or GeneOhm reduced the sensitivity to 85 % and 83 % respectively. Ribotype UK014/20 predominated. GDH NPV and GeneOhm and Illumigene sensitivities were reduced compared with adult studies. Quik Chek Complete and CCNA cannot reliably detect toxigenic CDI. A GDH first algorithm showed reduced sensitivity. In a high prevalence paediatric population, molecular methods alone are recommended over the use of GDH algorithm or culture and CCNA, as they demonstrate the best test performance characteristics.

Gait kinematics and kinetics in patients with chronic ankle instability and healthy controls: A statistical parametric mapping analysis.

BACKGROUND: Chronic ankle instability (CAI) is associated with changes in gait biomechanics which may be related to chronic dysfunction. Traditional statistical models may be limited in their ability to assess the complex 3D movement of the lower extremity during gait. Multivariate analysis of the lower extremity kinematics may reveal unique biomechanical differences associated with CAI. RESEARCH QUESTION: Do patients with CAI differ from healthy controls in their lower extremity biomechanics and GRF when comparing 3D biomechanics? METHODS: Thirty-nine young, active adults participated in this study. Data was collected using a 3D motion analysis system while patients walked and jogged. Statistical parametric mapping (SPM) was used to explore 3D GRF, kinematics and kinetics of the of the lower extremity of CAI and healthy patients. RESULTS: During walking, patients with CAI had greater inversion from 68-100% of gait cycle (p < 0.001, mean difference=3.2°). During jogging, patients with CAI had greater inversion from 20-92% (p < 0.001, mean difference=4.6°). Greater plantar flexion moments were found from 65-71% (p = 0.05, mean difference=347.4Nm/kg) and greater eversion moments were found from 95-100% (p = 0.03, mean difference=74.6Nm/kg) in the CAI group. No differences in GRF were found. SIGNIFICANCE: Greater inversion may present a potentially injurious position. A faulty position of the rearfoot may require greater muscle function in order to correct the position of the joint resulting in greater eversion moments at the ankle. However, this kinetic change does not appear to correct the ankle position.