Successful stent graft repair of multiple thoracoabdominal mycotic aortic aneurysms in the presence of Kommerell diverticulum and complicated by aortoesophageal fistula

We describe the management of a woman who presented with synchronous mycotic aortic aneurysms of the aortic arch in the presence of Kommerell diverticulum, the distal thoracic, and the juxtarenal aorta. A staged stent graft repair was undertaken due to rapid expansion of the aneurysms, which involved placement of multiple thoracic quadruple-fenestrated and infrarenal bifurcated stent grafts. Despite complications of an aortoesophageal fistula and transitory spinal cord ischemia, she has been managed successfully and is doing well at 36 months. This case illustrates that stent graft repair of mycotic aneurysms can offer a successful treatment option in selected patients

Vasopressin, depression, pain & preeclampsia

Preeclampsia (PreE) is a prevalent hypertensive disorder of pregnancy leading to a death every minute worldwide. Predictive and preventative challenges in PreE stems from its unclear early-pregnancy etiology. Arginine vasopressin (AVP) secretion, as measured by copeptin, activates the stress response system and is a novel, early pregnancy predictor of PreE. In addition, elevated AVP is associated with stress, depression and pain. Our Precision Healthcare goal is to understand how AVP-associated changes in depression and pain affect the phenotype of PreE to develop preventative and therapeutic modalities against it. We hypothesize that in humans, antecedent depression and pain affects early pregnancy AVP secretion/copeptin which will be differentially predictive of PreE. To address this hypothesis we aim to 1) determine the association of maternal plasma copeptin and measures of depression and pain throughout human gestation and 2) determine how depression and pain through gestation affects an early pregnancy copeptin based prediction model of preeclampsia

The efficient use of the maternity workforce and the implications for safety and quality in maternity care : a population-based, cross-sectional study

Background: The performance of maternity services is seen as a touchstone of whether or not we are delivering high-quality NHS care. Staffing has been identified in numerous reports as being a critical component of safe, effective, user-centred care. There is little evidence regarding the impact of maternity workforce staffing and skill mix on the safety, quality and cost of maternity care in the UK. Objectives: To understand the relationship between organisational factors, maternity workforce staffing and skill mix, cost and indicators of safe and high-quality care. Design and methods: Data included Hospital Episode Statistics (HES) from 143 NHS trusts in England in 2010–11 (656,969 delivery records), NHS Workforce Statistics, England, 2010–11, Care Quality Commission Maternity Survey of women’s experiences 2010 and NHS reference costs 2010/11. Ten indicators were derived from HES data. They included healthy mother and healthy baby outcomes and mode of birth. Adjustments were made for background characteristics and clinical risk. Data were analysed to examine the influence of organisational factors, staffing and costs using multilevel logistic regression models. A production function analysis examined the relationship between staffing, skill mix and output. Results: Outcomes were largely determined by women’s level of clinical risk [based on National Institute for Health and Care Excellence (NICE) guidance], parity and age. The effects of trust size and trust university status were small. Larger trust size reduced the chance of a healthy mother outcome and also reduced the likelihood of a healthy mother/healthy baby dyad outcome, and increased the chances of other childbirth interventions. Increased investment in staff did not necessarily have an effect on the outcome and experience measures chosen, although there was a higher rate of intact perineum and also of delivery with bodily integrity in trusts with greater levels of midwifery staffing. An analysis of the multiplicative effects of parity and clinical risk with the staffing variables was more revealing. Increasing the number of doctors had the greatest impact on outcomes in higher-risk women and increasing the number of midwives had the greatest impact on outcomes in lower-risk women. Although increased numbers of support workers impacted on reducing childbirth interventions in lower-risk women, they also had a negative impact on the healthy mother/healthy baby dyad outcomes in all women. In terms of maximising the capacity of a trust to deliver babies, midwives and support workers were found to be substitutes for each other, as were consultants and other doctors. However, any substitution between staff groups could impact on the quality of care given. Economically speaking, midwives are best used in combination with consultants and other doctors. Conclusions: Staffing levels have positive and negative effects on some outcomes, and deployment of doctors and midwives where they have most beneficial impact is important. Managers may wish to exercise caution in increasing the number of support workers who care for higher-risk women. There also appear to be limited opportunities for role substitution. Future work: Wide variations in outcomes remain after adjustment for sociodemographic and clinical risk, and organisational factors. Further research is required on what may be influencing unexplained variation such as organisational climate and culture, use of NICE guidelines in practice, variation of models of care within trusts and women’s choices. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Breaking down Barriers: Co-designed recommendations to reduce stakeholder identified NDIS access barriers for people with psychosocial disability

The Issue The National Disability Insurance Scheme (NDIS) commenced in 2016 and is designed to support people with all types of disability including those living with psychosocial disability. However, many thousands of Australians living with psychosocial disability have still not applied to access the Scheme and are consequently missing out on their right to receive valuable NDIS supports to advance their social and economic inclusion. The Project Aims The project aims were to work with stakeholders to 1. Understand the barriers to applying to the NDIS for people living with psychosocial disability, and 2. Identify solutions to remove or reduce these barriers and to synthesise these into a practical set of stakeholder-informed recommendations. Across all states and territories, 386 stakeholders collaborated on this project. Stakeholders included: 1. people living with psychosocial disability of mental distress; 2. their family and friends, and 3. workers and organisations engaged in supporting or advocating for them. The Approach The project was conducted over three phases: 1. A scoping review of literature to identify previously reported barriers to applying to the NDIS for people with psychosocial disability – used to inform phase 2 survey. 2. A national survey to identify current, stakeholder informed and prioritised barriers. 3. Co-design of practical, lived experience informed recommendations to address NDIS access barriers with stakeholders. The Barriers Stakeholders described ten broad and interconnected NDIS access barriers for people with psychosocial disability. These included: 1. Key information about NDIS is confusing or not accessible 2. Hard to get supports to help to apply - formal (services) and informal (family and friends) 3. Hard to obtain evidence required by the NDIA 4. Application process is too long, complicated, and inflexible 5. Application process is harmful to mental health and well-being 6. The application process does not accommodate for mental illness and psychosocial disability 7. The negative reputation of NDIA staff and culture 8. Disconnect between ‘disability’ and ‘recovery’ 9. Personal beliefs, fears and stigma, and 10. It is not worth it – NDIS won’t meet my needs anyway. Each of these is detailed within the report. The Recommendations Seven recommendations were identified, reviewed and refined by stakeholders. These recommendations are practical, lived-experience informed actions to address NDIS access barriers faced by people living with psychosocial disability. 1. Build, maintain and disseminate accurate, up-to-date, easily accessible information - Update, enhance and build upon best currently available information. Invest in and maintain the update of a single national source of information. Enhance the dissemination of this information including easy read downloadable one-pagers that can be printed and paper-based fliers to maximise accessibility. 2. Co-develop and co-deliver systemic training and establish workforce support champions – Co-develop and deliver continually available training for health and community service providers. GPs, public, community and private mental health, disability and social services require ongoing access to training about the psychosocial stream of the NDIS. Workforce support champions will provide expert support and guidance to complement this training so that workers can provide accurate and helpful support, advice and evidence to people who are considering or are applying for the NDIS. 3. Establish navigator positions – independent and psychosocial specific - Create a clear, independent NDIS Psychosocial specific Navigator role to assist individuals, family members and service providers throughout the NDIS application process. 4. Cover out-of-pocket expenses - Create funding streams or models of reimbursement to ensure that people have equitable access to the experts required to provide evidence of psychosocial disability without incurring out-of-pocket expenses. 5. Commission and fund an independent evaluation of the application process specifically for people with psychosocial disability - Independent evaluation of the impacts of: a) recent legislative changes; b) the future implementation of the Recovery Framework; and c) adoption and future implementation of the recommendations within this report, on the experiences of the NDIS application process for people living with psychosocial disability. 6. Co-develop and co-deliver recovery and psychosocial disability training for a. NDIA staff, b) NDIA partner staff (Local Area Coordinators - LACs), and c) NDIS service provider staff (community managed/controlled organisations) - All staff within these 3 distinct workforces need to have access to recovery-oriented, trauma-informed psychosocial disability training and education that is co-developed and co-delivered with people with psychosocial disability. 7. Commission and fund an independent review of NDIA culture and workforce issues - Review the impact of implementing the NDIS Psychosocial Recovery-Oriented Framework agenda on NDIA staffing practice and cultural issues. Conclusion Almost 400 stakeholders partnered with us to identify current barriers to applying for NDIS support. They then engaged with us to develop seven key, lived experience informed, recommendations to address those barriers. These seven practical action-oriented recommendations need urgent implementation to enable the people living with psychosocial disability who are most disadvantaged and most in need of NDIS support to be able to apply for that support. The feasibility and value of each of these recommendations is evidenced by them being raised across numerous previous national NDIS-focused reports including for example, the Tune Review and the ‘Mind the Gap’ report. Today, stakeholders are asking for more than policymakers’ awareness of the barriers that deny much needed NDIS access – although these too are re-iterated and further detailed within this report. Stakeholders call for immediate investment in these practical actions to ‘break down barriers’ to accessing NDIS support and by doing so, improve the lives of many Australians living with psychosocial disability

A patient-specific multi-modality abdominal aortic aneurysm imaging phantom

PURPOSE: Multimodality imaging of the vascular system is a rapidly growing area of innovation and research, which is increasing with awareness of the dangers of ionizing radiation. Phantom models that are applicable across multiple imaging modalities facilitate testing and comparisons in pre-clinical studies of new devices. Additionally, phantom models are of benefit to surgical trainees for gaining experience with new techniques. We propose a temperature-stable, high-fidelity method for creating complex abdominal aortic aneurysm phantoms that are compatible with both radiation-based, and ultrasound-based imaging modalities, using low cost materials. METHODS: Volumetric CT data of an abdominal aortic aneurysm were acquired. Regions of interest were segmented to form a model compatible with 3D printing. The novel phantom fabrication method comprised a hybrid approach of using 3D printing of water-soluble materials to create wall-less, patient-derived vascular structures embedded within tailored tissue-mimicking materials to create realistic surrounding tissues. A non-soluble 3-D printed spine was included to provide a radiological landmark. RESULTS: The phantom was found to provide realistic appearances with intravascular ultrasound, computed tomography and transcutaneous ultrasound. Furthermore, the utility of this phantom as a training model was demonstrated during a simulated endovascular aneurysm repair procedure with image fusion. CONCLUSION: With the hybrid fabrication method demonstrated here, complex multimodality imaging patient-derived vascular phantoms can be successfully fabricated. These have potential roles in the benchtop development of emerging imaging technologies, refinement of novel minimally invasive surgical techniques and as clinical training tools

Heterogeneity of quality of life in young people attending primary mental health services

AIMS: The utility of quality of life (QoL) as an outcome measure in youth-specific primary mental health care settings has yet to be determined. We aimed to determine: (i) whether heterogeneity on individual items of a QoL measure could be used to identify distinct groups of help-seeking young people; and (ii) the validity of these groups based on having clinically meaningful differences in demographic and clinical characteristics. METHODS: Young people, at their first presentation to one of five primary mental health services, completed a range of questionnaires, including the Assessment of Quality of Life–6 dimensions adolescent version (AQoL-6D). Latent class analysis (LCA) and multivariate multinomial logistic regression were used to define classes based on AQoL-6D and determine demographic and clinical characteristics associated with class membership. RESULTS: 1107 young people (12–25 years) participated. Four groups were identified: (i) no-to-mild impairment in QoL; (ii) moderate impairment across dimensions but especially mental health and coping; (iii) moderate impairment across dimensions but especially on the pain dimension; and (iv) poor QoL across all dimensions along with a greater likelihood of complex and severe clinical presentations. Differences between groups were observed with respect to demographic and clinical features. CONCLUSIONS: Adding multi-attribute utility instruments such as the AQoL-6D to routine data collection in mental health services might generate insights into the care needs of young people beyond reducing psychological distress and promoting symptom recovery. In young people with impairments across all QoL dimensions, the need for a holistic and personalised approach to treatment and recovery is heightened

In vitro and In vivo antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of action

Ethnopharmacological relevance: The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma. TB is prevalent in immune-compromised patients and it is evident that TB-drugs cause hepatotoxicity. The objective of the present study was therefore to evaluate the antimycobacterial activity of the ethanolic extract of E. natalensis against TB and its hepatoprotective and immunomodulatory activities. Materials and methods: The antimycobacterial, antioxidant, hepatoprotective, immunomodulatory activity and cytotoxicity of the ethanolic extract of the shoots of E. natalensis were determined in vitro. The mechanism of action of the antituberculosis activity was determined by investigating the inhibitory effect on mycothiol disulfide reductase enzyme. Furthermore, the acute, sub-acute toxicity (50-2000 mg/kg) and antimycobacterial effect (300 mg/kg) of E. natalensis shoot extract were investigated in Balb/c mice. Hepatoprotective activity of the extract (50-150 mg/kg) was evaluated on isoniazid and rifampicin (50 mg/kg; i.p.) induced hepatic damage in a rat model. Results: The minimum inhibitory concentration of the extract was found to be 125 µg/ml against Mycobacterium tuberculosis. The extracts fifty percent inhibitory concentration (IC50) against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical was found to be 22.55 µg/ml. The plant showed a hepatoprotective effect (50% at 12.5 µg/ml) and the ability to increase T-helper 1 cell cytokines; Interleukin 12, Interleukin 2 and Interferon α by up to 12 fold and the ability to decrease the T-helper 2 cell cytokine Interleukin 10 4 fold when compared to baseline cytokine production. No cellular toxicity was observed in primary peripheral blood mononuclear cells (PBMC's) and two secondary cell lines; U937 monocytes and Chang liver cells (a derivative of the HepG2 cell line). During mechanistic studies, the extract showed a 50% inhibition of mycothiol reductase activity at 38.62 µg/ml. During the acute and sub-acute studies, E. natalensis exhibited no toxic effect and the fifty percent lethal dose (LD50) was established to be above 2000 mg/kg. The extract was able to reduce the mycobacterial load (1.5-fold reduction) in infected mice. Isoniazid and rifampicin caused significant hepatic damage in rats, and the extract was able to reduce the toxicity by 15% and 40% at 50 and 150 mg/kg respectively. Conclusion: The present study supports the traditional usage of the plant against tuberculosis symptoms. The study showed the ability of E. natalensis shoot extract to inhibit mycobacterial growth, stimulate an appropriate immune response and have a hepatic protective effect. Due to the extract's significant results for hepatoprotective, immunomodulatory effects and antimycobacterial activity, it may prove to be effective to serve as an adjuvant for TB-patients

Early Evidence of Dose-dependent Pharmacodynamic Activity Following Treatment with SY-5609, a Highly Selective and Potent Oral CDK7 Inhibitor, in Patients with Advanced Solid Tumors

https://jdc.jefferson.edu/medoncposters/1012/thumbnail.jp

Experiences and Perspectives of Polycystic Kidney Disease Patients following a Diet of Reduced Osmoles, Protein, and Acid Precursors Supplemented with Water:A Qualitative Study

Background Salt, protein, acid precursors, and fluid intake have been identified as factors that influence cyst growth in ADPKD. Unfortunately, the feasibility of following these dietary restrictions/enhancements from a patient's point-of-view has yet to be studied. The purpose of this study is to understand better the experiences of patients following a relatively complex dietary prescription targeting these factors. Methods Twelve adults with ADPKD and kidney function >30ml/min/1.73m(2) were recruited from the University of Kansas Medical Center Polycystic Kidney Disease clinic. In a qualitative design, semi-structured interviews of participants were conducted following a four week dietary intervention (experimental diet lower in sodium, protein, and acid precursors, and supplemented with water) either face-to-face or by telephone. All interviews were recorded, transcribed verbatim, and checked for accuracy. Transcripts were analyzed thematically for emerging themes. Results Participants reported that eating less meat and more fruits and vegetables were the easiest components of the diet, whereas reaching the daily goal amount of fruits and vegetables and tracking the diet constantly were the most difficult components. Participants had little difficulty with fluid intake and reported the prescribed fluid goal as achievable. The tracking system for fruits and vegetables and protein was reported to be both helpful and intuitive, but tracking their intake on paper was tedious. Eating out was the most significant barrier to following the diet with some individuals avoiding restaurants in order to comply with the dietary prescription. Conclusion Participants on the experimental diet heightened their awareness of the consumption of dietary salt, protein, acid precursors, and fluid intake. Additionally, most participants believed adherence to the prescribed diet was feasible. However, participants wanted less cumbersome ways to track and monitor the diet, especially given that the prescribed diet is designed for lifelong adherence. Future studies should focus on targeting these specific dietary factors in larger groups of more ethnically and culturally diverse populations to help inform clinicians and how best to help diverse populations adhere to the dietary intervention

Undergraduate Biology Education Research Gordon Research Conference: A Meeting Report

The 2019 Undergraduate Biology Education Research Gordon Research Conference (UBER GRC), titled “Achieving Widespread Improvement in Undergraduate Education,” brought together a diverse group of researchers and practitioners working to identify, promote, and understand widespread adoption of evidence-based teaching, learning, and success strategies in undergraduate biology. Graduate students and postdocs had the additional opportunity to present and discuss research during a Gordon Research Seminar (GRS) that preceded the GRC. This report provides a broad overview of the UBER GRC and GRS and highlights major themes that cut across invited talks, poster presentations, and informal discussions. Such themes include the importance of working in teams at multiple levels to achieve instructional improvement, the potential to use big data and analytics to inform instructional change, the need to customize change initiatives, and the importance of psychosocial supports in improving undergraduate student well-being and academic success. The report also discusses the future of the UBER GRC as an established meeting and describes aspects of the conference that make it unique, both in terms of facilitating dissemination of research and providing a welcoming environment for conferees