Rural Clinical School - Research Publications

What works, why and how? A scoping review and logic model of rural clinical placements for allied health students

2020-11-22T00:42:20Z

Moran, A; Nancarrow, S; Cosgrave, C; Griffith, A; Memery, R 2020-09-14 What works, why and how? A scoping review and logic model of rural clinical placements for allied health students BACKGROUND: Allied health services are core to the improvement in health outcomes for remote and rural residents. Substantial infrastructure has been put into place to facilitate rural work-ready allied health practitioners, yet it is difficult to understand or measure how successful this is and how it is facilitated. METHODS: A scoping review and thematic synthesis of the literature using program logic was undertaken to identify and describe the contexts, mechanisms and outcomes of successful models of rural clinical placements for allied health students. This involved all empirical literature examining models of regional, rural and remote clinical placements for allied health students between 1995 and 2019. RESULTS: A total of 292 articles were identified; however, after removal of duplicates and article screening, 18 were included in the final synthesis. Australian papers dominated the evidence base (n = 11). Drivers for rural allied health clinical placements include: attracting allied health students to the rural workforce; increasing the number of allied health clinical placements available; exposing students to and providing skills in rural and interprofessional practice; and improving access to allied health services in rural areas. Depending on the placement model, a number of key mechanisms were identified that facilitated realisation of these drivers and therefore the success of the model. These included: support for students; engagement, consultation and partnership with key stakeholders and organisations; and regional coordination, infrastructure and support. Placement success was measured in terms of student, rural, community and/or program outcomes. Although the strength and quality of the evidence was found to be low, there is a trend for placements to be more successful when the driver for the placement is specifically reflected in the structure of the placement model and outcomes measured. This was seen most effectively in placement models that were driven by the need to meet rural community needs and upskill students in interprofessional rural practice. CONCLUSION: This study identifies the factors that can be manipulated to ensure more successful models of allied health rural clinical placements and provides an evidence based framework for improved planning and evaluation. Journal Article

Lessons Learned and New Challenges: Re-evaluation of End-User Assessment of a Skills-Based Training Program for Urology Trainees

2020-11-28T12:39:52Z

Flanders, D; Pirpiris, A; Corcoran, N; Forsyth, R; Grills, R 2019-03-12 Lessons Learned and New Challenges: Re-evaluation of End-User Assessment of a Skills-Based Training Program for Urology Trainees Objectives: To re-assess the perceived benefit and relevance of simulation sessions to Victorian urology trainees and to identify areas for potential improvement. Subjects and methods: All trainees attending skills training sessions between 2011 and 2016 were asked to complete a structured questionnaire at the completion of the session. The questionnaire included 11 topic areas ranging from the year of surgical training to degree of usefulness of the session, including several sections for free-text response to offer more detailed feedback. Sessions were examined both individually and collectively to assess end-user satisfaction with the structure and content of the program. Results: In total, 24 individual skills sessions were held over the 6-year period, with a total of 355 attendees. Of these, 331 attendees completed the majority of the questionnaire, a response rate of over 93%. Overall 88% of the surveyed attendees stated that they had both the support of their supervising consultant and the flexibility of workload to attend the session; 90% of trainees felt that there was adequate reading material provided prior to the skills session, an improvement from 76% in the previous study period; and 97% of those surveyed felt that the existing session structure was appropriate and the same proportion found the sessions both useful and interesting, compared with just 63% in the previous study period. Analysis of individual topics demonstrates some variability in outcome measures, but for nearly every assessed parameter, greater than 90% of participants agreed that the session fulfilled the expected criteria. New topics developed since the 2011 analysis, including renal transplant and vascular repair, also had high levels of satisfaction. The practical models used have been refined and achieved higher scores than those in the previous assessment period. Conclusion: The urology skills-based training program has been well received by the surveyed trainees and is now embedded and accepted as part of the Victorian training program. The format of the sessions has matured and the overall rating, both individually and collectively, was high. There has been a clear increase in satisfaction across most areas assessed when compared with previous feedback. Despite this, there remain areas that can be improved, such as the amount and quality of available equipment and the inclusion of video demonstrations of operative techniques. Journal Article

MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway

2020-11-28T12:39:52Z

Wilson, KR; Liu, H; Healey, G; Vuong, V; Ishido, S; Herold, MJ; Villadangos, JA; Mintern, JD 2018-07-12 MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway Major histocompatibility complex class II (MHC II) expression and turn-over are regulated via its ubiquitination by the membrane associated RING-CH 1 (MARCH1) E3 ligase. Unexpectedly, we show that MHC II ubiquitination also impacts MHC I. Lack of MARCH1 in B cells and dendritic cells (DCs) resulted in a significant reduction in surface MHC I expression. This decrease was not directly caused by changes in MARCH1 ubiquitination of MHC I but indirectly by altered MHC II trafficking in the absence of its ubiquitination. Deletion of MHC II in March1-/- cells restored normal MHC I surface expression and replacement of wild type MHC II by a variant that could not be ubiquitinated caused a reduction in MHC I expression. Furthermore, these cells displayed inefficient presentation of peptide and protein antigen via MHC I to CD8+ T cells. In summary, we describe an unexpected intersection between MHC I and MHC II such that the surface expression of both molecules are indirectly and directly regulated by MARCH1 ubiquitination, respectively. Journal Article

Paclitaxel-Induced Src Activation Is Inhibited by Dasatinib Treatment, Independently of Cancer Stem Cell Properties, in a Mouse Model of Ovarian Cancer

2020-11-28T12:39:52Z

Kadife, E; Chan, E; Luwor, R; Kannourakis, G; Findlay, J; Ahmed, N 2019-02-01 Paclitaxel-Induced Src Activation Is Inhibited by Dasatinib Treatment, Independently of Cancer Stem Cell Properties, in a Mouse Model of Ovarian Cancer Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer. Journal Article

Association between Gestational Weight Gain, Gestational Diabetes Risk, and Obstetric Outcomes: A Randomized Controlled Trial Post Hoc Analysis

2020-11-28T12:39:52Z

Simmons, D; Devlieger, R; van Assche, A; Galjaard, S; Corcoy, R; Adelantado, JM; Dunne, F; Desoye, G; Kautzky-Willer, A; Damm, P; Mathiesen, ER; Jensen, DM; Andersen, LLT; Lapolla, A; Dalfra, MG; Bertolotto, A; Wender-Ozegowska, E; Zawiejska, A; Hill, D; Snoek, FJ; van Poppel, MNM 2018-11-01 Association between Gestational Weight Gain, Gestational Diabetes Risk, and Obstetric Outcomes: A Randomized Controlled Trial Post Hoc Analysis Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m² <20 weeks gestation without GDM (n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24⁻28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p < 0.01), and a higher rate of caesarean section (38% vs. 27% p < 0.05). The GWG over the median at 35⁻37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p < 0.05). A post hoc comparison among women from the five sites with a GWG difference >3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester. Journal Article

Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9

2020-11-28T12:39:52Z

Croft, B; Ohnesorg, T; Hewitt, J; Bowles, J; Quinn, A; Tan, J; Corbin, V; Pelosi, E; van den Bergen, J; Sreenivasan, R; Knarston, I; Robevska, G; Dung, CV; Hutson, J; Harley, V; Ayers, K; Koopman, P; Sinclair, A 2018-12-14 Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9 Disorders of sex development (DSDs) are conditions affecting development of the gonads or genitalia. Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs remains unknown. SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying this have not been identified in humans. Here, we identified four DSD patients with overlapping duplications or deletions upstream of SOX9. Bioinformatic analysis identified three putative enhancers for SOX9 that responded to different combinations of testis-specific regulators. All three enhancers showed synergistic activity and together drive SOX9 in the testis. This is the first study to identify SOX9 enhancers that, when duplicated or deleted, result in 46,XX or 46,XY sex reversal, respectively. These enhancers provide a hitherto missing link by which SRY activates SOX9 in humans, and establish SOX9 enhancer mutations as a significant cause of DSD. Journal Article

Pembrolizumab Induced Ocular Hypotony With Near Complete Vision Loss, Interstitial Pulmonary Fibrosis and Arthritis

2020-11-28T12:39:52Z

Nguyen, M; Islam, MR; Lim, SW; Sahu, A; Tamjid, B 2019-09-23 Pembrolizumab Induced Ocular Hypotony With Near Complete Vision Loss, Interstitial Pulmonary Fibrosis and Arthritis Clinical outcomes for patients with advanced melanoma have improved significantly with the introduction of immune checkpoint inhibitors. These agents have distinct adverse effects with the potential for heightened host immune responses manifesting as an autoimmune reaction in any organ. We report a unique case who developed pembrolizumab induced arthritis, ocular hypotony with vision loss and pulmonary interstitial fibrosis. A 57-year old gentleman with advanced melanoma was treated with pembrolizumab and attained complete response with no evidence of disease on functional imaging. Treatment was well-tolerated with the only side effect being arthritis controlled with low dose steroids. Following a work related blunt trauma to the right eye, the patient developed bilateral visual impairment secondary to ocular hypotony. The ocular hypotony failed to respond to high-dose glucocorticoid and multiple surgeries. Intraoperatively, ciliary body atrophy was found. Pembrolizumab was ceased after the eye trauma and he remained in complete remission from melanoma. After a further 10 months, the patient developed symptomatic pulmonary fibrosis. There was moderate symptomatic improvement with nintedanib, an antifibrotic agent. This case describes two rare and unique adverse effects. Ocular adverse effects are extremely uncommon and this is the first case to report immune checkpoint inhibitor related ocular hypotony without uveitis to the best of our knowledge. Similarly, the incidence of severe pneumonitis is reported to be low, however limited data is available regarding pulmonary interstitial fibrosis. The occurrence of multiple adverse effects in this case including one occurring several months after cessation of treatment highlights the need for vigilance by clinicians who manage patients treated with immune checkpoint inhibitors. Further research is necessary with regards to rare adverse effects of immune checkpoint inhibitors and the relation of these to treatment administration. Journal Article

Dietary exclusion of fructose and lactose after positive breath tests improved rapid-transit constipation in children

2020-11-28T12:39:52Z

Waingankar, K; Lai, C; Punwani, V; Wong, J; Hutson, JM; Southwell, BR 2018-12-01 Dietary exclusion of fructose and lactose after positive breath tests improved rapid-transit constipation in children Aims: Exclusion of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) from the diet is effective in alleviating symptoms of irritable bowel syndrome (IBS) in adults. Rapid-transit constipation (RTC) is a recently discovered subset of chronic constipation and has been linked to food intolerance. The aim of this study was to audit the effect of specific FODMAP elimination diets in children with RTC. Methods: This was an audit of children presenting to a tertiary children's hospital surgeon with refractory chronic constipation who had rapid transit in the proximal colon on nuclear imaging; had hydrogen/methane breath tests for fructose, lactose, and/or sorbitol intolerance; and were advised to exclude positive sugar under clinical supervision. Patients filled in a questionnaire rating severity of constipation, abdominal pain, and pain on defecation with a visual analogue scale (VAS, 0 = none, 10 = high) and stool consistency for 6 months before and after dietary exclusion. Results: In responses from 29 children (5-15 years, 21 males), 70% eliminated fructose, and 40% eliminated lactose. There was a significant reduction in the severity of constipation (VAS mean ± SEM, pre 5.8 ± 0.5 vs post 3.3 ± 0.6, P < 0.0001), abdominal pain (5.1 ± 0.6 vs 2.8 ± 0.5, P = 0.0004), pain on defecation (5.8 ± 0.6 vs 2.6 ± 0.5, P < 0.0001), and increase in stool wetness (Bristol Stool Scale pre 3.3 ± 0.3 vs post 3.9 ± 0.2, P = 0.004). Conclusion: Children with RTC showed significant improvements in constipation and pain after excluding the sugar indicated by positive breath tests, suggesting that specific sugar-exclusion diets may have a role in the management of RTC in children. Journal Article

First reported case of Human Parechovirus encephalitis in an adult patient complicated by Refractory Status Epilepticus

2020-11-28T12:39:52Z

Chimunda, T; Subramanian, R; Smith, J; Mahony, A 2019-01-01 First reported case of Human Parechovirus encephalitis in an adult patient complicated by Refractory Status Epilepticus Human Parechovirus (HPeV) infections are common amongst children, particularly neonates. However, data in adult cases are lacking. We report a unique case of HPeV meningoencephalitis in an adult complicated by Refractory Status Epilepticus (RSE). Journal Article

Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

2020-11-28T12:39:52Z

Nichols, E; Szoeke, CEI; Vollset, SE; Abbasi, N; Abd-Allah, F; Abdela, J; Aichour, MTE; Akinyemi, RO; Alahdab, F; Asgedom, SW; Awasthi, A; Barker-Collo, SL; Baune, BT; Bejot, Y; Belachew, AB; Bennett, DA; Bijani, BBA; Bin Sayeed, MS; Brayne, C; Carpenter, DO; Carvalho, F; Catala-Lopez, F; Cerin, E; Choi, J-YJ; Dang, AK; Degefa, MG; Djalalinia, S; Dubey, M; Duken, EE; Edvardsson, D; Endres, M; Eskandarieh, S; Faro, A; Farzadfar, F; Fereshtehnejad, S-M; Fernandes, E; Filip, I; Fischer, F; Gebre, AK; Geremew, D; Ghasemi-Kasman, M; Gnedovskaya, EV; Gupta, R; Hachinski, V; Hagos, TB; Hamidi, S; Hankey, GJ; Haro, JM; Hay, SI; Irvani, SSN; Jha, RP; Jonas, JB; Kalani, R; Karch, A; Kasaeian, A; Khader, YS; Khalil, IA; Khan, EA; Khanna, T; Khoja, TAM; Khubchandani, J; Kisa, A; Kissimova-Skarbek, K; Kivimaki, M; Koyanagi, A; Krohn, KJ; Logroscino, G; Lorkowski, S; Majdan, M; Malekzadeh, R; Marz, W; Massano, J; Mengistu, G; Meretoja, A; Mohammadi, M; Mohammadi-Khanaposhtani, M; Mokdad, AH; Mondello, S; Moradi, G; Nagel, G; Naghavi, M; Naik, G; Nguyen, LH; Nguyen, TH; Nirayo, YL; Nixon, MR; Ofori-Asenso, R; Ogbo, FA; Olagunju, AT; Owolabi, MO; Panda-Jonas, S; Passos, VMDA; Pereira, DM; Pinilla-Monsalve, GD; Piradov, MA; Pond, CD; Poustchi, H; Qorbani, M; Radfar, A; Reiner, RC; Robinson, SR; Roshandel, G; Rostami, A; Russ, TC; Sachdev, PS; Safari, H; Safiri, S; Sahathevan, R; Salimi, Y; Satpathy, M; Sawhney, M; Saylan, M; Sepanlou, SG; Shafieesabet, A; Shaikh, MA; Sahraian, MA; Shigematsu, M; Shiri, R; Shiue, I; Silva, JP; Smith, M; Sobhani, S; Stein, DJ; Tabares-Seisdedos, R; Tovani-Palone, MR; Tran, BX; Tran, TT; Tsegay, AT; Ullah, I; Venketasubramanian, N; Vlassov, V; Wang, Y-P; Weiss, J; Westerman, R; Wijeratne, T; Wyper, GMA; Yano, Y; Yimer, EM; Yonemoto, N; Yousefifard, M; Zaidi, Z; Zare, Z; Feigin, VL; Vos, T; Murray, CJL 2019-01-01 Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 BACKGROUND: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists. METHODS: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages). FINDINGS: In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval [UI] 37·8-51·0), increased from 20.2 million (17·4-23·5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0-2·4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3-31·4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1-2·8) deaths. Overall, 28·8 million (95% UI 24·5-34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4-10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages. INTERPRETATION: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide. FUNDING: Bill & Melinda Gates Foundation. Journal Article

Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

2020-11-28T12:39:52Z

Feigin, VL; Nichols, E; Alam, T; Bannick, MS; Beghi, E; Blake, N; Culpepper, WJ; Dorsey, ER; Elbaz, A; Ellenbogen, RG; Fisher, JL; Fitzmaurice, C; Giussani, G; Glennie, L; James, SL; Johnson, CO; Kassebaum, NJ; Logroscino, G; Marin, B; Mountjoy-Venning, WC; Minh, N; Ofori-Asenso, R; Patel, AP; Piccininni, M; Roth, GA; Steiner, TJ; Stovner, LJ; Szoeke, CEI; Theadom, A; Vollset, SE; Wallin, MT; Wright, C; Zunt, JR; Abbasi, N; Abd-Allah, F; Abdelalim, A; Abdollahpour, I; Aboyans, V; Abraha, HN; Acharya, D; Adamu, AA; Adebayo, OM; Adeoye, AM; Adsuar, JC; Afarideh, M; Agrawal, S; Ahmadi, A; Ahmed, MB; Aichour, AN; Aichour, I; Aichour, MTE; Akinyemi, RO; Akseer, N; Al-Eyadhy, A; Salman, RA-S; Alahdab, F; Alene, KA; Aljunid, SM; Altirkawi, K; Alvis-Guzman, N; Anber, NH; Antonio, CAT; Arabloo, J; Aremu, O; Arnlov, J; Asayesh, H; Asghar, RJ; Atalay, HT; Awasthi, A; Ayala Quintanilla, BP; Ayuk, TB; Badawi, A; Banach, M; Banoub, JAM; Barboza, MA; Barker-Collo, SL; Barnighausen, TW; Baune, BT; Bedi, N; Behzadifar, M; Behzadifar, M; Bejot, Y; Bekele, BB; Belachew, AB; Bennett, DA; Bensenor, IM; Berhane, A; Beuran, M; Bhattacharyya, K; Bhutta, ZA; Biadgo, B; Bijani, A; Bililign, N; Bin Sayeed, MS; Blazes, CK; Brayne, C; Butt, ZA; Campos-Nonato, IR; Cantu-Brito, C; Car, M; Cardenas, R; Carrero, JJ; Carvalho, F; Castaneda-Orjuela, CA; Castro, F; Catala-Lopez, F; Cerin, E; Chaiah, Y; Chang, J-C; Chatziralli, I; Chiang, PP-C; Christensen, H; Christopher, DJ; Cooper, C; Cortesi, PA; Costa, VM; Criqui, MH; Crowe, CS; Damasceno, AAM; Daryani, A; De la Cruz-Gongora, V; Pio De la Hoz, F; De Leo, D; Degefa, MG; Demoz, GT; Deribe, K; Dharmaratne, SD; Diaz, D; Dinberu, MT; Djalalinia, S; Doku, DT; Dubey, M; Dubljanin, E; Duken, EE; Edvardsson, D; El-Khatib, Z; Endres, M; Endries, AY; Eskandarieh, S; Esteghamati, A; Esteghamati, S; Farhadi, F; Faro, A; Farzadfar, F; Farzaei, MH; Fatima, B; Fereshtehnejad, S-M; Fernandes, E; Feyissa, GT; Filip, I; Fischer, F; Fukumoto, T; Ganji, M; Gankpe, FG; Garcia-Gordillo, MA; Gebre, AK; Gebremichael, TG; Gelaw, BK; Geleijnse, JM; Geremew, D; Gezae, KE; Ghasemi-Kasman, M; Gidey, MY; Gill, PS; Gill, TK; Gnedovskaya, EV; Goulart, AC; Grada, A; Grosso, G; Guo, Y; Gupta, R; Gupta, R; Haagsma, JA; Hagos, TB; Haj-Mirzaian, A; Haj-Mirzaian, A; Hamadeh, RR; Hamidi, S; Hankey, GJ; Hao, Y; Haro, JM; Hassankhani, H; Hassen, HY; Havmoeller, R; Hay, SI; Hegazy, MI; Heidari, B; Henok, A; Heydarpour, F; Hoang, CL; Hole, MK; Rad, EH; Hosseini, SM; Hu, G; Igumbor, EU; Ilesanmi, OS; Irvani, SSN; Islam, SMS; Jakovljevic, M; Javanbakht, M; Jha, RP; Jobanputra, YB; Jonas, JB; Jozwiak, JJ; Jurisson, M; Kahsay, A; Kalani, R; Kalkonde, Y; Kamil, TA; Kanchan, T; Karami, M; Karch, A; Karimi, N; Kasaeian, A; Kassa, TD; Kassa, ZY; Kaul, A; Kefale, AT; Keiyoro, PN; Khader, YS; Khafaie, MA; Khalil, IA; Khan, EA; Khang, Y-H; Khazaie, H; Kiadaliri, AA; Kiirithio, DN; Kim, AS; Kim, D; Kim, Y-E; Kim, YJ; Kisa, A; Kokubo, Y; Koyanagi, A; Krishnamurthi, RV; Defo, BK; Bicer, BK; Kumar, M; Lacey, B; Lafranconi, A; Lansingh, VC; Latifi, A; Leshargie, CT; Li, S; Liao, Y; Linn, S; Lo, WD; Lopez, JCF; Lorkowski, S; Lotufo, PA; Lucas, RM; Lunevicius, R; Mackay, MT; Mahotra, NB; Majdan, M; Majdzadeh, R; Majeed, A; Malekzadeh, R; Malta, DC; Manafi, N; Mansournia, MA; Mantovani, LG; Marz, W; Mashamba-Thompson, TP; Massenburg, BB; Mate, KKV; McAlinden, C; McGrath, JJ; Mehta, V; Meier, T; Meles, HG; Melese, A; Memiah, PTN; Memish, ZA; Mendoza, W; Mengistu, DT; Mengistu, G; Meretoja, A; Meretoja, TJ; Mestrovic, T; Miazgowski, B; Miazgowski, T; Miller, TR; Mini, GK; Mirrakhimov, EM; Moazen, B; Mohajer, B; Mezerji, NMG; Mohammadi, M; Mohammadi-Khanaposhtani, M; Mohammadibakhsh, R; Mohammadnia-Afrouzi, M; Mohammed, S; Mohebi, F; Mokdad, AH; Monasta, L; Mondello, S; Moodley, Y; Moosazadeh, M; Moradi, G; Moradi-Lakeh, M; Moradinazar, M; Moraga, P; Velasquez, IM; Morrison, SD; Mousavi, SM; Muhammed, OS; Muruet, W; Musa, KI; Mustafa, G; Naderi, M; Nagel, G; Naheed, A; Naik, G; Najafi, F; Nangia, V; Negoi, I; Negoi, RI; Newton, CRJ; Ngunjiri, JW; Nguyen, CT; Nguyen, LH; Ningrum, DNA; Nirayo, YL; Nixon, MR; Norrving, B; Noubiap, JJ; Shiadeh, MN; Nyasulu, PS; Ogbo, FA; Oh, I-H; Olagunju, AT; Olagunju, TO; Olivares, PR; Onwujekwe, OE; Oren, E; Owolabi, MO; Mahesh, PA; Pakpour, AH; Pan, W-H; Panda-Jonas, S; Pandian, JD; Patel, SK; Pereira, DM; Petzold, M; Pillay, JD; Piradov, MA; Polanczyk, GV; Polinder, S; Postma, MJ; Poulton, R; Poustchi, H; Prakash, S; Prakash, V; Qorbani, M; Radfar, A; Rafay, A; Rafiei, A; Rahim, F; Rahimi-Movaghar, V; Rahman, M; Rahman, MHU; Rahman, MA; Rajati, F; Ram, U; Ranta, A; Rawaf, DL; Rawaf, S; Reinig, N; Reis, C; Renzaho, AMN; Resnikoff, S; Rezaeian, S; Rezai, MS; Gonzalez, CMR; Roberts, NLS; Roever, L; Ronfani, L; Roro, EM; Roshandel, G; Rostami, A; Sabbagh, P; Sacco, RL; Sachdev, PS; Saddik, B; Safari, H; Safari-Faramani, R; Safi, S; Safiri, S; Sagar, R; Sahathevan, R; Sahebkar, A; Sahraian, MA; Salamati, P; Zahabi, SS; Salimi, Y; Samy, AM; Sanabria, J; Santos, IS; Milicevic, MMS; Sarrafzadegan, N; Sartorius, B; Sarvi, S; Sathian, B; Satpathy, M; Sawant, AR; Sawhney, M; Schneider, IJC; Schottker, B; Schwebel, DC; Seedat, S; Sepanlou, SG; Shabaninejad, H; Shafieesabet, A; Shaikh, MA; Shakir, RA; Shams-Beyranvand, M; Shamsizadeh, M; Sharif, M; Sharif-Alhoseini, M; She, J; Sheikh, A; Sheth, KN; Shigematsu, M; Shiri, R; Shirkoohi, R; Shiue, I; Siabani, S; Siddiqi, TJ; Sigfusdottir, ID; Sigurvinsdottir, R; Silberberg, DH; Silva, JP; Silveira, DGA; Singh, JA; Sinha, DN; Skiadaresi, E; Smith, M; Sobaih, BH; Sobhani, S; Soofi, M; Soyiri, IN; Sposato, LA; Stein, DJ; Stein, MB; Stokes, MA; Sufiyan, MB; Sykes, BL; Sylaja, P; Tabares-Seisdedos, R; Ao, BJT; Tehrani-Banihashemi, A; Temsah, M-H; Temsah, O; Thakur, JS; Thrift, AG; Topor-Madry, R; Tortajada-Girbes, M; Tovani-Palone, MR; Tran, BX; Tran, KB; Truelsen, TC; Tsadik, AG; Car, LT; Ukwaja, KN; Ullah, I; Usman, MS; Uthman, OA; Valdez, PR; Vasankari, TJ; Vasanthan, R; Veisani, Y; Venketasubramanian, N; Violante, FS; Vlassov, V; Vosoughi, K; Vu, GT; Vujcic, IS; Wagnew, FS; Waheed, Y; Wang, Y-P; Weiderpass, E; Weiss, J; Whiteford, HA; Wijeratne, T; Winkler, AS; Wiysonge, CS; Wolfe, CDA; Xu, G; Yadollahpour, A; Yamada, T; Yano, Y; Yaseri, M; Yatsuya, H; Yimer, EM; Yip, P; Yisma, E; Yonemoto, N; Yousefifard, M; Yu, C; Zaidi, Z; Bin Zaman, S; Zamani, M; Zandian, H; Zare, Z; Zhang, Y; Zodpey, S; Naghavi, M; Murray, CJL; Vos, T 2019-05-01 Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 BACKGROUND: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. METHODS: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. FINDINGS: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247-308]) and second leading cause of deaths (9·0 million [8·8-9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34-44] and DALYs by 15% [9-21]) whereas their age-standardised rates decreased (deaths by 28% [26-30] and DALYs by 27% [24-31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6-46·1]), migraine (16·3% [11·7-20·8]), Alzheimer's and other dementias (10·4% [9·0-12·1]), and meningitis (7·9% [6·6-10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05-1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5-90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8-35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8-17·5] of DALYs are risk attributable). INTERPRETATION: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. FUNDING: Bill & Melinda Gates Foundation. Journal Article

Patient and clinician engagement with health information in the primary care waiting room: A mixed methods case study

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Woodward-Kron, R; Penry Williams, C; Elliott, K; Gall, J 2019-03-12 Patient and clinician engagement with health information in the primary care waiting room: A mixed methods case study Background. Primary care waiting rooms can be sites of health promotion and health literacy development through the provision of readily accessible health information. To date, few studies have considered patient engagement with televised health messages in the waiting room, nor have studies investigated whether patients ask their clinicians about this information. The aim of this study was therefore to examine patient (or accompanying person) and clinician engagement with waiting room health information, including televised health messages. Design and methods. The mixed methods case study was undertaken in a regional general practice in Victoria, Australia, utilising patient questionnaires, waiting room observations, and clinician logbooks and interviews. The qualitative data were analysed by content analysis; the questionnaire data were analysed using descriptive statistics. Results. Patients engaged with a range of health information in the waiting room and reportedly received health messages from this information. 44% of the questionnaire respondents (33 of 74) reported watching the television health program, and half of these reported receiving a take home health message from this source. Only one of the clinicians (N=9) recalled a patient asking about the televised health program. Conclusions. The general practice waiting room remains a site where people engage with the available health information, with a televised health 'infotainment' program receiving most attention from patients. Our study showed that consumption of health information was primarily passive and tended not to activate patient discussions with clinicians. Future studies could investigate any link between the health infotainment program and behaviour change. Journal Article

Nursing Research Priorities in Critical Care, Pulmonary, and Sleep: International Delphi Survey of Nurses, Patients, and Caregivers An Official American Thoracic Society Workshop Report

2020-11-28T12:39:52Z

George, M; Hernandez, C; Smith, S; Narsavage, G; Kapella, MC; Carno, M; Guttormson, J; Disler, RT; Hart, DE; Chlan, LL; Happ, MB; Chen, Z; Hetland, B; Hutchinson, AF; Jonsdottir, H; Redeker, NS; Schell-Chaple, H; Fletcher, M; Yorke, J 2020-01-01 Nursing Research Priorities in Critical Care, Pulmonary, and Sleep: International Delphi Survey of Nurses, Patients, and Caregivers An Official American Thoracic Society Workshop Report The objective of this workshop was to determine current nursing research priorities in critical care, adult pulmonary, and sleep conditions through input from consumer (patient, family, and formal and informal caregivers) and nursing experts around the world. Working groups composed of nurses and patients selected potential research priorities based on patient insight and a literature review of patient-reported outcomes, patient-reported experiences, and processes and clinical outcomes in the focal areas. A Delphi consensus approach, using a qualitative survey method to elicit expert opinion from nurses and consumers was conducted. Two rounds of online surveys available in English, Spanish, and Chinese were completed. A 75% or greater threshold for endorsement (combined responses from nursing and consumer participants) was determined a priori to retain survey items. A total of 837 participants (649 nurses and 188 patients, family, and/or caregivers) from 45 countries responded. Survey data were analyzed and nursing research priorities that comprise 23 critical care, 45 adult pulmonary, and 16 sleep items were identified. This project was successful in engaging a wide variety of nursing and consumer experts, applying a patient-reported outcome/patient-reported experience framework for organizing and understanding research priorities. The project outcome was a research agenda to inform, guide, and aid nurse scientists, educators, and providers, and to advise agencies that provide research and program funding in these fields. Journal Article

CAPTEM in Metastatic Well-Differentiated Intermediate to High Grade Neuroendocrine Tumors: A Single Centre Experience

2020-11-28T12:39:52Z

Sahu, A; Jefford, M; Lai-Kwon, J; Thai, A; Hicks, RJ; Michael, M 2019-01-01 CAPTEM in Metastatic Well-Differentiated Intermediate to High Grade Neuroendocrine Tumors: A Single Centre Experience Introduction: Capecitabine-temozolomide (CAPTEM) has significant activity in patients (pts) with metastatic low grade pancreatic neuroendocrine tumors (NETs). However, there is limited data regarding its activity in pts with metastatic well-differentiated intermediate and high grade pancreatic and nonpancreatic NETs. The objective of this study was to assess the functional imaging response, survival, and tolerability of CAPTEM in this population. Methods: A retrospective audit of pts with metastatic well-differentiated intermediate (WHO grade 2) or high grade (WHO grade 3) NETs treated at Peter MacCallum Cancer Centre between March 2013 and March 2017. Pts received capecitabine 750 mg/m2 orally twice daily (bd) from days1 to 14 and temozolomide 100 mg/m2 bd from days 10 to 14 every 28 days. Data regarding functional imaging response, progression-free and overall survival, and toxicities was collected. Results: Thirty-two pts received a median of 6 cycles (range: 2-16) of CAPTEM for grade 2 (n=21, 66%) or grade 3 (n=11, 34%), Ki67 <55% (n= 7, 21.9%) or Ki67 ≥55% (n= 4, 12.5 %) NET. Primary site included gastroenteropancreatic (n= 17, 53%), lung (n= 12, 37.5%), and unknown origin (n = 3, 9.4%). Twenty-two percent received CAPTEM as first-line therapy. After a median of 31 months of follow-up, the two-year overall survival (OS) was 42%, with a median OS of 24 months. There was a trend towards improved median progression-free survival (PFS) in pts with low grade 3 (Ki67<55%) versus high grade 3 (Ki67 ≥55%) NETs (15 vs 4 months, p= 0.11). Ten (31.3%) experienced grade 3/4 toxicity, with nausea (15.6%), thrombocytopaenia (12.5%), and fatigue (9.4%) the most common toxicities reported. Conclusion: CAPTEM has significant activity in patients with metastatic grades 2 and 3 NETs with manageable toxicity. The PFS benefit observed in the grade 3 subgroup with Ki67<55% warrants further evaluation in a larger randomized trial. Journal Article

Remote health workforce turnover and retention: what are the policy and practice priorities?

2020-11-28T12:39:52Z

Wakerman, J; Humphreys, J; Russell, D; Guthridge, S; Bourke, L; Dunbar, T; Zhao, Y; Ramjan, M; Murakami-Gold, L; Jones, MP 2019-12-16 Remote health workforce turnover and retention: what are the policy and practice priorities? BACKGROUND: Residents of remote communities in Australia and other geographically large countries have comparatively poorer access to high-quality primary health care. To inform ongoing policy development and practice in relation to remote area health service delivery, particularly in remote Indigenous communities, this review synthesizes the key findings of (1) a comprehensive study of workforce turnover and retention in remote Northern Territory (NT) of Australia and (2) a narrative review of relevant international literature on remote and rural health workforce retention strategies. This synthesis provides a valuable summary of the current state of international knowledge about improving remote health workforce retention. MAIN TEXT: Annual turnover rates of NT remote area nurses (148%) and Aboriginal health practitioners (80%) are very high and 12-month stability rates low (48% and 76%, respectively). In remote NT, use of agency nurses has increased substantially. Primary care costs are high and proportional to staff turnover and remoteness. Effectiveness of care decreases with higher turnover and use of short-term staff, such that higher staff turnover is always less cost-effective. If staff turnover in remote clinics were halved, the potential savings would be approximately A$32 million per annum. Staff turnover and retention were affected by management style and effectiveness, and employment of Indigenous staff. Review of the international literature reveals three broad themes: Targeted enrolment into training and appropriate education designed to produce a competent, accessible, acceptable and 'fit-for-purpose' workforce; addressing broader health system issues that ensure a safe and supportive work environment; and providing ongoing individual and family support. Key educational initiatives include prioritising remote origin and Indigenous students for university entry; maximising training in remote areas; contextualising curricula; providing financial, pedagogical and pastoral support; and ensuring clear, supported career pathways and continuing professional development. Health system initiatives include ensuring adequate funding; providing adequate infrastructure including fit-for-purpose clinics, housing, transport and information technology; offering flexible employment arrangements whilst ensuring a good 'fit' between individual staff and the community (especially with regard to cultural skills); optimising co-ordination and management of services that empower staff and create positive practice environments; and prioritising community participation and employment of locals. Individual and family supports include offering tailored financial incentives, psychological support and 'time out'. CONCLUSION: Optimal remote health workforce stability and preventing excessive 'avoidable' turnover mandates alignment of government and health authority policies with both health service requirements and individual health professional and community needs. Supportive underpinning policies include: Strong intersectoral collaboration between the health and education sectors to ensure a fit-for-purpose workforce;A funding policy which mandates the development and implementation of an equitable, needs-based formula for funding remote health services;Policies that facilitate transition to community control, prioritise Indigenous training and employment, and mandate a culturally safe work context; andAn employment policy which provides flexibility of employment conditions in order to be able to offer individually customised retention packages There is considerable extant evidence from around the world about effective retention strategies that contribute to slowing excessive remote health workforce turnover, resulting in significant cost savings and improved continuity of care. The immediate problem comprises an 'implementation gap' in translating empirical research evidence into actions designed to resolve existing problems. If we wish to ameliorate the very high turnover of staff in remote areas, in order to provide an equitable service to populations with arguably the highest health needs, we need political and executive commitment to get the policy settings right and ensure the coordinated implementation of multiple strategies, including better linking existing strategies and 'filling the gaps' where necessary. Journal Article

The role of stigma in the acceptance and disclosure of HIV among recently diagnosed men who have sex with men in Australia: A qualitative study

2020-11-28T12:39:52Z

Bilardi, JE; Hulme-Chambers, A; Chen, MY; Fairley, CK; Huffam, SE; Tomnay, JE 2019-11-08 The role of stigma in the acceptance and disclosure of HIV among recently diagnosed men who have sex with men in Australia: A qualitative study BACKGROUND: Our primary study aimed to explore the experiences of men who have sex with men (MSM) recently diagnosed with HIV and their partner notification practices. Themes relating to acceptance, and disclosure of, their HIV status strongly emerged during analysis in our larger study and are reported separately here. METHOD: Fifteen MSM participated in semi-structured interviews by phone or face to face about their experience of a recent HIV diagnosis. In this paper we report on how they received and accepted the diagnosis, who they disclosed their diagnosis to and what is needed to improve support for MSM recently diagnosed with HIV. RESULTS: MSM's reactions to their HIV diagnosis ranged from shock, devastation and anger to a calm acceptance and feeling HIV would not have a significant impact on their lives. MSM who reported strong social support networks, or knew others with HIV, seemed better able to cope with and accept their diagnosis than those with fewer support networks. Due to prevailing stigma around HIV, most MSM were very selective about who they disclosed their status to, often only telling partners perceived to be at risk but no, or only few, close friends. Regardless of how well men accepted their diagnosis, most did not disclose their status to family members for fear of rejection or causing distress due to ideologies based on outdated information about HIV. CONCLUSION: The prevailing stigma around HIV can have a significant impact on MSM's acceptance of, and willingness to disclose their HIV serostatus to others, and consequently the levels of professional and social support they receive. HIV-related stigma needs to be addressed through community campaigns which better educate the wider population about the current state of HIV prognosis and treatment. Journal Article

Implementation of an older person's nurse practitioner in rural aged care in Victoria, Australia: a qualitative study

2020-11-28T12:39:52Z

Ervin, K; Reid, C; Moran, A; Opie, C; Haines, H 2019-11-01 Implementation of an older person's nurse practitioner in rural aged care in Victoria, Australia: a qualitative study BACKGROUND: There are staff shortages nation-wide in residential aged care, which is only predicted to grow as the population ages in Australia. The aged care staff shortage is compounded in rural and remote areas where the health service workforce overall experiences difficulties in recruitment and retention. There is evidence that nurse practitioners fill important service gaps in aged care and rural health care but also evidence that barriers exist in introducing this extended practice role. METHODS: In 2018, 58 medical and direct care staff participated in interviews and focus groups about the implementation of an older person's nurse practitioner (OPNP) in aged care. All 58 interviewees had previously or currently worked in an aged care setting where the OPNP delivered services. The interviews were analysed using May's implementation theory framework to better understand staff perceptions of barriers and enablers when an OPNP was introduced to the workplace. RESULTS: The major perceived barrier to capacity of implementing the OPNP was a lack of material resources, namely funding of the role given the OPNP's limited ability to self-fund through access to the Medicare Benefits Schedule (MBS). Staff perceived that benefits included timely access to care for residents, hospital avoidance and improved resident health outcomes. CONCLUSION: Despite staff perceptions of more timely access to care for residents and improved outcomes, widespread implementation of the OPNP role may be hampered by a poor understanding of the role of an OPNP and the legislative requirement for a collaborative arrangement with a medical practitioner as well as limited access to the MBS. This study was not a registered trial. Journal Article

Stroke in malignancy: complexities of diagnosis and management: a case report.

2020-11-28T12:39:52Z

Siriratnam, P; Kraemer, T; Sahathevan, R 2019-08-20 Stroke in malignancy: complexities of diagnosis and management: a case report. BACKGROUND: Although there is an established association between cancer and stroke, the role of malignancy as a causative agent or comorbidity is not always clear. Moreover, there are no established guidelines on the acute treatment of cancer-associated stroke or optimal anticoagulation. This case report illustrates the significance of these practice gaps. CASE PRESENTATION: A 62-year-old Caucasian woman presented to our institute with acute neurological deficits and was found to have an occluded left middle cerebral artery on a computed tomographic angiogram. She was administered intravenous alteplase and underwent unsuccessful endovascular clot retrieval. Besides smoking and her age, she had no cerebrovascular risk factors, and the results of baseline investigations for the cause of stroke were negative. Subsequent computed tomography of the chest, abdomen, and pelvis showed metastatic malignancy, and in the context of a significantly elevated serum cancer antigen 19-9, we suspected a pancreatic primary cancer. A transthoracic echocardiogram demonstrated mitral regurgitation but no visible vegetation. The patient died of her illness. We made a diagnosis of cancer-associated stroke, specifically a likely case of nonbacterial thrombotic endocarditis. CONCLUSIONS: This case highlights the importance of having a high threshold of suspicion for malignancy as a cause of stroke. Journal Article

Structural equation modeling the "control of gut overgrowth" in the prevention of ICU-acquired Gram-negative infection

2020-11-28T12:39:52Z

Hurley, JC 2020-05-04 Structural equation modeling the "control of gut overgrowth" in the prevention of ICU-acquired Gram-negative infection BACKGROUND: Conceptually, the "control of gut overgrowth" (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. METHODS: Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups. RESULTS: In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. CONCLUSIONS: Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis. Journal Article

Chronically stimulated human MAIT cells are unexpectedly potent IL-13 producers

2020-11-28T12:39:52Z

Kelly, J; Minoda, Y; Meredith, T; Cameron, G; Philipp, M-S; Pellicci, DG; Corbett, AJ; Kurts, C; Gray, DHD; Godfrey, D; Kannourakis, G; Berzins, SP 2019-07-19 Chronically stimulated human MAIT cells are unexpectedly potent IL-13 producers Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize antigens derived from riboflavin biosynthesis. In addition to anti-microbial functions, human MAIT cells are associated with cancers, autoimmunity, allergies and inflammatory disorders, although their role is poorly understood. Activated MAIT cells are well known for their rapid release of Th1 and Th17 cytokines, but we have discovered that chronic stimulation can also lead to potent interleukin (IL)-13 expression. We used RNA-seq and qRT-PCR to demonstrate high expression of the IL-13 gene in chronically stimulated MAIT cells, and directly identify IL-13 using intracellular flow cytometry and multiplex bead analysis of MAIT cell cultures. This unexpected finding has important implications for IL-13-dependent diseases, such as colorectal cancer (CRC), that occur in mucosal areas where MAIT cells are abundant. We identify MAIT cells near CRC tumors and show that these areas and precancerous polyps express high levels of the IL-13 receptor, which promotes tumor progression and metastasis. Our data suggest that MAIT cells have a more complicated role in CRC than currently realized and that they represent a promising new target for immunotherapies where IL-13 can be a critical factor. Journal Article

Anticancer therapy within the last 30 days of life: results of an audit and re-audit cycle from an Australian regional cancer centre

2020-11-28T12:39:52Z

Nguyen, M; Kin, SNY; Shum, E; Wann, A; Tamjid, B; Sahu, A; Torres, J 2020-01-27 Anticancer therapy within the last 30 days of life: results of an audit and re-audit cycle from an Australian regional cancer centre BACKGROUND: The therapeutic landscape in medical oncology continues to expand significantly. Newer therapies, especially immunotherapy, offer the hope of profound and durable responses with more tolerable side effect profiles. Integrating this information into the decision making process is challenging for patients and oncologists. Systemic anticancer treatment within the last thirty days of life is a key quality of care indicator and is one parameter used in the assessment of aggressiveness of care. METHODS: A retrospective review of medical records of all patients previously treated at Goulburn Valley Health oncology department who died between 1 January 2015 and 30 June 2018 was conducted. Information collected related to patient demographics, diagnosis, treatment, and hospital care within the last 30 days of life. These results were presented to the cancer services meeting and a quality improvement intervention program was instituted. A second retrospective review of medical records of all patients who died between 1 July 2018 and 31 December 2018 was conducted in order to measure the effect of this intervention. RESULTS: The initial audit period comprised 440 patients. 120 patients (27%) received treatment within the last 30 days of life. The re-audit period comprised 75 patients. 19 patients (25%) received treatment within the last 30 days of life. Treatment rates of chemotherapy reduced after the intervention in contrast to treatment rates of immunotherapy which increased. A separate analysis calculated the rate of mortality within 30 days of chemotherapy from the total number of patients who received chemotherapy was initially 8% and 2% in the re-audit period. Treatment within the last 30 days of life was associated with higher use of aggressive care such as emergency department presentation, hospitalisation, ICU admission and late hospice referral. Palliative care referral rates improved after the intervention. CONCLUSION: This audit demonstrated that a quality improvement intervention can impact quality of care indicators with reductions in the use of chemotherapy within the last 30 days of life. However, immunotherapy use increased which may be explained by increased access and a better risk benefit balance. Journal Article

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

2020-11-28T12:39:52Z

Ahmed, N; Kadife, E; Raza, A; Short, M; Jubinsky, PT; Kannourakis, G 2020-03-01 Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease. Journal Article

The Role of Fibroblast Growth Factor 10 Signaling in Duodenal Atresia

2020-11-28T12:39:52Z

Jones, MLM; Sarila, G; Chapuis, P; Hutson, JM; King, SK; Teague, WJ 2020-03-10 The Role of Fibroblast Growth Factor 10 Signaling in Duodenal Atresia Introduction: Duodenal atresia (DA) is a congenital bowel obstruction requiring major surgery in the first week of life. Three morphological phenotypes are described, reflecting increasing degrees of obstruction and discontinuity of the duodenum. The cause of DA is not known. Tandler's original "solid cord" hypothesis conflicts with recent biological evidence, and is unable to account for differing DA types. In humans, a genetic etiology is supported by the association between Trisomy 21 and DA, and reports of familial inheritance patterns. Interruption of FGF10/FGFR2b signaling is the best demonstrated genetic link to DA in mice, with 35-75% of homozygous knockout embryos developing DA. Purpose: This review examines the current evidence surrounding the etiology of DA. We focus on research regarding FGF10/FGFR2b signaling and its role in duodenal and other intestinal atresia. Further, we outline planned future research in this area, that we consider necessary to validate and better understand this murine model in order to successfully translate this research into clinical practice. Conclusion: Determining the etiology of DA in humans is a clinical and scientific imperative. Fgf10/Fgfr2b murine models represent current science's best key to unlocking this mystery. However, further research is required to understand the complex role of FGF10/FGFR2b signaling in DA development. Such complexity is expected, given the lethality of their associated defects makes ubiquitous interruption of either Fgf10 or Fgfr2b genes an unlikely cause of DA in humans. Rather, local or tissue-specific mutation in Fgf10, Fgfr2b, or their downstream targets, is the hypothesized basis of DA etiology. Journal Article

Cross-sectional changes in weight status and weight related behaviors among Australian children and Australian Indigenous children between 2010 and 2015.

2020-11-28T12:39:52Z

Hardy, LL; MacNiven, R; Esgin, T; Mihrshahi, S 2019 Cross-sectional changes in weight status and weight related behaviors among Australian children and Australian Indigenous children between 2010 and 2015. BACKGROUND: Since 2006 there has been substantial long-term investment in school-based child obesity prevention programs in New South Wales (Australia). Whether these programs have led to population level improvements in children's weight status and weight-related behaviors are yet to be determined. The purpose of this study was to describe changes in children's weight status and weight-related behaviors, including Indigenous children, who are at greater risk of poorer health outcomes than non-Indigenous children. METHODS: Representative cross-sectional population surveys conducted in 2010 and 2015 among children age 5-16 years (n = 15,613). Objective measurements included height, weight, waist circumference, cardiorespiratory fitness, and fundamental movement skills. Indigenous status and indicators of weight-related behavior (i.e., diet, physical activity, school travel, screen-time) were measured by questionnaire with parents responding for children age <10 years and self-report by children age ≥10 years. RESULTS: The prevalences of overweight/obesity, obesity and abdominal obesity were higher in 2015, than 2010, and higher among Indigenous than non-Indigenous children at both timepoints. There were some small positive changes towards healthier weight-related behaviors between surveys among all children, but many unhealthy weight-related behaviors remain highly prevalent. The magnitude of changes and the 2015 prevalences of weight-related behaviors were generally similar for Indigenous and non-Indigenous children. CONCLUSIONS: Schools play an important role in health promotion, but our findings suggest the current approaches need re-thinking. Upstream factors that shape weight-related behaviors such as the regulation of the food industry and food environment, urban, neighborhood and public transport planning must be including in solutions to ensure populations can eat healthily and be physical active. Journal Article

Exploring the role-based challenges of providing culturally inclusive health care for maternal and child health nurses: Qualitative findings

2020-11-28T12:39:52Z

Malatzky, C; Shaburdin, ZM; Bourke, L 2020-05-01 Exploring the role-based challenges of providing culturally inclusive health care for maternal and child health nurses: Qualitative findings Aims: To explore how maternal and child health nurses (MCHNs) working in a specific regionally located service perceive and experience delivering health care to a diverse population. Design: Qualitative exploratory study. Methods: Qualitative interviews were conducted with MCHNs (N = 6) working in a particular regionally located service. Data were selectively coded, categorized and interpreted through a process of argument writing influenced by poststructuralist thought and Foucauldian conceptualizations of power. Results: The data analysed were interpreted into the following categories: (a) system-level expectations of the maternal and child health role; (b) what these system-level expectations mean for the role and practice of MCHNs; and (c) what MCHNs themselves report prioritizing in their work. The analysis suggests that a substantial hindrance to the development and support of culturally safe, inclusive and quality maternal and child health care lies in the very ways contemporary health institutions seek to discipline the routine practices of MCHNs. Journal Article

Clinical data and Pediatric Quality of Life Inventory (PedsQL (TM)) scores for children with duodenal atresia

2020-11-28T12:39:52Z

Vinycomb, TI; Browning, A; Jones, MLM; Hutson, JM; King, SK; Teague, WJ 2020-04-01 Clinical data and Pediatric Quality of Life Inventory (PedsQL (TM)) scores for children with duodenal atresia This article presents raw data obtained from a prospectively collected database of children with duodenal atresia at tertiary pediatric surgery hospital. For all potential participants, pertinent demographic, clinical and operative data was obtained from the database. Potential participants were then contacted and invited to complete a Pediatric Quality of Life Inventory (PedsQL™) 4.0 core score and gastrointestinal module questionnaires. Participant's response to each item in the questionnaires is provided, as well as their calculated health related quality of life scores. Data has the potential to be reused in future studies examining quality of life in duodenal atresia, paediatric gastrointestinal conditions, surgical neonatal conditions and children with trisomy 21. Further analysis and discussion is contained in related research article titled "Quality of life outcomes in children born with duodenal atresia" [1]. Journal Article

Context Matters: Findings from a Qualitative Study Exploring Service and Place Factors Influencing the Recruitment and Retention of Allied Health Professionals in Rural Australian Public Health Services

2020-11-28T12:39:52Z

Cosgrave, C 2020-08-01 Context Matters: Findings from a Qualitative Study Exploring Service and Place Factors Influencing the Recruitment and Retention of Allied Health Professionals in Rural Australian Public Health Services Chronic health workforce shortages significantly contribute to unmet health care needs in rural and remote communities. Of particular and growing concern are shortages of allied health professionals (AHPs). This study explored the contextual factors impacting the recruitment and retention of AHPs in rural Australia. A qualitative approach using a constructivist-interpretivist methodology was taken. Semi-structured interviews (n = 74) with executive staff, allied health (AH) managers and newly recruited AHPs working in two rural public health services in Victoria, Australia were conducted. Data was coded and categorised inductively and analysed thematically. The findings suggest that to support a stable and sustainable AH workforce, rural public sector health services need to be more efficient, strategic and visionary. This means ensuring that policies and procedures are equitable and accessible, processes are effective, and action is taken to develop local programs, opportunities and supports that allow AH staff to thrive and grow in place at all grade levels and life stages. This study reinforces the need for a whole-of-community approach to effectively support individual AH workers and their family members in adjusting to a new place and developing a sense of belonging in place. The recommendations arising from this study are likely to have utility for other high-income countries, particularly in guiding AH recruitment and retention strategies in rural public sector health services. Recommendations relating to community/place will likely benefit broader rural health workforce initiatives. Journal Article

A Role for MAIT Cells in Colorectal Cancer

2020-11-28T12:39:52Z

Berzins, SP; Wallace, ME; Kannourakis, G; Kelly, J 2020-05-20 A Role for MAIT Cells in Colorectal Cancer MAIT cells are MR1-restricted T cells that are well-known for their anti-microbial properties, but they have recently been associated with different forms of cancer. Several studies have reported activated MAIT cells within the microenvironment of colorectal tumors, but there is conjecture about the nature of their response and whether they are contributing to anti-tumor immunity, or to the progression of the disease. We have reviewed the current state of knowledge about the role of MAIT cells in colorectal cancer, including their likely influence when activated and potential sources of stimulation in the tumor microenvironment. The prospects for MAIT cells being used in clinical settings as biomarkers or as targets of new immunotherapies designed to harness their function are discussed. Journal Article

The Whole-of-Person Retention Improvement Framework: A Guide for Addressing Health Workforce Challenges in the Rural Context

2020-11-28T12:39:52Z

Cosgrave, C 2020-04-01 The Whole-of-Person Retention Improvement Framework: A Guide for Addressing Health Workforce Challenges in the Rural Context People living in rural places face unique challenges due to their geographic isolation and often experience poorer health outcomes compared to people living in major cities. The struggle to attract and retain an adequately-sized and skilled health workforce is a major contributing factor to these health inequities. Health professionals' decisions to stay or leave a rural position are multifaceted involving personal, organisational, social and spatial aspects. While current rural health workforce frameworks/models recognise the multidimensional and interrelated influences on retention, they are often highly complex and do not easily support the development of strategic actions. An accessible evidence-informed framework that addresses the complexity but presents the evidence in a manner that is straightforward and supports the development of targeted evidence- and place-informed retention strategies is required. The 'Whole-of-Person Retention Improvement Framework' (WoP-RIF) has three domains: Workplace/Organisational, Role/Career and Community/Place. The necessary pre-conditions for improving retention through strengthening job and personal satisfaction levels are set out under each domain. The WoP-RIF offers a person-centred, holistic structure that encourages whole-of-community responses that address individual and workforce level needs. It is a significant response to, and resource for, addressing avoidable rural health workforce turnover that rural health services and communities can harness in-place. Journal Article

Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CES-D and HAD-D Scales

2020-11-28T12:39:52Z

Covic, T; Pallant, JF; Tennant, A; Cox, S; Emery, P; Conaghan, PG 2009-02-07 Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CES-D and HAD-D Scales BACKGROUND: Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression. METHODS: Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression. RESULTS: Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D. CONCLUSION: The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates. Journal Article