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    The association between nutritional adequacy and 28-day mortality in the critically ill is not modified by their baseline nutritional status and disease severity
    (BMC, 2019-06-18) Lew, Charles Chin Han; Wong, Gabriel Jun Yung; Cheung, Ka Po; Fraser, Robert J L; Chua, Ai Ping; Chong, Mary Foong Fong; Miller, Michelle Deanne
    BACKGROUND: During the initial phase of critical illness, the association between the dose of nutrition support and mortality risk may vary among patients in the intensive care unit (ICU) because the prevalence of malnutrition varies widely (28 to 78%), and not all ICU patients are severely ill. Therefore, we hypothesized that a prognostic model that integrates nutritional status and disease severity could accurately predict mortality risk and classify critically ill patients into low- and high-risk groups. Additionally, in critically ill patients placed on exclusive nutritional support (ENS), we hypothesized that their risk categories could modify the association between dose of nutrition support and mortality risk. METHODS: A prognostic model that predicts 28-day mortality was built from a prospective cohort study of 440 patients. The association between dose of nutrition support and mortality risk was evaluated in a subgroup of 252 mechanically ventilated patients via logistic regressions, stratified by low- and high-risk groups, and days of exclusive nutritional support (ENS) [short-term (≤ 6 days) vs. longer-term (≥ 7 days)]. Only the first 6 days of ENS was evaluated for a fair comparison. RESULTS: The prognostic model demonstrated good discrimination [AUC 0.78 (95% CI 0.73–0.82), and a bias-corrected calibration curve suggested fair accuracy. In high-risk patients with short-term ENS (≤ 6 days), each 10% increase in goal energy and protein intake was associated with an increased adjusted odds (95% CI) of 28-day mortality [1.60 (1.19–2.15) and 1.47 (1.12–1.86), respectively]. In contrast, each 10% increase in goal protein intake during the first 6 days of ENS in high-risk patients with longer-term ENS (≥ 7 days) was associated with a lower adjusted odds of 28-day mortality [0.75 (0.57–0.99)]. Despite the opposing associations, the mean predicted mortality risks and prevalence of malnutrition between short- and longer-term ENS patients were similar. CONCLUSIONS: Combining baseline nutritional status and disease severity in a prognostic model could accurately predict 28-day mortality. However, the association between the dose of nutrition support during the first 6 days of ENS and 28-day mortality was independent of baseline disease severity and nutritional status.
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    Interagency collaboration in primary mental health care: lessons from the Partners in Recovery program
    (BMC, 2019-05-31) Henderson, Julie Anne; Javanparast, Sara; Baum, Fran; Freeman, Toby; Fuller, Jeffrey; Ziersch, Anna Marie; Mackean, Tamara Jade
    BACKGROUND: Collaborative care is a means of improving outcomes particularly for people with complex needs. The Partners in Recovery (PIR) program, established in Australia in 2012, provides care coordination to facilitate access to health and social support services for people with severe and persistent mental illness. Of the 48 PIR programs across Australia, 35 were led by Medicare Locals, the previous Australian regional primary health care organisation and nine involved Medicare Locals as partner organisations. AIMS: To identify features which enabled and hindered collaboration in PIR programs involving Medicare Locals and determine what can be learnt about delivering care to this population. METHODS: Data were collected from 50 interviews with senior staff at Medicare Locals and from eight focus groups with 51 mental health stakeholders in different Australian jurisdictions. RESULTS: Successful PIR programs were based upon effective collaboration. Collaboration was facilitated by dedicated funding, a shared understanding of PIR aims, joint planning, effective network management, mutual respect and effective communication. Collaboration was also enhanced by the local knowledge and population health planning functions of Medicare Locals. Jurisdictional boundaries and funding discontinuity were the primary barriers to collaboration.
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    A South African experience in applying the Adopt–Contextualise–Adapt framework to stroke rehabilitation clinical practice guidelines
    (BMC, 2019-06-06) Grimmer, K A; Louw, Quinette; Dizon, Janine M; Brown, Sjan-Mari; Ernstzen, Dawn; Wiysonge, Charles S
    BACKGROUND: Clinical practice guideline (CPG) activity has escalated internationally in the last 20 years, leading to increasingly sophisticated methods for CPG developers and implementers. Despite this, there remains a lack of practical support for end-users in terms of effectively and efficiently implementing CPG recommendations into local practice. This paper describes South African experiences in implementing international CPG recommendations for best practice stroke rehabilitation into local contexts, using a purpose-build approach. METHODS: Composite recommendations were synthesised from 16 international CPGs to address end-user questions about best practice rehabilitation for South African stroke survivors. End-user representatives on the project team included methodologists, policy-makers, clinicians, managers, educators, researchers and stroke survivors. The Adopt–Contextualise–Adapt model was applied as a decision-guide to streamline discussions on endorsement and development of implementation strategies. Where recommendations required contextualisation to address local barriers before they could be effectively implemented, prompts were provided to identify barriers and possible solutions. Where recommendations could not be implemented without additional local evidence (adaptation), options were identified to establish new evidence. FINDINGS: The structured implementation process was efficient in terms of time, effort, resources and problem solving. The process empowered the project team to make practical decisions about local uptake of international recommendations, develop local implementation strategies, and determine who was responsible, for what and when. Different implementation strategies for the same recommendation were identified for different settings, to address different barriers. CONCLUSION: The South African evidence translation experience could be useful for evidence implementers in other countries, when translating CPG recommendations developed elsewhere, into local practice.
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    Tissue and nitrogen-linked expression profiles of ammonium and nitrate transporters in maize
    (BMC, 2019-05-20) Dechorgnat, Julie; Francis, Karen L; Dhugga, Kanwarpal S; Rafalski, J. A; Tyerman, Stephen D; Kaiser, Brent N
    BACKGROUND: In order to grow, plants rely on soil nutrients which can vary both spatially and temporally depending on the environment, the soil type or the microbial activity. An essential nutrient is nitrogen, which is mainly accessible as nitrate and ammonium. Many studies have investigated transport genes for these ions in Arabidopsis thaliana and recently in crop species, including Maize, Rice and Barley. However, in most crop species, an understanding of the participants in nitrate and ammonium transport across the soil plant continuum remains undefined. RESULTS: We have mapped a non-exhaustive set of putative nitrate and ammonium transporters in maize. The selected transporters were defined based on previous studies comparing nitrate transport pathways conserved between Arabidopsis and Zea mays (Plett D et. al, PLOS ONE 5:e15289, 2010). We also selected genes from published studies (Gu R et. al, Plant and Cell Physiology, 54:1515-1524, 2013, Garnett T et. al, New Phytol 198:82-94, 2013, Garnett T et. al, Frontiers in Plant Sci 6, 2015, Dechorgnat J et. al, Front Plant Sci 9:531, 2018). To analyse these genes, the plants were grown in a semi-hydroponic system to carefully control nitrogen delivery and then harvested at both vegetative and reproductive stages. The expression patterns of 26 putative nitrogen transporters were then tested. Six putative genes were found not expressed in our conditions. Transcripts of 20 other genes were detected at both the vegetative and reproductive stages of maize development. We observed the expression of nitrogen transporters in all organs tested: roots, young leaves, old leaves, silks, cobs, tassels and husk leaves. We also followed the gene expression response to nitrogen starvation and resupply and uncovered mainly three expression patterns: (i) genes unresponsiveness to nitrogen supply; (ii) genes showing an increase of expression after nitrogen starvation; (iii) genes showing a decrease of expression after nitrogen starvation. CONCLUSIONS: These data allowed the mapping of putative nitrogen transporters in maize at both the vegetative and reproductive stages of development. No growth-dependent expression was seen in our conditions. We found that nitrogen transporter genes were expressed in all the organs tested and in many cases were regulated by the availability of nitrogen supplied to the plant. The gene expression patterns in relation to organ specificity and nitrogen availability denote a speciality of nitrate and ammonium transporter genes and their probable function depending on the plant organ and the environment.
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    Health deficits in community dwelling adults aged 40 to 75 years
    (BMC, 2019-05-27) Gordon, Susan J; Kidd, Michael Richard; Maeder, Anthony; Baker, Nicky; Marin, Tania; Grimmer, K A
    BACKGROUND: Middle and older years are associated with age related health deficits but how early this begins and progresses is poorly understood. Better understanding is needed to address early decline and support healthier ageing outcomes. METHODS: Seemingly healthy, community dwelling adults aged 40 to 75 years were recruited via local council and business networks. They completed online surveys about sleep quality, distress and physical activity, and two hours of objective testing of physiologic and anthropometric measures, mobility, cognition, grip strength, foot sensation, dexterity and functional hearing. Analysis compared outcomes for age, gender, and age and gender groups with population norms for 21 health assessments. The total number of non-compliant tests for each participant was calculated by summing the number of non-compliant tests, and the frequency of these scores across the sample was reported. Gender and age effects were tested using ANOVA models. Combined age and gender categories were used for subsequent logistic regression modelling, with females aged 40–49 years being the default comparator. RESULTS: Of 561 participants (67% female; mean age 60 years (SD 10.3)), everyone had at least one deficit and median deficits was 5 (IQR 2). More than 50% of participants did not meet anthropometric and exercise norms, while 30 to 40% had reduced functional hearing and cognition. Overall, men performed worse and deficits increased with age particularly for physical activity, audiology, mobility, anthropometry, oximetry and foot sensation. Heart rate, body temperature and dyspnoea were the only variables where compliance was within 95% of expected values. Multiple areas of functional decline were found in people aged in their 40s and 50s. CONCLUSIONS: The health deficits identified are mostly mutable hence identification and interventions to address the multi-system functional decline in people as young as 40 has the capacity to ensure healthier ageing.
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    Enrolment of families with overweight children into a program aimed at reducing childhood obesity with and without a weight criterion: a natural experiment
    (BMC, 2019-06-14) Esdaile, Emma; Hernandez, Emely; Moores, Carly J; Vidgen, Helen A
    BACKGROUND: Difficulties engaging families with overweight children to enrol into programs aimed at reducing childhood obesity have been well documented. During the implementation of the Parenting, Eating and Activity for Child Health Program (PEACH™) over a large geographical area (Queensland (QLD), Australia), a natural experiment developed. This experiment provided an opportunity to observe if there was a difference in enrolment for families with overweight children with a weight criterion (referred to as the period with a Targeted Eligibility Criterion (TEC)) compared to when a weight criterion was removed (the period referred to as Universal Eligibility Criterion (UEC)). We also examined the eligibility criterion’s relationship with attendance, parental concern about their child’s weight, estimation of overweight and obesity from parent-reported data. METHODS: A secondary analysis of baseline data from 926 overweight/obese children from 817 families enrolled in PEACH™ QLD was performed. Analyses were adjusted to control for the presence of clustered data. Bivariate statistics were performed using Pearson chi-square test with the second-order Rao-Scott correction, and Mann–Whitney U-test for non-parametric continuous variables. Generalized Estimating Equations (GEE) explored the association between weight status-based eligibility criteria and enrolment of overweight children. GEE were adjusted for sex, age and socioeconomic index and stratified for weight category. RESULTS: Compared to obese children, overweight children were almost twice as likely to be enrolled when the program did not have weight status-based eligibility criteria (during UEC period) (OR = 1.90 (CI 95% 1.35–2.68, p <  0.001)). Parents of overweight children enrolled during the UEC period were more likely to regard their child’s weight as less of a concern than during the TEC period (UEC 67% vs. TEC 45%, p = 0.036). Children whose parent-reported data underestimated their weight category were more likely to be enrolled while the program did not have weight-related eligibility criteria OR = 2.27 (CI 1.38–3.70, p <  0.01). Program session attendance did not appear to be impacted by the changes in eligibility criteria. CONCLUSIONS: The omission of weight criteria for healthy lifestyle programs is a consideration for health professionals and decision-makers alike when encouraging the enrolment of children who are overweight into healthy lifestyle programs.
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    Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
    (BMC, 2019-05-13) Pearce, Karma L; Hill, Amy; Tremellen, Kelton P
    Background Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation (metabolic endotoxemia) that triggers a systemic state of inflammation and resultant oxidative stress. Therefore, we hypothesised that this obesity related increase in intestinal permeability and resultant metabolic endotoxemia (ME) may activate inflammation within the male reproductive tract, leading to increased reactive oxygen species production, sperm oxidative stress and a decline in DNA integrity. Results Our pilot study of 37 infertile men confirmed a significant positive correlation between body mass index (BMI), increased intestinal permeability (serum zonulin), metabolic endotoxaemia (LBP), sperm DNA oxidative damage (seminal 8 OhDG) and increasing levels of sperm DNA fragmentation (Halosperm). Metabolic endotoxemia was positively correlated with increasing levels of sperm DNA oxidative damage with this relationship remaining significant, even after adjustment for relevant confounders such as age, BMI and days of abstinence. These observations suggest that metabolic endotoxemia and its associated oxidative stress may be a key driver of sperm DNA damage in obese men. Conclusion This study confirms a link between obesity, increasing intestinal permeability and endotoxin exposure, and oxidative mediated sperm DNA damage. This warrants further investigation to fully understand the effect of metabolic endotoxemia on male reproductive function which could result in the new therapies to improve male fertility potential.
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    The distribution and socioeconomic burden of Hepatitis C virus in South Australia: a cross-sectional study 2010–2016
    (BMC, 2019-05-08) Edmunds, Bernard Luke; Miller, Emma Ruth; Tsourtos, George
    BACKGROUND: Hepatitis C virus infection (HCV) is a communicable disease of increasing global importance with 1.75 million new infections and 400,000 related deaths annually. Until recently, treatment options have had low uptake and most infected people remain untreated. New Direct Acting Antiviral medications can clear the virus in around 95% of cases, with few side-effects. These medications are restricted in most countries but freely accessible in Australia, yet most people still remain untreated. This study applies a cross-sectional research design to investigate the socio-spatial distribution of HCV in South Australia, to identify vulnerable populations, and examine epidemiological factors to potentially inform future targeted strategies for improved treatment uptake. METHOD: HCV surveillance data were sourced from South Australia’s Communicable Diseases Control Branch and socio-economic population data from the Australian Bureau of Statistics from January 2010 to December 2016 inclusive. HCV cases were spatially mapped at postcode level. Multivariate logistic regression identified independent predictors of demographic risks for HCV notification and notification source. RESULTS: HCV notifications (n = 3356) were seven times more likely to be from people residing in the poorest areas with high rates of non-employment (75%; n = 1876) and injecting drug use (74%; n = 1862) reported. Notifications among Aboriginal and Torres Strait Islander people were around six times that of non-Indigenous people. HCV notifications negatively correlated (Spearman’s rho − 0.426; p < 0.001) with socio-economic status (residential postcode socio-economic resources Index). History of imprisonment independently predicted HCV diagnoses in lesser economically-resourced areas (RR1.5; p < 0.001). Independent predictors of diagnosis elsewhere than in general practices were non-employment (RR 4.6; p = 0.028), being male (RR 2.5; p < 0.001), and younger than mean age at diagnosis (RR 2.1; p = 0.006). CONCLUSIONS: Most people diagnosed with HCV were from marginalised sub-populations. Given general practitioners are pivotal to providing effective HCV treatment for many people in Australia a most concerning finding was that non-employed people were statistically less likely to be diagnosed by general practitioners. These findings highlight a need for further action aimed at improving healthcare access and treatment uptake to help reduce the burden of HCV for marginalised people, and progress the vision of eliminating HCV as a major public health threat.
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    Being unvaccinated and having a contact history increased the risk of measles infection during an outbreak: a finding from measles outbreak investigation in rural district of Ethiopia
    (BMC, 2019-04-25) Girmay, Abadi; Dadi, Abel F
    Background: Measles is one of the most contagious diseases caused by an acute viral illness called Morbillivirus that usually occurs as an outbreak in low-income countries. As of May 2016 measles suspected outbreak was reported from Sekota Zuria district. We investigated the outbreak to identify its possible sources and risk factors of acquiring the infection in the district. Method: We conducted a 1:2 unmatched case-control study in May 2016 in Sekota Zuria district, Northern Ethiopia. Cases involved in the study were lab confirmed and epidemiologically linked. Controls were those who had no clinical signs of measles and residing in the same communities where the cases were identified. An interviewer-administered questionnaire was used to collect the data. Data were cleaned and entered to Epi-info7 and analyzed using SPSS-20. A logistic regression analysis was conducted to identify risk factors associated with measles infection at a p-value ≤0.05. Results: 29 cases were identified during the outbreak investigation. The probable source of an outbreak was an index case who had a travel history to a district with a measles epidemic. Five samples were collected for confirmation of the diagnosis. No measles-related deaths were reported. The median age of cases and controls was 15 years (SD ± 7.8) and 11 years (SD ± 9.8), respectively. More than 55% of the cases were in age ≥ 15 years. In the multivariable analysis, being previously vaccinated for measles reduced the risk of measles infection by 83% (AOR, 95%CI = 0.17, 0.05–0.53) and having a contact history increased the risk of measles infection by 3.44 times (AOR, 95%CI = 3.44, 1.26–9.38). Conclusion: We confirmed a measles outbreak in Sekota Zuria district. The majority of the cases were in age ≥ 15 years. Being un-vaccinated and having a contact history with confirmed or suspected cases were increased the risk of measles infection. To catch up with missed children at the time of the first dose of measles vaccine and reduce their susceptibility, supplementary immunization activities (SIAs) or immunization campaigns shall be strengthened.
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    Biomedical applications of polyelectrolyte coated spherical gold nanoparticles
    (Springer, 2019-04-24) Fuller, Melanie A; Köper, Ingo
    Surface modified gold nanoparticles are becoming more and more popular for use in biomaterials due to the possibility for specific targeting and increased biocompatibility. This review provides a summary of the recent literature surrounding polyelectrolyte coatings on spherical gold nanoparticles and their potential biomedical applications. The synthesis and layer-by layer coating approach are briefly discussed together with common characterisation methods. The potential applications and recent developments in drug delivery, gene therapy, photothermal therapy and imaging are summarized as well as the effects on cellular uptake and toxicity. Finally, the future outlook for polyelectrolyte coated gold nanoparticles is explored, focusing on their use in biomedicine.
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    Strongyloidiasis in Ethiopia: systematic review on risk factors, diagnosis, prevalence and clinical outcomes
    (BMC, 2019-06-14) Terefe, Yitagele; Ross, Kirstin Elizabeth; Whiley, Harriet
    Background Strongyloidiasis is a gastrointestinal infection caused by the parasitic nematode Strongyloides stercoralis. It is estimated to infect up to 370 million people globally and is predominately found in tropical and subtropical areas of socioeconomic disadvantage. Main body This systematic literature review identified studies published in the last ten years on the risk factors, diagnosis, prevalence and/or clinical outcomes of strongyloidiasis in Ethiopia. The prevalence of S. stercoralis ranged from 0.2 to 11.1% in adults, 0.3% to 20.7% in children, 1.5% to 17.3% in HIV positive adults and 5% in HIV positive children. The identified studies primarily used microscopy based techniques that potentially underestimated the prevalence four fold compared with serology and PCR. Strongyloidiasis in children presents a particularly significant issue in Ethiopia as children often presented with anemia, which is associated with impaired mental and cognitive development. The most significant risk factor for strongyloidiasis was HIV status and although other risk factors were identified for helminth infections, none were statistically significant for S. stercoralis specifically. Several studies detected S. stercoralis in dogs and non-biting cyclorrhaphan flies. However, future research is needed to explore the role of these reservoirs in disease transmission. Conclusions This review demonstrated that strongyloidiasis is an overlooked and neglected disease in Ethiopia. There is a need for a systematic approach using a combination of molecular and serology based diagnostic methods to ascertain the true incidence and burden of strongyloidiasis in Ethiopia. Further research is also needed to break the cycle of transmission by identifying environmental reservoirs, risk factors and exploring the potential for zoonotic transfer.
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    A cross-country study of mis-implementation in public health practice
    (BioMed Central, 2019-03-06) Furtado, Karishma S; Budd, Elizabeth L; Armstrong, Rebecca; Pettman, Tahna; Reis, Rodrigo; Sung-Chan, Pauline; Wang, Zhaoxin; Brownson, Ross C
    Abstract Background Mis-implementation (i.e., the premature termination or inappropriate continuation of public health programs) contributes to the misallocation of limited public health resources and the sub-optimal response to the growing global burden of chronic disease. This study seeks to describe the occurrence of mis-implementation in four countries of differing sizes, wealth, and experience with evidence-based chronic disease prevention (EBCDP). Methods A cross-sectional study of 400 local public health practitioners in Australia, Brazil, China, and the United States was conducted from November 2015 to April 2016. Online survey questions focused on how often mis-termination and mis-continuation occur and the most common reasons programs end and continue. Results We found significant differences in knowledge of EBCDP across countries with upwards of 75% of participants from Australia (n = 91/121) and the United States (n = 83/101) reporting being moderately to extremely knowledgeable compared with roughly 60% (n = 47/76) from Brazil and 20% (n = 21/102) from China (p < 0.05). Far greater proportions of participants from China thought effective programs were never mis-terminated (12.2% (n = 12/102) vs. 1% (n = 2/121) in Australia, 2.6% (n = 2/76) in Brazil, and 1.0% (n = 1/101) in the United States; p < 0.05) or were unable to estimate how frequently this happened (45.9% (n = 47/102) vs. 7.1% (n = 7/101) in the United States, 10.5% (n = 8/76) in Brazil, and 1.7% (n = 2/121) in Australia; p < 0.05). The plurality of participants from Australia (58.0%, n = 70/121) and the United States (36.8%, n = 37/101) reported that programs often mis-continued whereas most participants from Brazil (60.5%, n = 46/76) and one third (n = 37/102) of participants from China believed this happened only sometimes (p < 0.05). The availability of funding and support from political authorities, agency leadership, and the general public were common reasons programs continued and ended across all countries. A program’s effectiveness or evidence-base—or lack thereof—were rarely reasons for program continuation and termination. Conclusions Decisions about continuing or ending a program were often seen as a function of program popularity and funding availability as opposed to effectiveness. Policies and practices pertaining to programmatic decision-making should be improved in light of these findings. Future studies are needed to understand and minimize the individual, organizational, and political-level drivers of mis-implementation.
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    NAV-KIDS2 trial: protocol for a multi-centre, staggered randomised controlled trial of a patient navigator intervention in children with chronic kidney disease
    (BioMed Central, 2019-04-18) van Zwieten, Anita; Caldwell, Patrina; Howard, Kirsten; Tong, Allison; Craig, Jonathan C; Alexander, Stephen; Howell, Martin; Armando, Teixeira-Pinto; Hawley, Carmel; Jesudason, Shilpa; Walker, Amanda; Mackie, Fiona; Kennedy, Sean; McTaggart, Steve; McCarthy, Hugh; Carter, Simon; Kim, Siah; Crafter, Sam; Woodleigh, Reginald; Guha, Chandana; Wong, Germaine
    Abstract Background Chronic kidney disease (CKD) is a devastating illness associated with increased mortality, reduced quality of life, impaired growth, neurocognitive impairment and psychosocial maladjustment in children. There is growing evidence of socioeconomic disparities in health outcomes among children with CKD. Patient navigators are trained non-medical personnel who assist patients with chronic conditions journey through the continuum of care and transit across different care settings. They help vulnerable and underserved populations to better understand their diagnosis, treatment options, and available resources, guide them through complex medical systems, and help them to overcome barriers to health care access. Given the complexity and chronicity of the disease process and concerns that current models of care may not adequately support the provision of high-level care in children with CKD from socioeconomically disadvantaged backgrounds, a patient navigator program may improve the provision of care and overall health of children with CKD. Methods The NAV-KIDS2 trial is a multi-centre, staggered entry, waitlisted randomised controlled trial assessing the health benefits and costs of a patient navigator program in children with CKD (stages 3–5, on dialysis, and with kidney transplants), who are of low socioeconomic backgrounds. Across 5 sites, 210 patients aged from 3 to 17 years will be randomised to immediate receipt of a patient navigator intervention for 24 weeks or waitlisting with standard care until receipt of a patient navigator at 24 weeks. The primary outcome is child self-rated health (SRH) 6-months after completion of the intervention. Other outcomes include utility-based quality of life, caregiver SRH, satisfaction with healthcare, progression of kidney dysfunction, other biomarkers, missed school days, hospitalisations and mortality. The trial also includes an economic evaluation and process evaluation, which will assess the cost-effectiveness, fidelity and barriers and enablers of implementing a patient navigator program in this setting. Discussion This study will provide clear evidence on the effectiveness and cost-effectiveness of a new intervention aiming to improve overall health and well-being for children with CKD from socioeconomically disadvantaged backgrounds, through a high quality, well-powered clinical trial. Trial registration Prospectively registered (12/07/2018) on the Australian New Zealand Clinical Trials Registry (ACTRN12618001152213).
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    Relapse rates after elective discontinuation of anti-TNF therapy in rheumatoid arthritis: a meta-analysis and review of literature
    (BioMed Central, 2019-03-08) Mangoni, Arduino Aleksander; Al Okaily, Fahdah; Almoallim, Hani; Al Rashidi, Seham; Mohammed, Reem H A; Barbary, Amal
    Abstract Background Inhibitors of tumor necrosis factor alpha (TNF-α) are current mainstay of therapies for rheumatoid arthritis (RA). The decision when to withdraw TNF-α inhibitors after achieving remission and the incidence of relapse rates with elective discontinuation are both important questions that demand intense survey in these patients. In this meta-analysis we aimed to estimate the magnitude of relapse rate after elective TNF-α inhibitor discontinuation in RA patients with remission. Methods Systematic searches of PubMed/MEDLINE, Cochrane Library databases, grey literature (unpublished and ongoing trials) from the WHO International Clinical Trials Registry Platform and the US National Institutes of Health were performed for studies reporting the outcomes of elective discontinuation of TNF-α inhibitor in RA patients after remission. Random-effects models for meta-analyses were conducted on extracted data. Results Out of 390 references screened, 16 RCTs were included. Meta-analysis of 1264 patient data revealed a relapse rate of 0.47 (95% CI 0.41–0.54). Sensitivity analysis showed that none of the studies had higher influence on the results. Conclusions Almost half of all the RA patients in remission relapse after elective TNF-α inhibitor discontinuation. This information might be useful when considering this management option with individual patients.
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    A critical account of the policy context shaping perinatal survival in Nepal: policy tension of socio-cultural versus a medical approach
    (BioMed Central, 2019-03-14) Paudel, Mohan; Javanparast, Sara; Dasvarma, Gouranga Lal; Newman, Lareen Ann
    Abstract Background Nepal formulated a range of policies related to maternal and neonatal survival, especially after the year 2000. Nevertheless, Nepal’s perinatal mortality remains high, particularly in disadvantaged regions. Policy analysis can uncover the underlying values, strategies and policy formulation processes that shape the potential to reduce in-country health inequities. This paper provides a critical account of the main policy documents relevant to perinatal survival in Nepal. Methods Six key policy documents covering the period 2000–2015 were reviewed using an adapted framework and were analyzed through qualitative content analysis. Results The analysis shows that the policies focused mainly on the system: improvement in provision of birthing facilities; targeting staff (Skilled Birth Attendants) and health service users by providing cash incentives to staff for bringing patients to services, and to users (pregnant women) to attend health institutions. Despite a growing focus on saving women and newborn babies, there is a poor policy focus and direction on preventing stillbirth. The policy documents were found to emphasize tensions between birthing at home and at health institutions on the one hand, and between strategies to provide culturally appropriate, woman-centered care in communities and medically orientated services on the other. Policies acknowledge the need to provide and address woman-centered care, equity, social inclusion, and a rights-based approach, and identify the community based approach as the mode of service delivery. Over and above this, all policy documents are aimed at the national level, and there is no specific policy direction for the separate ecological, cultural or geographic regions such as the mountainous region, which continues to exhibit higher mortality rates and has different cultural and demographic characteristics to the rest of Nepal. Conclusions To better address the continuing high perinatal mortality rates, particularly in disadvantaged areas, national health policies should pay more attention to the inequity in healthcare access and in perinatal outcomes by integrating both stillbirth prevention and neonatal survival as policy agenda items. To ensure effective translation of policy into practice, it is imperative to tailor the strategies according to acknowledged policy values such as rights, inclusion and socio-cultural identity.