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Background: Hearing loss is independently associated with a faster rate of cognitive decline in older adults and has been identified as a modifiable risk factor for dementia. The mechanism for this association is unknown, and there has been limited exploration of potential casual pathology. Objective: Our objective was to investigate whether there was an association between degree of audiometrically measured hearing loss (HL) and brain amyloid-β (Aβ) in a pre-clinical sample. Methods: Participants of the Australian Imaging and Biomarker Longitudinal Study (AIBL; n = 143) underwent positron emission tomography (PET) imaging and objective measurement of hearing thresholds within 5 years of imaging, as well as cognitive assessment within 2 years of imaging in this observational cohort study. Results: With one exception, study participants who had cognitive assessments within 2 years of their PET imaging (n = 113) were classified as having normal cognition. There was no association between cognitive scores and degree of hearing loss, or between cognitive scores and Aβ load. No association between HL and Aβ load was found once age was controlled for. As previously reported, positive Apolipoprotein E4 (APOE4) carrier status increased the risk of being Aβ positive (p = 0.002). Conclusion: Degree of HL was not associated with positive Aβ status.

Many modern histopathology laboratories are in the process of digitizing their workflows. Digitization of tissue images has made it feasible to research the augmentation or automation of clinical reporting and diagnosis. The application of modern computer vision techniques, based on deep learning, promises systems that can identify pathologies in slide images with a high degree of accuracy. Generative modeling is an approach to machine learning and deep learning that can be used to transform and generate data. It can be applied to a broad range of tasks within digital pathology, including the removal of color and intensity artifacts, the adaption of images in one domain into those of another, and the generation of synthetic digital tissue samples. This review provides an introduction to the topic, considers these applications, and discusses future directions for generative models within histopathology.

Background The impact of research findings on clinical practice usually remains uncertain and unmeasured. To address this problem, we examined the long-term clinical and economic impact of the Initiating Dialysis Early and Late (IDEAL) trial using data from the Australia and New Zealand Dialysis and Transplant Registry. Methods We performed a registry-based study including all incident adult dialysis patients in Australia and New Zealand from July 2000 to June 2018. A piecewise linear regression model was used to examine differences in mean estimated glomerular filtration rate (eGFR) at dialysis commencement for the years prior to (2000–2010) and following (2010–2018) publication of the IDEAL trial results. The return on investment (ROI) was calculated using the total cost of performing the IDEAL trial and the cost or savings accruing in Australia and New Zealand from changes in dialysis initiation practice. Results From July 2000 to June 2010, mean eGFR at dialysis commencement increased at a rate of 0.21 mL/min/1.73 m2/year [95% confidence interval (CI) 0.19–0.23]. After the IDEAL trial results were published, mean eGFR at dialysis commencement did not show any temporal change [−0.01 mL/min/1.73 m2/year (95% CI −0.03–0.01)]. The ROI of the IDEAL trial was AU$35.70/AU$1 spent, an estimated savings to the Australian and New Zealand health systems of up to AU$84 million/year. Conclusions The previous trend to higher eGFR at dialysis commencement changed following publication of the IDEAL trial results to a steady eGFR that has continued for a decade, avoiding unnecessary dialysis treatments and accruing savings to the Australian and New Zealand health systems.

OBJECTIVES Evaluate ET and TVFR in normal patients, PLFLGAS, LGLFAS, and classic pre and post TAVR. BACKGROUND Severe aortic stenosis (AS) is defined echocardiographically. Generating a pressure gradient to meet diagnostic criteria is dependent on left ventricular contractility, stroke volume, and ejection time. Abnormalities in these decrease the mean pressure gradient across the valve creating pathology termed low flow, low gradient AS. This occurs in two subtypes, low ejection fraction LFLGAS and paradoxical LFLGAS (PLFLGAS), in which EF is normal but stroke volume is

The International Society of Nephrology Global Kidney Health Atlas analyzed the current state of kidney care in Newly Independent States and Russia. Our results demonstrated that the Newly Independent States and Russia region was not an exception and showed the same effect of chronic kidney disease on health and its outcomes, facing many difficulties and challenges in terms of improving kidney care across the countries. This work summarized and presented demographics, health information systems, statistics, and national health policy of the region, as well as characteristics of the burden of chronic kidney disease and kidney failure (KF) of participating countries. Besides significant economic advancement in the region, the collected data revealed existing shortage in KF care providers, essential medications, and health product access for KF care. Moreover, there was low reporting of kidney replacement therapy (dialysis and kidney transplantation) quality indicators and low capacity for long-term hemodialysis, peritoneal dialysis, and kidney transplantation. The financial issues and funding structures for KF care across the region needs strategic support for fundamental changes and further advancement. This article emphasizes the urgent need for further effective regional and international collaborations and partnership for establishment of universal health care systems for KF management.

The International Society of Nephrology established the Global Kidney Health Atlas project to define the global capacity for kidney replacement therapy and conservative kidney care, and this second iteration was to describe the availability, accessibility, quality, and affordability of kidney failure (KF) care worldwide. This report presents results for the International Society of Nephrology North America and the Caribbean region. Relative to other regions, the North America and Caribbean region had better infrastructure and funding for health care and more health care workers relative to the population. Various essential medicines were also more available and accessible. There was substantial variation in the prevalence of treated KF in the region, ranging from 137.4 per million population (pmp) in Jamaica to 2196 pmp in the United States. A mix of public and private funding systems cover costs for nondialysis chronic kidney disease care in 60% of countries and for dialysis in 70% of countries. Although the median number of nephrologists is 18.1 (interquartile range, 15.3-29.5) pmp, which is approximately twice the global median of 9.9 (interquartile range, 1.2-22.7) pmp, some countries reported shortages of other health care workers. Dialysis was available in all countries, but peritoneal dialysis was underutilized and unavailable in Barbados, Cayman Islands, and Turks and Caicos. Kidney transplantation was primarily available in Canada and the United States. Economic factors were the major barriers to optimal KF care in the Caribbean countries, and few countries in the region have chronic kidney disease-specific national health care policies. To address regional gaps in KF care delivery, efforts should be directed toward augmenting the workforce, improving the monitoring and reporting of kidney replacement therapy indicators, and implementing noncommunicable disease and chronic kidney disease-specific policies in all countries.

Here we publish a new species of forest tree of the genus Drypetes Vahl (Putranjivaceae), D. umbricola D. J. Harris & Quintanar, which has a wide distribution in Central Africa (Cameroon, Central African Republic, Democratic Republic of the Congo, Gabon, and Republic of the Congo). It is known from 70 herbarium collections and additional sterile plot vouchers. A differential diagnosis, detailed morphological description, photographs, an illustration, and information about its habitat, distribution, and conservation status are provided.

β-Catenin is an important co-factor which binds multiple transcriptional molecules and mediates fibrogenic signaling pathways. Its role in kidney transplantation is unknown. We quantified binding of β-catenin within renal tubular epithelial cells to transcription factors, TCF1 and FoxO1, using a proximity ligation assay in 240 transplanted kidneys, and evaluated their pathological and clinical outcomes. β-Catenin/FoxO1 binding in 1-month protocol biopsies inversely correlated with contemporaneous chronic fibrosis, subsequent inflammation. and inflammatory fibrosis (P < .001). The relative binding of β-catenin/TCF1 versus β-catenin/FoxO1 (TF ratio) was the optimal biomarker, and abnormal in diverse fibrotic transplant diseases. A high 1-month TF ratio was followed by greater tubular atrophy and interstitial fibrosis scores, cortical inflammation, renal impairment, and proteinuria at 1 year (n = 131, all P < .001). The TF ratio was associated with reduced eGFR (AUC 0.817), mild fibrosis (AUC 0.717), and moderate fibrosis (AUC 0.769) using receiver operating characteristic analysis. An independent validation cohort (n = 76) confirmed 1-month TF was associated with 12-month moderate fibrosis (15.8% vs. 2.6%, P = .047), however, not with other outcomes or 10-year graft survival, which limits generalizabilty of these findings. In summary, differential binding of β-catenin to TCF1 rather than FoxO1 in renal tubular cells was associated with the fibrogenic response in transplanted kidneys.

Background: Peritoneal dialysis (PD) can offer patients more autonomy and flexibility compared with in-center hemodialysis (HD). However, burnout – defined as mental, emotional, or physical exhaustion that leads to thoughts of discontinuing PD – is associated with an increased risk of transfer to HD. We aimed to describe the perspectives of burnout among patients on PD and their caregivers. Methods: In this focus group study, 81 patients and 45 caregivers participated in 14 focus groups from 9 dialysis units in Australia, Hong Kong, and the United States. Transcripts were analyzed thematically. Results: We identified two themes. Suffering an unrelenting responsibility contributed to burnout, as patients and caregivers felt overwhelmed by the daily regimen, perceived their life to be coming to a halt, tolerated the PD regimen for survival, and had to bear the burden and uncertainty of what to expect from PD alone. Adapting and building resilience against burnout encompassed establishing a new normal, drawing inspiration and support from family, relying on faith and hope for motivation, and finding meaning in other activities. Conclusions: For patients on PD and their caregivers, burnout was intensified by perceiving PD as an unrelenting, isolating responsibility that they had no choice but to endure, even if it held them back from doing other activities in life. More emphasis on developing strategies to adapt and build resilience could prevent or minimize burnout.

The Osteosarcoma Surveillance Study was initiated in the United States in 2003 to monitor for a potential association between the osteoporosis treatment teriparatide and osteosarcoma. Osteosarcoma occurs at a background incidence rate of approximately 2.5 cases per million per year in US adults aged 40 years or older. For this study, incident cases of osteosarcoma diagnosed between January 1, 2003, and December 31, 2016, were identified through participating cancer registries in the United States. Information on prior exposure to medications and possible risk factors was obtained by self‐report (or proxy report) in telephone interviews. Exposure information was verified through medical record abstraction for a sample of patients. A standardized incidence ratio was estimated to compare the observed and expected numbers of osteosarcoma patients with a prior history of teriparatide treatment. Interviews were completed for 24% (1173) of patients diagnosed with osteosarcoma between 2003 and 2016; three reports of teriparatide use before diagnosis were identified. Based on the background incidence rate, the expected number of osteosarcoma cases among patients treated with teriparatide was 4.17. Given the three observed cases, the standardized incidence ratio was 0.72 (90% confidence interval [CI], 0.20 to 1.86). Demographic characteristics were similar for interviewed and noninterviewed patients. Agreement was >90% between self‐reported and chart‐recorded exposure to osteoporosis medications. Mean age of interviewed patients was 61 years; 53% of patients were male, 84% were white, and 5% were Hispanic. The prevalence of suspected risk factors for development of osteosarcoma among the osteosarcoma cohort was 19% for history of radiation and 4% for history of Paget's disease of bone. These findings showed that the incidence of osteosarcoma associated with teriparatide use during the 15‐year surveillance period was no different than would be expected based on the background incidence rate of osteosarcoma. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Background Overexpression of CD40 has been reported in patients with primary Sjogren’s syndrome (pSS). The increased CD40 expression promote autoimmune response and enhance inflammation in pSS. The aim of this study is to block CD40-CD154 interaction with CD40 DNA vaccine to slow the disease progression of SS in non-obese diabetic (NOD) mice. Methods Female NOD mice were treated with CD40 DNA vaccine, empty vector and normal saline. The salivary flow rate was measured, whereas lymphocytes infiltration in the salivary glands was assessed by histopathology. Expression of CD40 and B220 in salivary were examined by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. CD40, IL-1β, TNF-α and IL-6 levels in the salivary glands were detected by PCR. Serum anti-CD40 antibody was measured by ELISA. Serum anti-nuclear antibody (ANA) was monitored by immunofluorescence. Results NOD mice treated with CD40 DNA vaccine showed higher levels of anti-CD40 antibody compared with the controls. The expression of CD40 in the salivary glands of NOD mice in CD40 DNA vaccine group was decreased. The infiltration of lymphocytes was reduced in the salivary glands and saliva secretion was increased in the treatment group. The expression level of TNF-α and IL-6 in salivary glands were declined. The splenic dendritic cell and plasma cell populations were reduced and the level of ANA was decreased in NOD mice with CD40 DNA vaccine treatment. Conclusions CD40 DNA vaccine inhibits the immune response and reduce inflammation in epithelial tissues SS in non-obese diabetic (NOD) mice, suggesting that CD40 DNA vaccine could be a new therapeutic approach in treatment of pSS.

Purpose During preclinical testing, teriparatide caused a dose‐dependent increase in the incidence of osteosarcoma in rats. This study compared the incidence rate of osteosarcoma among patients aged ≥65 years treated with teriparatide vs a matched‐comparator cohort. Methods This population‐based comparative‐cohort study matched exposure details for each teriparatide user, identified via Medicare Part D prescription claims, and up to four comparators based on age, sex, zip code, date of claim for filled prescription, and number of unique therapeutic classes dispensed. Outcomes were identified via linkage with participating cancer registries. All US state cancer registries were invited to participate. Results Overall, 153 316 patients in the teriparatide cohort and 613 247 in the comparator cohort were linked to 811 osteosarcoma cases from 26 participating state cancer registries (68% of US patients aged ≥65 years diagnosed 2007‐2014). Analysis on a subset of cohorts revealed they were balanced for known osteosarcoma risk factors and Charlson comorbidity index. Mean duration of teriparatide treatment was 10 months. No osteosarcoma cases were observed in the teriparatide cohort; the incidence rate in the comparator cohort was consistent with the background incidence rate among adults aged ≥65 years. The incidence rate ratio was 0.0 (95% confidence interval, 0.0‐3.2). Conclusions For US patients aged ≥65 years, incidence of osteosarcoma among those treated with teriparatide ranges from 0 to 3.2 times the incidence of osteosarcoma in those treated with other medications. Given low incidence of osteosarcoma, this range of effect is inconsistent with a large absolute increase in osteosarcoma risk.

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Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology—Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

This paper presents the output of a workshop held at the 11th Annual Conference of EuPFI (European Paediatric Formulation Initiative), in September 2019 in Malmo, Sweden, on the development of multiparticulates and minitablets as pediatric formulations. The workshop focused on three specific facets of pediatric drug development, namely selection of the formulation platform, selection of the package or dosing device, and administration of minitablets/multiparticulates with soft food. The workshop discussion indicated significant interest in the use of these dosage forms, filled into stick-packs or capsules, as age-appropriate formulations for younger children, along with a growing consensus that larger sized tablets and capsules designed for adults are often also suitable for adolescents. Among the areas that were identified as technical challenges were: understanding the acceptability of multiparticulates and minitablets relative to alternate formulations; the need for a streamlined approach to compatibility testing with soft foods; the desire to avoid the need to co-administer these products with soft food; and the need for more suitable dosing devices.

Background Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimat...

Background and objectives Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically. Results Across 16 focus groups, 134 participants (range, 19–85 years old; 51% women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked outcomes were kidney function (importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: constraining day-to-day experience, impaired agency and control over health, and threats to future health and family. Conclusions Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact.

PURPOSE: Cardiopulmonary resuscitation in hospitalized patients with advanced cancer is associated with high rates of morbidity and mortality. Although advance care planning (ACP) in this population improves quality, patient satisfaction, hospice use, rates of harm, and health care costs, ACP documentation rates remain low. We observed changes in ACP documentation by internal medicine residents within a tertiary hospital’s inpatient oncology service after a mandatory training module and enterprise-wide modification in electronic health medical records (EHMR). METHODS: For patients admitted to the Cleveland Clinic oncology service, this 16-week retrospective review observed resident code status (CS) documentation through admission notes and direct EHMR orders before and after implementation of an ACP training module and CS best practice alert (BPA). In addition, residents were surveyed on perceived barriers to CS documentation. RESULTS: In 535 unique admissions (244 before BPA, 291 after BPA), residents exhibited a 14.4% increase (from 47.1% to 61.5%) in admission note CS documentation and an 18.2% increase (from 12.7% to 30.9%) in CS orders at time of discharge. The most common self-reported barrier to ACP documentation was forgetting to discuss, with first-, second-, and third-year residents admitting to feeling uncomfortable in orchestrating ACP conversations at rates of 58%, 6%, and 5%, respectively. CONCLUSION: Resident ACP documentation remains suboptimal in the high-risk cohort of hospitalized patients with advanced cancer. However, rates seem to be positively influenced by online modules and EHMR-based interventions. Additional efforts to improve the current practice and culture of ACP remain a crucial aspect in the quality and safety of our approach to patient care.

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multi-stakeholder engagement aimed at improving the availability and scope of integrated kidney care.

Background Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. Methods As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT). Results Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups. Conclusions These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.

Introduction Patients with glomerular disease experience symptoms that impair their physical and mental health while managing their treatments, diet, appointments and monitoring general and specific indicators of health and their illness. We sought to describe the perspectives of patients and their care partners on self-management in glomerular disease. Methods We conducted 16 focus groups involving adult patients with glomerular disease (n = 101) and their care partners (n = 34) in Australia, Hong Kong, the United Kingdom, and United States. Transcripts were analyzed thematically. Results We identified the following 4 themes: empowered in autonomy (gaining confidence through understanding, taking ownership of disease and treatment, learning a positive health approach); overwhelmed by compounding treatment burdens (financially undermined and depleted, demoralized by side effects and harms, frustrated by fragmented and inflexible care, fear of possible drug harms); striving for stability and normalcy (making personal sacrifices, maximizing life participation, attentiveness to bodily signs, avoiding precarious health states, integrating medicines into routines); and necessity of health-sustaining relationships (buoyed by social support, fulfilling meaningful responsibilities, sharing and normalizing experiences, seeking a trusting and respectful alliance). Conclusion Patients with glomerular disease and their care partners value their capacity for autonomy and disease ownership, stability of their health, and relationships that support self-management. Strategies directed at strengthening these factors may increase self-efficacy and improve the care and outcomes for patients with glomerular disease., Graphical abstract

Publisher Summary This chapter explores memory system organization. It is a major factor in determining computer performance. Different memory technologies such as dynamic random-access memory (DRAM), static random-access memory (SRAM), and hard disks offer trade-offs in capacity, speed, and cost. This chapter introduces cache and virtual memory organizations that use a hierarchy of memories to approximate an ideal large, fast, inexpensive memory. Main memory is typically built from DRAM, which is significantly slower than the processor. A cache reduces access time by keeping commonly used data in fast SRAM. Virtual memory increases the memory capacity by using a hard disk to store data that does not fit in the main memory. Caches and virtual memory add complexity and hardware to a computer system, but the benefits usually outweigh the costs. All modern personal computers use caches and virtual memory. Most processors also use the memory interface to communicate with input/output (I/O) devices. This is called “memory-mapped I/O.” Programs use load and store operations to access the I/O devices.

We would like to thank EPSRC impact acceleration fund (EP/K503940/1) for helping support this project. RR was supported as part of the James-Watt Scholarship during her PhD research at the Heriot-Watt University. Co-locating the gross tumour volume (GTV) on cone-beam computed tomography (CBCT) of non small cell lung cancer (NSCLC) patients receiving radiotherapy (RT) is difficult because of the lack of image contrast between the tumour and surrounding tissue. This paper presents a new image analysis approach, based on second-order statistics obtained from gray level co-occurrence matrices (GLCM) combined with level sets, for assisting clinicians in identifying the GTV on CBCT images. To demonstrate the potential of the approach planning CT images from 50 NSCLC patients were rigidly registered with CBCT images from fractions 1 and 10. Image texture analysis was combined with two level set methodologies and used to automatically identify the GTV on the registered CBCT images. The Dice correlation coefficients (μ± σ) calculated between the clinician-defined and image analysis defined GTV on the planning CT and the CBCT for three different parameterisations of the model were: 0.69 ± 0.19, 0.63 ± 0.17, 0.86 ± 0.13 on fraction 1 CBCT images and 0.70 ± 0.17, 0.62 ± 0.15, 0.86 ± 0.12 on fraction 10 CBCT images. This preliminary data suggests that the image analysis approach presented may have potential for clinicians in identifying the GTV in low contrast CBCT images of NSCLC patients. Additional validation and further work, particularly in overcoming the lack of gold standard reference images, are required to progress this approach. Postprint

Author(s): Yeung, Emily; Bello, AK; Levin, Adeera; Lunney, Meaghan; Osman, Mohamed A; Ye, Feng; Ashuntantang, Gloria; Bellorin-Font, Ezequiel; Benghanem Gharbi, Mohammed; Davison, Sara; Ghnaimat, Mohammad; Harden, Paul; Jha, Vivekanand; Kalantar-Zadeh, Kamyar; Kerr, Peter; Klarenbach, Scott; Kovesdy, Csaba; Luyckx, Valerie; Neuen, Brendon; O'Donoghue, Donal; Ossareh, Shahrzad; Perl, Jeffrey; Ur Rashid, Harun; Rondeau, Eric; See, Emily; Saad, Syed; Sola, Laura; Tchokhonelidze, Irma; Tesar, Vladimir; Tungsanga, Kriang; Turan Kazancioglu, Rumeyza; Wang, Angela Yee-Moon; Wiebe, Natasha; Yang, Chih-Wei; Zemchenkov, Alexander; Zhao, Minhui; Jager, Kitty J; Caskey, Fergus; Perkovic, Vlado; Jindal, Kailash; Okpechi, Ikechi G; Tonelli, Marcello; Feehally, John; Harris, David Ch; Johnson, David | Abstract: ObjectivesThe Global Kidney Health Atlas (GKHA) is a multinational, cross-sectional survey designed to assess the current capacity for kidney care across all world regions. The 2017 GKHA involved 125 countries and identified significant gaps in oversight, funding and infrastructure to support care for patients with kidney disease, especially in lower-middle-income countries. Here, we report results from the survey for the second iteration of the GKHA conducted in 2018, which included specific questions about health financing and oversight of end-stage kidney disease (ESKD) care worldwide.SettingA cross-sectional global survey.ParticipantsKey stakeholders from 182 countries were invited to participate. Of those, stakeholders from 160 countries participated and were included.Primary outcomesPrimary outcomes included cost of kidney replacement therapy (KRT), funding for dialysis and transplantation, funding for conservative kidney management, extent of universal health coverage, out-of-pocket costs for KRT, within-country variability in ESKD care delivery and oversight systems for ESKD care. Outcomes were determined from a combination of desk research and input from key stakeholders in participating countries.Results160 countries (covering 98% of the world's population) responded to the survey. Economic factors were identified as the top barrier to optimal ESKD care in 99 countries (64%). Full public funding for KRT was more common than for conservative kidney management (43% vs 28%). Among countries that provided at least some public coverage for KRT, 75% covered all citizens. Within-country variation in ESKD care delivery was reported in 40% of countries. Oversight of ESKD care was present in all high-income countries but was absent in 13% of low-income, 3% of lower-middle-income, and 10% of upper-middle-income countries.ConclusionSignificant gaps and variability exist in the public funding and oversight of ESKD care in many countries, particularly for those in low-income and lower-middle-income countries.

Dietary fibre fortified products have increased in popularity as health-conscious consumers seek convenient ways to increase fibre intake. Fibres from wholegrains are particularly desirable inclusions in food products because of their proven physiological health-benefits. When fortifying beverages with fibre, however, the insoluble dietary fibre components present in wholegrains often contribute to unpleasant gritty sensations making the products unpalatable. Consequently, designing wholegrain-fortified beverages with sufficient fibre-content to make health related fibre claims is a major challenge in the food manufacturing industry. This work aims to take a systematic approach in identifying the texture/mouthfeel related sensory impact and interaction between two commercial oat fibre ingredients (Oatwell28XF® and Milled Oats) when added to a model beverage system. Eighteen samples were prepared containing either or both the ingredients, at varying levels, and were assessed by a trained panel using conventional sensory descriptive techniques. The results indicate that the two different oat bran fibres produced distinct mouthfeel perceptions which could be attributed to the varying soluble and insoluble fibre content of the samples. Insoluble dietary fibre concentrations above 2% (w/w) resulted in particle-related sensory properties chalkiness, dryness and particle perception, which dominated the overall mouthfeel and textural sensory perception of the samples. Samples with predominantly soluble β-glucan, resulted in perceptions of smoothness, sliminess and stickiness residue, while thickness, mouthcoating and cloying sensations were driven by total fibre concentration, irrespective of fibre solubility. This work provides a solid foundation for food manufacturers aiming to rationally design and develop nutritionally superior fibre-fortified beverages and is relevant to fibre content concentrations required for labelling/nutrition claims for consumer products in many developed nations.

SUMMARYHousehold surveys are one of the most commonly used tools for generating insight into rural communities. Despite their prevalence, few studies comprehensively evaluate the quality of data derived from farm household surveys. We critically evaluated a series of standard reported values and indicators that are captured in multiple farm household surveys, and then quantified their credibility, consistency and, thus, their reliability. Surprisingly, even variables which might be considered ‘easy to estimate’ had instances of non-credible observations. In addition, measurements of maize yields and land owned were found to be less reliable than other stationary variables. This lack of reliability has implications for monitoring food security status, poverty status and the land productivity of households. Despite this rather bleak picture, our analysis also shows that if the same farm households are followed over time, the sample sizes needed to detect substantial changes are in the order of hundreds of surveys, and not in the thousands. Our research highlights the value of targeted and systematised household surveys and the importance of ongoing efforts to improve data quality. Improvements must be based on the foundations of robust survey design, transparency of experimental design and effective training. The quality and usability of such data can be further enhanced by improving coordination between agencies, incorporating mixed modes of data collection and continuing systematic validation programmes.

Contains fulltext : 203024.pdf (Publisher’s version ) (Open Access) In November 2017, the Kidney Disease: Improving Global Outcomes (KDIGO) initiative brought a diverse panel of experts in glomerular diseases together to discuss the 2012 KDIGO glomerulonephritis guideline in the context of new developments and insights that had occurred over the years since its publication. During this KDIGO Controversies Conference on Glomerular Diseases, the group examined data on disease pathogenesis, biomarkers, and treatments to identify areas of consensus and areas of controversy. This report summarizes the discussions on primary podocytopathies, lupus nephritis, anti-neutrophil cytoplasmic antibody-associated nephritis, complement-mediated kidney diseases, and monoclonal gammopathies of renal significance.

Image segmentation is one of the most important tasks in modern imaging applications, which leads to shape reconstruction, volume estimation, object detection and classification. One of the most popular active segmentation models are level set models which are used extensively as an important category of modern image segmentation technique with many different available models to tackle different image applications. Level sets are designed to overcome the topology problems during the evolution of curves in their process of segmentation while the previous algorithms cannot deal with this problem effectively. As a result there is often considerable investigation into the performance of several level set models for a given segmentation problem. It would therefore be helpful to know the characteristics of a range of level set models before applying to a given segmentation problem. In this paper we review a range of level set models and their application to image segmentation work and explain in detail their properties for practical use. Postprint

Effective communication within the patient–provider relationship is a key aspect of shared decision-making and associated with several positive patient outcomes. Although previous studies suggest that patients’ and providers’ conceptualization of what constitutes effective communication differ, there is no available literature discussing patient preferences for communication. The objective of this study was to determine the words and phrases pulmonary arterial hypertension patients prefer to hear when discussing their disease with their physician. A total of 227 pulmonary arterial hypertension patients completed a survey that included a 20-item questionnaire specifically designed to assess patient preference for words and phrases when discussing their disease and treatment; statistically significant differences were observed across all items of the questionnaire. Patients preferred their physician ask them how they have “been feeling” (63%) rather than how they have “been doing”. In addition, 96% of patients indicated that they wanted to hear that this is “… the best medicine for you ” rather than this is “the best medicine”. Considerably more patients (60%) indicated they want their physician to say, “We want you to have fewer symptoms” rather than “We want you to feel more normal.” They also indicated they wanted the “most effective” medicine (82%) rather than the “most aggressive” medicine (7%). The results of this study suggest that pulmonary arterial hypertension patients have strong preferences for the language their providers use when discussing their disease and treatment options. Given the role that effective communication has on important health outcomes, pulmonary arterial hypertension providers need to consider these findings when communicating with patients.

The glioma associated oncogene-1 (GLI1), a downstream effector of the embryonic Hedgehog pathway, was detected in chronic lymphocytic leukemia (CLL), but not normal adult cells. GLI1-activating mutations were identified in 10% of patients with CLL. However, what induces GLI1 expression in GLI1-unmutated CLL cells is unknown. Because signal transducer and activator of transcription 3 (STAT3) is constitutively activated in CLL cells, and sequence analysis detected putative STAT3-binding sites in the GLI1 gene promoter, we hypothesized that STAT3 induces the expression of GLI1. Western immunoblotting detected GLI1 in CLL cells from 7 of 7 patients, flow cytometry analysis confirmed that CD19+/CD5+ CLL cells co-express GLI1, and confocal microscopy showed co-localization of GLI1 and phosphorylated STAT3. Chromatin immunoprecipitation showed that STAT3 protein co-immunoprecipitated GLI1, as well as other STAT3-regulated genes. Transfection of CLL cells with STAT3-shRNA induced a mark decrease in GLI1 levels, suggesting that STAT3 binds to and induces the expression of GLI1 in CLL cells. An electromobility shift assay confirmed that STAT3 binds, and a luciferase assay showed that STAT3 activates the GLI1 gene. Transfection with GLI1-siRNA significantly increased the spontaneous apoptosis rate of CLL cells, suggesting that GLI1 inhibitors might provide therapeutic benefit to patients with CLL.

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases.

Background Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease. Methods Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory’s PerioCardio study; (3) weighted estimates from 4775 participants from Australia’s National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017–2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011–2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals. Results Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates. Conclusions Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia’s Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

The omission of outcomes that are of relevance to patients, clinicians, and regulators across trials in autosomal dominant polycystic kidney disease (ADPKD) limits shared decision making. The Standardized Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) Initiative convened an international consensus workshop on October 25, 2018, to discuss the identification and implementation of a potential core outcome set for all ADPKD trials. This article summarizes the discussion from the workshops and the SONG-PKD core outcome set. Key stakeholders including 11 patients/ caregivers and 47 health professionals (nephrologists, policy makers, industry, and researchers) attended the workshop. Four themes emerged: "Relevance of trajectory and impact of kidney function" included concerns about a patient's prognosis and uncertainty of when they may need to commence kidney replacement therapy and the lack of an early prognostic marker to inform long-term decisions; "Discerning and defining pain specific to ADPKD" highlighted the challenges in determining the origin of pain, adapting to the chronicity and repeated episodes of pain, the need to place emphasis on pain management, and to have a validated measure for pain; "Highlighting ADPKD consequences" encompassed cyst-related complications and reflected patient's knowledge because of family history and the hereditary nature of ADPKD; and "Risk for life-threatening but rare consequences" such as cerebral aneurysm meant considering both frequency and severity of the outcome. Kidney function, mortality, cardiovascular disease, and pain were established as the core outcomes for ADPKD.

Background: People with kidney failure typically receive kidney replacement therapy (KRT) in the form of dialysis or transplantation. However, studies have suggested that not all patients with kidney failure are best suited for KRT. Additionally, KRT is costly and not always accessible in resource-restricted settings. Conservative kidney management is an alternate kidney failure therapy, which focuses on symptom management, psychological health, spiritual care and family and social support. Despite the importance of conservative kidney management in kidney failure care, several barriers exist that impact its uptake and quality. Methods: The Global Kidney Health Atlas is an ongoing initiative of the International Society of Nephrology (ISN), which aims to monitor and evaluate the status of global kidney care worldwide. This study reports on findings from the 2018 Global Kidney Health Atlas survey, specifically addressing the availability, accessibility, uptake and quality of conservative kidney management. Results: Respondents from 160 countries completed the survey and 154 answered questions pertaining to conservative kidney management. Of these, 124 (81%) stated that conservative kidney management was available. Accessibility was low worldwide, particularly in low-income countries. Less than half of countries utilized multidisciplinary teams (46%), shared decision-making (32%), or provided psychological, cultural, or spiritual support (36%). One quarter provided relevant healthcare providers with training on conservative kidney management delivery.Conclusions: Overall, conservative kidney management is available in most countries; however, it is not optimally accessible or of the highest quality.

Rationale & Objective: Approximately 11% of people with kidney failure worldwide are treated with peritoneal dialysis (PD). This study examined PD use and practice patterns across the globe. Study Design: A cross-sectional survey. Setting & Participants: Stakeholders including clinicians, policy makers, and patient representatives in 182 countries convened by the International Society of Nephrology between July and September 2018. Outcomes: PD use, availability, accessibility, affordability, delivery, and reporting of quality outcome measures. Analytical Approach: Descriptive statistics. Results: Responses were received from 88% (n = 160) of countries and there were 313 participants (257 nephrologists [82%], 22 non-nephrologist physicians [7%], 6 other health professionals [2%], 17 administrators/policy makers/civil servants [5%], and 11 others [4%]). 85% (n = 156) of countries responded to questions about PD. Median PD use was 38.1 per million population. PD was not available in 30 of the 156 (19%) countries responding to PD-related questions, particularly in countries in Africa (20/41) and low-income countries (15/22). In 69% of countries, PD was the initial dialysis modality for ≤10% of patients with newly diagnosed kidney failure. Patients receiving PD were expected to pay 1% to 25% of treatment costs, and higher (>75%) copayments (out-of-pocket expenses incurred by patients) were more common in South Asia and low-income countries. Average exchange volumes were adequate (defined as 3-4 exchanges per day or the equivalent for automated PD) in 72% of countries. PD quality outcome monitoring and reporting were variable. Most countries did not measure patient-reported PD outcomes. Limitations: Low responses from policy makers; limited ability to provide more in-depth explanations underpinning outcomes from each country due to lack of granular data; lack of objective data. Conclusions: Large inter- and intraregional disparities exist in PD availability, accessibility, affordability, delivery, and reporting of quality outcome measures around the world, with the greatest gaps observed in Africa and South Asia.

Outcomes relevant to treatment decision-making are inconsistently reported in trials involving glomerular disease. Here, we sought to establish a consensus-derived set of critically important outcomes designed to be reported in all future trials by using an online, international two-round Delphi survey in English. To develop this, patients with glomerular disease, caregivers and health professionals aged 18 years and older rated the importance of outcomes using a Likert scale and a Best-Worst scale. The absolute and relative importance was assessed and comments were analyzed thematically. Of 1198 participants who completed Round 1, 734 were patients/caregivers while 464 were health care professionals from 59 countries. Of 700 participants that completed Round 2, 412 were patients/caregivers and 288 were health care professionals. Need for dialysis or transplant, kidney function, death, cardiovascular disease, remission-relapse and life participation were the most important outcomes to patients/caregivers and health professionals. Patients/caregivers rated patient-reported outcomes higher while health care professionals rated hospitalization, death and remission/relapse higher. Four themes explained the reasons for their priorities: confronting death and compounded suffering, focusing on specific targets in glomerular disease, preserving meaning in life, and fostering self-management. Thus, consistent reporting of these critically important outcomes in all trials involving glomerular disease is hoped to improve patient-centered decision-making.

The excess intake of dietary sodium is a key modifiable factor for reducing disease progression in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that the scored salt questionnaire (SSQ, a frequency questionnaire of nine sodium-rich food types) is a valid instrument to identify high dietary salt intake in ADPKD. The performance of the SSQ was evaluated in adults with ADPKD with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 during the screening visit of the PREVENT-ADPKD trial. High dietary sodium intake (HSI) was defined by a mean 24-hour urinary sodium excretion &ge, 100 mmol/day from two collections. The median 24-hr urine sodium excretion was 132 mmol/day (IQR: 112&ndash, 172 mmol/d) (n = 75, mean age: 44.6 &plusmn, 11.5 years old, 53% female), and HSI (86.7% of total) was associated with male gender and higher BMI and systolic blood pressure (p &lt, 0.05). The SSQ score (73 &plusmn, 23, mean &plusmn, SD) was weakly correlated with log10 24-hr urine sodium excretion (r = 0.29, p= 0.01). Receiving operating characteristic analysis showed that the optimal cut-off point in predicting HSI was an SSQ score of 74 (area under the curve 0.79, sensitivity 61.5%, specificity 90.0%, p &lt, 0.01). The evaluation of the SSQ in participants with a BMI &ge, 25 (n = 46) improved the sensitivity (100%) and the specificity (100%). Consumers with an SSQ score &ge, 74 (n = 41) had higher relative percentage intake of processed meats/seafood and flavourings added to cooking (p &lt, 0.05). In conclusion, the SSQ is a valid tool for identifying high dietary salt intake in ADPKD but its value proposition (over 24-hr urinary sodium measurement) is that it may provide consumers and their healthcare providers with insight into the potential origin of sodium-rich food sources.

© 2020 International Society of NephrologyThere is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5–10 years.

Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC 10). Intravenous transfer of ILC210 cells, but not non‐ILC 10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy., This study reveals a major protective role of the IL‐33/ILC2 axis in islet transplantation that could be potentiated as a therapeutic strategy. Adoptive transfer of ex vivo expanded IL‐10‐producing ILC2s (ILC210) significantly prolonged allograft survival.

Objective Periodontal disease is associated with chronic kidney disease (CKD), with both conditions being highly prevalent among Australia’s Aboriginal population. This paper reflects on the lessons learned following implementation of a periodontal intervention in the Central Australian region of the Northern Territory among Aboriginal adults with CKD. Results Between Oct 2016 and May 2019, research staff recruited 102 eligible participants. This was far below the anticipated recruitment rate. The challenges faced, and lessons learned, were conceptualised into five specific domains. These included: (1) insufficient engagement with the Aboriginal community and Aboriginal community-controlled organisations; (2) an under-appreciation of the existing and competing patient commitments with respect to general health and wellbeing, and medical treatment to enable all study commitments; (3) most study staff employed from outside the region; (4) potential participants not having the required number of teeth; (5) invasive intervention that involved travel to, and time at, a dental clinic. A more feasible research model, which addresses the divergent needs of participants, communities and service partners is required. This type of approach, with sufficient time and resourcing to ensure ongoing engagement, partnership and collaboration in co-design throughout the conduct of research, challenges current models of competitive, national research funding.