Showing papers by "David W. Johnson published in 2020"

TRY plant trait database : Enhanced coverage and open access

Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

Effects of Allopurinol on the Progression of Chronic Kidney Disease

Abstract: 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...

International Society for Peritoneal Dialysis practice recommendations: Prescribing high-quality goal-directed peritoneal dialysis:

Abstract: Lay summary The International Society for Peritoneal Dialysis last published a guideline on prescribing peritoneal dialysis (PD) in 2006. This focused on clearance of toxins and used a measure of waste product removal by dialysis using urea as an example. This guideline suggested that a specific quantity of small solute removal was needed to achieve dialysis `adequacy'. It is now generally accepted, however, that the well-being of the person on dialysis is related to many different factors and not just removal of specific toxins. This guideline has been written with the focus on the person doing PD. It is proposed that dialysis delivery should be `goal-directed'. This involves discussions between the person doing PD and the care team (shared decision-making) to establish care goals for dialysis delivery. The aims of these care goals are (1) to allow the person doing PD to achieve his/her own life goals and (2) to promote the provision of high-quality dialysis care by the dialysis team.Key recommendations 1. PD should be prescribed using shared decision-making between the person doing PD and the care team. The aim is to establish realistic care goals that (1) maintain quality of life for the person doing PD as much as possible by enabling them to meet their life goals, (2) minimize symptoms and treatment burden while (3) ensuring high-quality care is provided. 2. The PD prescription should take into account the local country resources, the wishes and lifestyle considerations of people needing treatment, including those of their families/caregivers', especially if providing assistance in their care. 3. A number of assessments should be used to help ensure the delivery of high-quality PD care. a. Patient reported outcome measures - this is a measure of how a person doing PD is experiencing life and his/her feeling of well-being. It should take into account the person's symptoms, impact of the dialysis regimen on the person's life, mental health and social circumstances. b. Fluid status is an important part of dialysis delivery. Urine output and fluid removed by dialysis both contribute to maintaining good fluid status. Regular assessment of fluid status, including blood pressure and clinical examination, should be part of routine care. c. Nutrition status should be assessed regularly through evaluation of the patient's appetite, clinical examination, body weight measurements and blood tests (potassium, bicarbonate, phosphate, albumin). Dietary intake of potassium, phosphate, sodium, protein, carbohydrate and fat may need to be assessed and adjusted as well. d. Removal of toxins. This can be estimated using a calculation called Kt/Vurea and/or creatinine clearance. Both are measures of the amount of dialysis delivered. There is no high-quality evidence regarding the need or benefit associated with the achievement of a specific target value for these measures. 4. The amount of kidney function that continues to remove waste products and the remaining urine volume should be known for all individuals doing PD. Management should focus on preserving this as long as possible. 5. For some people who require dialysis and who are old, frail or have a poor prognosis, there may be a quality of life benefit from a reduced dialysis prescription to minimize the burden of treatment. 6. In low and lower middle-income countries, every effort should be made to conform to the framework of these statements, taking into account resource limitations. 7. The principles of prescribing and assessing delivery of high-quality PD to children are the same as for adults. In all cases, the PD prescription should be designed to meet the medical, mental health social and financial needs of the individual child and family

Climate‐induced changes in the suitable habitat of cold‐water corals and commercially important deep‐sea fishes in the North Atlantic

Abstract: The deep sea plays a critical role in global climate regulation through uptake and storage of heat and carbon dioxide. However, this regulating service causes warming, acidification and deoxygenation of deep waters, leading to decreased food availability at the seafloor. These changes and their projections are likely to affect productivity, biodiversity and distributions of deep-sea fauna, thereby compromising key ecosystem services. Understanding how climate change can lead to shifts in deep-sea species distributions is critically important in developing management measures. We used environmental niche modelling along with the best available species occurrence data and environmental parameters to model habitat suitability for key cold-water coral and commercially important deep-sea fish species under present-day (1951-2000) environmental conditions and to project changes under severe, high emissions future (2081-2100) climate projections (RCP8.5 scenario) for the North Atlantic Ocean. Our models projected a decrease of 28%-100% in suitable habitat for cold-water corals and a shift in suitable habitat for deep-sea fishes of 2.0°-9.9° towards higher latitudes. The largest reductions in suitable habitat were projected for the scleractinian coral Lophelia pertusa and the octocoral Paragorgia arborea, with declines of at least 79% and 99% respectively. We projected the expansion of suitable habitat by 2100 only for the fishes Helicolenus dactylopterus and Sebastes mentella (20%-30%), mostly through northern latitudinal range expansion. Our results projected limited climate refugia locations in the North Atlantic by 2100 for scleractinian corals (30%-42% of present-day suitable habitat), even smaller refugia locations for the octocorals Acanella arbuscula and Acanthogorgia armata (6%-14%), and almost no refugia for P. arborea. Our results emphasize the need to understand how anticipated climate change will affect the distribution of deep-sea species including commercially important fishes and foundation species, and highlight the importance of identifying and preserving climate refugia for a range of area-based planning and management tools.

Soil fungal networks maintain local dominance of ectomycorrhizal trees.

Abstract: The mechanisms regulating community composition and local dominance of trees in species-rich forests are poorly resolved, but the importance of interactions with soil microbes is increasingly acknowledged. Here, we show that tree seedlings that interact via root-associated fungal hyphae with soils beneath neighbouring adult trees grow faster and have greater survival than seedlings that are isolated from external fungal mycelia, but these effects are observed for species possessing ectomycorrhizas (ECM) and not arbuscular mycorrhizal (AM) fungi. Moreover, survival of naturally-regenerating AM seedlings over ten years is negatively related to the density of surrounding conspecific plants, while survival of ECM tree seedlings displays positive density dependence over this interval, and AM seedling roots contain greater abundance of pathogenic fungi than roots of ECM seedlings. Our findings show that neighbourhood interactions mediated by beneficial and pathogenic soil fungi regulate plant demography and community structure in hyperdiverse forests.

Identifying Outcomes Important to Patients with Glomerular Disease and Their Caregivers.

Abstract: 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.

A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD).

Abstract: Background Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain.Methods To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.Results A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73m(2); 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.Conclusions In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.

The psychosocial impact of facial palsy: A systematic review.

Abstract: Purpose Facial palsy is a condition which can lead to significant changes in facial function and appearance. People with facial palsy often report psychosocial difficulties, including withdrawal from social activities, anxiety, negative body image, and low mood. This paper aimed to review all published research investigating the psychosocial impact of facial palsy on adults. Methods A systematic search of MEDLINE, CINAHL, EMBASE, PsycINFO, and AMED databases was performed. The quality of included studies was assessed, and data were extracted with regard to characteristics of participants; study methodology and design; outcome measures used; and psychosocial outcomes. Results Twenty-seven studies met inclusion criteria. A high proportion of people with facial palsy reported clinically significant levels of anxiety and depression, with greater difficulties typically reported by females, compared to males. Other difficulties consistently reported include low quality of life, poor social function, and high levels of appearance-related distress. Objective severity of facial palsy was consistently shown to not be associated with anxiety or depression, with psychological factors instead likely mediating the relationship between the severity of facial palsy and psychosocial well-being. Conclusions Irrespective of objective symptom severity, facial palsy has the potential to have a significant impact on psychosocial well-being and quality of life. The various methodological limitations of the included studies are discussed, along with clinical implications, including the need for greater access to psychological screening and interventions for people with facial palsy.

Meaning of empowerment in peritoneal dialysis: focus groups with patients and caregivers.

Abstract: Background While peritoneal dialysis (PD) can offer patients more independence and flexibility compared with in-center hemodialysis, managing the ongoing and technically demanding regimen can impose a burden on patients and caregivers. Patient empowerment can strengthen capacity for self-management and improve treatment outcomes. We aimed to describe patients' and caregivers' perspectives on the meaning and role of patient empowerment in PD. Methods Adult patients receiving PD (n = 81) and their caregivers (n = 45), purposively sampled from nine dialysis units in Australia, Hong Kong and the USA, participated in 14 focus groups. Transcripts were thematically analyzed. Results We identified six themes: lacking clarity for self-management (limited understanding of rationale behind necessary restrictions, muddled by conflicting information); PD regimen restricting flexibility and freedom (burden in budgeting time, confined to be close to home); strength with supportive relationships (gaining reassurance with practical assistance, comforted by considerate health professionals, supported by family and friends); defying constraints (reclaiming the day, undeterred by treatment, refusing to be defined by illness); regaining lost vitality (enabling physical functioning, restoring energy for life participation); and personal growth through adjustment (building resilience and enabling positive outlook, accepting the dialysis regimen). Conclusions Understanding the rationale behind lifestyle restrictions, practical assistance and family support in managing PD promoted patient empowerment, whereas being constrained in time and capacity for life participation outside the home undermined it. Education, counseling and strategies to minimize the disruption and burden of PD may enhance satisfaction and outcomes in patients requiring PD.

Survival after Kidney Transplantation during Childhood and Adolescence

Abstract: Background and objectives Survival in pediatric kidney transplant recipients has improved over the past five decades, but changes in cause-specific mortality remain uncertain. The aim of this retrospective cohort study was to estimate the associations between transplant era and overall and cause-specific mortality for child and adolescent recipients of kidney transplants. Design, setting, participants, & measurements Data were obtained on all children and adolescents (aged Results A total of 1810 recipients (median age at transplantation 14 years, 58% male, 52% living donor) were followed for a median of 13.4 years. Of these, 431 (24%) died, 174 (40%) from cardiovascular causes, 74 (17%) from infection, 50 (12%) from cancer, and 133 (31%) from other causes. Survival rates improved over time, with 5-year survival rising from 85% for those first transplanted in 1970–1985 (95% confidence interval [95% CI], 81% to 88%) to 99% in 2005–2015 (95% CI, 98% to 100%). This was primarily because of reductions in deaths from cardiovascular causes (adjusted hazard ratio [aHR], 0.25; 95% CI, 0.08 to 0.68) and infections (aHR, 0.16; 95% CI, 0.04 to 0.70; both for 2005–2015 compared with 1970–1985). Compared with patients transplanted 1970–1985, mortality risk was 72% lower among those transplanted 2005–2015 (aHR, 0.28; 95% CI, 0.18 to 0.69), after adjusting for potential confounders. Conclusions Survival after pediatric kidney transplantation has improved considerably over the past four decades, predominantly because of marked reductions in cardiovascular- and infection-related deaths.

Allograft failure in kidney transplant recipients whose primary kidney disease was anca-associated vasculitis

Abstract: Background: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium are injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. Methods: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on day 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), Beta-D-Glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. Findings: Of the 19 patients, 14 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA ([≥] 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. Interpretation: Bacterial DNA and toxins were discovered in virtual all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

Synthesis of Metastable Inorganic Solids with Extended Structures.

Abstract: The number of known inorganic compounds is dramatically less than predicted due to synthetic challenges, which often constrains products to only the thermodynamically most stable compounds. Consequently, a mechanism-based approach to inorganic solids with designed structures is the holy grail of solid state synthesis. This article discusses a number of synthetic approaches using the concept of an energy landscape, which describes the complex relationship between the energy of different atomic configurations as a function of a variety of parameters such as initial structure, temperature, pressure, and composition. Nucleation limited synthesis approaches with high diffusion rates are contrasted with diffusion limited synthesis approaches. One challenge to the synthesis of new compounds is the inability to accurately predict what structures might be local free energy minima in the free energy landscape. Approaches to this challenge include predicting potentially stable compounds thorough the use of structural homologies and/or theoretical calculations. A second challenge to the synthesis of metastable inorganic solids is developing approaches to move across the energy landscape to a desired local free energy minimum while avoiding deeper free energy minima, such as stable binary compounds, as reaction intermediates. An approach using amorphous intermediates is presented, where local composition can be used to prepare metastable compounds. Designed nanoarchitecture built into a precursor can be preserved at low reaction temperatures and used to direct the reaction to specific structural homologs.

A tRial Evaluating Mid Cut-Off Value Membrane Clearance of Albumin and Light Chains in HemoDialysis Patients: A Safety Device Study.

Abstract: Background: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. Methods: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. Results: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had ­diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction –0.7 g/L, 95% CI –1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ –9.1 mg/L, 95% CI –14.4 to –3.7; kappa-FLC: Δ –5.7 mg/L, 95% CI –9.8 to –1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. Conclusions: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. Trial Registration: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.

Imaging spectroscopy reveals the effects of topography and logging on the leaf chemistry of tropical forest canopy trees.

Abstract: Logging, pervasive across the lowland tropics, affects millions of hectares of forest, yet its influence on nutrient cycling remains poorly understood. One hypothesis is that logging influences phosphorus (P) cycling, because this scarce nutrient is removed in extracted timber and eroded soil, leading to shifts in ecosystem functioning and community composition. However, testing this is challenging because P varies within landscapes as a function of geology, topography and climate. Superimposed upon these trends are compositional changes in logged forests, with species with more acquisitive traits, characterized by higher foliar P concentrations, more dominant. It is difficult to resolve these patterns using traditional field approaches alone. Here, we use airborne light detection and ranging-guided hyperspectral imagery to map foliar nutrient (i.e. P, nitrogen [N]) concentrations, calibrated using field measured traits, over 400 km(2) of northeastern Borneo, including a landscape-level disturbance gradient spanning old-growth to repeatedly logged forests. The maps reveal that canopy foliar P and N concentrations decrease with elevation. These relationships were not identified using traditional field measurements of leaf and soil nutrients. After controlling for topography, canopy foliar nutrient concentrations were lower in logged forest than in old-growth areas, reflecting decreased nutrient availability. However, foliar nutrient concentrations and specific leaf area were greatest in relatively short patches in logged areas, reflecting a shift in composition to pioneer species with acquisitive traits. N:P ratio increased in logged forest, suggesting reduced soil P availability through disturbance. Through the first landscape scale assessment of how functional leaf traits change in response to logging, we find that differences from old-growth forest become more pronounced as logged forests increase in stature over time, suggesting exacerbated phosphorus limitation as forests recover.

Predicting ultrahigh risk multiple myeloma by molecular profiling: an analysis of newly diagnosed transplant eligible myeloma XI trial patients.

Abstract: The prognosis for newly diagnosed multiple myeloma (NDMM) has improved with the advent of new agents, but outcome in some patients remains very poor. Identifying patients with high-risk disease early opens up the prospect of stratified treatment [1–3]. Biomarkers including chromosomal aberrations t(4;14), t(14;16), and t(14;20) translocations, gain of 1q and deletion of 17p, detected by fluorescence in situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) and qRT-PCR-based translocation detection, have been associated with adverse outcome and co-occurrence of ≥2 such aberrations (a double-hit) is predictive of especially aggressive MM [4, 5]. Multiple gene expression profiles (GEP) have been reported to be associated with outcome, but so far only EMC92 and UAMS GEP70 have been developed into validated clinical tests, marketed as SKY92 MMprofiler and MyPRS, respectively [6–9]. To examine the combined predictive value of high-risk chromosomal abnormalities and SKY92 risk GEP we studied 329 NDMM patients from the NCRI Myeloma XI trial (ISRCTN49407852) who received intensive therapy (Supplementary Table 1) and validated findings in Medical Research Council (MRC) Myeloma IX trial patients (Supplementary Methods) [10, 11]. In both cohorts of patients purified (>95%) CD138-positive tumor cells were immunomagnetically selected and DNA and RNA were extracted using QIAGEN (Hilden, Germany) Allprep kits. Chromosomal aberrations, including high-risk lesions t(4;14), t(14;16), t(14;20), gain(1q), and del(17p), were assessed using qRT-PCR (Thermo Fisher, Darford, UK) and MLPA (MRC Holland, Amsterdam, The Netherlands), as previously reported (Supplementary Methods) [4]. GEP risk status was determined on a diagnostic Affymetrix GeneChip 3000 Dx v2.0 system (Thermo Fisher) using the SKY92 Members of the NCRI Haematology Clinical Studies Group are listed below Acknowledgements

A coaching program to improve dietary intake of patients with CKD: ENTICE-CKD

Abstract: Background and objectives The dietary self-management of CKD is challenging. Telehealth interventions may provide an effective delivery method to facilitate sustained dietary change. Design, setting, participants, & measurements This pilot, randomized, controlled trial evaluated secondary and exploratory outcomes after a dietitian-led telehealth coaching intervention to improve diet quality in people with stage 3–4 CKD. The intervention group received phone calls every 2 weeks for 3 months (with concurrent, tailored text messages for 3 months), followed by 3 months of tailored text messages without telephone coaching, to encourage a diet consistent with CKD guidelines. The control group received usual care for 3 months, followed by nontailored, educational text messages for 3 months. Results Eighty participants (64% male), aged 62±12 years, were randomized to the intervention or control group. Telehealth coaching was safe, with no adverse events or changes to serum biochemistry at any time point. At 3 months, the telehealth intervention, compared with the control, had no detectable effect on overall diet quality on the Alternative Health Eating Index (3.2 points, 95% confidence interval, −1.3 to 7.7), nor at 6 months (0.5 points, 95% confidence interval, −4.6 to 5.5). There was no change in clinic BP at any time point in any group. There were significant improvements in several exploratory diet and clinical outcomes, including core food group consumption, vegetable servings, fiber intake, and body weight. Conclusions Telehealth coaching was safe, but appeared to have no effect on the Alternative Healthy Eating Index or clinic BP. There were clinically significant changes in several exploratory diet and clinical outcomes, which require further investigation. Clinical Trial registry name and registration number: Evaluation of Individualized Telehealth Intensive Coaching to Promote Healthy Eating and Lifestyle in CKD (ENTICE-CKD), ACTRN12616001212448.

Identifying critically important vascular access outcomes for trials in haemodialysis : an international survey with patients, caregivers and health professionals

Abstract: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD.

Postoperative mortality in patients on chronic dialysis following elective surgery: A systematic review and meta-analysis.

Abstract: Rationale & objective: The prognostic significance of dialysis-dependent end-stage kidney disease on postoperative mortality is unclear This study aims to estimate the odds of postoperative mortality in patients receiving chronic dialysis undergoing elective surgery compared to patients with normal kidney function, and to examine the influence of comorbidities on the excess mortality risk Methods: A systematic search of studies published up to January 2020 was conducted using MEDLINE, EMBASE and CENTRAL databases Eligible studies reported postoperative 30-day or in-hospital mortality in chronic dialysis patients compared to patients with normal kidney function undergoing elective surgery Two investigators independently reviewed all abstracts and performed risk of bias assessments using the Newcastle-Ottawa Scale Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations, assessment, development and evaluation) Relative mortality risk estimates were obtained using random effects meta-analysis Heterogeneity was explored using meta-regression (PROSPERO CRD42017076565) Results: Forty-nine studies involving 41, 822 chronic dialysis and 10, 476, 321 non-dialysis patients undergoing elective surgery were included Patients on chronic dialysis had a greatly increased postoperative mortality odds compared to patients with normal kidney function The excess risk ranged from OR 108 (95%CI 73–159) following orthopaedic surgery to OR 40 (95%CI 32–49) after vascular surgery Adjustment for age and comorbidity attenuated the excess odds but remained higher for patients on chronic dialysis, irrespective of surgical discipline Meta-regression analysis demonstrated an inverse linear relationship between excess mortality risk and study-level mean age (slope -006; P = 0001) and diabetes prevalence (slope -002; p = 0001) Conclusions: Patients on chronic dialysis have an increased odds for postoperative mortality following elective surgery across all surgical disciplines This relationship is consistent among all studies, with the excess postoperative mortality attributable to end-stage kidney disease and chronic dialysis treatment may be lower among older patients with diabetes

A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.

Abstract: Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10–8): rs781716 (P = 4.71 × 10–9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10–8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10–9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10–8, OR = 0.45; P = 3.31 × 10–8, OR = 0.45; P = 1.09 × 10–8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10–8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10–6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821–55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Kidney care in low- and middle-income countries

Abstract: Optimal kidney care requires a trained nephrology workforce, essential healthcare services, and medications. This study aimed to identify the access to these resources on a global scale using data from the multinational survey conducted by the International Society of Nephrology (ISN) (Global Kidney Health Atlas (GKHA) project), with emphasis on developing nations. For data analysis, the 125 participating countries were sorted into the 4 World Bank income groups: low income (LIC), lower-middle income (LMIC), upper-middle income (UMIC), and high income (HIC). A severe shortage of nephrologists was observed in LIC and LMIC with < 5 nephrologists per million population. Many LIC were unable to access estimated glomerular filtration rate (eGFR) and albuminuria (proteinuria) tests in primary-care levels. Acute and chronic hemodialysis was available in most countries, although acute and chronic peritoneal dialysis access was severely limited in LIC (24% and 35%, respectively). Most countries had kidney transplantation access, except for LIC (12%). HIC and UMIC funded their renal replacement therapy (RRT) and renal medications primarily through public means, whereas LMIC and LIC required private and out-of-pocket contributions. In conclusion, this study found a huge gap in the availability and access to trained nephrology workforce, tools for diagnosis and management of CKD, RRT, and funding of RRT and essential medications in LIC and LMIC.

Study Protocol for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): A pragmatic, registry-based, multi-center, double-blind, randomized controlled trial evaluating the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on delayed graft function in deceased donor kidney transplantation

Abstract: Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. Australian New Zealand Clinical Trials Registry: ACTRN12617000358347 . Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488 . Registered on 4 February 2019.

Peritoneal dialysis-associated peritonitis outcomes reported in trials and observational studies: A systematic review.

Abstract: Background:Peritoneal dialysis (PD)-associated peritonitis carries significant morbidity, mortality, and is a leading cause of PD technique failure. This study aimed to assess the scope and variabi...