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Showing papers by "David W. Johnson published in 2017"


Journal ArticleDOI
TL;DR: Use of this therapy is increasing in some countries, but has proportionally decreased in parts of Europe and in Japan, and further growth in peritoneal dialysis use is required to enable this modality to become an integral part of renal replacement therapy programmes worldwide.
Abstract: As the global burden of chronic kidney disease continues to increase, so does the need for a cost-effective renal replacement therapy. In many countries, patient outcomes with peritoneal dialysis are comparable to or better than those with haemodialysis, and peritoneal dialysis is also more cost-effective. These benefits have not, however, always led to increased utilization of peritoneal dialysis. Use of this therapy is increasing in some countries, including China, the USA and Thailand, but has proportionally decreased in parts of Europe and in Japan. The variable trends in peritoneal dialysis use reflect the multiple challenges in prescribing this therapy to patients. Key strategies for facilitating peritoneal dialysis utilization include implementation of policies and incentives that favour this modality, enabling the appropriate production and supply of peritoneal dialysis fluid at a low cost, and appropriate training for nephrologists to enable increased utilization of the therapy and to ensure that rates of technique failure continue to decline. Further growth in peritoneal dialysis use is required to enable this modality to become an integral part of renal replacement therapy programmes worldwide.

348 citations


Journal ArticleDOI
01 Aug 2017-JAMA
TL;DR: The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study as discussed by the authors was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1).
Abstract: Importance Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain. Objective To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression. Design, Setting, and Participants The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m 2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred. Interventions Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months. Main Outcomes and Measures The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years. Results After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m 2 ; urine protein excretion, 2.40 g/d) and 2.1 years’ median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group ( P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P P = .02). Conclusions and Relevance Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial. Trial Registration clinicaltrials.gov Identifier:NCT01560052

308 citations


Journal ArticleDOI
09 May 2017-JAMA
TL;DR: This survey demonstrated significant interregional and intraregional variability in the current capacity for kidney care across the world, including important gaps in services and workforce.
Abstract: Importance Kidney disease is a substantial worldwide clinical and public health problem, but information about available care is limited. Objective To collect information on the current state of readiness, capacity, and competence for the delivery of kidney care across countries and regions of the world. Design, Setting, and Participants Questionnaire survey administered from May to September 2016 by the International Society of Nephrology (ISN) to 130 ISN-affiliated countries with sampling of key stakeholders (national nephrology society leadership, policy makers, and patient organization representatives) identified by the country and regional nephrology leadership through the ISN. Main Outcomes and Measures Core areas of country capacity and response for kidney care. Results Responses were received from 125 of 130 countries (96%), including 289 of 337 individuals (85.8%, with a median of 2 respondents [interquartile range, 1-3]), representing an estimated 93% (6.8 billion) of the world’s population of 7.3 billion. There was wide variation in country readiness, capacity, and response in terms of service delivery, financing, workforce, information systems, and leadership and governance. Overall, 119 (95%), 95 (76%), and 94 (75%) countries had facilities for hemodialysis, peritoneal dialysis, and kidney transplantation, respectively. In contrast, 33 (94%), 16 (45%), and 12 (34%) countries in Africa had facilities for hemodialysis, peritoneal dialysis, and kidney transplantation, respectively. For chronic kidney disease (CKD) monitoring in primary care, serum creatinine with estimated glomerular filtration rate and proteinuria measurements were reported as always available in only 21 (18%) and 9 (8%) countries, respectively. Hemodialysis, peritoneal dialysis, and transplantation services were funded publicly and free at the point of care delivery in 50 (42%), 48 (51%), and 46 (49%) countries, respectively. The number of nephrologists was variable and was low ( Conclusions and Relevance This survey demonstrated significant interregional and intraregional variability in the current capacity for kidney care across the world, including important gaps in services and workforce. Assuming the responses accurately reflect the status of kidney care in the respondent countries, the findings may be useful to inform efforts to improve the quality of kidney care worldwide.

259 citations


Journal ArticleDOI
TL;DR: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Department of Nephrology, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia; Renal Electrolyte Division.
Abstract: Peritoneal dialysis (PD) catheter-related infections are a major predisposing factor to PD-related peritonitis (1–3). The primary objective of preventing and treating catheter-related infections is to prevent peritonitis.Recommendations on the prevention and treatment of catheter-related infections were published previously together with recommendations on PD peritonitis under the auspices of the International Society for Peritoneal Dialysis (ISPD) in 1983 and revised in 1989, 1993, 1996, 2000, 2005, and 2010 (4–9). The present recommendations, however, focus on catheter-related infections, while peritonitis will be covered in a separate guideline.These recommendations are evidence-based where such evidence exists. The bibliography is not intended to be comprehensive. When there are many similar reports on the same area, the committee prefers to refer to the more recent publications. In general, these recommendations follow the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system for classification of the level of evidence and grade of recommendations in clinical guideline reports (10). Within each recommendation, the strength of recommendation is indicated as Level 1 (We recommend), Level 2 (We suggest), or Not Graded, and the quality of the supporting evidence is shown as A (high quality), B (moderate quality), C (low quality), or D (very low quality). The recommendations are not meant to be implemented in every situation indiscriminately. Each PD unit should examine its own pattern of infection, causative organisms, and sensitivities and adapt the protocols according to local conditions as necessary. Although many of the general principles presented here could be applied to pediatric patients, we focus on catheter-related infections in adult patients. Clinicians who take care of pediatric PD patients should refer to the latest consensus guideline in this area for detailed treatment regimen and dosage (11).

218 citations


Journal ArticleDOI
TL;DR: A consensus-based prioritized list of core outcomes for trials in hemodialysis will improve the relevance, efficiency, and comparability of trial evidence to facilitate treatment decisions and patients/caregivers gave higher priority to lifestyle-related outcomes than health professionals.

187 citations


Journal ArticleDOI
TL;DR: Unabated growth in the incidence of diabetic kidney disease, underpinned by a global imbalance between overnutrition and inadequate physical inactivity causing overweight and obesity, is the key driver of CKD burden.
Abstract: 2017 is an important year for the international nephrology community. March 9 was World Kidney Day, the theme this year being ‘Kidney disease and obesity: healthy lifestyles for healthy kidneys’, highlighting the crucial link between the kidneys and metabolic and cardiovascular health. In April, the Global Kidney Health Atlas, one of the largest health-related country capacity reviews in history, was launched at the World Congress of Nephrology in Mexico City. The Atlas, a first for the nephrology community, is a multinational cross-sectional survey designed to assess need and capacity for kidney care worldwide and provide the foundation for a global surveillance network for chronic kidney disease (CKD) care. CKD is an enormous public health issue, the tide of which continues to inexorably rise. In the 2015 Global Burden of Disease Study, kidney disease was the 12th most common cause of death, accounting for 1.1 million deaths worldwide.1 Overall CKD mortality has increased by 31.7% over the last 10 years, making it one of the fastest rising major causes of death, alongside diabetes and dementia.1 In the same study, CKD ranked as the 17th leading cause of global years lost of life, an 18.4% increase since 2005, and the third largest increase of any major cause of death.1 This is in stark contrast to other non-communicable diseases, for example cardiovascular disease and chronic obstructive pulmonary disease, where global years lost of life fell during the same time period (−10.2% and −3.0%, respectively).1 Unabated growth in the incidence of diabetic kidney disease, underpinned by a global imbalance between overnutrition and inadequate physical inactivity causing overweight and obesity, is the key driver of CKD burden. Between 2005 and 2015, the prevalence of diabetic kidney disease increased by 39.5% globally.1 In Mexico, the country with the highest CKD death rate in the world, …

148 citations


Journal ArticleDOI
Allison Tong1, Allison Tong2, Braden Manns3, Brenda R. Hemmelgarn3, David C. Wheeler4, Nicole Evangelidis1, Nicole Evangelidis2, Peter Tugwell5, Sally Crowe, Wim Van Biesen6, Wolfgang C. Winkelmayer7, Donal O'Donoghue8, Helen Tam-Tham3, Jenny I. Shen9, Jule Pinter2, Jule Pinter1, Nicholas Larkins1, Nicholas Larkins2, Sajeda Youssouf8, Sreedhar Mandayam7, Angela Ju2, Angela Ju1, Jonathan C. Craig2, Jonathan C. Craig1, Allan J. Collins, Andrew S. Narva, Bénédicte Sautenet, Billy Powell, Brenda Hurd, Brendan J. Barrett, Brigitte Schiller, Bruce F. Culleton, Carmel M. Hawley, Carol A. Pollock, Charmaine E. Lok, Christoph Wanner, Christopher T. Chan, Daniel E. Weiner, David Harris, David W. Johnson, David Rosenbloom, Dena E. Rifkin, Deshia Bookman, Edwina A. Brown, Elena Bavlovlenkov, Francesca Tentori, Jack Williams, Jane O. Schell, Jennifer E. Flythe, Joachim H. Ix, Jochen G. Raimann, Joel Andress, John W M Agar, John T. Daugirdas, John S. Gill, John W. Kusek, Kevan R. Polkinghorne, Kevin C. Abbott, Len Usyvat, Mahesh Krishnan, Marcello Tonelli, Mark R. Marshall, Martin Gallagher, Michael J. Germain, Michael Walsh, Michael Zappitelli, Michelle A. Josephson, Nilka Ríos Burrows, Orlando Houston, Peter G. Kerr, Peter Kotanko, Prabir Roy-Chaudhury, Rachael L. Morton, Raj Mehrotra, Rene van den Dorpel, Rita S. Suri, Ron Wald, Ronke Apata, Shalia Gibson, Sharrilyn Evered, Stephen Z. Fadem, Stephen P. McDonald, Steve Holt, Terence Kee, David Wheeler4, Tess Harris, Wolfgang C. Winkelmayer7, Jenny Shen9, Reva Parks 
TL;DR: Qualitative analyses of the workshop discussions are reported, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy, and recommending simple, inexpensive, and validated outcome measures that could be used in clinical care and trials.

146 citations



Journal ArticleDOI
TL;DR: Strategies to optimize clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed, and the added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted.
Abstract: Purpose of reviewWhen providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic

126 citations


Journal ArticleDOI
TL;DR: In absolute terms, dietary interventions may prevent one person in every 3000 treated for one year avoiding ESKD, although the certainty in this effect was very low, and confidence in the results was lowered.
Abstract: Background Dietary changes are routinely recommended in people with chronic kidney disease (CKD) on the basis of randomised evidence in the general population and non-randomised studies in CKD that suggest certain healthy eating patterns may prevent cardiovascular events and lower mortality. People who have kidney disease have prioritised dietary modifications as an important treatment uncertainty. Objectives This review evaluated the benefits and harms of dietary interventions among adults with CKD including people with end-stage kidney disease (ESKD) treated with dialysis or kidney transplantation. Search methods We searched the Cochrane Kidney and Transplant Specialised Register (up to 31 January 2017) through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) or quasi-randomised RCTs of dietary interventions versus other dietary interventions, lifestyle advice, or standard care assessing mortality, cardiovascular events, health-related quality of life, and biochemical, anthropomorphic, and nutritional outcomes among people with CKD. Data collection and analysis Two authors independently screened studies for inclusion and extracted data. Results were summarised as risk ratios (RR) for dichotomous outcomes or mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI) or in descriptive format when meta-analysis was not possible. Confidence in the evidence was assessed using GRADE. Main results We included 17 studies involving 1639 people with CKD. Three studies enrolled 341 people treated with dialysis, four studies enrolled 168 kidney transplant recipients, and 10 studies enrolled 1130 people with CKD stages 1 to 5. Eleven studies (900 people) evaluated dietary counselling with or without lifestyle advice and six evaluated dietary patterns (739 people), including one study (191 people) of a carbohydrate-restricted low-iron, polyphenol enriched diet, two studies (181 people) of increased fruit and vegetable intake, two studies (355 people) of a Mediterranean diet and one study (12 people) of a high protein/low carbohydrate diet. Risks of bias in the included studies were generally high or unclear, lowering confidence in the results. Participants were followed up for a median of 12 months (range 1 to 46.8 months). Studies were not designed to examine all-cause mortality or cardiovascular events. In very-low quality evidence, dietary interventions had uncertain effects on all-cause mortality or ESKD. In absolute terms, dietary interventions may prevent one person in every 3000 treated for one year avoiding ESKD, although the certainty in this effect was very low. Across all 17 studies, outcome data for cardiovascular events were sparse. Dietary interventions in low quality evidence were associated with a higher health-related quality of life (2 studies, 119 people: MD in SF-36 score 11.46, 95% CI 7.73 to 15.18; I2 = 0%). Adverse events were generally not reported. Dietary interventions lowered systolic blood pressure (3 studies, 167 people: MD -9.26 mm Hg, 95% CI -13.48 to -5.04; I2 = 80%) and diastolic blood pressure (2 studies, 95 people: MD -8.95, 95% CI -10.69 to -7.21; I2 = 0%) compared to a control diet. Dietary interventions were associated with a higher estimated glomerular filtration rate (eGFR) (5 studies, 219 people: SMD 1.08; 95% CI 0.26 to 1.97; I2 = 88%) and serum albumin levels (6 studies, 541 people: MD 0.16 g/dL, 95% CI 0.07 to 0.24; I2 = 26%). A Mediterranean diet lowered serum LDL cholesterol levels (1 study, 40 people: MD -1.00 mmol/L, 95% CI -1.56 to -0.44). Authors' conclusions Dietary interventions have uncertain effects on mortality, cardiovascular events and ESKD among people with CKD as these outcomes were rarely measured or reported. Dietary interventions may increase health-related quality of life, eGFR, and serum albumin, and lower blood pressure and serum cholesterol levels. Based on stakeholder prioritisation of dietary research in the setting of CKD and preliminary evidence of beneficial effects on risks factors for clinical outcomes, large-scale pragmatic RCTs to test the effects of dietary interventions on patient outcomes are required.

106 citations


Journal ArticleDOI
TL;DR: An endoAVF can be reliably created using a radiofrequency magnetic catheter-based system, without open surgery and with minimal complications and may be a viable alternative option for achieving AVFs for hemodialysis patients in need of vascular access.

Journal ArticleDOI
TL;DR: This paper presents a meta-analyses of the prophylactic and statistical literature reviews conducted at the 2016 US National Kidney Research Conference of the American Academy of Family Medicine and Surgeons (NAAS) and presented at the 2015 US National Institutes of Health (NIH) conference on “ regenerative medicine”.
Abstract: Imperial College Renal and Transplant Centre,1 Hammersmith Hospital, London, UK; University Health Network and the University of Toronto,2 Toronto, ON, Canada; Renal Division,3 Ghent University Hospital, Ghent, Belgium; Kidney Research Center,4 Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Yale School of Medicine,5 New Haven, CT, USA; Central Manchester and Manchester Children’s NHS Foundation Trust,6 Manchester, UK; Department of Nephrology,7 University of Queensland at Princess Alexandra Hospital, Brisbane, Australia; Tsuchiya General Hospital,8 Faculty of Medicine, Hiroshima University, Japan; Institute for Applied Clinical Sciences,9 Keele University, Stoke-on-Trent, UK; Pontificia Universidade Catolica do Parana,10 Curitiba, Parana, Brazil; Division of Nephrology,11 Cliniques universitaires Saint-Luc, Brussels, Belgium, et Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium; and St James’s University Hospital,12 Leeds, UK ISPD GUIDELINES/RECOMMENDATIONS

Journal ArticleDOI
TL;DR: In this paper, the authors used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative.
Abstract: Background Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ~1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. Methods We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative. Results We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (two families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). Conclusions This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results.

Journal ArticleDOI
TL;DR: In this paper, the authors show that electron correlation has a profound effect on the magnetic properties and dynamic stability of transition-metal dichalcogenides and bilayers, including a Hubbard-$U$ term in the density-functionaltheory calculations.
Abstract: With the emergence of graphene and other two-dimensional (2D) materials, transition-metal dichalcogenides have been investigated intensely as potential 2D materials using experimental and theoretical methods. ${\mathrm{VSe}}_{2}$ is an especially interesting material since its bulk modification exhibits a charge-density wave (CDW), the CDW is retained even for few-layer nanosheets, and monolayers of ${\mathrm{VSe}}_{2}$ are predicted to be ferromagnetic. In this work, we show that electron correlation has a profound effect on the magnetic properties and dynamic stability of ${\mathrm{VSe}}_{2}$ monolayers and bilayers. Including a Hubbard-$U$ term in the density-functional-theory calculations strongly affects the magnetocrystalline anisotropy in the $1T\ensuremath{-}{\mathrm{VSe}}_{2}$ structure while leaving the $2H$-polytype virtually unchanged. This demonstrates the importance of electronic correlations for the electrical and magnetic properties of $1T\ensuremath{-}{\mathrm{VSe}}_{2}$. The Hubbard-$U$ term changes the dynamic stability and the presence of imaginary modes of ferromagnetic $1T\ensuremath{-}{\mathrm{VSe}}_{2}$ while affecting only the amplitudes in the nonmagnetic phase. The Fermi surface of nonmagnetic $1T\ensuremath{-}{\mathrm{VSe}}_{2}$ allows for nesting along the CDW vector, but it plays no role in ferromagnetic $1T\ensuremath{-}{\mathrm{VSe}}_{2}$. Following the eigenvectors of the soft modes in nonmagnetic $1T\ensuremath{-}{\mathrm{VSe}}_{2}$ monolayers yields a CDW structure with a $4\ifmmode\times\else\texttimes\fi{}4$ supercell and Peierls-type distortion in the atomic positions and electronic structure. The magnetic order indicates the potential for spin-density-wave structures.

Journal ArticleDOI
TL;DR: In this article, the authors identified center-and patient-level predictors of peritoneal dialysis technique failure using Cox shared frailty models and showed that technique failure was significantly less likely in centers with larger proportions of patients treated with peritoneAL dialysis (>29%; adjusted hazard ratio, 0.83; 95% confidence interval, 073 to 0.94) and more likely in smaller centers.
Abstract: Background and objectives Technique failure is a major limitation of peritoneal dialysis. Our study aimed to identify center- and patient-level predictors of peritoneal dialysis technique failure. Design, setting, participants, & measurements All patients on incident peritoneal dialysis in Australia from 2004 to 2014 were included in the study using data from the Australia and New Zealand Dialysis and Transplant Registry. Center- and patient-level characteristics associated with technique failure were evaluated using Cox shared frailty models. Death-censored technique failure and cause-specific technique failure were analyzed as secondary outcomes. Results The study included 9362 patients from 51 centers in Australia. The technique failure rate was 0.35 (95% confidence interval, 0.34 to 0.36) episodes per patient-year, with a sevenfold variation across centers that was mainly associated with center-level characteristics. Technique failure was significantly less likely in centers with larger proportions of patients treated with peritoneal dialysis (>29%; adjusted hazard ratio, 0.83; 95% confidence interval, 0.73 to 0.94) and more likely in smaller centers ( Conclusions Technique failure varies widely across centers in Australia. A significant proportion of this variation is related to potentially modifiable center characteristics, including peritoneal dialysis center size, proportion of patients on peritoneal dialysis, and proportion of patients on peritoneal dialysis achieving target phosphate level.

Journal ArticleDOI
TL;DR: Several modifiable and nonmodifiable factors are associated with early technique failure in PD, and targeted interventions should be considered in high-risk patients to avoid the consequences of an unplanned transfer to hemodialysis therapy or death.

Journal ArticleDOI
TL;DR: The incidence of adverse sedation outcomes varied significantly with type of sedation medication, and use of ketamine only was associated with the best outcomes, resulting in significantly fewer SAEs and interventions than ketamine combined with propofol or fentanyl.
Abstract: Importance Procedural sedation for children undergoing painful procedures is standard practice in emergency departments worldwide. Previous studies of emergency department sedation are limited by their single-center design and are underpowered to identify risk factors for serious adverse events (SAEs), thereby limiting their influence on sedation practice and patient outcomes. Objective To examine the incidence and risk factors associated with sedation-related SAEs. Design, Setting, and Participants This prospective, multicenter, observational cohort study was conducted in 6 pediatric emergency departments in Canada between July 10, 2010, and February 28, 2015. Children 18 years or younger who received sedation for a painful emergency department procedure were enrolled in the study. Of the 9657 patients eligible for inclusion, 6760 (70.0%) were enrolled and 6295 (65.1%) were included in the final analysis. Exposures The primary risk factor was receipt of sedation medication. The secondary risk factors were demographic characteristics, preprocedural medications and fasting status, current or underlying health risks, and procedure type. Main Outcomes and Measures Four outcomes were examined: SAEs, significant interventions performed in response to an adverse event, oxygen desaturation, and vomiting. Results Of the 6295 children included in this study, 4190 (66.6%) were male and the mean (SD) age was 8.0 (4.6) years. Adverse events occurred in 736 patients (11.7%; 95% CI, 6.4%-16.9%). Oxygen desaturation (353 patients [5.6%]) and vomiting (328 [5.2%]) were the most common of these adverse events. There were 69 SAEs (1.1%; 95% CI, 0.5%-1.7%), and 86 patients (1.4%; 95% CI, 0.7%-2.1%) had a significant intervention. Use of ketamine hydrochloride alone resulted in the lowest incidence of SAEs (17 [0.4%]) and significant interventions (37 [0.9%]). The incidence of adverse sedation outcomes varied significantly with the type of sedation medication. Compared with ketamine alone, propofol alone (3.7%; odds ratio [OR], 5.6; 95% CI, 2.3-13.1) and the combinations of ketamine and fentanyl citrate (3.2%; OR, 6.5; 95% CI, 2.5-15.2) and ketamine and propofol (2.1%; OR, 4.4; 95% CI, 2.3-8.7) had the highest incidence of SAEs. The combinations of ketamine and fentanyl (4.1%; OR, 4.0; 95% CI, 1.8-8.1) and ketamine and propofol (2.5%; OR, 2.2; 95% CI, 1.2-3.8) had the highest incidence of significant interventions. Conclusions and Relevance The incidence of adverse sedation outcomes varied significantly with type of sedation medication. Use of ketamine only was associated with the best outcomes, resulting in significantly fewer SAEs and interventions than ketamine combined with propofol or fentanyl.

Journal ArticleDOI
TL;DR: Gaskins et al. as mentioned in this paper investigated the thermal, mechanical, electrical, optical, and structural properties of atomic layer deposited high-k dielectrics: Beryllium Oxide, aluminum oxide, Hafnium oxide, and aluminum nitride.
Abstract: Review—Investigation and Review of the Thermal, Mechanical, Electrical, Optical, and Structural Properties of Atomic Layer Deposited High-k Dielectrics: Beryllium Oxide, Aluminum Oxide, Hafnium Oxide, and Aluminum Nitride John T. Gaskins,a Patrick E. Hopkins,a,b,c,z Devin R. Merrill,d,e Sage R. Bauers,d Erik Hadland,d David C. Johnson,d,z Donghyi Koh,e,f Jung Hwan Yum,f Sanjay Banerjee,f,∗ Bradley J. Nordell,g Michelle M. Paquette,g Anthony N. Caruso,g William A. Lanford,h Patrick Henry,e Liza Ross,e Han Li,e Liyi Li,e Marc French,e Antonio M. Rudolph,e and Sean W. Kinge,∗,z

Journal ArticleDOI
TL;DR: The benefits and harms of antimicrobial strategies used to prevent peritonitis in PD patients are evaluated through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE.
Abstract: Background Peritoneal dialysis (PD) is an important therapy for patients with end-stage kidney disease and is used in more than 200,000 such patients globally. However, its value is often limited by the development of infections such as peritonitis and exit-site and tunnel infections. Multiple strategies have been developed to reduce the risk of peritonitis including antibiotics, topical disinfectants to the exit site and antifungal agents. However, the effectiveness of these strategies has been variable and are based on a small number of randomised controlled trials (RCTs). The optimal preventive strategies to reduce the occurrence of peritonitis remain unclear. This is an update of a Cochrane review first published in 2004. Objectives To evaluate the benefits and harms of antimicrobial strategies used to prevent peritonitis in PD patients. Search methods We searched the Cochrane Kidney and Transplant's Specialised Register to 4 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria RCTs or quasi-RCTs in patients receiving chronic PD, which evaluated any antimicrobial agents used systemically or locally to prevent peritonitis or exit-site/tunnel infection were included. Data collection and analysis Two authors independently assessed risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Main results Thirty-nine studies, randomising 4435 patients, were included. Twenty additional studies have been included in this update. The risk of bias domains were often unclear or high; risk of bias was judged to be low in 19 (49%) studies for random sequence generation, 12 (31%) studies for allocation concealment, 22 (56%) studies for incomplete outcome reporting, and in 12 (31%) studies for selective outcome reporting. Blinding of participants and personnel was considered to be at low risk of bias in 8 (21%) and 10 studies (26%) for blinding of outcome assessors. It should be noted that blinding of participants and personnel was not possible in many of the studies because of the nature of the intervention or control treatment. The use of oral or topical antibiotic compared with placebo/no treatment, had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 191 patients, low quality evidence: RR 0.45, 95% CI 0.19 to 1.04) and the risk of peritonitis (5 studies, 395 patients, low quality evidence: RR 0.82, 95% CI 0.57 to 1.19). The use of nasal antibiotic compared with placebo/no treatment had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 338 patients, low quality evidence: RR 1.34, 95% CI 0.62 to 2.87) and the risk of peritonitis (3 studies, 338 patients, low quality evidence: RR 0.94, 95% CI 0.67 to 1.31). Pre/perioperative intravenous vancomycin compared with no treatment may reduce the risk of early peritonitis (1 study, 177 patients, low quality evidence: RR 0.08, 95% CI 0.01 to 0.61) but has an uncertain effect on the risk of exit-site/tunnel infection (1 study, 177 patients, low quality evidence: RR 0.36, 95% CI 0.10 to 1.32). The use of topical disinfectant compared with standard care or other active treatment (antibiotic or other disinfectant) had uncertain effects on the risk of exit-site/tunnel infection (8 studies, 973 patients, low quality evidence, RR 1.00, 95% CI 0.75 to 1.33) and the risk of peritonitis (6 studies, 853 patients, low quality evidence: RR 0.83, 95% CI 0.65 to 1.06). Antifungal prophylaxis with oral nystatin/fluconazole compared with placebo/no treatment may reduce the risk of fungal peritonitis occurring after a patient has had an antibiotic course (2 studies, 817 patients, low quality evidence: RR 0.28, 95% CI 0.12 to 0.63). No intervention reduced the risk of catheter removal or replacement. Most of the available studies were small and of suboptimal quality. Only six studies enrolled 200 or more patients. Authors' conclusions In this update, we identified limited data from RCTs and quasi-RCTs which evaluated strategies to prevent peritonitis and exit-site/tunnel infections. This review demonstrates that pre/peri-operative intravenous vancomycin may reduce the risk of early peritonitis and that antifungal prophylaxis with oral nystatin or fluconazole reduces the risk of fungal peritonitis following an antibiotic course. However, no other antimicrobial interventions have proven efficacy. In particular, the use of nasal antibiotic to eradicate Staphylococcus aureus, had an uncertain effect on the risk of peritonitis and raises questions about the usefulness of this approach. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered and high quality RCTs to inform decision making about strategies to prevent peritonitis is striking.

Journal ArticleDOI
TL;DR: The hospital site was a source of variation in all study outcomes, and the network also predicted the use of pharmacotherapy and radiography, which illustrates frequent lack of use and large variation in administration of EBSTs in infants hospitalized from EDs.
Abstract: BACKGROUND AND OBJECTIVES: Studies characterizing hospitalizations in bronchiolitis did not identify patients receiving evidence-based supportive therapies (EBSTs). We aimed to evaluate intersite and internetwork variation in receipt of ≥1 EBSTs during the hospital management of infants diagnosed with bronchiolitis in 38 emergency departments of pediatric emergency research networks in Canada, the United States, Australia, New Zealand, the United Kingdom, Ireland, Spain, and Portugal. We hypothesized that there would be significant variation, adjusted for patient characteristics. METHODS: Retrospective cohort study of previously healthy infants aged RESULTS: Out of 3725 participants, 1466 (39%) were hospitalized, and 1023 out of 1466 participants (69.8%) received EBST. The use of EBST varied by site ( P P = .2). Significant multivariable predictors and their odds ratios (ORs) were as follows: age (0.9), oxygen saturation (1.3), apnea (3.4), dehydration (3.2), nasal flaring and/or grunting (2.4), poor feeding (2.1), chest retractions (1.9), and respiratory rate (1.2). The use of pharmacotherapy and radiography varied by network and site ( P CONCLUSIONS: More than 30% of infants hospitalized with bronchiolitis received no EBST. The hospital site was a source of variation in all study outcomes, and the network also predicted the use of pharmacotherapy and radiography.

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TL;DR: Evidence for induction therapy for lupus nephritis is inconclusive based on treatment effects on all-cause mortality, doubling of serum creatinine level, and end-stage kidney disease, and possible confounding by previous or subsequent therapy.


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TL;DR: Urgent-start PD appears to be a safe way to initiate urgent renal replacement therapy in patients without established dialysis access and has acceptably low early complication rates and similar long-term technique survival.
Abstract: BackgroundSignificant interest in the practice of urgent-start peritoneal dialysis (PD) is mounting internationally, with several observational studies supporting the safety, efficacy, and feasibil...

Journal ArticleDOI
TL;DR: In this article, the concept of effective area-based conservation measures (OECMs) is explored in the context of the UN Convention on Biological Diversity (CBD) Aichi Biodiversity Target 11 on marine protected areas and OECMs and its linkages to the Sustainable Development Goals (SDGs).

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TL;DR: In this paper, the authors argue that there are three ways to structure the learning processes in educational situations: cooperatively, competitively and individualistically, and that the processes used may have the most powerful influences on the desired outcomes.
Abstract: Two aspects of teacher education for cooperative learning are the content taught and the processes used to teach the content. Of the two, the processes used may have the most powerful influences on the desired outcomes. One important theory related to the processes of learning is social interdependence theory. It posits that there are three ways to structure the learning processes in educational situations: cooperatively, competitively and individualistically. To structure cooperation among participants, five basic elements are needed: positive interdependence, individual accountability, promotive interaction, social skills and group processing. The large body of research on social interdependence indicates that cooperative, compared to competitive and individualistic learning, tends to promote (a) higher levels of achievement, retention and transfer of what is taught; (b) long-term implementation; (c) the internalisation of the required attitudes values and behaviour patterns; (d) the integration...

Journal ArticleDOI
TL;DR: A special focus should be placed on examining clinically translatable strategies that might encourage improvements to the microbiome, thereby potentially reducing the risk of the development of chronic kidney disease.
Abstract: It is well-established that uremic toxins are positively correlated with the risk of developing chronic kidney disease and cardiovascular disease. In addition, emerging data suggest that gut bacteria exert an influence over both the production of uremic toxins and the development of chronic kidney disease. As such, modifying the gut microbiota may have the potential as a treatment for chronic kidney disease. This is supported by data that suggest that rescuing microbiota dysbiosis may: reduce uremic toxin production; prevent toxins and pathogens from crossing the intestinal barrier; and, reduce gastrointestinal tract transit time allowing nutrients to reach the microbiota in the distal portion of the gastrointestinal tract. Despite emerging literature, the gut-kidney axis has yet to be fully explored. A special focus should be placed on examining clinically translatable strategies that might encourage improvements to the microbiome, thereby potentially reducing the risk of the development of chronic kidney disease. This review aims to present an overview of literature linking changes to the gastrointestinal tract with microbiota dysbiosis and the development and progression of chronic kidney disease.

Journal ArticleDOI
TL;DR: Hyperphosphataemia in patients with chronic kidney disease, particularly those on dialysis, can be ameliorated by oral phosphate binders in conjunction with dietary phosphate restriction, but it remains uncertain whether they improve clinical outcomes.
Abstract: Hyperphosphataemia in patients with chronic kidney disease, particularly those on dialysis, can be ameliorated by oral phosphate binders in conjunction with dietary phosphate restriction. Although phosphate binders reduce serum phosphate in these patients, it remains uncertain whether they improve clinical outcomes. Calcium-based binders are frequently used, but their popularity is waning due to emerging evidence of accelerated vascular calcification. The use of aluminium-based binders has been limited by a perceived risk of aluminium accumulation. The non-calcium-based phosphate binders - sevelamer hydrochloride, lanthanum carbonate and sucroferric oxyhydroxide - have become available and subsidised by the Pharmaceutical Benefits Scheme for patients on dialysis. The pill burden and adverse effects (particularly gastrointestinal intolerance) associated with phosphate binders often contribute to poor medication adherence.

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TL;DR: The establishment of 3 to 5 high-priority core outcomes, to be measured and reported consistently in all trials in PD, will enable patients and clinicians to make informed decisions about the relative effectiveness of interventions, based upon outcomes of common importance.
Abstract: BackgroundWorldwide, approximately 11% of patients on dialysis receive peritoneal dialysis (PD). Whilst PD may offer more autonomy to patients compared with hemodialysis, patient and caregiver burn...

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09 Aug 2017-PLOS ONE
TL;DR: The majority of studies focus on ICS, with adrenal and growth suppression described, and substantial methodological concerns are identified, highlighting need for standardization with future research examining pediatric asthma medication safety.
Abstract: Objective To systematically review the literature and determine frequencies of adverse drug events (ADE) associated with pediatric asthma medications. Methods Following PRISMA guidelines, we systematically searched six bibliographic databases between January 1991 and January 2017. Study eligibility, data extraction and quality assessment were independently completed and verified by two reviewers. We included randomized control trials (RCT), case-control, cohort, or quasi-experimental studies where the primary objective was identifying ADE in children 1 month– 18 years old exposed to commercial asthma medications. The primary outcome was ADE frequency. Findings Our search identified 14,540 citations. 46 studies were included: 24 RCT, 15 cohort, 4 RCT pooled analyses, 1 case-control, 1 open-label trial and 1 quasi-experimental study. Studies examined the following drug classes: inhaled corticosteroids (ICS) (n = 24), short-acting beta-agonists (n = 10), long-acting beta-agonists (LABA) (n = 3), ICS + LABA (n = 3), Leukotriene Receptor Antagonists (n = 3) and others (n = 3). 29 studies occurred in North America, and 29 were industry funded. We report a detailed index of 406 ADE descriptions and frequencies organized by drug class. The majority of data focuses on ICS, with 174 ADE affecting 13 organ systems including adrenal and growth suppression. We observed serious ADE, although they were rare, with frequency ranging between 0.9–6% per drug. There were no confirmed deaths, except for 13 potential deaths in a LABA study including combined adult and pediatric participants. We identified substantial methodological concerns, particularly with identifying ADE and determining severity. No studies utilized available standardized causality, severity or preventability assessments. Conclusion The majority of studies focus on ICS, with adrenal and growth suppression described. Serious ADE are relatively uncommon, with no confirmed pediatric deaths. We identify substantial methodological concerns, highlighting need for standardization with future research examining pediatric asthma medication safety.

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TL;DR: The origins, growth, and progress of a national research network in pediatric emergency medicine in Canada is described, with a focus on the creation of new knowledge, the mentorship of new investigators and fellows in developing research projects, and promoting a pediatric emergency Medicine–focused research agenda guided by the pooling of expertise from individuals across the nation.
Abstract: OBJECTIVE The objective of the study was to describe the origins, growth, and progress of a national research network in pediatric emergency medicine. METHODS The success of Pediatric Emergency Research Canada (PERC) is described in terms of advancing the pediatric emergency medicine agenda, grant funding, peer-reviewed publications, mentoring new investigators, and global collaborations. RESULTS Since 1995, clinicians and investigators within PERC have grown the network to 15 active tertiary pediatric emergency medicine sites across Canada. Investigators have advanced the research agenda in numerous areas, including gastroenteritis, bronchiolitis, croup, head injury, asthma, and injury management. Since the first PERC Annual Scientific meeting in 2004, the attendance has increased by approximately 400% to 152 attendees, 65 presentations, and 13 project/investigator meetings. More than $33 million in grant funding has been awarded to the network, and has published 76 peer-reviewed articles. In 2011, PERC's success was recognized with a Top Achievement Award in Health Research from Canadian Institutes of Health Research and the Canadian Medical Association Journal. CONCLUSIONS Moving forward, PERC will continue to focus on the creation of new knowledge, the mentorship of new investigators and fellows in developing research projects, and promoting a pediatric emergency medicine-focused research agenda guided by the pooling of expertise from individuals across the nation. Through collaborations with networks across the globe, PERC will continue to strive for the conduct of high-quality, impactful research that improves outcomes in children with acute illness and injury.