Showing papers by "David W. Johnson published in 2018"
Adrian F. Hernandez1, Jennifer B. Green1, Salim Janmohamed2, Ralph B. D'Agostino3 +795 more•Institutions (7)
TL;DR: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events, and evidence-based glucagon-like peptide 1 receptor agonists should be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events.
1,064 citations
TL;DR: It is demonstrated that grassland plant species form specific associations with soil community members and that information on plant species distributions can improve predictions of soil community composition, indicating that specific associations between plant species and complex soil communities are key determinants of biodiversity patterns in grassland soils.
Abstract: There are numerous ways in which plants can influence the composition of soil communities. However, it remains unclear whether information on plant community attributes, including taxonomic, phylogenetic, or trait-based composition, can be used to predict the structure of soil communities. We tested, in both monocultures and field-grown mixed temperate grassland communities, whether plant attributes predict soil communities including taxonomic groups from across the tree of life (fungi, bacteria, protists, and metazoa). The composition of all soil community groups was affected by plant species identity, both in monocultures and in mixed communities. Moreover, plant community composition predicted additional variation in soil community composition beyond what could be predicted from soil abiotic characteristics. In addition, analysis of the field aboveground plant community composition and the composition of plant roots suggests that plant community attributes are better predictors of soil communities than root distributions. However, neither plant phylogeny nor plant traits were strong predictors of soil communities in either experiment. Our results demonstrate that grassland plant species form specific associations with soil community members and that information on plant species distributions can improve predictions of soil community composition. These results indicate that specific associations between plant species and complex soil communities are key determinants of biodiversity patterns in grassland soils.
189 citations
TL;DR: Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment, and defines distinct sub-groups of hyperdiploid MM.
Abstract: Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10−7), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10−14) and 1.68 (P=2.18 × 10−14), respectively. Patients with ‘double-hit’ defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10−27) for all patients and 3.19 (P=1.23 × 10−18) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10−15), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.
162 citations
TL;DR: This study shows that plant species with resource-acquisitive traits, such as high shoot nitrogen concentrations and thin roots, attract diverse communities of putative fungal pathogens and specialist saprotrophs, and a lower diversity of mycorrhizal fungi, resulting in strong plant growth suppression on soil occupied by the same species.
Abstract: Feedbacks between plants and soil microbial communities play an important role in vegetation dynamics, but the underlying mechanisms remain unresolved. Here, we show that the diversity of putative pathogenic, mycorrhizal, and saprotrophic fungi is a primary regulator of plant-soil feedbacks across a broad range of temperate grassland plant species. We show that plant species with resource-acquisitive traits, such as high shoot nitrogen concentrations and thin roots, attract diverse communities of putative fungal pathogens and specialist saprotrophs, and a lower diversity of mycorrhizal fungi, resulting in strong plant growth suppression on soil occupied by the same species. Moreover, soil properties modulate feedbacks with fertile soils, promoting antagonistic relationships between soil fungi and plants. This study advances our capacity to predict plant-soil feedbacks and vegetation dynamics by revealing fundamental links between soil properties, plant resource acquisition strategies, and the diversity of fungal guilds in soil.
136 citations
University of Alberta1, University of Yaoundé I2, Central University of Venezuela3, University of Hassan II Casablanca4, University of Leicester5, University of Sydney6, The George Institute for Global Health7, University of Oxford8, Translational Research Institute9, Princess Alexandra Hospital10, University of California, Irvine11, Bezmialem Foundation University12, University of British Columbia13, University of Calgary14, University of Cape Town15, College of Health Sciences, Bahrain16, St. Michael's Hospital17, University of Toronto18, University of Paris19, University of Ibadan20, Tbilisi State Medical University21, Chang Gung University22
TL;DR: Significant variation is found in the global density of nephrologists and nephrology trainees and shortages in all care providers inNephrology; the gap was more prominent in low-income countries, particularly in African and South Asian ISN regions.
112 citations
Children's Hospital at Westmead1, University of Calgary2, University of Hong Kong3, University College London4, University of British Columbia5, University of Ottawa6, Pontifícia Universidade Católica do Paraná7, Ghent University Hospital8, Baylor College of Medicine9, Center for Drug Evaluation and Research10, The George Institute for Global Health11, Princess Alexandra Hospital12, Los Angeles Biomedical Research Institute13, University of Chicago14, French Institute of Health and Medical Research15, Flinders University16
TL;DR: This report outlines implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes.
107 citations
Duke University1, University of Massachusetts Boston2, University of Hawaii at Manoa3, Scripps Institution of Oceanography4, University of Southampton5, Departamento de Oceanografia e Pescas6, Scottish Association for Marine Science7, Shirshov Institute of Oceanology8, International Union for Conservation of Nature and Natural Resources9, Monterey Institute of International Studies10, University of Plymouth11, University of Porto12
TL;DR: This work adapts marine reserve design principles to the distinctive biophysical environment of mid-ocean ridges, offers a framework for design and evaluation of these networks, and introduces projected climate-induced changes in the deep sea to the evaluation of reserve design.
Abstract: Mineral exploitation has spread from land to shallow coastal waters and is now planned for the offshore, deep seabed. Large seafloor areas are being approved for exploration for seafloor mineral deposits, creating an urgent need for regional environmental management plans. Networks of areas where mining and mining impacts are prohibited are key elements of these plans. We adapt marine reserve design principles to the distinctive biophysical environment of mid-ocean ridges, offer a framework for design and evaluation of these networks to support conservation of benthic ecosystems on mid-ocean ridges, and introduce projected climate-induced changes in the deep sea to the evaluation of reserve design. We enumerate a suite of metrics to measure network performance against conservation targets and network design criteria promulgated by the Convention on Biological Diversity. We apply these metrics to network scenarios on the northern and equatorial Mid-Atlantic Ridge, where contractors are exploring for seafloor massive sulfide (SMS) deposits. A latitudinally distributed network of areas performs well at (i) capturing ecologically important areas and 30 to 50% of the spreading ridge areas, (ii) replicating representative areas, (iii) maintaining along-ridge population connectivity, and (iv) protecting areas potentially less affected by climate-related changes. Critically, the network design is adaptive, allowing for refinement based on new knowledge and the location of mining sites, provided that design principles and conservation targets are maintained. This framework can be applied along the global mid-ocean ridge system as a precautionary measure to protect biodiversity and ecosystem function from impacts of SMS mining.
85 citations
Institute of Cancer Research1, Lund University2, German Cancer Research Center3, University of Arkansas for Medical Sciences4, Heidelberg University5, Erasmus University Rotterdam6, deCODE genetics7, University of Iceland8, University of Leeds9, University of Bonn10, University of Basel11, Royal Victoria Infirmary12, University of Duisburg-Essen13, Sahlgrenska University Hospital14, University of Cambridge15, University of London16, University of Manchester17, University of Warwick18, University College London19, University of Southampton20, Aarhus University Hospital21, Norwegian University of Science and Technology22, University of Ulm23, Broad Institute24
TL;DR: In this paper, the authors report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry.
Abstract: Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
82 citations
TL;DR: The results support the hypothesis that ECM and AM plants partition soil P sources, which may play an ecologically important role in promoting species coexistence in tropical and subtropical forests.
Abstract: Partitioning of soil phosphorus (P) pools has been proposed as a key mechanism maintaining plant diversity, but experimental support is lacking. Here, we provided different chemical forms of P to 15 tree species with contrasting root symbiotic relationships to investigate plant P acquisition in both tropical and subtropical forests. Both ectomycorrhizal (ECM) and arbuscular mycorrhizal (AM) trees responded positively to addition of inorganic P, but strikingly, ECM trees acquired more P from a complex organic form (phytic acid). Most ECM tree species and all AM tree species also showed some capacity to take up simple organic P (monophosphate). Mycorrhizal colonisation was negatively correlated with soil extractable P concentration, suggesting that mycorrhizal fungi may regulate organic P acquisition among tree species. Our results support the hypothesis that ECM and AM plants partition soil P sources, which may play an ecologically important role in promoting species coexistence in tropical and subtropical forests.
77 citations
05 Nov 2018
TL;DR: The role of instructors is evolving from the presenter of information to the designer of active learning processes, environments, and experiences that maximize student engagement.
Abstract: The role of instructors is evolving from the presenter of information to the designer of active learning processes, environments, and experiences that maximize student engagement. The more active a lesson, the more students tend to engage intellectually and emotionally in the learning activities. Cooperative learning is the foundation on which many of the active learning procedures are based. Cooperative learning is the instructional use of small groups so that students work together to maximize their own and each other’s learning. Most of the active learning procedures, such as problem-based learning, teamlearning, collaborative learning, and PALS, require that students work cooperatively in small groups to achieve joint learning goals. Cooperative learning is based on two theories: Structure-Process-Outcome theory and Social Interdependence theory. Four types of cooperative learning have been derived: formal cooperative learning, informal cooperative learning, cooperative base groups, and constructive controversy. There is considerable research confirming the effectiveness of cooperative learning. To be cooperative, however, five basic elements must be structured into the situation: positive interdependence, individual accountability, promotive interaction, social skills, and group processing.
74 citations
Singapore General Hospital1, Princess Alexandra Hospital2, University of Yaoundé I3, University of Alberta4, Central University of Venezuela5, University of Hassan II Casablanca6, University of Leicester7, University of Sydney8, The George Institute for Global Health9, University of Oxford10, University of California, Irvine11, Bezmialem Foundation University12, Monash University, Clayton campus13, Monash Medical Centre14, University of British Columbia15, University of Calgary16, University of Cape Town17, College of Health Sciences, Bahrain18, University of Toronto19, St. Michael's Hospital20, University of Paris21, University of Ibadan22, Tbilisi State Medical University23, Chang Gung University24, First Pavlov State Medical University of St. Peterburg25, Translational Research Institute26
TL;DR: Significant gaps in services for kidney care and funding that were most apparent in LICs and lower middle-income countries were demonstrated.
TL;DR: The conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours, and the rate of return visits to care reduced.
Abstract: Background Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011. Objectives To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies. Selection criteria We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events. Data collection and analysis One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach. Main results We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children. Authors' conclusions Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.
TL;DR: The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD.
Abstract: Introduction Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1–3) due to ADPKD. Methods and analysis A multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety. Ethics and dissemination The trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD. Trial registration number ANZCTR12614001216606.
TL;DR: A comprehensive set of factors perceived by emergency department staff and administrative leads to influence clinical pathway implementation within the complex and dynamic environments of community emergency department settings is explored.
Abstract: While clinical pathways have the potential to improve patient outcomes and reduce healthcare costs, their true impact has been limited by variable implementation strategies and suboptimal research designs. This paper explores a comprehensive set of factors perceived by emergency department staff and administrative leads to influence clinical pathway implementation within the complex and dynamic environments of community emergency department settings. This descriptive, qualitative study involved emergency health professionals and administrators of 15 community hospitals across Ontario, Canada. As part of our larger cluster randomized controlled trial, each site was in the preparation phase to implement one of two clinical pathways: pediatric asthma or pediatric vomiting and diarrhea. Data were collected from three sources: (i) a mediated group discussion with site champions during the project launch meeting; (ii) a semi-structured site visit of each emergency department; and (iii) key informant interviews with an administrative lead from each hospital. The Theoretical Domains Framework (TDF) was used to guide the interviews and thematically analyze the data. Domains within each major theme were then mapped onto the COM-B model—capability, opportunity, and motivation—of the Behaviour Change Wheel. Seven discrete themes and 58 subthemes were identified that comprised a set of barriers and enablers relevant to the planned clinical pathway implementation. Within two themes, three distinct levels of impact emerged, namely (i) the individual health professional, (ii) the emergency department team, and (iii) the broader hospital context. The TDF domains occurring most frequently were Memory, Attention and Decision Processes, Environmental Context and Resources, Behavioural Regulation, and Reinforcement. Mapping these barriers and enablers onto the COM-B model provided an organized perspective on how these issues may be interacting. Several factors were viewed as both negative and positive across different perspectives. Two of the seven themes were limited to one component, while four involved all three components of the COM-B model. Using a theory-based approach ensured systematic and comprehensive identification of relevant barriers and enablers to clinical pathway implementation in ED settings. The COM-B system of the Behaviour Change Wheel provided a useful perspective on how these factors might interact to effect change. ClinicalTrials.gov, NCT01815710
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TL;DR: Lymphoma occurs at similar rates in adult and paediatric recipients, but has been decreasing since the year 2000, and EBV-negative patients and those with diabetes or induction agent other than anti-CD25 monoclonal antibody are at substantially increased risk of PTLD.
Abstract: Background Differences in the epidemiology of post-transplant lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant recipients remain unclear. Methods Using the Australian and New Zealand Dialysis and Transplant Registry (1963-2015), the cumulative incidences of PTLD in children (age <20 years) and adults were calculated using a competing risk of death model and compared with age-matched population-based data using standardized incidence ratios (SIRs). Risk factors for PTLD were assessed using Cox proportional hazards regression. Results Among 23 477 patients (92% adult, 60% male), 505 developed PTLD, with 50 (10%) occurring in childhood recipients. The 25-year cumulative incidence of PTLD was 3.3% [95% confidence interval (CI) 2.9-3.6] for adult recipients and 3.6% (95% CI 2.7-4.8) for childhood recipients. Childhood recipients had a 30-fold increased risk of lymphoma compared with the age-matched general population [SIR 29.5 (95% CI 21.9-38.8)], higher than adult recipients [SIR 8.4 (95% CI 7.7-9.2)]. Epstein-Barr virus (EBV)-negative recipient serology [adjusted hazard ratio (aHR) 3.33 (95% CI 2.21-5.01), P < 0.001], year of transplantation [aHR 0.93 for each year after the year 2000 (95% CI 0.88-0.99), P = 0.02], induction with an agent other than anti-CD25 monoclonal antibody [aHR 2.07 (95% CI 1.16-3.70), P = 0.01] and having diabetes [aHR 3.49 (95% CI 2.26-5.38), P < 0.001] were independently associated with PTLD. Conclusions Lymphoma occurs at similar rates in adult and paediatric recipients, but has been decreasing since the year 2000. EBV-negative patients and those with diabetes or induction agent other than anti-CD25 monoclonal antibody are at substantially increased risk of PTLD.
TL;DR: A Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) consensus workshop was convened to discuss the development of a core outcome measure for vascular access, which advocated for a practical and flexible outcome measure with a simple actionable definition.
TL;DR: There appears to be no role for traditional immunotherapy as adjuvant treatment in patients with high risk localized kidney cancer following surgical resection, and new trials evaluating immune checkpoint inhibitors are planned.
TL;DR: The current understanding of the pathogenesis of arteriovenous fistula and graft failure is described, the biological effects of antiplatelet agents, fish oil supplementation, RAAS blockers and statins that may be beneficial in improving vascular access survival are described, results from clinical trials that have investigated the effect of these agents are investigated, and future therapeutic approaches combining these agents with novel treatment strategies are explored.
Abstract: In patients receiving hemodialysis, the provision of safe and effective vascular access using an arteriovenous fistula or graft is regarded as a critical priority by patients and health professionals. Vascular access failure is associated with morbidity and mortality, such that strategies to prevent these outcomes are essential. Inadequate vascular remodeling and neointimal hyperplasia resulting in stenosis and frequently thrombosis are critical to the pathogenesis of access failure. Systemic medical therapies with pleiotropic effects including antiplatelet agents, omega-3 polyunsaturated fatty acids (fish oils), statins, and inhibitors of the renin-angiotensin-aldosterone system (RAAS) may reduce vascular access failure by promoting vascular access maturation and reducing stenosis and thrombosis through antiproliferative, antiaggregatory, anti-inflammatory and vasodilatory effects. Despite such promise, the results of retrospective analyses and randomized controlled trials of these agents on arteriovenous fistula and graft outcomes have been mixed. This review describes the current understanding of the pathogenesis of arteriovenous fistula and graft failure, the biological effects of antiplatelet agents, fish oil supplementation, RAAS blockers and statins that may be beneficial in improving vascular access survival, results from clinical trials that have investigated the effect of these agents on arteriovenous fistula and graft outcomes, and it explores future therapeutic approaches combining these agents with novel treatment strategies.
TL;DR: In this paper, the authors focus on climate change impacts likely to affect these areas and the need to evaluate implications for the state of biodiversity features for which they have been established, and advocate a more precautionary approach, potentially setting aside more extensive areas and strictly limiting human uses and/or adopting high protection thresholds before any additional human use impacts are allowed.
TL;DR: Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially whensynbiotics administered for a period of 8 weeks and in individuals with liver disease.
Abstract: The gut–liver interaction suggests that modification of gut bacterial flora using probiotics and synbiotics may improve liver function. This systematic review and meta-analysis aimed to clarify the effect of probiotics and synbiotics consumption on the serum concentration of liver function enzymes. PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1980 to August 2017 for studies where adults consumed probiotics and/or synbiotics in controlled trials and changes in liver function enzymes were examined. A total of 17 studies (19 trials) were included in the meta-analysis. Random effects meta-analyses were applied. Probiotics and synbiotics significantly reduced serum alanine aminotransferase [− 8.05 IU/L, 95% confidence interval (CI) − 13.07 to − 3.04; p = 0.002]; aspartate aminotransferase (− 7.79 IU/L, 95% CI: − 13.93 to − 1.65; p = 0.02) and gamma-glutamyl transpeptidase (− 8.40 IU/L, 95% CI − 12.61 to − 4.20; p < 0.001). Changes in the serum concentration of alkaline phosphatase and albumin did not reach a statistically significant level. Changes to bilirubin levels were in favour of the control group (0.95 μmol/L, 95% CI 0.48–1.42; p < 0.001). Subgroup analysis suggested the existence of liver disease at baseline, synbiotics supplementation and duration of supplementation ≥ 8 weeks resulted in more pronounced improvement in liver function enzymes than their counterparts. Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially when synbiotics administered for a period ≥ 8 weeks and in individuals with liver disease.
TL;DR: It is revealed that preoperative physiologic passive knee HE ≥5° is present in one-third of patients who undergo revision ACLR, and was an independent significant predictor of graft failure after Revision ACLR with a >2-fold OR of subsequent graft rupture in revision ACL surgery.
Abstract: Background:The occurrence of physiologic knee hyperextension (HE) in the revision anterior cruciate ligament reconstruction (ACLR) population and its effect on outcomes have yet to be reported.Hypo...
TL;DR: Cognitive impairment is extremely common in hemodialysis patients, across numerous domains, and patients often experience multiple deficits simultaneously, so clinical care should be tailored to meet the needs of patients with different types of cognitive impairment.
Abstract: Background Mounting evidence indicates an increased risk of cognitive impairment in adults with end-stage kidney disease on dialysis, but the extent and pattern of deficits across the spectrum of cognitive domains are uncertain. Methods We conducted a cross-sectional study of 676 adult hemodialysis patients from 20 centers in Italy, aiming to evaluate the prevalence and patterns of cognitive impairment across five domains of learning and memory, complex attention, executive function, language and perceptual-motor function. We assessed cognitive function using a neuropsychological battery of 10 tests and calculated test and domain z-scores using population norms (age or age/education). We defined cognitive impairment as a z-score ≤ -1.5. Results Participants' median age was 70.9 years (range 21.6-94.1) and 262 (38.8%) were women. Proportions of impairment on each domain were as follows: perceptual-motor function 31.5% (150/476), language 41.2% (273/662), executive function 41.7% (281/674), learning and memory 42.2% (269/638), complex attention 48.8% (329/674). Among 474 participants with data for all domains, only 28.9% (n = 137) were not impaired on any domain, with 25.9% impaired on a single domain (n = 123), 17.3% on two (n = 82), 13.9% on three (n = 66), 9.1% on four (n = 43) and 4.9% (n = 23) on all five. Across patients, patterns of impairment combinations were diverse. Conclusions In conclusion, cognitive impairment is extremely common in hemodialysis patients, across numerous domains, and patients often experience multiple deficits simultaneously. Clinical care should be tailored to meet the needs of patients with different types of cognitive impairment and future research should focus on identifying risk factors for cognitive decline.
University of Alberta1, University of Yaoundé I2, Central University of Venezuela3, University of Hassan II Casablanca4, University of Leicester5, University of Sydney6, University of Oxford7, The George Institute for Global Health8, Princess Alexandra Hospital9, Translational Research Institute10, University of California, Irvine11, Bezmialem Foundation University12, Monash University, Clayton campus13, Monash Medical Centre14, University of Calgary15, College of Health Sciences, Bahrain16, University of Toronto17, St. Michael's Hospital18, University of Paris19, Uthman dan Fodiyo University20, Tbilisi State Medical University21, Chang Gung University22, First Pavlov State Medical University of St. Peterburg23, University of British Columbia24
TL;DR: This study demonstrated significant gaps in oversight, funding, and infrastructure supporting health services caring for patients with kidney disease, especially in low- and middle-income countries.
TL;DR: Sampling designs should quantify the diversity of mycorrhizal fungal genotypes and species at three key broad spatial scales in order to inform manipulation experiments and to test how mycor RH diversity both responds, and confers resilience to, environmental drivers.
Abstract: Contents Summary 1122 I. Introduction 1122 II. Are there consistent patterns in diversity of mycorrhizal fungal genotypes and species across space? 1125 III. What is the variation in functional traits and genes of mycorrhizal fungi at different taxonomic scales? 1125 IV. How will environmental change impact the relationships between genotypic and species diversity of mycorrhizal fungi and ecosystem function? 1126 V. Conclusions: considerations for future MEF research 1127 Acknowledgements 1127 References 1127 SUMMARY: Both genotypes and species of mycorrhizal fungi exhibit considerable variation in traits, and this variation can result in their diversity regulating ecosystem function. Yet, the nature of mycorrhizal fungal diversity-ecosystem function (MEF) relationships for both genotypes and species is currently poorly defined. New experiments should reflect the richness of genotypes and species in nature, but we still lack information about the extent to which fungal populations in particular are structured. Sampling designs should quantify the diversity of mycorrhizal fungal genotypes and species at three key broad spatial scales (root fragment, root system and interacting root systems) in order to inform manipulation experiments and to test how mycorrhizal fungal diversity both responds, and confers resilience to, environmental drivers.
University of California, Davis1, Children's Hospital of Eastern Ontario2, University of Melbourne3, Royal Children's Hospital4, University of Auckland5, Alberta Children's Hospital6, Princess Margaret Cancer Centre7, University of Toronto8, Brown University9, Instituto de Medicina Molecular10, Cincinnati Children's Hospital Medical Center11, Boston Children's Hospital12, University of the West of England13, Washington University in St. Louis14, Baylor College of Medicine15
TL;DR: A risk score for escalated care in bronchiolitis is derived that may be used to aid clinicians with management and disposition decisions and is based on variables measured in the emergency department predictive of this outcome.
Abstract: BACKGROUND AND OBJECTIVES: Early risk stratification of infants with bronchiolitis receiving airway support is critical for focusing appropriate therapies, yet the tools to risk categorize this subpopulation do not exist. Our objective was to identify predictors of “escalated care” in bronchiolitis. We hypothesized there would be a significant association between escalated care and predictors in the emergency department. We subsequently developed a risk score for escalated care. METHODS: We conducted a retrospective cohort study of previously healthy infants aged RESULTS: Of 2722 patients, 261 (9.6%) received escalated care. Multivariable predictors of escalated care were oxygen saturation CONCLUSIONS: We identified variables measured in the emergency department predictive of escalated care in bronchiolitis and derived a risk score to stratify risk of this outcome. This score may be used to aid management and disposition decisions.
TL;DR: Anaphylactoid reactions to the 21-h IV NAC protocol were uncommon and involved primarily cutaneous symptoms, while the protective effects of higher APAP concentrations are of interest in understanding the pathophysiology.
Abstract: Anaphylactoid reactions to intravenous (IV) N-acetylcysteine (NAC) are well-recognized adverse events during treatment for acetaminophen (APAP) poisoning. Uncertainty exists regarding their incidence, severity, risk factors, and management. We sought to determine the incidence, risk factors, and treatment of anaphylactoid reactions to IV NAC in a large, national cohort of patients admitted to hospital for acetaminophen overdose. This retrospective medical record review included all patients initiated on the 21-h IV NAC protocol for acetaminophen poisoning in 34 Canadian hospitals between February 1980 and November 2005. The primary outcome was any anaphylactoid reaction, defined as cutaneous (urticaria, pruritus, angioedema) or systemic (hypotension, respiratory symptoms). We examined the incidence, severity and timing of these reactions, and their association with patient and overdose characteristics using multivariable analysis. An anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses, of which 398 (75.4%) were cutaneous. Five hundred four (95.4%) reactions occurred during the first 5 h. Of 403 patients administered any medication for these reactions, 371 (92%) received an antihistamine. Being female (adjusted OR 1.24 [95%CI 1.08, 1.42]) and having taken a single, acute overdose (1.24 [95%CI 1.10, 1.39]) were each associated with more severe reactions, whereas higher serum APAP concentrations were associated with fewer reactions (0.79 [95%CI 0.68, 0.92]). Anaphylactoid reactions to the 21-h IV NAC protocol were uncommon and involved primarily cutaneous symptoms. While the protective effects of higher APAP concentrations are of interest in understanding the pathophysiology, none of the associations identified are strong enough to substantially alter the threshold for NAC initiation.
University of Sydney1, Children's Hospital at Westmead2, Westmead Hospital3, University of Eastern Piedmont4, University of Otago5, Johns Hopkins University6, University of Bari7, Karolinska Institutet8, University of Queensland9, Princess Alexandra Hospital10, University of Calgary11, Medical University of Lublin12, Medical University of Silesia13
TL;DR: Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis, and the association between DASH diet score and all-cause death was modified by age.
Abstract: Background Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain.Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category).Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients.Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.
University of Sydney1, Children's Hospital at Westmead2, University of Calgary3, University College London4, University of Ottawa5, Ghent University Hospital6, Baylor College of Medicine7, Princess Alexandra Hospital8, Translational Research Institute9, Kolling Institute of Medical Research10, Monash University, Clayton campus11, Royal Adelaide Hospital12, Health Science University13
TL;DR: Outcomes reported in clinical trials involving adults receiving hemodialysis are focused on surrogate outcomes, rather than clinical and patient-centered outcomes, and estimates of the comparative effectiveness of available interventions are unreliable and improvements over time have been inconsistent.
Institute of Cancer Research1, The Royal Marsden NHS Foundation Trust2, Salisbury NHS Foundation Trust3, University Hospital Southampton NHS Foundation Trust4, University of Birmingham5, St James's University Hospital6, University of Leeds7, University of Arkansas for Medical Sciences8, University of Newcastle9
TL;DR: A framework for identifying subclonal TP53 deletions by MLPA is presented, to improve patient stratification in MM and tailor therapy, enabling management strategies.
TL;DR: There was no association between fasting duration and any type of adverse event and the findings do not support delaying sedation to meet established fasting guidelines.
Abstract: Importance It is not clear whether adherence to preprocedural fasting guidelines prevent pulmonary aspiration and associated adverse outcomes during emergency department (ED) sedation of children. Objective To examine the association between preprocedural fasting duration and the incidence of sedation-related adverse outcomes in a large sample of children. Design, Setting, and Participants We conducted a planned secondary analysis of a multicenter prospective cohort study of children aged 0 to 18 years who received procedural sedation for a painful procedure in 6 Canadian pediatric EDs from July 2010 to February 2015. The primary risk factor was preprocedural fasting duration. Secondary risk factors were age, sex, American Society of Anesthesiologists classification, preprocedural and sedation medications, and procedure type. Main Outcomes and Measures Four outcomes were examined: (1) pulmonary aspiration, (2) the occurrence of any adverse event, (3) serious adverse events, and (4) vomiting. Results A total of 6183 children with a median age of 8.0 years (interquartile range, 4.0-12.0 years), of whom 6166 (99.7%) had healthy or mild systemic disease (American Society of Anesthesiologists levels I or II), were included in the analysis. Of these, 2974 (48.1%) and 310 (5.0%) children did not meet American Society of Anesthesiologists fasting guidelines for solids and liquids, respectively. There were no cases of pulmonary aspiration. There were 717 adverse events (11.6%; 95% CI, 10.8%-12.4%), of which 68 (1.1%; 95% CI, 0.9%-1.3%) were serious adverse events and 315 (5.1%; 95% CI, 4.6%-5.7%) were vomiting. The odds ratio (OR) of occurrence of any adverse event, serious adverse events, and vomiting did not change significantly with each additional hour of fasting duration for both solids (any adverse event: OR, 1.00; 95% CI, 0.98 to 1.02; serious adverse events, OR, 1.01; 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.97-1.03) and liquids (any adverse event: OR, 1.00; 95% CI, 0.98-1.02; serious adverse events: 1.01, 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.96-1.03). Conclusions and Relevance In this study, there was no association between fasting duration and any type of adverse event. These findings do not support delaying sedation to meet established fasting guidelines.