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1.
Plant Cell Environ ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38533601

ABSTRACT

As the global climate continues to change, plants will increasingly experience abiotic stress(es). Stomata on leaf surfaces are the gatekeepers to plant interiors, regulating gaseous exchanges that are crucial for both photosynthesis and outward water release. To optimise future crop productivity, accurate modelling of how stomata govern plant-environment interactions will be crucial. Here, we synergise optical and thermal imaging data to improve modelled transpiration estimates during water and/or nutrient stress (where leaf N is reduced). By utilising hyperspectral data and partial least squares regression analysis of six plant traits and fluxes in wheat (Triticum aestivum), we develop a new spectral vegetation index; the Combined Nitrogen and Drought Index (CNDI), which can be used to detect both water stress and/or nitrogen deficiency. Upon full stomatal closure during drought, CNDI shows a strong relationship with leaf water content (r2 = 0.70), with confounding changes in leaf biochemistry. By incorporating CNDI transformed with a sigmoid function into thermal-based transpiration modelling, we have increased the accuracy of modelling water fluxes during abiotic stress. These findings demonstrate the potential of using combined optical and thermal remote sensing-based modelling approaches to dynamically model water fluxes to improve both agricultural water usage and yields.

2.
Blood Adv ; 8(4): 832-841, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38163317

ABSTRACT

ABSTRACT: We previously reported high rates of undetectable minimal residual disease <10-4 (uMRD4) with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) followed by 2-year ibrutinib maintenance (I-M) in treatment-naïve chronic lymphocytic leukemia (CLL). Here, we report updated data from this phase 2 study with a median follow-up of 63 months. Of 85 patients enrolled, including 5 (6%) with deletion 17p or TP53 mutation, 91% completed iFCR and 2-year I-M. Five-year progression-free survival (PFS) and overall survival were 94% (95% confidence interval [CI], 89%-100%) and 99% (95% CI, 96%-100%), respectively. No additional deaths have occurred with this extended follow-up. No difference in PFS was observed by immunoglobulin heavy-chain variable region gene status or duration of I-M. High rates of peripheral blood (PB) uMRD4 were maintained (72% at the end of iFCR, 66% at the end of 2-year I-M, and 44% at 4.5 years from treatment initiation). Thirteen patients developed MRD conversion without clinical progression, mostly (77%) after stopping ibrutinib. None had Bruton tyrosine kinase (BTK) mutations. One patient had PLCG2 mutation. Six of these patients underwent ibrutinib retreatment per protocol. Median time on ibrutinib retreatment was 34 months. The cumulative incidence of atrial fibrillation was 8%. Second malignancy or nonmalignant hematologic disease occurred in 13%, mostly nonmelanoma skin cancer. Overall, iFCR with 2-year I-M achieved durably deep responses in patients with diverse CLL genetic markers. Re-emergent clones lacked BTK mutation and retained sensitivity to ibrutinib upon retreatment. This trial is registered at www.clinicaltrials.gov as #NCT02251548.


Subject(s)
Adenine/analogs & derivatives , Leukemia, Lymphocytic, Chronic, B-Cell , Piperidines , Vidarabine/analogs & derivatives , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Rituximab/adverse effects , Follow-Up Studies , Treatment Outcome , Cyclophosphamide/adverse effects
3.
PLoS Biol ; 22(1): e3002406, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38227562

ABSTRACT

Breast tumours are embedded in a collagen I-rich extracellular matrix (ECM) network, where nutrients are scarce due to limited blood flow and elevated tumour growth. Metabolic adaptation is required for cancer cells to endure these conditions. Here, we demonstrated that the presence of ECM supported the growth of invasive breast cancer cells, but not non-transformed mammary epithelial cells, under amino acid starvation, through a mechanism that required macropinocytosis-dependent ECM uptake. Importantly, we showed that this behaviour was acquired during carcinoma progression. ECM internalisation, followed by lysosomal degradation, contributed to the up-regulation of the intracellular levels of several amino acids, most notably tyrosine and phenylalanine. This resulted in elevated tyrosine catabolism on ECM under starvation, leading to increased fumarate levels, potentially feeding into the tricarboxylic acid (TCA) cycle. Interestingly, this pathway was required for ECM-dependent cell growth and invasive cell migration under amino acid starvation, as the knockdown of p-hydroxyphenylpyruvate hydroxylase-like protein (HPDL), the third enzyme of the pathway, opposed cell growth and motility on ECM in both 2D and 3D systems, without affecting cell proliferation on plastic. Finally, high HPDL expression correlated with poor prognosis in breast cancer patients. Collectively, our results highlight that the ECM in the tumour microenvironment (TME) represents an alternative source of nutrients to support cancer cell growth by regulating phenylalanine and tyrosine metabolism.


Subject(s)
Amino Acids , Breast Neoplasms , Humans , Female , Amino Acids/metabolism , Breast Neoplasms/metabolism , Extracellular Matrix/metabolism , Tyrosine/metabolism , Phenylalanine , Tumor Microenvironment
4.
Regul Toxicol Pharmacol ; 147: 105544, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38158034

ABSTRACT

Due to significant dietary supplement use in the US, product manufacturers must understand the importance of implementing a robust approach to establishing safety for all ingredients, including dietary ingredients, components, and finished dietary supplement products. Different regulatory pathways exist by which the safety of dietary ingredients can be established, and thus allowed to be marketed in a dietary supplement. For individual dietary ingredients, safety information may come from a variety of sources including history of safe use, presence of the ingredient in foods, and/or non-clinical and clinical data. On occasion safety data gaps are identified for a specific ingredient, particularly those of botanical origin. Modern toxicological methods and models can prove helpful in satisfying data gaps and are presented in this review. For finished dietary supplement products, issues potentially impacting safety to consider include claims, product labeling, overages, contaminants, residual solvents, heavy metals, packaging, and product stability. In addition, a safety assessment does not end once a product is marketed. It is important that manufacturers actively monitor and record the occurrence of adverse events reported in association with the use of their products, in accordance with the law. Herein, we provide a comprehensive overview of considerations for assessing dietary supplement safety.


Subject(s)
Dietary Supplements , Product Labeling , United States , United States Food and Drug Administration , Dietary Supplements/toxicity , Drug Packaging
5.
J Perinat Neonatal Nurs ; 37(3): 223-231, 2023.
Article in English | MEDLINE | ID: mdl-37494691

ABSTRACT

BACKGROUND: COVID-19-associated visitor restrictions altered parents' involvement in their infant's care in the neonatal intensive care unit (NICU). PURPOSE: The purpose of this article is to explore how restrictions affected parents' perceptions of experience in the NICU and to build a conceptual model of communication flow during times of crisis. METHODS: This qualitative study was set in a level III 52-bed NICU. Using data from an open-ended survey question, a multitiered thematic analysis was used. RESULTS: Four broad themes emerged: communication, gratitude, release, and containment of emotionality. These 4 themes interacted codependently and manifested differently as COVID-related visitor policies were put in place. Parents' characterization of communication also varied depending on the visitation policies. Before COVID, parents were more likely to reflect on communication. During COVID, parents expressed more gratitude, while containing negative emotions-sometimes using gratitude to soften the blow of bad feedback. IMPLICATIONS FOR PRACTICE AND RESEARCH: Our theoretical model suggests that gratitude may serve as a form of "reciprocal care" to providers during a period of crisis and extreme stress. Use of high-quality communication between providers and parents in the NICU is necessary to understand parental concerns or negative experience.


Subject(s)
COVID-19 , Intensive Care Units, Neonatal , Infant, Newborn , Infant , Humans , Qualitative Research , Parents , Surveys and Questionnaires
7.
Metabolites ; 13(4)2023 Mar 23.
Article in English | MEDLINE | ID: mdl-37110122

ABSTRACT

Untargeted metabolomics is a powerful tool for measuring and understanding complex biological chemistries. However, employment, bioinformatics and downstream analysis of mass spectrometry (MS) data can be daunting for inexperienced users. Numerous open-source and free-to-use data processing and analysis tools exist for various untargeted MS approaches, including liquid chromatography (LC), but choosing the 'correct' pipeline isn't straight-forward. This tutorial, in conjunction with a user-friendly online guide presents a workflow for connecting these tools to process, analyse and annotate various untargeted MS datasets. The workflow is intended to guide exploratory analysis in order to inform decision-making regarding costly and time-consuming downstream targeted MS approaches. We provide practical advice concerning experimental design, organisation of data and downstream analysis, and offer details on sharing and storing valuable MS data for posterity. The workflow is editable and modular, allowing flexibility for updated/changing methodologies and increased clarity and detail as user participation becomes more common. Hence, the authors welcome contributions and improvements to the workflow via the online repository. We believe that this workflow will streamline and condense complex mass-spectrometry approaches into easier, more manageable, analyses thereby generating opportunities for researchers previously discouraged by inaccessible and overly complicated software.

8.
Leukemia ; 37(4): 835-842, 2023 04.
Article in English | MEDLINE | ID: mdl-36717653

ABSTRACT

This study investigated ibrutinib plus obinutuzumab in relapsed/refractory CLL, evaluating tolerability of 3 sequencing regimens as well as overall safety and efficacy. Fifty-two patients were initially randomized 1:1:1 to receive either obinutuzumab 1 month before ibrutinib initiation, ibrutinib 1 month prior to obinutuzumab initiation, or to start both drugs concomitantly. Higher rates of infusion-related reactions were observed with the first sequence, and only the latter 2 cohorts were expanded. Grade 4 hematologic toxicity was uncommon, and notable all-grade non-hematologic toxicities included bruising (58%), hypertension (46%), arthralgia (38%), diarrhea (37%), transaminitis (35%), atrial fibrillation (21%), and serious infection (17%). Best overall response rate was 96% (including 40% CR and 56% PR). Best rates of undetectable minimal residual disease in peripheral blood and bone marrow were 27% and 19%, respectively. With a median follow-up of 41.5 months, four-year progression-free and overall survival rates are 74% and 93%, respectively. Correlative studies demonstrated that serum CCL4 and CXCL13 levels were associated with clinical response, and BH3 profiling revealed increased BCL-2 and BCL-xL dependence in CLL cells from patients on treatment. Overall, ibrutinib plus obinutuzumab was highly active, with a manageable safety profile, supporting further investigation of this type of approach in relapsed/refractory CLL.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Antibodies, Monoclonal, Humanized/adverse effects , Piperidines/therapeutic use , Recurrence , Antineoplastic Combined Chemotherapy Protocols/adverse effects
9.
Crit Care Med ; 51(1): 69-79, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36377890

ABSTRACT

OBJECTIVES: To determine the incidence and characteristics of ICU admissions in the Scottish population of patients treated with chronic kidney replacement therapy (KRT) over an 11-year period and determine factors associated with post-ICU admission mortality. DESIGN: Retrospective observational cohort study. SETTING: We analyzed admissions to Scottish intensive care environments between January 1, 2009, and December 31, 2019. PATIENTS: All patients receiving chronic KRT-including maintenance dialysis and kidney transplant-in Scotland. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics and factors associated with mortality using logistic regression and Cox proportional hazard models. From 10,657 unique individuals registered in the Scottish Renal Registry over the 11-year study period and alive as of January 1, 2009, 1,402 adult patients were identified as being admitted to a Scottish critical care setting. Between 2009 and 2019, admissions to ICU increased in a nonlinear manner driven by increases in admissions for renal causes and elective cardiac surgery. The ICU admission rate was higher among patients on chronic dialysis than in kidney transplant recipients (59.1 vs 19.9 per 1,000 person-years), but post-ICU mortality was similar (about 24% at 30 d and 40% at 1 year). Admissions for renal reasons were most common (20.9%) in patients undergoing chronic dialysis, whereas kidney transplant recipients were most frequently admitted for pneumonia (19.3%) or sepsis (12.8%). Adjusted Cox PH models showed that receiving invasive ventilation and vasoactive drugs was associated with an increased risk of death at 30 days post-ICU admission (HR, 1.75; 95% CI, 1.28-2.39 and 1.72; 95% CI, 1.28-2.31, respectively). CONCLUSIONS: With a growing population of kidney transplant recipients and the improved survival of patients on chronic dialysis, the number of ICU admissions is rising in the chronic KRT population. Mortality post-ICU admission is high for these patients.


Subject(s)
Intensive Care Units , Renal Dialysis , Adult , Humans , Incidence , Retrospective Studies , Renal Replacement Therapy , Cohort Studies , Hospital Mortality
10.
Plant Cell ; 34(12): 4840-4856, 2022 11 29.
Article in English | MEDLINE | ID: mdl-36040205

ABSTRACT

Selected ß-amino acids, such as ß-aminobutyric acid (BABA) and R-ß-homoserine (RBH), can prime plants for resistance against a broad spectrum of diseases. Here, we describe a genome-wide screen of fully annotated Arabidopsis thaliana T-DNA insertion lines for impaired in RBH-induced immunity (iri) mutants against the downy mildew pathogen Hyaloperonospora arabidopsidis, yielding 104 lines that were partially affected and four lines that were completely impaired in RBH-induced resistance (IR). We confirmed the iri1-1 mutant phenotype with an independent T-DNA insertion line in the same gene, encoding the high-affinity amino acid transporter LYSINE HISTIDINE TRANSPORTER 1 (LHT1). Uptake experiments with yeast cells expressing LHT1 and mass spectrometry-based quantification of RBH and BABA in leaves of lht1 mutant and LHT1 overexpression lines revealed that LHT1 acts as the main transporter for cellular uptake and systemic distribution of RBH and BABA. Subsequent characterization of lht1 mutant and LHT1 overexpression lines for IR and growth responses revealed that the levels of LHT1-mediated uptake determine the tradeoff between IR and plant growth by RBH and BABA.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Amino Acids/metabolism , Arabidopsis/metabolism , Plant Development , Amino Acid Transport Systems/genetics , Amino Acid Transport Systems/metabolism , Plant Diseases
11.
Pediatr Emerg Care ; 38(9): 417-422, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35947060

ABSTRACT

OBJECTIVES: Children with traumatic arrests represent almost one third of annual pediatric out-of-hospital cardiac arrests (OHCAs). However, traumatic arrests are often excluded from study populations because survival posttraumatic arrest is thought to be negligible. We hypothesized that children treated and transported by emergency medical services (EMS) personnel after traumatic OHCA would have lower survival compared with children treated after medical OHCA. METHODS: We performed a secondary, observational study of children younger than 18 years treated and transported by 78 EMS agencies in southwestern Pennsylvania after OHCA from 2010 to 2014. Etiology was determined as trauma or medical by EMS services. We analyzed patient, cardiac arrest, and resuscitation characteristics and ascertained vital status using the National Death Index. We used multivariable logistic regression to test the association of etiology with mortality after covariate adjustment. RESULTS: Forty eight of 209 children (23%) had traumatic OHCA. Children with trauma were older than those with medical OHCA (13.2 [3.8-15.9] vs 0.5 [0.2-2.4] years, P < 0.001). Prehospital return of spontaneous circulation frequency for trauma versus medical etiology was similar (90% vs 87%, P = 0.84). Patients with trauma had higher mortality (69% vs 45% P = 0.004). CONCLUSIONS: More than 8 of 10 children with EMS treated and transported OHCA achieved return of spontaneous circulation. Despite lower survival rates than medical OHCA patients, almost one third of children with a traumatic etiology survived throughout the study period. Future research programs warrant inclusion of children with traumatic OHCA to improve outcomes.


Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Cardiopulmonary Resuscitation/adverse effects , Child , Humans , Logistic Models , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/therapy , Survival Rate
12.
Eur J Radiol ; 153: 110368, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35636024

ABSTRACT

PURPOSE: Iodinated radiographic contrast media has been associated with an acute deterioration in renal function, termed contrast induced nephropathy (CIN). This review aims to establish the efficacy of prophylaxis interventions used in adult patients prior to intravenous exposure to iodinated contrast to reduce the risk of CIN. METHODS: An electronic search for published peer-reviewed articles was performed, supplemented with manual review of references from previous systematic reviews and the National Institute for Health and Care Excellence guidelines. Risk of bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Random-effect meta-analyses were used to assess CIN incidence, need for kidney replacement therapy (KRT), mortality, fluid overload and persistent kidney dysfunction. RESULTS: 22 studies assessing a range of interventions were included in the qualitative analysis. The incidence of CIN was reduced by the use of N-acetylcysteine compared to a control group of saline (risk difference = -0.07, 95% CI -0.13 to -0.01) but not by sodium bicarbonate compared to control group of saline (risk difference = -0.02, 95% CI -0.04 to 0.01). Published studies give no indication that prophylactic interventions have significant impact on the need for KRT, mortality or persistent renal impairment. CONCLUSION: Evidence for prophylaxis against CIN in patients receiving intravenous iodinated contrast is limited. There was an association with the use of NAC with reduced incidence of CIN following intravenous contrast but there was no impact on other clinical outcomes assessed. The clinical significance of these findings remains unclear and further research focusing on these clinical outcomes is required.


Subject(s)
Kidney Diseases , Renal Insufficiency , Acetylcysteine/therapeutic use , Adult , Contrast Media/adverse effects , Humans , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Renal Insufficiency/chemically induced , Sodium Bicarbonate/adverse effects
13.
Kidney Int ; 101(6): 1271-1281, 2022 06.
Article in English | MEDLINE | ID: mdl-35398477

ABSTRACT

There is substantial variability in the reported incidence and outcomes of acute kidney injury (AKI). The extent to which this is attributable to differences in source populations versus methodological differences between studies is uncertain. We used 4 population-based datasets from Canada, Denmark, and the United Kingdom to measure the annual incidence and prognosis of AKI and acute kidney disease (AKD), using a homogenous analytical approach that incorporated KDIGO creatinine-based definitions and subsets of the AKI/AKD criteria. The cohorts included 7 million adults ≥18 years of age between 2011 and 2014; median age 59-68 years, 51.9-54.4% female sex. Age- and sex-standardised incidence rates for AKI or AKD were similar between regions and years; range 134.3-162.4 events/10,000 person years. Among patients who met either KDIGO 48-hour or 7-day AKI creatinine criteria, the standardised 1-year mortality was similar (30.4%-38.5%) across the cohorts, which was comparable to standardised 1-year mortality among patients who met AKI/AKD criteria using a baseline creatinine within 8-90 days prior (32.0%-37.4%). Standardised 1-year mortality was lower (21.0%-25.5% across cohorts) among patients with AKI/AKD ascertained using a baseline creatinine >90 days prior. These findings illustrate that the incidence and prognosis of AKI and AKD based on KDIGO criteria are consistent across 3 high-income countries when capture of laboratory tests is complete, creatinine-based definitions are implemented consistently within but not beyond a 90-day period, and adjustment is made for population age and sex. These approaches should be consistently applied to improve the generalizability and comparability of AKI research and clinical reporting.


Subject(s)
Acute Kidney Injury , Acute Disease , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Adult , Creatinine , Female , Humans , Incidence , Male , Prognosis , Retrospective Studies
14.
Metab Eng ; 72: 133-149, 2022 07.
Article in English | MEDLINE | ID: mdl-35289291

ABSTRACT

Robust systematic approaches for the metabolic engineering of cell factories remain elusive. The available models for predicting phenotypical responses and mechanisms are incomplete, particularly within the context of compound toxicity that can be a significant impediment to achieving high yields of a target product. This study describes a Multi-Omic Based Production Strain Improvement (MOBpsi) strategy that is distinguished by integrated time-resolved systems analyses of fed-batch fermentations. As a case study, MOBpsi was applied to improve the performance of an Escherichia coli cell factory producing the commodity chemical styrene. Styrene can be bio-manufactured from phenylalanine via an engineered pathway comprised of the enzymes phenylalanine ammonia lyase and ferulic acid decarboxylase. The toxicity, hydrophobicity, and volatility of styrene combine to make bio-production challenging. Previous attempts to create styrene tolerant E. coli strains by targeted genetic interventions have met with modest success. Application of MOBpsi identified new potential targets for improving performance, resulting in two host strains (E. coli NST74ΔaaeA and NST74ΔaaeA cpxPo) with increased styrene production. The best performing re-engineered chassis, NST74ΔaaeA cpxPo, produced ∼3 × more styrene and exhibited increased viability in fed-batch fermentations. Thus, this case study demonstrates the utility of MOBpsi as a systematic tool for improving the bio-manufacturing of toxic chemicals.


Subject(s)
Escherichia coli , Metabolic Engineering , Escherichia coli/metabolism , Fermentation , Metabolic Engineering/methods , Phenylalanine/genetics , Phenylalanine/metabolism , Styrene/metabolism
15.
Public Health Res Pract ; 32(1)2022 Mar 10.
Article in English | MEDLINE | ID: mdl-35290993

ABSTRACT

This year, 2021, marks the 40th anniversary of the iconic Slip! Slop! Slap! campaign which launched Australia's status as a global leader in skin cancer prevention. Since the campaign first aired in the summer of 1980-81, notable successes have been achieved, with melanoma rates declining in younger age groups. While skin cancer prevention is rightly considered a triumph of Australian public health, challenges remain. Australia still has one of the highest rates of skin cancer in the world, with about 2000 deaths per year from the disease. Skin cancer also presents the highest cost burden to the health system of any cancer type. Despite this, government investment at the national level is lacking. It is more difficult than ever to collect valuable representative national data on population skin cancer prevention behaviours to underpin and evaluate programs, as the methodology used previously has become unfeasible. There has not been a national skin cancer prevention mass-media campaign for over a decade, indicating complacency from policy makers. State and territory governments could also do more to implement evidence-based policies aimed at protecting children from ultraviolet radiation. This paper sets out Australia's skin cancer prevention landscape in 2021, and makes the case for a renewed focus from government on sun protection to safeguard the significant gains made over four decades and to protect future generations from an almost entirely preventable cancer.


Subject(s)
Melanoma , Skin Neoplasms , Australia/epidemiology , Child , Humans , Melanoma/prevention & control , Public Health , Skin Neoplasms/epidemiology , Skin Neoplasms/prevention & control , Ultraviolet Rays
17.
Am J Surg ; 223(1): 6-11, 2022 01.
Article in English | MEDLINE | ID: mdl-34332744

ABSTRACT

BACKGROUND: Burnout, often regarded as an individual failing, rather than a systemic one, negatively impacts quality of care, patient safety and healthcare costs. Focusing on improving well-being can help mitigate burnout. This study examined protective factors that promote well-being and professional fulfillment in surgeons. METHODS: Using a purposive sample, 32 semi-structured 30-60-min interviews were conducted with surgeons of varying sub-specialties and rank. Abductive exploratory analysis was used to code and interpret interview transcripts and to build a conceptual model of surgeon well-being. RESULTS: Emergent protective factors were placed into one of three levels of implementation: individual, team-level, and institutional (figure). Individual factors for well-being included autonomy and adequate time to pursue non-clinical endeavors. Team-level factors consisted of adaptability, boundaries, and cohesion. Institutional factors related to diversifying performance evaluations and celebrating and recognizing individual value and contributions. CONCLUSIONS: The conceptual model developed from the results of this study highlights factors important to surgeons' professional well-being. This model can be used to guide quality improvement efforts.


Subject(s)
Burnout, Professional/prevention & control , Job Satisfaction , Specialties, Surgical/organization & administration , Surgeons/psychology , Adaptation, Psychological , Administrative Personnel/organization & administration , Burnout, Professional/psychology , Faculty, Medical/organization & administration , Faculty, Medical/psychology , Female , Hospitals, University/organization & administration , Humans , Male , Models, Organizational , Qualitative Research , Quality Improvement , Surgeons/organization & administration , Utah , Work-Life Balance/organization & administration
18.
Am J Kidney Dis ; 79(4): 488-496.e1, 2022 04.
Article in English | MEDLINE | ID: mdl-34298142

ABSTRACT

RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) definition of acute kidney injury (AKI) is frequently used in studies to examine the epidemiology of AKI. This definition is variably interpreted and applied to routinely collected health care data. The aim of this study was to examine this variation and to achieve consensus in how AKI should be defined for research using routinely collected health care data. SOURCES OF EVIDENCE AND STUDY DESIGN: Scoping review via searching Medline and EMBASE for studies using health care data to examine AKI by using the KDIGO creatinine-based definition. An international panel of experts formed to participate in a modified Delphi process to attempt to generate consensus about how AKI should be defined when using routinely collected laboratory data. CHARTING METHODS AND ANALYTICAL APPROACH: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping reviews was followed. For the Delphi process, 2 rounds of questions were distributed via internet-based questionnaires to all participants with a prespecified cutoff of 75% agreement used to define consensus. RESULTS: The scoping review found 174 studies that met the inclusion criteria. The KDIGO definition was inconsistently applied, and the methods for application were poorly described. We found 58 (33%) of papers did not provide a definition of how the baseline creatinine value was determined, and only 34 (20%) defined recovery of kidney function. Of 55 invitees to the Delphi process, 35 respondents participated in round 1, and 25 participated in round 2. Some consensus was achieved in areas related to how to define the baseline creatinine value, which patients should be excluded from analysis of routinely collected laboratory data, and how persistent chronic kidney disease or nonrecovery of AKI should be defined. LIMITATIONS: The Delphi panel members predominantly came from the United Kingdom, the United States, and Canada, and there were low response rates for some questions in round 1. CONCLUSIONS: The current methods for defining AKI using routinely collected data are inconsistent and poorly described in the available literature. Experts could not achieve consensus for many aspects of defining AKI and describing its sequelae. The KDIGO guidelines should be extended to include a standardized definition for how AKI should be defined when using routinely collected data.


Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Consensus , Creatinine , Expert Testimony , Humans
19.
Br J Anaesth ; 128(3): 546-561, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34763813

ABSTRACT

BACKGROUND: Treating pain in the context of chronic kidney disease (CKD) is challenging because of altered pharmacokinetics and pharmacodynamics, with an increased risk of toxicity and drug adverse events in this population. The aims of this systematic review and meta-analysis were to assess the prevalence of analgesic use and establish the risk of analgesics-related adverse events, in patients with CKD. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Medline, Embase, CINAHL, and CENTRAL were searched until January 2021. Random-effects meta-analyses and meta-regression were conducted to pool and summarise prevalence data and measures of association between analgesic use and adverse events. RESULTS: Sixty-two studies relevant to the prevalence of analgesic use and 33 to analgesic-related adverse events were included, combining data on 2.3 and 3 million individuals, respectively. Pooled analyses found that 41% (95% confidence interval [CI], 35-48) of the CKD population regularly use analgesia. The annual period prevalence was estimated at 50% for opioids and 21% for nonsteroidal anti-inflammatory drugs (NSAID). Overall, 20% and 7% of patients with CKD are on chronic opioid or NSAID therapy, respectively. Opioid use was associated with an increased risk of death (1.61; 95% CI, 1.12-2.31; n= 7, I2= 91%), hospitalisation (1.38; 95% CI, 1.32-1.45; n=2, I2=0%), and fractures (1.51; 95% CI, 1.16-1.96; n=3, I2=54%). CONCLUSION: High levels of analgesic consumption and related serious adverse outcomes were found in patients with CKD. Consideration needs to be given to how these patients are assessed and managed in order to minimise harms and improve outcomes. CLINICAL TRIAL REGISTRATION: CRD42019156491 (PROSPERO).


Subject(s)
Analgesics/administration & dosage , Analgesics/therapeutic use , Drug-Related Side Effects and Adverse Reactions/etiology , Pain/drug therapy , Pain/etiology , Renal Insufficiency, Chronic/complications , Animals , Humans
20.
Porcine Health Manag ; 7(1): 59, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34823594

ABSTRACT

BACKGROUND: In commercial pig farming, sick or injured sows are often treated by producers or hired staff. To date, limited quantitative data exists on treatment compliance and the possible effect on sow longevity post-treatment. The objective of the study was to quantify on-farm compliance of treatment selection, frequency, and dosage, as well as to investigate the association between body condition scores (BCS) and other sow-level factors on post-treatment cull risk. RESULTS: On-farm treatment records, including culling reason or reason of death up to 6 months post-treatment, production records and sow characteristics were obtained for 134 sows over an 8-week period. Treatment compliance was based on the accuracy of recorded treatments compared to the herd veterinarian's established treatment guidelines. Univariable and multivariable logistic regression models including treatment reason, treatment compliance, BCS, parity, production stage and production metrics, were constructed to investigate associations between those variables and sow culling or death. This study found low compliance for on-farm sow treatment protocols, with only 22.4% (30/134) of the sows receiving correct and complete treatment during the duration of the study. No effect of individual treatment components (drug, dosage, or frequency) on sow culling was observed. A trend for an interaction between treatment compliance and BCS was found, and parity and number of piglets born alive were identified as predictors for sow maintenance in the herd. CONCLUSIONS: On-farm sow treatment compliance was low, resulting in that approximately 80% of the enrolled sows were not treated according to existing guidelines. Non-compliance of treatment guidelines did not seem to affect the risk of culling in treated sows but may have prolonged any associated pain, recovery time and negatively impacted the sow welfare during that time period.

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