Epidemiology of renal replacement therapy for critically ill patients across seven health jurisdictions.

INTRODUCTION: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. METHODS: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the United States (USA) between 2006-2023, depending on data availability of each dataset. Patients with history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. RESULTS: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost four-fold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37-65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests differences in access to and provision of this therapy are contributing factors.

Disparities in access to and timing of interventional therapies for pulmonary embolism across the United States.

BACKGROUND: Interventional therapies (ITs) are an emerging treatment modality for pulmonary embolism (PE); however, the degree of racial, sex-based, and sociodemographic disparities in access and timing is unknown. OBJECTIVES: To investigate barriers to access and timing of ITs for PE across the United States. METHODS: A retrospective cohort study utilizing the Nationwide Inpatient Sample from 2016-2020 included adult patients with PE. The use of ITs (mechanical thrombectomy and catheter-directed thrombolysis) was identified via International Classification of Diseases 10th revision codes. Early IT was defined as procedure performed within the first 2 days after admission. RESULTS: A total of 27 805 273 records from the 2016-2020 Nationwide Inpatient Sample database were examined. There were 387 514 (1.4%) patients with PE, with 14 249 (3.6%) of them having undergone IT procedures (11 115 catheter-directed thrombolysis, 2314 thrombectomy, and 780 both procedures). After multivariate adjustment, factors associated with less use of IT included Black race (odds ratio [OR], 0.90; 95% CI, 0.86-0.94; P < .01), Hispanic race (OR, 0.73; 95% CI, 0.68-0.79; P < .01), female sex (OR, 0.88; 95% CI, 0.85-0.91; P < .01), treatment in a rural hospital (OR, 0.49; 95% CI, 0.44-0.54; P < .01), and lack of private insurance (Medicare OR, 0.77; 95% CI, 0.73-0.80; P < .01; Medicaid OR, 0.65; 95% CI, 0.61-0.69; P < .01; no coverage OR, 0.87; 95% CI, 0.82-0.93; P < .01). Among the patients who received IT, 11 315 (79%) procedures were conducted within 2 days of admission and 2934 (21%) were delayed. Factors associated with delayed procedures included Black race (OR, 1.12; 95% CI, 1.01-1.26; P = .04), Hispanic race (OR, 1.52; 95% CI, 1.28-1.80; P < .01), weekend admission (OR, 1.37; 95% CI, 1.25-1.51; P < .01), Medicare coverage (OR, 1.24; 95% CI, 1.10-1.40; P < .01), and Medicaid coverage (OR, 1.29; 95% CI, 1.12-1.49; P < .01). CONCLUSION: Significant racial, sex-based, and geographic barriers exist in overall access to IT for PE in the United States.

Preoperative oral fluoroquinolone antibiotics in elective colorectal surgery to prevent surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Preoperative treatment with oral neomycin combined with erythromycin or metronidazole is recommended to decrease the risk of surgical site infections (SSIs) in elective colorectal surgery. However, oral neomycin is not commercially available in Canada, and therefore it is not routinely used. Fluoroquinolones are widely available and have excellent activity against aerobic Gram-negative bacteria. The aim of this systematic review was to identify, critically appraise and summarize the evidence on the efficacy and safety of preoperative use of oral fluoroquinolone antibiotics for the prevention of SSIs in adult patients undergoing elective colorectal resection. METHODS: Following Cochrane guidelines, we included English-language randomized controlled trials (RCTs) comparing oral fluoroquinolones plus routine preoperative intravenous antibiotics against intravenous antibiotics alone from MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials( Ovid) and ClinicalTrials.gov. RESULTS: We included 3 RCTs (1136 patients). Risk of bias was uncertain in 2 trials and high in 1 trial. Preoperative oral fluoroquinolones led to significantly decreased total SSIs (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.32-0.57, I 2 = 0%), superficial incisional (RR 0.38, 95% CI 0.22-0.68, I 2 = 32%), deep incisional (RR 0.19, 95% CI 0.06-0.65, I 2 = 0%) and organ/space SSIs (RR 0.34, 95% CI 0.12-0.90, I 2 = 33%). There was also a significant reduction in anastomotic leaks (RR 0.22, 95% CI 0.06-0.87, I 2 = 0%). No antibiotic-related adverse events were reported. CONCLUSION: This review suggests that preoperative oral fluoroquinolones with intravenous antibiotics are superior to intravenous antibiotics alone for preventing SSIs after colorectal surgery. If neomycin is unavailable, oral fluoroquinolones should be considered as a reasonable alternative. Future trials are required to further compare the relative efficacy of oral antibiotic regimens.

Effect of Air Transport Delay on Mortality in Critical Illness: A Population-Based Cohort Study.

OBJECTIVE: For critically ill patients in remote areas, we assessed the association of transport delay via fixed wing air ambulance on 30-day mortality, excluding interhospital transports. METHODS: This was a retrospective cohort analysis of all such adult transports in Manitoba, Canada, over 5.4 years. Causal mediation analysis was used, with the Acute Physiology and Chronic Health Evaluation II Acute Physiology Score at the destination intensive care unit as the mediator. The covariates were age, sex, comorbidities, socioeconomic status, and physiologic variables from the sending site. RESULTS: The primary cohort was composed of 554 patients; 113 (20.4%) died within 30 days. The total transport delay (mean ± standard deviation) was 5.1 ± 1.7 hours. Compared with no delay, the average 5-hour transport delay was associated with an odds ratio for mortality of 1.34 with a 95% confidence interval from 40% lower to 270% higher, with 60% of the influence of total travel time attributable to worsening of patients' acute physiologic status during the delay in intensive care unit admission due to transport. CONCLUSIONS: Although these findings provide insufficient evidence for an effect of fixed wing air transport delay on mortality among critically ill patients, they underscore the need for additional and larger studies on this topic.

Assessment of Racial and Ethnic Differences in Oxygen Supplementation Among Patients in the Intensive Care Unit.

Importance: Pulse oximetry (SpO2) is routinely used for transcutaneous monitoring of blood oxygenation, but it can overestimate actual oxygenation. This is more common in patients of racial and ethnic minority groups. The extent to which these discrepancies are associated with variations in treatment is not known. Objective: To determine if there are racial and ethnic disparities in supplemental oxygen administration associated with inconsistent pulse oximeter performance. Design, Setting, and Participants: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC)-IV critical care data set. Included patients were documented with a race and ethnicity as Asian, Black, Hispanic, or White and were admitted to the intensive care unit (ICU) for at least 12 hours before needing advanced respiratory support, if any. Oxygenation levels and nasal cannula flow rates for up to 5 days from ICU admission or until the time of intubation, noninvasive positive pressure ventilation, high-flow nasal cannula, or tracheostomy were analyzed. Main Outcomes and Measures: The primary outcome was time-weighted average supplemental oxygen rate. Covariates included race and ethnicity, sex, SpO2-hemoglobin oxygen saturation discrepancy, data duration, number and timing of blood gas tests on ICU days 1 to 3, partial pressure of carbon dioxide, hemoglobin level, average respiratory rate, Elixhauser comorbidity scores, and need for vasopressors or inotropes. Results: This cohort included 3069 patients (mean [SD] age, 66.9 [13.5] years; 83 were Asian, 207 were Black, 112 were Hispanic, 2667 were White). In a multivariable linear regression, Asian (coefficient, 0.602; 95% CI, 0.263 to 0.941; P = .001), Black (coefficient, 0.919; 95% CI, 0.698 to 1.140; P < .001), and Hispanic (coefficient, 0.622; 95% CI, 0.329 to 0.915; P < .001) race and ethnicity were all associated with a higher SpO2 for a given hemoglobin oxygen saturation. Asian (coefficient, -0.291; 95% CI, -0.546 to -0.035; P = .03), Black (coefficient, -0.294; 95% CI, -0.460 to -0.128; P = .001), and Hispanic (coefficient, -0.242; 95% CI, -0.463 to -0.020; P = .03) race and ethnicity were associated with lower average oxygen delivery rates. When controlling for the discrepancy between average SpO2 and average hemoglobin oxygen saturation, race and ethnicity were not associated with oxygen delivery rate. This discrepancy mediated the effect of race and ethnicity (-0.157; 95% CI, -0.250 to -0.057; P = .002). Conclusions and Relevance: In this cohort study, Asian, Black, and Hispanic patients received less supplemental oxygen than White patients, and this was associated with differences in pulse oximeter performance, which may contribute to known race and ethnicity-based disparities in care.

High resolution data modifies intensive care unit dialysis outcome predictions as compared with low resolution administrative data set.

High resolution clinical databases from electronic health records are increasingly being used in the field of health data science. Compared to traditional administrative databases and disease registries, these newer highly granular clinical datasets offer several advantages, including availability of detailed clinical information for machine learning and the ability to adjust for potential confounders in statistical models. The purpose of this study is to compare the analysis of the same clinical research question using an administrative database and an electronic health record database. The Nationwide Inpatient Sample (NIS) was used for the low-resolution model, and the eICU Collaborative Research Database (eICU) was used for the high-resolution model. A parallel cohort of patients admitted to the intensive care unit (ICU) with sepsis and requiring mechanical ventilation was extracted from each database. The primary outcome was mortality and the exposure of interest was the use of dialysis. In the low resolution model, after controlling for the covariates that are available, dialysis use was associated with an increased mortality (eICU: OR 2.07, 95% CI 1.75-2.44, p<0.01; NIS: OR 1.40, 95% CI 1.36-1.45, p<0.01). In the high-resolution model, after the addition of the clinical covariates, the harmful effect of dialysis on mortality was no longer significant (OR 1.04, 95% 0.85-1.28, p = 0.64). The results of this experiment show that the addition of high resolution clinical variables to statistical models significantly improves the ability to control for important confounders that are not available in administrative datasets. This suggests that the results from prior studies using low resolution data may be inaccurate and may need to be repeated using detailed clinical data.

A 39-Year-Old Woman With Hemoptysis, Polydipsia, and Polyuria.

CASE PRESENTATION: A 39-year-old previously healthy woman presented to the hospital with a nonproductive cough, small-volume hemoptysis, and exertional dyspnea. In addition, she reported a 4-week history of progressive left-sided headache, retro-orbital pain, left ear conductive hearing loss, fever, chills, anorexia, and a 10-lb weight loss. She had no prior sick contacts or history of respiratory tract infections. She did not take any chronic medications or supplements. The patient was a lifelong nonsmoker. She worked as a field consultant in Northern Manitoba communities. While in the hospital, she developed new symptoms of "unquenchable thirst," polydipsia, and polyuria.

Impact of the Hemostasis and Thrombosis Research Society trainee workshop in recruiting the next generation of nonmalignant hematologists.

The United States is facing a shortage of physicians dedicated to nonmalignant hematology to meet future needs. The Hemostasis and Thrombosis Research Society (HTRS) developed a medical education program for trainees, "HTRS Trainee Workshops: Building a Career in Hemostasis and Thrombosis" in 2016. The aim of this study is to evaluate the impact of the workshop in recruiting the next generation of nonmalignant hematologists. Two surveys (post-workshop survey and alumni survey) were conducted. The post-workshop survey occurred within 30 days of each workshop and was completed by 81.9% (n = 185) of participants. Majority of respondents reported that the workshop had a positive impact to their practice and/or research (93.0%, n = 174) and career development (87.7%, n = 164). For the alumni survey which was conducted in 2018, 73 participants responded to the survey (38.2% response rate). Of the 38 respondents who had graduated from fellowship at the time of the survey, almost all chose a career in academic medicine. 41.7% (n = 15) reported their specialty as adult nonmalignant hematology and 25.0% (n = 9) as pediatric hematology/oncology with a nonmalignant hematology focus. 41.1% (n = 30) developed collaborative professional relationships, and 78.1% (n = 57) reported that the workshop had a positive influence in their choice to pursue nonmalignant hematology as a career. 67.1% (n = 49) were actively involved in research in nonmalignant hematology, with the most common being clinical research. This survey suggests that the HTRS Trainee Workshop is meeting its goals to recruit, train, and mentor the next generation of nonmalignant hematologists.

Anemia prevalence and incidence and red blood cell transfusion practices in aneurysmal subarachnoid hemorrhage: results of a multicenter cohort study.

BACKGROUND: Whether a restrictive strategy for red blood cell (RBC) transfusion is applied to patients with aneurysmal subarachnoid hemorrhage (aSAH) is unclear. To inform the design and conduct of a future clinical trial, we sought to describe transfusion practices, hemoglobin (Hb) triggers, and predictors of RBC transfusion in patients with aSAH. METHODS: This is a retrospective cohort study of all consecutively admitted adult patients with aSAH at four tertiary care centers from January 1, 2012, to December 31, 2013. Patients were identified from hospital administrative discharge records and existing local aSAH databases. Data collection by trained abstractors included demographic data, aSAH characteristics, Hb and transfusion data, other major aSAH cointerventions, and outcomes using a pretested case report form with standardized procedures. Descriptive statistics were used to summarize data, and regression models were used to identify associations between anemia, transfusion, and other relevant predictors and outcome. RESULTS: A total of 527 patients met inclusion eligibility. Mean (±SD) age was 57 ± 13 years, and 357 patients (67.7%) were female. The median modified Fisher grade was 4 (IQR 3-4). Mean nadir Hb was 98 ± 20 g/L and occurred on median admission day 4 (IQR 2-11). RBC transfusion occurred in 100 patients (19.0%). Transfusion rates varied across centers (12.1-27.4%, p = 0.02). Patients received a median of 1 RBC unit (IQR 1-2) per transfusion episode and a median total of 2 units (IQR 1-4). Median pretransfusion Hb for first transfusion was 79 g/L (IQR 74-93) and did not vary substantially across centers (78-82 g/L, p = 0.37). Of patients with nadir Hb < 80 g/L, 66.3% received a transfusion compared with 2.0% with Hb nadir ≥ 100 g/L (p < 0.0001). Predictors of transfusion were history of oral anticoagulant use, anterior circulation aneurysm, neurosurgical clipping, and lower Hb. Controlling for numerous potential confounders, transfusion was not independently associated with poor outcome. CONCLUSIONS: We observed that moderate anemia remains very common early in admission following SAH. Only one-fifth of patients with SAH received RBC transfusions, mostly in cases of significant anemia (Hb < 80 g/L), and this did not appear to be associated with outcome.

Cyanobacterial Community Composition and Bacteria-Bacteria Interactions Promote the Stable Occurrence of Particle-Associated Bacteria.

Within meso/eutrophic freshwater ecosystems the dominance of cyanobacterial blooms during summer months has substantial impacts on ecosystem function with the production of toxins and subsequent induction of hypoxia altering food web structures and biogeochemical cycles. Cyanobacterial aggregates are extensively colonized by heterotrophic bacteria that provide the cyanobacteria with key nutrients and contribute towards remineralisation of organic matter. Here we sampled from five sites within a shallow eutrophic pond over a 6 months period, relating changes in the abundance of particle-associated heterotrophic taxa to phytoplankton abundance, toxin gene copies and physiochemical properties. The abundance of a majority of particle-associated bacteria were stable, in that they persisted despite perturbation. Cyanobacterial species abundance more likely correlated with stable rather than unstable bacteria and unstable bacteria were associated with allochthonous (terrestrial) organic matter. The occurrence of the most stable bacteria was correlated with large numbers of other bacteria suggesting bacteria-bacteria interactions have implications for the stable occurrence of microorganisms on particles. Freshwater ecosystems are frequently inundated with fresh nutrients in the form of surface runoff and experience an increasing number of high temperature days. In addition to increasing the severity and longevity of cyanobacterial blooms, run-off changes the nature of the particle-associated community compromising stability. This disruption has the potential to drive changes in the carbon and nitrogen cycles and requires further attention.

Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer.

Intravesical Bacillus Camlette-Guérin (BCG) is the treatment of choice for non-muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesical BCG therapy is BCG-induced sepsis. We report a rare case in which a patient with end-stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre-transplant intravesical BCG treatment for high-grade non-invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years after BCG therapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post-transplant, he developed BCG-induced sepsis confirmed by cultures from urine, blood, and left native kidney biopsy. He died from disseminated BCG-induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesical BCG therapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness for BCG-related infections during pre-transplant assessment and post-transplant care of solid organ transplants recipients.

Tolerance of Listeria monocytogenes to Quaternary Ammonium Sanitizers Is Mediated by a Novel Efflux Pump Encoded by emrE.

A novel genomic island (LGI1) was discovered in Listeria monocytogenes isolates responsible for the deadliest listeriosis outbreak in Canada, in 2008. To investigate the functional role of LGI1, the outbreak strain 08-5578 was exposed to food chain-relevant stresses, and the expression of 16 LGI1 genes was measured. LGI1 genes with putative efflux (L. monocytogenes emrE [emrELm]), regulatory (lmo1851), and adhesion (sel1) functions were deleted, and the mutants were exposed to acid (HCl), cold (4°C), salt (10 to 20% NaCl), and quaternary ammonium-based sanitizers (QACs). Deletion of lmo1851 had no effect on the L. monocytogenes stress response, and deletion of sel1 did not influence Caco-2 and HeLa cell adherence/invasion, whereas deletion of emrE resulted in increased susceptibility to QACs (P < 0.05) but had no effect on the MICs of gentamicin, chloramphenicol, ciprofloxacin, erythromycin, tetracycline, acriflavine, and triclosan. In the presence of the QAC benzalkonium chloride (BAC; 5 µg/ml), 14/16 LGI1 genes were induced, and lmo1861 (putative repressor gene) was constitutively expressed at 4 °C, 37 °C, and 52 °C and in the presence of UV exposure (0 to 30 min). Following 1 h of exposure to BAC (10 µg/ml), upregulation of emrE (49.6-fold), lmo1851 (2.3-fold), lmo1861 (82.4-fold), and sigB (4.1-fold) occurred. Reserpine visibly suppressed the growth of the ΔemrELm strain, indicating that QAC tolerance is due at least partially to efflux activity. These data suggest that a minimal function of LGI1 is to increase the tolerance of L. monocytogenes to QACs via emrELm. Since QACs are commonly used in the food industry, there is a concern that L. monocytogenes strains possessing emrE will have an increased ability to survive this stress and thus to persist in food processing environments.

Sequence typing confirms that a predominant Listeria monocytogenes clone caused human listeriosis cases and outbreaks in Canada from 1988 to 2010.

Human listeriosis outbreaks in Canada have been predominantly caused by serotype 1/2a isolates with highly similar pulsed-field gel electrophoresis (PFGE) patterns. Multilocus sequence typing (MLST) and multi-virulence-locus sequence typing (MVLST) each identified a diverse population of Listeria monocytogenes isolates, and within that, both methods had congruent subtypes that substantiated a predominant clone (clonal complex 8; virulence type 59; proposed epidemic clone 5 [ECV]) that has been causing human illness across Canada for more than 2 decades.

Lipid peroxidation scavengers prevent the carbonylation of cytoskeletal brain proteins induced by glutathione depletion.

In this study, we investigated the possible link between lipid peroxidation (LPO) and the formation of protein carbonyls (PCOs) during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH depletor diethyl maleate (DEM) in the absence or presence of classical LPO scavengers: trolox, caffeic acid phenethyl ester (CAPE), and butylated hydroxytoluene (BHT). All three scavengers reduced DEM-induced lipid oxidation and protein carbonylation, suggesting that intermediates/products of the LPO pathway such as lipid hydroperoxides, 4-hydroxynonenal and/or malondialdehyde are involved in the process. Additional in vitro experiments revealed that, among these products, lipid hydroperoxides are most likely responsible for protein oxidation. Interestingly, BHT prevented the carbonylation of cytoskeletal proteins but not that of soluble proteins, suggesting the existence of different mechanisms of PCO formation during GSH depletion. In pull-down experiments, beta-actin and alpha/beta-tubulin were identified as major carbonylation targets during GSH depletion, although other cytoskeletal proteins such as neurofilament proteins and glial fibrillary acidic protein were also carbonylated. These findings may be important in the context of neurological disorders that exhibit decreased GSH levels and increased protein carbonylation such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis.

Current and future options for the treatment of chemotherapy-induced anaemia.

Chemotherapy-induced anaemia (CIA) is a significant source of morbidity in patients receiving treatment for cancer. There are three products currently available for the treatment of CIA: epoetin alfa, epoetin beta and darbepoetin alfa. Several organisations have published recommendations for the use of these agents. Several randomised, controlled trials have been conducted comparing the most popular dosing regimens of epoetin alfa and darbepoetin alfa, with conflicting results. Information regarding survival and adverse event data related to these agents continues to create debate. This review considers four new agents that are under development for the treatment of CIA.

Acute depletion of reduced glutathione causes extensive carbonylation of rat brain proteins.

This study was aimed at establishing whether oxidative stress induced by acute depletion of brain glutathione (GSH) is sufficient to generate protein carbonyls (PCOs). To this end, rat brain slices were incubated separately with the GSH depletors 1,3-bis[2-chloroethyl]-1-nitrosourea (BCNU) and diethyl maleate (DEM), and protein carbonylation was assessed on Western blots after derivatization with dinitrophenyl hydrazine. Incubation with 1 mM BCNU or 10 mM DEM for 2 hr decreased GSH levels by > 70%. Under these conditions the carbonylation of several proteins (40-120 kDa) increased by 2-3 fold. Isolation of carbonylated proteins showed that augmented PCOs represents a rise in the amount of oxidized protein. The iron chelator deferoxamine, the superoxide scavenger rutin and the H2O2 quencher dimethylthiourea all prevented DEM-induced protein carbonylation and lipid peroxidation (TBARS), indicating that the underlying mechanism involves the iron-catalyzed generation of hydroxyl radicals from H(2)O(2) (Fenton reaction). Inhibition of catalase activity with sodium azide and aminotriazole, and glutathione peroxidase activity with mercaptosuccinic acid did not increase PCOs or TBARS, suggesting that increased production of reactive oxygen species (ROS) rather than compromised cellular antioxidant defenses is the cause for the accumulation of H2O2 after GSH depletion. PCO formation was not affected by the xanthine oxidase inhibitor oxypurinol but it was reduced by SKF-525A and carbonyl cyanide 3-chlorophenylhydrazone, indicating that the microsomal monooxygenase system and the mitochondrial electron transport system are the major sources of ROS. Consistent with these findings, subcellular fractionation studies showed that mitochondria and synaptosomes are the major PCO-containing organelles. These results were also supported by the anatomic distribution of PCOs in brain. Our observations may be important in the context of multiple sclerosis where decreased GSH, mitochondrial dysfunction, excessive production of ROS, and increased protein carbonylation have all been reported.