The association of antiplatelet agents with mortality among patients with non-COVID-19 community-acquired pneumonia: a systematic review and meta-analysis.

Background: Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non-COVID-19 CAP remains uncertain. Objectives: To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non-COVID-19 CAP. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non-COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates. Results: We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; I 2  = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; I 2  = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; I 2  = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias. Conclusion: In hospitalized patients with non-COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low.

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 USA between 2006 and 2023, depending on data availability of each dataset. Patients with a 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 fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that 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.

Outcomes with severe pulmonary coccidioidomycosis and respiratory failure in the United States.

Background: Coccidioidomycosis is a fungal infection with presentations ranging from asymptomatic illness to severe pneumonia and respiratory failure. The outcomes of patients with severe pulmonary coccidioidomycosis requiring mechanical ventilation (MV) are not well understood. Methods: We performed a retrospective cohort analysis utilizing the Nationwide Inpatient Sample (NIS) from 2006 to 2017. Patients >18 years of age with a diagnosis of pulmonary coccidioidomycosis were included in the cohort. Results: A total of 11,045 patients were hospitalized with a diagnosis of pulmonary coccidioidomycosis during the study period. Of these, 826 (7.5%) patients required MV during their hospitalization with a mortality rate of 33.5% compared to 1.3% (p < 0.01) for patients not requiring MV. Results of the multivariable logistic regression model show that risk factors for MV included the history of neurological disorders and paralysis (OR 3.38[95% CI 2.70 to 4.20] p < 0.01; OR 3.13[95% CI 1.91 to 5.15] p < 0.01, respectively) and HIV (OR 1.63[95% 1.10 to 2.43] p < 0.01). Risk factors for mortality among patients requiring MV included older age (OR 1.24 per 10-year increase[95% CI 1.08 to 1.42] p < 0.01), coagulopathy (OR 1.61[95% CI 1.09 to 2.38] p = 0.01) and HIV (OR 2.83 [95% CI 1.32 to 6.10] p < 0.01). Conclusions: Approximately 7.5% of patients admitted with coccidioidomycosis in the United States require MV, and MV is associated with high mortality (33.5%).

Historique: La coccidioïdomycose est une infection fongique dont les manifestations vont d'une affection asymptomatique à une pneumonie grave et à une insuffisance respiratoire. Les résultats cliniques des patients atteints d'une coccidioïdomycose pulmonaire grave qui ont besoin d'une ventilation mécanique (VM) sont mal compris. Méthodologie: Les chercheurs ont procédé à une analyse de cohorte rétrospective au moyen d'un échantillon national de patients hospitalisés (NIS) entre 2006 et 2017. Les patients de plus de 18 ans ayant un diagnostic de coccidioïdomycose pulmonaire ont été inclus dans la cohorte. Résultats: Au total, 11 045 patients ont été hospitalisés à cause d'un diagnostic de coccidioïdomycose pulmonaire pendant la période de l'étude. De ce nombre, 826 (7,5 %) ont eu besoin d'une VM pendant leur hospitalisation, dont 33,5 % sont décédés par rapport à 1,3 % (p < 0,01) de ceux qui n'ont pas eu besoin de VM. Les résultats du modèle de régression logistique multivariable révèlent que les facteurs de risque de VM incluaient des antécédents de troubles neurologiques et de paralysie (rapport de cotes [RC] 3,38, IC à 95 % 2,70 à 4,20, p < 0,01; RC 3,13, IC à 95 % 1,91 à 5,15, p < 0,01, respectivement) et de virus de l'immunodéficience humaine (RC 1,63, IC à 95 % 1,10 à 2,43, p < 0,01). Les facteurs de risque de mortalité chez les patients qui avaient besoin de VM incluaient un âge plus avancé (RC 1,24 par tranche de dix ans, IC à 95 % 1,08 à 1,42, p < 0,01), une coagulopathie (RC 1,61, IC à 95 % 1,09 à 2,38, p = 0,01) et le virus de l'immunodéficience humaine (RC 2,83; IC à 95 % 1,32 à 6,10; p < 0,01). Conclusions: Environ 7,5 % des patients hospitalisés à cause d'une coccidioïdomycose aux États-Unis ont eu besoin d'une VM, laquelle est associée à un taux de mortalité élevé (33,5 %).

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.

Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality. METHODS AND ANALYSIS: A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI. ETHICS AND DISSEMINATION: This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04851015.

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.

qSOFA does not predict bacteremia in patients with severe manifestations of sepsis.

BACKGROUND: Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. METHODS: We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. RESULTS: Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. CONCLUSIONS: Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

HISTORIQUE: Les infections sanguines peuvent rester non diagnostiquées chez les patients septiques avant l'obtention des cultures sanguines, en raison d'une antibiothérapie antérieure. Les chercheurs ont puisé dans l'étude de cohorte FABLED pour déterminer si le score rapide de l'évaluation séquentielle d'insuffisance des organes (Sequential Organ Failure Assessment, qSOFA) pourrait dépister les patients à plus haut risque de bactériémie avec fiabilité, malgré la possibilité de cultures sanguines faussement négatives en raison d'une antibiothérapie antérieure. MÉTHODOLOGIE: Les chercheurs ont réalisé une étude diagnostique multicentrique chez des patients adultes ayant de graves manifestations de sepsis. Les patients ont été inscrits dans l'un des sept centres participants entre novembre 2013 et septembre 2018. Tous les patients de l'étude de cohorte FABLED avaient subi deux séries de cultures sanguines avant de recevoir une thérapie antimicrobienne, de même qu'une autre série de cultures sanguines dans les quatre heures suivant le début du traitement. Les participants ont été classés en fonction de leur score de qSOFA, un score d'au moins 2 étant considéré comme positif. RÉSULTATS: Chez les 325 patients ayant de graves manifestations de sepsis, un score de qSOFA positif (défini comme un score d'au moins 2) à l'admission était sensible à 58 % (IC à 95 %, 48 % à 67 %) et spécifique à 41 % (IC à 95 %, 34 % à 48 %) pour prédire la bactériémie. Chez les patients dont les cultures sanguines étaient négatives après la prise d'antimicrobiens, un score de qSOFA positif était sensible à 57 % (IC à 95 %, 42 % à 70 %) et spécifique à 42 % (IC à 95 %, 35 % à 49 %) pour dépister les patients atteints d'une bactériémie avant le début du traitement. CONCLUSIONS: Selon les résultats, le score de qSOFA ne peut pas être utilisé pour dépister les patients à risque de bactériémie occulte à cause de l'administration d'antibiotiques avant la culture sanguine.

Treatment in disproportionately minority hospitals is associated with an increased mortality in end-stage liver disease.

BACKGROUND: Racial and ethnic disparities are a barrier in delivery of healthcare across the USA. Care for minority patients tends to be clustered into a small number of providers at minority hospitals, which has been associated with worse clinical outcomes in several conditions. However, the outcomes of treatment in patients with end-stage liver disease (ESLD) at predominately minority hospitals are unknown. We investigated the burden of the problem. METHODS: We utilized the nationwide in-patient sample (NIS) to conduct a retrospective nationwide cohort analysis. All patients >18 years of age admitted with ESLD were included in the analysis. A multivariate logistic regression model was used to study the mortality rate among patients with ESLD treated at minority hospitals compared to nonminority hospitals. RESULTS: A total of 53 281 467 hospitalizations from the 2008 to 2014 NIS were analyzed. There were 163 470 patients with ESLD that met inclusion criteria. In-hospital mortality rates for all races were 8.0 and 8.1% in black and Hispanic minority hospitals, respectively, compared to 7.3% in nonminority hospitals (P < 0.01). On multivariate analysis, treatment of ESLD in black and Hispanic minority hospitals was associated with 11% [odds ratio (OR), 1.11; 95% confidence interval (CI), 1.03-1.20; P < 0.01] and 22% (OR, 1.22; 95% CI, 1.09-1.37; P < 0.01) increased odds of death, respectively, compared to treatment in nonminority hospitals regardless of patient's race. CONCLUSION: Patients with ESLD treated at minority hospitals are faced with an increased mortality rate regardless of patient's race. This study highlights another quality gap that needs improvement to affect overall survival among patients with ESLD.