Background: Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).
Methods: We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes. Thereafter, a simplified classifier (Euclidean distances) was used to assign the identified CS subphenotypes in three completed randomized controlled trials (RCTs) (OptimaCC, N = 57 [2011-2016, NCT01367743]; DOREMI, N = 192 [2017-2020, NCT03207165]; and CULPRIT-SHOCK, N = 434 [2013-2017, NCT01927549]) and explore heterogeneity of treatment effect with respect to 28-day mortality (primary outcome).
Findings: Four biomarker-driven CS subphenotypes ('adaptive', 'non-inflammatory', 'cardiopathic', and 'inflammatory') were identified separately in the two cohorts. Patients in the inflammatory and cardiopathic subphenotypes had the highest 28-day mortality (p (log-rank test) = 0.0099 and 0.0055 in the CardShock and FROG-ICU cohorts, respectively). Subphenotype membership significantly improved risk stratification when added to traditional risk factors including the Society for Cardiovascular Angiography and Interventions (SCAI) shock stages (increase in Harrell's C-index by 4% (p = 0.033) and 6% (p = 0.0068) respectively in the CardShock and the FROG-ICU cohorts). The simplified classifier identified CS subphenotypes with similar biological/molecular and outcome characteristics in the three independent RCTs. No significant interaction was observed between treatment effect and subphenotypes.
Interpretation: Subphenotypes with the highest concentration of biomarkers of endothelial dysfunction and inflammation (inflammatory) or myocardial injury/fibrosis (cardiopathic) were associated with mortality independently from the SCAI shock stages.
Funding: Dr Sabri Soussi was awarded the Canadian Institutes of Health Research (CIHR) Doctoral Foreign Study Award (DFSA) and the Merit Awards Program (Department of Anesthesiology and Pain Medicine, University of Toronto, Canada) for the current study.
Background: The COVID-19 pandemic highlighted the need for improved infectious aerosol concentrations through interventions that reduce the transmission of airborne infections. The aims of this review were to map the existing literature on interventions used to improve infectious aerosol concentrations in hospitals and understand challenges in their implementation.
Methods: We reviewed peer-reviewed articles identified on three databases, MEDLINE, Web of Science, and the Cochrane Library from inception to July 2024. 6417 articles were identified, 160 were reviewed and 18 were included.
Findings: Results on aerosol concentration were discussed in terms of three categories: (1) filtration and inactivation of aerosol particles; (2) effect of airflow and ventilation on aerosol concentrations; and (3) improvements or reduction in health conditions. The most common device or method that was outlined by researchers was high efficiency particulate air (HEPA) filters which were able to reduce aerosol concentrations under investigation across the included literature. Some articles were able to demonstrate the effectiveness of interventions in terms of improving health outcomes for patients.
Interpretation: The key finding is that infectious aerosol concentration improvement measures based on filtration, inactivation, improved air flow dynamics, and ventilation reduce the likelihood of nosocomial infections. However limitations of such approaches must be considered such as noise pollution and effects on ambient humidity. Whilst these efforts can contribute to improved air quality in hospitals, they should be considered with the other interacting factors such as microclimates, room dimensions and use of chemical products that effect air quality.
Funding: This study is funded by the National Institute for Health and Care Research (NIHR) (NIHR205439).
Background: While advancements in leukemia care have been made, the global quality of care remains a concern. This study utilizes a modified quality of care index (QCI) to assess the global status of leukemia care.
Methods: We analyzed data from the global burden of disease (GBD) study spanning 1990-2021. The QCI was constructed using principal component analysis, based on the weighted variances of key indicators. We compared the original QCI with our modified version, analyzed QCI trends across different age groups and leukemia subtypes, identified key influencing factors using linear mixed models (LMM), and used spatial autocorrelation analysis to verify the autocorrelation of the socio-demographic index (SDI) region. Then we employed the bayesian age-period-cohort (BAPC) model to predict future QCI trends.
Findings: Between 1990 and 2021, both the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) for leukemia exhibited a consistent decline. Our modified QCI method outperformed the original approach, particularly when the variance explained by the first principal component was below 80%, demonstrating higher correlation with the healthcare access and quality index (HAQI) (Pearson r = 0.91 vs. 0.89) and improved explanatory power (R2 = 0.82 vs. 0.79). Over past three decades, QCI was highest in San Marino (97.72%) and lowest in Fiji (3.51%), with significant regional variations across SDI levels (F = 133.40, p < 2e-16). High-SDI regions had the highest QCI (78.50%; 95% confidence interval: 77.20%, 79.70%). QCI trends varied by age, peaking at 94.49% in the 15-19 age group in 2021 and declining to 0.44% in the 75-79 age group. LMM analysis identified sex, age, year, SDI region, and leukemia subtype as significant QCI determinants. Spatial autocorrelation analysis confirmed positive autocorrelation within SDI regions (Global Moran's I = 0.87, p < 2e-16). Projections suggest a generally fluctuating upward trend in QCI for leukemia, reaching 79.58% by 2046.
Interpretation: The QCI serves as an effective metric for evaluating the quality of leukemia care. Our findings reveal a strong association between leukemia QCI and regional economic and educational development. Age is a critical factor, with an aging population contributing to a potential decline in QCI. These results underscore the urgent need for targeted interventions to enhance health services for older adults and to improve care quality in economically disadvantaged regions.
Funding: This study was supported by the National Natural Science Foundation of China (General Program) (No. 82370176) and the Key Research and Development Program of Hubei Province (No. CZKYXM2023036JZ).
Background: Given the chronic immune activation and inflammatory milieu associated with Long COVID and HIV, we assessed the prevalence of Long COVID in adults living with HIV; and investigated whether adults living with HIV were associated with increased chance of developing Long COVID compared to adults living without HIV.
Methods: In this systematic review and meta-analysis, we searched Medline, EMBASE, CINHAL, PubMed and CENTRAL from inception until June 14th, 2024, for observational studies that measured the prevalence of Long COVID in adults living with HIV and the odds of developing Long COVID following a SARS-CoV-2 infection in people living with HIV compared to people living without HIV. Reviews, case reports, randomised control trials and editorials were excluded. The search was conducted without language restrictions. We performed meta-analysis of proportions to synthesise prevalence estimates using logit transformation and a sensitivity analysis using mixed-effects logistic regression. We used random-effects meta-analyses to summarize the odds ratio (OR) of developing Long COVID in adults living with HIV compared to adults living without HIV and conducted a sensitivity analysis including only studies with covariate-adjusted estimates that was planned a-priori. We used ROBINS-E for the risk of bias assessment and GRADE to rate the certainty of evidence. We identified statistical heterogeneity using Cochran's Q test and quantified it using the I2 statistic. For the Q test, a P < 0.10 was considered statistically significant. PROSPERO registration: CRD42024577616.
Findings: Our search returned 831 results, of which 8 studies (4489 participants) were deemed eligible for inclusion in the systematic review and meta-analysis. The prevalence of Long COVID in adults with HIV was 43% (95% CI: 32-54%, 8 studies; 1227 participants; low certainty, I2 < 0.0001). The association of HIV status with Long COVID was inconclusive, with wide confidence intervals (OR: 1.16, 95% CI: 0.58-2.29; 4 studies; 3556 participants, low certainty, I2 = 0.013). When the analysis was restricted to studies reporting covariate-adjusted estimates, adults living with HIV were associated with a higher odds of Long COVID than those not living with HIV (OR: 2.21, 95% CI: 1.12-4.36; 2 studies; 374 participants, low certainty, I2 = 0.51).
Interpretation: Current evidence indicates that the prevalence of Long COVID in adults living with HIV may be high, suggesting the need for increased awareness and education of healthcare providers and policy makers. Evidence on whether HIV positivity increases the risk of Long COVID is limited and inconclusive, highlighting a need for further research to clarify this potential association.
Funding: None.
Background: Limited studies have suggested an effect of dietary choline intake on uric acid levels. We aim to investigate the associations between choline intake and hyperuricemia (HUA), as well as the mediating role of kidney function in this relationship, among the Chinese population aged 6-17 years.
Methods: Participants were divided into quartiles according to residual energy-adjusted dietary choline intake in our cross-sectional study. Dietary choline intake was assessed using the 24-h dietary recalls method over three consecutive days, including two weekdays and one weekend day. The primary outcome was the HUA prevalence. Based on recommendation in Clinical Paediatric Nephrology (3rd ed), HUA is defined based on fasting serum uric acid levels, with cutoffs varying by age and sex. The associations between choline intake and HUA were analysed using weighted logistic regression models, restricted cubic spline models, and linear regression models. The mediated proportions of estimated glomerular filtration rate (eGFR) in the associations were estimated with mediation effect models. The data for this study were collected from the China National Nutrition and Health Surveillance of Children and Lactating Mothers (2016-2017) conducted between October 2016 and December 2018. Eligible participants were identified through a database search conducted from October to December 2023.
Findings: Among the 10749 participants, 3398 (31.6%) individuals were found to have HUA. A negative dose-dependent relationship was found between dietary choline intake and HUA. Compared to participants in the lowest intake quartile of total choline, phosphatidylcholine, and betaine, those in the 4th quartile had lower odds of HUA, with odds ratio (OR) of 0.75 (95% confidence interval [95% CI], 0.63-0.90), 0.75 (95% CI, 0.64-0.89), and 0.75 (95% CI, 0.59-0.94), respectively. The eGFR mediated 10.60%-14.58% of the associations. Participants in the 4th quartile of lipid-soluble dietary choline exhibited 24.00% reduced odds of HUA compared to those in the lowest intake quartile, with an OR of 0.76 (95% CI, 0.64-0.90).
Interpretation: Moderate to high intake of dietary choline (181.20-357.92 mg/d), particularly phosphatidylcholine (120.22-207.58 mg/d), and betaine (189.24-282.37 mg/d), may reduce the odds of HUA by improving glomerular filtration function. Further interventional studies are needed to establish causal relationships.
Funding: This work was supported by the National Natural Science Foundation of China (82003443, 42375180), the Natural Science Foundation of Guangdong Province of China (2024A1515012088), and the Construction of High-level University of Guangdong (G624330422).
Background: Diabetic gastroenteropathy is associated with nausea, vomiting, bloating, pain, constipation, and diarrhoea. Current therapies are scarce. We tested faecal microbiota transplantation (FMT) for patients with type 1 diabetes and gastroenteropathy.
Methods: In a randomised, double-blinded, placebo-controlled pilot trial, adults with type 1 diabetes and moderate-to-severe gastrointestinal symptoms were randomised (1:1) to encapsulated FMT or placebo. Each patient received around 25 capsules containing 50 g of faeces, administered in a single dose. The placebo capsules contained glycerol, saline and food colouring. All patients received FMT as a second intervention. The primary endpoint was number of adverse events of severity grade 2 or more assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed four weeks after treatment. Public trial registration, ClinicalTrials.govNCT04749030.
Findings: We randomised 20 patients to FMT or placebo. Following this intervention, 26 adverse events of grade 2 or more occurred. Four patients in the FMT group reported seven adverse events, and five patients in the placebo group reported 19, with no differences between the groups. The most frequent adverse events were diarrhoea, bloating, and abdominal pain. No serious adverse events were related to the treatment. Patients who received FMT reduced their median Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome score from 58 (IQR 54-65) to 35 (32-48), whereas patients receiving placebo reduced their score from 64 (55-70) to 56 (50-77) (p = 0.01). The Irritable Bowel Syndrome Impact Scale score improved from 108 (101-123) to 140 (124-161) with FMT and 77 (53-129) to 92 (54-142) with placebo (p = 0.02). The Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (28-47) to 25 (14-31) after FMT and 47 (31-69) to 41 (36-64) after placebo (p = 0.03).
Interpretation: FMT was safe and improved clinical outcomes for patients with type 1 diabetes suffering from bowel symptoms.
Funding: Steno Collaborative Grant.
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