The prevalence of postacute sequelae of coronavirus disease 2019 in solid organ transplant recipients: Evaluation of risk in the National COVID Cohort Collaborative.

Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (P value < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status.

The Relative Risk of COVID-19 in Solid Organ Transplant Recipients Over Waves of the Pandemic.

Solid organ transplant recipients (SOTR) are at increased risk from COVID-19. Over time, the absolute risk of adverse outcomes after COVID-19 has decreased in both the non-immunosuppressed/immunocompromised (non-ISC) general population, and amongst SOTR. Using the N3C, we examined the absolute risk of mortality, major adverse renal or cardiac events, and hospitalization after COVID-19 diagnosis amongst non-ISC and SOTR populations over five waves of the pandemic (Wave 1: Ancestral COVID; Wave 2: Alpha; Wave 3: Delta; Wave 4: Omicron; Wave 5: Omicron). Within each wave, we determined the relative risk of each outcome for SOTR versus the non-ISC population based on crude event rates, and then used multivariable cox proportional hazards models and logistic regression to determine the adjusted risk of each outcome based on SOT status. Throughout the pandemic, including during the Omicron wave (Wave 5), SOTR were at greater absolute risk for each outcome than non-ISC patients (p-values all <0.001). The adjusted risk of SOT status for each outcome was relatively stable over time (aHR 1.28-1.61 for mortality; aHR 1.31-1.47 for MACE; aHR 1.72-1.90 for MARCE; aHR 1.75-2.07 for AKI; and aOR 1.53-1.81 for hospitalization). Despite a reduction in the absolute risk of COVID-19 complications, the relative risk for SOTR versus the non-ISC population has not improved.

Risk factors for severe outcomes of coronavirus disease 2019 through the waves of the pandemic: Comparing patients with and without solid organ transplantation.

BACKGROUND: While coronavirus disease 2019 (COVID-19) is no longer a public health emergency, certain patients remain at risk of severe outcomes. To better understand changing risk profiles, we studied the risk factors for patients with and without solid organ transplantation (SOT) through the various waves of the pandemic. METHODS: Using the National COVID Cohort Collaborative we studied a cohort of adult patients testing positive for COVID-19 between January 1, 2020, and May 2, 2022. We separated the data into waves of COVID-19 as defined by the Centers for Disease Control. In our primary outcome, we used multivariable survival analysis to look at various risk factors for hospitalization in those with and without SOT. RESULTS: A total of 3,570,032 patients were captured. We found an overall risk attenuation of adverse COVID-19-associated outcomes over time. In both non-SOT and SOT populations, diabetes, chronic kidney disease, and congestive heart failure were risk factors for hospitalization. For SOT specifically, longer time periods between transplant and COVID-19 were protective and age was a risk factor. Notably, asthma was not a risk factor for major adverse renal cardiovascular events, hospitalization, or mortality in either group. CONCLUSIONS: Our study provides a longitudinal view of the risks associated with adverse COVID-related outcomes amongst SOT and non-SOT patients, and how these risk factors evolved over time. Our work will help inform providers and policymakers to better target high-risk patients.

Sex and organ-specific risk of major adverse renal or cardiac events in solid organ transplant recipients with COVID-19.

While older males are at the highest risk for poor coronavirus disease 2019 (COVID-19) outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (January 1, 2020-June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID-19 diagnosis in those with and without SOT. We examined the exposure of age-stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3996 (36.4%) SOT and 91 646 (4.8%) non-SOT patients developed MARCE. Risk of post-COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non-SOT cohort (HR 0.89, 95% CI 0.81-0.98 for SOT and HR 0.61, 95% CI 0.60-0.62 for non-SOT [females vs. males]). This represents the largest COVID-19 SOT cohort to date and the first-time sex-age-stratified and allograft-specific COVID-19 outcomes have been explored in those with SOT.

The risk and consequences of breakthrough SARS-CoV-2 infection in solid organ transplant recipients relative to non-immunosuppressed controls.

Clinical outcomes in solid organ transplant (SOT) recipients with breakthrough COVID (BTCo) after two doses of mRNA vaccination compared to the non-immunocompromised/immunosuppressed (ISC) general population, are not well described. In a cohort of adult patients testing positive for COVID-19 between December 10, 2020 and April 4, 2022, we compared the cumulative incidence of BTCo in a non-ISC population to SOT recipients (overall and by organ type) using the National COVID Cohort Collaborative (N3C) including data from 36 sites across the United States. We assessed the risk of complications post-BTCo in vaccinated SOT recipients versus SOT with unconfirmed vaccination status (UVS) using multivariable Cox proportional hazards and logistic regression. BTCo occurred in 4776 vaccinated SOT recipients over a median of 149 days (IQR 99-233), with the highest cumulative incidence in heart recipients. The relative risk of BTCo was greatest in SOT recipients (relative to non-ISC) during the pre-Delta period (HR 2.35, 95% CI 1.80-3.08). The greatest relative benefit with vaccination for both non-ISC and SOT cohorts was in BTCo mortality (HR 0.37, 95% CI 0.36-0.39 for non-ISC; HR 0.67, 95% 0.57-0.78 for SOT relative to UVS). While the relative benefit of vaccine was less in SOT than non-ISC, SOT patients still exhibited significant benefit with vaccination.

Development of a chest X-ray machine learning convolutional neural network model on a budget and using artificial intelligence explainability techniques to analyze patterns of machine learning inference.

Objective: Machine learning (ML) will have a large impact on medicine and accessibility is important. This study's model was used to explore various concepts including how varying features of a model impacted behavior. Materials and Methods: This study built an ML model that classified chest X-rays as normal or abnormal by using ResNet50 as a base with transfer learning. A contrast enhancement mechanism was implemented to improve performance. After training with a dataset of publicly available chest radiographs, performance metrics were determined with a test set. The ResNet50 base was substituted with deeper architectures (ResNet101/152) and visualization methods used to help determine patterns of inference. Results: Performance metrics were an accuracy of 79%, recall 69%, precision 96%, and area under the curve of 0.9023. Accuracy improved to 82% and recall to 74% with contrast enhancement. When visualization methods were applied and the ratio of pixels used for inference measured, deeper architectures resulted in the model using larger portions of the image for inference as compared to ResNet50. Discussion: The model performed on par with many existing models despite consumer-grade hardware and smaller datasets. Individual models vary thus a single model's explainability may not be generalizable. Therefore, this study varied architecture and studied patterns of inference. With deeper ResNet architectures, the machine used larger portions of the image to make decisions. Conclusion: An example using a custom model showed that AI (Artificial Intelligence) can be accessible on consumer-grade hardware, and it also demonstrated an example of studying themes of ML explainability by varying ResNet architectures.

Treatments and Outcomes of Critically Ill Patients with Candida spp. Colonization of the Lower Respiratory Tract in Regina, Saskatchewan.

Background: Among critically ill patients receiving mechanical ventilation, Candida spp. are commonly detected in the lower respiratory tract (LRT). This is generally considered to represent colonization. Objective: To evaluate the use of antifungal treatments and the clinical outcomes of patients with Candida colonization of the LRT. Methods: This retrospective analysis involved consecutive patients admitted to the intensive care unit between April 2016 and May 2021with positive results on Candida spp. testing of LRT samples. Data related to antifungal treatment and clinical outcomes were analyzed descriptively, and multivariable logistic regression was performed. Results: Of 200 patients initially identified, 160 (80%) died in hospital. Antifungal therapy was given to 103 (51.5%) of the patients, with treatment being more likely among those with shock and those who received parenteral nutrition. Mortality was high among patients with positive Candida results on LRT culture, regardless of treatment. Multivariable logistic regression, with adjustment for age, sex, comorbidities, and sequential organ failure assessment (SOFA) score, showed that antifungal treatment was associated with lower odds of death (odds ratio 0.39, 95% confidence interval 0.17-0.87) compared with no treatment (p = 0.021). Conclusions: This study showed higher mortality rates than have been reported previously. Further investigation into the role of antifungal therapy among critically ill patients with Candida spp. colonization is required.

Contexte: Chez les patients gravement malades recevant une ventilation mécanique, les Candida spp. sont fréquemment détectées dans les voies respiratoires inférieures (VRI) ­ une situation généralement considérée comme une colonisation. Objectif: Évaluer l'utilisation d'un traitement antifongique et les résultats cliniques chez les patients présentant une colonisation par Candida dans les VRI. Méthodes: Cette analyse rétrospective portait sur des patients consécutifs de l'unité de soins intensifs ayant obtenu un résultat positif au test de Candida sur les isolats des VRI entre avril 2016 et mai 2021. Les données relatives au traitement antifongique et aux résultats cliniques ont été analysées de manière descriptive, et une régression logistique multivariable a été effectuée. Résultats: Parmi les 200 patients initialement recensés, 160 (80 %) sont décédés à l'hôpital. Une thérapie antifongique a été administrée à 103 (51,5 %) des patients, et le traitement était plus probable chez ceux en état de choc et ceux ayant reçu une nutrition parentérale. Les patients ayant été déclarés positifs pour la Candida dans la culture des VRI présentaient un taux de mortalité élevé, indépendamment du traitement. Une régression logistique multivariable, avec ajustement pour l'âge, le sexe, les comorbidités et le score SOFA (sequential organ failure assessment), a montré que le traitement antifongique était associé à une probabilité de décès réduite (rapport de cotes 0,39; intervalle de confiance à 95 % 0,17­0,87), par rapport à l'absence de traitement (p = 0,021). Conclusions: Cette étude a révélé des taux de mortalité plus élevés que ce qui avait été rapporté précédemment. Une enquête plus approfondie sur le rôle de la thérapie antifongique chez les patients gravement malades présentant une colonisation par Candida spp. est nécessaire.

Novel soluble epoxide hydrolase inhibitor protects mitochondrial function following stress.

Epoxyeicosatrienoic acids (EETs) are active metabolites of arachidonic acid that are inactivated by soluble epoxide hydrolase enzyme (sEH) to dihydroxyeicosatrienoic acid. EETs are known to render cardioprotection against ischemia reperfusion (IR) injury by maintaining mitochondrial function. We investigated the effect of a novel sEH inhibitor (sEHi) in limiting IR injury. Mouse hearts were perfused in Langendorff mode for 40 min and subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion. Hearts were perfused with 0.0, 0.1, 1.0 and 10.0 µmol·L(-1) of the sEHi N-(2-chloro-4-methanesulfonyl-benzyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (BI00611953). Inhibition of sEH by BI00611953 significantly improved postischemic left-ventricular-developed pressure and reduced infarct size following IR compared with control hearts, and similar to hearts perfused with 11,12-EETs (1 µmol·L(-1)) and sEH(-/-) mice. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 µmol·L(-1)), or the plasma membrane K(ATP) channels (pmK(ATP)) inhibitor (glibenclamide, 10 µmol·L(-1)) abolished the improved recovery by BI00611953 (1 µmol·L(-1)). Mechanistic studies in H9c2 cells demonstrated that BI0611953 decreased ROS generation, caspase-3 activity, proteasome activity, increased HIF-1∝ DNA binding, and delayed the loss of mitochondrial membrane potential (ΔΨ(m)) caused by anoxia-reoxygenation. Together, our data demonstrate that the novel sEHi BI00611953, a nicotinamide-based compound, provides significant cardioprotection against ischemia reperfusion injury.

COVID-19 in Solid Organ Transplantation: Results of the National COVID Cohort Collaborative.

Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant (SOT) recipients. The National COVID Cohort Collaborative was developed to facilitate analysis of patient-level data for those tested for COVID-19 across the United States. METHODS: In this study, we identified a cohort of SOT recipients testing positive or negative for COVID-19 (COVID+ and COVID-, respectively) between January 1, 2020, and November 20, 2020. Univariable and multivariable logistic regression were used to determine predictors of a positive result among those tested. Outcomes following COVID-19 diagnosis were also explored. RESULTS: Of 18 121 SOT patients tested, 1925 were positive (10.6%). COVID+ SOT patients were more likely to have a kidney transplant and be non-White race. Comorbidities were common in all SOT patients but significantly more common in those who were COVID+. Of COVID+ SOT, 42.9% required hospital admission. COVID+ status was the strongest predictor of acute kidney injury (AKI), rejection, and graft failure in the 90 d after testing. A total of 40.9% of COVID+ SOT experienced a major adverse renal or cardiac event, 16.3% experienced a major adverse cardiac event, 35.3% experienced AKI, and 1.5% experienced graft loss. CONCLUSIONS: In the largest US cohort of COVID+ SOT recipients to date, we identified patient factors associated with the diagnosis of COVID-19 and outcomes following infection, including a high incidence of major adverse renal or cardiac event and AKI.

Correction: mHealth Interventions to Promote Anti-Retroviral Adherence in HIV: Narrative Review.

[This corrects the article DOI: 10.2196/14739.].

mHealth Interventions to Promote Anti-Retroviral Adherence in HIV: Narrative Review.

BACKGROUND: Antiretrovirals (ARVs) are key in the management of HIV. Although no cure exists, ARVs help patients live healthy lives and prevent transmission to others. Adherence to complex regimens is paramount to outcomes and in avoiding the emergence of drug-resistant viruses. The goal of therapy is to reach an undetectable viral load. However, adherence is a common problem, stemming from issues such as mental health, chaotic home situations, and busy work schedules. Mobile health (mHealth) represents a new approach in improving medication adherence, and multiple studies have been performed in this area. OBJECTIVE: This study aims to review the current implementation of mHealth in the management of HIV among different groups of patients. METHODS: We used PubMed, Academic Search Elite, and 1 journal database with various search terms to review the current implementation of mHealth in HIV care. RESULTS: Titles and abstracts were screened, and 61 papers were identified and fully reviewed. The literature was divided into lower- and higher-income nations, as defined by the United Nations. A total of 20 studies with quantitative results were identified, with 10 being text- and SMS-based interventions (the majority of these being in lower-income countries) and 8 being smartphone-based apps (primarily in higher-income countries). The majority of these studies determined whether there was an effect on adherence or biochemical parameters (viral load and CD4 count). Various qualitative studies have also been conducted, and many have focused on determining the specific design of interventions that were successful (frequency of messaging, types of messages, etc) as well as priorities for patients with regard to mHealth interventions. CONCLUSIONS: There seems to be a role of mHealth in the management of HIV in lower-income nations; however, the optimal design of an intervention needs to be delineated. In higher-income countries, where the 2 significant risk factors were injection drugs and men who have sex with men, the benefit was less clear, and more research is needed.

Antimicrobial utilization data: Does point prevalence data correlate with defined daily doses?

We correlated antibiotic consumption measured by point prevalence survey with defined daily doses (DDD) across multiple hospitals. Point prevalence survey had a higher correlation (1) with monthly DDDs than annual DDDs, (2) in nonsurgical versus surgical wards, and (3) on high- versus low-utilization wards. Findings may be hospital specific due to hospital differences.

Synthesis of the phenoxonium cation of an alpha-tocopherol model compound crystallized with non-nucleophilic [B(C6F5)4]- and (CB11H6Br6)- anions.

The phenoxonium cation of a vitamin E model compound has been crystallized using the non-nucleophilic carborane and tetrakis(pentafluorophenyl)borate counteranions. The crystal structures confirm the assignment of the unusually stable phenoxonium cation and indicate that there is a substantial shortening of the carbon-oxygen bond lengths of the para-carbon atoms in the phenolic ring and a substantial increase of the carbon-oxygen bond length at the quaternary carbon. The crystallographic data are in excellent agreement with structural predictions from molecular orbital calculations.

Transformation of alpha-tocopherol (vitamin E) and related chromanol model compounds into their phenoxonium ions by chemical oxidation with the nitrosonium cation.

[reaction: see text] Alpha-tocopherol (alpha-TOH), the main oil component making up vitamin E, and its nonnatural solid 6-hydroxy-2,2,5,7,8-pentamethylchroman and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid structurally related analogues were oxidized quantitatively with 2 mol equiv of NO+ SbF6(-) in CH3CN at 233 K to form phenoxonium cations (alpha-TO+ SbF6(-)) in a chemically reversible two-electron/one-proton process. Solution-phase infrared spectroscopy, 1H and 13C NMR spectroscopy, and corresponding theoretical calculations of the spectroscopic data using density-based and wave-function-based models support the identity of the remarkably stable phenoxonium cations. The presence of an oxygen atom in the para position to the hydroxyl group and the chromanol ring structure appear to be important factors in stabilization of the phenoxonium ions, which raises the interesting possibility that the cations play a crucial role in the mode of action of vitamin E in biological systems. Although the phenoxonium cations are reactive toward nucleophiles such as water, they may be moderately stable in the hydrophobic (lipophilic) environment where vitamin E is known to occur naturally.