Use of latent class analysis and patient reported outcome measures to identify distinct long COVID phenotypes: A longitudinal cohort study.

OBJECTIVES: We sought to 1) identify long COVID phenotypes based on patient reported outcome measures (PROMs) and 2) determine whether the phenotypes were associated with quality of life (QoL) and/or lung function. METHODS: This was a longitudinal cohort study of hospitalized and non-hospitalized patients from March 2020 to January 2022 that was conducted across 4 Post-COVID Recovery Clinics in British Columbia, Canada. Latent class analysis was used to identify long COVID phenotypes using baseline PROMs (fatigue, dyspnea, cough, anxiety, depression, and post-traumatic stress disorder). We then explored the association between the phenotypes and QoL (using the EuroQoL 5 dimensions visual analogue scale [EQ5D VAS]) and lung function (using the diffusing capacity of the lung for carbon monoxide [DLCO]). RESULTS: There were 1,344 patients enrolled in the study (mean age 51 ±15 years; 780 [58%] were females; 769 (57%) were of a non-White race). Three distinct long COVID phenotypes were identified: Class 1) fatigue and dyspnea, Class 2) anxiety and depression, and Class 3) fatigue, dyspnea, anxiety, and depression. Class 3 had a significantly lower EQ5D VAS at 3 (50±19) and 6 months (54 ± 22) compared to Classes 1 and 2 (p<0.001). The EQ5D VAS significantly improved between 3 and 6 months for Class 1 (median difference of 6.0 [95% CI, 4.0 to 8.0]) and Class 3 (median difference of 5.0 [95% CI, 0 to 8.5]). There were no differences in DLCO between the classes. CONCLUSIONS: There were 3 distinct long COVID phenotypes with different outcomes in QoL between 3 and 6 months after symptom onset. These phenotypes suggest that long COVID is a heterogeneous condition with distinct subpopulations who may have different outcomes and warrant tailored therapeutic approaches.

Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol.

Background: People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population. Objective: The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination. Design: This is a prospective observational cohort study. Setting: Participating outpatient kidney programs within Ontario and British Columbia. Patients: Up to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T). Measurements: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity. Methods: Participants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose. Strengths and limitations: The adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population. Conclusions: This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) ont été touchées de façon disproportionnée par la pandémie de COVID-19 ayant notamment présenté des taux plus élevés d'infection, d'hospitalisation et de décès. Les données sur la réactivité aux stratégies de vaccination de la COVID-19 et à l'immunogénicité sont limitées, mais elles sont nécessaires pour développer des stratégies de vaccination dans cette population à risque. Objectif: Caractériser la réponse sérologique longitudinale à la vaccination contre la COVID-19. Conception: Étude de cohorte observationnelle prospective. Cadre: Les programmes ambulatoires de santé rénale participants en Ontario et en Colombie-Britannique. Sujets: Jusqu'à 2 500 personnes atteintes d'IRC G3B-5D recevant un vaccin contre la COVID-19, y compris des patients suivant des traitements de dialyse et des receveurs d'une greffe rénale (IRC G1T-5T). Mesures: Les anticorps IgG anti-SARS-CoV-2 (anti-spike, anti-domaine de liaison au récepteur, anti-nucléocapside) seront détectés par ELISA à partir du sérum ou de taches de sang séché. Un sous-groupe de sujets participera également à l'évaluation d'anticorps neutralisants dirigés contre les nouveaux variants préoccupants. Des cellules mononuclées de sang périphérique seront prélevées pour établir un profil immunitaire exploratoire de l'immunité cellulaire spécifique au SARS-CoV-2. Méthodologie: Les sujets seront recrutés avant ou après toute dose du vaccin contre la COVID-19 et se soumettront à des prélèvements sanguins pour les tests sérologiques à 1, 3, 6, 9 et 12 mois post-vaccination. Lorsque possible, des échantillons seront prélevés avant l'administration d'une dose ou d'un rappel. Les sujets demeureront dans l'étude pendant au moins un an après leur dernière dose de vaccin contre la COVID-19. Points forts et limites: La conception adaptative de l'étude permet d'apporter des modifications planifiées fondées sur de nouvelles données ou des changements rapides dans les politiques de santé publique entourant la vaccination. Les résultats sont limités par l'absence de certains prélèvements sanguins antérieurs (point temporels) en raison de la vaccination rapide de la population. Conclusion: Cette vaste étude sérologique multicentrique menée auprès de personnes atteintes de néphropathie fournira des données sur la cinétique de la réponse immunitaire à la vaccination contre le SARS-CoV-2 dans l'ensemble du spectre de l'IRC. Elle fournira des informations sur l'amplitude et la durée de l'immunité conférée par la vaccination contre la COVID-19 et permettra de caractériser les facteurs associés à la réponse immunitaire. Ces résultats serviront à orienter les recommandations de santé publique et les lignes directrices en matière d'immunisation pour les quatre millions de Canadiens et Canadiennes qui vivent avec l'IRC.

Clinical Outcomes and Vaccine Effectiveness for SARS-CoV-2 Infection in People Attending Advanced CKD Clinics: A Retrospective Provincial Cohort Study.

BACKGROUND: People with advanced CKD are at high risk of mortality and morbidity from coronavirus disease 2019 (COVID-19). We measured rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes in a large population attending advanced CKD clinics during the first 21 months of the pandemic. We examined risk factors for infection and case fatality, and we assessed vaccine effectiveness in this population. METHODS: In this retrospective cohort study, we analyzed data on demographics, diagnosed SARS-CoV-2 infection rates, outcomes, and associated risk factors, including vaccine effectiveness, for people attending a province-wide network of advanced CKD clinics during the first four waves of the pandemic in Ontario, Canada. RESULTS: In a population of 20,235 patients with advanced CKD, 607 were diagnosed with SARS-CoV-2 infection over 21 months. The case fatality rate at 30 days was 19% overall but declined from 29% in the first wave to 14% in the fourth. Hospitalization and intensive care unit (ICU) admission rates were 41% and 12%, respectively, and 4% started long-term dialysis within 90 days. Significant risk factors for diagnosed infection on multivariable analysis included lower eGFR, higher Charlson Comorbidity Index, attending advanced CKD clinics for more than 2 years, non-White ethnicity, lower income, living in the Greater Toronto Area, and long-term care home residency. Being doubly vaccinated was associated with lower 30-day case fatality rate (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.03 to 0.52). Older age (OR, 1.06 per year; 95% CI, 1.04 to 1.08) and higher Charlson Comorbidity Index (OR, 1.11 per unit; 95% CI, 1.01 to 1.23) were associated with higher 30-day case fatality rate. CONCLUSIONS: People attending advanced CKD clinics and diagnosed with SARS-CoV-2 infection in the first 21 months of the pandemic had high case fatality and hospitalization rates. Fatality rates were significantly lower in those who were doubly vaccinated. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10560922.mp3.

Double-Positive Anti-Glomerular Basement Membrane Antibody and Myeloperoxidase Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis Post COVID-19 mRNA vaccine: A Case Series of 4 Patients.

Rationale: Vaccines remain central to the management of COVID-19 pandemic, including the need for repeat doses of vaccines to boost immunity. There has been an accumulating case count of glomerulopathies temporally associated with COVID-19 vaccination. This case series presents 4 patients who developed double-positive anti-glomerular basement membrane antibody (anti-GBM) and myeloperoxidase (MPO) antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis after COVID-19 mRNA vaccination. This report contributes to our collective knowledge about the pathophysiology and clinical outcomes associated with this rare complication. Presenting Concerns of the Patient: Four patients developed nephritic syndrome within 1 to 6 weeks after receiving a COVID-19 mRNA vaccine (3 post Pfizer-BioNTech and 1 post Moderna vaccination). Three of the 4 patients also had hemoptysis. Diagnosis: Three of the 4 patients had double-positive serology, whereas the fourth patient had renal biopsy findings consistent with double-positive disease, although anti-GBM serology was negative. All patients had renal biopsy findings consistent with double-positive anti-GBM and ANCA-associated glomerulonephritis. Interventions: All 4 patients were treated with pulse steroids, cyclophosphamide, and plasmapheresis. Outcomes: Of the 4 patients, 1 demonstrated complete remission, 2 remained dialysis-dependent, and the fourth is deceased. Of the 2 patients who received repeat vaccination with COVID-19 mRNA vaccine, 1 patient had second serologic flare of anti-GBM in response to the vaccine. Novel Findings: This case series reinforces growing evidence that COVID-19 mRNA vaccine-induced glomerulonephritis is a rare but real phenomenon. Dual ANCA and anti-GBM nephritis can present after the first dose of COVID-19 mRNA vaccine or after several administrations of the vaccine. We are the first to report cases of double-positive MPO ANCA and anti-GBM nephritis after Pfizer-BioNTech vaccination. To our knowledge, we are also the first to report outcomes of repeat COVID-19 vaccination in patients with de novo flare of ANCA and anti-GBM nephritis temporally associated with COVID-19 vaccination.

Creating a provincial post COVID-19 interdisciplinary clinical care network as a learning health system during the pandemic: Integrating clinical care and research.

Introduction: Coronavirus Disease-2019 (COVID-19) affects multiple organ systems in the acute phase and also has long-term sequelae. Research on the long-term impacts of COVID-19 is limited. The Post COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN), conceived in July 2020, is a provincially funded resource that is modelled as a Learning Health System (LHS), focused on those people with persistent symptoms post COVID-19 infection. Methods: The PC-ICCN emerged through collaboration among over 60 clinical specialists, researchers, patients, and health administrators. At the core of the network are the post COVID-19 Recovery Clinics (PCRCs), which provide direct patient care that includes standardized testing and education at regular follow-up intervals for a minimum of 12 months post enrolment. The PC-ICCN patient registry captures data on all COVID-19 patients with confirmed infection, by laboratory testing or epi-linkage, who have been referred to one of five post COVID-19 Recovery Clinics at the time of referral, with data stored in a fully encrypted Oracle-based provincial database. The PC-ICCN has centralized administrative and operational oversight, multi-stakeholder governance, purpose built data collection supported through clinical operations geographically dispersed across the province, and research operations including data analytics. Results: To date, 5364 patients have been referred, with an increasing number and capacity of these clinics, and 2354 people have had at least one clinic visit. Since inception, the PC-ICCN has received over 30 research proposal requests. This is aligned with the goal of creating infrastructure to support a wide variety of research to improve care and outcomes for patients experiencing long-term symptoms following COVID-19 infection. Conclusions: The PC-ICCN is a first-in-kind initiative in British Columbia to enhance knowledge and understanding of the sequelae of COVID-19 infection over time. This provincial initiative serves as a model for other national and international endeavors to enable care as research and research as care.

Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe complications when Alpha and Delta were predominant variants of concern. Vaccine effectiveness after a third dose versus two doses for preventing SARS-CoV-2 infection and severe COVID-19 in the hemodialysis population against Omicron is not known. METHODS: We conducted a retrospective cohort study in Ontario, Canada, between December 1, 2021, and February 28, 2022, in the maintenance hemodialysis population who had received two versus three doses of mRNA COVID-19 vaccines. COVID-19 vaccination, SARS-CoV-2 infection, and related hospitalization and death were determined from provincial databases. The primary outcome was the first RT-PCR confirmed SARS-CoV-2 infection, and the secondary outcome was a SARS-CoV-2-related severe outcome, defined as either hospitalization or death. RESULTS: A total of 8457 individuals receiving in-center hemodialysis were included. At study initiation, 2334 (28%) individuals received three doses, which increased to 7468 (88%) individuals by the end of the study period. The adjusted hazard ratios (aHR) for SARS-CoV-2 infection (aHR, 0.58; 95% confidence interval [CI], 0.50 to 0.67) and severe outcomes (hospitalization or death) (aHR, 0.40; 95% CI, 0.28 to 0.56) were lower after three versus two doses of mRNA vaccine. Prior infection, independent of vaccine status, was associated with a lower risk of reinfection, with an aHR of 0.44 (95% CI, 0.27 to 0.73). CONCLUSIONS: Three-dose mRNA COVID-19 vaccination was associated with lower incidence of SARS-CoV-2 infection and severe SARS-CoV-2-related outcomes during the Omicron period compared with two doses.

Evaluating fatigue in patients recovering from COVID-19: validation of the fatigue severity scale and single item screening questions.

BACKGROUND: Fatigue is a common symptom in hospitalized and non-hospitalized patients recovering from COVID-19, but no fatigue measurement scales or questions have been validated in these populations. The objective of this study was to perform validity assessments of the fatigue severity scale (FSS) and two single-item screening questions (SISQs) for fatigue in patients recovering from COVID-19. METHODS: We examined patients ≥ 28 days after their first SARS-CoV-2 infection who were hospitalized for their acute illness, as well as non-hospitalized patients referred for persistent symptoms. Patients completed questionnaires through 1 of 4 Post COVID-19 Recovery Clinics in British Columbia, Canada. Construct validity was assessed by comparing FSS scores to quality of life and depression measures. Two SISQs were evaluated based on the ability to classify fatigue (FSS score ≥ 4). RESULTS: Questionnaires were returned in 548 hospitalized and 546 non-hospitalized patients, with scores computable in 96.4% and 98.2% of patients respectively. Cronbach's alpha was 0.96 in both groups. The mean ± SD FSS score was 4.4 ± 1.8 in the hospitalized and 5.2 ± 1.6 in the non-hospitalized group, with 62.5% hospitalized and 78.9% non-hospitalized patients classified as fatigued. Ceiling effects were 7.6% in the hospitalized and 16.1% in non-hospitalized patients. FSS scores negatively correlated with EQ-5D scores in both groups (Spearman's rho - 0.6 in both hospitalized and non-hospitalized; p < 0.001) and were higher among patients with a positive PHQ-2 depression screen (5.4 vs. 4.0 in hospitalized and 5.9 vs. 4.9 in non-hospitalized; p < 0.001). An SISQ asking whether there was "fatigue present" had a sensitivity of 70.6% in hospitalized and 83.2% in non-hospitalized patients; the "always feeling tired" SISQ, had a sensitivity of 70.5% and 89.6% respectively. CONCLUSIONS: Fatigue was common and severe in patients referred for post COVID-19 assessment. Overall, the FSS is suitable for measuring fatigue in these patients, as there was excellent data quality, strong internal consistency, and construct validity. However, ceiling effects may be a limitation in the non-hospitalized group. SISQs had good sensitivity for identifying clinically relevant fatigue in non-hospitalized patients but only moderate sensitivity in the hospitalized group, indicating that there were more false negatives.

An Elastic Net Regression Model for Identifying Long COVID Patients Using Health Administrative Data: A Population-Based Study.

Background: Long coronavirus disease (COVID) patients experience persistent symptoms after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Healthcare utilization data could provide critical information on the disease burden of long COVID for service planning; however, not all patients are diagnosed or assigned long COVID diagnostic codes. We developed an algorithm to identify individuals with long COVID using population-level health administrative data from British Columbia (BC), Canada. Methods: An elastic net penalized logistic regression model was developed to identify long COVID patients based on demographic characteristics, pre-existing conditions, COVID-19-related data, and all symptoms/conditions recorded >28-183 days after the COVID-19 symptom onset/reported (index) date of known long COVID patients (n = 2430) and a control group (n = 24 300), selected from all adult COVID-19 cases in BC with an index date on/before October 31, 2021 (n = 168 111). Known long COVID cases were diagnosed in a clinic and/or had the International Classification of Diseases, Tenth Revision, Canada (ICD-10-CA) code for "post COVID-19 condition" in their records. Results: The algorithm retained known symptoms/conditions associated with long COVID, demonstrating high sensitivity (86%), specificity (86%), and area under the receiver operator curve (93%). It identified 25 220 (18%) long COVID patients among the remaining 141 381 adult COVID-19 cases, >10 times the number of known cases. Known and predicted long COVID patients had comparable demographic and health-related characteristics. Conclusions: Our algorithm identified long COVID patients with a high level of accuracy. This large cohort of long COVID patients will serve as a platform for robust assessments on the clinical course of long COVID, and provide much needed concrete information for decision-making.

Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron. Methods: We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine. Binding antibody levels were determined by ELISA. Neutralization against wild type, Beta, Delta, and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike-pseudotyped lentivirus assay. Results: Forty-four KTRs were analyzed at 1 and 3 mo (n = 26) post-third dose. At 1 mo, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 mo, but the proportion of KTRs with a robust antibody response was unchanged; 38.5% KTRs maintained Omicron-specific neutralization at 3 mo. No clinical variables were significantly associated with Omicron-neutralizing antibodies, but antireceptor binding domain titers appeared to identify those with Omicron-specific neutralizing capacity. Conclusions: Over 50% of KTRs lack Omicron-specific neutralization capacity 1 mo post-third mRNA-vaccine dose. Antibody levels of responders were well preserved at 3 mo. Anti receptor binding domain antibody titers may identify patients with a detectable Omicron-neutralizing antibody response.

Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada.

BACKGROUND: Vaccination studies in the hemodialysis population have demonstrated decreased antibody response compared with healthy controls, but vaccine effectiveness for preventing SARS-CoV-2 infection and severe disease is undetermined. METHODS: We conducted a retrospective cohort study in the province of Ontario, Canada, between December 21, 2020, and June 30, 2021. Receipt of vaccine, SARS-CoV-2 infection, and related severe outcomes (hospitalization or death) were determined from provincial health administrative data. Receipt of one and two doses of vaccine were modeled in a time-varying cause-specific Cox proportional hazards model, adjusting for baseline characteristics, background community infection rates, and censoring for non-COVID death, recovered kidney function, transfer out of province, solid organ transplant, and withdrawal from dialysis. RESULTS: Among 13,759 individuals receiving maintenance dialysis, 2403 (17%) were unvaccinated and 11,356 (83%) had received at least one dose by June 30, 2021. Vaccine types were BNT162b2 (n=8455, 74%) and mRNA-1273 (n=2901, 26%); median time between the first and second dose was 36 days (IQR 28-51). The adjusted hazard ratio (HR) for SARS-CoV-2 infection and severe outcomes for one dose compared with unvaccinated was 0.59 (95% CI, 0.46 to 0.76) and 0.54 (95% CI, 0.37 to 0.77), respectively, and for two doses compared with unvaccinated was 0.31 (95% CI, 0.22 to 0.42) and 0.17 (95% CI, 0.1 to 0.3), respectively. There were no significant differences in vaccine effectiveness among age groups, dialysis modality, or vaccine type. CONCLUSIONS: COVID-19 vaccination is effective in the dialysis population to prevent SARS-CoV-2 infection and severe outcomes, despite concerns about suboptimal antibody responses.

Protocol for a Multistage Mixed-Methods Evaluation of Multidisciplinary Chronic Kidney Disease Care Quality Following Integration of Virtual and In-Person Care During the COVID-19 Pandemic.

Background: Multidisciplinary care of patients with chronic kidney disease (CKD) as it previously existed was predicated on an evidence and experience base of improved patient outcomes within an established and well-described service delivery model. The onset of the COVID-19 pandemic brought with it a departure from this established care delivery model toward integration of virtual care and in-person care. Objective: To develop an evaluation framework to determine whether this shift in service delivery models has affected quality of multidisciplinary kidney care and/or patient-clinician interactions and relationships. Design: A sequential multiphase, mixed-methods evaluation. Setting: All 15 British Columbia (BC) multidisciplinary kidney care clinics (KCCs). Participants: All patients and all clinicians in all KCCs across BC will be invited to participate in the planned evaluation. Measurements: Qualitative and quantitative feedback from patients and families living with CKD and KCC clinicians. Methods: The planned multiphase evaluation of virtual care integration in KCCs will be conducted across all 15 KCCs in the province of BC, Canada. The following phases are proposed: (1) review of current virtual care integration and practices, (2) assessment of patient and clinician experiences and perspectives via semi-structured interviews, (3) validation of those patient and clinician perspectives via survey of a larger sample, (4) compilation and analysis of all phases to provide informed recommendations for patient and visit format selection in a mixed in-person and virtual multidisciplinary clinic setting. Limitations: This work will not capture any information about the relationship between differences in virtual usage parameters and clinical outcomes or financial implications. Conclusions: There is no existing framework for either evaluation of multidisciplinary CKD care quality in a virtual setting or evaluation of care quality following a substantial change in service delivery models. The proposed evaluation protocol will enable better understanding of the nuances in kidney care delivery in this new format and inform how best to optimize the integration of virtual and pre-existing formats into kidney clinic care delivery beyond the pandemic. Beyond the current evaluation, this protocol may be of use for other jurisdictions to evaluate their own local instances of virtual care implementation and integration. The model may be adapted to evaluate quality of multidisciplinary kidney care delivery following other changes to clinic service delivery models.

Contexte: Les soins multidisciplinaires prodigués aux patients atteints d'insuffisance rénale chronique (IRC), tels qu'ils existaient auparavant, étaient fondés sur une base de preuves et d'expérience de l'amélioration des résultats pour les patients dans le cadre d'un modèle de prestation de services établi et bien décrit. Le début de la pandémie COVID-19 a créé une fracture par rapport à ce modèle établi de prestation de soins, à la faveur d'une intégration des soins virtuels et des soins en personne. Objectif: Élaborer un cadre d'évaluation permettant de déterminer si ce changement dans les modèles de prestation de services a eu une incidence sur la qualité des soins multidisciplinaires en santé rénale et/ou sur les interactions et les relations entre le patient et le clinicien. Type d'étude: Une évaluation multiphase séquentielle à méthodes mixtes. Cadre: Les 15 cliniques multidisciplinaires de soins rénaux (CMSR) de la C.-B. Participants: Tous les patients et cliniciens de toutes les CMSR de la Colombie-Britannique seront invités à participer à l'évaluation. Mesures: Les rétroactions qualitative et quantitative des patients atteints d'IRC et de leurs familles, ainsi que celles des cliniciens des CMSR. Méthodologie: L'évaluation multiphase prévue de l'intégration des soins virtuels dans les soins prodigués dans les CMSR sera menée dans les 15 CMSR de la Colombie-Britannique (C.-B.), au Canada. Les phases suivantes sont proposées: (1) examen de l'intégration et des pratiques actuelles en matière de soins virtuels, (2) évaluation des expériences et des perspectives des patients et des cliniciens par le biais d'entrevues semi-structurées, (3) validation de ces mêmes perspectives par le biais d'un sondage sur un échantillon plus large, (4) compilation et analyze des données recueillies lors de toutes les phases afin de fournir des recommandations éclairées pour le choix des patients et du format de la visite dans un contexte de clinique multidisciplinaire intégrant les consultations en personne et virtuelles. Limites: Ces travaux ne permettront pas de recueillir des informations sur la relation entre les différences dans les paramètres d'utilization virtuelle et les résultats cliniques ou les implications financières. Conclusion: En ce moment, il n'existe pas de cadre pour évaluer la qualité des soins multidisciplinaires en IRC dans un cadre virtuel ni pour évaluer la qualité des soins après un changement important dans les modèles de prestation de services. Le protocole d'évaluation proposé permettra de mieux comprendre les nuances dans la prestation des soins rénaux dans ce nouveau format et d'indiquer la meilleure façon d'optimiser l'intégration des formats virtuels et préexistants dans la prestation des soins en clinique rénale au-delà de la pandémie. Au-delà de l'évaluation actuelle, ce protocole pourra être utilisé par d'autres provinces pour évaluer leurs propres instances locales de mise en œuvre et d'intégration des soins virtuels. Le modèle peut être adapté pour évaluer la qualité de la prestation de soins multidisciplinaires aux reins à la suite d'autres changements apportés aux modèles de prestation de services en clinique.

Différences d'immunogénicité des vaccins anti-SRAS-CoV-2 mRNA-1273 (Moderna) et BNT162b2 (Pfizer-BioNTech) chez les patients dialysés.

CONTEXTE: Les différences d'immunogénicité entre les vaccins anti-SRAS-CoV-2 à ARNm n'ont pas été bien caractérisées chez les patients hémodialysés. Nous avons comparé la réponse sérologique chez les patients sous hémodialyse après la vaccination contre le SRAS-CoV-2 au moyen des vaccins BNT162b2 (Pfizer-BioNTech) et mRNA-1273 (Moderna). MÉTHODES: Nous avons procédé à une étude de cohorte observationnelle et prospective dans 2 centres universitaires de Toronto, au Canada, du 2 février au 20 juillet 2021, et avons inclus 129 et 95 patients qui ont reçu respectivement les vaccins anti-SRAS-CoV-2 BNT162b2 et mRNA-1273. Nous avons mesuré les taux d'anticorps IgG dirigés contre la protéine S (anti-S), contre le domaine de liaison au récepteur (ou RBD, pour receptor-binding domain [anti-RBD]) et contre la protéine de la nucléocapside (anti-N) du SRAS-CoV-2 6­7) puis 12 semaines après la deuxième dose de vaccin et nous avons comparé ces taux aux taux médians d'anticorps présents dans le sérum de 211 témoins convalescents qui avaient déjà contracté le SRAS-CoV-2. RÉSULTATS: Six à 7 semaines après la deuxième dose de vaccin, nous avons constaté que 51 patients sur 70 (73 %) ayant reçu le BNT162b2 et 83 patients sur 87 (95 %) ayant reçu le mRNA-1273, ont obtenu des taux équivalents à ceux du sérum de convalescents pour ce qui est de l'anticorps anti-S (p < 0,001). Chez ceux qui ont reçu le BNT162b2, 35 sur 70 (50 %) ont atteint le taux du sérum de convalescents pour l'anti-RBD, contre 69 sur 87 (79 %) de ceux qui ont reçu le mRNA-1273 (p < 0,001). Douze semaines après la deuxième dose, les taux d'anti-S et d'anti-RBD étaient significativement moindres chez les patients ayant reçu le BNT162b2 que chez ceux qui avaient reçu le mRNA-1273. Pour l'anti-S, 70 patients sur 122 (57,4 %) ayant reçu le BNT162b2 ont maintenu un taux équivalent à celui du sérum de convalescents, contre 68 sur 71 (96 %) de ceux qui avaient reçu le mRNA-1273 (p < 0,001). Pour l'anti-RBD, 47 patients sur 122 (38,5 %) ayant reçu le BNT162b2 ont maintenu des taux anti-RBD équivalant à celui du sérum de convalescents, contre 45 sur 71 (63 %) de ceux qui avaient reçu le mRNA-1273 (p = 0,002). INTERPRÉTATION: Chez les patients hémodialysés, le mRNA-1273 a généré une réponse humorale plus forte que le BNT162b2. Étant donné le déclin rapide de l'immunogénicité à 12 semaines chez les patients ayant reçu le BNT162b2, une troisième dose est recommandée chez les patients hémodialysés dans le cadre d'une première série, ce qui concorde avec les recommandations concernant d'autres populations vulnérables.

Mediators of the Effects of Canagliflozin (CANA) on Heart Failure (HF) and CV Death in Patients with Type 2 Diabetes (T2D) and Chronic Kidney Disease (CKD)

The benefits of CANA for HF in people with T2D at CV risk appeared to be statistically mediated by erythrocyte concentration, serum urate, and urinary albumin:creatinine ratio (UACR) in the CANVAS Program. CANA reduced the risk of HF in patients with T2D and CKD in CREDENCE. We explored potential mediators of CANA's effects on the composite of hospitalized HF (HHF) and CV death. Mediation analyses are hypothesis-generating observational analyses that calculate the effect of selected biomarkers on the overall treatment effect using time-varying Cox regression. We compared hazard ratios for the effect of randomized treatment from an unadjusted model versus a model adjusted for the average post-randomization level of the biomarker of interest. 62 routine clinical biomarkers and vital sign indicators were collected on all participants and tested as potential mediators. When multiple potential mediators represented a single pathway, those with the strongest univariable mediation were tested in multivariable models. 12 biomarkers, including 3 markers of volume/erythropoiesis (hematocrit [24%], hemoglobin [32%], erythrocytes [27%]), 2 markers of kidney function (UACR [28%], eGFR from wk 3 [7.4%]), and serum albumin (39%), serum protein (24%), lactate dehydrogenase (13%), systolic BP (10%), urine pH (8%), serum urate (7%) and gamma glutamyltransferase (4%), mediated the effect of CANA on HHF/CV death in univariable models. In the multivariable model, hemoglobin, UACR, serum urate and systolic BP maximized cumulative mediation (74%). A diverse set of potential mediators of CANA's effect on HHF/CV death were identified with serum albumin, hemoglobin (or its analogues) and UACR being the most important. The extent to which these mediators reflect underlying inflammatory, nutritional, volume-related or cardiorenal pathways is unclear and underscores the need for further research into the mechanisms of benefit of SGLT2 inhibitors. Disclosure: J. Li: Employee;Self;George Institute. B. Neal: Research Support;Self;Janssen Research & Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship;Self;Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. H.L. Heerspink: Consultant;Self;AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. C. Arnott: Employee;Self;George Institute for Global Health. C. Cannon: None. R. Agarwal: Other Relationship;Self;AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant;Self;Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship;Self;Bayer AG, Novo Nordisk Inc., Vascular Dynamics. D.M. Charytan: Advisory Panel;Self;Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee;Self;BAIM Institute. Research Support;Self;Janssen Pharmaceuticals, Inc. Other Relationship;Self;Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel;Self;AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. T. Greene: Other Relationship;Self;Janssen, Durect, and Pfizer. A. Levin: Consultant;Self;Janssen Pharmaceuticals, Inc. Research Support;Self;AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. R. Oh: Employee;Self;Janssen Pharmaceuticals, Inc. C.A. Pollock: Advisory Panel;Self;AstraZeneca, Boehringer Ingelheim Pharma euticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support;Self;Diabetes Australia. Speaker's Bureau;Self;AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship;Self;Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. D.C. Wheeler: Advisory Panel;Self;Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant;Self;AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker's Bureau;Self;Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. Y. Yavin: Employee;Self;Janssen Research & Development, LLC. H. Zhang: Employee;Self;Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel;Self;Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. G. Di Tanna: Employee;Self;George Institute for Global Health. V. Perkovic: Other Relationship;Self;See Other Relationship field. K.W. Mahaffey: Consultant;Self;Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support;Self;Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. M. Jardine: Other Relationship;Self;See Other Relationship field. Funding: Janssen Research & Development, LLC [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Effect of Canagliflozin on Total Hospitalization for Heart Failure Events in Patients with Type 2 Diabetes and Chronic Kidney Disease

Background: The sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of first hospitalization for heart failure (HHF) in the CREDENCE trial. The prevention of recurrent events is important to patients, clinicians and payers. In this post-hoc analysis, we evaluated the effect of canagliflozin on total HHF events. Methods: The CREDENCE trial compared canagliflozin or matching placebo and followed patients for a median of 2.6 years. The study included 4401 participants with type 2 diabetes, substantial albuminuria and estimated glomerular filtration rate (eGFR) 30 to <90 ml/min/1.73 m2 receiving renin-angiotensin system blockade. Negative binomial regression models were performed to assess the effect of canagliflozin on the total number of HHF events. Results: The mean age of participants was 63 years, with a mean eGFR of 56.3 ml/min/1.73 m2, while 50% had a history of previous cardiovascular disease and 15% had a history of heart failure. During the trial, 230 people experienced 326 total HHF events, with 166 having 1 event, 43 having 2 events, 15 having 3 events, and 6 having ≥4 events;thus, 42% of those experiencing at least 1 event went on to suffer a recurrent event during the follow up. Canagliflozin reduced first HHF events by 39% (hazard ratio [HR], 0.61;95% confidence interval [CI] 0.47-0.80;P <0.001;number needed to treat [NNT], 46;95% CI 29-124) and total HHF events by 36% (event rates of 22.0 and 34.8 participants with an event/1000 patient-years with canagliflozin and placebo, respectively;incidence rate ratio [RR], 0.64;95% CI 0.56-0.73;P <0.001). Conclusions: Canagliflozin significantly reduced first and recurrent HHF events. These findings provide further support for the benefit of continuing canagliflozin therapy after an index heart failure presentation to prevent recurrent HHF events. Disclosure: J. Li: Employee;Self;George Institute. M.J. Jardine: Other Relationship;Self;See Other Relationship field. B. Neal: Research Support;Self;Janssen Research & Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship;Self;Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. H.L. Heerspink: Consultant;Self;AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. C. Cannon: None. R. Agarwal: Other Relationship;Self;AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant;Self;Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship;Self;Bayer AG, Novo Nordisk Inc., Vascular Dynamics. D.M. Charytan: Advisory Panel;Self;Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee;Self;BAIM Institute. Research Support;Self;Janssen Pharmaceuticals, Inc. Other Relationship;Self;Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel;Self;AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. R. Edwards: Employee;Self;Janssen. T. Greene: Other Relationship;Self;Janssen, Durect, and Pfizer. A. Levin: Consultant;Self;Janssen Pharmaceuticals, Inc. Research Support;Self;AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. C.A. Pollock: Advisory Panel;Self;AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support;Self;Diabetes Australia. Speaker's Bureau;Self;AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship;Self;Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.C. Wheeler: Advisory Panel;Self;Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant;Self;AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker's Bureau;Self;Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. H. Zhang: Employee;Self;Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel;Self;Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. V. Perkovic: Other Relationship;Self;See Other Relationship field. K.W. Mahaffey: Consultant;Self;Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support;Self;Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. C. Arnott: Employee;Self;George Institute for Global Health. Funding: Janssen Research & Development, LLC [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute Declines in EGFR during Treatment with Canagliflozin and Its Implications for Clinical Practice: Insights from CREDENCE

Background: Canagliflozin (CANA) slows progression of chronic kidney disease (CKD) in people with type 2 diabetes. CANA also induces a reversible acute decline in estimated glomerular filtration rate (eGFR), which is believed to be a hemodynamic effect. Predictors of the initial decline and its association with long-term eGFR trajectories and safety outcomes are unknown. Methods: This post-hoc study of the CREDENCE trial included 4289 patients with type 2 diabetes and CKD who had eGFR measured at both baseline and week 3. Participants were categorized by percentage decline in eGFR at week 3: >10%, ≤10% to >0%, and ≤0%. Baseline characteristics associated with acute eGFR declines >10% were evaluated using logistic regression. Long-term eGFR decline and safety outcomes were estimated in each eGFR decline category by linear mixed effects models and Cox regression after adjustment for laboratory measures and medication use. Results: More participants in the CANA (956 [45%]) versus placebo (PBO) group (450 [21%]) had an acute eGFR decline >10% (p<0.001). A >30% decline occurred infrequently (89 [4%] with CANA and 39 [2%] with PBO;p<0.001). In the CANA but not in the PBO group, older age (OR CANA 1.17, 95% CI 1.05-1.31;per 10 years) and history of heart failure (OR CANA 0.77, 0.59-0.99) were associated with a higher and lower likelihood of an acute eGFR decline >10%, respectively (both p for interaction <0.05). Following the initial eGFR change, long-term eGFR trajectories as well as overall safety profiles were similar across eGFR decline categories (all p values >0.05). Results were consistent when other decline thresholds (>20%) were used and in subgroup analysis by baseline eGFR (30-<45, 45-<60, and 60-<90 ml/min/1.73 m2). Conclusions: Although acute eGFR declines >10% occurred in nearly half of all patients following initiation of CANA, the benefit of CANA compared with placebo was observed regardless of the acute eGFR decline and safety profiles were similar. Disclosure: M. Oshima: Research Support;Self;Japan Society for the Promotion of Science Program for Fostering Globally Talented Researchers. M.J. Jardine: Other Relationship;Self;See Other Relationship field. R. Agarwal: Other Relationship;Self;AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant;Self;Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship;Self;Bayer AG, Novo Nordisk Inc., Vascular Dynamics. C. Cannon: None. D.M. Charytan: Advisory Panel;Self;Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee;Self;BAIM Institute. Research Support;Self;Janssen Pharmaceuticals, Inc. Other Relationship;Self;Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel;Self;AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. R. Edwards: Employee;Self;Janssen. T. Greene: Other Relationship;Self;Janssen, Durect, and Pfizer. A. Levin: Consultant;Self;Janssen Pharmaceuticals, Inc. Research Support;Self;AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. K.W. Mahaffey: Consultant;Self;Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support;Self;Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. B. Neal: Research Support;Self;Janssen Research & Development LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship;Self;Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. C.A. Pollock: Advisory Panel;Self;AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support;Self;Diabetes Australia. Speaker's Bureau;Self;AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship;Self;Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.C. Wheeler: Advisory Panel;Self;Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant;Self;AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker's Bureau;Self;Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. H. Zhang: Employee;Self;Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel;Self;Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. V. Perkovic: Other Relationship;Self;See Other Relationship field. H.L. Heerspink: Consultant;Self;AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. Funding: Janssen Research & Development, LLC [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors.

BACKGROUND: Angiotensin receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors could alter mortality from coronavirus disease 2019 (COVID-19), but existing meta-analyses that combined crude and adjusted results may be confounded by the fact that comorbidities are more common in ARB/ACE inhibitor users. METHODS: We searched PubMed/MEDLINE/Embase for cohort studies and meta-analyses reporting mortality by preexisting ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex, and prevalence of cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease between users and nonusers of ARBs/ACE inhibitors at the study level during data synthesis. RESULTS: In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease. ARB/ACE inhibitor use was associated with significantly lower mortality after controlling for potential confounding factors (odds ratio 0.77 [95% confidence interval: 0.62, 0.96]). In contrast, meta-analysis of ARB/ACE inhibitor use was not significantly associated with mortality when all studies were combined with no adjustment made for confounders (0.87 [95% confidence interval: 0.71, 1.08]). CONCLUSIONS: ARB/ACE inhibitor use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes, and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality from COVID-19 because of indication bias.

INTRODUCTION: Les antagonistes des récepteurs de l'angiotensine (ARA) et/ou les inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) feraient varier la mortalité liée à la COVID-19, mais il est possible que les méta-analyses actuelles qui combinaient les résultats bruts et ajustés soient invalidées du fait que les comorbidités sont plus fréquentes chez les utilisateurs d'ARA/IECA. MÉTHODES: Nous avons effectué des recherches dans les bases de données PubMed/MEDLINE/Embase pour trouver des études de cohorte et des méta-analyses qui portent sur la mortalité associée à un traitement préexistant par ARA/IECA chez les patients hospitalisés atteints de la COVID-19. Nous avons utilisé la métarégression à effets aléatoires pour calculer les rapports de cotes regroupés de mortalité ajustés en fonction du déséquilibre de l'âge, du sexe, et de la prévalence des maladies cardiovasculaires, de l'hypertension, du diabète sucré et de l'insuffisance rénale chronique entre les utilisateurs et les non-utilisateurs d'ARA/IECA dans le cadre de l'étude durant la synthèse des données. RÉSULTATS: Dans les 30 études portant sur 17 281 patients, 22 %, 68 %, 25 % et 11 % avaient respectivement une maladie cardiovasculaire, de l'hypertension, le diabète sucré et de l'insuffisance rénale chronique. L'utilisation des ARA/IECA a été associée à une mortalité significativement plus faible après avoir tenu compte des facteurs confusionnels potentiels (rapport de cotes 0,77 [intervalle de confiance à 95 % : 0,62, 0,96]). En revanche, la méta-analyse sur l'utilisation des ARA/IECA n'a pas été associée de façon significative à la mortalité lorsque toutes les études ont été combinées sans ajustement sur les facteurs confusionnels (0,87 [intervalle de confiance à 95 % : 0,71, 1,08]). CONCLUSIONS: L'utilisation des ARA/IECA a été associée à la diminution de la mortalité au sein des cohortes de patients atteints de la COVID-19 après l'ajustement en fonction de l'âge, du sexe, des maladies cardiovasculaires, de l'hypertension, du diabète et de l'insuffisance rénale chronique. Les méta-analyses non ajustées peuvent ne pas permettre de déterminer si les ARA/IECA sont associés à la mortalité liée à la COVID-19 en raison du biais d'indication.