Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD): Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial.

Background: Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) is a quality improvement intervention designed to enhance access to kidney transplantation and living kidney donation. We conducted a cluster-randomized clinical trial to evaluate the effect of the intervention versus usual care on completing key steps toward receiving a kidney transplant. Objective: To prespecify the statistical analysis plan for the EnAKT LKD trial. Design: The EnAKT LKD trial is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized, superiority, clinical trial. Randomization was performed at the level of the chronic kidney disease (CKD) programs (the "clusters"). Setting: Twenty-six CKD programs in Ontario, Canada. Participants: More than 10 000 patients with advanced CKD (ie, patients approaching the need for dialysis or receiving maintenance dialysis) with no recorded contraindication to receiving a kidney transplant. Methods: The trial data (including patient characteristics and outcomes) will be obtained from linked administrative health care databases (the "registry"). Stratified covariate-constrained randomization was used to allocate the 26 CKD programs (1:1) to provide the intervention or usual care from November 1, 2017, to December 31, 2021 (4.17 years). CKD programs in the intervention arm received the following: (1) support for local quality improvement teams and administrative needs; (2) tailored education and resources for staff, patients, and living kidney donor candidates; (3) support from kidney transplant recipients and living kidney donors; and (4) program-level performance reports and oversight by program leaders. Outcomes: The primary outcome is completing key steps toward receiving a kidney transplant, where up to 4 unique steps per patient will be considered: (1) patient referred to a transplant center for evaluation, (2) a potential living kidney donor begins their evaluation at a transplant center to donate a kidney to the patient, (3) patient added to the deceased donor transplant waitlist, and (4) patient receives a kidney transplant from a living or deceased donor. Analysis plan: Using an intent-to-treat approach, the primary outcome will be analyzed using a patient-level constrained multistate model adjusting for the clustering in CKD programs. Trial Status: The EnAKT LKD trial period is November 1, 2017, to December 31, 2021. We expect to analyze and report the results once the data for the trial period is available in linked administrative health care databases. Trial Registration: The EnAKT LKD trial is registered with the U.S. National Institute of Health at clincaltrials.gov (NCT03329521 available at https://clinicaltrials.gov/ct2/show/NCT03329521). Statistical Analytic Plan: Version 1.0 August 26, 2022.

Contexte: EnAKT LKD est une intervention d'amélioration de la qualité visant à améliorer l'accès à la transplantation rénale et au don vivant de rein. Nous avons mené un essai clinique randomisé par grappes afin d'évaluer l'effet de l'intervention, par rapport aux soins habituels, sur le taux d'étapes clés réalisées dans le processus de réception d'une greffe de rein. Objectif: Exposer les grandes lignes du plan d'analyse statistique de l'essai EAKT LKD. Conception: EAKT LKD est un essai clinique pragmatique ouvert, à deux bras, en groupes parallèles, basé sur un registre, et randomisé en grappes. La randomisation a été réalisée au niveau des programmes d'insuffisance rénale chronique (IRC) (les « grappes ¼). Cadre: 26 programmes d'IRC en Ontario (Canada). Sujets: Plus de 10 000 patients atteints d'IRC de stade avancé (des patients approchant le besoin de dialyse ou recevant une hémodialyse d'entretien) sans contre-indication documentée à la greffe rénale. Méthodologie: Les données de l'essai (y compris les caractéristiques et les résultats des patients) seront obtenues à partir de bases de données administratives en santé (le « registre ¼). La randomisation stratifiée avec contraintes de covariables a servi à répartir les 26 programmes d'IRC (1:1) selon qu'ils allaient fournir l'intervention ou les soins habituels entre le 1er novembre 2017 et le 31 décembre 2021 (4,17 ans). Les programmes d'IRC du bras d'intervention ont eu droit au soutien suivant: (1) des équipes locales d'amélioration de la qualité et du soutien administratif; (2) de l'information et des ressources sur mesure pour le personnel, les patients et les donneurs vivants; (3) du soutien de la part de receveurs et de donneurs vivants; et (4) des rapports sur le rendement au niveau du programme et une surveillance assurée par les chefs de programme. Résultats: Le principal critère d'évaluation est le taux d'étapes clés accomplies vers la réception d'une greffe de rein, où jusqu'à quatre étapes uniques par patient seront comptabilisées: (1) le patient est aiguillé vers un centre de transplantation pour évaluation; (2) un possible donneur vivant de rein contacte un centre de transplantation pour un receveur en particulier et amorce son évaluation; (3) le patient est ajouté à la liste d'attente pour une transplantation d'un donneur décédé, et (4) le patient reçoit une greffe de rein d'un donneur vivant ou décédé. Plan d'analyse: Selon une approche fondée sur l'intention de traiter, le critère d'évaluation principal sera analysé au niveau du patient en utilisant un modèle multiétats contraint, corrigé dans les programmes d'IRC en fonction du regroupement. Statut de l'essai: L'essai EnAKT LKD s'est tenu du 1er novembre 2017 au 31 décembre 2021. Nous analyserons les résultats et en rendrons compte dès que les données seront disponibles dans les bases de données administratives couplées du système de santé.

The bidirectional association between diabetes and long-COVID-19 - A systematic review.

Some evidence suggests that diabetes may be a risk factor for the development of post-acute sequelae of COVID-19 (PASC). Recent data also indicate that new-onset diabetes may be a complication of COVID-19. Here, we review the existing evidence. Following PRISMA guidelines, we conducted a systematic review through August 8, 2022. We included longitudinal studies reporting on the risk of PASC (i.e., sequelae that extend beyond four weeks after initial infection) in people with and without diabetes, and studies reporting on the risk of new-onset diabetes in people with vs without COVID-19 with a minimum of 4-weeks of follow-up. All studies were published in English. Among 5,532 studies screened, 39 were included in the final review. Among 25 studies reporting on diabetes and PASC, 44 % (n = 11) identified diabetes as a significant risk factor for PASC (increased relative risk ranging from 7 % to 342 %) while 56 % (n = 14) did not. Among 14 studies reporting on new-onset diabetes, 12 (86 %) reported that COVID-19 (vs no COVID) was significantly associated with new-onset diabetes with increased risks ranging from 11 % to 276 %. COVID-19 survivors may be at increased risk for new-onset diabetes, but whether pre-existing diabetes is also a risk factor for PASC remains unclear.

Understanding Racial Disparities in COVID-19-Related Complications: Protocol for a Mixed Methods Study.

BACKGROUND: In the United States, the COVID-19 pandemic has magnified the disproportionate and long-standing health disparities experienced by Black communities. Although it is acknowledged that social determinants of health (SDOH) rather than biological factors likely contribute to this disparity, few studies using rigorous analytic approaches in large, information-rich community-based data sets are dedicated to understanding the underlying drivers of these racial disparities. OBJECTIVE: The overall aim of our study is to elucidate the mechanisms by which racial disparities in severe COVID-19 outcomes arise, using both quantitative and qualitative methods. METHODS: In this protocol, we outline a convergent parallel mixed methods approach to identifying, quantifying, and contextualizing factors that contribute to the dramatic disparity in COVID-19 severity (ie, hospitalization, mortality) in Black versus white COVID-19 patients within the integrated health care system of Kaiser Permanente Georgia (KPGA). Toward this end, we will generate two quantitative cohorts of KPGA members with a confirmed COVID-19 diagnosis between January 1, 2020, and September 30, 2021: (1) an electronic medical record (EMR) cohort including routinely captured data on diagnoses, medications, and laboratory values, and a subset of patients hospitalized at Emory Healthcare to capture additional in-hospital data; and (2) a survey cohort, where participants will answer a range of questions related to demographics (eg, race, education), usual health behaviors (eg, physical activity, smoking), impact of COVID-19 (eg, job loss, caregiving responsibilities), and medical mistrust. Key outcomes of interest for these two cohorts include hospitalization, mortality, intensive care unit admission, hospital readmission, and long COVID-19. Finally, we will conduct qualitative semistructured interviews to capture perceptions of and experiences of being hospitalized with COVID-19 as well as related interactions with KPGA health care providers. We will analyze and interpret the quantitative and qualitative data separately, and then integrate the qualitative and quantitative findings using a triangulation design approach. RESULTS: This study has been funded by a Woodruff Health Sciences grant from December 2020 to December 2022. As of August 31, 2022, 31,500 KPGA members diagnosed with COVID-19 have been included in the EMR cohort, including 3028 who were hospitalized at Emory Healthcare, and 482 KPGA members completed the survey. In addition, 20 KPGA members (10 Black and 10 white) have been interviewed about their experiences navigating care with COVID-19. Quantitative and qualitative data cleaning and coding have been completed. Data analysis is underway with results anticipated to be published in December 2022. CONCLUSIONS: Results from this mixed methods pilot study in a diverse integrated care setting in the southeastern United States will provide insights into the mechanisms underpinning racial disparities in COVID-19 complications. The quantitative and qualitative data will provide important context to generate hypotheses around the mechanisms for racial disparities in COVID-19, and may help to inform the development of multilevel strategies to reduce the burden of racial disparities in COVID-19 and its ongoing sequelae. Incorporating contextual information, elucidated from qualitative interviews, will increase the efficacy, adoption, and sustainability of such strategies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38914.

The Use of a Self-triage Tool to Predict COVID-19 Cases and Hospitalizations in the State of Georgia.

INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic has created significant burden on healthcare systems throughout the world. Syndromic surveillance, which collects real-time data based on a range of symptoms rather than laboratory diagnoses, can help provide timely information in emergency response. We examined the effectiveness of a web-based COVID-19 symptom checking tool (C19Check) in the state of Georgia (GA) in predicting COVID-19 cases and hospitalizations. METHODS: We analyzed C19Check use data, COVID-19 cases, and hospitalizations from April 22-November 28, 2020. Cases and hospitalizations in GA were extracted from the Georgia Department of Public Health data repository. We used the Granger causality test to assess whether including C19Check data can improve predictions compared to using previous COVID-19 cases and hospitalizations data alone. Vector autoregression (VAR) models were fitted to forecast cases and hospitalizations from November 29 - December 12, 2020. We calculated mean absolute percentage error to estimate the errors in forecast of cases and hospitalizations. RESULTS: There were 25,861 C19Check uses in GA from April 22-November 28, 2020. Time-lags tested in Granger causality test for cases (6-8 days) and hospitalizations (10-12 days) were significant (P= <0.05); the mean absolute percentage error of fitted VAR models were 39.63% and 15.86%, respectively. CONCLUSION: The C19Check tool was able to help predict COVID-19 cases and related hospitalizations in GA. In settings where laboratory tests are limited, a real-time, symptom-based assessment tool can provide timely and inexpensive data for syndromic surveillance to guide pandemic response. Findings from this study demonstrate that online symptom-checking tools can be a source of data for syndromic surveillance, and the data may help improve predictions of cases and hospitalizations.

Diabetes as a Risk Factor for Long-COVID-19-A Scoping Review

Background: Diabetes is a key risk factor for severe COVID-19 (i.e., hospitalization, mortality) . Whether diabetes is also a risk factor for post-acute sequelae of COVID-19 (PASC) , also known as long COVID, is unknown. Methods: We conducted a scoping literature review on January 27, 2022 using the keyword terms 'long hauler', 'long COVID-19', 'post-acute sequalae', and 'persistent COVID-19' combined with the operator OR, with AND 'diabetes', AND 'COVID-19 [MeSH Term]'. We included all peer-reviewed full-text observational research studies published in English between January 1, 2020 and January 27, 2022 that reported on the risk of PASC in people with and without diabetes with a minimum of 4-weeks follow-up after COVID-19 diagnosis, and narratively synthesized results. Results: Among 39 studies identified, seven were included in the review and are summarized in Table 1. Overall, we found that 43% of studies identified diabetes as a potent risk factor for PASC (all odds ratios were >4) . However, this conclusion is limited by the heterogeneity of studies with regard to PASC definitions (e.g., ongoing symptoms of fatigue, cough, dyspnea etc.) , populations at risk (hospitalized vs. non-hospitalized populations) , and follow-up times (range 4 weeks to 7 months) . Conclusions: More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for PASC. In the meantime, careful monitoring of people with diabetes for development of PASC may be advised.

Racial and Ethnic Differences and Clinical Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) Presenting to the Emergency Department.

BACKGROUND: Since the introduction of remdesivir and dexamethasone for severe COVID-19 treatment, few large multi-hospital-system US studies have described clinical characteristics and outcomes of minority COVID-19 patients who present to the emergency department (ED). METHODS: This cohort study from the Cerner Real World Database (87 US health systems) from 1 December 2019 to 30 September 2020 included PCR-confirmed COVID-19 patients who self-identified as non-Hispanic Black (Black), Hispanic White (Hispanic), or non-Hispanic White (White). The main outcome was hospitalization among ED patients. Secondary outcomes included mechanical ventilation, intensive care unit care, and in-hospital mortality. Descriptive statistics and Poisson regression compared sociodemographics, comorbidities, receipt of remdesivir or dexamethasone, and outcomes by racial/ethnic groups and geographic region. RESULTS: 94 683 COVID-19 patients presented to the ED. Blacks comprised 26.7% and Hispanics 33.6%. Nearly half (45.1%) of ED patients presented to hospitals in the South. 31.4% (n = 29 687) were hospitalized. Lower proportions of Blacks were prescribed dexamethasone (29.4%; n = 7426) compared with Hispanics (40.9%; n = 13 021) and Whites (37.5%; n = 14 088). Hospitalization risks, compared with Whites, were similar in Blacks (RR: .94; 95% CI: .82-1.08; P = .4) and Hispanics (.99; .81-1.21; P = .91), but risk of in-hospital mortality was higher in Blacks (1.18; 1.06-1.31; P = .002) and Hispanics (1.28; 1.13-1.44; P < .001). CONCLUSIONS: Minority patients were overrepresented among COVID-19 ED patients, and while their risks of hospitalization were similar to Whites, in-hospital mortality risk was higher. Interventions targeting upstream social determinants of health are needed to reduce racial/ethnic disparities in COVID-19.

A Quality Improvement Intervention to Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) in Patients With Chronic Kidney Disease: Clinical Research Protocol of a Cluster-Randomized Clinical Trial.

BACKGROUND: Many patients with kidney failure will live longer and healthier lives if they receive a kidney transplant rather than dialysis. However, multiple barriers prevent patients from accessing this treatment option. OBJECTIVE: To determine if a quality improvement intervention provided in chronic kidney disease (CKD) programs (vs. usual care) enables more patients with no recorded contraindications to kidney transplant to complete more steps toward receiving a kidney transplant. DESIGN: This protocol describes a pragmatic 2-arm, parallel-group, open-label, registry-based, cluster-randomized clinical trial-the Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) trial. SETTING: All 26 CKD programs in Ontario, Canada, with a trial start date of November 1, 2017. The original end date of March 31, 2021 (3.4 years) has been extended to December 31, 2021 (4.1 years) due to the COVID-19 pandemic. PARTICIPANTS: During the trial, the 26 CKD programs are expected to care for more than 10 000 adult patients with CKD (including patients approaching the need for dialysis and patients receiving dialysis) with no recorded contraindications to a kidney transplant. INTERVENTION: Programs were randomly allocated to provide a quality improvement intervention or usual care. The intervention has 4 main components: (1) local quality improvement teams and administrative support; (2) tailored education and resources for staff, patients, and living kidney donor candidates; (3) support from kidney transplant recipients and living kidney donors; and (4) program-level performance reports and oversight by program leaders. PRIMARY OUTCOME: The primary outcome is the number of key steps completed toward receiving a kidney transplant analyzed at the cluster level (CKD program). The following 4 unique steps per patient will be counted: (1) patient referred to a transplant center for evaluation, (2) at least one living kidney donor candidate contacts a transplant center for an intended recipient and completes a health history questionnaire to begin their evaluation, (3) patient added to the deceased donor transplant wait list, and (4) patient receives a kidney transplant from a living or deceased donor. PLANNED PRIMARY ANALYSIS: Study data will be obtained from Ontario's linked administrative healthcare databases. An intent-to-treat analysis will be conducted comparing the primary outcome between randomized groups using a 2-stage approach. First stage: residuals are obtained from fitting a regression model to individual-level variables ignoring intervention and clustering effects. Second stage: residuals from the first stage are aggregated at the cluster level as the outcome. LIMITATIONS: It may not be possible to isolate independent effects of each intervention component, the usual care group could adopt intervention components leading to contamination bias, and the relatively small number of clusters could mean the 2 arms are not balanced on all baseline prognostic factors. CONCLUSIONS: The EnAKT LKD trial will provide high-quality evidence on whether a multi-component quality improvement intervention helps patients complete more steps toward receiving a kidney transplant. TRIAL REGISTRATION: Clinicaltrials.gov; identifier: NCT03329521.

CONTEXTE: Plusieurs patients atteints d'insuffisance rénale vivront plus longtemps et en meilleure santé s'ils reçoivent une greffe de rein plutôt que des traitements de dialyze. De nombreux obstacles empêchent cependant les patients d'accéder à la transplantation. OBJECTIF: Déterminer si une intervention visant l'amélioration de la qualité menée dans les programs d'insuffisance rénale chronique (IRC) permettrait à davantage de patients sans contre-indications à une greffe d'aller plus loin (comparativement aux soins habituels) dans le processus menant à la transplantation. TYPE D'ÉTUDE: Ce protocole décrit un essai clinique pragmatique ouvert, à deux bras, en groupes parallèles, à répartition aléatoire en grappes et fondé sur un registre ­ l'essai Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD). CADRE: Les 26 programs d'IRC de l'Ontario (Canada). L'essai a débuté le 1er novembre 2017 et devait initialement se terminer le 31 mars 2021 (3,4 ans); cette date a été reportée au 31 décembre 2021 (4,1 ans) en raison de la pandémie de COVID-19. SUJETS: Au cours de l'essai, on estime que les 26 programs d'IRC prendront en charge plus de 10 000 adultes atteints d'IRC (y compris des patients approchant le besoin de dialyze et des patients dialysés) sans contre-indications à une greffe. INTERVENTIONS: Les programs ont été répartis aléatoirement pour intégrer une intervention d'amélioration de la qualité ou pour prodiguer les soins habituels. L'intervention consiste en quatre composantes principales: (1) des équipes locales d'amélioration de la qualité et de soutien administratif; (2) de l'information et des ressources sur mesure pour le personnel, les patients et les donneurs vivants; (3) du soutien pour les receveurs et les donneurs vivants; et (4) des rapports sur le rendement au niveau du program et une surveillance assurée par les chefs de program. PRINCIPAUX RÉSULTATS: Le principal critère d'évaluation est le nombre d'étapes clés complétées en vue de la réception d'une greffe de rein tel qu'analysé au niveau de la grappe (program d'IRC). Pour chaque patient, quatre étapes spécifiques seront comptabilisées: (I) le patient est aiguillé vers un center de transplantation pour évaluation; (II) au moins un donneur vivant de rein contacte un center de transplantation pour un receveur en particulier et amorce son évaluation en remplissant un questionnaire sur ses antécédents médicaux; (III) le patient est ajouté à la liste d'attente pour une transplantation d'un donneur décédé, et (IV) le patient reçoit une greffe de rein d'un donneur vivant ou décédé. PRINCIPALE ANALYZE ENVISAGÉE: Les données sont tirées des bases de données administratives du système de santé ontarien. Une analyze en intention de traiter sera effectuée en comparant le principal critère d'évaluation entre les groupes répartis aléatoirement à l'aide d'une approche en deux étapes. Première étape: obtention de valeurs résiduelles en adaptant un modèle de régression aux variables de niveau individuel et en ignorant les effets de l'intervention et du regroupement. Deuxième étape: les valeurs résiduelles de la première étape agrégées au niveau du groupe constitueront le résultat. LIMITES: Il pourrait ne pas être possible d'isoler les effets indépendants de chaque composante de l'intervention. L'équipe prodiguant les soins habituels pourrait adopter des composantes de l'intervention menant à un biais de contamination. Le nombre relativement faible de groupes pourrait signifier que les deux bras ne sont pas équilibrés sur tous les facteurs pronostiques de base. CONCLUSION: L'essai EnAKT LKD fournira des données de haute qualité sur la question de savoir si une intervention à composantes multiples visant l'amélioration de la qualité aide effectivement les patients à franchir davantage d'étapes vers une transplantation rénale.

A Framework for Mobilizing Health Care to Respond to the Community Within the COVID-19 Pandemic.

Cultural mistrust of government with regard to health issues has pressed the need to engage trusted community leaders with influence and reach in disproportionately affected communities to ensure that essential public health activities related to COVID-19 occur among populations experiencing disproportionate impact from the pandemic. In April of 2020, a Georgia-based integrated academic health care system created a Community Outreach and Health Disparities Collaborative to unite trusted community leaders from faith-based, civic, and health-sector organizations to work with the health system and Emory University to develop tailored approaches and mobilize support within the context of the communities' cultural and individual needs to reduce the burden of COVID-19. We describe the framework used to join health care and academic collaborators with community partners to mobilize efforts to address the disproportionate impact of COVID-19 on racial, ethnic, and socioeconomic minority groups. The framework outlines a series of steps taken that led to a community-driven collaboration designed to engage local influential community leaders as partners in improving access to care for disproportionately affected communities, collaborations that could be replicated by other large health care systems. This framework can also be applied to other chronic diseases or future public health emergencies to improve communication, education, and health care access for communities experiencing disproportionate impact.