Kidney Outcomes and Trajectories of Tubular Injury and Function in Critically Ill Persons with and without Coronavirus-2019 (preprint)

Background Coronavirus disease-2019 (COVID-19) may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point. To better understand mechanisms of AKI in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.Methods The COVID-19 Host Response and Outcomes (CHROME) study prospectively enrolled patients admitted to intensive care units in Washington state with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival. We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.Results At ICU admission, mean age was 55\(\pm\)16 years; 45% required mechanical ventilation; and mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater incidence of MAKE (95% CI 1.05, 2.74) and a 741% greater incidence of KRT (95% CI 1.69, 32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and eGFR increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.Conclusions Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction.

ADHERENCE TO BIOLOGIC THERAPIES IN INFLAMMATORY RHEUMATIC DISEASES: INFLUENCE OF ROUTE OF ADMINISTRATION

BackgroundInflammatory rheumatic diseases are a debilitating disease affecting the joints and periarticular structures and leading, more or less rapidly, to cartilage and bone destruction. It is a major source of chronic pain and physical, psychological, and social disability, it affect approximately 1% of the world's population [1]. For more than 20 years, biotherapies have revolutionized the treatment of these inflammatory diseases and have largely contributed to the improvement of their prognosis [2]. Adherence to biologic therapies conditions the effectiveness of the treatments then the improvement of patients' quality of life [3].ObjectivesTo evaluate and compare adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) according to the route of administration and the molecule used (Infliximab, Tocilizumab, Etanercept, Adalimumab, Certolizumab, and Golimumab) in patients with inflammatory rheumatic diseases.MethodsThis is a descriptive cross-sectional study with repeated data collection, bi-centric carried out in the rheumatology departments and outpatient clinics at Charles Nicolle Hospital and Rabta Hospital in Tunis and conducted over a period of 01 year and 02 months between 02/02/2021 and 30/04/2022. 71 adult patients with rheumatoid arthritis, spondyloarthritis or juvenile idiopathic arthritis were recruited, their adherence rate in the last 3 months before inclusion should be ≥80%. The collection of socio-demographic, clinical and therapeutic data was established with the help of a pre-established form, from medical files completed by questioning the patients during a direct interview or through a telephone communication. Adherence rate was calculated by determining the ratio of treatments cures (number of biologic injections taken during a year divided by the number of annual biologic injections prescribed).ResultsWithin the study population, adherence was estimated at 85.9%;in the group of patients using intravenous biotherapy was 82.1% (Infliximab 86%, Tocilizumab 75% p=0.04) and in the group of patients using subcutaneous treatment was 89.9% (Golimumab 94%, Etanercept 92%, Certolizumab 89%, Adalimumab 87% p=0.3). Adherence to biologic therapy was significantly higher in the subcutaneous group than in the intravenous group (p=0.01). The causes of poor adherence presented by the patients in this study were: stock-outs of biological treatment and delay in renewal by the national health insurance (CNAM) in thirty-eight cases (54%p<0.001), intercurrent infections in thirty-three cases (46% p=0.005) and the COVID 19 pandemic and its consequences in thirty patients (42%,p=0.28).ConclusionAdherence to biologic treatment is influenced by the route of administration, drugs type, intercurrent infections and drugs availability. All this factors must be treated to improve therapeutic adherence then the efficiency of the biologic therapy which conditions the preservation of physical capacities and an improvement in the quality of life.References[1]Adhésion médicamenteuse et représentations des patients atteints de rhumatisme inflammatoire chronique sous biothérapie: étude ADREP'RI.: 84. Betegnie AL.[2]2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. Singh JA, Saag KG, Bridges SL, Akl EA et al. janv 2016;68(1):1‑26.[3]Adherence to biologic DMARD therapies in rheumatoid arthritis. Expert Opin Biol Ther. Koncz T, Pentek M, Brodszky V, Ersek K, Orlewska E, Gulacsi L. sept 2010;10(9):1367‑78.[4]Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic drugs: a cross-sectional study. Mena-Vazquez N, Manrique-Arija S, Yunquera-Romero L, Ureña-Garnica I, Rojas-Gimenez et al.. Rheumatol Int [Internet]. oct 2017 [cité 30 oct 2022];37(10):1709‑18.[5]Adherence to Anti-Tumor Necrosis Factor Therapy Administered Subcutaneously and Associated Factors in Patients with Rheumatoid Arthritis. Salaffi F, Carotti M, Di Carlo M, Farah S, Gutierrez M. J Clin Rheumatol. déc 2015;21(8):419‑25.Acknowledgements:N L.Disclosure of InterestsNone Declared.

Does telehealth affect the adherence to ART among patients with HIV? A systematic review and meta-analysis.

BACKGROUND: Several studies have shown different effects of telehealth interventions on adherence to Antiretroviral therapy (ART) among people living with HIV. This study conducted a meta-analysis of Randomized Controlled Trials (RCTs) to estimate the pooled effect of telehealth interventions on the treatment adherence of HIV patients. METHODS: The researchers conducted literature searches in Scopus, PubMed, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials databases. In addition, open grey was systematically searched until January 2022 for RCTs around the effects of telehealth on adherence to treatment ART among patients with HIV. Each study's methodological quality was assessed using the Cochrane Collaboration tool. Pooled Standard Mean Differences (SMD) and Risk Ratio (RR) with 95% CI were calculated using the random effects model. RESULTS: In total, 12 eligible articles were considered in the present systematic review. A random-effects meta-analysis using 5 RCTs yielded the pooled RR estimate of 1.18 (95% CI: 1.03 to 1.35, p < 0.05); I2 = 0, suggesting the adherence to treatment among patients with HIV who received telehealth intervention was significantly 18% upper than control groups. Moreover, the random effects analysis of SMD showed a positive effect for telehealth with SMR = 0.36 (95% CI: 0.22 to 0.49, p < 0.05); I2 = 91.9%, indicating that telehealth intervention increased ART adherence to the treatment group compared to the control group. CONCLUSION: Telehealth intervention as a new modality of health care service delivery could be a valuable strategy to improve ART adherence among patients with HIV. It can strengthen the capacity of HIV care services. On a large scale, telehealth can be utilized as a supplementary component for ART delivery and retention toward successful adherence to the therapy.

Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19.

To identify and characterize clinical decline after completion of dexamethasone in severe COVID-19 and determine whether interleukin (IL)-6 and other inflammatory biomarkers predict the occurrence of clinical decline. DESIGN: Prospective observational cohort. SETTING: ICUs in three University of Washington affiliated hospitals between July 2020 and April 2021. PATIENTS: Patients admitted to an ICU with COVID-19 who completed a course of dexamethasone. MEASUREMENTS AND MAIN RESULTS: We identified 65 adult patients with severe COVID-19 who completed a 10-day course of dexamethasone, of whom 60 had plasma samples collected within 3 days of dexamethasone completion. We measured IL-6 with a clinical-grade electrochemiluminescent assay and a larger panel of inflammatory biomarkers (IL-8, Monocyte Chemoattractant Protein-1, Monocyte Inflammatory Protein-1 alpha, interferon gamma, C-X-C Motif Chemokine Ligand 10, WBC, bicarbonate) with a research immunoassay. We defined clinical decline by the occurrence of incident severe kidney injury, incident or escalating shock or fever, worsening hypoxemia, or death within 5 days of completion of dexamethasone. We estimated risk for clinical decline by standardized log2 transformed biomarker concentration using multivariable logistic regression. Clinical decline post-dexamethasone was common, occurring in 49% of patients (n = 32). Among all biomarkers, IL-6 levels were most strongly associated with clinical decline. After adjustment for age, sex, and study site, the odds of post-dexamethasone clinical decline were 7.33 times higher per one sd increase in log2 transformed IL-6 concentrations (adjusted odds ratio, 7.33; CI, 2.62-20.47; p < 0.001). The discriminatory power of IL-6 for clinical decline was high (cross-validated mean area under the receiver operating characteristic curve, 0.90; 95% CI, 0.79-0.95). CONCLUSIONS: Clinical decline after completion of dexamethasone for severe COVID-19 is common. IL-6 concentrations obtained prior to completion of dexamethasone may have utility in identifying those at highest risk for subsequent worsening. If validated, future work might test whether plasma IL-6 could be used as a tool for a personalized approach to duration of dexamethasone treatment in severe COVID-19.

Cell division tracing combined with single-cell transcriptomics reveals new cell types and differentiation paths in the regenerating mouse lung (preprint)

Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of new therapeutic approaches for lung diseases. We combined new mouse models that allow diphtheria toxin (DTA)-mediated depletion of specific epithelial cell types and GFP-labeling of dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncovered new cell types, some of which likely represent epithelial precursors, propose goblet cells as progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also found that DTA-expressing cells can persist in the lung, express specific inflammatory factors, and resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to defined epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.

Presence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 on Admission Is Associated With Decreased Mortality in COVID-19 Critical Illness.

To determine whether the early serologic response in COVID-19 critical illness is associated with hospital mortality. To evaluate if time-to-seroconversion differs by receipt of dexamethasone therapy. DESIGN: Patients were prospectively enrolled within 24 hours of ICU admission from two University of Washington Hospitals. Plasma was collected on enrollment and on days 3, 7, 10, and 14. SETTING: ICUs between March 2020 and April 2021. PATIENTS: Consecutive adults with COVID-19 admitted to an ICU. MEASUREMENTS AND MAIN RESULTS: We measured longitudinal total antispike protein antibody levels (anti-S abs) and total antinucleocapsid antibody levels (anti-N ab) using a U.S. Food and Drug Administration-authorized Roche instrument. We evaluated whether detectable anti-S abs on ICU admission were associated with host factors, initial disease severity, and hospital mortality. We evaluated whether dexamethasone therapy was associated with time-to-seroconversion. Among 93 unvaccinated participants, 47 (51%) had detectable anti-S abs on ICU admission. There was no difference in Acute Physiology and Chronic Health Evaluation II score or time between first positive severe acute respiratory syndrome coronavirus-2 PCR and ICU admission in those with detectable versus undetectable anti-S abs. Adjusting for age, body mass index, and sex, patients with detectable anti-S abs had a lower risk of inhospital death (hazard ratio, 0.40; 95% CI, 0.17-0.94; p = 0.04). Among 21 patients with undetectable anti-S abs on ICU admission and serial measurements available, time-to-seroconversion was not significantly affected by receipt of dexamethasone therapy. CONCLUSIONS: In COVID-19 critical illness, a significant proportion of patients do not have detectable antibodies at ICU admission, and this is independent of severity of illness. Detectable anti-S abs were associated with lower risk of inhospital death. Despite concern that corticosteroids may impair an appropriate antiviral serologic response, early antibody kinetics were not significantly affected by administration of dexamethasone; however, CIs were wide and require further study.

Assessment of obesity risk factors in Algerian children during COVID-19 lockdown

COVID-19 is a global pandemic, which has subsequently spread rapidly at all the countries of the world. The first measures taken to limit its spread were the imposition of social distancing and the lockdown. Although these measures are essential, they have important impacts on the behavior of individuals, their health and their lifestyles. The purpose of this study was to know the effect of the confinement on children. We carried out a cross-sectional prospective study on 100 children from the commune of Constantine, Algeria, including 54 boys and 46 girls, aged from 5 to 14 years old. Anthropometric measurements and a validated questionnaire have been completed. Our results showed that lockdown had a negative impact on the physical activity of children (decreased from 79% to 25%). Additionally, daily sitting time in front of TV and computer screens has increased compared to the pre-lockdown period. The frequency of obesity by sex, according to the WHO 2007 z-score references, is more frequent in boys than in girls, whether before or during confinement with a non-significant difference between genders. The high frequency observed of childhood obesity during the lockdown was also associated with eating habits and socio-economic status. This study allowed us to know the negative effects of confinement and its relationship with obesity in children. However, if we really wish to circumscribe the evolution of the phenomenon, it is necessary to act on the various factors identified as each having a share of responsibility in its occurrence.

Collateral effects of SARS-CoV-2 on active behaviors and body composition in Algerian school aged children

The SARS-CoV-2 pandemic had changed drastically the social life of children and youth, including their ability to adhere the physical activity (PA) recommendations. This study highlights the impact of the SARS-CoV-2 lockdown on children's daily physical activity, sedentary behaviors and sleep duration. It also determined the impact of this specific context on adiposity and cardio-metabolic indicators among children aged from 9 to 12 years old from Constantine-Algeria. Children were divided into 2 groups according to the practice of PA, a cross-sectional study was conducted at 2 different times. The first time, was before the SARS-CoV-2 pandemic, where the pre-lockdown lifestyle and PA data were collected via a validated questionnaire. The second time was during the lockdown, where the same questionnaire was asked to children's parents via telephonic interviews. A significant decline in the frequencies of PA patterns by 3.8 hours has been observed in the study population. In parallel, sedentary behaviors has been significantly increased by 4.5 hours in equal proportions between swimmers and sedentary children per day. Half of the children decreased their night sleep duration by an average of 54 minutes. This new lifestyle context induced by the lockdown was associated with an increase in body weight (3.69..0.9 kg) and body mass index (2.1..0.48 kg/m2) in the whole study population. These results might increase the prevalence of cardio-metabolic complications associated with overweight and obesity observed in the population of children and adolescents in Constantine in the near future.

A scope of mobile health solutions in COVID-19 pandemics.

BACKGROUND AND AIM: COVID-19 has become an international emergency. The use of digital solutions can be effective in managing, preventing, and overcoming the further spread of infectious disease outbreaks. Accordingly, the use of mobile-health (m-health) technologies has the potential to promote public health. This review aimed to study the application of m-health solutions for the management of the COVID-19 outbreak. METHODS: The search strategy was done in Medline (PubMed), Embase, IEEE, and Google Scholar by using related keywords to m-health and COVID-19 on July 6, 2020. English papers that used m-health technologies for the COVID-19 outbreak were included. RESULTS: Of the 2046 papers identified, 16 were included in this study. M-health had been used for various aims such as early detection, fast screening, patient monitoring, information sharing, education, and treatment in response to the COVID-19 outbreak. M-health solutions were classified into four use case categories: prevention, diagnosis, treatment, and protection. The mobile phone-based app and short text massaging were the most frequently used modalities, followed by wearables, portable screening devices, mobile-telehealth, and continuous telemetry monitor during the pandemics. CONCLUSION: It appears that m-health technologies played a positive role during the COVID-19 outbreak. Given the extensive capabilities of m-health solutions, investigation and use of all potential applications of m-health should be considered for combating the current Epidemics and mitigating its negative impacts.