FOUNTAIN: a modular research platform for integrated real-world evidence generation.

BACKGROUND: Real-world evidence (RWE) plays a key role in regulatory and healthcare decision-making, but the potentially fragmentated nature of generated evidence may limit its utility for clinical decision-making. Heterogeneity and a lack of reproducibility in RWE resulting from inconsistent application of methodologies across data sources should be minimized through harmonization. METHODS: This paper's aim is to describe and reflect upon a multidisciplinary research platform (FOUNTAIN; FinerenOne mUlti-database NeTwork for evidence generAtIoN) with coordinated studies using diverse RWE generation approaches and explore the platform's strengths and limitations. With guidance from an executive advisory committee of multidisciplinary experts and patient representatives, the goal of the FOUNTAIN platform is to harmonize RWE generation across a portfolio of research projects, including research partner collaborations and a common data model (CDM)-based program. FOUNTAIN's overarching objectives as a research platform are to establish long-term collaborations among pharmacoepidemiology research partners and experts and to integrate diverse approaches for RWE generation, including global protocol execution by research partners in local data sources and common protocol execution in multiple data sources through federated data networks, while ensuring harmonization of medical definitions, methodology, and reproducible artifacts across all studies. Specifically, the aim of the multiple studies run within the frame of FOUNTAIN is to provide insight into the real-world utilization, effectiveness, and safety of finerenone across its life-cycle. RESULTS: Currently, the FOUNTAIN platform includes 9 research partner collaborations and 8 CDM-mapped data sources from 7 countries (United States, United Kingdom, China, Japan, The Netherlands, Spain, and Denmark). These databases and research partners were selected after a feasibility fit-for-purpose evaluation. Six multicountry, multidatabase, cohort studies are ongoing to describe patient populations, current standard of care, comorbidity profiles, healthcare resource use, and treatment effectiveness and safety in different patient populations with chronic kidney disease and type 2 diabetes. Strengths and potential limitations of FOUNTAIN are described in the context of valid RWE generation. CONCLUSION: The establishment of the FOUNTAIN platform has allowed harmonized execution of multiple studies, promoting consistency both within individual studies that employ multiple data sources and across all studies run within the platform's framework. FOUNTAIN presents a proposal to efficiently improve the consistency and generalizability of RWE on finerenone.

Antihyperglycemic treatment patterns for chronic kidney disease and type 2 diabetes.

OBJECTIVE: Patients with type 2 diabetes (T2D) are at high risk for developing chronic kidney disease (CKD). The onset of incident CKD may complicate glycemic control among these patients. This study aimed to characterize antihyperglycemic medication use after incident CKD onset among patients with T2D to inform disease management. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with incident CKD and prior T2D were identified from the Optum electronic health records database between March 2013 and September 2021. Patterns of antihyperglycemic use were assessed during the 1-year baseline period and after incident CKD diagnosis and described by baseline hemoglobin A1C (HbA1C) level (controlled [< 7%] vs elevated [≥ 7%]) and CKD severity. RESULTS: The study consisted of 262,395 patients, of whom 51% had elevated HbA1C. After CKD onset, 23.9% of patients initiated new antihyperglycemics within 1 year. Patients with elevated HbA1C had shorter time to new treatment initiation compared with those with controlled HbA1C (median, 28.7 vs 83.7 months). Patients with elevated urine albumin-to-creatinine ratio (uACR) had shorter median time to new treatment initiation (39.9-42.4 months) than those with normal uACR (59.8 months). Less than 7% of patients with stage 3 CKD and even smaller percentages of patients with higher stages of CKD utilized glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. CONCLUSIONS: Treatment of T2D was considerably heterogenous by HbA1C level and CKD severity in patients with incident CKD. Current agents may not sufficiently fulfill the unmet need of T2D management in patients with CKD.

Early Clinical Experience of Finerenone in People with Chronic Kidney Disease and Type 2 Diabetes in Japan-A Multi-Cohort Study from the FOUNTAIN (FinerenOne mUltidatabase NeTwork for Evidence generAtIoN) Platform.

Background: In the phase 3 clinical trials FIGARO-DKD and FIDELIO-DKD, finerenone reduced the risk of cardiovascular and kidney events among people with chronic kidney disease (CKD) and type 2 diabetes (T2D). Evidence regarding finerenone use in real-world settings is limited. Methods: A retrospective cohort study (NCT06278207) using two Japanese nationwide hospital-based databases provided by Medical Data Vision (MDV) and Real World Data Co., Ltd. (RWD Co., Kyoto Japan), converted to the OMOP common data model, was conducted. Persons with CKD and T2D initiating finerenone from 1 July 2021, to 30 August 2023, were included. Baseline characteristics were described. The occurrence of hyperkalemia after finerenone initiation was assessed. Results: 1029 new users of finerenone were included (967 from MDV and 62 from RWD Co.). Mean age was 69.5 and 72.4 years with 27.3% and 27.4% being female in the MDV and RWD Co. databases, respectively. Hypertension (92 and 95%), hyperlipidemia (59 and 71%), and congestive heart failure (60 and 66%) were commonly observed comorbidities. At baseline, 80% of persons were prescribed angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists were prescribed in 72% and 30% of the study population, respectively. The incidence proportions of hyperkalemia were 2.16 and 2.70 per 100 persons in the MDV and RWD Co. databases, respectively. There were no hospitalizations associated with hyperkalemia observed in either of the two datasets. Conclusions: For the first time, we report the largest current evidence on the clinical use of finerenone in real-world settings early after the drug authorization in Japan. This early evidence from clinical practice suggests that finerenone is used across comorbidities and comedications.

Treatment patterns of antidiabetic and kidney protective therapies among patients with type 2 diabetes mellitus and chronic kidney disease in Colombia. The KDICO descriptive study.

BACKGROUND: Type 2 diabetes mellitus is one of the most common causes of chronic kidney disease (CKD) worldwide and prevalence of 1.75 per 100 inhabitants in Colombia. The aim of this study was to describe the treatment patterns of a group of patients with type 2 diabetes mellitus and CKD in an outpatient setting from Colombia. METHODS: A cross-sectional study in adult patients with type 2 diabetes mellitus and CKD identified in the Audifarma S.A. administrative healthcare database between April 2019 and March 2020 was performed. Sociodemographic, clinical and pharmacological variables were considered and analyzed. RESULTS: A total of 14,722 patients with type 2 diabetes mellitus and CKD were identified, predominantly male (51%), with a mean age of 74.7 years. The most common treatment patterns of type 2 diabetes mellitus included the use of metformin monotherapy (20.5%), followed by the combination of metformin + dipeptidyl peptidase-4 inhibitor (13.4%). Regarding the use of drugs with nephroprotective properties, the most prescribed treatments were angiotensin receptor blockers (67.2%), angiotensin converting enzyme inhibitors (15.8%), sodium glucose cotransporter 2 inhibitors (SGLT2i) (17.0%) and glucagon-like peptide-1 analogs (GLP1a) (5.2%). CONCLUSION: In Colombia, the majority of patients with type 2 diabetes mellitus and CKD identified in this study were treated with antidiabetic and protective medications to ensure adequate metabolic, cardiovascular, and renal control. The management of type 2 diabetes mellitus and CKD may be improved if the beneficial properties of new groups of antidiabetics (SGLT2i, GLP1a), as well as novel mineralocorticoid receptor antagonists, are considered.

Quality of life, self-reported outcomes and impact of education among people with moderate and severe hemophilia A: An integrated perspective from a Latin American country.

Collecting and interpreting self-reported outcomes among people with hemophilia A supports the understanding of the burden of the disease and its treatment to improve holistic care. However, in Colombia, this information is limited. Therefore, this study aimed to describe the knowledge, perception and burden of hemophilia A from the patients' perspective. A cross-sectional study was conducted in the context of a hemophilia educational bootcamp held from November 29th to December 1st, 2019, in Medellin, Colombia. The bootcamp was organized by a hemophilia patient association responsible for contacting and inviting patients with hemophilia A (PwHA). Information on patients' health beliefs, treatment experiences, and health-related quality of life (HRQoL) was obtained through focus groups, individual interviews and the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. A total of 25 moderate or severe PwHA were enrolled in this study and completed the PROBE questionnaire. Acute pain was the most frequently reported symptom, with 88% of the patients reporting the use of pain medication. Difficulty with activities of daily living was reported by 48%. Furthermore, 52% reported having more than 2 spontaneous bleeding events in the last year. Treatment was administered at home for 72% of patients, with regular prophylaxis as the most common treatment regimen. In terms of overall HRQoL, the median EQ-5D VAS score was 80 (IQR: 50-100). PwHA in Colombia still suffer from disease complications related to bleeding events, pain and disability that affect their HRQoL, which highlights the need to develop patient-centered initiatives to improve the wellness of this population.

Characteristics of patients with chronic kidney disease and Type 2 diabetes initiating finerenone in the USA: a multi-database, cross-sectional study.

Aim: Finerenone is safe and efficacious for treating patients with chronic kidney disease (CKD) and Type 2 diabetes (T2D). Evidence on the use of finerenone in clinical practice is lacking. Objective: To describe demographic and clinical characteristics of early adopters of finerenone in the United States, according to sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and urine albumin-creatinine ratio (UACR) levels. Methods: Multi-database, observational, cross-sectional study, using data from two US databases (Optum Claims and Optum EHR). Three cohorts were included: finerenone initiators with prior CKD-T2D, finerenone initiators with prior CKD-T2D and concomitant SGLT2i use, finerenone initiators with prior CKD-T2D stratified according to UACR. Results: In total, 1015 patients were included, 353 from Optum Claims and 662 from Optum EHR. Mean age was 72.0 and 68.4 years in Optum claims and EHR, respectively. Median eGFR was 44 and 44 ml/min/1.73 m2; and median UACR was 132 (28-698)/365 (74-1185.4) mg/g, in Optum Claims and EHR, respectively. 70.5/70.4% were taking renin-angiotensin system inhibitors, 42.5/53.3% SGLT2i. Overall, 9.0/6.3% of patients had baseline UACR <30 mg/g, 15.0/20.2% had UACR 30-300 mg/g, and 14.4/27.6% had UACR >300 mg/g. Conclusion: Current management of patients with CKD-T2D reflects use of finerenone independently from background therapies and clinical characteristics, suggesting implementation of therapeutic strategies based on different modes of action.

Cardiovascular and renal outcomes among patients with type 2 diabetes using SGLT2 inhibitors added to metformin: a population-based cohort study from the UK.

INTRODUCTION: Large numbers of patients with type 2 diabetes receive treatment with a sodium-glucose co-transporter-2 inhibitor (SGLT2i). We investigated whether the cardiorenal preventative effects found in clinical trials are also seen in clinical practice where patient characteristics and adherence to treatment differ. RESEARCH DESIGN AND METHODS: Using UK primary care electronic health records, we followed two cohorts of patients with type 2 diabetes prescribed metformin: SGLT2is (N=12 978) and a matched comparator of patients not using an SGLT2i at the start of follow-up (N=44 286). Independent follow-ups were performed to identify the study outcomes: cardiovascular (CV) composite (comprising non-fatal myocardial infarction (MI)/ischemic stroke (IS) requiring hospitalization and CV death), severe renal disease, and all-cause mortality. Cox regression was used to estimate adjusted HRs. RESULTS: Mean follow-up was 2.3 years (SGLT2i cohort) and 2.1 years (comparison cohort). Mean age was 59.6 years (SD ±10.2, SGLT2i cohort) and 60.4 years (SD ±10.0, comparison cohort). SGLT2i new users were associated with a reduced risk of the CV composite (HR 0.75, 95% CI: 0.61 to 0.93), severe renal disease (HR 0.55, 95% CI: 0.46 to 0.67), and all-cause mortality (HR 0.56, 95% CI: 0.49 to 0.63), with risk reductions similar irrespective of baseline chronic kidney disease. Reduced risks were seen for IS (HR 0.51, 95% CI: 0.36 to 0.74) but not MI (HR 0.98, 95% CI: 0.74 to 1.28). Results were consistent in sensitivity analyses. CONCLUSIONS: In this population-based study, SGLT2is were associated with significant CV, renal and survival benefits among individuals with type 2 diabetes on metformin; the CV benefit was driven by a reduced risk of ischemic stroke.

Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe.

Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma.Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions.Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients.Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .

Cardiovascular events and mortality in chronic kidney disease in primary care patients with previous type 2 diabetes and/or hypertension. A population-based epidemiological study (KIDNEES).

BACKGROUND: Chronic Kidney Disease (CKD), Type 2 Diabetes (T2D) and Hypertension (HTN) are frequently associated with adverse outcomes. We aimed to estimate the impact of a prior diagnosis of T2D and/or HTN on clinical characteristics, cardiovascular events (CVE) and all-cause mortality (ACM) of patients with CKD. METHODS: We conducted a retrospective cohort study based on primary care electronic health records of people without atherosclerotic cardiovascular disease, aged 18-90 years with incident CKD between January 1, 2007, and December 31, 2017. The association between CKD groups classified according to prior diagnosis of T2D and/or HTN and risk of ACM and CVE at follow-up was evaluated with Cox and Fine-Gray regression models, respectively. RESULTS: 398,477 patients were included. Median age was 74 years and 55.2% were women. Individuals were classified as CKD with HTN (51.9%), CKD with T2D (3.87%), CKD with HTN/T2D (31.4%) and CKD without HTN/T2D (12.9%). In the multivariate analysis, with the CKD without HTN/T2D group as reference, the ACM Hazard Ratio (HR) was 0.74 (95%CI 0.72-0.75) for the CKD with HTN group, 0.81 (95%CI 0.79-0.83) for CKD with HTN/T2D and 1.14 (95%CI 1.10-1.19) for the CKD with T2D group. The sub distribution HRs for CVE were 1.40 (95%CI 1.34-1.47), 1.70 (95%CI 1.61-1.80) and 1.37 (95%CI 1.26-1.48), respectively. CONCLUSION: In patients with CKD, the risk of ACM and CVE differed in patients with previous HTN and/or T2D. These comorbidities can help identify individuals at higher risk of adverse outcomes and improve the management of patients with CKD in primary care.

Development and external validation of prediction models for adverse health outcomes in rheumatoid arthritis: A multinational real-world cohort analysis.

BACKGROUND: Identification of rheumatoid arthritis (RA) patients at high risk of adverse health outcomes remains a major challenge. We aimed to develop and validate prediction models for a variety of adverse health outcomes in RA patients initiating first-line methotrexate (MTX) monotherapy. METHODS: Data from 15 claims and electronic health record databases across 9 countries were used. Models were developed and internally validated on Optum® De-identified Clinformatics® Data Mart Database using L1-regularized logistic regression to estimate the risk of adverse health outcomes within 3 months (leukopenia, pancytopenia, infection), 2 years (myocardial infarction (MI) and stroke), and 5 years (cancers [colorectal, breast, uterine] after treatment initiation. Candidate predictors included demographic variables and past medical history. Models were externally validated on all other databases. Performance was assessed using the area under the receiver operator characteristic curve (AUC) and calibration plots. FINDINGS: Models were developed and internally validated on 21,547 RA patients and externally validated on 131,928 RA patients. Models for serious infection (AUC: internal 0.74, external ranging from 0.62 to 0.83), MI (AUC: internal 0.76, external ranging from 0.56 to 0.82), and stroke (AUC: internal 0.77, external ranging from 0.63 to 0.95), showed good discrimination and adequate calibration. Models for the other outcomes showed modest internal discrimination (AUC < 0.65) and were not externally validated. INTERPRETATION: We developed and validated prediction models for a variety of adverse health outcomes in RA patients initiating first-line MTX monotherapy. Final models for serious infection, MI, and stroke demonstrated good performance across multiple databases and can be studied for clinical use. FUNDING: This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Incidence and risk factors for mortality and end-stage renal disease in people with type 2 diabetes and diabetic kidney disease: a population-based cohort study in the UK.

INTRODUCTION: We aimed to determine the incidence of, and risk factors for all-cause/cardiovascular disease (CVD) mortality, and end-stage renal disease (ESRD) among people with type 2 diabetes with/without diabetic kidney disease (DKD) in the UK general population. RESEARCH DESIGN AND METHODS: We undertook a population-based cohort study using primary care UK electronic health records. We followed 8413 people with type 2 diabetes and DKD and a matched comparison cohort of people with type 2 diabetes without DKD. Risk factors for all-cause/CVD mortality (using both cohorts) and ESRD (DKD cohort only) were evaluated by estimating HRs with 95% CIs using Cox regression. RESULTS: In the DKD cohort (mean age 66.7 years, 62.4% male), incidence rates per 1000 person-years were 50.3 (all-cause mortality), 8.0 (CVD mortality) and 6.9 (ESRD). HRs (95% CIs; DKD vs comparison cohort) were 1.49 (1.35 to 1.64) for all-cause mortality and 1.60 (1.24 to 2.05) for CVD mortality. In general, higher all-cause mortality risks were seen with older age, underweight (body mass index <20 kg/m2), reduced renal function, and cardiovascular/liver disease, and lower risks were seen with being female or overweight. In the DKD cohort, higher risks of ESRD were seen with reduced renal function at baseline, high material deprivation, cancer and non-insulin glucose-lowering drugs, and a lower risk was seen with overweight (≥25 kg/m2). CONCLUSIONS: Annually, one death will occur among every 20 people with type 2 diabetes and DKD. The identified risk factors in this study will help identify people with type 2 diabetes at most risk of death and progression of kidney disease, and help to direct effective management strategies.

Serological response to nifurtimox in adult patients with chronic Chagas disease: An observational comparative study in Argentina.

Nifurtimox is indicated in Chagas disease but determining its effectiveness in chronic disease is hindered by the length of time needed to demonstrate negative serological conversion. We manually reviewed long-term follow-up data from hospital records of patients with chronic Chagas disease (N = 1,497) in Argentina diagnosed during 1967-1980. All patients were aged ≥18 years at diagnosis and were either treated with nifurtimox (n = 968) or received no antitrypanosomal treatment (n = 529). The primary endpoint was negative seroconversion (the "event"), defined as a change from positive to negative in the serological or parasitological laboratory test used at diagnosis. Time to event was from baseline visit to date of endpoint event or censoring. The effectiveness of nifurtimox versus no treatment was estimated with Cox proportional hazard regression using propensity scores with overlap weights to calculate the hazard ratio and 95% confidence interval. The nifurtimox group was younger than the untreated group (mean, 32.4 vs. 40.3 years), with proportionally fewer females (47.9% vs. 60.1%), and proportionally more of the nifurtimox group than the untreated group had clinical signs and symptoms of Chagas disease at diagnosis (28.9% vs. 14.0%). Median maximum daily dose of nifurtimox was 8.0 mg/kg/day (interquartile range [IQR]: 8.0-9.0) and median treatment duration was 44 days (IQR: 1-90). Median time to event was 2.1 years (IQR: 1.0-4.5) for nifurtimox-treated and 2.4 years (IQR: 1.0-4.2) for untreated patients. Accounting for potential confounders, the estimated hazard ratio (95% confidence interval) for negative seroconversion was 2.22 (1.61-3.07) favoring nifurtimox. Variable treatment regimens and follow-up duration, and an uncommonly high rate of spontaneous negative seroconversion, complicate interpretation of this epidemiological study, but with the longest follow-up and largest cohort analyzed to date it lends weight to the benefit of nifurtimox in adults with chronic Chagas disease. Trial registration: The study protocol was registered at ClinicalTrials.gov: NCT03784391.

Thirty-Day Outcomes of Children and Adolescents With COVID-19: An International Experience.

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.

Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study.

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. METHODS: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization. RESULTS: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%). CONCLUSION: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.

Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study.

OBJECTIVES: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. METHODS: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. RESULTS: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. CONCLUSION: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. TRIAL REGISTRATION: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.

Use of dialysis, tracheostomy, and extracorporeal membrane oxygenation among 842,928 patients hospitalized with COVID-19 in the United States.

OBJECTIVE: To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). DESIGN: A network cohort study. SETTING: Seven databases from the United States containing routinely-collected patient data: HealthVerity, Premier, IQVIA Hospital CDM, IQVIA Open Claims, Optum EHR, Optum SES, and VA-OMOP. PATIENTS: Patients hospitalized with a clinical diagnosis or a positive test result for COVID-19. INTERVENTIONS: Dialysis, tracheostomy, and ECMO. MEASUREMENTS AND MAIN RESULTS: 842,928 patients hospitalized with COVID-19 were included (22,887 from HealthVerity, 77,853 from IQVIA Hospital CDM, 533,997 from IQVIA Open Claims, 36,717 from Optum EHR, 4,336 from OPTUM SES, 156,187 from Premier, and 10,951 from VA-OMOP). Across the six databases, 35,192 (4.17% [95% CI: 4.13% to 4.22%]) patients received dialysis, 6,950 (0.82% [0.81% to 0.84%]) had a tracheostomy, and 1,568 (0.19% [95% CI: 0.18% to 0.20%]) patients underwent ECMO over the 30 days following hospitalization. Use of ECMO was more common among patients who were younger, male, and with fewer comorbidities. Tracheostomy was broadly used for a similar proportion of patients regardless of age, sex, or comorbidity. While dialysis was generally used for a similar proportion among younger and older patients, it was more frequent among male patients and among those with chronic kidney disease. CONCLUSION: Use of dialysis among those hospitalized with COVID-19 is high at around 4%. Although less than one percent of patients undergo tracheostomy and ECMO, the absolute numbers of patients who have undergone these interventions is substantial.

Characteristics, outcomes, and mortality amongst 133,589 patients with prevalent autoimmune diseases diagnosed with, and 48,418 hospitalised for COVID-19: a multinational distributed network cohort analysis.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. DESIGN: Multinational network cohort study. SETTING: Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). PARTICIPANTS: All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. MAIN OUTCOME MEASURES: 30-day complications during hospitalisation and death. RESULTS: We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged ≥50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%).Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). CONCLUSIONS: Patients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC: Patients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications.There is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions. WHAT THIS STUDY ADDS: Most people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities.Patients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19.A variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases.For people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season.

Prognosis of patients with malignant mesothelioma by expression of programmed cell death 1 ligand 1 and mesothelin in a contemporary cohort in Finland.

OBJECTIVES: We aimed to describe mesothelin (MSLN) and programmed cell death 1 ligand 1 (PD-L1) tumour overexpression amongst patients with malignant mesothelioma (MM), and their associations with survival, amongst a cohort of patients with MM in Finland. METHODS: Between 2004 and 2017, 91 adults with histologically confirmed MM were identified from the Auria Biobank in Finland and followed-up using linked data from electronic health records and national statistics. Biomarker content in tumour cell membranes was determined using automated Immunohistochemistry on histological sections. Stained tumour sections were scored for MSLN and PD-L1 intensity. Adjusted associations between MSLN/PD-L1 co-expression and mortality were evaluated by estimating hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression. RESULTS: Biomarker overexpression occurred in 52 patients for MSLN and 34 patients for PD-L1 and was associated with tumour histology and certain comorbidities. Fifteen per cent of patients had a tumour that overexpressed both biomarkers; r =-0.244, p-value: 0.02. Compared with MSLN+/PD-L1+ patients, HRs (95% CIs) for death were 4.18 (1.71-10.23) for MSLN-/PD-L1+ patients, 3.03 (1.35-6.77) for MSLN-/PD-L1- patients, and 2.13 (0.97-4.67) for MSLN+/PD-L1- patients. CONCLUSIONS: Both MSLN and PD-L1 markers were independent prognostic indicators in patients with MM. Overexpression of MSLN was associated with longer survival; yet their combined expression gave a better indication of survival. The risk of death was four times higher amongst MSLN-/PD-L1+ patients than in MSLN+/PD-L1+ patients.

Baseline phenotype and 30-day outcomes of people tested for COVID-19: an international network cohort including >3.32 million people tested with real-time PCR and >219,000 tested positive for SARS-CoV-2 in South Korea, Spain and the United States.

Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems' response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.