Background‘Treatment burden’, defined as both the workload and impact of treatment regimens on function and well-being, has been associated with poor adherence and unfavourable outcomes. Previous research focused on treatment workload but our understanding of treatment impact is limited. This research aimed to systematically review qualitative research to identify: 1) what are the treatment generated disruptions experienced by patients across all chronic conditions and treatments? 2) what strategies do patients employ to minimise these treatment generated disruptions?Methods and FindingsThe search strategy centred on: treatment burden and qualitative methods. Medline, CINAHL, Embase, and PsychINFO were searched electronically from inception to Dec 2013. No language limitations were set. Teams of two reviewers independently conducted paper screening, data extraction, and data analysis. Data were analysed using framework synthesis informed by Cumulative Complexity Model. Eleven papers reporting data from 294 patients, across a range of conditions, age groups and nationalities were included. Treatment burdens were experienced as a series of disruptions: biographical disruptions involved loss of freedom and independence, restriction of meaningful activities, negative emotions and stigma; relational disruptions included strained family and social relationships and feeling isolated; and, biological disruptions involved physical side-effects. Patients employed “adaptive treatment work” and “rationalised non-adherence” to minimise treatment disruptions. Rationalised non-adherence was sanctioned by health professionals at end of life; at other times it was a “secret-act” which generated feelings of guilt and impacted on family and clinical relationships.ConclusionsTreatments generate negative emotions and physical side effects, strain relationships and affect identity. Patients minimise these disruptions through additional adaptive work and/or by non-adherence. This affects physical outcomes and care relationships. There is a need for clinicians to engage with patients in honest conversations about treatment disruptions and the ‘adhere-ability’ of recommended regimens. Patient-centred practice requires management plans which optimise outcomes and minimise disruptions.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

Background Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. MethodsIn this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296.Findings Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0•98, 95% CI 0•84-1•14) or combination use exposure (1•01, 0•90-1•15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0•91, 95% CI 0•68-1•21; with heterogeneity of >40%) or combination use (0•95, 0•83-1•07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0•88, 95% CI 0•79-0•99) and non-significant for monotherapy (0•85, 0•69-1•05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute res...

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.

Importance COVID-19 is causing high mortality worldwide. Developing models to quantify the risk of poor outcomes in infected patients could help develop strategies to shield the most vulnerable during de-confinement. Objective To develop and externally validate COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission (COVER-H), requiring intensive services (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis. Design Multinational, distributed network cohorts. Setting We analyzed a federated network of electronic medical records and administrative claims data from 13 data sources and 6 countries, mapped to a common data model. Participants Model development used a patient population consisting of >2 million patients with a general practice (GP), emergency room (ER), or outpatient (OP) visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The model was validated on patients with a GP, ER, or OP visit in 2020 with a confirmed or suspected COVID-19 diagnosis across four databases from South Korea, Spain and the United States. Outcomes Age, sex, historical conditions, and drug use prior to index date were considered as candidate predictors. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. Results Overall, 43,061 COVID-19 patients were included for model validation, after initial model development and validation using 6,869,127 patients with influenza or flu-like symptoms. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, and kidney disease) which combined with age and sex could discriminate which patients would experience any of our three outcomes. The models achieved high performance in influenza. When transported to COVID-19 cohorts, the AUC ranges were, COVER-H: 0.73-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.82-0.90. Calibration was overall acceptable, with overestimated risk in the most elderly and highest risk strata. Conclusions and relevance A 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and death. The models could aid in providing reassurance for low risk patients and shield high risk patients from COVID-19 during de-confinement to reduce the virus' impact on morbidity and mortality.

Background

Data sharing statement: Analyses were performed locally in compliance with all applicable data privacy laws. Although the underlying data is not readily available to be shared, authors contributing to this paper have direct access to the data sources used in this study. All results (e.g. aggregate statistics, not presented at a patient-level with redactions for minimum cell count) are available for public inquiry. These results are inclusive of site-identifiers by contributing data sources to enable interrogation of each contributing site. All analytic code and result sets are made available at: https://github.com/ohdsi-studies/Covid19CharacterizationCharybdis

Objectives To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children/adolescents diagnosed or hospitalized with COVID-19. Secondly, to describe health outcomes amongst children/adolescents diagnosed with previous seasonal influenza. Design International network cohort. Setting Real-world data from European primary care records (France/Germany/Spain), South Korean claims and US claims and hospital databases. Participants Diagnosed and/or hospitalized children/adolescents with COVID-19 at age <18 between January and June 2020; diagnosed with influenza in 2017-2018. Main outcome measures Baseline demographics and comorbidities, symptoms, 30-day in-hospital treatments and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome (ARDS), multi-system inflammatory syndrome (MIS-C), and death. Results A total of 55,270 children/adolescents diagnosed and 3,693 hospitalized with COVID-19 and 1,952,693 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were all more common among those hospitalized vs diagnosed with COVID-19. The most common COVID-19 symptom was fever. Dyspnea, bronchiolitis, anosmia and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital treatments for COVID-19 included repurposed medications (<10%), and adjunctive therapies: systemic corticosteroids (6.8% to 37.6%), famotidine (9.0% to 28.1%), and antithrombotics such as aspirin (2.0% to 21.4%), heparin (2.2% to 18.1%), and enoxaparin (2.8% to 14.8%). Hospitalization was observed in 0.3% to 1.3% of the COVID-19 diagnosed cohort, with undetectable (N<5 per database) 30-day fatality. Thirty-day outcomes including pneumonia, ARDS, and MIS-C were more frequent in COVID-19 than influenza. Conclusions Despite negligible fatality, complications including pneumonia, ARDS and MIS-C were more frequent in children/adolescents with COVID-19 than with influenza. Dyspnea, anosmia and gastrointestinal symptoms could help differential diagnosis. A wide range of medications were used for the inpatient management of pediatric COVID-19.