ORCID Profile
0000-0002-3950-6346
Current Organisations
Erasmus MC
,
University of Oxford
,
European Health Data and Evidence Network (EHDEN
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Publisher: Elsevier BV
Date: 04-2017
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 06-2016
DOI: 10.1302/2046-3758.56.2000568
Abstract: High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long-term outcome in patients undergoing primary total hip arthroplasty (THA). We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015. Our search strategy identified 1082 studies of which 115 studies were included for full article review. Following review, 17 articles were found that investigated surrogate markers of long-term outcome. These included one systematic review, one randomised control trial (RCT), one case control study and 13 case series. Validated surrogate markers included Radiostereometric Analysis (RSA) and Einzel-Bild-Röntgen-Analyse (EBRA), each measuring implant migration and wear. We identified five RSA studies (one systematic review and four case series) and four EBRA studies (one RCT and three case series). Patient Reported Outcome Measures (PROMs) at six months have been investigated but have not been validated against long-term outcomes. This systematic review identified two validated surrogate markers of long-term primary THA outcome: RSA and EBRA, each measuring implant migration and wear. We recommend the consideration of RSA in the pre-market testing of new implants. EBRA can be used to investigate acetabular wear but not femoral migration. Further studies are needed to validate the use of PROMs for post-market surveillance. Cite this article: T. T. Malak, J. A. J. Broomfield, A. J. R. Palmer, S. Hopewell, A. Carr, C. Brown, D. Prieto-Alhambra, S. Glyn-Jones. Surrogate markers of long-term outcome in primary total hip arthroplasty: A systematic review. Bone Joint Res 2016 :206–214. DOI: 10.1302/2046-3758.56.2000568.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Cold Spring Harbor Laboratory
Date: 17-06-2020
DOI: 10.1101/2020.06.15.20130328
Abstract: SARS-CoV-2 is straining healthcare systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate between patients requiring hospitalization and those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision making during the pandemic. However, the model is at high risk of bias according to the Prediction model Risk Of Bias ASsessment Tool and has not been externally validated. We followed the OHDSI framework for external validation to assess the reliability of the C-19 model. We evaluated the model on two different target populations: i) 41,381 patients that have SARS-CoV-2 at an outpatient or emergency room visit and ii) 9,429,285 patients that have influenza or related symptoms during an outpatient or emergency room visit, to predict their risk of hospitalization with pneumonia during the following 0 to 30 days. In total we validated the model across a network of 14 databases spanning the US, Europe, Australia and Asia. The internal validation performance of the C-19 index was a c-statistic of 0.73 and calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data the model obtained c-statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US and South Korean datasets respectively. The calibration was poor with the model under-estimating risk. When validated on 12 datasets containing influenza patients across the OHDSI network the c-statistics ranged between 0.40-0.68. The results show that the discriminative performance of the C-19 model is low for influenza cohorts, and even worse amongst COVID-19 patients in the US, Spain and South Korea. These results suggest that C-19 should not be used to aid decision making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.
Publisher: Cold Spring Harbor Laboratory
Date: 18-09-2020
DOI: 10.1101/2020.09.15.20195545
Abstract: A plethora of medicines have been repurposed or used as adjunctive therapies for COVID-19. We characterized the utilization of medicines as prescribed in routine practice amongst patients hospitalized for COVID-19 in South Korea, China, Spain, and the USA. International network cohort Hospital electronic health records from Columbia University Irving Medical Centre (NYC, USA), Stanford (CA, USA), Tufts (MA, USA), Premier (USA), Optum EHR (USA), department of veterans affairs (USA), NFHCRD (Honghu, China) and HM Hospitals (Spain) and nationwide claims from HIRA (South Korea) patients hospitalized for COVID-19 from January to June 2020 Prescription/dispensation of any medicine on or 30 days after hospital admission date Number and percentage of users overall and over time 71,921 people were included: 304 from China, 2,089 from Spain, 7,599 from South Korea, and 61,929 from the USA. A total of 3,455 medicines were identified. Common repurposed medicines included hydroxychloroquine ( % in NFHCRD to 85.4% in HM), azithromycin (4.9% in NFHCRD to 56.5% in HM), lopinavir/ritonavir ( % in all US but 34.9% in HIRA and 56.5% in HM), and umifenovir (0% in all except 78.3% in NFHCRD). Adjunctive medicines were used with great variability, with the ten most used treatments being (in descending order): bemiparin, enoxaparin, heparin, ceftriaxone, aspirin, vitamin D, famotidine, vitamin C, dexamethasone, and metformin. Hydroxychloroquine and azithromycin increased rapidly in use in March-April but declined steeply in May-June. Multiple medicines were used in the first months of COVID-19 pandemic, with substantial geographic and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed medicines. 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. Drug repurposing is a common approach in the clinical management of novel diseases and conditions for which there are no available pharmacotherapies Hydroxychloroquine was widely used in the management of COVID-19 patients during the early phases of the pandemic Recent NIH (and other) guidelines recommend the use of concomitant therapies including immune-based, antithrombotic, antibiotic and other treatments This study demonstrates great variability and extensive drug repurposing and utilization in the management of COVID-19 patients. A wide range of adjunctive treatments has been used, including antithrombotics, antibiotics, H2 receptor antagonists, and systemic corticosteroids. Emerging clinical data on the safety and efficacy of hydroxychloroquine and azithromycin impacted their rise and rapid decline in use internationally Conversely, the use of corticosteroids grew only in more recent months, with little use in the early stages of the pandemic (January to April)
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/BMJOPEN-2020-047258
Abstract: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.
Publisher: Cold Spring Harbor Laboratory
Date: 03-09-2020
DOI: 10.1101/2020.09.02.20185173
Abstract: COVID-19 may differentially impact people with obesity. We aimed to describe and compare the demographics, comorbidities, and outcomes of obese patients with COVID-19 to those of non-obese patients with COVID-19, or obese patients with seasonal influenza. We conducted a cohort study based on outpatient/inpatient care, and claims data from January to June 2020 from the US, Spain, and the UK. We used six databases standardized to the OMOP common data model. We defined two cohorts of patients diagnosed and/or hospitalized with COVID-19. We created corresponding cohorts for patients with influenza in 2017-2018. We followed patients from index date to 30 days or death. We report the frequency of socio-demographics, prior comorbidities, and 30-days outcomes (hospitalization, events, and death) by obesity status. We included 627 044 COVID-19 (US: 502 650, Spain: 122 058, UK: 2336) and 4 549 568 influenza (US: 4 431 801, Spain: 115 224, UK: 2543) patients. The prevalence of obesity was higher among hospitalized COVID-19 (range: 38% to 54%) than diagnosed COVID-19 (30% to 47%), or diagnosed (15% to 47%) or hospitalized (27% to 48%) influenza patients. Obese hospitalized COVID-19 patients were more often female and younger than non-obese COVID-19 patients or obese influenza patients. Obese COVID-19 patients were more likely to have prior comorbidities, present with cardiovascular and respiratory events during hospitalization, require intensive services, or die compared to non-obese COVID-19 patients. Obese COVID-19 patients were more likely to require intensive services or die compared to obese influenza patients, despite presenting with fewer comorbidities. We show that obesity is more common amongst COVID-19 than influenza patients, and that obese patients present with more severe forms of COVID-19 with higher hospitalization, intensive services, and fatality than non-obese patients. These data are instrumental for guiding preventive strategies of COVID-19 infection and complications. The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, and IQVIA. The University of Oxford received funding related to this work from the Bill & Melinda Gates Foundation (Investment ID INV-016201 and INV-019257). APU has received funding from the Medical Research Council (MRC) [MR/K501256/1, MR/N013468/1] and Fundación Alfonso Martín Escudero (FAME) (APU). VINCI [VA HSR RES 13-457] (SLD, MEM, KEL). JCEL has received funding from the Medical Research Council (MR/K501256/1) and Versus Arthritis (21605). No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, Department of Veterans Affairs or the United States Government, NHS, or the Department of Health, England. Previous evidence suggests that obese in iduals are a high risk population for COVID-19 infection and complications. We searched PubMed for articles published from December 2019 until June 2020, using terms referring to SARS-CoV-2 or COVID-19 combined with terms for obesity. Few studies reported obesity and most of them were limited by small s le sizes and restricted to hospitalized patients. Further, they used different definitions for obesity (i.e. some reported together overweight and obesity, others only reported obesity with BMI kg/m 2 ). To date, no study has provided detailed information on the characteristics of obese COVID-19 patients, such as the prevalence of comorbidities or COVID-19 related outcomes. In addition, despite the fact that COVID-19 has been often compared to seasonal influenza, there are no studies assessing whether obese patients with COVID-19 differ from obese patients with seasonal influenza. We report the largest cohort of obese patients with COVID-19 and provide information on more than 29 000 aggregate characteristics publicly available. Our findings were consistent across the participating databases and countries. We found that the prevalence of obesity is higher among COVID-19 compared to seasonal influenza patients. Obese patients with COVID-19 are more commonly female and have worse outcomes than non-obese patients. Further, they have worse outcomes than obese patients with influenza, despite presenting with fewer comorbidities. Our results show that in iduals with obesity present more comorbidities and worse outcomes for COVID-19 than non-obese patients. These findings may be useful in guiding clinical practice and future preventative strategies for obese in iduals, as well as provide useful data to support subsequent association studies focussed on obesity and COVID-19.
Publisher: National Institute for Health and Care Research
Date: 11-2021
DOI: 10.3310/HTA25660
Abstract: Although routine NHS data potentially include all patients, confounding limits their use for causal inference. Methods to minimise confounding in observational studies of implantable devices are required to enable the evaluation of patients with severe systemic morbidity who are excluded from many randomised controlled trials. Stage 1 – replicate the Total or Partial Knee Arthroplasty Trial (TOPKAT), a surgical randomised controlled trial comparing unicompartmental knee replacement with total knee replacement using propensity score and instrumental variable methods. Stage 2 – compare the risk benefits and cost-effectiveness of unicompartmental knee replacement with total knee replacement surgery in patients with severe systemic morbidity who would have been ineligible for TOPKAT using the validated methods from stage 1. This was a cohort study. Data were obtained from the National Joint Registry database and linked to hospital inpatient (Hospital Episode Statistics) and patient-reported outcome data. Stage 1 – people undergoing unicompartmental knee replacement surgery or total knee replacement surgery who met the TOPKAT eligibility criteria. Stage 2 – participants with an American Society of Anesthesiologists grade of ≥ 3. The patients were exposed to either unicompartmental knee replacement surgery or total knee replacement surgery. The primary outcome measure was the postoperative Oxford Knee Score. The secondary outcome measures were 90-day postoperative complications (venous thromboembolism, myocardial infarction and prosthetic joint infection) and 5-year revision risk and mortality. The main outcome measures for the health economic analysis were health-related quality of life (EuroQol-5 Dimensions) and NHS hospital costs. In stage 1, propensity score stratification and inverse probability weighting replicated the results of TOPKAT. Propensity score adjustment, propensity score matching and instrumental variables did not. Stage 2 included 2256 unicompartmental knee replacement patients and 57,682 total knee replacement patients who had severe comorbidities, of whom 145 and 23,344 had linked Oxford Knee Scores, respectively. A statistically significant but clinically irrelevant difference favouring unicompartmental knee replacement was observed, with a mean postoperative Oxford Knee Score difference of 2 points using propensity score stratification no significant difference was observed using inverse probability weighting. Unicompartmental knee replacement more than halved the risk of venous thromboembolism [relative risk 0.33 (95% confidence interval 0.15 to 0.74) using propensity score stratification relative risk 0.39 (95% confidence interval 0.16 to 0.96) using inverse probability weighting]. Unicompartmental knee replacement was not associated with myocardial infarction or prosthetic joint infection using either method. In the long term, unicompartmental knee replacement had double the revision risk of total knee replacement [hazard ratio 2.70 (95% confidence interval 2.15 to 3.38) using propensity score stratification hazard ratio 2.60 (95% confidence interval 1.94 to 3.47) using inverse probability weighting], but half of the mortality [hazard ratio 0.52 (95% confidence interval 0.36 to 0.74) using propensity score stratification insignificant effect using inverse probability weighting]. Unicompartmental knee replacement had lower costs and higher quality-adjusted life-year gains than total knee replacement for stage 2 participants. Although some propensity score methods successfully replicated TOPKAT, unresolved confounding may have affected stage 2. Missing Oxford Knee Scores may have led to information bias. Propensity score stratification and inverse probability weighting successfully replicated TOPKAT, implying that some (but not all) propensity score methods can be used to evaluate surgical innovations and implantable medical devices using routine NHS data. Unicompartmental knee replacement was safer and more cost-effective than total knee replacement for patients with severe comorbidity and should be considered the first option for suitable patients. Further research is required to understand the performance of propensity score methods for evaluating surgical innovations and implantable devices. This trial is registered as EUPAS17435. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 66. See the NIHR Journals Library website for further project information.
Publisher: Cold Spring Harbor Laboratory
Date: 30-10-2020
DOI: 10.1101/2020.10.29.20222083
Abstract: 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. International network cohort. Real-world data from European primary care records (France/Germany/Spain), South Korean claims and US claims and hospital databases. Diagnosed and/or hospitalized children/adolescents with COVID-19 at age between January and June 2020 diagnosed with influenza in 2017-2018. 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. 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 ( %), 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 per database) 30-day fatality. Thirty-day outcomes including pneumonia, ARDS, and MIS-C were more frequent in COVID-19 than influenza. 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. Most of the early COVID-19 studies were targeted at adult patients, and data concerning children and adolescents are limited. Clinical manifestations of COVID-19 are generally milder in the pediatric population compared with adults. Hospitalization for COVID-19 affects mostly infants, toddlers, and children with pre-existing comorbidities. ⍰ This study comprehensively characterizes a large international cohort of pediatric COVID-19 patients, and almost 2 million with previous seasonal influenza across 5 countries. ⍰ Although uncommon, pneumonia, acute respiratory distress syndrome (ARDS) and multi-system inflammatory syndrome (MIS-C) were more frequent in children and adolescents diagnosed with COVID-19 than in those with seasonal influenza. ⍰ Dyspnea, bronchiolitis, anosmia and gastrointestinal symptoms were more frequent in COVID-19, and could help to differentiate pediatric COVID-19 from influenza. ⍰ A plethora of medications were used during the management of COVID-19 in children and adolescents, with great heterogeneity in the use of antiviral therapies as well as of adjunctive therapies.
Publisher: Cold Spring Harbor Laboratory
Date: 27-11-2020
DOI: 10.1101/2020.11.25.20229088
Abstract: To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). A network cohort study. 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 hospitalized with a clinical diagnosis or a positive test result for COVID-19. Dialysis, tracheostomy, and ECMO. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2020
DOI: 10.1038/S41467-020-18849-Z
Abstract: Comorbid conditions appear to be common among in iduals 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 in iduals 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 in iduals being hospitalised with COVID-19.
Publisher: Cold Spring Harbor Laboratory
Date: 12-11-2021
DOI: 10.1101/2021.11.10.21266128
Abstract: To examine temporal trends in incidence of arthroscopic subacromial decompression (ASAD) surgery internationally during conduct and after publication of placebo controlled trials finding no evidence of meaningful benefit of ASAD for shoulder impingement. Observational study of incidence rates. Large routinely collected datasets were used: outpatient data from Belgium and UK, and insurance claims and outpatient data from US. UK data were from Clinical Practice Research Datalink and Belgium and US data were from IQVIA. US and UK data spanned 2005 – 2019 and Belgium data 2011 – 2019. Patients were eligible for inclusion in the study if they had at least one visit recorded in the database in a given year and cases were defined as patients undergoing ASAD for the first time in their records in a given year. We calculated incidence of ASAD over time, overall and stratified by age and sex. Characteristics of patients undergoing ASAD were also assessed over time. UK incidence has fallen since a peak of 4.7 per 10,000 person years in 2011 (when the CSAW trial began) to 1.8 in 2019. US incidence shows no clear pattern and remains consistently higher than the UK, at 11.5 per 100,000 person years in 2019. Changes in incidence patterns were similar across different age groups and sexes. The number of cases in Belgium was too small for meaningful conclusions. We found ASAD rates have fallen in the UK during conduct and after publication of two large surgical RCTs from the UK and Finland that questioned the effectiveness of ASAD for shoulder impingement. A similar impact on clinical practice has not been seen in US. Further work to understand the barriers or concerns preventing international uptake of high quality evidence into clinical practice is needed. This is the most comprehensive study of ASAD incidence we are aware of. Routinely collected datasets were used to assess proportions of the patients undergoing this procedure in several countries Standardised case definitions were used across databases to increase comparability of findings Temporal changes in database coverage and quality of reporting can influence findings. The observed variation in ASAD incidence may not be entirely attributable to changes in ASAD surgery rates.
Publisher: BMJ
Date: 11-05-2021
DOI: 10.1136/BMJ.N1038
Abstract: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. Multinational network cohort study. Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. 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 ( %) 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 ( %) 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. 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.
Publisher: Cold Spring Harbor Laboratory
Date: 14-10-2020
DOI: 10.1101/2020.10.13.20211821
Abstract: To describe comorbidities, symptoms at presentation, medication use, and 30-day outcomes after a diagnosis of COVID-19 in pregnant women, in comparison to pregnant women with influenza. Multinational network cohort A total of 6 databases consisting of electronic medical records and claims data from France, Spain, and the United States. Pregnant women with ≥ 1 year in contributing databases, diagnosed and/or tested positive, or hospitalized with COVID-19. The influenza cohort was derived from the 2017-2018 influenza season. Baseline patient characteristics, comorbidities and presenting symptoms 30-day inpatient drug utilization, maternal complications and pregnancy-related outcomes following diagnosis/hospitalization. 8,598 women diagnosed (2,031 hospitalized) with COVID-19 were included. Hospitalized women had, compared to those diagnosed, a higher prevalence sof pre-existing comorbidities including renal impairment (2.2% diagnosed vs 5.1% hospitalized) and anemia (15.5% diagnosed vs 21.3% hospitalized). The ten most common inpatient treatments were systemic corticosteroids (29.6%), enoxaparin (24.0%), immunoglobulins (21.4%), famotidine (20.9%), azithromycin (18.1%), heparin (15.8%), ceftriaxone (7.9%), aspirin (7.0%), hydroxychloroquine (5.4%) and amoxicillin (3.5%). Compared to 27,510 women with influenza, dyspnea and anosmia were more prevalent in those with COVID-19. Women with COVID-19 had higher frequency of cesarean-section (4.4% vs 3.1%), preterm delivery (0.9% vs 0.5%), and poorer maternal outcomes: pneumonia (12.0% vs 2.7%), ARDS (4.0% vs 0.3%) and sepsis (2.1% vs 0.7%). COVID-19 fatality was negligible (N in each database respectively). Comorbidities that were more prevalent with COVID-19 hospitalization (compared to COVID-19 diagnosed) in pregnancy included renal impairment and anemia. Multiple medications were used to treat pregnant women hospitalized with COVID-19, some with little evidence of benefit. Anosmia and dyspnea were indicative symptoms of COVID-19 in pregnancy compared to influenza, and may aid differential diagnosis. Despite low fatality, pregnancy and maternal outcomes were worse in COVID-19 than influenza. Compared to non-pregnant women of reproductive age, pregnant women are less likely to experience typical COVID-19 symptoms, such as fever and myalgia. Obesity, high maternal age, and comorbid hypertension and diabetes are risk factors for severe COVID-19 among pregnant women. Despite relatively high rates of pneumonia and need for oxygen supplementation, fatality rates in pregnant women with COVID-19 are generally low ( %). Although not often recorded, dyspnea and anosmia were more often seen in pregnant women with COVID-19 than in women with seasonal influenza, in 6 databases from 3 countries (US, France, Spain). Renal impairment and anemia were more common among hospitalized than diagnosed women with COVID-19 during pregnancy. Despite limited data on benefit-risk in pregnancy, a large number of medications were used for inpatient management of COVID-19 in pregnant women: approximately 1 in 3 received corticosteroids (some may have been given for a pregnancy-related indication rather than for COVID-19 treatment), 1 in 4 enoxaparin, and 1 in 5 immunoglobulin, famotidine and azithromycin. Compared to influenza, there was a higher frequency of pregnancy-related complications (cesarean section and preterm deliveries), as well as poorer maternal outcomes (pneumonia, acute respiratory distress syndrome, sepsis, acute kidney injury, and cardiovascular and thromboembolic events) seen in pregnant women diagnosed with COVID-19.
Publisher: Cold Spring Harbor Laboratory
Date: 27-05-2020
DOI: 10.1101/2020.05.26.20112649
Abstract: 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. We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries. We developed and validated 3 scores using 6,869,127 patients with a general practice, emergency room, or outpatient visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The scores were validated on patients with confirmed or suspected COVID-19 diagnosis across five databases from South Korea, Spain and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death iii) death in the 30 days after index date. Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated 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: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration was overall acceptable. A 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and fatality. 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.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2020
Publisher: Cold Spring Harbor Laboratory
Date: 25-04-2020
DOI: 10.1101/2020.04.22.20074336
Abstract: In this study we phenotyped in iduals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared in iduals hospitalised with COVID-19 to those previously hospitalised with influenza. We report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]). These patients were then compared with patients hospitalised with influenza in 2014-19. 34,128 (US: 8,362, South Korea: 7,341, Spain: 18,425) in iduals hospitalised with COVID-19 were included. Between 4,811 (HM) and 11,643 (CUIMC) unique aggregate characteristics were extracted per patient, with all summarised in an accompanying interactive website ( evidence.ohdsi.org/Covid19CharacterizationHospitalization/ ). Patients were majority male in the US (CUIMC: 52%, PHD: 52%, UC HDC: 54%, VA OMOP: 94%,) and Spain (SIDIAP: 54%, HM: 60%), but were predominantly female in South Korea (HIRA: 60%). Age profiles varied across data sources. Prevalence of asthma ranged from 4% to 15%, diabetes from 13% to 43%, and hypertensive disorder from 24% to 70% across data sources. Between 14% and 33% were taking drugs acting on the renin-angiotensin system in the 30 days prior to hospitalisation. Compared to 81,596 in iduals hospitalised with influenza in 2014-19, patients admitted with COVID-19 were more typically male, younger, and healthier, with fewer comorbidities and lower medication use. We provide a detailed characterisation of patients hospitalised with COVID-19. Protecting groups known to be vulnerable to influenza is a useful starting point to minimize the number of hospital admissions needed for COVID-19. However, such strategies will also likely need to be broadened so as to reflect the particular characteristics of in iduals hospitalised with COVID-19.
Publisher: Cold Spring Harbor Laboratory
Date: 12-06-2020
DOI: 10.1101/2020.06.11.20125849
Abstract: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85 0.69 - 1.05) and marginally significant for mono/combination users (0.88 0.79 - 0.99). We observed, however, no significant difference between drug-classes for COVID-19 hospitalization or pneumonia risk across all comparisons. There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.
Publisher: JMIR Publications Inc.
Date: 17-06-2020
Abstract: ARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the “prediction model risk of bias assessment” criteria, and it has not been externally validated. he aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases. e followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia. he internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68. ur results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.
Publisher: The Endocrine Society
Date: 27-07-2020
Abstract: The cardiovascular (CV) safety of oral bisphosphonates (oBPs) is uncertain. Determine the risk of CV events in oBP users referred for bone mineral density (BMD) testing compared with matched controls. Cohort study. Danish national prescription registry enriched with local hospital data from Odense. In iduals aged ≥45 years referred for BMD testing. oBP. Hospitalization for any CV event. Secondary study outcomes were specific CV events. Negative (inguinal hernia surgery and ingrown toenail) and positive (fragility fracture) control outcomes assessed systemic bias. Cox proportional hazards models were fitted to estimate hazard ratio (HR) and 95% confidence intervals. There were 2565 oBP users (82.6% women) and 4568 (82.3% women) propensity score–matched controls. Alendronate accounted for 96% of oBP prescription. A total of 406 (15.8%) CV events occurred in oBP users (rate = 73.48 [66.67-80.98]) rate = events ided by person-time and 837 (18.3%) events in controls (rate = 104.73 [97.87-112.07]) with an adjusted HR of 0.68 (95% CI 0.60-0.77). Additional adjustment for BMD did not attenuate estimates (HR 0.67 95% CI 0.58-0.78]. Similar results were seen for secondary outcomes where risk reductions were seen regarding atrial fibrillation, stroke, heart failure, and aneurysms. Positive and negative control outcome analyses identified minimal residual confounding. Oral BP users experienced a 33% reduced risk of CV events. This observational real-world study adds to a growing body of evidence for cardioprotection by oBP that warrants testing in a randomized setting.
Publisher: BMJ
Date: 19-12-2013
DOI: 10.1136/BMJ.F6956
Publisher: Wiley
Date: 30-10-2018
DOI: 10.1002/PDS.4673
Abstract: The diagnosis of hip osteoarthritis is subject to several uncertainties, especially in primary care. The aims of this study were to determine (i) the diagnostic accuracy of coding of hip osteoarthritis by primary care physicians in the UK Clinical Practice Research Datalink (CPRD), (ii) the relative influence of radiographic and clinical parameters on diagnostic accuracy, and (iii) the accuracy of the diagnosis date. An extract of all patients aged over 65 years, with a Read code for hip osteoarthritis listed between January 1995 and December 2014, was obtained from CPRD. A random s le was selected of 170 participants. A questionnaire concerning data in medical records on relevant clinical and radiographic criteria used to establish the diagnosis of hip osteoarthritis was distributed to primary care physicians of participants. Using diagnostic criteria, we formulated thresholds for diagnosis based on clinical, radiographic, and combined grounds. One hundred nineteen completed questionnaires were returned (70% response rate). The positive predictive value (PPV) of hip osteoarthritis codes, based on radiological criteria, was 79.8%. The PPV, based on clinical criteria, was 79.0%, with substantial but not complete overlap. Overall 12% of diagnoses were not confirmed. In 42% of cases, there was disparity between date of diagnosis in CPRD and the medical record. Median difference in date was ±425 days (interquartile range, 18-1448 days). Despite the difficulties in reaching a diagnosis of hip osteoarthritis in primary care, CPRD Read codes have a sufficiently high PPV for most research uses. However, the accuracy of diagnosis date may not be as reliable.
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJOPEN-2020-046712
Abstract: Total hip arthroplasty (THA) surgery for elderly people with multimorbidity increases the risk of serious health hazards including mortality. Whether such background morbidity reduces the clinical benefit is less clear. To evaluate how pre-existing health status, using multiple approaches, influences risks of, and quality of life benefits from, THA. Longitudinal record linkage study of a UK s le linking their primary care to their secondary care records. A total of 6682 patients were included, based on the recording of the diagnosis of hip osteoarthritis in a national primary care register and the recording of the receipt of THA in a national secondary care register. Data were extracted from the primary care register on background health and morbidity status using five different constructs: Charlson Comorbidity Index, Electronic Frailty Index (eFI) and counts of comorbidity disorders (from list of 17), prescribed medications and number of primary care visits prior to recording of THA. (1) Postoperative complications and mortality (2) postoperative hip pain and function using the Oxford Hip Score (OHS) and health-related quality of life using the EuroQoL (EQ)-5D score. Perioperative complication rate was 3.2% and mortality was 0.9%, both increased with worse preoperative health status although this relationship varied depending on the morbidity construct: the eFI showing the strongest relationship but number of visits having no predictive value. By contrast, the benefits were not reduced in those with worse preoperative health, and improvement in both OHS and EQ-5D was observed in all the morbidity categories. Independent of preoperative morbidity, THA leads to similar substantial improvements in quality of life. These are offset by an increase in medical complications in some subgroups of patients with high morbidity, depending on the definition used. For most elderly people, their other health disorders should not be a barrier for THA.
Publisher: Wiley
Date: 18-02-2020
DOI: 10.1002/JBMR.3961
Abstract: Oral bisphosphonates (oBPs) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate-severe CKD. This study examined the association between oBPs and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an estimated glomerular filtration rate (eGFR) <45/mL/min/1.73 m
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJOPEN-2020-046713
Abstract: The median age for total hip arthroplasty (THA) is over 70 years with the corollary that many in iduals have multiple multimorbidities. Despite the predicted improvement in quality of life, THA might be denied even to those with low levels of multimorbidity. To evaluate how pre-existing levels of multimorbidity influence the likelihood and timing of THA. Longitudinal record linkage study of a UK s le linking their primary care to their secondary care records. A total of 28 025 patients were included, based on the recording of the diagnosis of hip osteoarthritis in a national primary care register, Clinical Practice Research Datalink. Data were extracted from the database on background health and morbidity status using five different constructs: Charlson Comorbidity Index, Electronic Frailty Index and counts of chronic diseases (from list of 17), prescribed medications and number of primary care visits prior to recording of osteoarthritis. The record of having received a THA as recorded in the primary care record and the linked secondary care database: Hospital Episode Statistics. 40% had THA: median follow 10 months (range 1–17 years). Increased multimorbidity was associated with a decreased likelihood of undergoing THA, irrespective of the method of assessing multimorbidity although the impact varied by approach. Markers of pre-existing ill health influence the decision for THA in the elderly with end-stage hip osteoarthritis, although these effects are modest for indices of multimorbidity other than eFI. There is evidence of this influence being present even in people with moderate decrements in their health, despite the balance of benefits to risk in these in iduals being positive.
Publisher: JMIR Publications Inc.
Date: 05-04-2021
DOI: 10.2196/21547
Abstract: SARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the “prediction model risk of bias assessment” criteria, and it has not been externally validated. The aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases. We followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia. The internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68. Our results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.
Publisher: Cold Spring Harbor Laboratory
Date: 21-07-2020
DOI: 10.1101/2020.07.17.20156059
Abstract: Concern has been raised in the rheumatological community regarding recent regulatory warnings that hydroxychloroquine used in the COVID-19 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation, or psychosis associated with hydroxychloroquine as used for rheumatoid arthritis (RA). New user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and US). RA patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine (active comparator) and followed up in the short (30-day) 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 (HR), with estimates pooled where I 2 %. 918,144 and 290,383 users of hydroxychloroquine and sulfasalazine, respectively, were included. No consistent risk of psychiatric events was observed with short-term hydroxychloroquine (compared to sulfasalazine) use, with meta-analytic HRs of 0.96 [0.79-1.16] for depression, 0.94 [0.49-1.77] for suicide/suicidal ideation, and 1.03 [0.66-1.60] for psychosis. No consistent long-term risk was seen, with meta-analytic HRs 0.94 [0.71-1.26] for depression, 0.77 [0.56-1.07] for suicide/suicidal ideation, and 0.99 [0.72-1.35] for psychosis. Hydroxychloroquine as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation, or psychosis compared to sulfasalazine. No effects were seen in the short or long term. Use at higher dose or for different indications needs further investigation. Registered with EU PAS Reference number EUPAS34497 ( www.encepp.eu/encepp/viewResource.htm?id=34498 ). The full study protocol and analysis source code can be found at hdsi-studies/Covid19EstimationHydroxychloroquine . Recent regulatory warnings have raised concerns of potential psychiatric side effects of hydroxychloroquine at the doses used to treat COVID-19, generating concern in the rheumatological community Serious psychiatric adverse events such as suicide, acute psychosis, and depressive episodes have been identified by the US Food and Drug Administration (FDA) adverse events reporting system and at case report level This is the largest study on the neuro-psychiatric safety of hydroxychloroquine to date, including ,000 users treated for their RA in country-level or private health care systems in Germany, the UK, and the US We find no association between the use of hydroxychloroquine and the risk of depression, suicide/suicidal ideation, or severe psychosis compared to sulfasalazine Our data shows no association between hydroxychloroquine treatment for RA and risk of depression, suicide or psychosis compared to sulfasalazine. These findings do not support stopping or switching hydroxychloroquine treatment as used for RA due to recent concerns based on COVID-19 treated patients.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Spain
Location: United Kingdom of Great Britain and Northern Ireland
Location: Netherlands
No related grants have been discovered for Daniel Prieto-Alhambra.