Risk of thrombotic events and other complications in anticoagulant users infected with SARS‑CoV‑2: an observational cohort study in primary health care in SIDIAP (Catalonia, Spain)

COVID-19; Anticoagulants orals; Esdeveniments trombòtics; Atenció primàriaCOVID-19; Oral anticoagulants; Thrombotic events; Primary health careCOVID-19; Anticoagulantes orales; Eventos trombóticos; Atención primariaBackground: The risk of thromboembolic events and COVID-19 complications in anticoagulated patients once hos‑ pitalized has been widely analyzed. We aim to assess these outcomes in primary health care (PHC) patients chronically treated with oral anticoagulants (OAC) in comparison with non-treated. Methods: Cohort study including adults with COVID-19 diagnosis in the PHC records in Catalonia, Spain; from March to June 2020. Patients were matched between exposed and non-exposed to OAC based on age and gender in a 1:2 design. Data source is the Information System for Research in Primary Care (SIDIAP). Results: We included 311,542 individuals with COVID-19. After propensity score matching, we obtained a cohort of 20,360 people, 10,180 exposed and 10,180 non-exposed to OAC. Their mean age was 79.9 and 52.1% were women. Patients exposed to OAC had a higher frequency of comorbidities than non-exposed. Anticoagulated patients had a higher risk of hospital admission (IRR 1.16, 95% CI 1.03–1.29), and of stroke and pulmonary embolism than nonanticoagulated (IRR 1,80, 95% CI 1.06–3.06). The risk of pneumonia was not diferent between groups (IRR 1.04, 95% CI 0.84–1.30). We found a lower risk of death in patients exposed to OAC (IRR 0.60, 95% CI 0.55–0.65). Conclusions: OAC users in our study had more comorbidities and were older than non-users, well known risks for hospitalization being confrmed with our results. We also found in our study that OAC exposure was not associated to an increased risk in the mortality rate, and it was associated with higher risks of hospital admission and thrombo‑ embolic events, although we cannot assess the efect of the interventions applied during hospital admission on the outcomes studied, as our database is a PHC database

Sex and gender differences in the use of oral anticoagulants for non-valvular atrial fibrillation: A population-based cohort study in primary health care in Catalonia

Objectives: To describe the sex and gender differences in the treatment initiation and in the socio-demographic and clinical characteristics of all patients initiating and oral anticoagulant (OAC), and the sex and gender differences in prescribed doses and adherence and persistence to the treatment of those receiving direct oral anticoagulants (DOAC). Material and methods: Cohort study including patients with non-valvular atrial fibrillation (NVAF) who initiated OAC in 2011-2020. Data proceed from SIDIAP, Information System for Research in Primary Care, in Catalonia, Spain. Results: 123,250 people initiated OAC, 46.9% women and 53.1% men. Women were older and the clinical characteristics differed between genders. Women had higher risk of stroke than men at baseline, were more frequently underdosed with DOAC and discontinued the DOAC less frequently than men. Conclusion: We described the dose adequacy of patients receiving DOAC, finding a high frequency of underdosing, and significantly higher in women in comparison with men. Adherence was generally high, only with higher levels in women for rivaroxaban. Persistence during the first year of treatment was also high in general, being significantly more persistent women than men in the case of dabigatran and edoxaban. Dose inadequacy, lack of adherence and of persistence can result in less effective and safe treatments. It is necessary to conduct studies analysing sex and gender differences in health and disease

Automatic Estimation of the Most Likely Drug Combination in Electronic Health Records Using the Smooth Algorithm: Development and Validation Study

Electronic health records; Data mining; Drug combinationRegistres sanitaris electrònics; Mineria de dades; Combinació de fàrmacsRegistros electrónicos de salud; Procesamiento de datos; Combinación de fármacosBackground: Since the use of electronic health records (EHRs) in an automated way, pharmacovigilance or pharmacoepidemiology studies have been used to characterize the therapy using different algorithms. Although progress has been made in this area for monotherapy, with combinations of 2 or more drugs the challenge to characterize the treatment increases significantly, and more research is needed. Objective: The goal of the research was to develop and describe a novel algorithm that automatically returns the most likely therapy of one drug or combinations of 2 or more drugs over time. Methods: We used the Information System for Research in Primary Care as our reference EHR platform for the smooth algorithm development. The algorithm was inspired by statistical methods based on moving averages and depends on a parameter Wt, a flexible window that determines the level of smoothing. The effect of Wt was evaluated in a simulation study on the same data set with different window lengths. To understand the algorithm performance in a clinical or pharmacological perspective, we conducted a validation study. We designed 4 pharmacological scenarios and asked 4 independent professionals to compare a traditional method against the smooth algorithm. Data from the simulation and validation studies were then analyzed. Results: The Wt parameter had an impact over the raw data. As we increased the window length, more patient were modified and the number of smoothed patients augmented, although we rarely observed changes of more than 5% of the total data. In the validation study, significant differences were obtained in the performance of the smooth algorithm over the traditional method. These differences were consistent across pharmacological scenarios. Conclusions: The smooth algorithm is an automated approach that standardizes, simplifies, and improves data processing in drug exposition studies using EHRs. This algorithm can be generalized to almost any pharmacological medication and model the drug exposure to facilitate the detection of treatment switches, discontinuations, and terminations throughout the study period

Effectiveness and safety of oral anticoagulants for non-valvular atrial fibrillation: a population-based cohort study in primary healthcare in Catalonia

Oral anticoagulants; Atrial fibrillation; Primary healthcareAnticoagulants orals; Fibril·lació auricular; Atenció primària de salutAnticoagulantes orales; Fibrilación auricular; Atención primaria de saludObjectives: Our objective was to analyse effectiveness and safety of oral anticoagulants (OAC) for stroke prevention in non-valvular atrial fibrillation. Material and methods: Population-based cohort study including adults initiating oral anticoagulants, either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA), during 2011–2020. Data source: SIDIAP, capturing information from the electronic health records of Primary Health Care in Catalonia, Spain. Study outcomes: stroke, cerebral and gastrointestinal (GI) haemorrhage, assessed by patients’ subgroups according to different clinical characteristics. Results: We included 90,773 patients. Male sex, older than 75, previous event, peripheral artery disease, deep vein thrombosis, or receiving antiplatelets, antidiabetics or proton pump inhibitors (PPI) was associated with higher stroke risk. For DOAC-treated, treatment switch increased stroke risk, while being adherent had a protective effect. Men, antidiabetic treatment or a previous event increased the risk of cerebral bleeding. Receiving direct oral anticoagulants had a protective effect in comparison to vitamin K antagonists. For DOAC-treated, treatment switch increased, and adherence decreased the bleeding risk. Men, people with chronic kidney disease or a previous event posed an increased risk of gastrointestinal bleeding, whereas receiving PPI had a protective effect. For DOAC-treated, switch was associated with a higher bleeding risk. Conclusion: Being men, a previous event and DOAC-switch posed a higher risk for all study outcomes. direct oral anticoagulants had a protective effect against cerebral bleeding in comparison to vitamin K antagonists. Adherence to direct oral anticoagulants resulted in lower risk of stroke and cerebral bleeding. We found no differences in the risk of stroke and gastrointestinal bleeding when we compared direct oral anticoagulants vs. vitamin K antagonists

Sex and gender differences in the use of oral anticoagulants for non-valvular atrial fibrillation: a population-based cohort study in primary health care in Catalonia

Oral anticoagulants; Atrial fibrillation; Gender differencesAnticoagulants orals; Fibril·lació auricular; Diferències de gènereAnticoagulantes orales; Fibrilación auricular; Diferencias de géneroObjectives: To describe the sex and gender differences in the treatment initiation and in the socio-demographic and clinical characteristics of all patients initiating an oral anticoagulant (OAC), and the sex and gender differences in prescribed doses and adherence and persistence to the treatment of those receiving direct oral anticoagulants (DOAC). Material and methods: Cohort study including patients with non-valvular atrial fibrillation (NVAF) who initiated OAC in 2011–2020. Data proceed from SIDIAP, Information System for Research in Primary Care, in Catalonia, Spain. Results: 123,250 people initiated OAC, 46.9% women and 53.1% men. Women were older and the clinical characteristics differed between genders. Women had higher risk of stroke than men at baseline, were more frequently underdosed with DOAC and discontinued the DOAC less frequently than men. Conclusion: We described the dose adequacy of patients receiving DOAC, finding a high frequency of underdosing, and significantly higher in women in comparison with men. Adherence was generally high, only with higher levels in women for rivaroxaban. Persistence during the first year of treatment was also high in general, being significantly more persistent women than men in the case of dabigatran and edoxaban. Dose inadequacy, lack of adherence and of persistence can result in less effective and safe treatments. It is necessary to conduct studies analysing sex and gender differences in health and disease

Diagnostic and Therapeutic Management of Urinary Tract Infections in Catalonia, Spain: Protocol for an Observational Cohort Study

Urinary tract infection; Primary health care; Anti-bacterial agentsInfecció del tracte urinari; Atenció primària de salut; Agents antibacteriansInfección del tracto urinario; Atención primaria de salud; Agentes antibacterianosBackground: Antibiotic resistance is an individual and public health problem; multidrug-resistant infections could cause an estimated 10 million deaths worldwide by 2050. Unnecessary use of antimicrobials is the most important cause of resistance generation in the community, and an estimated 80% of antimicrobials are prescribed in primary health care, frequently for urinary tract infections (UTIs). Objective: This paper presents the protocol for the first phase of the Urinary Tract Infections in Catalonia (Infeccions del tracte urinari a Catalunya) project. We aim to examine the epidemiology of the different types of UTIs in Catalonia (an autonomous community in Spain) and their diagnostic and therapeutic management by health professionals. Furthermore, we aim to evaluate the correlation between types and total consumption of antibiotics for recurrent UTIs in 2 cohorts of women with the presence and severity of infectious complications of urological origin, especially pyelonephritis and sepsis, and 2 potentially serious infections: pneumonia and COVID-19. Methods: The study is a population-based observational cohort study including adults with a diagnosis of UTI registered in the Information System for the Development of Research in Primary Care (in Catalan: Sistema d’informació per al desenvolupament de la investigació en atenció primària), the Minimum Basic Data Sets of Hospital Discharges and Emergency Departments (in Catalan: Conjunt mínim bàsic de dades a l’hospitalització d'aguts i d’atenció urgent), and data from the Hospital Dispensing Medicines Register (in Catalan: Medicació hospitalària de dispensació ambulatòria) of Catalonia from the period between 2012 and 2021. We will evaluate the variables obtained from the databases to analyze the proportion of different types of UTIs, the percentage of adequate antibiotic treatments prescribed or received for recurrent UTIs according to the national guidelines, and the proportion of UTIs with complications. Results: We expect to describe the epidemiology of UTIs in Catalonia from 2012 to 2021, as well as describe the diagnostic and therapeutic management of UTIs by health professionals. Conclusions: We expect to find a high percentage of UTI cases with inadequate management according to the national guidelines, considering that on many occasions UTIs are treated with second- or third-line antibiotic therapies with a preference for the longest regimens. Furthermore, the use of antibiotic suppressive therapies, or prophylaxis, in recurrent UTIs will likely be highly variable. Moreover, we aim to determine whether women with recurrent UTIs treated with antibiotic suppressive therapies have a higher incidence and severity of potentially serious future infections, with special attention to acute pyelonephritis, urosepsis, COVID-19, and pneumonia, compared to women who receive antibiotic treatment after they present with a UTI. This is an observational study of data from administrative databases that will not allow causality analysis. The limitations of the study will be handled according to the appropriate statistical methods

Outcomes of COVID-19 Infection in People Previously Vaccinated Against Influenza: Population-Based Cohort Study Using Primary Health Care Electronic Records

COVID-19; SARS-CoV-2; Electronic health records; Influenza vaccines; Primary health careCOVID-19; SARS-CoV-2; Registres sanitaris electrònics; Vacunes contra la grip; Atenció primària de salutCOVID-19; SARS-CoV-2; Registros de salud electrónicos; Vacunas contra la gripe; Atención primaria de saludBackground: A possible link between influenza immunization and susceptibility to the complications of COVID-19 infection has been previously suggested owing to a boost in the immunity against SARS-CoV-2. Objective: This study aimed to investigate whether individuals with COVID-19 could have benefited from vaccination against influenza. We hypothesized that the immunity resulting from the previous influenza vaccination would boost part of the immunity against SARS-CoV-2. Methods: We performed a population-based cohort study including all patients with COVID-19 with registered entries in the primary health care (PHC) electronic records during the first wave of the COVID-19 pandemic (March 1 to June 30, 2020) in Catalonia, Spain. We compared individuals who took an influenza vaccine before being infected with COVID-19, with those who had not taken one. Data were obtained from Information System for Research in Primary Care, capturing PHC information of 5.8 million people from Catalonia. The main outcomes assessed during follow-up were a diagnosis of pneumonia, hospital admission, and mortality. Results: We included 309,039 individuals with COVID-19 and compared them on the basis of their influenza immunization status, with 114,181 (36.9%) having been vaccinated at least once and 194,858 (63.1%) having never been vaccinated. In total, 21,721 (19%) vaccinated individuals and 11,000 (5.7%) unvaccinated individuals had at least one of their outcomes assessed. Those vaccinated against influenza at any time (odds ratio [OR] 1.14, 95% CI 1.10-1.19), recently (OR 1.13, 95% CI 1.10-1.18), or recurrently (OR 1.10, 95% CI 1.05-1.15) before being infected with COVID-19 had a higher risk of presenting at least one of the outcomes than did unvaccinated individuals. When we excluded people living in long-term care facilities, the results were similar. Conclusions: We could not establish a protective role of the immunity conferred by the influenza vaccine on the outcomes of COVID-19 infection, as the risk of COVID-19 complications was higher in vaccinated than in unvaccinated individuals. Our results correspond to the first wave of the COVID-19 pandemic, where more complications and mortalities due to COVID-19 had occurred. Despite that, our study adds more evidence for the analysis of a possible link between the quality of immunity and COVID-19 outcomes, particularly in the PHC setting

Stellar Properties of z ~ 8 Galaxies in the Reionization Lensing Cluster Survey

Measurements of stellar properties of galaxies when the universe was less than one billion years old yield some of the only observational constraints of the onset of star formation. We present here the inclusion of \textit{Spitzer}/IRAC imaging in the spectral energy distribution fitting of the seven highest-redshift galaxy candidates selected from the \emph{Hubble Space Telescope} imaging of the Reionization Lensing Cluster Survey (RELICS). We find that for 6/8 \textit{HST}-selected $z\gtrsim8$ sources, the $z\gtrsim8$ solutions are still strongly preferred over $z\sim$1-2 solutions after the inclusion of \textit{Spitzer} fluxes, and two prefer a $z\sim 7$ solution, which we defer to a later analysis. We find a wide range of intrinsic stellar masses ($5\times10^6 M_{\odot}$ -- $4\times10^9$ $M_{\odot}$), star formation rates (0.2-14 $M_{\odot}\rm yr^{-1}$), and ages (30-600 Myr) among our sample. Of particular interest is Abell1763-1434, which shows evidence of an evolved stellar population at $z\sim8$, implying its first generation of star formation occurred just $< 100$ Myr after the Big Bang. SPT0615-JD, a spatially resolved $z\sim10$ candidate, remains at its high redshift, supported by deep \textit{Spitzer}/IRAC data, and also shows some evidence for an evolved stellar population. Even with the lensed, bright apparent magnitudes of these $z \gtrsim 8$ candidates (H = 26.1-27.8 AB mag), only the \textit{James Webb Space Telescope} will be able further confirm the presence of evolved stellar populations early in the universe.Comment: 8 pages, 3 figures, 2 table

z~7 galaxy candidates from NICMOS observations over the HDF South and the CDF-S and HDF-N GOODS fields

We use ~88 arcmin**2 of deep (>~26.5 mag at 5 sigma) NICMOS data over the two GOODS fields and the HDF South to conduct a search for bright z>~7 galaxy candidates. This search takes advantage of an efficient preselection over 58 arcmin**2 of NICMOS H-band data where only plausible z>~7 candidates are followed up with NICMOS J-band observations. ~248 arcmin**2 of deep ground-based near-infrared data (>~25.5 mag, 5 sigma) is also considered in the search. In total, we report 15 z-dropout candidates over this area -- 7 of which are new to these search fields. Two possible z~9 J-dropout candidates are also found, but seem unlikely to correspond to z~9 galaxies. The present z~9 search is used to set upper limits on the prevalence of such sources. Rigorous testing is undertaken to establish the level of contamination of our selections by photometric scatter, low mass stars, supernovae (SNe), and spurious sources. The estimated contamination rate of our z~7 selection is ~24%. Through careful simulations, the effective volume available to our z>~7 selections is estimated and used to establish constraints on the volume density of luminous (L*(z=3), or -21 mag) galaxies from these searches. We find that the volume density of luminous star-forming galaxies at z~7 is 13_{-5}^{+8}x lower than at z~4 and >25x lower (1 sigma) at z~9 than at z~4. This is the most stringent constraint yet available on the volume density of >~L* galaxies at z~9. The present wide-area, multi-field search limits cosmic variance to <20%. The evolution we find at the bright end of the UV LF is similar to that found from recent Subaru Suprime-Cam, HAWK-I or ERS WFC3/IR searches. The present paper also includes a complete summary of our final z~7 z-dropout sample (18 candidates) identified from all NICMOS observations to date (over the two GOODS fields, the HUDF, galaxy clusters).Comment: 13 pages, 6 figures, 6 tables, accepted for publication in the Astrophysical Journal, replaced to match accepted version, see http://firstgalaxies.org/astronomers-area/ for a link to a complete reduction of the NICMOS observations over the two GOODS field

HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen

Background. The objective of this study was to quantify human immunodeficiency virus (HIV) type 1 RNA decay and dolutegravir (DTG) concentrations in the semen of HIV-infected patients receiving DTG-based first-line therapy