Drug Exposure During Pregnancy: A Case-Control Study from a Primary Care Database.

Objective: Drug exposure during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. We used available electronic health records (EHRs) to describe the use of medications during the first trimester in pregnant women and to compare drug exposure between those women who had an abortion (either elective or spontaneous) compared to those who had live births. Materials and Methods: Case-control study of abortions, either elective or spontaneous (cases), and live birth pregnancies (controls) in Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (Catalan Primary Health electronic health records) from 2012 to 2020. Exposure to drugs during first trimester of pregnancy was considered to estimate the association with abortion by conditional logistic regression and adjusted by health conditions and other drugs exposure. Results: Sixty thousand three hundred fifty episodes of abortions were matched to 118,085 live birth pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs. 7.2%, p < 0.001), smoking (4.5% vs. 3.6%, p < 0.001), and previous abortions (9.9% vs. 7.8%, p < 0.001). Anxiety (30.3% and 25.1%, p < 0.001), respiratory diseases (10.6% and 9.2%, p < 0.001), and migraine (8.2% and 7.3%, p < 0.001), for cases and controls, respectively, were the most frequent baseline conditions. Cases had lower rate of drug exposure, 40,148 (66.5%) versus 80,449 (68.1%), p < 0.001. Association with abortion was found for systemic antihistamines (adjusted odds ratio [ORadj] 1.23, 95% confidence interval [CI] 1.19-1.27), antidepressants (ORadj 1.11, 95% CI 1.06-1.17), anxiolytics (ORadj 1.31, 95% CI 1.26-1.73), and nonsteroidal anti-inflammatory drugs (ORadj 1. 63, 95% CI 1.59-1.67). Conclusions: These high rates of drug exposures during the first trimester of pregnancy highlights the relevance of informed prescription to women with childbearing potential.

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

Objectives: 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.

Drug exposure during pregnancy in primary care: an algorithm and observational study from SIDIAP database, Catalunya, Spain.

OBJECTIVES: To develop an algorithm to identify pregnancy episodes in women at childbearing age using SIDIAP (Information System for the Improvement of Research in Primary Care) data (Catalunya, Spain).To describe drugs dispensed during gestation. DESIGN: Construction of an algorithm to identify all pregnancy episodes occurred from January 2011 to June 2020 in women aged 12-50. The variables used to create the algorithm include first day of last menstrual period, reasons for pregnancy termination and diagnoses registered in the primary healthcare records. Population-based cohort study including the pregnancy episodes identified by the algorithm. SETTING: Catalonia, Spain. PARTICIPANTS: All women aged 12-50 with at least one pregnancy episode occurred during January 2011-June 2020. INTERVENTIONS: No interventions performed. PRIMARY AND SECONDARY OUTCOME MEASURES: Identification of pregnancy episodes through an algorithm and description of drug exposure. RESULTS: We identified 327 865 pregnancy episodes in 250 910 people with a mean age of 31.3 years. During the study period, 83.4% of the episodes were exposed to at least one drug. The most frequent groups dispensed were iron preparations (48% of pregnancy episodes), iodine therapy (40.2%), analgesics and antipyretics (28%), penicillins (19.8%), vitamin B12 plus folic acid (19.7%) and non-steroidal anti-inflammatory drugs (NSAIDs, 15.1%). The supplements were more frequently dispensed at least twice, and the drugs for acute conditions were mainly dispensed only once during the pregnancy episode. CONCLUSIONS: We developed an algorithm to automatically identify the pregnancy periods in SIDIAP.We described prescription drugs used during pregnancy. The most used ones were supplements, analgesics, NSAID or antibiotics.SIDIAP might be an efficient database to study drug safety during pregnancy and the consequences of drug use in the offspring. TRIAL REGISTRATION NUMBER: EUPAS37675.

Risk of partial school closure for COVID-19 by socio-economic level in the period 2020-22.

BACKGROUND: The objective was to analyse the risk of partial school closure by economic level in Barcelona city. METHODS: In this ecological study, the risk of partial school closure for the academic years 2020-21 and 2021-22 was estimated by dividing the total number of days that each child was in quarantine or isolation by the total number of days that each child was at risk to be in quarantine or isolation in the academic year. The association between partial school closure risk and mean income by district was estimated with the Spearman rho. RESULTS: The lower the mean income, the higher the risk of partial closure (Spearman rho = 0.83; P-value = 0.003) during the academic year 2020-21. Specifically, the children from the district with the lowest income had a six times greater risk of partial school closure compared with those from the highest-income district. This risk did not show a significant socioeconomic gradient in the academic year 2021-22. CONCLUSIONS: The risk of partial school closure presented an inverse socioeconomic gradient in the city of Barcelona according to average income by district in the academic year 2020-21. This distribution was not observed in the academic year 2021-22.

Longitudinal treatment patterns in patients recently diagnosed with type 2 diabetes mellitus in Catalonia.

AIM: To investigate initial and subsequent treatments prescribed to newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: Data from SIDIAP (Information System for Research in Primary Care) including all recorded incident T2DM patients in primary care between 2015 and 2020. We used descriptive statistics and different graphical techniques to describe the most frequent longitudinal patterns. RESULTS: A total of 86,854 patients were included. 78.3 % of the patients began treatment with a single metformin medication and 21.7 % began with a combination therapy (CT). Metformin was the most frequent treatment as first and third-line therapy, while the CT of metformin with DPP4i or sulfonylurea was more prevalent as second-line. Most common first to third-line pattern was initial metformin for 15 months, adding a second antidiabetic in the second line, staying in CT for 6 months, and switching back to single metformin. Treatment patterns varied depending on HbA1c levels, with higher levels (>8 %) being associated with changes to CT and lower levels with switches to monotherapy or temporary discontinuation. CONCLUSION: The study described in detail the different treatment patterns in incident T2DM patients in Catalonia, its adherence to the guidelines, and how the changes are associated to the HbA1c dynamics.

Impact of Second-Line Combination Treatment for Type 2 Diabetes Mellitus on Disease Control: A Population-Based Cohort Study.

BACKGROUND: Type 2 diabetes mellitus is a chronic disease affecting millions of people worldwide. Achieving and maintaining glycemic control is essential to prevent or delay complications and different strategies are available as second-line treatment options for patients with type 2 diabetes who do not achieve glycemic control with metformin monotherapy. OBJECTIVE: The aim of this work is to describe the impact of initiating a combination treatment to reduce glycated hemoglobin in patients with type 2 diabetes with insufficient glycemic control. METHODS: We included patients with a type 2 diabetes diagnosis between 2015 and 2020 at the Information System for Research in Primary Care (SIDIAP) database in Catalonia, Spain. The primary outcome was the time to glycated hemoglobin control (≤ 7%) during the first 720 days, expressed as the restricted mean survival time. Adjusted differences of the restricted mean survival time were compared to analyze the performance of each treatment versus the combination with a sulfonylurea. Adherence was calculated as the medication possession ratio using an algorithm to model treatment exposure. RESULTS: A total of 28,425 patients were analyzed. The most frequent combinations were those with sulfonylureas and dipeptidyl peptidase-4 inhibitors. All treatments reduced glycated hemoglobin and the restricted mean survival time for the sulfonylurea treatment was 455 (451-459) days although combinations with glucagon-like peptide-1 and insulin reached glycemic control earlier, - 126 days (- 152 to - 100, p < 0.001) and - 69 days (- 88 to - 50, p < 0.001), respectively. Adherence was high in all groups apart from the insulin combination and had a significant effect in reducing glycated hemoglobin except in sodium-glucose cotransporter type 2 inhibitors and insulin. Glucagon-like peptide-1 and sodium-glucose cotransporter type 2 inhibitors showed significant reductions in weight. CONCLUSIONS: Patients achieved the glycated hemoglobin goal with second-line treatments. Glucagon-like peptide-1 and insulin combinations achieved the goal earlier than sulfonylurea combinations. Adherence significantly reduced the time to glycated hemoglobin control except for the combination with sodium-glucose cotransporter type 2 inhibitors.

Atherosclerosis, Cardiovascular Disease, and COVID-19: A Narrative Review.

Atherosclerosis is a chronic inflammatory and degenerative process that mainly occurs in large- and medium-sized arteries and is morphologically characterized by asymmetric focal thickenings of the innermost layer of the artery, the intima. This process is the basis of cardiovascular diseases (CVDs), the most common cause of death worldwide. Some studies suggest a bidirectional link between atherosclerosis and the consequent CVD with COVID-19. The aims of this narrative review are (1) to provide an overview of the most recent studies that point out a bidirectional relation between COVID-19 and atherosclerosis and (2) to summarize the impact of cardiovascular drugs on COVID-19 outcomes. A growing body of evidence shows that COVID-19 prognosis in individuals with CVD is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with CVD after COVID-19. The most common treatments for CVD may influence COVID-19 outcomes. Thus, their implication in the infection process is briefly discussed in this review. A better understanding of the link among atherosclerosis, CVD, and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.

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 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.

Risk of psychiatric events in women treated with isotretinoin: a self-controlled study with SIDIAP database.

BACKGROUND: Since isotretinoin marketing, reports of psychiatric events have been noted. Howeverto date, a relation between these events and acne or isotretinoin treatment has not been clearly established. Our objective was to analyze the incidence of psychiatric events in women receiving isotretinoin. METHODS: Self-controlled study including women treated with isotretinoin from July 2014 to December 2018. Data source was SIDIAP, a primary health care-based database from Catalonia, Spain. Risk of psychiatric events was analyzed during the isotretinoin exposure and during the previous and posterior periods of non-exposure. RESULTS: We included 4,738 women in the study, 25.3% of them had history psychiatric disorders prior to receiving isotretinoin. During the follow-up, 782 (16.5%) patients were diagnosed with new mental disorders and 925 (19.5%) received new psychotropic drug prescriptions. We found a trend to an increase of new events when the previous non-exposure and the isotretinoin exposure periods were compared, with no significant differences. Incident psychiatric events during isotretinoin exposure was significantly higher in those patients with previous psychiatric history. CONCLUSIONS: We cannot conclude any causality between acne and isotretinoin and the appearance of new psychiatric events. However, we contribute to the evidence with a more robust methodological approach, which minimizes the effect of confounding variables.

Antidiabetic treatment and COVID-19 Outcomes: A population-based cohort study in primary health care in Catalonia during the first wave of the pandemic.

AIMS: To analyse if antidiabetic treatment was associated with better COVID-19 outcomes in type 2 diabetic patients, measured by hospital admission and mortality rates as severe outcomes. METHODS: Cohort study including COVID-19 patients registered in the Primary Care electronic records, in March-June 2020, comparing exposed to metformin in monotherapy with exposed to any other antidiabetic. DATA SOURCE: SIDIAP (Information System for Research in Primary Care), which captures clinical information of 5,8 million people from Catalonia, Spain. RESULTS: We included 31,006 diabetic patients infected with COVID-19, 43.7% previously exposed to metformin, 45.5% of them in monotherapy. 16.4% were admitted to hospital and 15.1% died. Users of insulin in monotherapy (OR 1.29, 95% CI 1.11-1.50), combined with metformin (OR 1.38, 1.13-1.69) or IDPP4 alone (OR 1.29, 1.03-1.63) had higher risk of severe outcomes than those in metformin monotherapy. Users of any insulin (OR 1.61, 1.32-1.97) or combined with metformin (OR 1.69, 1.30-2.20) had a higher risk of mortality. CONCLUSIONS: Patients receiving metformin monotherapy in our study showed a lower risk of hospitalization and death in comparison to those treated with other frequent antidiabetic agents. We cannot distinguish if better outcomes are related with the antidiabetic therapy or with other factors, such as metabolic control or interventions applied during the hospital admission.

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

BACKGROUND: 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.

Type 2 Diabetes Mellitus and COVID-19: A Narrative Review.

Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder. The incidence and prevalence of patients with T2DM are increasing worldwide, even reaching epidemic values in most high- and middle-income countries. T2DM could be a risk factor of developing complications in other diseases. Indeed, some studies suggest a bidirectional interaction between T2DM and COVID-19. A growing body of evidence shows that COVID-19 prognosis in individuals with T2DM is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with T2DM after SARS-CoV-2 infection. The most common treatments for T2DM may influence SARS-CoV-2 and their implication in infection is briefly discussed in this review. A better understanding of the link between TD2M and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.

Initiation and Single Dispensing in Cardiovascular and Insulin Medications: Prevalence and Explanatory Factors.

BACKGROUND: Adherence problems have negative effects on health, but there is little information on the magnitude of non-initiation and single dispensing. OBJECTIVE: The aim of this study was to estimate the prevalence of non-initiation and single dispensation and identify associated predictive factors for the main treatments prescribed in Primary Care (PC) for cardiovascular disease (CVD) and diabetes. METHODS: Cohort study with real-world data. Patients who received a first prescription (2013-2014) for insulins, platelet aggregation inhibitors, angiotensin-converting enzyme inhibitors (ACEI) or statins in Catalan PC were included. The prevalence of non-initiation and single dispensation was calculated. Factors that explained these behaviours were explored. RESULTS: At three months, between 5.7% (ACEI) and 9.1% (antiplatelets) of patients did not initiate their treatment and between 10.6% (statins) and 18.4% (ACEI) filled a single prescription. Body mass index, previous CVD, place of origin and having a substitute prescriber, among others, influenced the risk of non-initiation and single dispensation. CONCLUSIONS: The prevalence of non-initiation and single dispensation of CVD medications and insulin prescribed in PC in is high. Patient and health-system factors, such as place of origin and type of prescriber, should be taken into consideration when prescribing new medications for CVD and diabetes.