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Purpose To validate COVID-19 information records in The Pharmacoepidemiological Research Database for Public Health System (BIFAP) of Spain. Methods The recorded COVID-19 cases in primary care or positive test registries (gold-standard) were identified among vaccinated patients against COVID-19 infection and their matched unvaccinated controls, between December 2020 and October 2021. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were estimated for primary care records. Results Among 21,702 patients with positive tests and 20,866 with recorded COVID-19 diagnoses, the sensitivity, specificity, PPV and NPV were, respectively, 79.98 percent, 99.95 percent, 80.24 percent, and 99.94 percent among vaccinated, and 78.67 percent, 99.96 percent, 84.51 percent and 99.94 percent among controls. Conclusions Primary care COVID-19 diagnosis recorded in BIFAP showed that sensitivity was similar and PPV was slightly lower among vaccinated than unvaccinated controls. Among the elderly, COVID-19 diagnosis was less recorded. These findings permit the design of informed algorithms for performing COVID-19-related studies. [ABSTRACT FROM AUTHOR]

Background Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown. Methods We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18–64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan–Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021. Results In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2–66.4%) 7–34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1–69.9%) for mRNA-1273 and 52.0% (41.8–63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4–89.9%), 66.1% (54.9–77.5%), and 60.2% (55.5–64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (−55.3% to 81.1%). Conclusions Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant. [ABSTRACT FROM AUTHOR]

Objective: To establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada. Methods: A retrospective cohort study was performed according to a similar protocol. First‐users of VKAs or DOACs with a diagnosis of non‐valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time‐dependant way. Risk estimates were pooled using a random effect model. Results: 421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96). Conclusions: This study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs. [ABSTRACT FROM AUTHOR]

• The incidence of Guillain-Barré was 5.4–6.5/106 girl-years in Spain in 2002–2016. • Incidence peaked during the last period of the study (2007–2016) with 11 GBS cases. • Out of 11 GBS cases, 4 (36%) reported infections as the potential triggers. • 3 cases were vaccinated against papillomavirus ever before (7.87/106 girl-years) • The adjusted risk of GBS after HPV vaccination was not different from non-exposed. Studies of the association of Guillain-Barré Syndrome (GBS) with papillomavirus vaccination (HPVv; scheduled from 2007) have provided contradicting results, probably due to the low frequency of this disease. We aimed at estimating that risk relative to non-vaccination among girls, by using the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP). A cohort study of girls aged 9–18 years during 2007–2016 free of GBS or HPVv was selected and followed up to GBS diagnosis. Follow-up time was divided by time-varying HPVv exposure and confounders. Crude Incidence rates (IR per 1,000,000 person-years (py)) and adjusted Hazard Ratios (HR) of GBS were estimated anytime after vaccination compared to non-exposed periods. HRs were also estimated for the first 90 days after HPVv (risk-window) and thereafter. Out of 388,849 girls, of which 154,255 were vaccinated, 6 'confirmed' GBS cases occurred during non-exposure periods (IR of 5.83 per million person-years; 95% CI: 2.62–12.97) and 3 'confirmed' cases anytime after vaccination (IR of 7.87; 95% CI: 2.54–24.39). The resulting adjusted HR anytime after vaccination was 1.24 (95% CI: 0.19–8.00). All three cases occurred after the risk window of 90 days with an HR of 1.77 (95% CI: 0.25–12.54) for post-exposure periods as compared with non-exposure. Since zero cases occurred during the risk window, no HR could be estimated for exposed periods. Incidences of GBS were in line with the range previously reported for young people, supporting the potential of BIFAP for performing studies on GBS. However, a lack of power may be present for quantifying the relative risk of such a rare disease after the vaccination among the study cohort, where we can only exclude an increased risk of 8-times relative to no vaccination. [ABSTRACT FROM AUTHOR]

Objective: As for other auto-immune processes, thyroiditis is monitored after vaccinations. The aim was to estimate the baseline incidence of thyroiditis among girls, before investigating papillomavirus vaccination as a potential risk factor. Methods: Observational cohort study including girls aged 9-18 years and registered between 2002-2016 in the Spanish Primary Care Database for Pharmacoepidemiological Research. Girls were followed until a thyroiditis occurred, 19 years of age, left the cohort, died, or the study ended. Anonymized records were reviewed for diagnosis confirmation (endocrine discharge letter and/or free-text comments) in a random sample. Incidence rate (IR) per 105 person years (/105 py) was estimated. Results: The cohort numbered 480,169 girls, of whom 641 had a record of thyroiditis: 346 autoimmune thyroiditis; 17 thyroiditis of other types; and 278 unspecified. Incidence of recorded thyroiditis increased with age, from 23.96 at age 9 years to 47.91 at age 14 years, and stabilized around 31.06-34.43 among girls aged 15-18 years. Of the 98 records reviewed, 60.2% were 'confirmed' cases, 32.7% 'possible' and 7.1% were discarded. After correction for discarded cases, IR=20.83 'confirmed' cases, increasing to 32.12/105 py when 'confirmed' plus 'possible' cases were included. Between 2002-2005, incidences were lower (16.28 and 20.93 cases/105 py) than in the period 2007-2016 (21.17 and 33.78 cases/105 py) for 'confirmed' and 'confirmed' plus 'possible', respectively. Conclusion: Two-thirds of the recorded thyroiditis included confirmatory evidence. The incidence of thyroiditis among girls increased with age and in the later period, and remained stable among girls aged 15-18 years. [ABSTRACT FROM AUTHOR]

Purpose Inflammatory bowel disease (IBD) recording validation among girls in the Spanish Primary Care Database For Pharmacoepidemiological Research (BIFAP). Methods: In this observational study, girls aged 9 to 18 years registered in BIFAP between 2002 and 2016, were followed up until there was a recorded IBD diagnosis or a referral to specialist indicating IBD. Anonymized profiles were reviewed to retrieve diagnosis confirmation (a positive colonoscopy or biopsy, specialist, or physician's comments mentioning the IBD diagnosis) or discarding (negative procedure results, alternative diagnosis, or family history). "possible" IBD were profiles missing that evidence, or had suspected IBD. The prescriptions of intestinal anti‐inflammatory agents, azatioprine, and mercaptopurine were collected. The prevalence of IBD was estimated after review. Results: Out of 480 634 girls, 323 had a first ever recorded IBD, of which, 37.8% (N = 122) were "confirmed" incident IBD diagnosis, 19.8% (N = 64) discarded and 38.7% (N = 125) "possible" IBD. Additionally, 12 IBD records (3.7%) referred to prevalent IBD. Prescriptions were recorded in 94.3% (confirmed), 63.2% (possible), 83.3% (prevalent), and 3.1% (discarded) IBD cases. Prevalence was 52.83 "confirmed" or 93.58/105 girls when "possible" IBD were added. Conclusions: For a third of the girls, the first recorded IBD included evidence confirming the diagnosis while most of those with missing evidence had treatment indicated for IBD. For research focused in sensitivity, an algorithm including "possible" plus "confirmed" episodes is recommended, whereas only "confirmed" to guarantee higher predictive value. Prevalence suggests that IBD is not a rare disease among girls. [ABSTRACT FROM AUTHOR]

Purpose: Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) is a population based database administered by the AEMPS (Spanish Agency for Medicines) of longitudinal electronic medical records (EMR) of patients attended in primary care. Its main purpose is to serve as source of information for independent studies on drug safety and support of medicines regulation activities. This article aim is to describe the characteristics of BIFAP, how to access the database and a summary of its potential for research. Methods: Health problems are registered by primary care physicians as episodes of care and include socio‐demographic data, results of diagnostic procedures, lifestyle data, general data, and interventions. A proportion of data on hospitalizations and specialist care are currently available through linkage with other data sources. EMRs of the Spanish healthcare system are provided by the regional administrations. Specific data extraction and standardization processes are performed. Results: BIFAP includes data from 12 million patients starting in 2001 and updated annually. Validation of drug and diagnosis definitions has been ascertained. Participation in international collaborative projects and a number of articles in peer reviewed journals reflect its contribution to the knowledge of the risks associated with medicines and drug utilization patterns. Conclusions: BIFAP is a useful tool for generating scientific evidence on medicines related issues, helping regulatory decision making in Europe. The main strengths of BIFAP are related to large sample size, population‐based, longitudinal nature and annual update of data. BIFAP shares common challenges with similar data sources including accurate and efficient identification of health outcomes and of treatment exposure. [ABSTRACT FROM AUTHOR]

Background: In Spain, girls and women are vaccinated against human papillomavirus (HPV) in the primary care setting, according to a national vaccination program. Vaccination is voluntary and the cost is covered by the public health system. Objectives: The aim of the study was to estimate the incidence and patterns of HPV vaccination amongst girls in Spain. Methods: A cohort study was performed using the information recorded in the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP) from 7.4 million patients from eight Spanish regions, between 2001 and 2013 (56% of the regional population). Data available in BIFAP include patient age, sex, lifestyle factors, clinical events, specialist referrals, prescriptions, and vaccinations as recorded by the primary care physician (PCP) or administering nurse. The study cohort comprised all girls aged 11–18 years registered in BIFAP between 1 January 2007 and 31 December 2013 who had at least 1 year of clinical record information with their PCP (inclusion criteria). The date the inclusion criteria were met was designated as the start date of the study cohort contribution. In order to estimate the incidence of HPV vaccination, girls forming the study cohort were followed from start date until there was a recorded HPV vaccination, they reached 19 years of age or died, the end of available information, or 31 December 2013. The person-time of all patients forming the study cohort was taken into account in the incidence estimations. The cumulative incidence (CuIn) of vaccination by birth cohort, year and region was estimated using life-tables (proportion of vaccination by intervals in which the denominator is the initial population corrected for losses). Results: Out of 273,098 girls forming the study population, 81,461 were vaccinated during 2007–2013. Age ranged from 12 to 14 years at first dose in 86.0% of vaccinated girls; 54.1% received a quadrivalent vaccine, 21.9% a bivalent vaccine, and 24.0% an unknown type. Out of the vaccinated population, 87.9% received three doses, 8.2% two and 3.9% one dose, at a maximum of 7 years of follow-up. By calendar year and region, the CuIn reached 70.0–95.8% for birth cohorts between 1993 and 1999, 28.6–99.0% for births cohorts between 1990 and 1992, and exceptionally, 70.6–99.8% for births cohorts between 2000 and 2002 in three regions. Conclusions: According to BIFAP primary care data, a high incidence of vaccination among girls aged 13–15 years was observed. Vaccination among younger and older girls was less common although they reached high incidence in those regions that included girls aged 11–18 years in mass programs. Most vaccination patterns adjusted to a three-dose regimen, as recommended. [ABSTRACT FROM AUTHOR]

Purpose: In Spain, a human papillomavirus (HPV) vaccine was firstly marketed in 2006 and mainly administered in primary care (PC) practices for girls/women or schools. As for all vaccines, a valid data source is required for research on observational effectiveness or safety. The objective of this study is to identify and validate HPV vaccinations recorded among women in The Primary Care Database For Pharmacoepidemiological Research (BIFAP) from 2007. Methods: BIFAP includes a Vaccination File filled by PC practitionners and pediatricians. Information on women with HPV vaccinations recorded at any age was identified and validated according to whether (1) doses adhered to the following standard intervals: 27 to 269 days between first and second doses, >55 days between second and third doses, and <366 between first and third doses, and (2) additional information recorded in clinical records confirmed (through recording the brand, batch, expiring date, administration site, or vaccination comment) or refuted the vaccination and date. The latter was retrieved through manual review of anonymous records randomly selected. Results: One hundred seventeen thousand seventy‐three women with HPV vaccination records were identified (mean age 14.7 years); 82.5% had three jabs, 87.3% in recommended intervals. A sample of 978 patients' records, including 2245 jabs, was reviewed. Of the 363 jabs with additional information, 91% confirmed the vaccination. Confirmatory data was more frequent when doses strictly adhered to recommendations (96.8%‐100%) than not (60.0%‐85.7%). Conclusions: In BIFAP, a cohort of women vaccinated against HPV, mostly with three doses in recommended intervals, was identified. Although additional information about the vaccination was scarce, when present, it highly confirmed it, making BIFAP a potential data source for HPV vaccine research. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The “case‐population” design has been proposed for the surveillance of rare events like Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), wherein a registry of cases is combined with sales data from the source population in order to estimate crude odds ratios (ORs). A major drawback of this method is the inability to distinguish between new and non‐new users of drugs, which for the study of hypersensitivity reactions is of utmost importance. Methods: We have explored an approach in which the exposure to the drugs of interest in the source population is inferred from a primary health care database (BIFAP), which helped us to identify drug initiators among all users and additionally adjust for potential confounders. A total of 44 SJS/TEN cases from the Registry and 44 000 controls randomly sampled from BIFAP and matched with cases for index date were included. We estimated the adjusted ORs (AORs) and 95% confidence intervals (CI) of SJS/TEN associated with the new use of 13 drugs (for which we had at least two exposed cases) through a conditional logistic regression model. Results: AORs (95% CI) were estimated for phenytoin, 4618 (434‐49112); cotrimoxazole, 1142 (163‐8015); allopurinol, 160 (36‐709); dexamethasone, 38 (1.33‐1077); ibuprofen, 33 (8.6‐124); lorazepam, 27 (5.8‐124); paracetamol, 13 (2.8‐62); levofloxacine, 12 (1.24‐120); amoxicillin, 6.9 (1.39‐35); pantoprazole, 6.5 (0.10‐420); metamizole, 6.3 (0.69‐57); amoxicillin clavulanic acid, 4.2 (0.53‐34); and omeprazole, 1.34 (0.06‐31). The inclusion of non‐new users dramatically decreased the AORs for all drugs. Conclusions: The case‐population approach using a registry of cases and a primary health care database proved feasible and efficient for the active surveillance of SJS/TEN. [ABSTRACT FROM AUTHOR]

Background: Missing data are often an issue in electronic medical records (EMRs) research. However, there are many ways that people deal with missing data in drug safety studies. Aim: To compare the risk estimates resulting from different strategies for the handling of missing data in the study of venous thromboembolism (VTE) risk associated with antiosteoporotic medications (AOM). Methods: New users of AOM (alendronic acid, other bisphosphonates, strontium ranelate, selective estrogen receptor modulators, teriparatide, or denosumab) aged ≥50 years during 1998–2014 were identified in two Spanish (the Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria [BIFAP] and EpiChron cohort) and one UK (Clinical Practice Research Datalink [CPRD]) EMR. Hazard ratios (HRs) according to AOM (with alendronic acid as reference) were calculated adjusting for VTE risk factors, body mass index (that was missing in 61% of patients included in the three databases), and smoking (that was missing in 23% of patients) in the year of AOM therapy initiation. HRs and standard errors obtained using cross-sectional multiple imputation (MI) (reference method) were compared to complete case (CC) analysis – using only patients with complete data – and longitudinal MI – adding to the cross-sectional MI model the body mass index/smoking values as recorded in the year before and after therapy initiation. Results: Overall, 422/95,057 (0.4%), 19/12,688 (0.1%), and 2,051/161,202 (1.3%) VTE cases/participants were seen in BIFAP, EpiChron, and CPRD, respectively. HRs moved from 100.00% underestimation to 40.31% overestimation in CC compared with cross-sectional MI, while longitudinal MI methods provided similar risk estimates compared with cross-sectional MI. Precision for HR improved in cross-sectional MI versus CC by up to 160.28%, while longitudinal MI improved precision (compared with cross-sectional) only minimally (up to 0.80%). Conclusion: CC may substantially affect relative risk estimation in EMR-based drug safety studies, since missing data are not often completely at random. Little improvement was seen in these data in terms of power with the inclusion of longitudinal MI compared with cross-sectional MI. The strategy for handling missing data in drug safety studies can have a large impact on both risk estimates and precision. [ABSTRACT FROM AUTHOR]

Background: Uterine fibroids (UFs) are the most common benign tumour in women, and many undergo hysterectomy or uterus-preserving procedures (UPPs) to manage their symptoms. We aimed to validate the recording of UFs in a primary care database, The Health Improvement Network (THIN), and to determine the incidence of UFs in the UK.Methods: In this observational study, women in THIN aged 15-54 years between January 2000 and December 2009 with no previous record of UFs, hysterectomy or UPPs were identified. Individuals were followed up until there was a Read code indicating UFs, they reached 55 years of age or died, or the study ended. Among those without a UF code, women were identified with a code for hysterectomy, UPPs or heavy menstrual bleeding (HMB). Anonymized patient profiles from each category were randomly selected and reviewed. Subsequently, primary care physicians were asked to complete questionnaires to verify the diagnosis for a randomly selected subgroup.Results: In total, 737,638 women were identified who met the initial inclusion criteria. The numbers of women with a code for UFs, hysterectomy, UPPs and HMB were 9380, 11,002, 3220 and 60,915, respectively; the proportions of confirmed cases of UFs were 88.8, 29.7, 57.7 and 15.9 %. The estimated number of women with UFs was 23,140 (64.0 % without a recorded UF diagnosis). The overall incidence of UFs was 5.8 per 1000 woman-years.Conclusions: UFs were confirmed in a high proportion of women with UF Read codes. However, almost two-thirds of cases were identified among women with a code for hysterectomy, UPPs or HMB. These results show that UFs are under-recorded in UK primary care, and suggest that primary care physicians tend to code the symptoms of UFs more often than the diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence of hysterectomy and uterus-preserving procedures (UPPs) among women with uterine fibroids (UFs) and the incidence of further procedures after a UPP.Study Design: This was an observational study using a primary care database, The Health Improvement Network (THIN). Women in THIN with UFs aged 15-54 years between January 2000 and December 2009 were eligible for study. The UPPs examined were myomectomy, endometrial ablation (EA) and uterine artery embolization (UAE). Using Read codes, women were followed up until one of the following was met: there was a record of hysterectomy or UPPs, they died or the study ended (end of 2010).Results: The cumulative incidence of hysterectomy or UPPs was 23.6% at 1 year, and 40.9% after the follow-up period (median 3.6 years). At the end of the follow-up period, the cumulative incidences of hysterectomy, myomectomy, EA and UAE were 33.0%, 3.9%, 6.4% and 1.9%, respectively. For women initially treated with a UPP, the cumulative incidence of second procedures was 11.5% at 1 year. At the end of the follow-up period (median 2.7 years), the cumulative incidence of further procedures was 26.1%, and the cumulative incidences of women undergoing hysterectomy, myomectomy, EA and UAE were 19.0%, 4.3%, 3.4% and 1.4%, respectively.Conclusions: Women considering UPPs for the management of UFs should be made aware that the incidence of further treatments is high, with hysterectomy being the most frequent procedure undergone. [ABSTRACT FROM AUTHOR]

Purpose: We aimed at estimating the incidence of diabetic retinopathy (DR) and maculopathy (DMP) among newly diagnosed type 1 (t1DM) and type 2 diabetic patients (t2DM) in the United Kingdom primary care system. The incidence of DMP among patients with DR was also estimated. Method: We conducted a cohort study using The Health Improvement Network database. The cohort included 64,983 incident diabetic patients (97.3% were t2DM) aged 1–84 years diagnosed between 2000 and 2007. This cohort was followed from the date of diabetes diagnosis until recording of DR or DMP in two separate follow-ups. Follow-up was censored at 85 years of age, death, or end of 2008. An additional follow-up was conducted from DR to DMP diagnosis using similar censoring reasons. DR and DMP cumulative incidences were calculated as well as incidence rates (IR; cases per 1,000 person-years) per calendar period (2000–2001 and 2006–2007). Results: Follow-up for DR: 9 years after diabetes diagnosis, 28% of t2DM and 24% of t1DM patients had developed DR (7,899 incident DR cases). During the first 2 years with diabetes, the IR was almost 2 times higher in patients diagnosed with diabetes in 2006–2007 (47.7) than among those diagnosed in 2000–2001 (24.5). Follow-up for DMP: 9 years after diabetes diagnosis, 3.6% of t2DM and 4.4% of t2DM patients had developed DMP (912 incident DMP cases). During the first 2 years with diabetes, the IR was three times higher in patients diagnosed with diabetes in 2006–2007 (5.8) than among those diagnosed in 2000–2001 (1.8). Macular oedema occurred in 0.8% of patients. Conclusions: In a cohort of incident diabetes, 28% of patients developed retinopathy and 4% maculopathy within the first 9 years. The 2-year IRs of DR and DMP were higher in patients diagnosed with diabetes during the period 2006–2007 than in those diagnosed during the 2000–2001 period. [ABSTRACT FROM AUTHOR]

Background: Discontinuation of low-dose acetylsalicylic acid (ASA) leads to an increased risk of cardiovascular and cerebrovascular events in patients taking low-dose ASA for secondary cardiovascular prevention. However, little is known about the rate of discontinuation in everyday clinical practice. Objectives: To assess the rate of low-dose ASA discontinuation in primary care, and identify factors that predict discontinuation. Methods: The Health Improvement Network, a large UK primary care database, was used to identify patients aged 50-84 years who received at least two consecutive prescriptions for lowdose ASA for secondary cardiovascular or cerebrovascular prevention in 2000-2007 (n = 35,639). Discontinuation was defined as a period of at least 90 days after completion of the last prescribed course of ASA during which no repeat prescription was issued. Results: During the study, 11,729 patients (32.9%) discontinued ASA therapy (mean follow-up 2.5 years). The discontinuation rate was lower in patients with ASA indicated for myocardial infarction than for other indications. The diagnosis of gastrointestinal disorders during the study (overall odds ratio: 1.74; 95% confidence interval: 1.61-1.88) was associated with increased rates of ASA discontinuation, whereas co-prescription of a proton pump inhibitor from the start of ASA therapy was associated with a decreased rate of discontinuation (odds ratio: 0.80; 95% confidence interval: 0.75-0.86). Co-prescription of several other cardioprotective medications was also associated with a reduced risk of discontinuation, as were increasing age, prior hospitalization and overall number of co-medications. Conclusion: Continuous co-prescription of a PPI with low-dose ASA may improve adherence and outcomes, particularly in patients at both cardiovascular and gastrointestinal risk. [ABSTRACT FROM AUTHOR]

Summary: Background: The leading comorbidities and causes of death in patients with chronic obstructive pulmonary disease (COPD) are lung cancer and cardiovascular disease. The aim of this study was to establish the incidence of lung cancer, myocardial infarction and heart failure in patients with COPD in UK primary care. Methods: The General Practice Research Database (GPRD) was used to identify a cohort of 1927 patients with a first recorded diagnosis of COPD. This cohort was followed for up to 5 years to identify new diagnoses of lung cancer, myocardial infarction and heart failure. Mortality was also assessed. The relative risk (RR) of each outcome in the COPD cohort was compared with that in a control cohort with no diagnosis of COPD. Results: The risk of lung cancer was significantly increased in individuals with a diagnosis of COPD compared with those with no COPD diagnosis (RR: 3.33; 95% confidence interval [CI]: 2.33–4.75; adjusted for age, sex and smoking status). A diagnosis of COPD was also associated with a significant increase in the risk of heart failure (age- and sex-adjusted RR: 2.94; 95% CI: 2.46–3.51) and death (age- and sex-adjusted RR: 2.76; 95% CI: 2.45–3.12), but not myocardial infarction (age- and sex-adjusted RR: 1.18; 95% CI: 0.81–1.71). Conclusions: Patients with a diagnosis of COPD are at significantly increased risk of lung cancer, heart failure and death compared with the general population. They do not appear to be at increased risk of myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster.Methods: In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR.Findings: Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion.Interpretation: Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.Funding: None. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain. In this retrospective cohort study, girls in BIFAP aged 9–18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis. Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79–1.76] for exposed (1.25 [0.77–2.04] for bi- and 1.15 [0.76–1.76] for quadri-valent vaccines) and 1.26 [0.74–2.14] for post-exposed periods. HR was 1.50 [0.87–2.59] for the 1st dose, 1.13 [0.66–1.91] for the 2nd and 1.11 [0.71–1.72] for the 3rd one. When the diagnosis date was moved back, the risk was 1.14 [0.76–1.70] for exposed period, being 1.80 [0.86–3.76] and 1.40 [0.74–2.66] after 1st dose of bi- and quadri-valent, respectively. We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1st HPV vaccination dose than after subsequent doses, a dose–effect was not confirmed. Results remained similar after applying a lag time. [ABSTRACT FROM AUTHOR]

• Feasibility of estimating pertussis vaccination covering using 7 European healthcare databases. • The majority of children were vaccinated at the recommended age of vaccination. • Two estimation methods provided comparable coverage estimates. • Benchmarking using national coverage estimates showed comparable results. • The approached used provided reliable estimates for pertussis vaccination coverage. The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing healthcare databases in Europe. The objective of this paper was to assess the feasibility of using electronic healthcare databases to estimate dose-specific acellular pertussis (aP) and whole cell pertussis (wP) vaccine coverage. Seven electronic healthcare databases in four European countries (Denmark (n = 2), UK (n = 2), Spain (n = 2) and Italy (n = 1)) participated in this study. Children were included from birth and followed up to age six years. Vaccination exposure was obtained from the databases and classified by type (aP or wP), and dose 1, 2 or 3. Coverage was estimated using period prevalence. For the 2006 birth cohort, two estimation methods for pertussis vaccine coverage, period prevalence and cumulative incidence were compared for each database. The majority of the 2,575,576 children included had been vaccinated at the country-specific recommended ages. Overall, the estimated dose 3 coverage was 88–97% in Denmark (birth cohorts from 2003 to 2014), 96–100% in the UK (2003–2014), 95–98% in Spain (2004–2014) and 94% in Italy (2006–2007). The estimated dose 3 coverage per birth cohort in Denmark and the UK differed by 1–6% compared with national estimates, with our estimates mostly higher. The estimated dose 3 coverage in Spain differed by 0–2% with no consistent over- or underestimation. In Italy, the estimates were 3% lower compared with the national estimates. Except for Italy, for which the two coverage estimation methods generated the same results, the estimated cumulative incidence coverages were consistently 1–10% lower than period prevalence estimates. This study showed that it was possible to provide consistent estimates of pertussis immunisation coverage from the electronic healthcare databases included, and that the estimates were comparable with the national estimates. [ABSTRACT FROM AUTHOR]

• This paper describes 9 electronic healthcare datasources covering more than 40 million persons. • Background rates for 11 events of interest and pertussis vaccine coverage were benchmarked. • All datasources were fit-for-purpose to generate reliable evidence on vaccine coverage, benefits and risks. The public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. Characterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. The databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of events were comparable in magnitude and age-distribution between databases with the same characteristics. Several conditions (persistent crying and somnolence) were not captured by the databases for which outcomes were restricted to hospital discharge diagnoses. The database characterisation programs and workflows allowed for an efficient, transparent and standardised description and verification of electronic healthcare databases which may participate in pertussis vaccine coverage, benefit and risk studies. This approach is ready to be used for other vaccines/events to create readiness for participation in other vaccine related studies. [ABSTRACT FROM AUTHOR]