Validity of the Penn Alcohol Craving Scale (PACS) for the Adolescent Colombian Population.

INTRODUCTION: Addiction behaviors are primary contributors to mental health issues among adolescents, often utilized as coping mechanisms or emotional regulation tools. This study aimed to establish the content validity of the Penn Alcohol Craving Scale (PACS) for Colombian adolescents, recognized for its representation of the cognitive-emotional aspects of craving. METHODOLOGY: This quantitative research focused on instrument validation. Seven subject matter experts evaluated the scale in terms of pertinence, relevance, usefulness, sufficiency, clarity, and appearance. Data analysis was conducted using SPSS version 22, calculating internal consistency and the Content Validity Index. Qualitative feedback from experts was compiled in an Excel matrix, facilitating grammatical and semantic adjustments to the instrument. RESULTS: Cronbach's Alpha values for each item and the scale exceeded 0.8. Content Validity Index scores exceeded 0.7 in four out of five evaluated criteria. These results supported retaining all scale items in the Colombian version. CONCLUSIONS: The content validation process yielded an instrument that satisfied expert opinion regarding conceptual constructs and explanatory power for the Colombian adolescent population.

Effect of regulatory interventions on agomelatine use in Spain: A multiple intervention time-series analysis in a nationwide electronic healthcare record database.

BACKGROUND: Liver injury is an important identified risk for agomelatine and several measures were put in place to prevent and minimize such risk. The study aims to assess the impact of four interventions on the incidence of agomelatine use, particularly among patients aged ≥75 in Spain between 2011 and 2018. METHODS: Quasi-experimental interrupted time-series analysis to examine data from a nationwide electronic healthcare record database (BIFAP). Quarterly cumulative incidence of agomelatine use per 100 000 patients was calculated and the impact of four regulatory interventions was quantified. RESULTS: The incidence of agomelatine use decreased by 85% and 87% from first quarter 2011 to last quarter 2018 in patients below and above 75 years old, respectively. Regulatory actions taken were not associated with an immediate and significant falling level of use or slope. The incidence was less than expected 6 months after the first and third intervention for patients below and above 75 years old, and more than expected after the second and fourth intervention for both populations, though these analyses were underpowered to observe significant results. The downward trend became less pronounced, reaching a residual level of use, which remained stable in the last segment of the study period. CONCLUSION: New users of agomelatine decreased throughout the study period, starting before interventions took place. The effect of specific interventions might be masked by the progressive decrease tendency, constant over the study period. The effects of external factors that might overlap, unintended consequences, and issues concerning statistical modeling in situations where rates are already falling, should be considered when interpreting the results.

Drug utilization study on immediate release Fentanyl in Spain. Prevalence, incidence, and indication.

PURPOSE: We aimed to characterize the trends of immediate release fentanyl (IRF) use in Spain between 2012 and 2017 and indication for its use. IRF drugs are rapid-acting opioids approved to treat breakthrough cancer pain (BTCP) in patients already receiving maintenance opioid therapy for chronic cancer pain. A substantial increase in consumption of IRF has been observed with emerging cases of abuse and dependence, most of them in noncancer patients. METHODS: An ecological descriptive consumption study with aggregated data from drug dispensed by community pharmacies and reimbursed by the National Health System in which Defined Daily Doses per 10 000 inhabitants (DID) were calculated and a retrospective cohort study using data from the Spanish Database for Pharmacoepidemiological Research in Primary Care in which participants entered the cohort study after 1 year with the Primary Care Practitioners were performed. Annual prevalence and incidence rate of IRF use were estimated by sex and calendar year. Potential indication was also assessed. RESULTS: IRF use in Spain increased from 2.1 DID in 2012 to 3.8 DID in 2017. The incidence rate and prevalence increased in 53% and 74%, respectively. Patients without previous cancer or BCTP diagnosis represented 27% of incident users, predominantly women. Half of patients with noncancer-related diagnosis had a musculoskeletal disorder linked to the first IRF prescription. CONCLUSIONS: National consumption and new IRF users in Spain increased over the study period and one quarter of patients did not have a BTCP or cancer diagnosis registered in their clinical record.

Anxiety in young people: Analysis from a machine learning model.

The study addresses the detection of anxiety symptoms in young people using artificial intelligence models. Questionnaires such as the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7) are used to collect data, with a focus on early detection of anxiety. Three machine learning models are employed: Support Vector Machine (SVM), K Nearest Neighbors (KNN), and Random Forest (RF), with cross-validation to assess their effectiveness. Results show that the RF model is the most efficient, with an accuracy of 91 %, surpassing previous studies. Significant predictors of anxiety are identified, such as parental education level, alcohol consumption, and social security affiliation. A relationship is observed between anxiety and personal and family history of mental illness, as well as with characteristics external to the model, such as family and personal history of depression. The analysis of the results highlights the importance of considering not only clinical but also social and family aspects in mental health interventions. It is suggested that the sample size be expanded in future studies to improve the robustness of the model. In summary, the study demonstrates the usefulness of artificial intelligence in the early detection of anxiety in young people and highlights the relevance of addressing multidimensional factors in the assessment and treatment of this condition.

Mental health conditions of Colombian adolescent population: An approach to risk.

OBJECTIVE: To determine the mental health conditions of adolescents in the city of Manizales, Colombia, and explore risk regarding gender-based differences. MATERIALS AND METHODS: Quantitative, nonexperimental, descriptive research with associative scope. A total of 316 adolescents were assessed using five scales to evaluate mental health conditions: the Perceived Stress Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale, Penn Alcohol Craving Scale and The Substance Dependence Severity Scale. Univariate and bivariate analysis was performed, Chi square and Odds Ratio were tested. RESULTS: The findings indicated that being female is a risk factor for high levels of perceived stress, depressive episodes and anxiety. Additionally, adolescents who are not attending school are at higher risk for dependence and abuse of psychoactive substances. Conversely, being female acts as a protective factor against dependence on psychoactive substances. CONCLUSIONS: The findings suggest a higher tendency among the participants towards experiencing depressive episodes. Regarding perceived stress, 71.5% of the participants fell into the low category, while 70.6% experienced a current episode of generalized anxiety.

COVID-19 Distribution in Pregnancy, Drug Use Patterns and COVID-19 Medication during the Pandemic in Spain: Data from Real-World Electronic Health Records.

Although pregnant women were considered a risk population for COVID-19, little is known of their drug use during the pandemic. We aimed to investigate COVID-19 distribution, drug use patterns and COVID-19 medication. We conducted a retrospective cohort of validated pregnancies aged 15-49 years, from January 2020 to December 2022, using the BIFAP database. An identified cohort of pregnant women with COVID-19 was matched by age, gestational age, length of pregnancy and outcome to a cohort free of COVID-19 (8413 vs. 24,975). We performed a descriptive analysis on COVID-19 cases, estimated the drug use patterns and assessed COVID-19-specific drugs within the week prior/after diagnosis, stratified by pandemic wave and gestational week. The results showed that 72% of pregnant women with COVID-19 received at least one prescription vs. 66.6% of those free of COVID-19, with analgesics, antibiotics and thyroid hormones being the most prescribed drugs in both groups. In the COVID-19 group, they were antithrombotics (40 prescriptions per 100 women), analgesic/NSAIDs (19.64/6.29) and antibiotics (6.95). COVID-19 cases gradually increased, peaking at the fifth and second waves. Prescription rates were similar when compared to pre-pandemic studies. The use of drugs compatible with COVID-19 treatments was in line with recommendations.

Lack of association between COVID-19 vaccines and miscarriage onset using a case-crossover design.

Pregnant women might have an increased risk of SARS-COV-2 infection. Although evidence towards the efficacy and safety of COVID-19 is growing still there is room for improvement on the knowledge towards pregnancy adverse events, such as miscarriage. We explored the association of COVID-19 vaccine with the risk of miscarriages using the Real-World. We identified a cohort of vaccinated pregnancies using the BIFAP database which contains systematically recorded data on care patients in Spain (N = 4054). We then restricted it to those women who had a miscarriage using a validated algorithm (N = 607). Among them, we performed a case-crossover design to evaluate the effect of intermittent exposures on the risk of miscarriage. Adjusted Odds Ratio with their confidence intervals were calculated using two analytical approaches: conditional logistic regression and Generalized Linear Mixed-Effects Models. A total of 225 (37.1%) were aged 35-39 years. The most common comorbidities were asthma, migraine, gastritis, and hypothyroidism. A total of 14.7% received only one dose of COVID-19 and 85.3% two doses, respectively. A total of 36.8% of women with one dose and 27.6% with two doses received the vaccine 7 days prior to the miscarriage. Corresponding adjusted estimates for the risk of miscarriage using the conditional logistic regression where as follows: 1.65 (95% CI 0.85-3.23) when using as the sum of 3 control moments among women with one dose, 1.02 (95% CI 0.72-1.46) among women with two doses and 1.03 (95% CI 0.72, 1.46) using the whole study population. Very similar results were obtained when conducting the Generalized Linear Mixed-Effects Models. There was no overall increased risk of miscarriage onset associated with COVID-19 vaccine although contradictory results were found according to the number of doses. Further studies are required with larger sample sizes to assess this association.

Antithrombotic Use Patterns in COVID-19 Patients from Spain: A Real-World Data Study.

Antithrombotics have been widely used to treat and prevent COVID-19-related thrombosis; however, studies on their use at population levels are limited. We aimed to describe antithrombotic use patterns during the pandemic in Spanish primary care and hospital-admitted patients with COVID-19. Methods: A real-world data study was performed. Data were obtained from BIFAP's electronic health records. We investigated the antithrombotic prescriptions made within ±14 days after diagnosis between March 2020 and February 2022, divided their use into prior and new/naive groups, and reported their post-discharge use. Results: We included 882,540 individuals (53.4% women), of whom 78,499 were hospitalized. The median age was 44.7 (IQR 39-59). Antithrombotics were prescribed in 37,183 (4.6%) primary care subjects and 42,041 (53.6%) hospital-admitted patients, of whom 7505 (20.2%) and 20,300 (48.3%), respectively, were naive users. Prior users were older and had more comorbidities than new users. Enoxaparin was the most prescribed antithrombotic in hospitals, with higher prescription rates in new than prior users (2348.2, IQR 2390-3123.1 vs. 1378, IQR 1162-1751.6 prescriptions per 10,000 cases, p = 0.002). In primary care, acetylsalicylic acid was the most used antithrombotic, with higher use rates in prior than in naïve users. Post-discharge use occurred in 6686 (15.9%) subjects (median use = 10 days, IQR 9-30). Conclusions: Our study identified a consensus on prescribing antithrombotics in COVID-19 patients, but with low use rates in hospitals.

[Primary health care: challenges for implementation in Latin America]. / La Atención Primaria de Salud: desafíos para su implementación en América Latina.

A development process, marked by the re-appearance of the primary health care as the core of health systems, has emerged in Latin America. Governments have made a commitment to renew this strategy as the basis of their health systems. However, these health systems are mainly faced with re-introducing equity values, and there are common challenges such as providing the health systems with trained human resources in sufficient numbers, overcoming the fragmentation/segmentation of the systems, ensuring financial sustainability, improving governance, quality of care and information systems, expanding coverage, preparing to face the consequences of an aging population, the changing epidemiological profile, and increase in the response capacity of the public health system. This article is intended to provide a comprehensive view of the progress and challenges of the inclusion of primary care health systems in Latin American countries.

A Clinical Prediction Rule for Thrombosis in Critically Ill COVID-19 Patients: Step 1 Results of the Thromcco Study.

The incidence of thrombosis in COVID-19 patients is exceptionally high among intensive care unit (ICU)-admitted individuals. We aimed to develop a clinical prediction rule for thrombosis in hospitalized COVID-19 patients. Data were taken from the Thromcco study (TS) database, which contains information on consecutive adults (aged ≥ 18) admitted to eight Spanish ICUs between March 2020 and October 2021. Diverse logistic regression model analysis, including demographic data, pre-existing conditions, and blood tests collected during the first 24 h of hospitalization, was performed to build a model that predicted thrombosis. Once obtained, the numeric and categorical variables considered were converted to factor variables giving them a score. Out of 2055 patients included in the TS database, 299 subjects with a median age of 62.4 years (IQR 51.5-70) (79% men) were considered in the final model (SE = 83%, SP = 62%, accuracy = 77%). Seven variables with assigned scores were delineated as age 25-40 and ≥70 = 12, age 41-70 = 13, male = 1, D-dimer ≥ 500 ng/mL = 13, leukocytes ≥ 10 × 103/µL = 1, interleukin-6 ≥ 10 pg/mL = 1, and C-reactive protein (CRP) ≥ 50 mg/L = 1. Score values ≥28 had a sensitivity of 88% and specificity of 29% for thrombosis. This score could be helpful in recognizing patients at higher risk for thrombosis, but further research is needed.

[Non-inferiority studies efficacy and safety: review of methodological and statistical aspects in clinical trials and non-interventional studies with medicinal products.] / Estudios de no inferioridad de eficacia y seguridad: revisión e interpretación de aspectos metodológicos y estadísticos en ensayos clínicos y estudios observacionales con medicamentos.

Non-inferiority studies are increasingly more common for introducing new medicines in the market. Despite being situations where the use of this study design is justified, there is not a common analytical approach on how to conduct them. Pursuing a rigorous methodology, both in the study conduction and in its disseminations, is critical to ensure robust results to enable regulatory agencies and clinicians to reach valid conclusions and decisions which ultimately will benefit clinical practice. Most of the published reviews focus on the efficacy outcomes of non-inferiority clinical trials. We are unaware of other reviews that goes beyond and includes specific aspects for non-interventional designs and for studies focused on safety. Moreover, this review provides a simple and practical perspective with a minimum mathematical content on this complex type of studies.

Los estudios de no inferioridad son cada vez más frecuentes para introducir nuevos medicamentos en el mercado. Aunque existen situaciones en las que su uso está justificado, no existe un enfoque analítico único y conservador. Para arrojar resultados fiables y de calidad, deben seguir una estricta metodología, tanto en la ejecución como en la difusión de los resultados, la cual permita, tanto a las agencias reguladoras como a los clínicos, establecer conclusiones válidas y decisiones que repercutan en beneficio de la práctica clínica. La mayor parte de las revisiones publicadas se centran en los ensayos clínicos de no inferioridad de eficacia. En esta revisión se contemplan, además, los diseños observacionales y los aspectos específicos de los estudios de seguridad. Todo ello desde un punto de vista práctico y sencillo, con un contenido matemático mínimo.

Thromboembolic Events in a Socio-Economically Disadvantaged Population with COVID-19 Admitted to a Medicalized Hotel in Madrid.

Background: The social determinants of health (SDOH) of patients with COVID-19-related thrombosis have been scarcely explored. Our objective was to investigate the cases of thrombosis in a group of socially disadvantaged populations with COVID-19. Methods: We investigated the thrombotic events that occurred in a cohort of migrant and Spanish patients with COVID-19 that were admitted to a medicalized hotel in Madrid. Demographic data, past medical history, and socio-economic backgrounds, such as monthly household income, level of education, and living conditions, were explored to determine the factors related to thrombosis. Results: A cohort of 383 subjects (mean age 55.4 ± 14.6 years old, 69% male), of which 58% were migrants, was studied. Fourteen (3.6%) cases of thrombosis were reported. Thrombosis was more frequent in Spanish than in migrant individuals (OR 5.3, 95%CI 1.4-19.5, p = 0.005). Neither a low monthly household income nor a low education level showed a statistical association with thrombosis (p ≥ 0.05). History of venous thromboembolism (OR 8.1, 95%CI 2.2-28.6) and being a current smoker (OR 4.7, 95%CI 1.3-16.0) were factors associated with thrombosis. Conclusions: The SDOH studied were not associated with thrombosis; however, further investigation must be performed to investigate the socio-economic conditions of subjects with COVID-19 with adverse outcomes such as thrombotic events.

The Risk of SARS-CoV-2 Infection in Pregnant Women: An Observational Cohort Study Using the BIFAP Database.

BACKGROUND: It has been suggested that women experiencing during pregnancy several physiological and immunological changes that might increase the risk of any infection including the SARS-CoV-2. OBJECTIVE: We aimed to quantify the risk of SARS-CoV-2 infection during pregnancy compared with women with no pregnancies. METHODS: We used data from the BIFAP database and a published algorithm to identify all pregnancies during 2020. Pregnancies were matched (1:4) by age region, and length of pregnancy with a cohort of women of childbearing age. All women with SARS-CoV-2 infection before entering the study were discarded. We estimated incidence rates of SARS-CoV-2 with 95% confidence intervals (CIs) expressed by 1000 person-months as well as Kaplan-Meier figures overall and also stratified according to pregnancy period: during pregnancy, at puerperium (from end of pregnancy up to 42 days) and after pregnancy. (from 43 days after pregnancy up to end pf study period (i.e., June 2021). We conducted a Cox regression to assess risk factors for SARS-COV infection. The incidence rate of SARS-CoV-2 infection expressed by 1000 person-months were. RESULTS: There was a total of 103,185 pregnancies and 412,740 matched women at childbearing, with a mean age of 32.3 years. The corresponding incidence rates of SARS-CoV-2 infection according to cohorts were: 2.44 cases per 1000 person-months (confidence interval (CI) 95%: 2.40-2.50) and 4.29 (95% CI: 4.15-4.43) for comparison cohort. The incidence rate ratio (IRR) of SARS-CoV-2 was 1.76 (95% CI: 1.69-1.83). When analyzing according to pregnancy period, the IRRs were 1.30 (95% CI: 11.20-1.41) during the puerperium and 1.19 (95% CI: 41.15-1.23) after pregnancy. In addition to pregnancy itself, other important risk factors were obesity (1.33 (95% CI: 1.23-1.44)) and diabetes (1.23 (95% CI: 11.00-1.50). CONCLUSION: Pregnant women are at increased risk of SARS-CoV-2 infection compared with women of childbearing age not pregnant. Nevertheless, there is a trend towards reverting during puerperium and after pregnancy.

Flecainide and risk of skin neoplasms: Results of a large nested case-control study in Spain and Denmark.

Background: A previous study in Denmark suggested an increased melanoma risk associated with the use of flecainide. Objective: To study the association between flecainide use and the risk of melanoma and non-melanoma skin cancer in Spain and Denmark. Methods: We conducted a multi-database case-control study in (database/study period) Spain (SIDIAP/2005-2017 and BIFAP/2007-2017) and Denmark (Danish registries/2001-2018). We included incident cases of melanoma or non-melanoma skin cancer (NMSC) aged ≥18 with ≥2 years of previous data (≥10 years for Denmark) before the skin cancer and matched them to controls (10:1 by age and sex). We excluded persons with immunosuppression or previous cancer. We defined ever-use as any prescription fill and high-use as a cumulative dose of at least 200 g (reference: never-use). We categorized a cumulative dose for a dose-response assessment. We used conditional logistic regression to compute ORs (95% CI) adjusted for photosensitizing, anti-neoplastic, disease-specific drugs and comorbidities. Results: The total numbers of melanoma/NMSC cases included were 7,809/64,230 in SIDIAP, 4,661/31,063 in BIFAP, and 27,978/152,821 in Denmark. In Denmark, high-use of flecainide was associated with increased adjusted ORs of skin cancer compared with never-use [melanoma: OR 1.97 (1.38-2.81); NMSC: OR 1.34 (1.15-1.56)]. In Spain, an association between high-use of flecainide and NMSC was also observed [BIFAP: OR 1.42 (1.04-1.93); SIDIAP: OR 1.19 (0.95-1.48)]. There was a non-significant dose-response pattern for melanoma in Denmark and no apparent dose-response pattern for NMSC in any of the three databases. We found similar results for ever-use of flecainide. Conclusion: Flecainide use was associated with an increased risk of melanoma (Denmark only) and NMSC (Denmark and Spain) but without substantial evidence of dose-response patterns. Further studies are needed to assess for possible unmeasured confounders.

Student Attitudes Contribute to the Effectiveness of a Genomics CURE.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.

[Quarantine by COVID-19 in a health professional: psychological, social and family dimensions]. / Cuarentena por COVID-19 en un profesional de la salud: dimensión psicológica, social y familiar.

OBJECTIVE: To analyze the psychological, social and family dimensions of a health professional quarantined by COVID-19. METHOD: Case report. A matrix was used as a daily log to collect information from the three dimensions analyzed. The anonymity of the person was respected at all times. RESULTS: A case study is presented with the main milestones in the daily life of a health professional during the 14 days of quarantine. In the psychological dimension, feelings of fear and uncertainty in the face of risk are highlighted, in the social dimension the importance of the accompaniment of family and friends who strengthened the adaptability to the process stands out, and in the family dimension the relevance of affective bonds and permanent communication. CONCLUSION: The aspects developed in the different dimensions should be considered by those who participate in the management and follow-up of cases in primary care, as they are the possibility of strengthening the neuronal and hormonal mechanism through family and social support. Being a health professional and having knowledge on the subject can generate a greater effect of involuntary isolation related to the risk of COVID-19. This is not only clinical, but also psychological, social and family. In this sense those who manage the cases should consider the integrality in health conditions.

ADVANCE system testing: Benefit-risk analysis of a marketed vaccine using multi-criteria decision analysis and individual-level state transition modelling.

BACKGROUND: 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 electronic health record (eHR) databases in Europe. Proof-of-concept studies were designed to assess the proposed processes and system for generating the required evidence to perform B/R assessment and near-real time monitoring of vaccines. We aimed to test B/R methodologies for vaccines, using the comparison of the B/R profiles of whole-cell (wP) and acellular pertussis (aP) vaccine formulations in children as an example. METHODS: We used multi-criteria decision analysis (MCDA) to structure the B/R assessment combined with individual-level state transition modelling to build the B/R effects table. In the state transition model, we simulated the number of events in two hypothetical cohorts of 1 million children followed from first pertussis dose till pre-school-entry booster (or six years of age, whichever occurred first), with one cohort receiving wP, and the other aP. The benefits were reductions in pertussis incidence and complications. The risks were increased incidences of febrile convulsions, fever, hypotonic-hyporesponsive episodes, injection-site reactions and persistent crying. Most model parameters were informed by estimates (coverage, background incidences, relative risks) from eHR databases from Denmark (SSI), Spain (BIFAP and SIDIAP), Italy (Pedianet) and the UK (RCGP-RSC and THIN). Preferences were elicited from clinical and epidemiological experts. RESULTS: Using state transition modelling to build the B/R effects table facilitated the comparison of different vaccine effects (e.g. immediate vaccine risks vs long-term vaccine benefits). Estimates from eHR databases could be used to inform the simulation model. The model results could be easily combined with preference weights to obtain B/R scores. CONCLUSION: Existing B/R methodology, modelling and estimates from eHR databases can be successfully used for B/R assessment of vaccines.

ADVANCE system testing: Can safety studies be conducted using electronic healthcare data? An example using pertussis vaccination.

INTRODUCTION: The Accelerated Development of Vaccine benefit-risk Collaboration in Europe (ADVANCE) public-private collaboration, aimed to develop and test a system for rapid benefit-risk monitoring of vaccines using healthcare databases in Europe. The objective of this proof-of-concept (POC) study was to test the feasibility of the ADVANCE system to generate incidence rates (IRs) per 1000 person-years and incidence rate ratios (IRRs) for risks associated with whole cell- (wP) and acellular- (aP) pertussis vaccines, occurring in event-specific risk windows in children prior to their pre-school-entry booster. METHODS: The study population comprised almost 5.1 million children aged 1 month to <6 years vaccinated with wP or aP vaccines during the study period from 1 January 1990 to 31 December 2015. Data from two Danish hospital (H) databases (AUH and SSI) and five primary care (PC) databases from, UK (THIN and RCGP RSC), Spain (SIDIAP and BIFAP) and Italy (Pedianet) were analysed. Database-specific IRRs between risk vs. non-risk periods were estimated in a self-controlled case series study and pooled using random-effects meta-analyses. RESULTS: The overall IRs were: fever, 58.2 (95% CI: 58.1; 58.3), 96.9 (96.7; 97.1) for PC DBs and 8.56 (8.5; 8.6) for H DBs; convulsions, 7.6 (95% CI: 7.6; 7.7), 3.55 (3.5; 3.6) for PC and 12.87 (12.8; 13) for H; persistent crying, 3.9 (95% CI: 3.8; 3.9) for PC, injection-site reactions, 2.2 (95% CI 2.1; 2.2) for PC, hypotonic hypo-responsive episode (HHE), 0.4 (95% CI: 0.4; 0.4), 0.6 (0.6; 0.6) for PC and 0.2 (0.2; 0.3) for H; and somnolence: 0.3 (95% CI: 0.3; 0.3) for PC. The pooled IRRs for persistent crying, fever, and ISR, adjusted for age and healthy vaccinee period were higher after wP vs. aP vaccination, and lower for convulsions, for all doses. The IRR for HHE was slightly lower for wP than aP, while wP was associated with somnolence only for dose 1 and dose 3 compared with aP. CONCLUSIONS: The estimated IRs and IRRs were comparable with published data, therefore demonstrating that the ADVANCE system was able to combine several European healthcare databases to assess vaccine safety data for wP and aP vaccination.

ADVANCE system testing: Can coverage of pertussis vaccination be estimated in European countries using electronic healthcare databases: An example.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.